Combining nano-physical and computational investigations to understand the nature of “aging” in dermal collagen

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Quantitative accuracy of computed tomography perfusion under low-dose conditions, measured using a hollow-fiber phantom

Abstract

Purpose

The purpose of this study was to investigate the quantitative accuracy under low-dose conditions on computed tomography (CT) perfusion using a hollow-fiber phantom that had the theoretical absolute values of perfusion indices.

Materials and methods

Our phantom comprised two components, i.e., a hollow-fiber hemodialyzer to pump the diluted contrast material and a surrounding syringe-shaped X-ray-absorbing body to simulate the absorption of X-rays by a brain and cranium. We performed CTP scans on the phantom under various dose conditions ranging from 20 to 140 mA using a 64-row CT scanner, measuring experimental cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) values using a deconvolution algorithm.

Results

The theoretical value of the CBV was within the 95% confidence interval of CBV values measured under 80 mA. The CBV measured under low-dose settings and all CBF values measured were smaller than the theoretically calculated ones, and all MTT values measured were larger. All measured values of the CBV, CBF, MTT, and TTP decreased with an increase in image noise under lower dose conditions.

Conclusion

It is difficult to define a low-dose limit in clinical scan conditions because of the complex characteristics of perfusion indices.

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Thin-section CT findings of thoracolithiasis

Abstract

Purpose

To review thin-section CT findings of thoracolithiasis.

Materials and methods

Thirty-three thin-section CT scans of 9 patients with thoracolithiasis diagnosed between 2008 and 2016 were reviewed for the location, shape, longest diameter, and calcification of each freely mobile nodule (thoracolith) and for the presence of coexisting abnormalities.

Results

The mean age of 9 patients (5 women) was 65.8 years (SD 14.9; range 37–83 years). Eight were > 50 years of age. Three patients had two thoracoliths, and the remaining 6 patients had one. Thoracoliths were in the left (n = 9) or right (n = 3) pleural cavity, with most in the lower pleural cavity. Nine thoracoliths were found to be larger at follow-up. The median diameters of the 12 thoracoliths were 4.9 mm (range 2.1–10.6 mm) and 6.2 mm (range 3.6–11.0 mm) on the initial and latest follow-up CT scans, respectively. Concomitant old granulomatous disease (n = 6) and diffuse systemic sclerosis-related interstitial lung disease (n = 2) were noted.

Conclusion

Thoracolithiasis can manifest as one or two small calcified nodules. It tends to occur in the left lower pleural cavity, occur in a patient aged > 50 years, be larger on follow-up, and coincide with other diseases.

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Editorial Board and Contents

Publication date: May 2017
Source:Trends in Immunology, Volume 38, Issue 5





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Schistosomiasis

Schistosomiasis: Diseases of liver, gastrointestinal tract and bladder caused by schistosomes, trematode worms that parasitize people. Infection is from infested water.

There are three main species of these trematode worms (flukes) --Schistosoma haematobium, S. japonicum, and S. mansoni -- that cause disease in humans. The larval forms of the parasite live in freshwater snails. The cercaria (form of the parasite) is liberated from the snail, burrows into skin, transforms to the schistosomulum stage, and migrates to the urinary tract (S. haematobium), liver or intestine (S. japonicum, S.mansoni) where the adult worms develop. Eggs are shed into the urinary tract or the intestine and hatch to form miracidia (yet another form of the parasite) which then infect snails, completing the life cycle of the parasite.

Adult schistosome worms can cause very serious tissue damage. Some schistosomes which cannot live within man nonetheless cause swimmer's itch.

Schistosomiasis is also called bilharzia after the short-lived German physician Theodor Bilharz (1825-1862).

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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Characterization of β-lactamase activity using isothermal titration calorimetry

Publication date: Available online 25 April 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Wen-Jing Wang, Qian Wang, Ye Zhang, Rui Lu, Yi-Lin Zhang, Ke-Wu Yang, Jin-e Lei, Yuan He
BackgroundHydrolysis of β-lactam antibiotic by β-lactamase is the most common mechanism of β-lactam resistance in clinical isolates. Timely detection and characterization of β-lactamases are therefore of utmost biomedical importance. Conventional spectrophotometric method is time-consuming and cannot provide thermodynamic information on β-lactamases.MethodsA new assay was developed for the study of β-lactamase activity in protein solutions (Metallo-β-lactamase L1) and in clinical bacterial cells, based on heat-flow changes derived from enzymatic hydrolysis of β-lactams using isothermal titration calorimetry.Results(1) The thermokinetic parameters of three antibiotics (penicillin G, cefazolin and imipenem) and the inhibition constant of an azolylthioacetamide inhibitor were determined using the calorimetric assay. The results from the calorimetric assays were consistent with the data from the spectrophotometric assay. (2) The values of heat change in the calorimetric assay using two clinical Escherichia coli strains correlated well with their antibiotic susceptibility results from the broth dilution experiment. The subtypes of β-lactamase were also determined in the calorimetric assay.ConclusionsThe ITC assay is a reliable and fast method to study β-lactamase enzyme kinetics and inhibition. It can also provide thermodynamic information on antibiotic hydrolysis, which has been taken advantage of in this work to study β-lactamase activity in two clinical Escherichia coli isolates.General significanceAs the first calorimetric study of β-lactamase activity, it may provide a new assay to assist biomedical validation of new β-lactamase inhibitors, and also has potential applications on rapid antibiotic susceptibility testing and screening β-lactamase producing bacteria.

Graphical abstract

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A new cryptic host defense peptide identified in human 11-hydroxysteroid dehydrogenase-1 β-like: from in silico identification to experimental evidence

Publication date: Available online 26 April 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): A. Bosso, L. Pirone, R. Gaglione, K. Pane, A. Del Gatto, L. Zaccaro, S. Di Gaetano, D. Diana, R. Fattorusso, E. Pedone, V. Cafaro, H.P. Haagsman, A. van Dijk, M.R. Scheenstra, A. Zanfardino, O. Crescenzi, A. Arciello, M. Varcamonti, E.J.A. Veldhuizen, A. Di Donato, E. Notomista, E. Pizzo
BackgroundHost defence peptides (HDPs) are evolutionarily conserved components of innate immunity. Human HDPs, produced by a variety of immune cells of hematopoietic and epithelial origin, are generally grouped into two families: beta structured defensins and variably-structured cathelicidins. We report the characterization of a very promising cryptic human HDP, here called GVF27, identified in 11-hydroxysteroid dehydrogenase-1 β-like protein.MethodsConformational analysis of GVF27 and its propensity to bind endotoxins were performed by NMR, Circular Dichroism, Fluorescence and Dynamic Light Scattering experiments. Crystal violet and WST-1 assays, ATP leakage measurement and colony counting procedures were used to investigate antimicrobial, anti-biofilm, cytotoxicity and hemolytic activities. Anti-inflammatory properties were evaluated by ELISA.ResultsGVF27 possesses significant antibacterial properties on planktonic cells and sessile bacteria forming biofilm, as well as promising dose dependent abilities to inhibit attachment or eradicate existing mature biofilm. It is unstructured in aqueous buffer, whereas it tends to assume a helical conformation in mimic membrane environments as well as it is able to bind lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Notably it is not toxic towards human and murine cell lines and triggers a significant innate immune response by attenuating expression levels of pro-inflammatory interleukins and release of nitric oxide in LPS induced macrophages.ConclusionHuman GVF27 may offer significant advantages as leads for the design of human-specific therapeutics.General significanceHuman cryptic host defence peptides are naturally no immunogenic and for this they are a real alternative for solving the lack of effective antibiotics to control bacterial infections.

Graphical abstract

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Biosynthesis-inspired deracemizative production of d-luciferin by combining luciferase and thioesterase

Publication date: Available online 25 April 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Juri Maeda, Dai-ichiro Kato, Masatoshi Okuda, Masahiro Takeo, Seiji Negoro, Kazunari Arima, Yuji Ito, Kazuki Niwa
Due to the strict enantioselectivity of firefly luciferase, only d-luciferin can be used as a substrate for bioluminescence reactions. Unfortunately, luciferin racemizes easily and accumulation of nonluminous l-luciferin has negative influences on the light emitting reaction. Thus, maintaining the enantiopurity of luciferin in the reaction mixture is one of the most important demands in bioluminescence applications using firefly luciferase. In fireflies, however, l-luciferin is the biosynthetic precursor of d-luciferin, which is produced from the L-form undergoing deracemization. This deracemization consists of three successive reactions: l-enantioselective thioesterification by luciferase, in situ epimerization, and hydrolysis by thioesterase. In this work, we introduce a deracemizative luminescence system inspired by the biosynthetic pathway of d-luciferin using a combination of firefly luciferase from Luciola cruciata (LUC-G) and fatty acyl-CoA thioesterase II from Escherichia coli (TESB). The enzymatic reaction property analysis indicated the importance of the concentration balance between LUC-G and TESB for efficient d-luciferin production and light emission. Using this deracemizative luminescence system, a highly sensitive quantitative analysis method for l-cysteine was constructed. This LUC-G-TESB combination system can improve bioanalysis applications using the firefly bioluminescence reaction by efficient deracemization of D-luciferin.



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Improving antimicrobial prescribing practice for sore throat symptoms in a general practice setting

Acute sore throat is a common presentation in primary care settings. We aimed to improve our compliance with national antibiotic guidelines for sore throat symptoms to 90% in 3 months' time period. The national guidelines are based on Centor criteria. A retrospective audit of 102 patient records with sore throat symptoms presenting between 1 January to 30 December 2015 showed that over 50% were given antibiotics. Those who were prescribed antibiotics, 27% did not meet NICE criteria and 85% of patients were given immediate antibiotic prescription. Centor criteria was documented in just 2% of cases. Compliance with correct antibiotic course length was 15%. Antibiotic choice and dose was correct in 94% and 92% of cases respectively. Antibiotic frequency was correctly prescribed in 100% of patients.

We introduced interventions that included oral and poster presentations to multidisciplinary team, dissemination of guidelines through internal e-mail and systemic changes to GP electronic patient record system EMIS. This involved creating an automated sore throat template and information page. On re-auditing of 71 patients, after two PDSA cycles, compliance with NICE criteria was 87% with a significant reduction in immediate prescribing (66%). Centor criteria documentation was 42%. Correct antibiotic course length was prescribed in over 30% of cases. Other antibiotic regimen parameters (choice, dose and frequency) were correct in 100% of cases.

The initial results demonstrated that significant changes were needed. In particular, reducing the amount of antibiotics prescribed by increasing compliance with NICE criteria and ensuring all parameters of antibiotic prescription were correct. We showed that significant sustainable improvement is achievable through carefully devised automated systemic changes that provides critical information in readily accessible format, and does not solely rely on prescribers' knowledge and initiative. The outcome of these interventions are a decrease in immediate antibiotic prescription, significant increase in Centor criteria documentation and an increase in compliance with the correct course length of antibiotics. All these measures would contribute to reduction in antimicrobial resistance and improvement in patient care in the community. Future work must focus on improving compliance with correct antibiotic course length.

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Improving access for Urgent patients in Paediatric Neurology

Referral and flow management is an important part of outpatient care; some patients require to be seen earlier than the next available appointment because of the nature of their presentation. We did not have a clear pathway for urgent patients being referred to our pediatric neurology service. When we reviewed this process in our Quality Improvement meeting we identified wide variation in the length of time such patients wait to be seen in clinic ranging from 2 to 11 weeks. Only 25% of patients identified as requiring urgent clinic appointments were seen in clinic within 2 weeks of triage.

A new triage system was designed to identify urgent patients consistently. Three PDSA cycles tested change ideas: the first cycle tested introducing an urgent triage system, the second cycle tested giving urgent appointments directly from the triage decision utilising clinic cancellations and the third PDSA tested double notification of appointments for all urgent patients using the call centre and the neurology specialist nurses.

After the third PDSA the percentage of patients seen within 2 weeks of triage increased from 25% to 80%. This change was tested across one clinic initially then tested across two more clinics. Our balancing measure, the third available routine appointment, remained stable indicating that improving access to emergency patients did not affect the waiting time for routine appointments.

With good management of triage it is possible to improve access for urgent patients to be seen in clinic without impact on availability of routine appointments, resulting in better quality of care and patient satisfaction. Earlier appointments also improve clinic attendance rates.

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SWITCH: Al Wakra Hospital Journey to 90% Hand Hygiene Practice Compliance, 2011 - 2015

Hand Hygiene is the cheapest and simplest way to prevent the spread of infection, however international compliance is below than 40% (WHO, 2009). In the experience of Al Wakra Hospital, the improvement in hand hygiene compliance highlighted not just interventions towards training and education but also behavioral motivation and physical allocations of hand hygiene appliances and equipment.

Through motivating the behavioral, emotional, physical and intellectual dimensions of the different healthcare worker professions, hand hygiene compliance has increased from 60.78% in 2011 to 94.14% by the end of December 2015. It took 25 months of continuous and collaborative work with different healthcare workers to reach the 90% hand hygiene target.

"Together, we have reached our goals and together we fight against infections! Because we always strive for excellence in everything we do – that is our vision here in Al Wakra Hospital."

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Transitional care management in the outpatient setting

Patients who are high risk high cost (HRHC), those with severe or multiple medical issues, and the chronically ill elderly are major drivers of rising health care costs.1 The HRHC patients with complex health conditions and functional limitations may likely go to emergency rooms and hospitals, need more supportive services, and use long-term care facilities.2 As a result, these patient populations are vulnerable to fragmented care and "falling through the cracks".2 A large county health and hospital system in California, USA introduced evidence-based interventions in accordance with the Triple AIM3 focused on patient-centered health care, prevention, health maintenance, and safe transitions across the care continuum. The pilot program embedded a Transitional Care Manager (TCM) within an outpatient Family Medicine clinic to proactively assist HRHC patients with outreach assistance, problem-solving and facilitating smooth transitions of care. This initiative is supported by a collaborative team that included physicians, nurses, specialists, health educator, and pharmacist. The initial 50 patients showed a decrease in Emergency Department (ED) encounters (pre-vs post intervention: 33 vs 17) and hospital admissions (pre-vs post intervention: 32 vs 11), improved patient outcomes, and cost saving. As an example, one patient had 1 ED visit and 5 hospital admission with total charges of $217,355.75 in the 6 months' pre-intervention with no recurrence of ED or hospital admissions in the 6 months of TCM enrollment. The preliminary findings showed improvement of patient-centered outcomes, quality of care, and resource utilization however more data is required.

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Reducing returns to theatre for neck of femur fracture patients

The Royal United Hospital, Bath, admits approximately 550 patients with neck of femur fractures per year. The risks from returning to theatre for this patient group are often life-threatening. Post-operative wound ooze was noted to cause a significant rate of return to theatre, with increased lengths of stay and patient morbidity.

A wound closure protocol was agreed by the consultant body. This information was disseminated by email and teaching sessions to all members of the multidisciplinary team, including surgeons, theatre staff and ortho-geriatricians. The plan-do-study-act model for improvement was used to reduce rates of returns to theatre for wound ooze. Interventions included cyclical teaching during each trainee rotation, updated inductions, posters, email reminders and scrub team involvement to open the protocol sutures unprompted.

The primary outcome measure was returns to theatre for wound complications. Baseline data showed 4 returns to theatre over a two month period (4.40% of patients). Length of stay for each patient affected by wound ooze was also compared to the departmental mean. In the 6 month intervention period there was one return to theatre (0.36% of patients). The observed reduction saved the department an estimated £13,831 in length of stay alone.

The standardisation of wound closure protocol, with continued reinforcement to all members of the multidisciplinary team, improves patient outcome in this group. Mobilising a group of clinicians across a variety of specialities, with one common goal, is highly effective for patients, improves multidisciplinary working and reduces cost.

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Increasing Patient Safety Event Reporting in an Emergency Medicine Residency

Patient safety event reporting is an important component for fostering a culture of safety. Our tertiary care hospital utilizes a computerized patient safety event reporting system that has been historically underutilized by residents and faculty, despite encouragement of its use. The objective of this quality project was to increase patient safety event reporting within our Emergency Medicine residency program. Knowledge of event reporting was evaluated with a survey. Eighteen residents and five faculty participated in a formal educational session on event reporting followed by feedback every two months on events reported and actions taken. The educational session included description of which events to report and the logistics of accessing the reporting system. Participants received a survey after the educational intervention to assess resident familiarity and comfort with using the system. The total number of events reported was obtained before and after the educational session. After the educational session, residents reported being more confident in knowing what to report as a patient safety event, knowing how to report events, how to access the reporting tool, and how to enter a patient safety event. In the 14 months preceding the educational session, an average of 0.4 events were reported per month from the residency. In the nine months following the educational session, an average of 3.7 events were reported per month by the residency. In addition, the reported events resulted in meaningful actions taken by the hospital to improve patient safety, which were shared with the residents. Improvement efforts including an educational session, feedback to the residency of events reported, and communication of improvements resulting from reported events successfully increased the frequency of safety event reporting in an Emergency Medicine residency.

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The Value of a Surgical Assessment Unit Ultrasound Facility

Ultrasound scan (USS) is a common and important mode of investigation for emergency surgical admissions. Delay in investigation often leads to delayed diagnosis and treatment, and possible extended length of stay (LOS), which has clinical, cost and service provision implications. We aim to investigate the clinical impact on patient care and the cost-effectiveness of a pilot Surgical Assessment Unit (SAU) USS facility. We performed a retrospective data collection on 100 consecutive SAU inpatients who had an USS investigation on the ward since the introduction of the facility, matched by 100 consecutive SAU inpatients who had an USS in the radiology department before the pilot study. Results of the audit show SAU USS has a reduced mean LOS by 1.44 days compared to departmental USS, and led to more same day discharge than departmental USS (20 vs. 5), thus avoiding unnecessary overnight stay. It also significantly reduced mean waiting time from admission to investigation by 5.21 hours, which can be translated into improved patient and staff satisfaction. All these findings are both statistically and clinically significant. The estimated cost of each SAU USS is comparable to the average departmental USS (£29.71 vs. £30.80). Using the average cost of an excess bed day = £273, SAU USS has produced an estimated saving of £394.72/patient. This does not include saved opportunistic costs such as prevented elective operation cancellations, fines incurred from surgery waiting time/A+E breaches etc. To conclude SAU USS has a significant positive impact on patient care in surgical admissions by reducing LOS and investigation waiting time, as well as facilitating same day discharge.

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Exploring contacts of eRF1 with the 3′-terminus of the P site tRNA and mRNA stop signal in the human ribosome at various translation termination steps

Publication date: Available online 27 April 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Konstantin N. Bulygin, Dmitri M. Graifer, Codjo Hountondji, Ludmila Yu Frolova, Galina G. Karpova
Here we employed site-directed cross-linking with the application of tRNA and mRNA analogues bearing an oxidized ribose at the 3′-terminus to investigate mutual arrangement of the main components of translation termination complexes formed on the human 80S ribosome bound with P site deacylated tRNA using eRF1•eRF3•GTP or eRF1 alone. In addition, we applied a model complex obtained in the same way with eRF1•eRF3•GMPPNP. We found that eRF3 content in the complexes with GTP and GMPPNP is similar, proving that eRF3 does not leave the ribosome after GTP hydrolysis. Our cross-linking data allowed determining locations of the 3′-terminus of the P site tRNA relatively the eRF1 M domain and of the mRNA stop signal toward the N domain and the ribosomal decoding site at the nucleotide-peptide resolution level. Our results indicate that locations of these components do not change after peptide release up to post-termination pre-recycling state, and the positioning of the mRNA stop signal remains similar to that when eRF1 recognizes it. Besides, we found that in all the complexes studied eRF1 shielded the N-terminal part of ribosomal protein eS30 from the interaction with the nucleotide adjacent to stop codon observed with pre-termination ribosome free of eRFs. Altogether, our findings brought important information on contacts of the key structural elements of eRF1, tRNA and mRNA in the ribosomal complexes including those mimicking different translation termination steps, thereby providing a deeper understanding of molecular mechanisms underlying events occurring in the course of protein synthesis termination in mammals.



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UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST)

Abstract

Background

Soft tissue sarcomas (STS) are rare tumours arising in mesenchymal tissues. Gastrointestinal stromal tumour (GIST) is the commonest STS and arises within the wall of the gastrointestinal (GI) tract. While most GISTs occur in the stomach they do occur in all parts of the GI tract. As with other STS, it is important that GISTs are managed by expert teams, to ensure consistent and optimal treatment, as well as recruitment to clinical trials, and the ongoing accumulation of further knowledge of the disease. The development of appropriate guidance, by an experienced panel referring to the evidence available, is therefore a useful foundation on which to build progress in the field.

Methodology

British Sarcoma Group guidelines for the management of GIST were initially developed by a panel of physicians experienced in the management of GIST. This current version has been updated and amended with reference to other European and US guidance. We have received input from representatives of all diagnostic and treatment disciplines as well as patient representatives. Levels of evidence and strength of recommendation gradings are those used by ESMO adapted from those published by the Infectious Disease Society of America.

Conclusions

The guidelines cover aetiology, genetics and underlying molecular mechanisms, diagnosis and initial investigations, staging and risk stratification, surgery, neoadjuvant and adjuvant therapy, the management of advanced disease and follow-up. The importance of mutational analysis in guiding treatment is highlighted, since this can indicate the most effective treatment and avoid administration of ineffective drugs, emphasising the need for management in specialist centres.

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Skating on thin ice: The thawing Arctic threatens an environmental catastrophe

Print section Print Rubric:  Efforts to limit global warming will not stop the Arctic melting Print Headline:  Skating on thin ice Print Fly Title:  The Arctic UK Only Article:  standard article Issue:  How to have a better death Fly Title:  Skating on thin ice Location:  KIRKENES, TROMSO and WASHINGTON, DC Main image:  20170429_FBP001_0.jpg “DUE to the global warming, please keep the Snowhotel door closed” reads a sign at the entrance to what appears to be a giant white mound near Kirkenes, close to Norway’s Arctic border with Russia. The owners want to preserve the frozen friezes of unicorns, reindeer and butterflies that adorn its walls. Patches of translucence in the ceilings of the hotel’s 25 icy rooms suggest the warmth outside is winning. Artificial snow helps build the structure anew each ...

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A thaw point: As the Arctic melts the world’s weather suffers

Print section Print Rubric:  As the Arctic melts the rest of the world suffers Print Headline:  A thaw point Print Fly Title:  Sea levels and storms UK Only Article:  standard article Issue:  How to have a better death Fly Title:  A thaw point SHRINKING Arctic ice is sure to have unwelcome effects elsewhere on the planet. But what, precisely? Glaciologists and meteorologists are working furiously to understand two particularly complex issues that may cause huge upheavals: the stability of the Greenland ice sheet and its potential contribution to rising sea levels; and extreme weather elsewhere in the world that might result from the demise of the Arctic’s white wastes. Since the 1970s the Arctic has been the main cause of rising sea levels around the world. Over two-thirds of the Arctic’s contribution derives from ice loss from Greenland, according to the latest SWIPA report. But little is known about how Greenland’s vast ice sheet ...

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Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma [Research]

Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons, Cav-1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav-1 overexpression can preserve motor and cognitive function in the brain trauma setting is unknown. Here, we generated a neuron-targeted Cav-1–overexpressing transgenic (Tg) mouse [synapsin-driven Cav-1 (SynCav1 Tg)] and subjected it to a controlled cortical impact model of brain trauma and measured biochemical, anatomic, and behavioral changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav-1 and membrane/lipid raft localization of postsynaptic density protein 95, NMDA receptor, and tropomyosin receptor kinase B. When subjected to a controlled cortical impact, SynCav1 Tg mice demonstrated preserved hippocampal-dependent fear learning and memory, improved motor function recovery, and decreased brain lesion volume compared with wild-type controls. Neuron-targeted overexpression of Cav-1 in the adult brain prevents hippocampal-dependent learning and memory deficits, restores motor function after brain trauma, and decreases brain lesion size induced by trauma. Our findings demonstrate that neuron-targeted Cav-1 can be used as a novel therapeutic strategy to restore brain function and prevent trauma-associated maladaptive plasticity.—Egawa, J., Schilling, J. M., Cui, W., Posadas, E., Sawada, A., Alas, B., Zemljic-Harpf, A. E., Fannon-Pavlich, M. J., Mandyam, C. D., Roth, D. M., Patel, H. H., Patel, P. M., Head, B. P. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma.

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Reactive Oxygen Species Production Induced by Pore Opening in Cardiac Mitochondria: The Role of Complex II [Bioenergetics]

Succinate-driven reverse electron transport (RET) through complex I is hypothesized be a major source of ROS that induce permeability transition pore (PTP) opening and damage the heart during ischemia/reperfusion. Since RET can only generate ROS when mitochondria are fully polarized, however, this mechanism is self-limiting once PTP open during reperfusion. In the companion manuscript, we showed that ROS production after PTP opening can be sustained when complex III is damaged (simulated by antimycin). Here we show that complex II can also contribute to sustained ROS production in isolated rabbit cardiac mitochondria following inner membrane pore formation induced by either alamethicin or Ca-induced PTP opening. Two conditions are required to maximize malonate-sensitive ROS production by complex II in isolated mitochondria: a) complex II inhibition by atpenin A5 or complex III inhibition by stigmatellin that results in succinate-dependent reduction of the dicarboxylate binding site of complex II (site IIf ); b) pore opening in the inner membrane resulting in rapid efflux of succinate/fumarate and other dicarboxylates capable of competitively binding to site IIf. The decrease in matrix [dicarboxylates] allows O2 access to reduced site IIf, thereby making electron donation to O2 possible, explaining the rapid increase in ROS production provided that site IIf is reduced. Because ischemia is known to inhibit complexes II and III and increase matrix succinate/fumarate levels, we hypothesize that by allowing dicarboxylate efflux from the matrix, PTP opening during reperfusion may activate sustained ROS production by this mechanism after RET-driven ROS production has ceased.

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Immunoglobulin domain interface exchange as a platform technology for the generation of Fc heterodimers and bispecific antibodies [Protein Structure and Folding]

Bispecific antibodies (bsAbs) are of significant importance to the development of novel antibody-based therapies, and heavy chain (Hc) heterodimers represent a major class of bispecific drug candidates. Current technologies for the generation of Hc heterodimers are suboptimal and often suffer from contamination by homodimers posing purification challenges. Here, we introduce a new technology based on biomimicry wherein the protein-protein interfaces of two different immunoglobulin (Ig) constant domain pairs are exchanged in part or fully to design new heterodimeric domains. The method can be applied across Igs to design Fc heterodimers and bsAbs. We investigated interfaces from human IgA CH3, IgD CH3, IgG1 CH3, IgM CH4, T-cell receptor (TCR) α/β, and TCR γ/δ constant domain pairs and found that they successfully drive human IgG1 CH3 or IgM CH4 heterodimerization to levels similar to or above those of reference methods. A comprehensive interface exchange between the TCR α/β constant domain pair and the IgG1 CH3 homodimer was evidenced by x-ray crystallography and used to engineer examples of bsAbs for cancer therapy. Parental antibody pairs were rapidly reformatted into scalable bsAbs which were free of homodimer traces by combining interface exchange, asymmetric Protein A binding, and the scFv x Fab format. In summary, we successfully built several new CH3- or CH4-based heterodimers which may prove useful for designing new bsAb-based therapeutics and anticipate that our approach could be broadly implemented across the Ig constant domain family. To our knowledge, CH4-based heterodimers have not been previously reported.

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O-Linked N-acetylglucosamine transferase 1 regulates global histone H4 acetylation via stabilization of the non-specific lethal protein NSL3 [Enzymology]

The human MOF-containing histone acetyltransferase (HAT) NSL (non-specific lethal) complex comprises 9 subunits including the O-linked N-acetylglucosamine (O-GlcNAc) transferase (isoform 1) (OGT1). However, whether O-GlcNAc transferase activity of OGT1 controls HAT activity of the NSL complex and whether OGT1 physically interacts with the other NSL complex subunits remains unclear. Here, we demonstrate that OGT1 regulates the activity of the NSL complex by mainly acetylating histone H4K16, K5, and K8 via O-GlcNAcylation and stabilization of the NSL complex subunit NSL3. Knocking down or overexpressing OGT1 in human cells remarkably affected the global acetylation of histone H4 residues K16, K5, and K8. Because OGT1 is a subunit of the NSL complex, we also investigated the function of OGT1 in this complex. Co-transfection/co-immunoprecipitation experiments combined with in vitro O-GlcNAc transferase assays confirmed that OGT1 specifically binds to and O-GlcNAcylates NSL3. In addition, WGA-affinity purification clarified the occurrence of O-GlcNAc modification on NSL3 in cells. Moreover, O-GlcNAcylation of NSL3 by wild type OGT1 (OGT1wt) stabilized NSL3. This stabilization was lost after co-transfection of NSL3 with an OGT1 mutant, OGT1C964A that lacks O-GlcNAc transferase activity. Furthermore, stabilization of NSL3 by OGT1wt significantly increased the global acetylation levels of H4K5, K8, and K16 in cells. These results suggest that OGT1 regulates the activity of the NSL complex by stabilizing NSL3.

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Reactive Oxygen Species Production Induced by Pore Opening in Cardiac Mitochondria: The Role of Complex III [Bioenergetics]

Recent evidence has implicated succinate-driven reverse electron transport (RET) through complex I as a major source of damaging reactive oxygen species (ROS) underlying reperfusion injury after prolonged cardiac ischemia. However, this explanation may be incomplete, because RET on reperfusion is self-limiting and therefore transient. RET can only generate ROS when mitochondria are well-polarized, and ceases when permeability transition pores (PTP) open during reperfusion. Since prolonged I/R also damages electron transport complexes, we investigated whether such damage could lead to ROS production after PTP opening has occurred. Using isolated cardiac mitochondria, we demonstrate a novel mechanism by which antimycin-inhibited complex III generates significant amounts of ROS in the presence of Mg2+ and NAD+ and the absence of exogenous substrates upon inner membrane pore formation by alamethicin or Ca2+-induced PTP opening. We show that H2O2 production under these conditions is related to Mg2+-dependent NADH generation by malic enzyme. H2O2 production is blocked by stigmatellin, indicating its origin from complex III, and by piericidin, demonstrating importance of NADH-related ubiquinone reduction for ROS production under these conditions. For maximal ROS production, the rate of NADH generation has to be equal or below that of NADH oxidation, as further increases in [NADH] elevate ubiquinol-related complex III reduction beyond the optimal range for ROS generation. These results suggest that if complex III is damaged during ischemia, PTP opening may result in succinate/malate-fueled ROS production from complex III due to activation of malic enzyme by increases in matrix [Mg2+], [NAD+] and [ADP].

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The Crystal Structure of Mammalian Inositol 1,3,4,5,6-Pentakisphosphate 2-Kinase Reveals a New Zinc Binding Site and Key Features for Protein Function [Signal Transduction]

Inositol 1,3,4,5,6-pentakisphosphate 2-kinases (IP5 2-Ks) comprise a family of enzymes in charge of synthesizing inositol hexakisphosphate (IP6) in eukaryotic cells. This protein and its product IP6 present many roles in cells, participating in mRNA export, embryonic development, and apoptosis. We reported previously that the full-length IP5 2-K from Arabidopsis thaliana (At) is a zinc metallo-enzyme including two separated lobes (the N and C lobes). We have also shown conformational changes in IP5 2-K and have identified the residues involved in substrate recognition and catalysis. However, the specific features of mammalian IP5 2-Ks remain unknown. To this end, we report here the first structure for a murine IP5 2-K in complex with ATP/IP5 or IP6. Our structural findings indicated that the general folding in N and C lobes is conserved with AtIP5 2-K. A helical scaffold in the C lobe constitutes the inositol phosphate (IP)-binding site, which, along with the participation of the N lobe, endows high specificity to this protein. However, we also noted large structural differences between the orthologous from these two eukaryotic kingdoms. These differences include a novel zinc-binding site and regions unique to the mammalian IP5 2-K, as an unexpected basic patch on the protein surface. In conclusion, our findings have uncovered distinct features of a mammalian IP5 2-K and set the stage for investigations into protein-protein or protein-RNA interactions important for IP5 2-K function and activity.

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Heat shock protein 90 (Hsp90) promotes opioid-induced anti-nociception by an ERK Mitogen Activated Protein Kinase (MAPK) mechanism in mouse brain [Neurobiology]

Recent advances in developing opioid treatments for pain with reduced side effects have focused on the signaling cascades of the mu opioid receptor (MOR). However, few such signaling targets have been identified for exploitation. To address this need, we explored the role of Heat shock protein 90 (Hsp90) in opioid-induced MOR signaling and pain, which has only been studied in 4 previous papers. First, in 4 cell models of MOR signaling, we found that Hsp90 inhibition for 24 hours with the inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) had different effects on protein expression and opioid signaling in each line, suggesting that cell models may not be reliable for predicting pharmacology with this protein. We thus developed an in vivo model using CD-1 mice with intracerebroventricular (icv) injection of 17-AAG for 24 hours. We found that Hsp90 inhibition strongly blocked morphine-induced anti-nociception in models of post-surgical and HIV neuropathic pain, but only slightly blocked anti-nociception in a naïve tail flick model, while enhancing morphine-induced precipitated withdrawal. Seeking a mechanism for these changes, we found that Hsp90 inhibition blocks ERK MAPK activation in the periaqueductal grey (PAG) and caudal brain stem. We tested these signaling changes by inhibiting ERK in the above pain models, and found that ERK inhibition could account for all of the changes in anti-nociception induced by Hsp90 inhibition. Taken together, these findings suggest that Hsp90 promotes opioid-induced anti-nociception by an ERK mechanism in mouse brain, and that Hsp90 could be a future target for improving the therapeutic index of opioid drugs.

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Skeletal overgrowth-causing mutations mimic an allosterically activated conformation of guanylyl cyclase-B that is inhibited by 2,4,6,-trinitrophenyl ATP [Signal Transduction]

Activating mutations in the receptor for C-type natriuretic peptide (CNP), guanylyl cyclase B (GC-B, also known as Npr2 or NPR-B), increase cellular cGMP and cause skeletal overgrowth, but how these mutations affect GTP catalysis is poorly understood. The A488P and R655C mutations were compared with the known mutation V883M. Neither mutation affected GC-B concentrations. The A488P mutation decreased the EC50 5-fold, increased Vmax 2.6-fold, and decreased the Km 13-fold, while the R655C mutation decreased the EC50 5-fold, increased the Vmax 2.1-fold, and decreased the Km 4.7-fold. Neither mutation affected maximum activity at saturating CNP concentrations. Activation by R655C did not require disulfide bond formation. Surprisingly, the A488P mutant only activated the receptor when it was phosphorylated. In contrast, the R655C mutation converted GC-B-7A from CNP unresponsive to CNP responsive. Interestingly, neither mutant was activated by ATP, and the Km and Hill coefficient of each mutant assayed in the absence of ATP were similar to those of wild-type GC-B assayed in the presence of ATP. Finally, 1 mM 2,4,6,-trinitrophenyl ATP inhibited all three mutants by as much as 80% but failed to inhibit WT-GC-B. We conclude that: 1) the A488P and R655C missense mutations result in a GC-B conformation that mimics the allosterically activated conformation, 2) GC-B phosphorylation is required for CNP-dependent activation by the A488P mutation, 3) the R655C mutation abrogates the need for phosphorylation in receptor activation, and 4) an ATP analog selectively inhibits the GC-B mutants, indicating that a pharmacologic approach could reduce GC-B dependent human skeletal overgrowth.

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G protein-coupled Estrogen Receptor 1 (GPER1)/GPR30 Increases ERK1/2 Activity Through PDZ-dependent and -independent Mechanisms [Signal Transduction]

G protein-coupled receptor 30 (GPR30), also called G protein-coupled estrogen receptor 1 (GPER1), is thought to play important roles in breast cancer and cardiometabolic regulation, but many questions remain about ligand activation, effector coupling, and subcellular localization. We showed recently that GPR30 interacts through the C-terminal type I PDZ motif with SAP97 and protein kinase A (PKA)-anchoring protein (AKAP) 5, which anchor the receptor in the plasma membrane and mediate an apparently constitutive decrease in cAMP production independently of Gi/o. Here, we show that GPR30 also constitutively increases ERK1/2 activity. Removing the receptor PDZ motif or knocking down specifically AKAP5 inhibited the increase, showing that this increase also requires the PDZ interaction. However, the increase was inhibited by pertussis toxin (PTX) as well as by wortmannin, but not by AG1478, indicating that Gi/o and phosphoinositide 3-kinase (PI3K) mediate the increase independently of epidermal growth factor receptor (EGFR) transactivation. FK506 and okadaic acid also inhibited the increase, implying that a protein phosphatase is involved. The proposed GPR30 agonist G-1 also increased ERK1/2 activity, but this increase was only observed at a level of receptor expression below that required for the constitutive increase. Furthermore, deleting the PDZ motif did not inhibit the G-1-stimulated increase. Based on these results, we propose that GPR30 increases ERK1/2 activity via two Gi/o-mediated mechanisms; a PDZ-dependent apparently constitutive mechanism, and a PDZ-independent G-1-stimulated mechanism.

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Binding of DEAD-box helicase Dhh1 to the 5'UTR of ASH1 mRNA represses localized translation of ASH1 in yeast cells [RNA]

Local translation of specific mRNAs is regulated by dynamic changes in their subcellular localization, and these changes are due to complex mechanisms controlling cytoplasmic mRNA transport. The budding yeast Saccharomyces cerevisiae is well suited to studying these mechanisms because many of its transcripts are transported from the mother cell to the budding daughter cell. Here, we investigated the translational control of ASH1 mRNA after transport and localization. We show that although ASH1 transcripts were translated after they reached the bud-tip, some mRNAs were bound by the RNA-binding protein Puf6 and were non-polysomal. We also found that the DEAD-box helicase Dhh1 complexed with the untranslated ASH1 mRNA and Puf6. Loss of Dhh1 affected local translation of ASH1 mRNA and resulted in delocalization of ASH1 transcript in the bud. Forcibly shifting the non-polysomal ASH1 mRNA into polysomes was associated with Dhh1 dissociation. We further demonstrated that Dhh1 is not recruited to ASH1 mRNA co-transcriptionally, suggesting that it could bind to ASH1 mRNA within the cytoplasm. Of note, Dhh1 bound to the 5 UTR of ASH1 mRNA and inhibited its translation in vitro. These results suggest that after localization to the bud tip, a portion of the localized ASH1 mRNA becomes translationally inactive, because of binding of Dhh1 and Puf6 to the 5' and 3' UTRs of ASH1 mRNA.

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The prognostic value of dynamic contrast-enhanced MRI contrast agent transfer constant Ktrans in cervical cancer is explained by plasma flow rather than vessel permeability

The prognostic value of dynamic contrast-enhanced MRI contrast agent transfer constant Ktrans in cervical cancer is explained by plasma flow rather than vessel permeability

British Journal of Cancer advance online publication, April 27 2017. doi:10.1038/bjc.2017.121

Authors: Ben R Dickie, Chris J Rose, Lucy E Kershaw, Stephanie B Withey, Bernadette M Carrington, Susan E Davidson, Gillian Hutchison & Catharine M L West

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Excess of a Rassf1-targeting microRNA, miR-193a-3p, perturbs cell division fidelity

Excess of a Rassf1-targeting microRNA, miR-193a-3p, perturbs cell division fidelity

British Journal of Cancer advance online publication, April 27 2017. doi:10.1038/bjc.2017.110

Authors: Sofia Pruikkonen & Marko J Kallio

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Extended RAS analysis and correlation with overall survival in advanced pancreatic cancer

Extended RAS analysis and correlation with overall survival in advanced pancreatic cancer

British Journal of Cancer advance online publication, April 27 2017. doi:10.1038/bjc.2017.115

Authors: Michael Haas, Steffen Ormanns, Sibylle Baechmann, Anna Remold, Stephan Kruger, Christoph B Westphalen, Jens T Siveke, Patrick Wenzel, Anna Melissa Schlitter, Irene Esposito, Detlef Quietzsch, Michael R Clemens, Erika Kettner, Ruediger P Laubender, Andreas Jung, Thomas Kirchner, Stefan Boeck & Volker Heinemann

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A meta-analysis comparing the risk of metastases in patients with rectal cancer and MRI-detected extramural vascular invasion (mrEMVI) vs mrEMVI-negative cases

A meta-analysis comparing the risk of metastases in patients with rectal cancer and MRI-detected extramural vascular invasion (mrEMVI) vs mrEMVI-negative cases

British Journal of Cancer advance online publication, April 27 2017. doi:10.1038/bjc.2017.99

Authors: Muhammed R S Siddiqui, Constantinos Simillis, Chris Hunter, Manish Chand, Jemma Bhoday, Aurelie Garant, Te Vuong, Giovanni Artho, Shahnawaz Rasheed, Paris Tekkis, Al-Mutaz Abulafi & Gina Brown

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Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study

Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study

British Journal of Cancer advance online publication, April 27 2017. doi:10.1038/bjc.2017.103

Authors: Luca Triggiani, Filippo Alongi, Michela Buglione, Beatrice Detti, Riccardo Santoni, Alessio Bruni, Ernesto Maranzano, Frank Lohr, Rolando D’Angelillo, Alessandro Magli, Alberto Bonetta, Rosario Mazzola, Nadia Pasinetti, Giulio Francolini, Gianluca Ingrosso, Fabio Trippa, Sergio Fersino, Paolo Borghetti, Paolo Ghirardelli & Stefano Maria Magrini

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Protein signature characterizing Helicobacter pylori strains of patients with autoimmune atrophic gastritis, duodenal ulcer and gastric cancer

Helicobacter pylori (H. pylori) represents a key factor in the etiology of autoimmune atrophic gastritis (AAG), duodenal ulcer (DU) and gastric cancer (GC). The aim of this study was t...

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Effects of Electrical Stimulation on Cell Proliferation and Apoptosis

Abstract

The application of exogenous electrical stimulation (ES) to cells in order to manipulate cell apoptosis and proliferation has been widely investigated as a possible method of treatment in a number of diseases. Alteration of the transmembrane potential of cells via ES can affect various intracellular signaling pathways which are involved in the regulation of cellular function. Controversially, several types of ES have proved to be effective in both inhibiting or inducing apoptosis, as well as increasing proliferation. However, the mechanisms through which ES achieves this remain fairly unclear. The aim of this review was to comprehensively summarize current findings from in vitro and in vivo studies on the effects of different types of ES on cell apoptosis and proliferation, highlighting the possible mechanisms through which ES induced these effects and define the optimum parameters at which ES can be used. Through this we hope to provide a greater insight into how future studies can most effectively use ES at the clinical trial stage. This article is protected by copyright. All rights reserved

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Mortality of Necrotising Fasciitis: relative influence of individual and hospital-level factors, a Nationwide Multi-Level Study, France, 2007-2012

Abstract

Background

Necrotising soft-tissue infections (NSTI) are rare, life-threatening conditions.

Objectives

We aimed to assess whether admitting hospital characteristics were associated with NSTI mortality.

Methods

We studied the French nationwide hospital discharge database (retrospective national cohort). All patients admitted in 2007-2012 with an ICD-10 code of necrotising fasciitis were eligible. We extracted data on the patients (age, sex, ICU admission, co-morbidities) and hospitals (public vs private proprietary; for public hospitals, teaching, yes/no; and number of NSTI admissions, ≥3 NSTI cases/year, yes/no). Multivariable analyses were performed to identify independent predictors of day-28 mortality and in-hospital mortality using mixed logistic regression and Cox proportional hazards models, respectively.

Results

We identified 1537 patients (915 males) with a median age of 60 (IQR, 48-75) years, admitted to 326 hospitals, public (82%) and admitting fewer than three NSTI cases/year (93%). Overall, 364 patients died (23·7%; 95%CI, 21·6-25·9). Patients treated in public teaching centres with ≥3NSTI cases annually had lower day-28 mortality (adjusted odds ratio [aOR], 0·68; 95%CI, 0·46-0·99; p=0·045) and in-hospital mortality rates than patients treated in local hospitals, even after adjusting for potentially relevant individual risk factors. No significant association was found between mortality and inter-hospital transfer.

Conclusions

Our finding highlighted an increased survival in teaching centres with high NSTI volume procedures. If confirmed in other settings, these findings reinforce the importance of expertise in early diagnosis and management of this condition.

This article is protected by copyright. All rights reserved.

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Duration and exclusiveness of breastfeeding and risk of childhood atopic diseases

Abstract

Background

Breastfeeding may have immune modulatory effects that influence the development of childhood allergic sensitization and atopic diseases. We aimed to examine the associations of breastfeeding with childhood allergic sensitization, inhalant or food allergy and eczema, and whether any association was affected by disease-related modification of the exposure or modified by maternal history of maternal history of allergy, eczema or asthma.

Methods

This study among 5,828 children was performed in a population-based prospective cohort from fetal life onwards. We collected information on duration (<2 months, 2-4 months, 4-6 months and ≥6 months) and exclusiveness (non-exclusive vs. exclusive for 4 months) of breastfeeding in infancy by postal questionnaires. At age 10 years, inhalant and food allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy by a postal questionnaire. Data on parental-reported eczema were available from birth until age 10 years.

Results

We observed no association of breastfeeding with any allergic sensitization, physician-diagnosed allergy, or combination of these outcomes. Shorter breastfeeding duration was associated with an overall increased risk of eczema (p-value for trend <0.05). Non-exclusively breastfed children had an overall increased risk of eczema (aOR (95% CI): 1.11 (1.01, 1.23)), compared with children exclusively breastfed for 4 months. Risk period-specific sensitivity analyses, additional adjustment for ointment use for eczema at age 2 months, and cross-lagged modeling showed no consistent results for disease-related modification of the exposure. Results were not modified by maternal history of allergy, eczema or asthma (lowest p-value for interaction =0.13).

Conclusions

Shorter duration or non-exclusiveness of breastfeeding is associated with a weak overall increased risk of eczema but not allergic sensitization or physician-diagnosed allergy at age 10 years

This article is protected by copyright. All rights reserved.

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Patterns of care and predictors of adjuvant therapies in elderly patients with glioblastoma: An analysis of the National Cancer Database

BACKGROUND

The objectives of this study were to characterize patterns of care and to identify predictors for adjuvant therapy in elderly patients with glioblastoma in the modern era.

METHODS. The National Cancer Database was queried for patients aged 70 years and older with glioblastoma diagnosed from January 1, 2004 through December 31, 2012. Multinomial logistic regression was used to identify predictors for receiving adjuvant therapy. Survival outcomes were estimated using the Kaplan-Meier method and were analyzed using Cox regression models and the log-rank test.

RESULTS

In total, 14,886 patients were identified. Of these, 8214 patients (55.2%) received combined-modality therapy with chemotherapy and radiation (CRT), 3955 (26.6%) received no adjuvant therapy, 2065 (13.9%) received radiation therapy (RT) alone, and 652 (4.4%) received chemotherapy (CT) alone after undergoing resection. The receipt of CRT increased in frequency over the study interval, from 40.3% in 2004 to 59.8% in 2012. Younger patients (ages 70-75 years) were more likely to receive CRT than no adjuvant therapy (P < .0001 for all other age groups) or adjuvant RT alone (P < .0001 for all other age groups). Combined-modality therapy with adjuvant CRT produced improved survival outcomes, and the highest median overall survival was 9.2 months.

CONCLUSIONS

In this analysis of elderly patients who had glioblastoma diagnosed from 2004 through 2012, a significant increase in the receipt of combined-modality therapy was observed. Combined-modality treatment produces improved survival outcomes and should be considered as adjuvant treatment for carefully selected elderly patients. Cancer 2017. © 2017 American Cancer Society.

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Impact of sleep, fatigue, and systemic inflammation on neurocognitive and behavioral outcomes in long-term survivors of childhood acute lymphoblastic leukemia

BACKGROUND

Long-term survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive impairment, which may be associated with fatigue, sleep problems, systemic inflammation, and oxidative stress. We examined these associations among survivors of childhood ALL treated with chemotherapy only.

METHODS

Survivors of childhood ALL (male, n = 35 and female, n = 35; mean age, 14.3 years [standard deviation, 4.7 years] and mean years from diagnosis, 7.4 years [standard deviation, 1.9 years]) completed neurocognitive testing, behavioral ratings, and reported sleep quality and fatigue symptoms 5 years after diagnosis. Serum was collected concurrently and assayed for interleukin (IL)-1β and IL-6, tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hsCRP), malondialdehyde, myeloperoxidase, and oxidized low-density lipoprotein. General linear modeling was used to assess associations among biomarkers and functional outcomes, adjusting for age and stratified by sex.

RESULTS

Survivors performed worse than population norms on executive function and processing speed and reported more behavioral problems (P < .05 adjusted for multiple comparison). In female survivors, fatigue was associated with poor executive function (r = 0.41; P = .02), processing speed (r = 0.56; P < .001), and attention (r = 0.36-0.55; P < .05). Female survivors with frequent nighttime awakening displayed more inattention (P = .01), hyperactivity (P = .03), and aggression (P = .01). Worse executive function, processing speed, and behavioral symptoms were observed in female survivors with higher levels of IL-6, IL-1β, and hsCRP (P < .05). Male survivors with high levels of TNF-α demonstrated worse organization (P = .03), but no significant associations between neurocognitive outcomes and sleep/fatigue measures were observed.

CONCLUSION

Neurocognitive function in female survivors of childhood ALL appears more susceptible to the effects of sleep disturbance and fatigue. Systemic inflammation may play a role in neurocognitive impairment and behavioral symptoms. Cancer 2017. © 2017 American Cancer Society.

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Comparing outcomes of matched related donor and matched unrelated donor hematopoietic cell transplants in adults with B-Cell acute lymphoblastic leukemia

BACKGROUND

Allogeneic hematopoietic cell transplantation (HCT) using human leukocyte antigen (HLA)–matched related donors (RDs) and allogeneic HCT using HLA-matched unrelated donors (URDs) produce similar outcomes for patients with acute myelogenous leukemia, whereas the donor source has been reported to be a predictor of outcomes in myelodysplastic syndrome.

METHODS

Post-HCT outcomes for 1458 acute lymphoblastic leukemia patients from 2000 to 2011 were analyzed, and RD and URD transplants were compared.

RESULTS

The median age was 37 years (range, 18-69 years). In the multivariate analysis, HLA 8/8 allele–matched URD recipients had similar transplant-related mortality (TRM) and all-cause mortality in comparison with RD recipients (hazard ratios [HRs], 1.16 [95% confidence interval (CI), 0.91-1.48] and 1.01 [95% CI, 0.85-1.19], respectively); 7/8 URD recipients had a greater risk of TRM and all-cause mortality in comparison with RD recipients (HRs, 1.92 [95% CI, 1.47-2.52] and 1.29 [95% CI, 1.05-1.58], respectively). The risk of TRM and all-cause mortality was also greater for 7/8 URD recipients versus 8/8 URD recipients. Compared with RD recipients, both 8/8 and 7/8 URD recipients had a lower risk of relapse (HRs, 0.77 [95% CI, 0.62-0.97] and 0.75 [95% CI, 0.56-1.00], respectively). Both 8/8 and 7/8 URD recipients had a greater risk of acute graft-versus-host disease (GVHD; HRs, 2.18 [95% CI, 1.76-2.70] and 2.65 [95% CI, 2.06-3.42], respectively) and chronic GVHD (HRs, 1.28 [95% CI, 1.06-1.55] and 1.46 [95% CI, 1.14-1.88], respectively) in comparison with RD recipients.

CONCLUSIONS

In the absence of RD transplantation, 8/8 URD transplantation is a viable alternative with similar survival outcomes, whereas 7/8 URD transplantation is associated with poorer overall survival. Cancer 2017. © 2017 American Cancer Society.

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Science, Innovation and the Future of Humanity

J Mol Microbiol Biotechnol 2017;27:128-132

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Purification and Biochemical and Kinetic Properties of an Endo-Polygalacturonase from the Industrial Fungus Aspergillus sojae

An endo-polygalacturonase secreted by Aspergillus sojae was characterized after being purified to homogeneity from submerged cultures with orange peel as the sole carbon source by gel filtration and ion-exchange chromatographies. According to SDS-PAGE and analytical isoelectric focusing analyses, the enzyme presents a molecular weight of 47 kDa and pI value of 4.2. This enzyme exhibits considerable stability under highly acidic to neutral conditions (pH 1.5-6.5) and presents a half-life of 2 h at 50°C. Besides its activity towards pectin and polygalacturonic acid, the enzyme displays pectin-releasing activity, acting best in a pH range of 3.3-5.0. Thin-layer chromatographic analysis revealed that tri-galacturonate is the main enzymatic end product of polygalacturonic acid hydrolysis, indicating that it is an endo-polygalacturonase. The enzyme exhibits Michaelis-Menten kinetics, with K_M and V_MAX values of 0.134 mg/mL and 9.6 µmol/mg/min, respectively, and remained stable and active in the presence of SO₂, ethanol, and various cations assayed except Hg²⁺.
J Mol Microbiol Biotechnol 2017;27:102-109

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Synthetic, Switchable Enzymes

The construction of switchable, radiation-controlled, aptameric enzymes - “swenzymes” - is, in principle, feasible. We propose a strategy to make such catalysts from 2 (or more) aptamers each selected to bind specifically to one of the substrates in, for example, a 2-substrate reaction. Construction of a combinatorial library of candidate swenzymes entails selecting a set of a million aptamers that bind one substrate and a second set of a million aptamers that bind the second substrate; the aptamers in these sets are then linked pairwise by a linker, thus bringing together the substrates. In the presence of the substrates, some linked aptamer pairs catalyze the reaction when exposed to external energy in the form of a specific frequency of low-intensity, nonionizing electromagnetic or acoustic radiation. Such swenzymes are detected via a separate product-capturing aptamer that changes conformation on capturing the product; this altered conformation allows it (1) to bind to every potential swenzyme in its vicinity (thereby giving a higher probability of capture to the swenzymes that generate the product) and (2) to bind to a sequence on a magnetic bead (thereby permitting purification of the swenzyme plus product-capturing aptamer by precipitation). Attempts to implement the swenzyme strategy may help elucidate fundamental problems in enzyme catalysis.
J Mol Microbiol Biotechnol 2017;27:117-127

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Serum phosphorus levels and fracture following renal transplantation

Abstract

Purpose

Increased fracture rates are observed in renal transplant recipients (RTRs) compared with the general population. Risk factors include age, diabetes, dialysis vintage, immunosuppression, and mineral and bone disorders(1). Low serum phosphorus levels occur post-transplantation; however its relationship with fracture risk has not been evaluated. The purpose of this study was to evaluate risk factors for fracture in RTRs at a single tertiary referral centre.

Methods

A retrospective cross-sectional analysis of 146 patients (75M, 71F) who had been referred for dual energy x-ray densitometry (DXA) post-renal transplantation was performed. Aetiology of end stage kidney disease (ESKD), duration of dialysis, parathyroidectomy history, immunosuppression regimen, bone mineral density (BMD), biochemistry and fractures were documented. Statistical analyses included univariable and multivariable regression.

Results

The mean age of patients was 54 years and mean time post-transplantation 6.7 years. 79 fractures occurred in 52 patients (35%), with 40 fractures occurring post-transplantation. Ankle/foot fractures were most common (48%). Lower serum phosphorus levels and declining FN T-score and were associated with fractures in both univariable and multivariable regression analyses after adjusting for age, gender, weight, eGFR and pre-transplant history of fracture (p=0.011 and p=0.042 respectively). The relationship between serum phosphorus and fracture remained significant independent of FN T-score, parathyroid hormone levels, parathyroidectomy status and prednisolone use.

Conclusion

Fracture was common post-renal transplantation. Lower serum phosphorus levels and declining FN T-scores were associated with fractures. The mechanism of this previously unreported observation requires further evaluation in prospective studies.

This article is protected by copyright. All rights reserved.

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Cancer Drug Fund didn’t deliver value ‘to patients or society’

A fund that spent more than £1 billion on expensive new cancer drugs in England had little clinical benefit, a study of 29 medicines has concluded

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Cancer Drug Fund didn’t deliver value ‘to patients or society’

A fund that spent more than £1 billion on expensive new cancer drugs in England had little clinical benefit, a study of 29 medicines has concluded

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The impact of mood on empathy for pain: Evidence from an EEG study

Abstract

The current work investigated whether the neural correlates of empathy for pain are altered by mood valence of observers. Following mood induction, participants watched pictures representing painful or nonpainful situations. We used EEG to record neural activity and assessed event-related desynchronization at central sites during pain observation. Greater mu desynchronization was observed during painful relative to nonpainful situations in positive and neutral mood but not in negative mood. We also found that the pain empathy effect, indexed by mu suppression differences between painful and nonpainful conditions, was smaller in negative than in neutral and positive mood, while this effect was similar between neutral and positive mood. The current study demonstrates that observers' mood states influence the motoric component of empathy for pain, and specifically the negative mood suppresses the motoric empathic resonance for others' pain.

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Metabolite Profile and Antiproliferative Effects in HaCaT Cells of a Salix reticulata Extract

Planta Med
DOI: 10.1055/s-0043-109098

Phenolic constituents of Salix reticulata (Salicaceae) and antiproliferative activity of an extract and individual compounds were investigated in immortalized human non-tumorigenic keratinocytes (HaCaT). A MeOH extract from aerial parts afforded several flavonoids, including luteolin and apigenin glycosides (2–5 and 9) and catechin (1), two procyanidin fractions, and the phenolic glucosides picein (6), triandrin (7), and salicortin (8). In an adenosine triphosphate assay, the MeOH extract reduced cell viability by approximately 60 % at a concentration of 100 µg/mL. Cell proliferation was assessed with a BrdU incorporation ELISA assay. The extract inhibited proliferation of HaCaT cells in a concentration-dependent manner, with approximately 50 % inhibition at 100 µg/mL. In time-lapse assays, the extract showed distinct inhibitory effects on cell migration at concentrations of 12.5, 25, and 50 µg/mL. The activity of selected constituents was also determined. Luteolin-7-O-β-glucuronide (3) significantly inhibited cell proliferation at concentrations of 10 and 50 µM. In contrast, luteolin-7-O-β-glucopyranoside (2) and a procyanidin fraction (P1) had only weak effects, while picein (6) and salicortin (8) did not affect cell proliferation. Luteolin-7-O-β-glucuronide (10 µM) and, to a lesser extent, the procyanidin fraction (10 µg/mL) also inhibited cell migration.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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miR-130A as a diagnostic marker to differentiate malignant mesothelioma from lung adenocarcinoma in pleural effusion cytology

BACKGROUND

Malignant pleural mesothelioma is a rare tumor with a dismal prognosis, usually presenting with recurrent effusions. However, the majority of malignant pleural effusions are due to lung adenocarcinoma (AdC). The distinction between these tumors has considerable therapeutic and medicolegal implications and can be very challenging both histologically and cytologically. Appropriate immunohistochemistry (IHC) is required to support the diagnosis. MicroRNA (miRNA) expression analysis could be a viable diagnostic tool for distinguishing between these tumors. The purpose of the current study was to assess the reliability of miRNAs as diagnostic markers to differentiate epithelioid malignant mesothelioma (MM) from lung AdC.

METHODS

Bioinformatic analysis of publicly searchable data sets regarding miRNA expression profiling was performed to select the most significant differentially expressed miRNAs. These were analyzed by quantitative polymerase chain reaction on histologic (41 MM cases and 40 lung AdC cases) and cytological (26 MM cases and 27 lung AdC cases) specimens and the diagnostic performances were assessed.

RESULTS

miR-130a, miR-193a, miR-675, miR-141, miR-205, and miR-375 were found to be the best distinguishing markers. Of these, only miR-130a was significantly overexpressed in MM compared with lung AdC (P =.029 in histologic and P =.014 in cytological samples). miR-130a demonstrated a sensitivity of 77%, a specificity of 67%, a positive predictive value of 69%, a negative predictive value of 75%, and an accuracy of 72% in identifying MM.

CONCLUSIONS

The diagnostic performances of miR-130a expression analysis and IHC appear to be similar. miR-130a quantification could be used reliably as second-level diagnostic tool to differentiate MM from lung AdC in pleural effusion cytology, mainly in those cases with ambiguous or negative IHC. Further validation is needed. Cancer Cytopathol 2017. © 2017 American Cancer Society.

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The prevalence and course of preinvasive cervical lesions during pregnancy in a Northern Nigerian Teaching Hospital

Fadimatu Bakari, Muhammad A Abdul, Saad A Ahmed

Annals of African Medicine 2017 16(2):74-80

Background: In spite of knowledge of the causes and prevention of cervical cancer, screening programs for cervical cancer have not yet been fully implemented in most developing countries including Nigeria. Documented data on the prevalence of preinvasive cervical lesion in pregnancy are scarce in our environment. Objectives: To determine the prevalence, risk factors, and course of preinvasive cervical lesion in pregnant women attending an antenatal clinic in Ahmadu Bello University Teaching Hospital (ABUTH) Zaria, Northern Nigeria Study Design: This was a cross-sectional longitudinal study. Setting: The study was conducted in an antenatal clinic of ABUTH Zaria. Materials and Methods: A prospective cross-sectional longitudinal analysis was carried out at an Antenatal Clinic of ABUTH Zaria, Nigeria. A total of 250 consecutive pregnant women who fulfilled the inclusion criteria and have given their consent were recruited into the study at the time of their first prenatal (booking clinic) visit for antenatal care. Data from the pregnant women were obtained using a pro forma to evaluate sociodemographic characteristics and risk factors for preinvasive disease. Conventional Papanicolaou smear was taken using the standard procedure. The cytopathologic findings of initial and postpartum Pap smear were documented in the pro forma. Prevalence, persistence, progression, and regression rates of preinvasive diseases were determined. Results: Out of the 250 pregnant women who had cervical cytology by Pap smear during the study, 15 had preinvasive cervical lesion, giving a prevalence rate of 6%; 13 (87%) were low-grade squamous intraepithelial lesion (LGSIL) while 2 (13%) were high-grade squamous intraepithelial lesion (HGSIL). Negative smears were seen in 158 women (63.2%). Inflammatory and other conditions of the cervix which are technically negative smears made up the remaining 30.8%. At postpartum follow-up of the 13 women with LGSIL, 2 (15.4%) became negative while persistence of the disease was observed in 9 (69.2%) of the cases. Two women with LGSIL were lost to follow-up. Of the two women with HGSIL, persistence of the disease was seen in one woman (50%) and regression of the disease was seen in the other woman. Risk factors that were found to be associated with preinvasive cervical lesion were age at coitarche <16 years, number of sexual partners since coitarche, and previous history of sexually transmitted infection and human immunodeficiency virus. Parity, smoking, and use of contraception were found not to be significant risk factors. Conclusion: Preinvasive lesion of the cervix is relatively common among antenatal clients in our center. Antenatal clients with HGSIL should have a repeat smear at the end of the puerperium before treatment. Routine Pap smear should be offered to all antenatal clients in our setting.

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The cell biology and role of resorptive cells in diseases: A review

Prashant Babaji, Raghu Devanna, Kiran Jagtap, Vishwajit Rampratap Chaurasia, Jeethu John Jerry, Basanta Kumar Choudhury, Dinesh Duhan

Annals of African Medicine 2017 16(2):39-45

Resorptive cells are responsible for the resorption of mineralized matrix of hard tissues. Bone-resorbing cells are called osteoclasts; however, they can resorb mineralized dental tissues or calcified cartilage and then they are called odontoclasts and chondroclasts, respectively. Resorptive cells form when mononuclear precursors derived from a monocyte–macrophage cell lineage are attracted to certain mineralized surfaces and subsequently fuse and adhere onto them for exerting their resorbing activity. These cells are responsible for degradation of calcified extracellular matrix composed of organic molecules and hydroxyapatite. The activity of these cells can be observed in both physiological and pathological processes throughout life and their activity is mainly required in bone turnover and growth, spontaneous and induced (orthodontic) tooth movement, tooth eruption, and bone fracture healing, as well as in pathological conditions such as osteoporosis, osteoarthritis, and bone metastasis. In addition, they are responsible for daily control of calcium homeostasis. Clastic cells also resorb the primary teeth for shedding before the permanent teeth erupt into the oral cavity.

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Burden of informal caregivers of stroke survivors: Validation of the Zarit burden interview in an African population

Frank Aiwansoba Imarhiagbe, AU Asemota, BA Oripelaye, JE Akpekpe, AA Owolabi, AO Abidakun, FM Akemokwe, VO Ogundare, AL Azeez, JO Osakue

Annals of African Medicine 2017 16(2):46-51

Background: Informal care giving can be burdensome particularly where the option of institutionalized informal care scarcely exist. Objective: To look at the burden of informal caregivers of stroke survivors using the Zarit burden interview (ZBI). Method: 64 stroke survivors were assessed for demographics of age, gender, duration of follow-up since discharged from in-patient care, modified Rankin score at the time of discharge and at the time of evaluation for this study and the most important informal care giver at home was also assessed for whether care giving was telling on their health or life in any negative way. All the caregivers were subsequently assessed with the ZBI. Results: Mean age of most important informal care givers was 40.67 ± 14.27 years and the sex distribution was 33(51.6%) female and 29(45.4%) males. 21(32.8%) reported that caregiving was a health burden. Mean ZBI scores were significantly higher (30.19 ± 14.81 vs 20.30 ± 12.96, P < 0.01) in those that reported that caregiving was telling on their health. ZBI overall rating of burden of caregiving was also significantly associated with whether caregiving was telling on the health of caregiver (P = 0.01) and also symmetrically agreed with whether the burden of caregiving was telling on health (k = 0.33, P< 0.01). The sensitivity and specificity of ZBI were 70% and 68.4% respectively on ROC statistics (AUC = 0.67, P = 0.017). Conclusion: Reported burden of informal caregiving of about 33% is in our opinion huge. The moderate sensitivity and specificity of the ZBI means it could be safely used in the population studied.

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Acanthomatous ameloblastoma in anterior mandibular region of a young patient: A rare case report

Sridevi Ugrappa, Ajay Jain, Neeraj Kumar Fuloria, Shivkanya Fuloria

Annals of African Medicine 2017 16(2):85-89

Ameloblastoma is the most known of the epithelial odontogenic benign tumor. It is slow growing and locally aggressive in nature and most commonly seen in the posterior mandible. Various histopathological variants exist, among which acanthomatous type of ameloblastoma is one of the rarest types. Acanthomatous ameloblastoma is usually seen in older aged human population and most commonly reported in canine region of dogs in literature. Here, we report a rare case of acanthomatous ameloblastoma in a young male patient involving mandibular anterior region crossing the midline with recurrence over a period of 2 years of follow-up after surgical resection.

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Neonatal sepsis in a Nigerian private tertiary hospital: Bacterial isolates, risk factors, and antibiotic susceptibility patterns

Emmanuel Olushola Shobowale, Adaobi U Solarin, Charles John Elikwu, Kenneth Ikenna Onyedibe, Ibironke J Akinola, Abiodun A Faniran

Annals of African Medicine 2017 16(2):52-58

Background/Objectives: Neonatal sepsis is an important cause of morbidity and mortality in the pediatric age group in spite of several attempts at mitigating its effects. This article determines the prevalence of neonatal sepsis and the pathogens responsible for sepsis as well as risk factors and outcome at the Babcock University Teaching Hospital. Methods: A retrospective analysis of laboratory records of consecutive babies delivered within and outside our hospital suspected of having sepsis over a 1-year period. Results: The isolation rate was 34% from 100 neonates with the predominant pathogens being coagulase-negative staphylococci (CONS), Staphylococcus aureus, and Klebsiella pneumoniae. The risk factors for sepsis were age <3 days (P = 0.03) and prematurity (P < 0.001). The mortality rate was 12% with risk factors for mortality being birth weight <2500 g (P = 0.005), prematurity (P = 0.036), premature rupture of membranes (P = 0.007), and delivery outside a tertiary hospital (P = 0.007). Meropenem, ciprofloxacin, and amikacin showed the highest rates of in vitro efficacy. Conclusion: We highlight the prevalent pathogens in our local facility to be a combination of CONS, S. aureus, and K. pneumoniae with susceptibility patterns showing meropenem, ciprofloxacin, and amikacin to be our most effective antimicrobials in vitro.

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Comparing indications for cardiovascular admissions into a Nigerian and an Israeli Hospital

Ogba Joseph Ukpabi, Kelechukwu Uwanurochi

Annals of African Medicine 2017 16(2):70-73

Background: Changing epidemiologic profile with increase in cardiovascular risk factors is well documented in literature. Our study sought to see how this is reflected in cardiovascular admissions into medical wards of a Nigerian and an Israeli hospital. Objective: To compare the range and pattern of cardiovascular admissions encountered in a Nigerian hospital and an Israel hospital. Methods: This was a retrospective study of admission records of patients admitted into both Federal Medical Centre (FMC), Umuahia, Abia State, Nigeria, and Sheba Medical Centre, Israel. Results: Ischemic heart disease (IHD) was the most prevalent among the Israeli hospital's admissions but ranks very low as an indication for admission in Nigeria. The most common causes of admission in Nigeria were hypertension and heart failure (HF). The spectrum of cardiovascular diseases (CVDs) was very limited in the Nigerian hospital, indicating disparity in diagnostic capacity. Conclusion: There were more patients with CVD as a cause of medical admission in the Israel hospital as compared to the Nigerian hospital. Hypertension and HF were prevalent indications for CVD in FMC, Umuahia, Nigeria, while hypertension and IHD were the prevalent indications for admission in Sheba Medical Centre, Israel. Future studies are needed to monitor spectrum and frequency of cardiovascular admissions in view of evolving epidemiological transition in developing countries.

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Risk perception of hepatitis B infection and uptake of hepatitis B vaccine among students of tertiary institution in Jos

MP Chingle, IA Osagie, H Adams, D Gwomson, N Emeribe, AI Zoakah

Annals of African Medicine 2017 16(2):59-64

Background: Hepatitis B virus (HBV) Infection is endemic in Nigeria. Healthcare students are more vulnerable because of direct contact with patients' body fluids and blood. Risk perception of HBV and HB vaccine uptake are also poor. The aim of this study was to assess the level of risk perception of hepatitis B infection, and uptake of the HBV vaccine, between medical and other students of the University of Jos. Methods: A comparative cross sectional study was conducted among 1,200 students of the departments of Medicine, Nursing sciences and Public Administration, University of Jos (400 from each arm) using a pretested self-administered questionnaire. A five point Likert scoring system was used to assess risk perception. Data was analyzed using SPSS version 20. A P -value of <0.05 was considered significant. Results: Awareness on HB vaccine prevention was high (88.4%) among University of Jos students. Awareness was similar among medical and nursing students (36.2% and 36.0% respectively) but lower among public administration student (27.8%), P< 0.001. The overall risk perception was 76.8%. This was also similar for medical and nursing students (40.7% and 40.1% respectively), but lower for public administration students (9.1%), P< 0.001. Risk perception is 5x higher among medical students compared to public administration students (OR = 5.22, 95% CI = 2.19 – 12.93; P < 0.001). The uptake of full dose HB vaccine was 60.2%, 20.6% and 15.1% for medical, nursing and public administration students respectively. Medical students are 4x more likely to go for HB vaccination compared with public administration students (OR=3.62; 95% CI=2.39 – 5.48; P< 0.001). Conclusions: Awareness and risk perception on HBV infection are high among University of Jos students, but uptake of HB vaccine is low. Findings are worst for non-health students.

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Pediatric otorhinolaryngology emergencies at the Jos University Teaching Hospital: Study of frequency, management, and outcomes

Adeyi A Adoga, Emoche T Okwori, John P Yaro, Andrew A Iduh

Annals of African Medicine 2017 16(2):81-84

Background: Studies from Nigeria on pediatric otorhinolaryngology (ORL) emergencies are rare in literature with most focusing on emergencies involving individual systems. Objective: The aim of this study is to determine the prevalence of all ORL emergencies among children in our region to provide a baseline data for future health planning. Patients and Methods: This is a 1-year retrospective cross-sectional study of patients aged 16 years and below presenting to the Accident and Emergency Department of the Jos University Teaching Hospital, Jos, Nigeria. Results: A total of 203 otolaryngology emergencies were attended of which 129 (63.5%) were pediatric emergencies. Records of 87 patients were retrievable with age range 2 months to 15 years (mean 3.44 years; standard deviation ± 3.35). There were 55 males and 32 females with a male to female ratio of 1.7:1. The majority of cases were aged under 5 years (64; 73.6%). Acute tonsillitis accounted for 32 (36.7%) cases with 6 (6.9%) having peritonsillar abscesses. Acute pharyngitis accounted for 11 (12.6%) presentations followed closely by foreign bodies (FBs) in the ear with 10 (11.5%) presentations. FB in the throat occurred in 4 (4.6%) patients who had removal under general anesthesia. Three (3.4%) cases of maxillofacial injuries occurred as a result of insurgent terror attacks and 3.4% presented following corrosive substance ingestion. Conservative management was commenced in 76 (87.4%) patients, 23 (26.4%) had surgery with 68 (78.2%) admitted and discharged, 18 (20.7%) treated as outpatients, and 1 (1.1%) died on admission. Otolaryngologists attended most (95.4%) patients. Conclusion: Pediatric ORL emergencies are common in our region involving a wide range of pathologies. Expansion is required in the ORL training of the emergency room physician to enhance emergency services.

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Blood pressure variation and its correlates among patients undergoing hemodialysis for renal failure in Benin City, Nigeria

Enajite I Okaka, Chimezie G Okwuonu

Annals of African Medicine 2017 16(2):65-69

Background: Blood pressure (BP) variation is commonly encountered during hemodialysis (HD) procedure. Both intradialysis hypotension and hypertension have implications for outcome of treatment and overall morbidity and mortality of the patients. Methodology: A retrospective study was carried out in the dialysis unit of a tertiary health institution in Benin City among patients who had HD for acute kidney injury (AKI) or chronic kidney disease (CKD) over a 3-year period. Data retrieved included age, gender, type of kidney disease, cause of kidney disease, systolic BP at onset of dialysis and at end of dialysis, and diastolic BP (DBP) at onset of and at end of dialysis. Results: Complete data were available for 217 patients. One hundred and seven patients (49.3%) had no significant change in BP; 30.9% had intradialytic hypertension (IDHT) while 19.8% had intradialytic hypotension (IDH). IDH was more prevalent among patients with diabetic kidney disease while IDHT was more common among patients with hypertensive nephropathy (P = 0.002). Female patients had higher mean BP parameters compared to male patients pre- and post-dialysis, but only changes in DBP were statistically significant (P = 0.029). Patients with CKD had higher mean BP parameters pre- and post-dialysis compared to patients with acute AKI and the differences were statistically significant. Conclusion: Females had higher mean BP parameters than males. Patients with CKD had higher mean BP parameters compared with AKI patients. IDHT is a significant problem among patients on HD in our center. Measures to curtail this trend should be instituted with the goal of reducing morbidity and mortality.

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Right atrial extension of a giant retroperitoneal leiomyosarcoma

Sonal Saran, Pushpinder Singh Khera, Parul Gautam, Poonam Elhence

Annals of African Medicine 2017 16(2):90-93

Leiyomyosarcoma of vascular origin is uncommonly seen but mostly occurring in the inferior vena cava. We report a case of young male who presented with giant retroperitoneal leiyomyosarcoma which extended into the right atrium along Inferior vena cava.

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Long-Acting Release Formulation of Exendin-4 Based on Biomimetic Mineralization for Type 2 Diabetes Therapy

ACS Nano

DOI: 10.1021/acsnano.7b01809

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Chiral Metal-Oxide Nanofilms by Cellulose Template Using Atomic Layer Deposition Process

ACS Nano

DOI: 10.1021/acsnano.7b01051

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Biocatalytic activity of Monascus mycelia depending on physiology and high sensitivity to product concentration

Cell suspension culture using mycelia as whole cell biocatalyst for production of orange Monascus pigments has been carried out successfully in a nonionic surfactant micelle aqueous solution. Thus, selection of m...

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Cloning and characterization of the Type I Baeyer–Villiger monooxygenase from Leptospira biflexa

Baeyer–Villiger monooxygenases are recognized by their ability and high selectivity as oxidative biocatalysts for the generation of esters or lactones using ketones as starting materials. These enzymes represe...

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The prognostic value of dynamic contrast-enhanced MRI contrast agent transfer constant Ktrans in cervical cancer is explained by plasma flow rather than vessel permeability

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Excess of a Rassf1-targeting microRNA, miR-193a-3p, perturbs cell division fidelity

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Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study

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Extended RAS analysis and correlation with overall survival in advanced pancreatic cancer

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A meta-analysis comparing the risk of metastases in patients with rectal cancer and MRI-detected extramural vascular invasion (mrEMVI) vs mrEMVI-negative cases

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TEMPO functionalized C 60 fullerene deposited on gold surface for catalytic oxidation of selected alcohols

Abstract

C₆₀TEMPO₁₀ catalytic system linked to a microspherical gold support through a covalent S-Au bond was developed. The C₆₀TEMPO₁₀@Au composite catalyst had a particle size of 0.5–0.8 μm and was covered with the fullerenes derivative of 2.3 nm diameter bearing ten nitroxyl groups; the organic film showed up to 50 nm thickness. The catalytic composite allowed for the oxidation under mild conditions of various primary and secondary alcohols to the corresponding aldehyde and ketone analogues with efficiencies as high as 79–98%, thus giving values typical for homogeneous catalysis, while retaining at the same time all the advantages of heterogeneous catalysis, e.g., easy separation by filtration from the reaction mixture. The catalytic activity of the resulting system was studied by means of high pressure liquid chromatography. A redox mechanism was proposed for the process. In the catalytic cycle of the oxidation process, the TEMPO moiety was continuously regenerated in situ with an applied primary oxidant, for example, O₂/Fe³⁺ system. The new intermediate composite components and the final catalyst were characterized by various spectroscopic methods and thermogravimetry.

Graphical abstract

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