Inducing remission of Type 2 diabetes in the Caribbean: findings from a mixed methods feasibility study of a low-calorie liquid diet-based intervention in Barbados.

AIM: In a high proportion of people with recently diagnosed Type 2 diabetes, a short (2-3-month) low-calorie diet is able to restore normal glucose and insulin metabolism. The aim of this study was to determine the feasibility of this approach in Barbados. METHODS: Twenty-five individuals with Type 2 diabetes diagnosed within past 6 years, not on insulin, BMI ≥ 27 kg/m2 were recruited. Hypoglycaemic medication was stopped on commencement of the 8-week liquid (760 calorie) diet. Insulin response was assessed in meal tests at baseline, 8 weeks and 8 months. Semi-structured interviews, analysed thematically, explored participants' experiences. 'Responders' were those with fasting plasma glucose (FPG) < 7 mmol/l at 8 weeks. RESULTS: Ten men and 15 women (mean age 48, range 26-68 years) participated. Mean (sd) BMI was 34.2 kg/m2 (6.0); FPG 9.2 mmol/l (2.2). Mean weight loss at 8 weeks and 8 months was 10.1 kg [95% confidence interval (CI) 8.1, 12.0] and 8.2 kg (95% CI 5.8, 10.6); FPG was lower by 2.2 mmol/l (95% CI 1.2, 3.2) and 1.7 mmol/l (95% CI 0.8, 2.7) respectively. Nine of 11 (82%) of those who lost ≥ 10 kg were 'responders' compared with 6 of 14 (43%) who lost < 10 kg (P = 0.048). The 30-min insulin increment was higher in responders at baseline and follow-up (P ≤ 0.01). A food culture based on starchy foods and pressures to eat large amounts at social events were among the challenges identified by participants. CONCLUSIONS: The feasibility of this approach to weight loss and diabetes remission in a predominantly black population in Barbados was demonstrated

Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

The puzzle of self-reported weight gain in a month of fasting (Ramadan) among a cohort of Saudi families in Jeddah, Western Saudi Arabia

<p>Abstract</p> <p>Background</p> <p>During Ramadan fast, approximately one billion Muslims abstain from food and fluid between the hours of sunrise to sunset, and usually eat a large meal after sunset and another meal before sunrise. Many studies reported good health-related outcomes of fasting including weight loss. The objective of this study is to identify the local pattern of expenditure on food consumption, dietary habits during Ramadan and correlate that to self-reported weight gain after Ramadan in a group of families in Jeddah, Western Saudi Arabia.</p> <p>Methods</p> <p>A Cross-section study using a pre-designed questionnaire to identify the local pattern of expenditure on food consumption, dietary habits during Ramadan and correlate that to self-reported weight gain after Ramadan in a representative cohort of Saudis living in Jeddah. It was piloted on 173 nutrition students and administered by them to their families.</p> <p>Results</p> <p>A total of 173 Saudi families were interviewed. One out of 5 indicated that their expenditure increases during Ramadan. Approximately two thirds of the respondents (59.5%) reported weight gain after Ramadan. When asked about their perspective explanations for that: 40% attributed that to types of foods being rich in fat and carbohydrates particularly date in (Sunset meal) 97.7% and rice in (Dawn meal) 80.9%. One third (31.2%) indicated that it was due to relative lack of physical exercise in Ramadan and 14.5% referred that to increase in food consumption. Two thirds (65.2%) of those with increased expenditure reported weight gain.</p> <p>Conclusion</p> <p>Surprisingly weight gain and not weight loss was reported after Ramadan by Saudis which indicates timely needed life-style and dietary modification programs for a population which reports one of the highest prevalence rates of diabetes.</p

Immunohistochemical expression of mitochondrial membrane complexes (MMCs) I, III, IV and V in malignant and benign periampullary epithelium: a potential target for drug therapy of periampullary cancer?

<p>Abstract</p> <p>Background</p> <p>Mitochondrial membrane complexes (MMCs) are key mediators of cellular oxidative phosphorylation, and inhibiting them could lead to cell death. No published data are available on the relative abundance of MMCs in different periampullary cancers. Therefore, we studied the expression profile of MMCs I, III, IV and V in periampullary cancers, reactive pancreatitis, normal pancreas and chronic pancreatitis.</p> <p>Methods</p> <p>This was a retrospective study on tissue microarrays constructed from formalin-fixed paraffin-embedded tissue from 126 consecutive patients (cancer = 104, chronic pancreatitis = 22) undergoing pancreatic resections between June 2001 and June 2006. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied.</p> <p>Results</p> <p>MMCs I, III, IV and V were highly expressed (p < 0.05) in all primary periampullary cancers compared with metastatic lymph nodes and adjacent benign pancreas. MMCs III, IV and V were highly expressed in all cancers regardless of type compared with chronic pancreatitis (p < 0.05). Higher expression of MMCs I and V was associated with better survival and may, in part, relate to lower expression of these MMCs in poorly differentiated tumours compared with well and moderately differentiated tumours.</p> <p>Conclusions</p> <p>Differential expression of MMCs III, IV and V in primary periampullary cancers compared with adjacent benign periampullary tissue and chronic pancreatitis is a novel finding, which may render them attractive anticancer targets.</p

Association between expatriation and HIV awareness and knowledge among injecting drug users in Kabul, Afghanistan: A cross-sectional comparison of former refugees to those remaining during conflict

BACKGROUND: Little is known about human immunodeficiency virus (HIV) awareness among Afghan injecting drug users (IDUs), many of whom initiated injecting as refugees. We explored whether differences in HIV awareness and knowledge exist between Afghan IDUs who were refugees compared to those never having left Afghanistan. METHODS: A convenience sample of IDUs in Kabul, Afghanistan was recruited into a cross-sectional study through street outreach over a one year period beginning in 2005. Participants completed an interviewer-administered questionnaire and underwent voluntary counseling and testing for HIV, syphilis, hepatitis B surface antigen, and hepatitis C antibody. Differences in HIV awareness and specific HIV knowledge between IDU who lived outside the country in the last decade versus those who had not were assessed with logistic regression. RESULTS: Of 464 IDUs, 463 (99%) were male; median age and age at first injection were 29 and 25 years, respectively. Most (86.4%) had lived or worked outside the country in the past ten years. Awareness of HIV was reported by 46.1%; those having been outside the country in the last decade were significantly more likely to have heard of HIV (48.3% vs. 31.7%; OR = 2.00, 95% CI: 1.14 – 3.53). However, of those aware of HIV, only 38.3% could name three correct transmission routes; specific HIV knowledge was not significantly associated with residence outside the country. CONCLUSION: Accurate HIV knowledge among Afghan IDUs is low, though former refugees had greater HIV awareness. Reported high-risk injecting behavior was not significantly different between IDU that were refugees and those that did not leave the country, indicating that all Afghan IDU should receive targeted prevention programming

The Fourth Bioelectronic Medicine Summit "Technology Targeting Molecular Mechanisms": current progress, challenges, and charting the future.

There is a broad and growing interest in Bioelectronic Medicine, a dynamic field that continues to generate new approaches in disease treatment. The fourth bioelectronic medicine summit "Technology targeting molecular mechanisms" took place on September 23 and 24, 2020. This virtual meeting was hosted by the Feinstein Institutes for Medical Research, Northwell Health. The summit called international attention to Bioelectronic Medicine as a platform for new developments in science, technology, and healthcare. The meeting was an arena for exchanging new ideas and seeding potential collaborations involving teams in academia and industry. The summit provided a forum for leaders in the field to discuss current progress, challenges, and future developments in Bioelectronic Medicine. The main topics discussed at the summit are outlined here

The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays

Background Tumour-associated lymphocytes (TALs) have been linked with good prognosis in several solid tumours. This study aimed to evaluate the prognostic significance of CD3, CD8 and CD20 positive lymphocytes in pancreatic ductal adenocarcinoma. Methods After histological re-evaluation of the tumours of 81 patients who underwent surgical resection for exclusively pancreatic ductal adenocarcinoma, tissue micro-arrays (TMA) were constructed and immunohistochemistry was performed for CD3, CD8 and CD20. The number of lymphocytes within specific tumour compartments (i.e. stromal and intratumoural) was quantified. X-tile software (Yale School of Medicine, CT, USA) was used to stratify patients into 'high’ and 'low’ for each of the lymphocytes stained and their association with survival. Receiver operating curves (ROC) were constructed to evaluate the association between the TALs, alone and in combination, with clinicopathological features. Results CD3 and CD8 positive lymphocytes were associated with grade of tumour differentiation. The presence of intratumoural CD3 positive cells was associated with improved survival (p = 0.028), and intratumoural and stromal CD3 in combination also correlated with improved survival (p = 0.043). When CD20 positive lymphocyte levels were high, survival improved (p = 0.029) and similar results were seen for CD20 in combination with intratumoural CD3 (p = 0.001) and stromal CD8 (p = 0.013). Conclusions This study has shown a correlation between the presence of TALs and survival in pancreatic ductal adenocarcinoma

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Basic science of osteoarthritis

Osteoarthritis (OA) is a prevalent, disabling disorder of the joints that affects a large population worldwide and for which there is no definitive cure. This review provides critical insights into the basic knowledge on OA that may lead to innovative end efficient new therapeutic regimens. While degradation of the articular cartilage is the hallmark of OA, with altered interactions between chondrocytes and compounds of the extracellular matrix, the subchondral bone has been also described as a key component of the disease, involving specific pathomechanisms controlling its initiation and progression. The identification of such events (and thus of possible targets for therapy) has been made possible by the availability of a number of animal models that aim at reproducing the human pathology, in particular large models of high tibial osteotomy (HTO). From a therapeutic point of view, mesenchymal stem cells (MSCs) represent a promising option for the treatment of OA and may be used concomitantly with functional substitutes integrating scaffolds and drugs/growth factors in tissue engineering setups. Altogether, these advances in the fundamental and experimental knowledge on OA may allow for the generation of improved, adapted therapeutic regimens to treat human OA.(undefined

When Too Much Is Not Enough: Obsessive-Compulsive Disorder as a Pathology of Stopping, Rather than Starting

Background: In obsessive-compulsive disorder (OCD), individuals feel compelled to repeatedly perform security-related behaviors, even though these behaviours seem excessive and unwarranted to them. The present research investigated two alternative ways of explaining such behavior: (1) a dysfunction of activation—a starting problem—in which the level of excitation in response to stimuli suggesting potential danger is abnormally strong; versus (2) a dysfunction of termination— a stopping problem—in which the satiety-like process for shutting down security-related thoughts and actions is abnormally weak. Method: In two experiments, 70 patients with OCD (57 with washing compulsions, 13 with checking compulsions) and 72 controls were exposed to contamination cues—immersing a hand in wet diapers —and later allowed to wash their hands, first limited to 30 s and then for as long as desired. The intensity of activation of security motivation was measured objectively by change in respiratory sinus arrythmia. Subjective ratings (e.g., contamination) and behavioral measures (e.g., duration of hand washing) were also collected. Results: Compared to controls, OCD patients with washing compulsions did not differ significantly in their levels of initial activation to the threat of contamination; however, they were significantly less able to reduce this activation by engaging in the corrective behavior of hand-washing. Further, the deactivating effect of hand-washing in OCD patients with checkin