Ιατρικά Άρθρα Αλέξανδρος Γ. Σφακιανάκης: 04/23/17

Κυριακή 23 Απριλίου 2017

Editorial Board Page

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5

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Vascularized Fascia Lata for Prevention of Postoperative Parotid Fistula Arising From Partial Parotidectomy During Neck Dissection

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5
Author(s): Lijuan Zeng, Canhua Jiang, Ning Li, Wen Liu, Fei Wang, Feng Guo
PurposePostoperative parotid fistula can occur after partial parotidectomy, which is a routine surgical procedure during neck dissection of oral cancers arising from or close to the oropharyngeal area. The aim of this study was to evaluate the reliability of vascularized fascia lata for the prevention of postoperative parotid fistula after neck dissection.Materials and MethodsA retrospective review was conducted of patients with oral cancer who underwent ablative resection involving the parotid tail and reconstruction using the anterolateral thigh (ALT) flap with a vascularized fascia lata paddle. The vascularized fascia lata paddle was used to seal off the parotid stump by tightly suturing the edges of the fascia lata and parotid wound together.ResultsTwenty-three patients (18 men and 5 women) with primary oral cancer arising from or close to the oropharyngeal area were enrolled. The mean area of parotid defect was 16.7 cm² and the mean area of fascia lata harvested was 21.8 cm². All flaps survived. Pressure dressing or anticholinergic drugs were not used in any case. During the follow-up period, there was no clinical evidence of the development of parotid fistula.ConclusionThe vascularized fascia lata paddle is a reliable option for the prevention of postoperative parotid fistula after neck dissection of oral cancer.

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Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5

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AAOMS Author Disclosure forms

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5

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Reader's circle

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5

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Evidence-Based Practice: Research Opportunities

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5
Author(s): James R. Hupp

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Journal of Oral and Maxillofacial Surgery

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5

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Regarding “Novel Transoral Approach to the Posterolateral Maxilla and Infratemporal Region”

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5
Author(s): Zachary S. Peacock, Leonard B. Kaban

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In Reply

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5
Author(s): Marco F. Caminiti, David K. Lam

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News and Announcements

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5

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Update on Craniomaxillofacial Trauma

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5
Author(s): Edward Ellis

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Evaluation of Stress Response During Mesiodens Extraction Under General Anesthesia Using Heart Rate Variability

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5
Author(s): Hye-Won Hwang, Hong-Keun Hyun, Young-Jae Kim, Jung-Wook Kim, Teo Jeon Shin
PurposeStress related to dental treatment can be associated with negative outcomes. Heart rate variability (HRV) is an objective measurement of autonomic nervous system activity. Therefore, HRV was used to identify autonomic nervous system reactions during mesiodens extraction under general anesthesia in children.Materials and MethodsElectrocardiography was performed with customized software during treatment. HRV parameters were analyzed according to time and frequency domains during each dental procedure (local anesthesia, incision, flap, bone removal, extraction of mesiodens, and suturing). The relations of HRV parameters to age also were determined.ResultsTotal autonomic nervous system activity decreased markedly after local anesthesia injection. Depending on the responses of sympathetic nerve activity, patients were categorized in a stress group and a nonstress group. The ratio of low-frequency power (LF) to high-frequency power (HF), an indication of sympathetic and parasympathetic balance, increased in the stress group after incision and flap formation. Conversely, the LF/HF ratio decreased during treatment in the nonstress group. However, HR, widely used to evaluate stress responses, did not change statistically during mesiodens extraction in either group. HRV parameters did not differ statistically according to age.ConclusionsThe internal stress related to mesiodens extraction can be evaluated more objectively with HRV parameters than with conventional methods. Sympathetic nerve activity in the stress group differed from that in the nonstress group during the treatment procedures.

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Condyle Excursion Angle, Articular Eminence Inclination, and Temporomandibular Joint Morphologic Relations With Disc Displacement

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5
Author(s): Katharina Alves Rabelo, Saulo Leonardo Sousa Melo, Marianna Guanaes Gomes Torres, Paulo Sérgio F. Campos, Patrícia Meira Bento, Daniela Pita de Melo
PurposeThe aim of this study was to evaluate the relations of the condyle excursion angle (CEA) and the morphology and morphometry of the articular eminence to disc displacement (DD) using magnetic resonance imaging (MRI) of symptomatic patients.Materials and MethodsMRIs of 199 temporomandibular joints (TMJs) were evaluated. Qualitative and quantitative morphologic analyses were performed with tools available in PACS 11.0 (Carestream Health, Inc, Rochester, NY). The articular eminence inclination (AEI), eminence height (EH), CEA, and articular eminence morphologic shape were evaluated. Statistical analyses were used to evaluate any possible association of the variables with DD in the closed- and open-mouth positions, age, and gender. The significance level was set at .05.ResultsElderly women (>60 yr) presented higher prevalence values (43.26%). There was no statistical correlation between DD and gender (P = .4290). Higher mean values of the AEI and EH were associated with box-shaped eminences. The EH, AEI, and CEA were not related to the presence or absence of DD and the different types of DD. The AEI (P = .002) and CEA (P < .001) values were higher for TMJs with disc reduction in the open-mouth position.ConclusionDisc position in the closed- and open-mouth positions is not influenced by articular eminence morphology; however, the AEI and CEA have an influence on disc reduction.

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Comprehensive Genomic Profiling of Central Giant Cell Lesions Identifies Clinically Relevant Genomic Alterations

Publication date: May 2017
Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5
Author(s): Brett Bezak, Heidi Lehrke, Julia Elvin, Laurie Gay, David Schembri-Wismayer, Christopher Viozzi
PurposeComprehensive genomic profiling (CGP) can simultaneously detect clinically relevant genomic alterations (CRGAs) in hundreds of cancer-related genes and direct treatment toward patient-specific therapy options for many tumors. This pilot study aimed to use CGP to describe CRGAs present in central giant cell lesions (CGCLs) to characterize any possible underlying genomic drivers of CGCLs.Materials and MethodsWith institutional review board approval, electronic medical records were searched for patients with histologically confirmed CGCLs who underwent biopsy at Mayo Clinic from 2000 through 2014. Clinical characteristics were recorded from the medical records. At least 50 ng of DNA was extracted from formalin-fixed paraffin-embedded archival CGCL specimens by use of hybridization-capture, adaptor ligation–based libraries targeting all exons from 315 cancer-related genes plus select introns from 28 genes commonly rearranged in cancer. Samples were sequenced to high, uniform coverage and assessed for all 4 classes of genomic alterations: base substitutions, small insertions and deletions, rearrangements, and copy number alterations.ResultsOf 8 CGCL specimens, 3 (37.5%) harbored CRGAs, including base substitutions in BRAF, GNAS, and KRAS that are predicted to be oncogenic. In 1 sample, focal high-level amplification of the MITF gene was detected. Rearrangement in the PDGFRB gene was identified in a fourth sample, although the significance of this alteration is uncertain.ConclusionsThis pilot study shows that a relatively high frequency of CRGAs (37.5%) can be identified in CGCLs by use of CGP. Furthermore, 25% of CGCLs analyzed had somatic mutations predicted to activate the mitogen-activated protein kinase signaling pathway, suggesting it may be a driver of the aggressive behavior of these lesions. On the basis of this study, genomic profiling of a larger cohort of CGCLs to validate these observations, as well as correlate mutations with aggressive versus nonaggressive biological behavior and therapeutic responses, appears warranted.

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FoxO3a suppression and VPS34 activity are essential to anti-atrophic effects of leucine in skeletal muscle

Abstract

Our aim is to gain insight into the mechanisms underlying the anti-atrophic effects of leucine, namely, the way that this amino acid can restrain the up-regulation of MuRF1 and Mafbx/Atrogin-1 in muscle atrophy. Male rats received dietary leucine supplementation for 1–3 days, during which time their hind limbs were immobilized. Our results showed that leucine inhibited Forkhead Box O3 (FoxO3a) translocation to cell nuclei. In addition, leucine was able to reverse the expected reduction of FoXO3a ubiquitination caused by immobilization. Unexpectedly, leucine promoted these effects independently of the Class I PI3K/Akt pathway. Vacuolar protein sorting 34 (VPS34; a Class III PI3K) was strongly localized in nuclei after immobilization and leucine supplementation was able to prevent this effect. In experiments on cultured primary myotubes, dexamethasone led to the localization of VPS34 in the nucleus. In addition, the pharmacological inhibition of VPS34 blocked VPS34 nuclear localization and impaired the protective effect of leucine upon myotube trophicity. Finally, the pharmacological inhibition of VPS34 in primary myotubes prevented the protective effects of leucine upon MuRF1 and Mafbx/Atrogin-1 gene expression. Autophagy-related target genes were not responsive to leucine. Thus, we demonstrate that the anti-atrophic effect of leucine is dependent upon FoxO3a suppression and VPS34 activity.

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Lung Organoids and Their Use To Study Cell-Cell Interaction

Abstract

Purpose of Review

The lung research field has pioneered the use of organoids for the study of cell-cell interactions.

Recent Findings

The use of organoids for airway basal cells is routine. However, the development of organoids for the other regions of the lung is still in its infancy. Such cultures usually rely on cell-cell interactions between the stem cells and a putative niche cell for their growth and differentiation.

Summary

The use of co-culture organoid systems has facilitated the in vitro cultivation of previously inaccessible stem cell populations, providing a novel method for dissecting the molecular requirements of these cell-cell interactions. Future technology development will allow the growth of epithelial-only organoids in more defined media and also the introduction of specific non-epithelial cells for the study of cell interactions. These developments will require an improved understanding of the epithelial and non-epithelial cell types present in the lung and their lineage relationships.

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The Key Genes of Chronic Pancreatitis which Bridge Chronic Pancreatitis and Pancreatic Cancer Can be Therapeutic Targets

Abstract

An important question in systems biology is what role the underlying molecular mechanisms play in disease progression. The relationship between chronic pancreatitis and pancreatic cancer needs further exploration in a system view. We constructed the disease network based on gene expression data and protein-protein interaction. We proposed an approach to discover the underlying core network and molecular factors in the progression of pancreatic diseases, which contain stages of chronic pancreatitis and pancreatic cancer. The chronic pancreatitis and pancreatic cancer core network and key factors were revealed and then verified by gene set enrichment analysis of pathways and diseases. The key factors provide the microenvironment for tumor initiation and the change of gene expression level of key factors bridge chronic pancreatitis and pancreatic cancer. Some new candidate genes need further verification by experiments. Transcriptome profiling-based network analysis reveals the importance of chronic pancreatitis genes and pathways in pancreatic cancer development on a system level by computational method and they can be therapeutic targets.

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Lung Organoids and Their Use To Study Cell-Cell Interaction

Abstract

Purpose of Review

The lung research field has pioneered the use of organoids for the study of cell-cell interactions.

Recent Findings

Summary

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Myricetin suppresses invasion and promotes cell death in human placental choriocarcinoma cells through induction of oxidative stress

Publication date: 28 July 2017
Source:Cancer Letters, Volume 399
Author(s): Changwon Yang, Whasun Lim, Fuller W. Bazer, Gwonhwa Song
Myricetin is a bioactive compound found in a variety of vegetables and fruits, and its anti-cancer effects are well known. In this study, we confirmed that myricetin reduced proliferation of two choriocarcinoma cell lines (JAR and JEG-3) and also promoted apoptosis and regulated cell cycle progression in a dose-dependent manner in JAR and JEG-3 cells. In addition, we found that invasive and pro-angiogenic properties of malignant JAR and JEG-3 trophoblast cells were attenuated by myricetin treatment via MAPK and PI3K/AKT signaling pathways. In addition, we found that ROS production, lipid peroxidation, glutathione depletion, and loss of mitochondrial membrane potentials were enhanced in JAR and JEG-3 cells treated with myricetin. Moreover, myricetin augmented cytosolic Ca²⁺ release from the endoplasmic reticulum associated with modulation of ER stress in JAR and JEG-3 cells. Our results also revealed that myricetin had synergistic antiproliferative effects with current chemotherapeutics, etoposide and cisplatin, on choriocarcinoma cells. Collectively, results of the present study provide strong evidence for the potential of myricetin to be an effective therapeutic for the prevention of human placental choriocarcinomas.

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Melittin inhibits tumor growth and decreases resistance to gemcitabine by downregulating cholesterol pathway gene CLU in pancreatic ductal adenocarcinoma

Publication date: 28 July 2017
Source:Cancer Letters, Volume 399
Author(s): Xinjing Wang, Jing Xie, Xiongxiong Lu, Hongzhe Li, Chenlei Wen, Zhen Huo, Junjie Xie, Minmin Shi, Xiaomei Tang, Hao Chen, Chenghong Peng, Yuan Fang, Xiaxing Deng, Baiyong Shen
Melittin is a Chinese traditional medicine for treating chronic inflammation, immunological diseases and cancers, however, the efficacy of melittin and its mechanism for treating pancreatic ductal adenocarcinoma (PDAC) are still unknown. Here we investigated the anti-cancer activity of melittin and its regulated mechanism(s) in the PDAC models. Melittin was found to suppress tumor growth by promoting cell apoptosis and cell-cycle arrest. Interestingly, the microarray analyses demonstrated that melittin significantly regulated cholesterol biosynthesis pathway during treatment. For instance, the cholesterol pathway gene clusterin (CLU) was highly downregulated by melittin which also enhanced gemcitabine sensitivity in PDAC cells by inhibiting CLU expression. In contrast, overexpression of CLU significantly diminished melittin mediated tumor suppression and gemcitabine sensitization, suggesting that CLU is the target of melittin. Furthermore, in the xenograft mouse model, the combination therapy of melittin and gemcitabine is more efficacious for inhibiting PDAC tumor growth than either single regimen. Taken together, our study has indicated that melittin is capable of suppressing tumor growth and promoting gemcitabine sensitivity in PDAC by downregulating cholesterol pathway.

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Editorial Board

Publication date: 1 July 2017
Source:Cancer Letters, Volume 397

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Nearly a third of tests and treatments are unnecessary: CIHI [News]

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Litigious future for Big Sugar? [Correction]

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Toward ending hepatitis C virus infection: What are the next steps? [Commentary]

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Red hot foot ... keep Charcot arthropathy in mind [Letters]

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Team-based versus traditional primary care models and short-term outcomes after hospital discharge [Research]

BACKGROUND:

Strategies to reduce hospital readmission have been studied mainly at the local level. We assessed associations between population-wide policies supporting team-based primary care delivery models and short-term outcomes after hospital discharge.

METHODS:

We extracted claims data on hospital admissions for any cause from 2002 to 2009 in the province of Quebec. We included older or chronically ill patients enrolled in team-based or traditional primary care practices. Outcomes were rates of readmission, emergency department visits and mortality in the 90 days following hospital discharge. We used inverse probability weighting to balance exposure groups on covariates and used marginal structural survival models to estimate rate differences and hazard ratios.

RESULTS:

We included 620 656 index admissions involving 312 377 patients. Readmission rates at any point in the 90-day post-discharge period were similar between primary care models. Patients enrolled in team-based primary care practices had lower 30-day rates of emergency department visits not associated with readmission (adjusted difference 7.5 per 1000 discharges, 95% confidence interval [CI] 4.2 to 10.8) and lower 30-day mortality (adjusted difference 3.8 deaths per 1000 discharges, 95% CI 1.7 to 5.9). The 30-day difference for mortality differed according to morbidity level (moderate morbidity: 1.0 fewer deaths per 1000 discharges in team-based practices, 95% CI 0.3 more to 2.3 fewer deaths; very high morbidity: 4.2 fewer deaths per 1000 discharges, 95% CI 3.0 to 5.3; p < 0.001).

INTERPRETATION:

Our study showed that enrolment in the newer team-based primary care practices was associated with lower rates of postdischarge emergency department visits and death. We did not observe differences in readmission rates, which suggests that more targeted or intensive efforts may be needed to affect this outcome.

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Secrecy on cost of publicly funded hep C treatment [News]

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Recommendations on hepatitis C screening for adults [Guideline]

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Dementia-friendly communities: where home care and mental health intersect [Editorial]

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A 68-year-old man with an incidentally discovered pituitary lesion [Practice]

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Zopiclone overdose and flumazenil rescue [Letters]

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Urinary tract infection in children [Practice]

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What "learning" machines will mean for medicine [News]

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Ocular involvement in sarcoidosis [Practice]

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Stopping "steady stream" of overdose deaths a public health priority [News]

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In good hands [Humanities]

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Grace in impossible places [Coda]

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Bed bug dermatitis: detection dog as a useful survey tool for environmental research of Cimex lectularius

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Hair diameter evaluation in different regions of the safe donor area in Asian populations

Abstract

Background

There is little information about how hair diameter differences within the safe donor area. Thicker or thinner hair may be needed depending on the recipient area, hairline design, and surgical purpose.

Methods

Thirty-eight non-alopecic subjects (19 males and 19 females) were evaluated. The safe donor area was defined as the area contained within 28 cm from the horizontal plane of the upper border of the hair rim to the vertical line of the bilateral external acoustic meatus. Seven zones were defined starting 2 cm on each side (bilateral 4 cm) from the mid-occiput to the temporal side. The diameters of 10 randomly selected anagen hairs were measured from each of the seven zones.

Results

The results showed significant differences in hair diameter by zone between males and females (P < 0.0001). In general, hair diameter tended to decrease from zone 3 to 7.

Conclusion

Our results suggest that safe donor areas between zones 4 and 7 could be useful for specific hair transplantation surgeries requiring thinner hair, such as eyebrows, eyelashes, and female hairline correction surgery, whereas hair from zones 1–3 could be more useful for those requiring thicker hair, such as male and female pattern hair loss. Our data could be clinically valuable for planning hair transplant surgery and choosing the most optimal donor region.

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Chronic bullous disease of childhood with IgG reactivity to p200 antigen

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Early clinical presentations and progression of calciphylaxis

Abstract

Background

Untreated calciphylaxis is a fatal disease of intra- and extravascular calcification, most commonly presenting in end-stage renal disease (ESRD) patients. While early identification is critical for timely treatment, early-stage clinical and histopathological descriptions have not, to our knowledge, been elucidated. As early clinical recognition is essential to prompt definitive histopathological diagnosis, this study describes a range of clinical and histopathological manifestations of early-stage calciphylaxis.

Methods

Five patients with clinical photographs of lesions of early-phase calciphylaxis were chosen from a recent database of 101 patients. Their clinical histories were reviewed and correlated with their respective clinical and histopathological images of early-stage disease and progression of the disease.

Results

Two of the five patients were identified early to have calciphylaxis and were promptly initiated on aggressive, multimodal therapy, resulting in complete resolution and remission of calciphylaxis. The other three patients were also recognized in early stages, one without renal disease, although the disease had progressed to more advanced stages associated with greater morbidity and mortality.

Conclusions

These cases demonstrate that calciphylaxis may be clinically misdiagnosed due to ill-defined presentations, particularly in the early stages without the characteristic features of livedo racemosa and ulceration. However, recognition in the early stages is critical to implement timely treatment. As such, definitively diagnostic skin biopsy should be considered early in suspected cases to confirm the diagnosis of calciphylaxis and ensure prompt management of this lethal disease.

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Melanoma in situ of lentigo maligna type in a young woman

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A wake-up call to dermatologists – climate change affects the skin

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Serratia marcescens: an Italian story

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The use of topical minoxidil to accelerate nail growth: a pilot study

Abstract

Linear nail growth rate is affected by various conditions, one of which is the level of blood flow. Our supposition was that topical minoxidil, which has vasodilatory properties, can increase the rate of nail growth. The aim of this study was to determine the impact of topical minoxidil on nail growth. A 5% topical minoxidil solution was applied twice daily to the fingernails of 32 participants. Two groups of 16 participants were randomly chosen. In one group, the applications were made to the right index and left ring fingernails, and, in the other, the left index and right ring fingernails. During each visit (weekly during the first month and every 2 weeks during the second month), the nail length of six fingernails (index, middle, and ring of both hands) was measured using a digital caliper. Beginning in the first week, the mean nail length of the treated nails was greater than that of nails in the untreated group with statistical significance. There were no systemic or cutaneous side effects. During the first month, the mean growth of the treated nails was 4.27 mm/month compared with 3.91 mm/month in the untreated nails (P = 0.003). These findings suggest that a 5% concentration of topical minoxidil can stimulate nail growth with increased growth beginning in the first week of application. The results may have important implications for the treatment of nail disorders; however, a comparable study involving participants with nail disorders is highly recommended.

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Burning mouth syndrome: results of screening tests for vitamin and mineral deficiencies, thyroid hormone, and glucose levels—experience at Mayo Clinic over a decade

Abstract

Background

Burning mouth syndrome (BMS) is a disorder characterized by chronic mouth pain in the absence of objective clinical abnormalities. Vitamin or mineral deficiencies may have a role in BMS, but data regarding the prevalence and relevance of hematinic deficiencies are conflicting. We aimed to determine the frequency of specific laboratory abnormalities in patients with BMS.

Methods

We retrospectively reviewed the results of screening blood tests in patients with BMS at our institution between January 2003 and December 2013.

Results

Among 659 patients with BMS, the most common decreased values or deficiencies were vitamin D₃ (15%), vitamin B₂ (15%), vitamin B₆ (5.7%), zinc (5.7%), vitamin B₁ (5.3%), thyrotropin (TSH) (3.2%), vitamin B₁₂ (0.8%), and folic acid (0.7%). Laboratory values for fasting blood glucose and TSH were increased in 23.7% and 5.2%, respectively.

Conclusions

In patients with symptoms of BMS, our results suggest it is reasonable to screen for fasting blood glucose, vitamin D (D₂ and D₃), vitamin B₆, zinc, vitamin B₁, and TSH. Deficiencies of vitamin B₁₂ and folic acid were rare (<1% abnormal).

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Chronic, unilateral, and erythematous lesions on the foot of a pediatric patient – a clinicopathological challenge

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Is prostate cancer different in black men? Answers from 3 natural history models

BACKGROUND

Black men in the United States have substantially higher prostate cancer incidence rates than the general population. The extent to which this incidence disparity is because prostate cancer is more prevalent, more aggressive, and/or more frequently diagnosed in black men is unknown.

METHODS

The authors estimated 3 independently developed models of prostate cancer natural history in black men and in the general population using an updated reconstruction of prostate-specific antigen screening, based on the National Health Interview Survey in 2005 and on prostate cancer incidence data from the Surveillance, Epidemiology, and End Results program during 1975 through 2000. By using the estimated models, the natural history of prostate cancer was compared between black men and the general population.

RESULTS

The models projected that from 30% to 43% (range across models) of black men develop preclinical prostate cancer by age 85 years, a risk that is (relatively) 28% to 56% higher than that in the general population. Among men who had preclinical disease onset, black men had a similar risk of diagnosis (range, 35%-49%) compared with the general population (32%-44%), but their risk of progression to metastatic disease by the time of diagnosis was from 44% to 75% higher than that in the general population.

CONCLUSIONS

Prostate cancer incidence patterns implicate higher incidence of preclinical disease and higher risk of metastatic progression among black men. The findings suggest screening black men earlier than white men and support further research into the benefit-harm tradeoffs of more aggressive screening policies for black men. Cancer 2017. © 2017 American Cancer Society.

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Prostate cancer in black men: Is it time for personalized screening approaches?

Evidence is accumulating that a “1-size-fits-all” screening approach to prostate cancer may not be what is most appropriate. Therefore, the use of personalized screening approaches in higher risk men, particularly black men, warrants further policy consideration. See also pages 000-000.

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Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli-sani cohort and cellular models

Meta-analytic data on the effect of coffee in prostate cancer risk are controversial. Caffeine as a bioactive compound of coffee has not yet been studied in deep in vitro. Our study aimed at evaluating in a population cohort the effect of Italian-style coffee consumption on prostate cancer risk and at investigating in vitro the potential antiproliferative and antimetastatic activity of caffeine on prostate cancer cell lines. 6,989 men of the Moli-sani cohort aged ≥50 years were followed for a mean of 4.24 ± 1.35 years and 100 new prostate cancer cases were identified. The European Prospective Investigation into Cancer and Nutrition-Food Frequency Questionnaire was used for the dietary assessment and the evaluation of Italian-style coffee consumption. Two human prostate cancer cell lines, PC-3 and DU145, were tested with increasing concentrations of caffeine, and their proliferative/metastatic features were evaluated. The newly diagnosed prostate cancer participants presented lower coffee consumption (60.1 ± 51.3 g/day) compared to the disease-free population (74.0 ± 51.7 g/day) (p < 0.05). Multiadjusted analysis showed that the subjects at highest consumption (>3 cups/day) had 53% lower prostate cancer risk as compared to participants at the lowest consumption (0–2 cups/day) (p = 0.02). Both human prostate cancer cell lines treated with caffeine showed a significant reduction in their proliferative and metastatic behaviors (p < 0.05). In conclusion, reduction by Italian-style coffee consumption of prostate cancer risk (>3 cups/day) was observed in epidemiological level. Caffeine appeared to exert both antiproliferative and antimetastatic activity on two prostate cancer cell lines, thus providing a cellular confirmation for the cohort study results.

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IgG4-related disease presenting as posterior scleritis and vitritis, progressing to multifocal orbital involvement

IgG4-related disease (IgG4-RD) is a rare, chronic inflammatory condition that may involve nearly every organ system. Originally identified as a cause of autoimmune pancreatitis, its characteristic histological and clinical features have been found in a wide variety of inflammatory presentations, including the eye and orbit. Here we describe an example of a case of IgG4-RD initially presenting as scleritis and vitritis, with further progression to multifocal bilateral orbital involvement. Tissue biopsy of an orbital mass was highly characteristic of IgG4-RD histology and a rapid clinical response to corticosteroids was observed. This case highlights IgG4-RD as a rare cause of intraocular inflammation that may progress to involve the orbit.

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Intradiaphragmatic hybrid lesion: surgical decision-making and value of minimal invasive surgery

Hybrid lesions (HLs) have elements of congenital pulmonary airway malformation and extrapulmonary sequestration (EPS) and belong to the congenital lung lesions. EPS usually arises in the thorax or the abdomen but rarely in the diaphragm. The preoperative diagnostic work-up based on chest radiograph, ultrasound (US) and CT often shows imprecise results. Therefore, the exact localisation of the lesion can only be ascertained intraoperatively. Here we present a patient, with an intradiaphragmatic HL, and demonstrate the difficulties of surgical decision making regarding the localisation of the lesion and discuss the value of minimal invasive surgery.

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An unusual cause for diffuse pulmonary nodules

Description

We present the case of a 67-year-old woman with a 3-week history of dysphagia in the absence of any respiratory or constitutional symptoms. A lifelong non-smoker with no significant medical comorbidities, it was thought unusual that a routine chest radiograph (figure 1) demonstrated diffuse, small, irregular nodules throughout her lung fields. The diagnosis of primary lung adenocarcinoma was made on the basis of a CT-guided biopsy (figure 2). It is likely that this atypical presentation and radiological appearance of primary malignancy is related to the erosion of tumour into one of the pulmonary arteries thus disseminating the neoplasm throughout the lungs. The cause for the patient’s symptoms was attributed to malignant involvement of the central nervous system.

Figure 1

Chest X-ray.

Figure 2

CT scan of the chest.

To distinguish between...

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Complicated small bowel diverticular disease: a case series

Small bowel diverticulosis of the jejunum and ileum is an uncommon finding with a prevalence rate of 0.2% to 1.3% at autopsy and 0.3% to 1.9% on small bowel studies. Diagnosis can be difficult because there are no pathognomonic features or clinical symptoms that are specific for small bowel diverticulosis. Though rare, it is critical to keep the possibility of small bowel diverticulosis in mind when evaluating cases of malabsorption, chronic abdominal pain, haemorrhage, perforation and intestinal obstruction, especially in patients with connective tissue disorders, a family history of diverticula and a personal history of colonic diverticulosis. Guidelines for the treatment of complicated small bowel diverticulosis are not clearly defined. However, the consensus in treatment is to do a small bowel resection with primary anastomosis. We report three interesting cases of jejunoileal diverticula that presented in an occult manner and later progressed to more emergent manifestations.

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Respiratory difficulty with palatal, laryngeal and respiratory muscle tremor in adult-onset Alexanders disease

Sleep apnoea and respiratory difficulties are reported in adult-onset Alexander’s disease (AOAD), an autosomal-dominant leukodystrophy that presents mainly with progressive ataxia. We demonstrate for the first time that the respiratory symptoms can result from association of palatal tremor with a similar tremor of laryngeal and respiratory muscles that interrupts normal inspiration and expiration.

A 60-year-old woman presented with progressive ataxia, palatal tremor and breathlessness. MRI revealed medullary atrophy, bilateral T2 hyperintensities in the dentate nuclei and hypertrophic olivary degeneration (HOD). AOAD was confirmed genetically with a positive glial fibrillary acidic protein (GFAP) mutation. Electrophysiological study revealed 1.5 Hz rhythmic laryngeal and respiratory muscle activity. Her respiratory symptoms were significantly improved at night with variable positive pressure ventilation.

This case illustrates that palatal tremor in AOAD, and potentially in other conditions, may be associated with treatable breathlessness due to a similar tremor of respiratory muscles.

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Dynamic interaction of trace gases (VOCs, ozone, and NO x ) in the rural atmosphere of sub-tropical India

Abstract

The atmospheric chemistry and health implications of pollutants are important scientific concerns in the rural atmosphere. The current study investigates the estimation of seasonal and diurnal variability of VOCs, ozone, and NOx in the rural area located in a tropical region of India during the year 2013–2014. Results showed that most of the targeted VOCs were higher in winter followed by summer and autumn. The diurnal variability of aromatic hydrocarbons showed similar pattern with different amplitudes as maxima and minima during morning (07:00–10:00 h) or evening (16:00–19:00 h) and daytime (10:00–16:00 h), respectively. The sum of aromatic VOCs are found to be in the range from 27.3 to 87.9 μg/m³. In addition to this, O₃ and NOx were observed as 45.04 ± 15.19 μg/m³ and 12.41 ± 3.49 μg/m³, respectively, during the observation period. The estimated VOC/NOx ratios (ranged from 3.4 to 3.7) indicated that the selected rural area was VOC limited in terms of ozone sensitivity. The sources of the VOCs have been explained by characteristic ratios, correlation, and principal component analysis. Further, ozone-forming potential (OFP) of the targeted aromatic VOCs has been evaluated using maximum incremental reactivity which suggested toluene (benzene) contributed the largest (lowest) in the ozone formation. Exposure assessment in terms of lifetime cancer and non-cancer risks lies within the acceptable range of USEPA guidelines.

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Patterns, predictors and persistence of chronic sedative use: a population-based observational study of older adults in British Columbia, Canada

Abstract

Background

Benzodiazepines and benzodiazepine-like sedatives (zopiclone, zolpidem and zaleplon) are commonly prescribed to treat anxiety and insomnia but are contraindicated for chronic use. We sought to study the persistence, over multiple years, of chronic use of benzodiazepines and benzodiazepine-like sedatives among community-dwelling adults in British Columbia, Canada.

Methods

This is a retrospective analysis of linked health data for adults aged 50 to 69 in 2004 who resided in British Columbia, Canada, between 2004 and 2013. We assigned subjects to one of four groups according to the total number of days of benzodiazepines and benzodiazepine-like sedatives that they were dispensed from retail pharmacies in each observation year. We estimated logistic regression models to measure associations between the odds of chronic sedative use and explanatory variables. We computed transition probability matrices that depict likelihood of changes in sedative utilization levels across years.

Results

Nearly one in ten (9.4%) community-dwelling older adults in British Columbia filled prescriptions with more than 90 days' worth of benzodiazepines or benzodiazepine-like sedatives in 2013. The odds of such chronic sedative use were higher for people who were older, had lower income, were sicker, or lived in rural communities; odds were lower for people with Chinese or South Asian surnames and for men who were married. Controlling for other factors, chronic users of sedatives in 2008 were 15 times more likely than non-users of sedatives in 2008 to be chronic sedative users in 2013 (OR = 14.73; 95% CI = [14.24, 15.24]). Approximately two out of every five older British Columbians who were chronic sedative users in 2013 had been chronic users of sedatives 10 years prior. Two out of every three chronic sedative users in 2004 were either chronic users (57%) or dead (16%) by 2013.

Interpretation

Chronic use of sedatives is prevalent and persistent among older adults in British Columbia. The persistence of chronic sedative use between when patients were 50 to 59 years old and when they were 60 to 69 years old suggests that earlier interventions to curb chronic sedative use may be warranted even if patients do not experience significant risks until later ages.

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FAK phosphorylation plays a central role in thrombin-induced RPE cell migration

Publication date: Available online 23 April 2017
Source:Cellular Signalling
Author(s): E.D. Aguilar-Solis, A.M. López-Colomé, I. Lee-Rivera, A. Alvarez-Arce, E. López
The migration of retinal pigment epithelial (RPE) cells is an important step in various pathologic conditions including subretinal neovascularization (SRN), proliferative vitreoretinopathy (PVR) and, importantly, as a consequence of retinal surgery. Therefore, the elucidation of the mechanisms underlying RPE trans-differentiation and migration is essential for devising effective treatments aimed to the prevention of these disorders. A common event in these pathologies is the alteration of the blood-retina barrier (BRB), which allows the interaction of RPE cells with thrombin, a pro-inflammatory protease contained in serum. Our previous work has demonstrated that thrombin induces RPE cell cytoskeletal remodeling and migration, hallmark processes in the development of PVR; however, the molecular mechanisms involved are still unclear. Cell migration requires the disassembly of focal adhesions induced by Focal Adhesion Kinase (FAK) phosphorylation, together with the formation of actin stress fibers. The aim of the present work was to identify thrombin-activated signaling pathways leading to FAK phosphorylation and to determine FAK participation in thrombin-induced RPE cell migration. Results demonstrate that the activation of PAR1 by thrombin induces FAK autophosphorylation at Y397 and the subsequent phosphorylation of Y576/577 within the activation loop. FAK phosphorylation was shown to be under the control of c/nPKC and PI3K/PKC-ζ, as well as by Rho/ROCK, since the inhibition of these pathways prevented thrombin-induced FAK phosphorylation and the consequent disassembly of focal adhesions, in parallel to FAK-dependent actin stress fiber formation and RPE cell migration. These findings demonstrate, for the first time, that thrombin stimulation of RPE cell transformation and migration are regulated by FAK tyrosine phosphorylation. Thus, targeting FAK phosphorylation may provide a strategical basis for PVR treatment.

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Author Guidelines

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Primary HPV testing verification: A retrospective ad-hoc analysis of screening algorithms on women doubly tested for cytology and HPV

Background

To evaluate human papillomavirus (HPV) testing as a primary screening tool, we retrospectively analyzed data comparing (1) HPV testing to the algorithms of the ATHENA Study: (2) cytology alone, (3) cytology with ASCUS triage in women 25–29 and (4) cotesting ≥ 30 or (5) cotesting ≥ 25.

Methods

We retrospectively analyzed data from women tested with both cytology and HPV testing from 2010 to 2013. Cumulative risk (CR) for CIN3+ was calculated. Crude and verification bias adjusted (VBA) sensitivity, specificity, predictive values, likelihood ratios, colposcopy rate, and screening test numbers were compared.

Results

About 15,173 women (25–95, 7.1% <30) had both HPV and cytological testing. Nearly 1,184 (8.4%) had biopsies. About 19.4% had positive cytology, 14.5% had positive HPV. HPV testing unassociated with ASCUS was requested in 40% of women <30, versus 84% ≥30, with similar HPV16/18 genotyping results (68% vs. 70%). 84 CIN3+ were detected with the following 3-year cumulative risk (CR) (95% confidence interval): HPV+/ASCUS+, 46% (32–66%), HPV+/NILM 30% (15–58%), HPV−/ASCUS+ 12% (6–23%), and HPV−/NILM 0.8% (0.2–3.6%). HPV had higher specificity 57% (54–60%) than cotesting ≥30 52% (49–55%). HPV sensitivity 78% (69–87%), positive 12.3% (9.8–15.3%), negative 97 (96–98%) predictive values, positive 1.8 (1.6–2.1) and negative likelihood ratios 0.6 (0.5-0.6), were not significantly different. Cotesting increased colposcopy rate and doubled testing per CIN3+ diagnosed. Conclusion: While HPV−/NILM cotesting results are associated with low CIN3+ risk, HPV testing had similar screening performance to cotesting and to cytology alone. Additionally, HPV testing and cytology incur false negatives in nonoverlapping subsets of patients.

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Issue Information

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IJMS, Vol. 18, Pages 816: CoQ10 Deficiency May Indicate Mitochondrial Dysfunction in Cr(VI) Toxicity

To investigate the toxic mechanism of hexavalent chromium Cr(VI) and search for an antidote for Cr(VI)-induced cytotoxicity, a study of mitochondrial dysfunction induced by Cr(VI) and cell survival by recovering mitochondrial function was performed. In the present study, we found that the gene expression of electron transfer flavoprotein dehydrogenase (ETFDH) was strongly downregulated by Cr(VI) exposure. The levels of coenzyme 10 (CoQ10) and mitochondrial biogenesis presented by mitochondrial mass and mitochondrial DNA copy number were also significantly reduced after Cr(VI) exposure. The subsequent, Cr(VI)-induced mitochondrial damage and apoptosis were characterized by reactive oxygen species (ROS) accumulation, caspase-3 and caspase-9 activation, decreased superoxide dismutase (SOD) and ATP production, increased methane dicarboxylic aldehyde (MDA) content, mitochondrial membrane depolarization and mitochondrial permeability transition pore (MPTP) opening, increased Ca2+ levels, Cyt c release, decreased Bcl-2 expression, and significantly elevated Bax expression. The Cr(VI)-induced deleterious changes were attenuated by pretreatment with CoQ10 in L-02 hepatocytes. These data suggest that Cr(VI) induces CoQ10 deficiency in L-02 hepatocytes, indicating that this deficiency may be a biomarker of mitochondrial dysfunction in Cr(VI) poisoning and that exogenous administration of CoQ10 may restore mitochondrial function and protect the liver from Cr(VI) exposure.

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Elucidating the Aβ42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer’s Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data

Abstract

Background

Amyloid beta (Aβ) oligomers play a critical role in the pathogenesis of Alzheimer's disease (AD) and represent a promising target for drug development. Tramiprosate is a small-molecule Aβ anti-aggregation agent that was evaluated in phase III clinical trials for AD but did not meet the primary efficacy endpoints; however, a pre-specified subgroup analysis revealed robust, sustained, and clinically meaningful cognitive and functional effects in patients with AD homozygous for the ε4 allele of apolipoprotein E4 (APOE4/4 homozygotes), who carry an increased risk for the disease. Therefore, to build on this important efficacy attribute and to further improve its pharmaceutical properties, we have developed a prodrug of tramiprosate ALZ-801 that is in advanced stages of clinical development. To elucidate how tramiprosate works, we investigated its molecular mechanism of action (MOA) and the translation to observed clinical outcomes.

Objective

The two main objectives of this research were to (1) elucidate and characterize the MOA of tramiprosate via an integrated application of three independent molecular methodologies and (2) present an integrated translational analysis that links the MOA, conformation of the target, stoichiometry, and pharmacokinetic dose exposure to the observed clinical outcome in APOE4/4 homozygote subjects.

Method

We used three molecular analytical methods—ion mobility spectrometry–mass spectrometry (IMS–MS), nuclear magnetic resonance (NMR), and molecular dynamics—to characterize the concentration-related interactions of tramiprosate versus Aβ42 monomers and the resultant conformational alterations affecting aggregation into oligomers. The molecular stoichiometry of the tramiprosate versus Aβ42 interaction was further analyzed in the context of clinical pharmacokinetic dose exposure and central nervous system Aβ42 levels (i.e., pharmacokinetic–pharmacodynamic translation in humans).

Results

We observed a multi-ligand interaction of tramiprosate with monomeric Aβ42, which differs from the traditional 1:1 binding. This resulted in the stabilization of Aβ42 monomers and inhibition of oligomer formation and elongation, as demonstrated by IMS–MS and molecular dynamics. Using NMR spectroscopy and molecular dynamics, we also showed that tramiprosate bound to Lys16, Lys28, and Asp23, the key amino acid side chains of Aβ42 that are responsible for both conformational seed formation and neuronal toxicity. The projected molar excess of tramiprosate versus Aβ42 in humans using the dose effective in patients with AD aligned with the molecular stoichiometry of the interaction, providing a clear clinical translation of the MOA. A consistent alignment of these preclinical-to-clinical elements describes a unique example of translational medicine and supports the efficacy seen in symptomatic patients with AD. This unique "enveloping mechanism" of tramiprosate also provides a potential basis for tramiprosate dose selection for patients with homozygous AD at earlier stages of disease.

Conclusion

We have identified the molecular mechanism that may account for the observed clinical efficacy of tramiprosate in patients with APOE4/4 homozygous AD. In addition, the integrated application of the molecular methodologies (i.e., IMS-MS, NMR, and thermodynamics analysis) indicates that it is feasible to modulate and control the Aβ42 conformational dynamics landscape by a small molecule, resulting in a favorable Aβ42 conformational change that leads to a clinically relevant amyloid anti-aggregation effect and inhibition of oligomer formation. This novel enveloping MOA of tramiprosate has potential utility in the development of disease-modifying therapies for AD and other neurodegenerative diseases caused by misfolded proteins.

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Freshman Biology, #SciArt, and The Amoeba Sisters

In this post from my microbiology/education blog, I describe another "artistic" approach to learning introductory biology. Two fine #SciArt communicators, "The Amoeba Sisters," offered to judge some of the artwork my first year biology students created.

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Efficiency of Ustekinumab in Crohn's Disease with Severe Psoriasiform Rash Induced by Biotherapies in an Adolescent

Abstract

Ustekinumab is approved for the treatment of psoriasis in adolescents and for the treatment of moderate to severe Crohn's disease (CD) in adults, but data are lacking in pediatric CD. We report a case of severe psoriasis induced by biotherapies in an adolescent with CD that improved after switching to ustekinumab (90 mg at weeks 0, 2, and 4 and then every 8 weeks). The patient had not experienced CD relapse after 1 year of follow-up. Ustekinumab can be an alternative therapy for psoriasis induced by biotherapies when conventional treatment fails and can maintain remission of CD.

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Nerve Root(s)

In season 3, episode 18 of Star Trek: Deep Space Nice Dr. Bashir has to deal with his deepest fears. One of these fears has to do with the fact that he graduated second in his medical school class because he mistook a "pre-ganglionic fiber for a post-ganglionic nerve." Dr. Bashir is not alone. I see this lead to 2 errors every day in our trainees. The clinical implication is zero, because the referring physicians also don't make this distinction (two wrongs do make a right, apparently). This brings us to our two common errors.

First, take a look at the image below:

spinal-nerves-in-detail-showing-dorsal-r

Note that there are 2 nerve roots (dorsal and ventral) on each side (left and right). When you say a lumbar disc compresses a nerve root in the central spinal canal, you need to add an "s," because these dorsal and ventral nerve roots travels down together in the cauda equina. Next time you look at an axial T2-WI of the lumbar spine, see if you can see two distinct nerve roots on either side.

Second, note that once we're post-ganglionic, we're dealing with a nerve, not a root anymore. So, if you're talking about a nerve root outside the foramen, you're anatomically incorrect (like a Ken doll). The same goes for the "nerve roots" of the brachial plexus and the famous Randy Travis Drinks Cold Beer mnemonic for the brachial plexus anatomy (sorry, Randy).

Reference

Basic anatomy that everyone ignores.

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Gait instability in valproate-treated patients: Call to measure ammonia levels

Objective

Hyperammonemia induced by valproate (VPA) treatment may lead to several neurological and systemic symptoms as well as to seizure exacerbation. Gait instability and recurrent falls are rarely mentioned as symptoms, especially not as predominant ones.

Methods

We report five adult patients with frontal lobe epilepsy (FLE) who were treated with VPA and in whom a primary adverse effect was unstable gait and falls.

Results

There were four males and one female patients with FLE, 25-42-year-old, three following epilepsy surgery. All of them were treated with antiepileptic drug polytherapy. Gait instability with falls was one of the principal sequelae of the treatment. Patients also exhibited mild encephalopathy (all patients) and flapping tremor (three patients) that developed following the addition of VPA (three patients) and with chronic VPA treatment (two patients). VPA levels were within the reference range. Serum ammonia levels were significantly elevated (291-407 μmole/L, normal 20-85) with normal or slightly elevated liver enzymes. VPA dose reduction or discontinuation led to the return of ammonia levels to normal and resolution of the clinical symptoms, including seizures, which disappeared in two patients and either decreased in frequency or became shorter in duration in the other three.

Conclusions

Gait instability due to hyperammonemia and VPA treatment is probably under-recognized in many patients. It can develop when the VPA levels are within the reference range and with normal or slightly elevated liver enzymes.

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Identification of a Novel Alternatively Spliced Form of Inflammatory Regulator SWAP-70-Like Adapter of T Cells

Activation of naive CD4+ T cells results in the development of several distinct subsets of effector Th cells, including Th2 cells that play a pivotal role in allergic inflammation and helminthic infections. SWAP-70-like adapter of T cells (SLAT), also known as Def6 or IBP, is a guanine nucleotide exchange factor for small GTPases, which regulates CD4+ T cell inflammatory responses by controlling Ca2+/NFAT signaling. In this study, we have identified a novel alternatively spliced isoform of SLAT, named SLAT2, which lacks the region encoded by exons 2–7 of the Def6 gene. SLAT2 was selectively expressed in differentiated Th2 cells after the second round of in vitro stimulation, but not in differentiated Th1, Th17, or regulatory T (Treg) cells. Functional assays revealed that SLAT2 shared with SLAT the ability to enhance T cell receptor- (TCR-) mediated activation of NFAT and production of IL-4 but was unable to enhance TCR-induced adhesion to ICAM-1. Ectopic expression of SLAT2 or SLAT in Jurkat T cells resulted in the expression of distinct forms of filopodia, namely, short versus long ones, respectively. These results demonstrate that modulating either SLAT2 or SLAT protein expression could play critical roles in cytokine production and actin reorganization during inflammatory immune responses.

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A State-of-the-Art Review on Mapping and Localization of Mobile Robots Using Omnidirectional Vision Sensors

Nowadays, the field of mobile robotics is experiencing a quick evolution, and a variety of autonomous vehicles is available to solve different tasks. The advances in computer vision have led to a substantial increase in the use of cameras as the main sensors in mobile robots. They can be used as the only source of information or in combination with other sensors such as odometry or laser. Among vision systems, omnidirectional sensors stand out due to the richness of the information they provide the robot with, and an increasing number of works about them have been published over the last few years, leading to a wide variety of frameworks. In this review, some of the most important works are analysed. One of the key problems the scientific community is addressing currently is the improvement of the autonomy of mobile robots. To this end, building robust models of the environment and solving the localization and navigation problems are three important abilities that any mobile robot must have. Taking it into account, the review concentrates on these problems; how researchers have addressed them by means of omnidirectional vision; the main frameworks they have proposed; and how they have evolved in recent years.

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The Role of Phosphorus Slag in Steam-Cured Concrete

Steam curing is an effective method to increase the hydration degree of binder containing phosphorus slag. The role of phosphorus slag in steam-cured concrete was investigated by determining the hydration heat, hydration products, nonevaporable water content, pore structure of paste, and the compressive strength and chloride ion permeability of concrete. The results show that elevated steam curing temperature does not lead to new crystalline hydration products of the composite binder containing phosphorus slag. Elevating steam curing temperature enhances the early hydration heat and nonevaporable water content of the binder containing phosphorus slag more significantly than increasing steam curing time, and it also results in higher late-age hydration degree and finer pore structure. For steam-cured concrete containing phosphorus slag, elevating curing temperature from 60°C to 80°C tends to decrease the late-age strength and increase the chloride permeability. However, at constant curing temperature of 60°C, the steam-cured concrete containing phosphorus slag can achieve satisfied demoulding strength and late-age strength and chloride permeability by extending the steam curing duration.

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Identification of “BRAF-Positive” Cases Based on Whole-Slide Image Analysis

A key requirement for precision medicine is the accurate identification of patients that would respond to a specific treatment or those that represent a high-risk group, and a plethora of molecular biomarkers have been proposed for this purpose during the last decade. Their application in clinical settings, however, is not always straightforward due to relatively high costs of some tests, limited availability of the biological material and time, and procedural constraints. Hence, there is an increasing interest in constructing tissue-based surrogate biomarkers that could be applied with minimal overhead directly to histopathology images and which could be used for guiding the selection of eventual further molecular tests. In the context of colorectal cancer, we present a method for constructing a surrogate biomarker that is able to predict with high accuracy whether a sample belongs to the “BRAF-positive” group, a high-risk group comprising V600E BRAF mutants and BRAF-mutant-like tumors. Our model is trained to mimic the predictions of a 64-gene signature, the current definition of BRAF-positive group, thus effectively identifying histopathology image features that can be linked to a molecular score. Since the only required input is the routine histopathology image, the model can easily be integrated in the diagnostic workflow.

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Dynamic Modeling, Control, and Analysis of a Solar Water Pumping System for Libya

In recent years, one of the suitable solar photovoltaic (PV) applications is a water pumping system. The simplest solar PV pumping system consists of PV array, DC-DC converter, DC motor, and water pump. In this paper, water pumping system sizing for Libya is evaluated based on a daily demand using HOMER software, and dynamic modeling of a solar PV water pumping system using a Permanent Magnet DC (PMDC) motor is presented in Matlab/Simulink environment. The system performance with maximum power point tracking (MPPT) based on Fractional Open Circuit Voltage (FOCV) is evaluated with and without a battery storage system. In some applications, a rated voltage is needed to connect a PMDC motor to a PV array through a DC-DC converter and in other applications the input voltage can vary. The evaluation of the system is based on the performance during a change in solar irradiation. Using Matlab/Simulink, simulation results are assessed to see the efficiency of the system when it is operating at a specific speed or at the MPPT. The results show that an improvement in the system efficiency can be achieved when the PMDC motor is running at a specific speed rather than at the peak PV power point.

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Modeling and Identification of Podded Propulsion Unmanned Surface Vehicle and Its Course Control Research

The response model of podded propulsion unmanned surface vehicle (USV) is established and identified; then considering the USV has characteristic of high speed, the course controller with fast convergence speed is proposed. The idea of MMG separate modeling is used to establish three-DOF planar motion model of the podded propulsion USV, and then the model is simplified as a response model. Then based on field experiments, the parameters of the response model are obtained by the method of system identification. Unlike ordinary ships, USV has the advantages of fast speed and small size, so the controller needs fast convergence speed and strong robustness. Based on the theory of multimode control, a fast nonsingular terminal sliding mode (FNTSM) course controller is proposed. In order to reduce the chattering of system, disturbance observer is used to compensate the disturbance to reduce the control gain and RBF neural network is applied to approximate the symbolic function. At the same time, fuzzy algorithm is employed to realize the mode soft switching, which avoids the unnecessary chattering when the mode is switched. Finally the rapidity and robustness of the proposed control approach are demonstrated by simulations and comparison studies.

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Brain perfusion during rapid-eye-movement sleep successfully identifies amnestic mild cognitive impairment

Publication date: June 2017
Source:Sleep Medicine, Volume 34
Author(s): Pauline Brayet, Dominique Petit, Andrée-Ann Baril, Nadia Gosselin, Jean-François Gagnon, Jean-Paul Soucy, Serge Gauthier, Marie-Jeanne Kergoat, Julie Carrier, Isabelle Rouleau, Jacques Montplaisir
IntroductionProdromal markers of Alzheimer's disease (AD) have been derived from wakefulness. However, brain perfusion during rapid-eye movement (REM) sleep could be a sensitive marker of amnestic mild cognitive impairment (aMCI), as activation of REM sleep relies more on the cholinergic system.MethodsEight subjects with aMCI, and 16 controls, underwent two single-photon emission computed tomography (SPECT) scans with tracer injected during REM sleep then wakefulness.ResultsPerfusion in the anterior cingulate cortex was significantly decreased in aMCI cases compared to controls for both conditions. That defect was much larger and more severe in REM sleep (1795 voxels) compared to wakefulness (398 voxels), and extended to the middle cingulate cortex and the olfactory cortex. Hypoperfusion in the anterior cingulate cortex during REM sleep allowed better classification than hypoperfusion found in wakefulness (93.8 vs 81.3%).ConclusionREM sleep imaging is a valuable tool with which to identify individuals at risk of developing AD.

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In vitro PGPR properties and osmotic tolerance of different Azospirillum native strains and their effects on growth of maize under drought stress

Publication date: Available online 23 April 2017
Source:Microbiological Research
Author(s): Julia E. García, Guillermo Maroniche, Cecilia Creus, Ramón Suárez-Rodríguez, José Augusto Ramirez-Trujillo, María D. Groppa
Osmotic variations in the soil can affect bacterial growth diminishing the number of inoculated bacteria. In a scenario of water deficit having tolerant bacteria would be beneficial to achieve a better response of the plant to stress. Thus, selection of more resistant bacteria could be useful to design new inoculants to be used in arid zones. In this sense, a group of Azospirillum isolates deposited in INTA collection was characterized in order to select strains tolerant to osmotic stress. The results obtained demonstrated that Az19 strain has similar in vitro PGPR characteristics to Az39, the most used strain in Argentina for inoculants industries, with the advantage of a better tolerance to osmotic and salt stress. Inoculation of maize plants with this strain resulted in a better response against water deficit compared to Az39 strain, encouraging us to further study the behavior of this strain in greenhouse and field trials in view of developing new inoculants suitable for areas with water deficit.

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In vitro PGPR properties and osmotic tolerance of different Azospirillum native strains and their effects on growth of maize under drought stress

Duplicated internal auditory canal with inner ear malformation: Case report and literature review

Publication date: Available online 23 April 2017
Source:Auris Nasus Larynx
Author(s): Yoshitaka Takanashi, Tetsuaki Kawase, Yasuko Tatewaki, Jun Suzuki, Izumi Yahata, Yuuri Nomura, Kazuha Oda, Hiromitsu Miyazaki, Yukio Katori
Internal auditory canal anomalies are rare. Narrow internal auditory canal is believed to occur as a result of aplasia or hypoplasia of the vestibulocochlear nerve. Narrow duplication of the internal auditory canal is considered to be very rare. Narrow duplication of the internal auditory canal with inner ear malformation has been reported in only 3 cases. We present 2 cases of narrow duplication of the internal auditory canal with inner ear malformation. The first case had inner ear malformation on only one side and the second case had inner ear malformation on both sides. The embryogenesis may be different between internal auditory canal and inner ear.

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Nivolumab in Second-Line Treatment for Advanced non-Small Cell Lung Cancer with Squamous Cell Histology: A Perspective Based on Pharmacological Costs

recently, Gridelli et al1 have presented the conclusions emerging from an International Experts Panel Meeting of the Italian Association of Thoracic Oncology. From this Experts Panel Meeting nivolumab, a novel programmed cell death 1 (PD-1) immune checkpoint inhibitor, emerged the second-line treatment for patients with advanced non-small cell lung cancer (NSCLC) with squamous cell histology. The introduction of active new agents, such as nivolumab, for the second-line treatment of advanced NSCLC with squamous cell histology2,3 is associated with a relevant increase of costs and it is therefore important to make a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as progression free survival (PFS) and overall survival (OS).

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The relationship between tumor location and outcome in patients with early-stage lung cancer

We read with interest the recent article by Shaverdian et al,1 based on a single institution cohort of 122 patients with stage I (T1-2AN0M0) lung cancer. They reported that on multivariable analysis tumors in the lower lobes were associated with worse relapse-free and overall survival (HR=2.8 and 2.3 respectively) after treatment with stereotactic body radiotherapy. One hypothesis is that because such tumors may be more mobile,2 they may be more prone to inaccuracies in radiotherapy targeting.

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TWiV 438: Drs. TWiV go to Washington

On the eve of the March for Science, the TWiV team gathers at ASM Headquarters in Washington, DC with guests Stefano and Susie to talk about the state of science communication.

Hosts: Vincent Racaniello...

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A Review of Neanderthal: the Strange Saga of the Minnesota Iceman, Part 1

Heuvelmans-2016-cover-340-px-tiny-April-

A book on a perennially popular and notorious mystery animal case has finally been translated into English...

-- Read more on ScientificAmerican.com

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Preoperative implant selection for unilateral breast reconstruction using 3D imaging with the Microsoft Kinect sensor

This study aimed to investigate whether breast volume measured preoperatively with a Kinect 3D sensor could be used to determine the most appropriate implant size for reconstruction.

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Preoperative implant selection for unilateral breast reconstruction using 3D imaging with the Microsoft Kinect sensor

Duplicated internal auditory canal with inner ear malformation: Case report and literature review

Internal auditory canal anomalies are rare. Narrow internal auditory canal is believed to occur as a result of aplasia or hypoplasia of the vestibulocochlear nerve. Narrow duplication of the internal auditory canal is considered to be very rare. Narrow duplication of the internal auditory canal with inner ear malformation has been reported in only 3 cases. We present 2 cases of narrow duplication of the internal auditory canal with inner ear malformation. The first case had inner ear malformation on only one side and the second case had inner ear malformation on both sides.

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Endophenotyping in idiopathic adult onset cervical dystonia

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. (Albanese et al., 2013) Idiopathic adult onset cervical dystonia (IAOCD) is considered to be an autosomal dominant genetic condition due to partially penetrant gene/s.(Stojanovic et al., 1995; Waddy et al., 1991) Hence most of the cases appear to be sporadic with a positive family history in 15-25%.(Waddy et al., 1991) Several genes have been mapped for families, which include members with cervical dystonia (Almasy et al., 1997; Charlesworth et al., 2012; Fuchs et al., 2009; Fuchs et al., 2013; Leube et al., 1996; Valente et al., 2001; Xiao et al., 2012) but in several other families with cervical dystonia linkage to these known genetic loci has been excluded.

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Acute Bacterial Meningitis and Systemic Abscesses due to Streptococcus dysgalactiae subsp. equisimilis Infection

Disseminated abscesses due to group G β-hemolytic Streptococcus dysgalactiae were observed in a 57-year-old cirrhotic patient with the skin being the putative way of entry for the pathogen. S. dysgalactiae is a rare agent in human infections responsible for acute pyogenic meningitis. The mortality rate associated with S. dysgalactiae bacteraemia and meningitis may be as high as 50%, particularly in the presence of endocarditis or brain abscesses. In our patient, main sites of infections were meningitis and ventriculitis, spondylodiscitis, septic arthritis, and soft-tissue infections. In contrast, no endocarditis was evidenced. Cirrhosis-related immune suppression was considered as a pathophysiological cofactor for the condition. Fortunately, clinical status improved after long-term (3 months) antimicrobial therapy.

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The interactive role of CB1 receptors and L-type calcium channels in hippocampal long-term potentiation in rats

Publication date: Available online 23 April 2017
Source:Brain Research Bulletin
Author(s): Hamidreza Komaki, Fargol Saadat, Siamak Shahidi, Abdolrahman Sarihi, Parisa Hasanein, Alireza Komaki
'Long-term potentiation (LTP) of synaptic responses is a widely researched model of synaptic plasticity that occurs during learning and memory. The cannabinoid system is an endogenous system that modulate this kind of synaptic plasticity. In addition, voltage dependent calcium channels is essential for induction of LTP at some synapses in the hippocampus. However, there is currently debate over the interaction between L-type calcium channels and cannabinoid system on the synaptic plasticity. In this study, we examined the effects of an acute administration of the cannabinoid antagonist AM251 following a chronic administration of the Ca²⁺ channel blocker verapamil on LTP induction in the hippocampal dentate gyrus(DG) of rats. Male Wistar rats were administered verapamil(10,25,50mg/kg) or saline intraperitoneally(IP) daily for 13 days(n=10/group). After this treatment period, animals were anesthetized with an IP injection of urethane; the recording and stimulating electrodes were positioned in the DG and the perforant pathway. After obtaining a steady state baseline response, a single IP injection of saline or AM251(1 or 5mg/kg) was administered. LTP was induced by high-frequency stimulation(HFS). The population spike(PS) amplitude and the slope of excitatory postsynaptic potentials(EPSP) were compared between the experimental groups. The acute administration of the CB1 antagonist AM251 increased LTP induction. The EPSP slopes and PS amplitude in the verapamil and AM251 groups differed after HFS, such that AM251 increased LTP, whereas verapamil decreased LTP induction. These findings suggest that there are functional interactions between the L-type calcium channels and cannabinoid system in this model of synaptic plasticity in the hippocampus.

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The antimicrobial peptide hBD2 promotes itch through Toll-like receptor 4 signaling in mice

The psoriasis biomarker hBD2 produces a robust scratching response in a TLR4-dependent manner in mice. TRPV1 is a downstream mediator of hBD2-induced itch. These findings suggest that hBD2 might act as an endogenous pruritogen in psoriatic itch.

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Acute Bacterial Meningitis and Systemic Abscesses due to Streptococcus dysgalactiae subsp. equisimilis Infection

Inhibition of Allogeneic Cytotoxic T Cell (CD8+) Proliferation Via Polymer-Induced Treg (CD4+) Cells

Publication date: Available online 23 April 2017
Source:Acta Biomaterialia
Author(s): Ning Kang, Wendy M. Toyofuku, Xining Yang, Mark D. Scott
T cell-mediated immune rejection remains a barrier to successful transplantation. Polymer-based bioengineering of cells may provide an effective means of preventing allorecognition and the proliferation of cytotoxic (CD8⁺) T lymphocytes (CTL). Using MHC-disparate murine splenocytes modified with succinimidyl valerate activated methoxypoly(ethylene glycol) [SVA-mPEG] polymers, the effects of leukocyte immunocamouflage on CD8⁺ and CD4⁺ alloproliferation and T regulatory (Treg) cell induction were assessed in a mixed lymphocyte reaction (MLR) model. Polymer-grafting effectively camouflaged multiple leukocyte markers (MHC class I and II, TCR and CD3) essential for effective allorecognition. Consequent to the polymer-induced immunocamouflage of the cell membrane, both CD8⁺ and CD4⁺ T cell alloproliferation were significantly inhibited in a polymer dose-dependent manner. The loss of alloproliferation correlated with the induction of Treg cells (CD4⁺CD25⁺Foxp3⁺). The Tregs, surprisingly, arose primarily via differentiation of naive, non-proliferating, CD4⁺ cells. Of biologic importance, the polymer-induced Treg were functional and exhibited potent immunosuppressive activity on allogeneic CTL proliferation. These results suggest that immunocamouflage-mediated attenuation of alloantigen-TCR recognition can prevent the tissue destructive allogeneic CD8⁺ T cell response, both directly and indirectly, through the generation/differentiation of functional Tregs. Immunocamouflage induced tolerance could be clinically valuable in attenuating T cell-mediated transplant rejection and in the treatment of autoimmune diseases.Statement of significanceWhile our previous studies have demonstrated that polymer-grafting to MHC disparate leukocytes inhibits CD4+ cell proliferation, the effects of PEGylation of on the alloproliferation of CD8+ cytotoxic T cells (CTL) was not examined. As shown here, PEGylation of allogeneic leukocytes prevents the generation of the CTL response responsible for acute rejection. The loss of CTL proliferation is consequent to the polymer-based attenuation of allorecognition and the induction of T regulatory cells (Tregs). Interestingly, the Tregs are primarily generated via the differentiation of non-proliferating naive T cells. Importantly, the Tregs are functional and effectively induce a tolerogenic environment when transferred to an alloresponsive environment. The use of polymer-modified leukocytes provides a unique approach to effectively maximize the biologic production of functional Tregs both in vitro and in vivo. By using this approach it may be possible to attenuate unwanted alloresponses (e.g., graft rejection) or to While our previous studies have demonstrated that polymer-grafting to MHC disparate leukocytes inhibits CD4+ cell proliferation, the effects of PEGylation of on the alloproliferation of CD8+ cytotoxic T cells (CTL) was not examined. As shown here, PEGylation of allogeneic leukocytes prevents the generation of the CTL response responsible for acute rejection. The loss of CTL proliferation is consequent to the polymer-based attenuation of allorecognition and the induction of T regulatory cells (Tregs). Interestingly, the Tregs are primarily generated via the differentiation of non-proliferating naive T cells. Importantly, the Tregs are functional and effectively induce a tolerogenic environment when transferred to an alloresponsive environment. The use of polymer-modified leukocytes provides a unique approach to effectively maximize the biologic production of functional Tregs both in vitro and in vivo. By using this approach it may be possible to attenuate unwanted alloresponses (e.g., graft rejection) or to

Graphical abstract

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Ipsilateral sagittal split ramus osteotomy to facilitate reconstruction of the temporomandibular joint after resection of condylar osteochondroma

We report the outcomes of 12 patients with osteochondroma of the mandibular condyle who were treated by condylectomy with sagittal split ramus osteotomy (SSRO) between January 2011 and October 2015. Variables assessed before and after operation were imaging, appearance, maximum mouth opening, maximum mandibular protrusion, lateral excursion, and function of the temporomandibular joint (TMJ). Patients were followed up for a mean (range) of 21 (13 - 30) months. Outcomes were satisfactory with no complications or recurrence.

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Ablative surgery for Parkinson’s disease: Is there still a role for pallidotomy in the deep brain stimulation era?

Publication date: Available online 23 April 2017
Source:Clinical Neurology and Neurosurgery
Author(s): Bruno Spindola, Marco Antônio Leite, Marco Orsini, Erich Fonoff, José Alberto Landeiro, Bruno Lima Pessoa
Posteroventral pallidotomy has already been considered the surgical procedure of choice for Parkinson's disease patients with motor complications. Recently, however, several factors led to its replacement by deep brain stimulation. Nevertheless, pallidotomy has a well-documented efficacy and safety evidence regarding the reduction of parkinsonian motor symptoms. Yet, there may be manysituations where it may be considered as a better option than neuromodulation. Herein we review those possible conditions, giving emphasis to the costs, which we found to be the most limiting factor. Importantly, a cost comparison between deep brain stimulation and pallidotomy was also provided.

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Identification of clinical and paraclinical findings predictive for headache occurrence during spontaneous subarachnoid hemorrhage

Publication date: Available online 23 April 2017
Source:Clinical Neurology and Neurosurgery
Author(s): Srdjan Ljubisavljevic, Vuk Milosevic, Aleksandar Stojanov, Marina Ljubisavljevic, Olivera Dunjic, Miroslava Zivkovic
ObjectivesHeadache is recognized as the main but unwarranted symptom of subarachnoid hemorrhage (SAH). There are no enough findings identified as predictive for headache occurrence in SAH. We evaluated the clinical and paraclinical factors predictive for headache occurrence in SAH.Patients and MethodsWe retrospectively analyzed medical records of 431 consecutive non traumatic SAH patients (264 females and 167 males), ages from 19 to 91 years, presenting with headache (70.3%) and without headache (29.7%) during period of 11years.ResultsAmong all tested parameters, as negative predictors for headache occurrence were recognized: patients' ages (OR 0.97 [95%CI: 0.96–0.99], p=0.025), persistence of coagulation abnormality (OR 0.23 [95%CI: 0.08–0.67], p=0.006), atrial fibrilation (OR 0.23 [95%CI: 0.09–0.59], p=0.002), chronic renal failure (OR 0.26 [95%CI: 0.09–0.76], p=0.014) and more diseases (OR 0.11 [95%CI: 0.04–0.32], p<0.0001), as higher clinical score (OR 0.94 [95%CI: 0.90–0.99], p=0.018) including positive neurological findings (OR 0.34 [95%CI: 0.21–0.55], p<0.001) and loss of consciousness (OR 0.22 [95%CI: 0.12–0.39], p<0.001) at the SAH onset, while the complaint of neck stiffness was identified as its positive predictor (OR 1.93 [95%CI: 1.19–3.10], p=0.007).ConclusionsAlthough diagnosis based solely on clinical presentation is not reliable and speculative, our findings could provide physicians with evidence to consider SAH not only in conditions of its headache occurrence but also in those with headache absence.

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miziA patient with autoimmune limb-girdle myasthenia, and a brief review of this treatable condition.

Publication date: Available online 23 April 2017
Source:Clinical Neurology and Neurosurgery
Author(s): Domizia Vecchio, Claudia Varrasi, Cristoforo Comi, Paolo Ripellino, Roberto Cantello
Limb-girdle myasthenia gravis (LGM) is an uncommon clinical picture related to an antibody-mediated blockage of the neuromuscular junction. We describe a 44-year old man who presented with a proximal limbs' weakness that resembled a myopathic disorder. The repetitive nerve stimulation at 3Hz showing a decremental response suggested myasthenia, that was confirmed by the presence of an increased titer of anti-acetylcholine receptor antibodies (AChRAbs), and of hyperplastic foci at thymus histology. Symptomatic treatment with pyridostigmine was not effective, whereas the patient improved adding Azathioprine. In conclusion, a myopathic-like clinical picture in a adult could be caused by LMG. Thymus pathology, or (rarely) increased AChRAbs could support the diagnosis of LGM.

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Peripheral Membrane Associations of Matrix Metalloproteinases

Publication date: Available online 23 April 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Steven R. Van Doren, Tara C. Marcink, Rama K. Koppisetti, Alexander Jurkevich, Yan G. Fulcher
Water soluble matrix metalloproteinases (MMPs) have been regarded as diffusing freely in the extracellular matrix. Yet multiple MMPs are also observed at cell surfaces. Their membrane-proximal activities include sheddase activities, collagenolysis, bacterial killing, and intracellular trafficking reaching as far as the nucleus. The catalytic domains of MMP-7 and MMP-12 bind bilayers peripherally, each in two different orientations, by presenting positive charges and a few hydrophobic groups to the surface. Related peripheral membrane associations are predicted for other soluble MMPs. The peripheral membrane associations may support pericellular proteolysis and endocytosis. The isolated soluble domains of MT1-MMP can also associate with membranes. NMR assays suggest transient association of the hemopexin-like domains of MT1-MMP and MMP-12 with lipid bilayers. Peripheral association of soluble MMP domains with bilayers or heparin sulfate proteoglycans probably concentrates them near the membrane. This could increase the probability of forming complexes with membrane-associated proteins, such as those targeted for proteolysis. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman.

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Work first then play: Prior task difficulty increases motivation-related brain responses in a risk game

Publication date: Available online 23 April 2017
Source:Biological Psychology
Author(s): Barbara Schmidt, Patrick Mussel, Roman Osinsky, Björn Rasch, Stefan Debener, Johannes Hewig
Task motivation depends on what we did before. A recent theory differentiates between tasks that we want to do and tasks that we have to do. After a have-to task, motivation shifts towards a want-to task. We measured this shift of motivation via brain responses to monetary feedback in a risk game that was used as want-to task in our study. We tested 20 healthy participants that were about 28 years old in a within-subjects design. Participants worked on a Stroop task (have-to task) or an easier version of the Stroop task as a control condition and played a risk game afterwards (want-to task). After the Stroop task, brain responses to monetary feedback in the risk game were larger compared to the easier control task, especially for feedback indicating higher monetary rewards. We conclude that higher amplitudes of feedback-related brain responses in the risk game reflect the shift of motivation after a have-to task towards a want-to task.

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Neural correlates of evoked phantom limb sensations

Publication date: Available online 23 April 2017
Source:Biological Psychology
Author(s): J. Andoh, M. Diers, C. Milde, C. Köppe, D. Kleinböhl, H. Flor
Previous work showed the existence of changes in the topographic organization within the somatosensory cortex (SI) in amputees with phantom limb pain, however, the link between nonpainful phantom sensations such as cramping or tingling or the percept of the limb and cortical changes is less clear.We used functional magnetic resonance imaging (fMRI) in a highly selective group of limb amputees who experienced inducible and reproducible nonpainful phantom sensations. A standardized procedure was used to locate body sites eliciting phantom sensations in each amputee. Selected body sites that could systematically evoke phantom sensations were stimulated using electrical pulses in order to induce phasic phantom sensations. Homologous body parts were also stimulated in a group of matched controls.Activations related to evoked phantom sensations were found bilaterally in SI and the intraparietal sulci (IPS), which significantly correlated with the intensity of evoked phantom sensations. In addition, we found differences in intra- and interhemispheric interaction between amputees and controls during evoked phantom sensations. We assume that phantom sensations might be associated with a functional decoupling between bilateral SI and IPS, possibly resulting from transcallosal reorganization mechanisms following amputation.

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The new issue is now available.Journal of the Study of School Music Educational Practice

Vol.11

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Vol.65 No.2

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The new issue is now available.Kozo Kogaku Ronbunshu. A (Journal of Structural Engineering. A)

Vol.62A

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Vol.65 No.1

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The new issue is now available.Japanese Journal of Medical Physics (Igakubutsuri)

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Vol.6

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New Jersey State Microbe

index.php?option=com_jlibrary&view=artic

Met with two New Jersey State Senators, two Assemblymen, a lobbyist, and two senior administrators in NJ colleges. They all think the idea of a State Microbe is great. It will give people from New Jersey something to be proud of. More details will be posted as the story develops. Thank you.

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Πληροφορίες

Κυριακή 23 Απριλίου 2017

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