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IntroductionHyperinflation is a common procedure to clear secretion, increase lung compliance and enhance oxygenation in mechanically ventilated patients. Hyperinflation can be provided as manual hyperinflation (MHI) or ventilator hyperinflation (VHI), where outcomes depend upon the methods of application. Hence it is crucial to assess the application of techniques employed in Sri Lanka due to observed variations from recommended practices.ObjectiveThis study is aimed to evaluate the application and parameters used for MHI and VHI by physiotherapists in intensive care units (ICUs) in Sri Lanka.MethodologyAn online survey was conducted among physiotherapists who are working in ICUs in Sri Lanka using WhatsApp groups and other social media platforms.ResultsA total of 96 physiotherapists responded. The survey comprised of three sections to obtain information about socio-demographic data, MHI practices and VHI practices. Most of the respondents (47%) worked in general hospitals and 74% of participants had a bachelor's degree in physiotherapy; 31.3% had 3-6 years of experience; 93.8% used hyperinflation, and 78.9% used MHI. MHI was performed routinely and as needed to treat low oxygen levels, abnormal breath sounds, and per physician orders while avoiding contraindications. Self-inflation bags are frequently used for MHI (40.6%). Only a few participants (26%) used a manometer or tracked PIP. In addition to the supine position, some participants (37.5%) used the side-lying position. Most physiotherapists followed the recommended MHI technique: slow squeeze (57.3%), inspiratory pause (45.8%), and quick release (70.8%). VHI was practised by 19.8%, with medical approval and it was frequently performed by medical staff compared to physiotherapists. Treatment time, number of breaths, and patient positioning varied, and parameters were not well-defined.ConclusionThe study found that MHI was not applied with the recommended PIP, and VHI parameters were not identified. The study indicates a need to educate physiotherapists about current VHI and MHI practice guidelines.

Data annotation in NLP is a costly and time-consuming task, traditionally handled by human experts who require extensive training to enhance the task-related background knowledge. Besides, labeling social media texts is particularly challenging due to their brevity, informality, creativity, and varying human perceptions regarding the sociocultural context of the world. With the emergence of GPT models and their proficiency in various NLP tasks, this study aims to establish a performance baseline for GPT-4 as a social media text annotator. To achieve this, we employ our own dataset of tweets, expertly labeled for stance detection with full inter-rater agreement among three annotators. We experiment with three techniques: Zero-shot, Few-shot, and Zero-shot with Chain-of-Thoughts to create prompts for the labeling task. We utilize four training sets constructed with different label sets, including human labels, to fine-tune transformer-based large language models and various combinations of traditional machine learning models with embeddings for stance classification. Finally, all fine-tuned models undergo evaluation using a common testing set with human-generated labels. We use the results from models trained on human labels as the benchmark to assess GPT-4's potential as an annotator across the three prompting techniques. Based on the experimental findings, GPT-4 achieves comparable results through the Few-shot and Zero-shot Chain-of-Thoughts prompting methods. However, none of these labeling techniques surpass the top three models fine-tuned on human labels. Moreover, we introduce the Zero-shot Chain-of-Thoughts as an effective strategy for aspect-based social media text labeling, which performs better than the standard Zero-shot and yields results similar to the high-performing yet expensive Few-shot approach.

BackgroundDiabetic polyneuropathy (DPN) is a notable microvascular complication of DM, affecting 16%-66% globally. DPN often leads to proprioceptive deficits in the lower limbs (LL), leading to impaired functional performance. However, evidence supporting proprioceptive rehabilitation programs (PRP) for DPN remains scarce.AimsThis pilot study aims to evaluate the effectiveness of a novel 12-week PRP on LL static and dynamic proprioception and shed light on the potential benefits of PRP for DPN population.MethodsRandomized Controlled Trail was conducted among 30 DPN patients (age 53.25±7.72 years, BMI 24.01±1.41 and DM duration 9.48±6.45 years), randomly allocated to intervention (n = 15) or control (n = 15) groups. The intervention group received PRP 3 times/week for 12 weeks. The control group received no exercise. Both groups received regular diabetic care. Static and dynamic proprioception of both LL were assessed at baseline, 6 weeks and 12 weeks. Position-reposition test was used to assess ankle joint position sense by obtaining difference between target and reproduced angles. Error in detecting knee angle and speed were obtained by performing Lower Limb Matching and Sense of Movement tests respectively to assess dynamic proprioception.ResultsTwo-way ANOVA and paired comparisons revealed, no significant improvement in proprioceptive deficits at 6 weeks (p>0.05), but significant improvement was achieved at 12-weeks (pConclusionsNovel 12-week PRP may yield a significant reduction in LL proprioceptive deficits among DPN patients. Future RCTs with larger samples should compare the effectiveness of this PRP compared with conventional rehabilitation programs.

ObjectivesThis study examined the evidence of the prevalence of psychological distress and poor sleep among medical students and its associations during an economic crisis.DesignThis was a cross-sectional study using an online questionnaire. It included the Depression Anxiety Stress Scales and Pittsburgh Sleep Quality Index (PSQI).Setting and participantsThis study included medical undergraduates from a large metropolitan university in Sri Lanka.Primary and secondary outcome measuresWe assessed the prevalence of psychological distress, sleep quality, and factors associated with psychological distress. To evaluate the associations, we used logistic regression.ResultsThe majority (69.2%) had some form of distress (depression, anxiety or stress), while 23% had distress in all three. Anxiety was the most prevalent (50.7%). Poor sleep quality was reported in 41%. The highest contribution to global PSQI was from sleep latency, duration, and daytime dysfunction subscales. In bivariate analysis, sleep quality was directly related to depression (t245.65 = -6.75, pConclusionsPoor sleep quality and psychological distress are high among the undergraduates. The findings emphasize the importance of addressing sleep quality and psychological wellbeing in medical undergraduates. Further research with larger and more diverse samples is needed for a more comprehensive understanding of the factors associated with psychological distress among undergraduates.

Falls can be identified as one of the main issues in elderly population which can lead to serious consequences. Elderly population can be subdivided as community dwelling older adults and institutionalized older adults. The components of health-related physical fitness factors play an important role in the perspective of healthy ageing. The objective of the study was to determine the prevalence of falls and to compare health-related physical fitness factors between different fall categories among institutionalized older adults. This descriptive cross-sectional study comprised of one hundred and seventy-two elders above 60 years of age, living in registered elder's homes in Kandy District. The prevalence of falls was determined by the number of falls reported by the subjects. They were further categorized as non-fallers, fallers, and frequent fallers depending on the number of falls. Body Mass Index (BMI) for body composition, 2-minute walk test for cardiovascular endurance, 30 second sit to stand test for muscle strength and endurance, hand grip strength for upper body strength, chair sit and reach test for lower body flexibility and back scratch test for upper body flexibility were the measures used to assess health-related physical fitness factors. The prevalence of falls is presented as percentage and the health-related factors were compared between the three faller categories using one-way ANOVA and pairwise comparison was performed using Scheffe test. The prevalence of falls was 47.1%. There was a significant difference in BMI, cardiovascular endurance, and lower body flexibility between the three categories of fallers. Higher BMI, lower cardiovascular endurance and lower flexibility in the lower body were associated with increased prevalence of falls (p0.05). The findings suggest that, BMI, cardiovascular endurance, and lower body flexibility must be addressed and managed, while designing intervention programs for falls prevention among institutionalized older adults.

People's quality of life (QOL) has been disrupted globally in the wake of the pandemic in recent times. This was mainly due to global economic crises fuelled by the coronavirus (COVID- 19) and other related factors. Sri Lanka, too, was facing major social and economic constraints in the period 2021-2022. Thus, all communities islandwide have been economically disturbed. Among others, people with Visual Impairment and Blindness (VIB) have been pushed to severely disadvantageous positions, financially and otherwise. A sample from three geographical locations in Sri Lanka; and eleven individuals representing diverse cadres in Sri Lankan society were purposively selected for the study based on the existence of the majority of the visually impaired community using a mixed approach. Descriptive statistics were utilised to analyse the identified socio-economic characteristics. Ordered probit regression was employed to determine the mediating effect of socio-economic status on income levels. Word Cloud illustrates the factors affecting the QOL. Most severely impaired individuals are more likely to earn a lower rate of income. This situation has degraded their lives and poor QOL. Participants' responses elucidate that facilities, resources, education, opportunities, income, employment, and government activities would enhance their QOL. The study adds value to society by recognising VIB people, helping them gain financial independence and strengthening them without marginalising the impaired community. The proposed policies in this study would be valuable for these social groups to address their wealth concerns.

Introduction: Hyperinflation is a common procedure to clear secretion, increase lung compliance and enhance oxygenation in mechanically ventilated patients. Hyperinflation can be provided as manual hyperinflation (MHI) or ventilator hyperinflation (VHI), where outcomes depend upon the methods of application. Hence it is crucial to assess the application of techniques employed in Sri Lanka due to observed variations from recommended practices. Objective: This study is aimed to evaluate the application and parameters used for MHI and VHI by physiotherapists in intensive care units (ICUs) in Sri Lanka. Methodology: An online survey was conducted among physiotherapists who are working in ICUs in Sri Lanka using WhatsApp groups and other social media platforms. Results: A total of 96 physiotherapists responded. The survey comprised of three sections to obtain information about socio-demographic data, MHI practices and VHI practices. Most of the respondents (47%) worked in general hospitals and 74% of participants had a bachelor's degree in physiotherapy; 31.3% had 3–6 years of experience; 93.8% used hyperinflation, and 78.9% used MHI. MHI was performed routinely and as needed to treat low oxygen levels, abnormal breath sounds, and per physician orders while avoiding contraindications. Self-inflation bags are frequently used for MHI (40.6%). Only a few participants (26%) used a manometer or tracked PIP. In addition to the supine position, some participants (37.5%) used the side-lying position. Most physiotherapists followed the recommended MHI technique: slow squeeze (57.3%), inspiratory pause (45.8%), and quick release (70.8%). VHI was practised by 19.8%, with medical approval and it was frequently performed by medical staff compared to physiotherapists. Treatment time, number of breaths, and patient positioning varied, and parameters were not well-defined. Conclusion: The study found that MHI was not applied with the recommended PIP, and VHI parameters were not identified. The study indicates a need to educate physiotherapists about current VHI and MHI practice guidelines. [ABSTRACT FROM AUTHOR]

Data annotation in NLP is a costly and time-consuming task, traditionally handled by human experts who require extensive training to enhance the task-related background knowledge. Besides, labeling social media texts is particularly challenging due to their brevity, informality, creativity, and varying human perceptions regarding the sociocultural context of the world. With the emergence of GPT models and their proficiency in various NLP tasks, this study aims to establish a performance baseline for GPT-4 as a social media text annotator. To achieve this, we employ our own dataset of tweets, expertly labeled for stance detection with full inter-rater agreement among three annotators. We experiment with three techniques: Zero-shot, Few-shot, and Zero-shot with Chain-of-Thoughts to create prompts for the labeling task. We utilize four training sets constructed with different label sets, including human labels, to fine-tune transformer-based large language models and various combinations of traditional machine learning models with embeddings for stance classification. Finally, all fine-tuned models undergo evaluation using a common testing set with human-generated labels. We use the results from models trained on human labels as the benchmark to assess GPT-4's potential as an annotator across the three prompting techniques. Based on the experimental findings, GPT-4 achieves comparable results through the Few-shot and Zero-shot Chain-of-Thoughts prompting methods. However, none of these labeling techniques surpass the top three models fine-tuned on human labels. Moreover, we introduce the Zero-shot Chain-of-Thoughts as an effective strategy for aspect-based social media text labeling, which performs better than the standard Zero-shot and yields results similar to the high-performing yet expensive Few-shot approach. [ABSTRACT FROM AUTHOR]

Background: Diabetic polyneuropathy (DPN) is a notable microvascular complication of DM, affecting 16%-66% globally. DPN often leads to proprioceptive deficits in the lower limbs (LL), leading to impaired functional performance. However, evidence supporting proprioceptive rehabilitation programs (PRP) for DPN remains scarce. Aims: This pilot study aims to evaluate the effectiveness of a novel 12-week PRP on LL static and dynamic proprioception and shed light on the potential benefits of PRP for DPN population. Methods: Randomized Controlled Trail was conducted among 30 DPN patients (age 53.25±7.72 years, BMI 24.01±1.41 and DM duration 9.48±6.45 years), randomly allocated to intervention (n = 15) or control (n = 15) groups. The intervention group received PRP 3 times/week for 12 weeks. The control group received no exercise. Both groups received regular diabetic care. Static and dynamic proprioception of both LL were assessed at baseline, 6 weeks and 12 weeks. Position-reposition test was used to assess ankle joint position sense by obtaining difference between target and reproduced angles. Error in detecting knee angle and speed were obtained by performing Lower Limb Matching and Sense of Movement tests respectively to assess dynamic proprioception. Results: Two-way ANOVA and paired comparisons revealed, no significant improvement in proprioceptive deficits at 6 weeks (p>0.05), but significant improvement was achieved at 12-weeks (p<0.05) in the intervention group. Mean errors in Pposition re-position(R:p<0.001, L;p<0.001) and Lower limb matching (R:p<0.001, L;p<0.001) tests reduced by 5° and 10° respectively, indicating a70% improvement in the intervention group. Error of detecting speed reduced only on right side by 0.041ms-1 accounting for a 42% improvement. No improvements were observed in the control group. Conclusions: Novel 12-week PRP may yield a significant reduction in LL proprioceptive deficits among DPN patients. Future RCTs with larger samples should compare the effectiveness of this PRP compared with conventional rehabilitation programs. [ABSTRACT FROM AUTHOR]

BackgroundLive oral rotavirus vaccines (LORVs) have significantly reduced rotavirus hospitalizations and deaths worldwide. However, LORVs are less effective in low- and middle-income countries (LMICs). Next-generation rotavirus vaccines (NGRVs) may be more effective but require administration by injection or a neonatal oral dose, adding operational complexity. Healthcare providers (HPs) were interviewed to assess rotavirus vaccine preferences and identify delivery issues as part of an NGRV value proposition.ObjectiveDetermine HP vaccine preferences about delivering LORVs compared to injectable (iNGRV) and neonatal oral (oNGRV) NGRVs.Methods64 HPs from Ghana, Kenya, Malawi, Peru, and Senegal were interviewed following a mixed-method guide centered on three vaccine comparisons: LORV vs. iNGRV; LORV vs. oNGRV; oNGRV vs. iNGRV. HPs reviewed attributes for each vaccine in the comparisons, then indicated and explained their preference. Additional questions elicited views about co-administering iNGRV+LORV for greater public health impact, a possible iNGRV-DTP-containing combination vaccine, and delivering neonatal doses.ResultsAlmost all HPs preferred oral vaccine options over iNGRV, with many emphasizing an aversion to additional injections. Despite this strong preference, HPs described challenges delivering oral doses. Preferences for LORV vs. oNGRV were split, marked by disparate views on rotavirus disease epidemiology and the safety, need, and feasibility of delivering neonatal vaccines. Although overwhelmingly enthusiastic about an iNGRV-DTP-containing combination option, several HPs had concerns. HP views were divided on the feasibility of co-administering iNGRV+LORV, citing challenges around logistics and caregiver sensitization.ConclusionOur findings provide valuable insights on delivering NGRVs in routine immunization. Despite opposition to injectables, openness to co-administering LORV+iNGRV to improve efficacy suggests future HP support of iNGRV if adequately informed of its advantages. Rationales for LORV vs. oNGRV underscore needs for training on rotavirus epidemiology and stronger service integration. Expressed challenges delivering existing LORVs merit further examination and indicate need for improved delivery.

eHealth Literacy Scale (eHEALS) is the most widely used, valid and reliable tool to assess eHealth literacy skills, but no culturally appropriate tool exists to assess these skills among Sinhala-speaking Sri Lankans, including health professionals. This study aimed to cross-culturally adapt the original eHEALS from English to Sinhala and evaluate its psychometric properties. The study was conducted in two phases. The first phase involved translation and cross-cultural validation of the questionnaire. The second phase involved a cross-sectional survey conducted online among 268 health science students from a state university in Sri Lanka to confirm the psychometric properties of the questionnaire. An analysis of test-retest reliability was conducted with a subset of 72 students. The pre-final version of Sinhala eHEALS (Si-eHEALS) was developed following the cross-cultural adaptation process. The mean score of Si-eHEALS was 28.51±4.87. A satisfactory level of internal consistency was achieved (Cronbach's alpha = 0.91). The test-retest reliability was acceptable (intraclass correlation coefficient -.776). Content validity index of Si-eHEALS was.97. The principal component analysis supported the unidimensionality of the scale, explaining 61.2 variance. There was a significant positive association between Si-eHEALS score with academic year (rs = .146, p = .017), self-rated internet skills (rs = .122, p = .046), usefulness of internet in health decision making (rs = .212, p < .001) and importance of ability to access health resources on the internet (rs = .230, p < .001), confirming concurrent validity. No significant difference based on gender (U = 5854, p = .550) and degree program (X2(2) = 2.965, p = .564) was found, confirming discriminant validity. In line with many previous validation studies, our study demonstrated good psychometric properties for Si-eHEALS. Si-eHEALS is a valid and reliable tool that assesses eHealth literacy in Sinhala speaking Sri Lankans, particularly health professionals.

IntroductionUnderstanding parents' and children's mental health issues would help design population-specific intervention programs. The present study explored parents' perceived stress and child emotions and behavior during the COVID-19 lockdown among Sri Lankan families.MethodsA cross-sectional survey was conducted among Sri Lankan parents of children aged 11 to 17 years. Validated instruments (Perceived Stress Scale-PSS and Strengths and Difficulties Questionnaire-SDQ) evaluated parental stress, child emotions, and hyperactivity/inattention. Multiple linear regression assessed the predictors of mental health issues, including the interaction between age and gender.ResultsThree hundred fifty-five parents responded to the survey (mothers:76%). One-third of parents experienced difficulties with their children during the pandemic. Emotions and hyperactivity-inattention problems measured via the SDQ scale were high among 38% of children, while the perceived stress was high in 79.2% of parents. Overall, child emotions and hyperactivity-inattention increased with decreasing age, increasing parent stress, having middle-income compared to high-income, and having a family member/close relative tested positive for COVID-19. Hyperactivity-inattention (29.3%) was more than the emotional problems (22%) among children. The emotional problems were reported more with increasing parent stress, while child hyperactivity-inattention alone was reported more with decreasing age, middle-income compared to high-income families, and increasing parent stress. Also, the interaction effect of age and gender indicated that higher age was related to greater parent-reported hyperactivity-inattention problems in males.ConclusionsThe findings highlight how the COVID-19 crisis and social isolation have contributed to increased parental stress and child emotional and hyperactivity-inattention problems. In addition to cautioning the healthcare workers, socio-culturally appropriate preventive and supportive mental health programs may help deal with further waves of COVID-19 or any other adverse circumstances.

BackgroundThere have been conflicting findings on the effect of body mass index (BMI) on lung functions in children. Therefore, we studied the relationship between spirometry parameters and BMI among healthy Sri Lankan school children aged 5-7 years.MethodsA cross-sectional study was conducted among 296 school children (5-7-year-old) without apparent lung disease. Recruitment was done with stratified random sampling. Spirometry parameters, FEV1, FVC, PEFR, and FEV1/FVC ratio were determined. The acceptable and reproducible spirometry recordings were included in the analysis. Simple and multivariate linear regression analysis examined possible associations of lung function parameters with BMI, socio-demographic variables and indoor risk factors. Also, the mediator effect of gender on lung function through BMI was explored.ResultsThe participants' mean age (SD) was 6.4 (0.65) years. One-third were thin/severely thin (37%). A statistically significant difference in FVC (p = 0.001) and FEV1 (p = 0.001) was observed between BMI groups (obesity/overweight, normal, and thinness). Yet, PEFR or FEV1/FVC did not significantly differ among BMI groups (p = 0.23 and p = 0.84). Multivariate regression analysis showed that FEV1 and FVC were significantly associated with BMI, child's age, gender, family income, father's education, having a pet, and exposure to mosquito coil smoke. Interaction between gender and BMI for lung functions was not significant. The thin children had significantly lower FVC (OR: -0.04, 95%CI: -0.077, -0.012, p = 0.008) and FEV1 (OR: -0.04, 95%CI: -0.075, -0.014, p = 0.004) than normal/overweight/obese children. Family income demonstrated the greatest effect on lung functions; FVC and FEV1 were 0.25L and 0.23L smaller in low-income than the high-income families.ConclusionLower lung function parameters (FVC and FEV1) are associated with thinness than normal/overweight/obese dimensions among children without apparent lung disease. It informs that appropriate nutritional intervention may play a role in improving respiratory health.

BackgroundWe investigated differences in risk of stroke, with all-cause mortality as a competing risk, in people newly diagnosed with atrial fibrillation (AF) who were commenced on either direct oral anticoagulants (DOACs) or warfarin treatment.Methods and resultsWe conducted a retrospective cohort study of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database (a network of 500 English general practices). We compared long term exposure to DOAC (n = 5,168) and warfarin (n = 7,451) in new cases of AF not previously treated with oral anticoagulants. Analyses included: survival analysis, estimating cause specific hazard ratios (CSHR), Fine-Gray analysis for factors affecting cumulative incidence of events occurring over time and a cumulative risk regression with time varying effects.We found no difference in CSHR between stroke 1.08 (0.72-1.63, p = 0.69) and all-cause mortality 0.93 (0.81-1.08, p = 0.37), or between the anticoagulant groups. Fine-Gray analysis produced similar results 1.07 (0.71-1.6 p = 0.75) for stroke and 0.93 (0.8-1.07, p = 0.3) mortality. The cumulative risk of mortality with DOAC was significantly elevated in early follow-up (67 days), with cumulative risk decreasing until 1,537 days and all-cause mortality risk significantly decreased coefficient estimate:: -0.23 (-0.38-0.01, p = 0.001); which persisted over seven years of follow-up.ConclusionsIn this large, contemporary, real world primary care study with longer follow-up, we found no overall difference in the hazard of stroke between warfarin and DOAC treatment for AF. However, there was a significant time-varying effect between anti-coagulant regimen on all-cause mortality, with DOACs showing better survival. This is a key methodological observation for future follow-up studies, and reassuring for patients and health care professionals for longer duration of therapy.

Objectives: This study examined the evidence of the prevalence of psychological distress and poor sleep among medical students and its associations during an economic crisis. Design: This was a cross-sectional study using an online questionnaire. It included the Depression Anxiety Stress Scales and Pittsburgh Sleep Quality Index (PSQI). Setting and participants: This study included medical undergraduates from a large metropolitan university in Sri Lanka. Primary and secondary outcome measures: We assessed the prevalence of psychological distress, sleep quality, and factors associated with psychological distress. To evaluate the associations, we used logistic regression. Results: The majority (69.2%) had some form of distress (depression, anxiety or stress), while 23% had distress in all three. Anxiety was the most prevalent (50.7%). Poor sleep quality was reported in 41%. The highest contribution to global PSQI was from sleep latency, duration, and daytime dysfunction subscales. In bivariate analysis, sleep quality was directly related to depression (t245.65 = -6.75, p<0.001)., anxiety (t313.45 = -6.45, p <0.001), and stress (t94.22 = -5.14, p <0.001). In multinomial logistic regression models, sleep quality was independently associated with depression, anxiety and stress. In addition, frequent contact with friends was inversely associated with depression and anxiety. Also, social media use was inversely linked to depression, anxiety and stress. Clinical-year students had lower depression and anxiety than non-clinical students. Engaging in mindfulness activities was inversely associated with depression. However, models explained only a moderate amount of variance (Nagelkerke R-squared values were 0.21, 0.18, and 0.13 for depression, anxiety and stress, respectively). Conclusions: Poor sleep quality and psychological distress are high among the undergraduates. The findings emphasize the importance of addressing sleep quality and psychological wellbeing in medical undergraduates. Further research with larger and more diverse samples is needed for a more comprehensive understanding of the factors associated with psychological distress among undergraduates. [ABSTRACT FROM AUTHOR]

A Mediterranean dietary pattern is widely recommended for the prevention of chronic disease. We sought to define the most likely effects of the Mediterranean diet on vascular disease and mortality.We searched MEDLINE, EMBASE and the Cochrane Central Register without language restriction for randomized controlled trials comparing Mediterranean to control diets. Data on study design, patient characteristics, interventions, follow-up duration, outcomes and adverse events were sought. Individual study relative risks (RR) were pooled to create summary estimates.Six studies with a total of 10950 participants were included. Effects on major vascular events (n = 477), death (n = 693) and vascular deaths (n = 315) were reported for 3, 5 and 4 studies respectively. For one large study (n = 1000) there were serious concerns about the integrity of the data. When data for all studies were combined there was evidence of protection against major vascular events (RR 0.63, 95% confidence interval 0.53-0.75), coronary events (0.65, 0.50-0.85), stroke (0.65, 0.48-0.88) and heart failure (0.30, 0.17-0.56) but not for all-cause mortality (1.00, 0.86-1.15) or cardiovascular mortality (0.90, 0.72-1.11). After the study of concern was excluded the benefit for vascular events (0.69, 0.55-0.86) and stroke (0.66, 0.48-0.92) persisted but apparently positive findings for coronary events (0.73, 0.51-1.05) and heart failure (0.25, 0.05-1.17) disappeared.The Mediterranean diet may protect against vascular disease. However, both the quantity and quality of the available evidence is limited and highly variable. Results must be interpreted with caution.

Segmentation is the process of partitioning an image into subdivisions and can be applied to medical images to isolate anatomical or pathological areas for further analysis. This process can be done manually or automated by the use of image processing computer packages. Atlas-based segmentation automates this process by the use of a pre-labelled template and a registration algorithm. We developed an ovine brain atlas that can be used as a model for neurological conditions such as Parkinson's disease and focal epilepsy. 17 female Corriedale ovine brains were imaged in-vivo in a 1.5T (low-resolution) MRI scanner. 13 of the low-resolution images were combined using a template construction algorithm to form a low-resolution template. The template was labelled to form an atlas and tested by comparing manual with atlas-based segmentations against the remaining four low-resolution images. The comparisons were in the form of similarity metrics used in previous segmentation research. Dice Similarity Coefficients were utilised to determine the degree of overlap between eight independent, manual and atlas-based segmentations, with values ranging from 0 (no overlap) to 1 (complete overlap). For 7 of these 8 segmented areas, we achieved a Dice Similarity Coefficient of 0.5-0.8. The amygdala was difficult to segment due to its variable location and similar intensity to surrounding tissues resulting in Dice Coefficients of 0.0-0.2. We developed a low resolution ovine brain atlas with eight clinically relevant areas labelled. This brain atlas performed comparably to prior human atlases described in the literature and to intra-observer error providing an atlas that can be used to guide further research using ovine brains as a model and is hosted online for public access.

Malaria remains a major global public health problem with an estimated 200 million cases detected in 2012. Although the most advanced candidate malaria vaccine (RTS,S) has shown promise in clinical trials, its modest efficacy and durability have created uncertainty about the impact of RTS,S immunization (when used alone) on global malaria transmission. Here we describe the development and characterization of a novel modified vaccinia virus Ankara (MVA)-based malaria vaccine which co-expresses the Plasmodium yoelii circumsporozoite protein (CSP) and IL-15. Vaccination/challenge studies showed that C57BL/6 mice immunized with the MVA-CSP/IL15 vaccine were protected significantly better against a P. yoelii 17XNL sporozoite challenge than either mice immunized with an MVA vaccine expressing only CSP or naïve controls. Importantly, the levels of total anti-CSP IgG were elevated about 100-fold for the MVA-CSP/IL15 immunized group compared to mice immunized with the MVA-CSP construct that does not express IL-15. Among the IgG subtypes, the IL-15 expressing MVA-CSP vaccine induced levels of IgG1 (8 fold) and IgG2b (80 fold) higher than the MVA-CSP construct. The significantly enhanced humoral responses and protection detected after immunization with the MVA-CSP/IL15 vaccine suggest that this IL-15 expressing MVA construct could be considered in the development of future malaria immunization strategies.

BACKGROUND:Vascular leak is the hallmark of severe dengue infections and leads to complications such as shock and multi-organ failure. Although many mediators have been implicated in the vascular leak in dengue, the role of sphingosine 1-phosphate (S1P) has not been investigated. METHOLODOLOGY/PRINCIPAL FINDINGS:As S1P has been shown to be important in barrier integrity, we assessed the S1P levels in 28 patients with acute dengue and 12 healthy individuals. The S1P levels were significantly lower in patients with acute dengue (p = 0.002) and the levels in patients with grade IV dengue haemorrhagic fever (DHF) were significantly lower than those with dengue fever (p = 0.005). We then investigated the kinetics of S1P levels throughout the course of the illness in another 32 patients in serum samples obtained twice a day. We found that S1P levels were low throughout the course of illness and S1P levels were

MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of the two isoforms are largely uncharacterized. Previously, we showed the role of MeCP2E1 in neuronal maturation and reported MeCP2E1 as the major protein isoform in the adult mouse brain, embryonic neurons and astrocytes. Recently, we showed that DNA methylation at the regulatory elements (REs) within the Mecp2 promoter and intron 1 impact the expression of Mecp2 isoforms in differentiating neural stem cells. This current study is aimed for a comparative analysis of temporal, regional and cell type-specific expression of MeCP2 isoforms in the developing and adult mouse brain. MeCP2E2 displayed a later expression onset than MeCP2E1 during mouse brain development. In the adult female and male brain hippocampus, both MeCP2 isoforms were detected in neurons, astrocytes and oligodendrocytes. Furthermore, MeCP2E1 expression was relatively uniform in different brain regions (olfactory bulb, striatum, cortex, hippocampus, thalamus, brainstem and cerebellum), whereas MeCP2E2 showed differential enrichment in these brain regions. Both MeCP2 isoforms showed relatively similar distribution in these brain regions, except for cerebellum. Lastly, a preferential correlation was observed between DNA methylation at specific CpG dinucleotides within the REs and Mecp2 isoform-specific expression in these brain regions. Taken together, we show that MeCP2 isoforms display differential expression patterns during brain development and in adult mouse brain regions. DNA methylation patterns at the Mecp2 REs may impact this differential expression of Mecp2/MeCP2 isoforms in brain regions. Our results significantly contribute towards characterizing the expression profiles of Mecp2/MeCP2 isoforms and thereby provide insights on the potential role of MeCP2 isoforms in the developing and adult brain.

Despite advances in clinical imaging and grading our understanding of retinal immune responses and their morphological correlates in experimental autoimmune uveoretinitis (EAU), has been hindered by the requirement for post-mortem histology. To date, monitoring changes occurring during EAU disease progression and evaluating the effect of therapeutic intervention in real time has not been possible. We wanted to establish whether optical coherence tomography (OCT) could detect intraretinal changes during inflammation and to determine its utility as a tool for accurate scoring of EAU. EAU was induced in C57BL/6J mice and animals evaluated after 15, 26, 36 and 60 days. At each time-point, contemporaneous Spectralis-OCT scanning, topical endoscopic fundal imaging (TEFI), fundus fluorescein angiography (FFA) and CD45-immunolabelled histology were performed. OCT features were further characterised on retinal flat-mounts using immunohistochemistry and 3D reconstruction. Optic disc swelling and vitreous opacities detected by OCT corresponded to CD45+ cell infiltration on histology. Vasculitis identified by FFA and OCT matched perivascular myeloid and T-cell infiltrates and could be differentiated from unaffected vessels. Evolution of these changes could be followed over time in the same eye. Retinal folds were visible and found to encapsulate mixed populations of activated myeloid cells, T-cells and microglia. Using these features, an OCT-based EAU scoring system was developed, with significant correlation to validated histological (Pearson r(2) = 0.6392, P

BACKGROUND:The aetiological role of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) has been widely researched for more than three decades, with conflicting findings. In the absence of a large, adequately powered single case-control study, a meta-analysis of all available case-control studies is the most rigorous way of identifying any potential association between HPV and OSCC. We present the first global meta-analysis of case-control studies investigating the role of HPV in OSCC. METHODS:Case-control studies investigating OSCC tissue for presence of HPV DNA were identified. 21 case-control studies analyzing a total of 1223 cases and 1415 controls, met our inclusion criteria. HPV detection rates were tabulated for each study and all studies were assessed for quality. The random effects method was used to pool the odds ratios (OR). RESULTS:From all OSCC specimens included in this meta-analysis, 35% (426/1223) were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20). Meta-regression analysis did not find a significant association between OR and any of the quality domains. Influence analysis was non-significant for the effect of individual studies on the pooled estimate. Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76) than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91). CONCLUSIONS:Uncertainty around the aetiological role of HPV in OSCC is due largely to the small number and scale of appropriately designed studies. Our meta-analysis of these studies suggests that HPV increases the risk of OSCC three-fold. This study provides the strongest evidence to date of an HPV-OSCC association. The importance of these findings is that prophylactic vaccination could be of public health benefit in prevention of OSCC in countries with high OSCC incidence.

BACKGROUND:HLA class I and class II alleles have been shown to be associated with the development of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in different populations. However, the majority of studies have been based on limited numbers of patients. In this study we aimed to investigate the HLA-class I and class II alleles that are positively and negatively associated with the development of DSS in a cohort of patients with DHF and also the alleles associated with development of DHF during primary dengue infections in a Sri Lankan population. METHODOLOGY/PRINCIPAL FINDINGS:The allele frequencies of HLA class I and class II alleles were compared in 110 patients with DHF and 119 individuals from the population who had never reported a symptomatic dengue infection at the time of recruitment. We found that HLA-A*31 (corrected P = 0.01) and DRB1*08 (corrected P = 0.009) were associated with susceptibility to DSS when infected with the dengue virus, during secondary dengue infection. The frequency of DRB1*08 allele was 28.7 times higher than in the normal population in patients with DSS. HLA-A*31 allele was increased 16.6 fold in DHF who developed shock when compared to those who did not develop shock. A*24 (corrected P = 0.03) and DRB1*12 (corrected P = 0.041) were strongly associated with the development of DHF during primary dengue infection. CONCLUSIONS/SIGNIFICANCE:These data suggest that certain HLA alleles confer susceptibility/protection to severe dengue infections. As T cell epitope recognition depend on the HLA type of an individual, it would be now important to investigate how epitope specific T cells associate with primary and secondary dengue infections and in severe dengue infections.