Alzheimer's disease (AD) is characterized by fibrillar deposits of amyloid-β (Aβ) peptides and neurofibrillary tangles of Tau proteins. Aβ peptides are composed of 37−49 residues, among which the Aβ 42 isoform is particularly toxic and aggregation-prone and is enriched in the plaques of AD brains and thus considered central to the development of AD. Therefore, disaggregation and disruption provide potential therapeutic approaches to reduce, inhibit, and even reverse Aβ aggregation. Here we capture the atomic-level details of the interactions between sigmoid Aβ 42 fibril 2MXU or 5KK3 and either natural tanshinone compounds TS1 or TS0 or negatively charged ER, proposing two unprecedented disassembly mechanisms. Natural TS1 or TS0 prefers to insert into the cavity together with part at the surface of the 2MXU to open up the mouth and twist the conformation, destroying the ordered growth of subsequent monomers along the fibril axis. For the more compact two-fold 5KK3, attachment of TS1 or TS0 at the surface including some inserted in cavity results in the separation of the two folds. In the two sigmoid fibril systems, it is no longer applicable for the routine criteria to assess Aβ 42 fibril disassembly by introduction of these drugs, such as either reduced H-bond number, decreased β-sheet contents, or both. ER, like-charged to Aβ 42 fibril, is especially exceptional, and departs utterly from the neutral ones to disassemble Aβ 42 fibril. Besides the inapplicable routine criteria, positive binding energy between ER and Aβ 42 fibril also deviates from the hypotheses of "ligands exhibiting greater affinity for the β-amyloid peptide are effective at altering its aggregation and inhibiting cell toxicity" (Cairo et al.et al., Biochemistry 2002, 41, 8620−8629) but results in stronger disassembly effect on the two kinds of sigmoid Aβ 42 fibrils than neutral TS0 or TS1. The disassembly power of charged ER molecules derives from its stronger deformation ability to the conformation of Aβ 42 fibril than the neutral ones, twisting the one-fold 2MXU into tapered-shape and separating two-fold 5KK3 in two parts further, which is in great agreement with experimental observations (Irwin et al.et al. Biomacromolecules 2013, 14 (1), 264−274). The unusual disassembly mechanisms fill the gaps and offer an alternative direction in engineering new inhibitors to treat AD.

Objective The main purpose of this study was to investigate the pooled prevalence of prediabetes and type-2 diabetes in the general population of Malaysia. Method We systematically searched Medline (PubMed), Embase, Web of Science, Google Scholar and Malaysian Journals Online to identify relevant studies published between January 1, 1995, and November 30, 2021, on the prevalence of type-2 diabetes in Malaysia. Random-effects meta-analyses were used to obtain the pooled prevalence of diabetes and prediabetes. Subgroup analyses also used to analyze to the potential sources of heterogeneity. Meta- regression was carried to assess associations between study characteristics and diabetes prevalence. Three independent authors selected studies and conducted the quality assessment. The quality of the final evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Of 2689 potentially relevant studies, 786 titles and abstract were screened. Fifteen studies with 103063 individuals were eligible to be included in the meta-analyses. The pooled prevalence of diabetes was 14.39% (95% CI, 12.51%–16.38%; I2 = 98.4%, 103063 participants from 15 studies). The pooled prevalence of prediabetes was 11.62% (95% CI, 7.17%–16.97%; I2 = 99.8, 88702 participants from 9 studies). The subgroup analysis showed statistically significant differences in diabetes prevalence by the ethical sub-populations with highest in Indians (25.10%; 95% CI, 20.19%–30.35%), followed by Malays (15.25%; 95% CI, 11.59%–19.29%), Chinese (12.87%; 95% CI, 9.73%–16.37%), Bumiputeras (8.62%; 95% CI, 5.41%–12.47%) and others (6.91%; 95% CI, 5.71%–8.19%). There was no evidence of publication bias, although heterogeneity was high (I2 ranged from 0.00% to 99·8%). The quality of evidence based on GRADE was low. Conclusions Results of this study suggest that a high prevalence of prediabetes and diabetes in Malaysia. The diabetes prevalence is associated with time period and increasing age. The Malaysian government should develop a comprehensive approach and strategy to enhance diabetes awareness, control, prevention, and treatment. Trial registration Trial registration no. PROSPERO CRD42021255894; https://clinicaltrials.gov/.

INTRODUCTIONAcinetobacter baumannii is usually associated with respiratory tract, urinary tract and bloodstream infections. Recent reports suggest that it is increasingly causing skin and soft tissue infections. It is also evolving as a multidrug resistant organism that can be difficult to treat. We present a fatal case of multidrug resistant A. baumannii soft tissue infection and review of relevant literature.PRESENTATION OF CASEA 41 year old morbidly obese man, with history of alcoholic liver disease presented with left superficial pre-tibial abrasions and cellulitis caused by multidrug resistant (MDR) A. baumannii. In spite of early antibiotic administration he developed extensive myositis and fat necrosis requiring extensive and multiple surgical debridements. He deteriorated despite appropriate antibiotic therapy and multiple surgical interventions with development of multi-organ failure and died.DISCUSSIONManaging Acinetobacter infections remains difficult due to the array of resistance and the pathogens ability to develop new and ongoing resistance. The early diagnosis of necrotizing soft tissue infection may be challenging, but the key to successful management of patients with necrotizing soft tissue infection are early recognition and complete surgical debridement.CONCLUSIONA. baumannii is emerging as an important cause of severe, life-threatening soft tissue infections. Multidrug resistant A. baumannii soft tissue infections may carry a high mortality in spite of early and aggressive treatment. Clinicians need to consider appropriate early empirical antibiotic coverage or the use of combination therapy to include MDR A. baumannii as a cause of skin and soft tissue infections.

We aimed to determine the pooled prevalence of diabetic foot ulcers in Pakistan. MEDLINE (PubMed), Web of Science, Google scholars, and local databases were systematically searched for studies published up to August 10, 2022, on the prevalence of foot ulcers among diabetic patients in Pakistan. Random-effects meta-analysis was used to generate summary estimates. Subgroup analysis and meta-regression models were used to address the issue of high heterogeneity. Two authors independently identified eligible articles, collected data, and performed a risk of bias analysis. Twelve studies were included in the meta-analysis (14201, range 230–2199, diabetic patients), of which 7 were of “high” quality. The pooled prevalence of diabetic foot ulcers was 12.16% (95% CI: 5.91–20.23%). We found significant between-study heterogeneity (I2 = 99.3%; p < 0.001) but no statistical evidence of publication bias (p = 0.8544). Subgroup meta-analysis found significant differences in foot ulcer prevalence by publication year and by the duration of diabetes. An increasing trend was observed during the last two decades, with the prevalence of diabetic foot ulcers being the highest in the latest period from 2011 to 2022 (19.54%) than in the early 2000 s (4.55%). This study suggests that the prevalence of diabetic foot ulcers in Pakistan is relatively high, with significant variation between provinces. Further study is required to identify ways for early detection, prevention, and treatment in the population.

Orphaned and abandoned wells are emblematic of the challenges of abandoned infrastructure. With over 2.5 million idle wells in the United States, this is a large problem that requires engagement across the public, private, non-profit, and civic sectors. This article conducts a focused case study on orphaned and abandoned well reclamation in Pennsylvania. Elite interviews, government document review, and scholarly literature reveal the barriers to effective collaboration across the sectors, but also substantial potential. Using the public-private-citizen partnership (PC2) and collaborative governance regime (CGR) frameworks, the article proposes a PC2 CGR that could leverage the influx of federal well plugging funds for greater effectiveness in solving this big problem. The case also holds lessons for other states and other sources of abandoned infrastructure.