Δευτέρα, 12 Φεβρουαρίου 2018
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Paediatric Endobronchial Ultrasound-guided transbronchial needle aspiration: Anaesthetic and procedural considerations
Indian Journal of Anaesthesia 2018 62(2):150-151
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Fluoroscopic-guided paramedian approach to subarachnoid block in patients with ankylosing spondylitis: A case series
Indian Journal of Anaesthesia 2018 62(2):142-144
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Indian Journal of Anaesthesia 2018 62(2):94-102
Advances in ultrasound guided regional anaesthesia and introduction of newer long acting local anaesthetics have given clinicians an opportunity to apply novel approaches to block peripheral nerves with ease. Consequently, improvements in outcomes such as quality of analgesia, early rehabilitation and patient satisfaction have been observed. In this article we will review some of the newer regional anaesthetic techniques, long acting local anaesthetics and adjuvants, and discuss evidence for key outcomes such as cancer recurrence and safety with ultrasound guidance.
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Indian Journal of Anaesthesia 2018 62(2):155-155
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Comparison of the ProSeal laryngeal mask airway with the I-Gel™ in the different head-and-neck positions in anaesthetised paralysed children: A randomised controlled trial
Indian Journal of Anaesthesia 2018 62(2):103-108
Background and Aims: Head and neck movements alter the shape of the pharynx, resulting in changes in the oropharyngeal leaking pressures and ventilation with supragottic airway devices. We compared the effect of the different head-and-neck positions on the oropharyngeal leak pressures and ventilation with the I-Gel™ and ProSeal™ laryngeal mask airway (PLMA) in anaesthetised paralysed children. Methods: A total of 70 children were randomly assigned to receive PLMA (n = 35) or I-Gel™ (n = 35) for airway management. Oropharyngeal leak pressure in maximum flexion, maximum extension and the neutral position was taken as the primary outcome. Peak inspiratory pressures (PIPs), expired tidal volume, ventilation score and fibreoptic grading were also assessed. Results: No significant difference was noted in oropharyngeal leak pressures of PLMA and I-Gel™ during neutral (P = 0.34), flexion (P = 0.46) or extension (P = 0.18). PIPs mean (standard deviation [SD]) were significantly higher (17.7 [4.03] vs. 14.6 [2.4] cm H2O, P = 0.002) and expired tidal volume mean [SD] was significantly lower (5.5 [1.6] vs. 6.9  ml/kg, P = 0.0017) with I-Gel™ compared to PLMA. Fibreoptic grading and ventilation score were comparable in both the groups in all the three head-and-neck positions. Conclusion: PLMA and I-Gel™, both recorded similar oropharyngeal leaking pressures in all the three head-and-neck positions. However, higher peak pressures and lower expired tidal volume in maximum flexion of the neck while ventilating with I-Gel may warrant caution and future evaluation.
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Indian Journal of Anaesthesia 2018 62(2):147-148
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A prospective randomised controlled study for evaluation of high-volume low-concentration intraperitoneal bupivacaine for post-laparoscopic cholecystectomy analgesia
Indian Journal of Anaesthesia 2018 62(2):109-114
Background and Aims: Low-volume high-concentration bupivacaine irrigation of the peritoneal cavity has been reported to be ineffective for short-term analgesia after laparoscopic cholecystectomy (LC). This study was conducted to evaluate the effectiveness of intraperitoneal instillation of high-volume low-concentration bupivacaine for post-operative analgesia in LC. Methods: Sixty patients undergoing LC were included in this prospective, double-blind, randomised study. Patients were divided into two (n = 30) groups. In Group S, intraperitoneal irrigation was done with 500 ml of normal saline. In Group B, 20 ml of 0.5% (100 mg) bupivacaine was added to 480 ml of normal saline for intraperitoneal irrigation during and after surgery. Post-operative pain was assessed by numeric pain rating scale (NRS) at fixed time intervals. Duration of analgesia (DOA), total rescue analgesic requirement (intravenous tramadol), presence of shoulder pain, nausea and vomiting were recorded for the initial 24 h post-operatively. Results: Mean DOA in Group S was 0.06 ± 0.172 h (3.6 ± 10.32 min) and that in Group B was 19.35 ± 8.64 h (P = 0.000). Cumulative requirement of rescue analgesic in 24 h in Group S was 123.33 ± 43.01 mg and that in Group B was 23.33 ± 43.01 mg (P = 0.000). There was no significant difference in incidence of shoulder pain, nausea and vomiting between the groups. Conclusion: High-volume low-concentration of intraperitoneal bupivacaine significantly increases post-operative DOA and reduces opioid requirement after LC.
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Reply to Grocott HP, regarding their comment on 'Jet insufflator for cannot intubate cannot ventilate situation: An Indian Jugaad'
Indian Journal of Anaesthesia 2018 62(2):153-153
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Airway management in the presence of cervical spine instability: A cross-sectional survey of the members of the Indian Society of Neuroanaesthesiology and Critical Care
Indian Journal of Anaesthesia 2018 62(2):115-120
Background and Aims: There is a paucity of clinical practice guidelines for the ideal approach to airway management in patients with cervical spine instability (CSI). The aim of this survey was to evaluate preferences, perceptions and practices regarding airway management in patients with CSI among neuroanaesthesiologists practicing in India. Methods: A 25-item questionnaire was circulated for cross-sectional survey to 378 members of the Indian Society of Neuroanaesthesiology and Critical Care (ISNACC) by E-mail. We sent four reminders and again submitted our survey to non-responders during the 2017 annual ISNACC meeting. Apart from demographic information, the survey captured preferred methods of intubation and airway management for patients with CSI and their justification. Regression analysis was used to identify factors associated with the use of indirect technique for intubation. Results: Only 122 out of the 378 anaesthesiologists responded to our survey. Most respondents were senior consultants, working in training hospitals, and performed ≥25 intubations per year for CSI patients. The majority of neuroanaesthesiologists (78.7%; n = 96) preferred indirect techniques for elective intubation. However, 45 anaesthesiologists (36.9%) preferred indirect techniques for emergency intubation. In an adjusted analysis, preference for patients to be conscious during intubation was significantly associated with the use of indirect techniques (odds ratio = 3.79; confidence interval = 1.52–9.49, P < 0.01). Conclusions: Among ISNACC members, indirect techniques are preferred for elective intubation of patients with CSI, while direct laryngoscopy is preferred for emergency intubation.
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Performance of the Indian Journal of Anaesthesia in 2017: How did we do and where do we go from here?
Indian Journal of Anaesthesia 2018 62(2):91-93
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Comparison of different doses of intravenous lignocaine on etomidate-induced myoclonus: A prospective randomised and placebo-controlled study
Indian Journal of Anaesthesia 2018 62(2):121-126
Background and Aims: Etomidate-induced myoclonus (EM) is observed in 50%–80% of unpremedicated patients. Low-dose lignocaine has been shown to attenuate but not abolish the EM. The aim of this prospective, randomised controlled study was to compare the different doses of lignocaine on the incidence and severity of EM. Methods: Two hundred adult patients were randomly assigned into four groups to receive saline placebo (Group I) or IV lignocaine 0.5 mg/kg (Group II), 1 mg/kg (Group III) or 1.5 mg/kg (Group IV) 2 min before injection etomidate 0.3 mg/kg IV. The patients were assessed for the EM using a four-point intensity scoring system. Our primary outcome was the incidence of myoclonus at 2 min (EM2). The incidence of myoclonus at 1 min (EM1) and severity of myoclonus constituted the secondary outcomes. ANOVA and Pearson Chi-square test were used for statistical analysis and P < 0.05 was considered as statistically significant. Results: The incidence of EM was significantly reduced in Groups III [(EM1: 32% vs. 60%, P = 0.009); (EM2: 42% vs. 76%, P = 0.001)] and IV (EM2: 54% vs. 76%, P = 0.035) compared with Group I. Lignocaine 1 mg/kg and 1.5 mg/kg significantly reduced the incidence of severe myoclonus at 2 min (14% each) compared to Groups I (42%, P = 0.003) and II (32%, P = 0.032). Conclusion: Lignocaine 1 mg/kg and 1.5 mg/kg IV pretreatment significantly reduces the incidence of EM, with maximum attenuation observed with 1 mg/kg.
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Indian Journal of Anaesthesia 2018 62(2):145-147
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Indian Journal of Anaesthesia 2018 62(2):127-130
Background and Aims: Fast tracking (FT) for more efficacious use of resources may be difficult after living donor liver transplantation (LDLT) due to a partial liver graft, complex vascular anastomoses and longer operating time. Our study was aimed at reporting our experience with FT (on table extubation) in LDLT recipients. A secondary objective of our study was to look at defining a subgroup of patients who could be prospectively planned for FT. Methods: We studied the demographics and outcomes of 15 LDLT recipients extubated immediately in the operating suite based on an uneventful intraoperative course, haemodynamic stability after graft reperfusion and improvement of metabolic parameters post-implantation and vascular anastomoses. Results: Twelve recipients were males, and mean age, body mass index (BMI) and Model for End Stage Liver Disease (MELD) score were 43 ± 12 years, 23 ± 3 kg/m2 and 15.5 ± 6, respectively, most were Child–Turcotte–Pugh Class B. Diabetes and hypothyroidism were present in 1 and 2 patients, respectively. Post-extubation, none required immediate re-intubation and one patient needed non-invasive ventilation for 2 h. Conclusion: Fast tracked recipients were young, with a low BMI, low MELD scores, minimal comorbidities and good immediate graft function post-reperfusion.
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Erector spinae plane block an effective block for post-operative analgesia in modified radical mastectomy
Indian Journal of Anaesthesia 2018 62(2):148-150
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Pulmonary hypertension and post-operative outcome in renal transplant: A retrospective analysis of 170 patients
Indian Journal of Anaesthesia 2018 62(2):131-135
Background and Aims: Renal transplant is the best possible treatment for patients suffering with end-stage renal disease (ESRD). Cardiovascular events are the commonest factors contributing to perioperative morbidity and mortality in this population. These patients have a high incidence (up to 60%) of pulmonary hypertension (PH) and that may affect the perioperative outcome. Methods: In this study, we aimed to study the impact of PH on perioperative outcome after renal transplant. PH was defined as patients with pulmonary artery systolic pressure ≥35 mmHg on pre-operative echocardiography. Medical records of 170 patients who had undergone renal transplantation in the past 3 years were reviewed. Primary outcome was delayed graft functioning and secondary outcomes were perioperative complications such as hypotension, arrhythmias, need of post-operative mechanical ventilation, atelectasis and pulmonary oedema. Results: We observed 46.5% incidence of PH in ESRD patients. Compared to patients without PH, more patients with PH had postoperative hypotension (26.58% vs. 9.89%, P = 0.004) and delayed graft functioning (8.8% vs. 1.1%, P = 0.026). On multivariate analysis, however, PH was not an independent predictor of delayed graft functioning. Conclusion: In ESRD patients, although PH is not an independent predictor of delayed graft functioning, patients having PH are more prone for perioperative hypotension and delayed graft functioning after renal transplant.
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Indian Journal of Anaesthesia 2018 62(2):152-152
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Anaesthetic management of an infant posted for ventricular septal defect closure with right-sided eventration of diaphragm
Indian Journal of Anaesthesia 2018 62(2):136-138
Eventration of the diaphragm is a rare entity, characterised by abnormal elevation of a dome of diaphragm. In this condition, the diaphragm is composed of fibrous tissue with few or no interspersed muscle fibres. Eventration can be congenital or acquired. Congenital eventration results from inadequate development of muscles or absence of phrenic nerve. The common cause of acquired eventration is injury to the phrenic nerve from traumatic birth injury or surgery for heart disease. The perioperative anaesthetic management of diaphragmatic eventration along with ventricular septal defect with severe pulmonary hypertension makes this case both challenging and unique.
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Indian Journal of Anaesthesia 2018 62(2):154-154
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Erector spinae plane block may aid weaning from mechanical ventilation in patients with multiple rib fractures: Case report of two cases
Indian Journal of Anaesthesia 2018 62(2):139-141
Uncontrolled pain in patients with rib fracture leads to atelectasis and impaired cough which can progress to pneumonia and respiratory failure necessitating mechanical ventilation. Of the various pain modalities, regional anaesthesia (epidural and paravertebral) is better than systemic and oral analgesics. The erector spinae plane block (ESPB) is a new modality in the armamentarium for the management of pain in multiple rib fractures, which is simple to perform and without major complications. We report a case series where ESPB helped in weaning the patients from mechanical ventilation. Further randomised controlled studies are warranted in comparing their efficacy in relation to other regional anaesthetic techniques.
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Rapidly progressive neovascular glaucoma following coronary artery bypass graft surgery in a patient with type 1 diabetes mellitus: a case report
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DOI: 10.1039/C7PP00350A, Paper
Four novel metal-free organic dyes (CFB1, CFB2, CFT1, CFT2) based on indeno[2,1-b] carbazole donors were synthesized and their absorption spectra, photovoltaic performances, and electrochemical properties were evaluated. The differences in...
The content of this RSS Feed (c) The Royal Society of Chemistry
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Age- and sex-specific Canadian utility norms, based on the 2013-2014 Canadian Community Health Survey [Research]
Although many Canadian studies have provided disease-specific or patient group–specific utility scores, the utility score norms currently available for the general Canadian population are outdated. Canadian guideline recommendations for the economic evaluation of health technologies advocate for utilities reflecting those of the general population and for stratified analyses when results are heterogeneous; as such, there is also a need for age-, sex- and jurisdiction-specific utility score norms.METHODS:
We used data from the 2013–2014 Canadian Community Health Survey. We used the Health Utilities Index Mark 3 to calculate utility scores. We estimated means (with 95% confidence intervals [CIs]) and medians (with interquartile ranges [IQRs]) for utility scores. In addition to Canadian-level measures, we stratified all utility score norms by respondents’ age, sex, and province or territory of residence. We weighted respondents’ answers and computed 95% CIs using sampling weights and bootstrap weights provided by Statistics Canada to extrapolate the study findings to the Canadian population.RESULTS:
Respondents to the 2013–2014 Canadian Community Health Survey represented 30 014 589 community-dwelling Canadians 12 years of age and older (98% of the Canadian population); half of the respondents were female (50.6%), and the weighted average age was 44.8 (95% CI 44.7–44.9) years. The mean and median self-reported utility scores for Canadians were estimated at 0.863 (95% CI 0.861–0.865) and 0.927 (IQR 0.838–0.972), respectively.INTERPRETATION:
This study provides utility score norms for several age-, sex-and jurisdiction-specific strata in Canada. These results will be useful for future cost–utility analyses and could serve as benchmark values for comparisons with future studies.
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Health systems are currently subject to unprecedented financial strains. Inappropriate test use wastes finite health resources (overuse) and delays diagnoses and treatment (underuse). As most patient care is provided in primary care, it represents an ideal setting to mitigate waste.Objective
To identify overuse and underuse of diagnostic tests in primary care.Design
Systematic review and meta-analysis.Data sources and eligibility criteria
We searched MEDLINE and Embase from January 1999 to October 2017 for studies that measured the inappropriateness of any diagnostic test (measured against a national or international guideline) ordered for adult patients in primary care.Results
We included 357 171 patients from 63 studies in 15 countries. We extracted 103 measures of inappropriateness (41 underuse and 62 overuse) from included studies for 47 different diagnostic tests.
The overall rate of inappropriate diagnostic test ordering varied substantially (0.2%–100%)%).
17 tests were underused >50% of the time. Of these, echocardiography (n=4 measures) was consistently underused (between 54% and 89%, n=4). There was large variation in the rate of inappropriate underuse of pulmonary function tests (38%–78%, n=8).
Eleven tests were inappropriately overused >50% of the time. Echocardiography was consistently overused (77%–92%), whereas inappropriate overuse of urinary cultures, upper endoscopy and colonoscopy varied widely, from 36% to 77% (n=3), 10%–54% (n=10) and 8%–52% (n=2), respectively.Conclusions
There is marked variation in the appropriate use of diagnostic tests in primary care. Specifically, the use of echocardiography (both underuse and overuse) is consistently poor. There is substantial variation in the rate of inappropriate underuse of pulmonary function tests and the overuse of upper endoscopy, urinary cultures and colonoscopy.PROSPERO registration number
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Exploring the lived experience and chronic low back pain beliefs of English-speaking Punjabi and white British people: a qualitative study within the NHS
Disabling chronic low back pain (CLBP) is associated with negative beliefs and behaviours, which are influenced by culture, religion and interactions with healthcare practitioners (HCPs). In the UK, HCPs encounter people from different cultures and ethnic backgrounds, with South Asian Indians (including Punjabis) forming the largest ethnic minority group. Better understanding of the beliefs and experiences of ethnic minorities with CLBP might inform effective management.Objectives
To explore the CLBP beliefs and experiences of English-speaking Punjabi and white British people living with CLBP, explore how beliefs may influence the lived experience of CLBP and conduct cross-cultural comparisons between the two groups.Design
Qualitative study using semistructured interviews set within an interpretive description framework and thematic analysis.Setting
A National Health Service hospital physiotherapy department, Leicester, UK.Participants
10 CLBP participants (5 English-speaking Punjabi and 5 white British) purposively recruited from physiotherapy waiting lists.Results
Participants from both groups held negative biomedical CLBP beliefs such as the ‘spine is weak’, experienced unfulfilling interactions with HCPs commonly due to a perceived lack of support and negative psychosocial dimensions of CLBP with most participants catastrophising about their CLBP. Specific findings to Punjabi participants included (1) disruption to cultural-religious well-being, as well as (2) a perceived lack of understanding and empathy regarding their CLBP from the Punjabi community. In contrast to their white British counterparts, Punjabi participants reported initially using passive coping strategies; however, all participants reported a transition towards active coping strategies.Conclusion
CLBP beliefs and experiences, irrespective of ethnicity, were primarily biomedically orientated. However, cross-cultural differences included cultural-religious well-being, the community response to CLBP experienced by Punjabi participants and coping styles. These findings might help inform management of people with CLBP.
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Soft chemotherapy is very effective in older patients when added to targeted treatment in an aggressive breast cancer subtype
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IJERPH, Vol. 15, Pages 316: PM Origin or Exposure Duration? Health Hazards from PM-Bound Mercury and PM-Bound PAHs among Students and Lecturers
IJERPH, Vol. 15, Pages 316: PM Origin or Exposure Duration? Health Hazards from PM-Bound Mercury and PM-Bound PAHs among Students and Lecturers
International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15020316
Authors: Grzegorz Majewski Kamila Widziewicz Wioletta Rogula-Kozłowska Patrycja Rogula-Kopiec Karolina Kociszewska Tomasz Rozbicki Małgorzata Majder-Łopatka Mariusz Niemczyk
This study assessed inhalation exposure to particulate matter (PM1)-bound mercury (Hgp) and PM1-bound polycyclic aromatic hydrocarbons (PAHs) among university students. For this purpose, simultaneous indoor (I) and outdoor (O) measurements were taken from two Polish technical universities (in Gliwice and Warsaw) located in distinct areas with respect to ambient concentrations and major sources of PM. The indoor geometric mean concentrations of Hgp were found to be 1.46 pg·m−3 and 6.38 pg·m−3 in Warsaw and Gliwice, while the corresponding outdoor concentrations were slightly lower at 1.38 pg·m−3 and 3.03 pg·m−3, respectively. A distinct pattern was found with respect to PAH concentrations with estimated I/O values of 22.2 ng·m−3/22.5 ng·m−3 in Gliwice and 10.9 ng·m−3/11.12 ng·m−3 in Warsaw. Hazard quotients (HQs) as a result of exposure to Hgp for students aged 21 ranged from 3.47 × 10−5 (Warsaw) to 1.3 × 10−4 (Gliwice) in terms of reasonable maximum exposure (RME). The non-cancer human health risk value related to Hgp exposure was thus found to be below the acceptable risk level value of 1.0 given by the US EPA. Daily exposure values for lecture hall occupants, adjusted to the benzo(a)pyrene (BaP) toxicity equivalent (BaPeq), were 2.9 and 1.02 ng·m−3 for the Gliwice and Warsaw students, respectively. The incremental lifetime cancer risk (ILCR) values with respect to exposure to PM1-bound PAHs during the students’ time of study were 5.49 × 10−8 (Warsaw) and 1.43 × 10−7 (Gliwice). Thus, students’ exposure to indoor PAHs does not lead to increased risk of lung cancer.
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Child health and developmental inequities exist in all countries. Comprehensive and robust concepts of disadvantage are fundamental to growing an evidence base that can reveal the extent of inequities in childhood, and identify modifiable leverage points for change. We conceptualise and test a multidimensional framework of child disadvantage aligned to a social determinants and bioecological perspective.Methods
The Longitudinal Study of Australian Children is a nationally representative sample of two cohorts of Australian children, including the birth cohort of 5107 infants, which commenced in May 2004. The analysis focused on disadvantage indicators collected at age 4–5 years. Confirmatory factor analysis was used to test a theoretically informed model of disadvantage. Concurrent validity was examined through associations with academic performance at 8–9 years.Results
The model comprising four latent factors of sociodemographic (10 indicators), geographical environments (three indicators), health conditions (three indicators) and risk factors (14 indicators) was found to provide a better fit for the data than alternative models. Each factor was associated with academic performance, providing evidence of concurrent validity.Conclusion
The study provides a theoretically informed and empirically tested framework for operationalising relative child disadvantage. Understanding and addressing inequities will be facilitated by capturing the complexity of children’s experiences of disadvantage across the multiple environments in which their development unfolds.
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Impact of free access to leisure facilities and community outreach on inequalities in physical activity: a quasi-experimental study
There are large inequalities in levels of physical activity in the UK, and this is an important determinant of health inequalities. Little is known about the effectiveness of community-wide interventions to increase physical activity and whether effects differ by socioeconomic group.Methods
We conducted interrupted time series and difference-in-differences analyses using local administrative data and a large national survey to investigate the impact of an intervention providing universal free access to leisure facilities alongside outreach and marketing activities in a deprived local authority area in the northwest of England. Outcomes included attendances at swimming and gym sessions, self-reported participation in gym and swim activity and any physical activity.Results
The intervention was associated with a 64% increase in attendances at swimming and gym sessions (relative risk 1.64, 95% CI 1.43 to 1.89, P<0.001), an additional 3.9% of the population participating in at least 30 min of moderate-intensity gym or swim sessions during the previous four weeks (95% CI 3.6 to 4.1) and an additional 1.9% of the population participating in any sport or active recreation of at least moderate intensity for at least 30 min on at least 12 days out of the last four weeks (95% CI 1.7 to 2.1). The effect on gym and swim activity and overall levels of participation in physical activity was significantly greater for the more disadvantaged socioeconomic group.Conclusions
The study suggests that removing user charges from leisure facilities in combination with outreach and marketing activities can increase overall population levels of physical activity while reducing inequalities.
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Survival in relation to multimorbidity patterns in older adults in primary care in Barcelona, Spain (2010-2014): a longitudinal study based on electronic health records
Several studies have analysed the characteristics of multimorbidity patterns but none have evaluated the relationship with survival. The purpose of this study was to compare survival across older adults with different chronic multimorbidity patterns (CMPs).Methods
Prospective longitudinal observational study using electronic health records for 190 108 people aged ≥65 years in Barcelona, Spain (2009–2014). CMPs were identified by cluster analysis. Mortality rates were estimated using the Catalan population structure and individual time at risk. Survival according to CMP (Cox regression) was analysed using hazard ratios (HRs) and 95% confidence intervals (CIs) with stratification by sex and age group (65–79, 80–94) and adjustment for age at onset, deprivation index, number of chronic conditions and invoiced drugs.Results
The highest mortality rates were observed in men, adults aged 80–94 years, socially disadvantaged quintiles and people prescribed more drugs and with fewer conditions. Using the musculoskeletal pattern as the reference category, men with the digestive-respiratory pattern had a higher risk of death, with adjusted HRs of 6.16 (95% CI 5.37 to 7.06) in the 65–79 age group and 2.62 (95% CI 2.31 to 2.97) in the 80–94 age group. In women, the cardiovascular pattern was associated with the highest risk, with adjusted HRs of 6.34 (95% CI 5.28 to 7.61) in the 65–79 age group and 3.05 (95% CI 2.73 to 3.41) in the 80–94 age group. These patterns were also associated with the highest mortality rates.Conclusions
Mortality and survival vary according to CMPs in older adults stratified by sex and age. Our findings are useful for guiding the design and implementation of clinical management strategies.
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With rapid population growth, especially in low-income and middle-income countries, the generation of waste is increasing at an unprecedented rate. For example, annual global waste arising from waste electrical and electronic equipment alone will have increased from 33.8 to 49.8 million tonnes between 2010 and 2018. Despite incineration and other waste treatment techniques, landfill still dominates waste disposal in low-income and middle-income countries. There is usually insufficient funding for adequate waste management in these countries and uptake of more advanced waste treatment technologies is poor. Without proper management, many landfills represent serious hazards as typified by the landslide in Shenzhen, China on 20 December 2015. In addition to formal waste recycling systems, approximately 15million people around the world are involved in informal waste recycling, mainly for plastics, metals, glass and paper. This review examines emerging public health challenges, in particular within low-income and middle-income countries, associated with the informal sector. While informal recyclers contribute to waste recycling and reuse, the relatively primitive techniques they employ, combined with improper management of secondary pollutants, exacerbate environmental pollution of air, soil and water. Even worse, insufficient occupational health measures expose informal waste workers to a range of pollutants, injuries, respiratory and dermatological problems, infections and other serious health issues that contribute to low life expectancy. Integration of the informal sector with its formal counterparts could improve waste management while addressing these serious health and livelihood issues. Progress in this direction has already been made notably in several Latin American countries where integrating the informal and formal sectors has had a positive influence on both waste management and poverty alleviation.
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Longitudinal analysis of cardiovascular disease risk profile in neighbourhood poverty subgroups: 5-year results from an afterschool fitness programme in the USA
The WHO calls for affordable population-based prevention strategies for reducing the global burden of cardiovascular disease (CVD) on morbidity and mortality; however, effective, sustainable and accessible community-based approaches for CVD prevention in at-risk youth have yet to be identified. We examined the effects of implementing a daily park-based afterschool fitness programme on youth CVD risk profiles over 5 years and across area poverty subgroups.Methods
The study included 2264 youth (mean age 9.4 years, 54% male, 50% Hispanic, 47% non-Hispanic black, 70% high/very high area poverty) in Miami, Florida, USA. We used three-level repeated measures mixed models to determine the longitudinal effects of programme participation on modifiable CVD outcomes (2010–2016).Results
Duration of programme participation was significantly associated with CVD risk profile improvements, including body mass index (BMI) z-score, diastolic/systolic blood pressure, skinfold thicknesses, waist–hip ratio, sit-ups, push-ups, Progressive Aerobic Cardiovascular Endurance Run (PACER) score, 400 m run time, probability of developing systolic/diastolic hypertension and overweight/obesity in high/very high poverty neighbourhoods (P<0.001). Diastolic blood pressure decreased 3.4 percentile points (95% CI –5.85 to –0.85), 8.1 percentile points (95% CI –11.98 to –4.26), 6.1 percentile points (95% CI –11.49 to –0.66), 7.6 percentile points (95% CI –15.33 to –0.15) and 11.4 percentile points (95% CI –25.32 to 2.61) for 1–5 years, respectively, in high/very high poverty areas. In contrast, significant improvements were found only for PACER score and waist–hip ratio in low/mid poverty areas.Conclusion
This analysis presents compelling evidence demonstrating that park-based afterschool programmes can successfully maintain or improve at-risk youth CVD profiles over multiple years.
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Previous studies show contradictory findings on the relationship between health and intergenerational living arrangements (ILAs), which may be due to variation in who selects themselves into and out of ILA. Addressing the selectivity into ILA and the health of the older generation, we assess whether there is a health-protective or health-damaging effect of ILA. We locate our study in the Russian context, where ILA is prevalent and men’s health has become a public health issue.Methods
We apply a fixed-effects logistic regression to self-rated health status of 11 546 men aged 25 years or older who participated in at least two waves in the Russian Longitudinal Monitoring Survey from 1994 to 2015. To further isolate the health effect of ILA, we observe only associations after transitioning into or out of ILA.Results
A transition into co-residence with an unhealthy older generation increases men’s odds of reporting poor health (OR=0.64, CI 0.44 to 0.93). A transition out of co-residence with a healthy older generation decreases men’s odds of reporting fine health by 63% (OR=0.37, CI 0.28 to 0.50), whereas continuing to live with an unhealthy older generation decreases the odds by half (OR=0.49, CI 0.38 to 0.63).Conclusions
We reveal a health interlinkage between co-residing generations by finding a detrimental health effect of co-residence with an unhealthy older generation. No longer living with an older generation who was in fine health also negatively affects men’s health. Future studies should address heterogeneity related to the health of older generations, unobserved time-constant characteristics of younger generations and selectivity into/out of ILA.
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Depression is an important contributor to the global burden of disease. Besides several known individual-level factors that contribute to depression, there is a growing recognition that neighbourhood environment can also profoundly affect mental health. This study assessed associations between three neighbourhood constructs—socioeconomic deprivation, residential instability and income inequality—and depression among adult twin pairs. The twin design is used to examine the association between neighbourhood constructs and depression, controlling for selection factors (ie, genetic and shared environmental factors) that have confounded purported associations.Methods
We used multilevel random-intercept Poisson regression among 3738 same-sex twin pairs from a community-based twin registry to examine the association between neighbourhood constructs and depression. The within-pair association controls for confounding by genetic and environmental factors shared between twins within a pair, and is the main parameter of interest. Models were adjusted for individual-level income, education and marital status, and further by neighbourhood-level population density.Results
When twins were analysed as individuals (phenotypic model), all neighbourhood constructs were significantly associated with depression. However, only neighbourhood socioeconomic deprivation showed a significant within-pair association with depression. A 10-unit within-pair difference in neighbourhood socioeconomic deprivation was associated with 6% greater depressive symptoms (1.06, 95% CI 1.01 to 1.11); the association did not substantially change in adjusted models.Conclusion
This study provides new evidence linking neighbourhood socioeconomic deprivation with greater depression. Future studies should employ longitudinal designs to better test social causation versus social selection.
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Associations of neighbourhood crime with adverse pregnancy outcomes among women in Chicago: analysis of electronic health records from 2009 to 2013
Adverse pregnancy outcomes are associated with higher cardiovascular disease risk among mothers and future health problems of offspring. Neighbourhood crime may contribute to adverse pregnancy outcomes by increasing chronic stress, yet the association has been relatively understudied.Methods
Electronic health records from 34 383 singleton births at a single hospital in Chicago (2009–2013) were geocoded and linked to 1-year rates of police-recorded crime at the neighbourhood (Chicago community area) level. Crimes included homicide, assault/battery, criminal offences and incivilities. Cross-sectional associations of total neighbourhood crime rates with hypertensive disease of pregnancy (HDP: pre-eclampsia/gestational hypertension), preterm birth (PTB), spontaneous preterm birth (sPTB) and small-for-gestational-age (SGA) birth were assessed using multilevel logistic regression with community-area random intercepts. Models controlled for maternal and infant characteristics and neighbourhood poverty. We then assessed associations between individual crime categories and all outcomes.Results
Total neighbourhood crime rates ranged from 11.6 to 303.5 incidents per 1000 persons per year (mean: 61.5, SD: 40.3). A 1-SD higher total neighbourhood crime rate was associated with higher odds of HDP (OR: 1.06, 95% CI 1.00 to 1.13), PTB (OR: 1.09, 95% CI 1.03 to 1.15), sPTB (OR: 1.09, 95% CI 1.03 to 1.16) and SGA (OR: 1.05, 95% CI 1.01 to 1.10) in fully adjusted models. Associations were generally consistent across crime categories, although only assault/battery and incivilities were associated with HDP.Conclusions
Higher neighbourhood crime rates were associated with small but significant increases in the odds of adverse pregnancy outcomes. Interventions that cultivate safer neighbourhoods may be a promising approach for improving pregnancy outcomes.
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The influence of marijuana use on human fertility has not been well studied. We evaluated the association between female and male use of marijuana and fecundability in Pregnancy Study Online, a prospective cohort of North American couples.Methods
Female participants completed a baseline questionnaire on which they reported lifestyle and behavioural factors, including frequency of marijuana use within the previous 2 months. Male partners completed an optional baseline questionnaire on similar factors, including marijuana use. Women completed follow-up questionnaires every 8 weeks for 12 months or until pregnancy, initiation of fertility treatment or loss to follow-up, whichever came first. The analysis was restricted to 4194 women (1125 couples) with ≤6 cycles of pregnancy attempt time at study enrolment (2013–2017). Fecundability ratios (FR) and 95% CIs were estimated using proportional probabilities regression models, with adjustment for potential confounders.Results
Men (14.2%) were more likely than women (11.6%) to be marijuana users. FRs for female marijuana use <1 and ≥1 time/week relative to non-use were 0.99 (95% CI 0.85 to 1.16) and 0.98 (95% CI 0.80 to 1.20), respectively. FRs for male marijuana use <1 and ≥1 time/week relative to non-use were 0.87 (95% CI 0.66 to 1.15) and 1.24 (95% CI 0.90 to 1.70), respectively. Associations for frequent marijuana use (≥1 time/week) were attenuated among non-smoking men (FR=1.21, 95% CI 0.84 to 1.74), but stronger among men reporting intercourse ≥4 times/week (FR=1.35, 95% CI 0.72 to 2.53).Conclusions
In this preconception cohort study, there was little overall association between female or male marijuana use and fecundability.
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Do flexible work policies improve parents health? A natural experiment based on the UK Millennium Cohort Study
There is limited evidence of the impact of policies to promote work–family balance on family health. Exploiting the introduction of the UK Flexible Working Act (2003), we examined whether a policy that grants parents the right to request flexible work influences their health and well-being.Methods
Using the UK Millennium Cohort Study, we focus on 6424 mothers employed in 2001–2002, when the cohort child was 9 months old, until their child’s seventh birthday. We used a difference-in-differences (DiD) approach to compare changes in outcomes before and after the policy among mothers most likely to benefit and mothers unlikely to benefit from the policy.Results
Flexible working increased in a small group of mothers (n=548) whose employer did not offer work flexibility before the reform (treatment group). By contrast, among mothers whose employer already offered flexible work before the reform (control group, n=5810), there was little change or a slight decline in flexible working. DiD estimates suggest that the policy was associated with an increase in flexible working (37.5 percentage points, 95% CI 32.9 to 41.6), but it had no impact on self-rated health (–1.6 percentage points, 95% CI –4.4 to 1.1), long-term illness (–1.87 percentage points, 95% CI –4.3 to 0.5) or life satisfaction scores (β=0.04, 95% CI –0.08 to 0.16).Conclusion
The Flexible Working Act increased flexible working only among a small group of mothers who had not yet the right to request work flexibility, but it had no impact on their health and well-being. Policies promoting work flexibility may require stronger incentives for both parents and employers.
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Iodine intake from supplements and diet during pregnancy and child cognitive and motor development: the INMA Mother and Child Cohort Study
The effect of mild-to-moderate maternal iodine deficiency on the neuropsychological development of their offspring is uncertain. We aimed to assess the association between iodine status during pregnancy and the cognitive and motor development of children at 4–5 years.Methods
We conducted a prospective cohort study in four Spanish regions with recruitment of pregnant women between 2003 and 2008 and follow-up of their children up to 4–5 years (mean (SD)=4.8 (0.6)). Cognitive and motor function was assessed in 1803 children using the McCarthy Scales of Children’s Abilities. Dietary iodine and supplementation were measured through questionnaires twice during pregnancy. Urinary iodine concentration (UIC) was measured in spot samples. The residuals of a regression of UIC against creatinine were used to define a variable corrected for creatinine (UIC~Cr).Results
Neither iodine supplements nor iodised salt consumption or maternal UIC were associated with cognitive or motor function. After adjusting for creatinine, children of women with UIC~Cr <100 µg/L had 3.93 (95% CI –6.18 to –1.69) general cognitive scores lower than the reference (150–249 µg/L). Dietary iodine was inversely associated with motor scores and milk but not other dairy products or seafood consumption accounted for this association (beta: –1.36; 95% CI –2.12 to –0.61; per one daily milk serving).Conclusions
We found an association between low maternal urinary iodine and lower cognitive scores in childhood, although only when corrected for creatinine, adding to the evidence that iodine deficiency may have potential harmful effects on neurodevelopment. Iodine supplementation does not appear to improve child’s neurodevelopment at 4–5 years.
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Microscopic study on the concretion of ceramics in the “Nanhai I” shipwreck of China, Southern Song Dynasty (1,127–1,279 A.D.)
“Nanhai I” shipwreck of China Southern Song Dynasty is the oldest and the most integrally preserved shipwreck in the world. The related conservation and archeological research have caught great attention of different experts all over the world. In this study, different types of concretion covered on the surface of the ceramics in “Nanhai I” shipwreck were analyzed by X-ray diffractometer, micro-Raman spectrometer, and scanning electron microscope equipped with energy dispersive spectroscopy. Based on the analyses, we found that the grey concretion was mainly composed of quartz, aragonite, and calcite while the reddish concretion was mainly composed of pyrite and quartz. Our study indicated that the formation process of the grey concretion probably included the crystallization and transformation of aragonite, while the corrosion of iron implements and crystallization of pyrite were highly involved in the formation of reddish concretion.
Concretion of ceramics in the “Nanhai I” shipwreck consisted two major parts. Formation of the grey part included crystallization and transformation of aragonite. Formation of pyrite framboids were involved in the formation of reddish part.
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FT-Raman spectroscopy, µ-EDXRF spectrometry, and microhardness analysis of the dentin of primary and permanent teeth
The chemical compositions (organic and inorganic contents) and mechanical behaviors of the dentin of permanent and deciduous teeth were analyzed and compared using X-ray fluorescence spectrometry (µ-EDXRF) Fourier transform Raman spectroscopy (FT-Raman) and a microhardness test (HD). Healthy fresh human primary and permanent molars (n = 10) were selected, The buccal surfaces facing upwards were stabilized in an acrylic plate, flattened, polished, and submitted to the µ-EDXRF, FT-Raman, and HD analysis. The results of the analysis were subjected to ANOVAs and Mann-Whitney U/Student's t multiple comparisons tests. The data showed similar values for the dentin of the primary and permanent teeth in P content, organic content (amide I peak), inorganic content ( – 430 and 590), and microhardness, Nevertheless, Ca content and Ca/P weight ratio were higher, and the peak was lower in the dentin of the permanent teeth compared to primary teeth. It be concluded that despite permanent teeth showed more Ca element, both substrates showed similar behavior of chemical and physical properties.
The dentine substrate of primary teeth presents the lowest Ca content and Ca/P weight ratio and the permanent human dentine showed the lowest peak.
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IJMS, Vol. 19, Pages 555: Impact of DNA and RNA Methylation on Radiobiology and Cancer Progression
International Journal of Molecular Sciences doi: 10.3390/ijms19020555
Authors: Hsiang-Cheng Chi Chung-Ying Tsai Ming-Ming Tsai Kwang-Huei Lin
Radiotherapy is a well-established regimen for nearly half the cancer patients worldwide. However, not all cancer patients respond to irradiation treatment, and radioresistance is highly associated with poor prognosis and risk of recurrence. Elucidation of the biological characteristics of radioresistance and development of effective prognostic markers to guide clinical decision making clearly remain an urgent medical requirement. In tumorigenic and radioresistant cancer cell populations, phenotypic switch is observed during the course of irradiation treatment, which is associated with both stable genetic and epigenetic changes. While the importance of epigenetic changes is widely accepted, the irradiation-triggered specific epigenetic alterations at the molecular level are incompletely defined. The present review provides a summary of current studies on the molecular functions of DNA and RNA m6A methylation, the key epigenetic mechanisms involved in regulating the expression of genetic information, in resistance to irradiation and cancer progression. We additionally discuss the effects of DNA methylation and RNA N6-methyladenosine (m6A) of specific genes in cancer progression, recurrence, and radioresistance. As epigenetic alterations could be reversed by drug treatment or inhibition of specific genes, they are also considered potential targets for anticancer therapy and/or radiotherapy sensitizers. The mechanisms of irradiation-induced alterations in DNA and RNA m6A methylation, and ways in which this understanding can be applied clinically, including utilization of methylation patterns as prognostic markers for cancer radiotherapy and their manipulation for anticancer therapy or use as radiotherapy sensitizers, have been further discussed.
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Extranodal follicular dendritic cell sarcoma (FDCS) is a very rare tumour, only reported in case reports and case series. It poses diagnostic and management challenge both to the clinician and pathologist. We present such a rare case of duodenal FDCS in a 56-year-old woman who was recently managed in our institution. Repeated pre surgical biopsies were non-diagnostic and the final diagnosis was made only after surgical excision of the tumour and with the help of histopathological and immunohistochemical studies. The patient had a complete en block resection of the tumour and was discharged home well 5 days postsurgery. To the best of our knowledge, this is the first case of FDCS reported arising from the duodenum.
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A 17-year-old girl presented with fever, myalgia, vomiting for 1 month and oliguria and dyspnoea for 4 days. She was tachycardic,hypertensive, with pedal oedema and decreased breath sounds. She had high serum creatinine (3 mg/dL), anaemia, thrombocytopenia, leucocytosis and eosinophilia with schistocytes. Lactate dehydrogenase, transaminases were high , with low haptoglobin and high ferritin (5269 ng/mL). Complement C3/C4 and fibrinogen were normal. Urinalysis showed large blood and protein and stool studies were negative. Her ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was normal. Kidney biopsy showed acute interstitial nephritis (AIN) in addition to thrombotic angiopathy. The differentials - haemolytic uraemic syndrome (HUS), thrombotic thrombocytopenia (TTP) and haemophagocytic lymphohistiocytosis (HLH) were ruled out. Her genetic testing was abnormal for large CFHR1–CFHR3 homozygous deletion and heterozygous missense variant in exon 2 of DGKE making the diagnosis of atypical HUS. She received eculizumab and was discharged on oral steroids for AIN and biweekly eculizumab infusions with excellent recovery.
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An 18-year-old Caucasian woman presented with a 2-week history of a pruritic rash commencing on the face and spreading distally to the trunk and limbs. There were no associated systemic symptoms. Her medical history was unremarkable and there was a family history of hypothyroidism. Physical examination revealed extensive confluent scaly erythema with islands of sparing on the trunk and scaling of the scalp. There was hyperkeratotic plugging of the hair follicles (figure 1 and figure 2). There was a waxy orange keratoderma affecting the palms and soles with associated painful fissuring (figure 3). A clinical diagnosis of pityriasis rubra pilaris (PRP) was made. Histopathology of involved skin showed focal parakeratosis and orthokeratosis alternating in both horizontal and vertical directions with an underlying perivascular inflammatory infiltrate. The patient had a raised thyroid stimulating hormone (TSH) and normal T4 indicative of subclinical hypothyroidism. Treatment for her...
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Bilobed gallbladder is a rare form of duplication of gallbladder. Preoperative diagnosis is important to avoid peroperative complications; however, it is also a challenge as imaging reports are often confounding. A case of bilobed gallbladder managed successfully laparoscopically is presented.
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Spontaneous pneumomediastinum is the presence of free air within the mediastinum that is not associated with trauma. It is a rare, self-limiting condition that can cause widespread subcutaneous surgical emphysema. We present the case of a 12-year-old boy who presented with widespread spontaneous surgical emphysema and pneumomediastinum, with no history of trauma or respiratory tract disease. We discuss our assessment of him and management with our multidisciplinary team (MDT), and whether radiological investigations including CT are helpful in such cases. In conclusion, we hypothesised that the child’s coughing was the most likely cause of the tracheal rupture leading to the spontaneous surgical emphysema. Spontaneous pneumomediastinum in the paediatric patient is extremely rare. This case highlights how spontaneous pneumomediastinum can be successfully managed conservatively, and how MDT input can be helpful in guiding management in such unusual cases.
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A 58-year-old right-handed woman presented to our institution with a 1-month history of polydipsia and polyuria. She had a remote history of neurofibroma excision by dermatology and, on examination, was noted to meet the clinical diagnostic criteria for neurofibromatosis type 1. Laboratory investigations revealed hypernatraemia and elevated serum osmolality, accompanied by reduced urinary osmolality. A subsequent water deprivation test confirmed central diabetes insipidus, which responded to treatment with desmopressin. MRI of the brain showed pituitary enlargement, which raised the possibility of an underlying pituitary adenoma or, alternatively, lymphocytic hypophysitis. Both conditions have rarely been described in neurofibromatosis.
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Acute rheumatic fever presenting as complete heart block: report of an adolescent case and review of literature
A 14-year-old boy suffering from chronic rheumatic heart disease came to the emergency department with recurrent episodes of presyncope and syncope. He was found to have complete heart block (CHB) and required temporary pacemaker insertion. Further workup revealed that CHB was secondary to acute rheumatic carditis. His atrioventricular (AV) conduction abnormalities recovered in a stepwise fashion over 5 days while he was being treated with corticosteroids, without the need for permanent pacemaker insertion. This case illustrates that acute rheumatic carditis can rarely present with advanced AV conduction block, which may be reversible.
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Purpose of Reviews
Complex diseases are caused by a combination of genetic and environmental factors, creating a challenge for understanding the disease mechanisms. Understanding the interplay between genes and environmental factors is important, as genes do not operate in isolation but rather in complex networks and pathways influenced by environmental factors. The advent of new technologies has made a massive amount of genetic data available, and various statistical methods have been developed to analyze genetic data and to identify interactions between genes and the environment, i.e., gene-environment (G-E) interactions.
In this review article, we introduce various statistical methods for identifying G-E interactions using case-control designs. We review a range of disease risk models for modeling the joint effects of genetic and environmental factors such as multiplicative and additive models. We then introduce various inference methods under these disease risk models, which include a standard prospective likelihood, case-only designs, a retrospective likelihood that exploits a gene-environment independence assumption to boost power, and an empirical Bayes type approach that uses the independence assumption in a data-adaptive way. Several tests for detecting genetic associations in the presence of G-E interactions are also introduced, which include a joint test and a maximum score test that provides a unified approach by integrating a class of disease risk models to maximize over a class of score tests.
There are several challenges of G-E interaction analysis that include replication issues. While more powerful statistical methods for detecting interactions are helpful, ultimately studies with larger sample sizes are needed to identify interactions through consortium-based studies to achieve adequate power for G-E analysis.
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IJMS, Vol. 19, Pages 554: The Influences of Soybean Agglutinin and Functional Oligosaccharides on the Intestinal Tract of Monogastric Animals
IJMS, Vol. 19, Pages 554: The Influences of Soybean Agglutinin and Functional Oligosaccharides on the Intestinal Tract of Monogastric Animals
International Journal of Molecular Sciences doi: 10.3390/ijms19020554
Authors: Li Pan Mohammed Farouk Guixin Qin Yuan Zhao Nan Bao
Soybean agglutinin (SBA) is a non-fiber carbohydrate-related protein and the main anti-nutritional factor that exists in soybean or soybean products. SBA possesses a specific binding affinity for N-glyphthalide-d-galactosamine or galactose and has a covalently linked oligosaccharide chain. SBA mediates negative effects on animal intestinal health by influencing the intestinal structure, barrier function, mucosal immune system, and the balance of the intestinal flora. Functional oligosaccharides are non-digestible dietary oligosaccharides that are commonly applied as prebiotics since the biological effects of the functional oligosaccharides are to increase the host health by improving mucosal structure and function, protecting the integrity of the intestinal structure, modulating immunity, and balancing the gastrointestinal microbiota. The purpose of this review is to describe the structure and anti-nutritional functions of SBA, summarize the influence of SBA and functional oligosaccharides on the intestinal tract of monogastric animals, and emphasize the relationship between SBA and oligosaccharides. This review provides perspectives on applying functional oligosaccharides for alleviating the anti-nutritional effects of SBA on the intestinal tract.
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Morphological and morphometric assessment of the elements of the ureterovesical junction in children was performed in the present study in different age groups ranging from 24 weeks of gestation to 16 years old. We tried to answer the question whether, in human ontogenesis, there is a period of anatomical predisposition to primary vesicoureteral reflux. The study included 210 urinary bladders with juxtavesical parts of the ureters that had been obtained from routine autopsies. As a result of the study, we showed that provided the pregnancy is uncomplicated there is no inherited susceptibility that would account for reducing or disturbing the development of ureterovesical junction elements. Based on the analysis of our results concerning the anatomy and morphological changes taking place in the elements of the ureterovesical junction in different age groups, one could put forward a hypothesis that anatomical predisposition to primary vesicoureteral reflux occurs in age group II, i.e. between 28 and 37 weeks of gestation. The parameters that define interrelations between elements of the ureterovesical junction and that are considered essential for normal functioning of antireflux mechanism were still observed in age group VI in our study. This suggests that these relations are not unambiguous in children with normally structured and functionally competent vesicoureteral junction.
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Thalamic Deep Brain Stimulation Salvages Failed Focused Ultrasound Thalamotomy for Essential Tremor: A Case Report
Stereotact Funct Neurosurg
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The role of unfolded protein response and ER-phagy in quantum dots-induced nephrotoxicity: an in vitro and in vivo study
Unfolded protein response (UPR) and endoplasmic reticulum (ER)-phagy are essential for cell homeostasis. Quantum dots (QDs), which have been widely used for biomedical applications, can accumulate in the kidney tissues and may cause renal dysfunction. However, the molecular mechanism of QDs-induced nephrotoxicity is still obscure. The present study was aimed to elucidate the role and mechanism of UPR and ER-phagy in QDs-induced nephrotoxicity. Herein, human embyronic kidney (HEK) cells were exposed to 15, 30, 45, and 60 nM cadmium telluride (CdTe)-QDs for 12 and 24 h. And CdTe-QDs (30–60 nM) inhibited the HEK cell viability. The clathrin-dependent endocytosis was determined as the main pathway of CdTe-QDs cellular uptake. Within cells, CdTe-QDs disrupted ER ultrastructure and induced UPR and FAM134B-dependent ER-phagy. Blocking UPR with inhibitors or siRNA rescued the FAM134B-dependent ER-phagy, which was triggered by CdTe-QDs. Moreover, suppression of UPR or FAM134B-dependent ER-phagy restored the cell vability. In vivo, mice were intravenously injected with 8 and 16 nmol/kg body weight CdTe-QDs for 24 h. Kidney was shown as one of highest distributed organs of CdTe-QDs, resulting in renal dysfunction, as well as UPR and FAM134B-dependent ER-phagy in it. Thus, for the first time, we demonstrated that ER-phagy can be triggered by nanomaterials both in vitro and in vivo. In addition, blocking of UPR and ER-phagy showed protective effects against CdTe-QDs-induced toxicity in kideny cells. Notably, a secreted alkaline phosphatase reporter gene system has been developed as a sensitive and rapid method for evaluating the ER quality under the exposure of nanomaterials.
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To study the feasibility of designing a human cadaveric simulation model of real CSF leak for rhinology training.
The laboratory investigation took place at the surgical academic center of Prince Sultan Military Medical City between 2016 and 2017. Five heads of human cadaveric specimens were cannulated into the intradural space through two frontal bone holes. Fluorescein-dyed fluid was injected intracranialy, then endoscopic endonasal iatrogenic skull base defect was created with observation of fluid leak, followed by skull base reconstruction. The outcome measures included subjective assessment of integrity of the design, the ability of creating real CSF leak in multiple site of skull base and the possibility of watertight closure by various surgical techniques.
The fluid filled the intradural space in all specimens without spontaneous leak from skull base or extra sinus areas. Successfully, we demonstrated fluid leak from all areas after iatrogenic defect in the cribriform plate, fovea ethmoidalis, planum sphenoidale sellar and clival regions. Watertight closure was achieved in all defects using different reconstruction techniques (overly, underlay and gasket seal closure).
The design is simulating the real patient with CSF leak. It has potential in the learning process of acquiring and maintaining the surgical skills of skull base reconstruction before direct involvement of the patient. This model needs further evaluation and competence measurement as training tools in rhinology training.
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Association of the nod-like receptor 3 (NLRP3) gene variability with recurrent aphthous stomatitis in the Czech population
Recurrent aphthous stomatitis (RAS) is a multifactorial disease with unclear etiopathogenesis in which disturbance of immunological processes maybe involved. The aim of our study was to investigate three single nucleotide polymorphisms (SNPs) rs3806265, rs4612666, rs10754558 in NOD-like receptor 3 (NLRP3), the gene encoding the component of inflammasome, in patients with RAS and healthy controls in the Czech population.
A total of 207 subjects were included in this case-control study. Sixty-four patients with RAS and 143 healthy controls were genotyped by a method based on polymerase chain reaction using 5′ nuclease TaqMan® assays. Detailed anamnestic, clinical and laboratory data were obtained from all subjects.
The allele and genotype frequencies of NLRP3 polymorphisms (rs10754558 and rs3806265) between both groups were similar. However, statistically significant differences in NLRP3 rs4612666 genotypes between the patients with RAS and controls were found; carriers of the TT genotype had a higher risk of developing RAS than subjects with the CT+CC genotypes (OR=14.69, 95%CI=1.73-124.72, P=0.004, Pcorr<0.05). No associations between NLRP3 haplotypes and RAS were observed.
Our study indicates that the NLRP3 rs4612666 polymorphism may be involved in the development of RAS in the Czech population.
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Short-Term Effects of Cold Liquids on the Pharyngeal Swallow in Preterm Infants with Dysphagia: A Pilot Study
Cold stimulation reduces airway compromise in adults with dysphagia. However, there is no sufficient evidence to support its use in the pediatric population. The primary goal of this pilot study is to assess the effect of cold liquid on the pharyngeal swallow mechanism in preterm infants with dysphagia. We hypothesized that thermal stimulation from cold liquid will decrease the risk of airway compromise in dysphagic preterm infants. Nine preterm infants with clinical symptoms of dysphagia were included. Video fluoroscopic swallow studies were used to assess the swallowing mechanism of each participant. The occurrence of swallow dysfunctions under room temperature liquid swallows (RTS) vs. short period cold liquid swallows (CS) was compared. Paired t test was used to test significance. The occurrence of deep penetration (p = 0.007) and aspiration (p = 0.002) decreased significantly in the CS condition compared with the RTS condition. There was a trend of less nasopharyngeal reflux with CS but did not reach statistical significance (p = 0.084). No differences were noted for mild penetration (p = 0.824). CS reduced airway compromise in dysphagic preterm infants compared to RTS. These data provide important information regarding the immediate effects of CS on pharyngeal swallowing in preterm infants with dysphagia. However, further investigation regarding its sustained effects is required before introducing to clinical practice.
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Enhanced efficacy of AZD3759 and radiation on brain metastasis from EGFR mutant non-small cell lung cancer
The prognosis of patients with brain metastasis (BM) is poor. In this study, we demonstrated that AZD3759, an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration, combined with radiation enhanced the antitumor efficacy in BM model from EGFR mutant (EGFRm) NSCLC. Besides, the antitumor activity displayed no difference between radiation concurrently with AZD3759 and radiation sequentially with AZD3759. Mechanistically, we found that two factors determined the enhanced efficacy: cells with EGFRm which were sensitive to AZD3759, and a relative high concentration of AZD3759. We have validated mechanisms underlying the radio-sensitizing effect of AZD3759, which were involved in decreased cell proliferation and survival, and suppressed repair of DNA damage. Moreover, our study found that AZD3759 inhibited both the non-homologous end joining (NHEJ) and homologous recombination (HR) DNA double stands breaks (DSBs) repair pathway, and abrogated the G2/M checkpoint to suppress DNA damage repair. We also detected the BBB penetration of AZD3759 when combined with cranial radiation. The results showed the BBB penetration of AZD3759 was decreased within 24 hours after radiation, however, the free concentration of AZD3759 in brain kept at a high level in the context of radiation. In conclusion, our findings suggest that AZD3759 combined with radiation enhances the antitumor activity in BM from EGFRm NSCLC, this combination therapy may be an effective treatment option for BM from EGFRm NSCLC. This article is protected by copyright. All rights reserved.
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IJMS, Vol. 19, Pages 552: Biochemical Mechanism of Rhododendrol-Induced Leukoderma
International Journal of Molecular Sciences doi: 10.3390/ijms19020552
Authors: Shosuke Ito Kazumasa Wakamatsu
RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol (RD))—a skin-whitening ingredient—was reported to induce leukoderma in some consumers. We have examined the biochemical basis of the RD-induced leukoderma by elucidating the metabolic fate of RD in the course of tyrosinase-catalyzed oxidation. We found that the oxidation of racemic RD by mushroom tyrosinase rapidly produces RD-quinone, which gives rise to secondary quinone products. Subsequently, we confirmed that human tyrosinase is able to oxidize both enantiomers of RD. We then showed that B16 cells exposed to RD produce high levels of RD-pheomelanin and protein-SH adducts of RD-quinone. Our recent studies showed that RD-eumelanin—an oxidation product of RD—exhibits a potent pro-oxidant activity that is enhanced by ultraviolet-A radiation. In this review, we summarize our biochemical findings on the tyrosinase-dependent metabolism of RD and related studies by other research groups. The results suggest two major mechanisms of cytotoxicity to melanocytes. One is the cytotoxicity of RD-quinone through binding with sulfhydryl proteins that leads to the inactivation of sulfhydryl enzymes and protein denaturation that leads to endoplasmic reticulum stress. The other mechanism is the pro-oxidant activity of RD-derived melanins that leads to oxidative stress resulting from the depletion of antioxidants and the generation of reactive oxygen radicals.
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IJMS, Vol. 19, Pages 553: Stabilization of Immobilized Lipases by Intense Intramolecular Cross-Linking of Their Surfaces by Using Aldehyde-Dextran Polymers
IJMS, Vol. 19, Pages 553: Stabilization of Immobilized Lipases by Intense Intramolecular Cross-Linking of Their Surfaces by Using Aldehyde-Dextran Polymers
International Journal of Molecular Sciences doi: 10.3390/ijms19020553
Authors: Alejandro Orrego Rohollah Ghobadi Sonia Moreno-Perez Adriana Mendoza Gloria Fernandez-Lorente Jose Guisan Javier Rocha-Martin
Immobilized enzymes have a very large region that is not in contact with the support surface and this region could be the target of new stabilization strategies. The chemical amination of these regions plus further cross-linking with aldehyde-dextran polymers is proposed here as a strategy to increase the stability of immobilized enzymes. Aldehyde-dextran is not able to react with single amino groups but it reacts very rapidly with polyaminated surfaces. Three lipases—from Thermomyces lanuginosus (TLL), Rhizomucor miehiei (RML), and Candida antarctica B (CALB)—were immobilized using interfacial adsorption on the hydrophobic octyl-Sepharose support, chemically aminated, and cross-linked. Catalytic activities remained higher than 70% with regard to unmodified conjugates. The increase in the amination degree of the lipases together with the increase in the density of aldehyde groups in the dextran-aldehyde polymer promoted a higher number of cross-links. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of those conjugates demonstrates the major role of the intramolecular cross-linking on the stabilization of the enzymes. The highest stabilization was achieved by the modified RML immobilized on octyl-Sepharose, which was 250-fold more stable than the unmodified conjugate. The TLL and the CALB were 40-fold and 4-fold more stable than the unmodified conjugate.
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