Trends in monkeypox transmission: Investigation into 30 most affected countries

This research is based on the analysis of Monkeypox transmission, from may 7, 2022 to October 11, 2022, in 30 most affected countries around the globe. The most affected countries are selected through the cut point of at least 100 reported confirmed cases of infected persons over the aforementioned time span. We novely argue the exhibition of distributional similarities between the viral flow and well known power law in context of this neglected zoonotic disease. Moreover, model-based evidence suggesting the capability of pathogen to spread far and wide around its nucleus, are collected and presented. It is estimated that 70 % of the reported confirmed cases belonged to 20 % of the top most affected countries. Also, 70 % of the reported transmission was inflicted in 34 % of the days of reporting at least one case, on average

Investigating the association between the autophagy markers LC3B, SQSTM1/p62, and dram and autophagy-related genes in glioma

High-grade gliomas are extremely fatal tumors, marked by severe hypoxia and therapeutic resistance. Autophagy is a cellular degradative process that can be activated by hypoxia, ultimately resulting in tumor advancement and chemo-resistance. Our study aimed to examine the link between autophagy markers\u27 expression in low-grade gliomas (LGGs) and high-grade gliomas (HGGs). In 39 glioma cases, we assessed the protein expression of autophagy markers LC3B, SQSTM1/p62, and DRAM by immunohistochemistry (IHC) and the mRNA expression of the autophagy genes PTEN, PI3K, AKT, mTOR, ULK1, ULK2, UVRAG, Beclin 1, and VPS34 using RT-qPCR. LC3B, SQSTM1/p62, and DRAM expression were positive in 64.1%, 51.3%, and 28.2% of glioma cases, respectively. The expression of LC3B and SQSTM1/p62 was notably higher in HGGs compared to LGGs. VPS34 exhibited a significant differential expression, displaying increased fold change in HGGs compared to LGGs. Additionally, it exhibited robust positive associations with Beclin1 (rs = 0.768), UVRAG (rs = 0.802), and ULK2 (rs = 0.786) in HGGs. This underscores a potential association between autophagy and the progression of gliomas. We provide preliminary data for the functional analysis of autophagy using a cell culture model and to identify potential targets for therapeutic interventions

Caught in Each Other\u27s Traps : Factors perpetuating incentive-linked prescribing deals between physicians and the pharmaceutical industry

Background: Despite known adverse impacts on patients and health systems, incentive-linked prescribing, which describes the prescribing of medicines that result in personal benefits for the prescriber, remains a widespread and hidden impediment to quality of healthcare. We investigated factors perpetuating incentive-linked prescribing among primary care physicians in for-profit practices (referred to as private doctors - PDs), using Pakistan as a case study.Methods: Our mixed-methods study synthesised insights from a survey of 419 systematically sampled PDs and 68 semi-structured interviews with PDs (n=28), pharmaceutical sales representatives (SRs) (n=12), and provincial and national policy actors (n=28). For the survey, we built a verified database of all registered PDs within Karachi, Pakistan\u27s most populous city, administered an electronic questionnaire in-person and descriptively analysed the data. Semi-structured interviews incorporated a vignette-based exercise and data was analysed using an interpretive approach.Results: Our survey showed that 90% of PDs met pharmaceutical SRs weekly. Three interlinked factors perpetuating incentive-linked prescribing we identified were: gaps in understanding of conflicts of interest and loss of values among doctors; financial pressures on doctors operating in a (largely) privately financed health-system, exacerbated by competition with unqualified healthcare providers; and aggressive incentivisation by pharmaceutical companies, linked to low political will to regulate an over-saturated pharmaceutical market.Conclusion: Regular interactions between pharmaceutical companies and PDs are normalised in our study setting. Progress on regulating these is hindered by the substantial role of incentive-linked prescribing in the financial success of physicians and pharmaceutical industry employees. A first step towards addressing the entrenchment of incentive-linked prescribing may be to reduce opposition to restrictions on incentivisation of physicians from stakeholders within the pharmaceutical industry, physicians themselves, and policy-makers concerned about curtailing growth of the pharmaceutical industry

Kidney disease in childhood cancer survivors treated with radiation therapy: A PENTEC comprehensive review

Purpose: Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunction, including kidney, bladder, and hypertension, for pediatric malignancies. The effect of chemotherapy was also considered.Methods and materials: We conducted a comprehensive PubMed search of peer-reviewed manuscripts published from 1990 to 2017 for investigations on RT-associated GU toxicities in children treated for cancer. We retrieved 3271 articles with 100 fulfilling criteria for full review, 24 with RT dose data and 13 adequate for modeling. Endpoints were heterogenous and grouped according to National Kidney Foundation: grade ≥1, grade ≥2, and grade ≥3. We modeled whole kidney exposure from total body irradiation (TBI) for hematopoietic stem cell transplant and whole abdominal irradiation (WAI) for patients with Wilms tumor. Partial kidney tolerance was modeled from a single publication from 2021 after the comprehensive review revealed no usable partial kidney data. Inadequate data existed for analysis of bladder RT-associated toxicities.Results: The 13 reports with long-term GU outcomes suitable for modeling included 4 on WAI for Wilms tumor, 8 on TBI, and 1 for partial renal RT exposure. These reports evaluated a total of 1191 pediatric patients, including: WAI 86, TBI 666, and 439 partial kidney. The age range at the time of RT was 1 month to 18 years with medians of 2 to 11 years in the various reports. In our whole kidney analysis we were unable to include chemotherapy because of the heterogeneity of regimens and paucity of data. Age-specific toxicity data were also unavailable. Wilms studies occurred from 1968 to 2011 with mean follow-ups 8 to 15 years. TBI studies occurred from 1969 to 2004 with mean follow-ups of 4 months to 16 years. We modeled risk of dysfunction by RT dose and grade of toxicity. Normal tissue complication rates ≥5%, expressed as equivalent doses, 2 Gy/fx for whole kidney exposures occurred at 8.5, 10.2, and 14.5 Gy for National Kidney Foundation grades ≥1, ≥2, and ≥3, respectively. Conventional Wilms WAI of 10.5 Gy in 6 fx had risks of ≥grade 2 toxicity 4% and ≥grade 3 toxicity 1%. For fractionated 12 Gy TBI, those risks were 8% and \u3c3%, respectively. Data did not support whole kidney modeling with chemotherapy. Partial kidney modeling from 439 survivors who received RT (median age, 7.3 years) demonstrated 5 or 10 Gy to 100% kidney gave a \u3c5% risk of grades 3 to 5 toxicity with 1500 mg/m2 carboplatin or no chemo. With 480 mg/m2 cisplatin, a 3% risk of ≥grade 3 toxicity occurred without RT and a 5% risk when 26% kidney received ≥10 Gy. With 63 g/m2 of ifosfamide, a 5% risk of ≥grade 3 toxicity occurred with no RT, and a 10% toxicity risk occurred when 42% kidney received ≥10 Gy.Conclusions: In patients with Wilms tumor, the risk of toxicity from 10.5 Gy of WAI is low. For 12 Gy fractionated TBI with various mixtures of chemotherapy, the risk of severe toxicity is low, but low-grade toxicity is not uncommon. Partial kidney data are limited and toxicity is associated heavily with the use of nephrotoxic chemotherapeutic agents. Our efforts demonstrate the need for improved data gathering, systematic follow-up, and reporting in future clinical studies. Current radiation dose used for Wilms tumor and TBI appear to be safe; however, efforts in effective kidney-sparing TBI and WAI regimens may reduce the risks of renal injury without compromising cure

Effectiveness of spaced repetition for clinical problem solving amongst undergraduate medical students studying paediatrics in Pakistan

Background: Studies using spaced repetition for teaching and learning in undergraduate clinical rotations such as paediatrics are limited, even more so in the South Asian region. Therefore, this study aimed to identify the effectiveness of utilizing spaced repetition compared to traditional learning methods among undergraduate medical students during their paediatric rotation at a medical university in Pakistan.Methods: Bahria University Medical and Dental College (BUMDC) conducted quasii-experimental research in Karachi. Four topics were identified from the Year 5 Pediatrics curriculum to be used in the study, using which the study content was developed along with 50 multiple choice questions (MCQs) for assessment. All BUMDC Year 5 medical students rotating in Pediatrics were included and randomly allocated to the control or intervention group. In the control group, they provided the students with traditional study methods consisting of books and lectures to learn topics. In the intervention group, we created an Anki flashcard deck of the same topics to enable learning via spaced repetition. The researchers conducted a pretest and post test assessment of the 50 MCQs in both groups at the beginning and after the four-week study interval. The data were analysed using SPSS 19.Results: A total of 115 BUMDC medical students agreed to participate in the study; 70 (59.1%) were in the intervention group, and 45 (41.7%) were in the control group. The pretest mean score of the control group was 27.96 ± 3.70, and the posttest mean score was 27.22 ± 5.02, with no statistically significant difference at the 95% confidence level. The mean score of the pretest for the intervention group was 27.93 ± 4.53, and that of the posttest was 30.8 ± 4.56, with a statistically significant difference at the 95% confidence level. The intervention showed a significant effect size of 0.8.Conclusion: The use of spaced repetitions resulted in significantly greater scores for medical students studying paediatrics than for those using more traditional methods of learning, compromising medical books and lectures. Considering that medical students need to retain a vast amount of information, using spaced repetition through flashcards can be a more effective learning tool that is more cost-efficient and time-efficient than traditional learning methods

ACTION APAC: Understanding perceptions, attitudes and behaviours in obesity and its management across south and Southeast Asia

To identify perceptions and attitudes among people with obesity (PwO) and healthcare professionals (HCPs) toward obesity and its management in nine Asia-Pacific (APAC) countries, a cross-sectional online survey was conducted among adult PwO with self-reported body mass index of ≥25 kg/m2 (≥27 kg/m2 , Singapore), and HCPs involved in direct patient care. In total, 10 429 PwO and 1901 HCPs completed the survey. Most PwO (68%) and HCPs (84%) agreed that obesity is a disease; however, a significant proportion of PwO (63%) and HCPs (41%) believed weight loss was the complete responsibility of PwO and only 43% of PwO discussed weight with an HCP in the prior 5 years. Most respondents acknowledged that weight loss would be extremely beneficial to PwO\u27s overall health (PwO 76%, HCPs 85%), although nearly half (45%) of PwO misperceived themselves as overweight or of normal weight. Obesity was perceived by PwO (58%) and HCPs (53%) to negatively impact PwO forming romantic relationships. HCPs cited PwOs\u27 lack of interest (41%) and poor motivation (37%) to lose weight as top reasons for not discussing weight. Most PwO (65%) preferred lifestyle changes over medications to lose weight. PwO and HCPs agreed that lack of exercise and unhealthy eating habits were the major barriers to weight loss. Our data highlights a discordance between the understanding of obesity as a disease and the actual behaviour and preferred approaches to manage it among PwO and HCPs. The study addresses a need to align these gaps to deliver optimal care for PwO

Factors associated with safe and successful postoperative day 1 discharge after lung operations: A systematic review and meta-analysis

Background: A shorter length of stay (LOS) is associated with fewer hospital-acquired adverse conditions and decreased utilization of hospital resources. While modern perioperative care protocols have enabled some ambitious surgical teams to achieve discharge as early as within postoperative day 1 (POD1), most other teams remain cautious about such an approach due to the perceived risk of missing postoperative complications and increased readmission rates. We aimed to identify factors that would help guide surgical teams aiming for safe and successful POD1 discharge after lung resection.Methods: We searched the PubMed, Embase, Scopus, Web of Science and CENTRAL databases for articles comparing perioperative characteristics in patients discharged within POD1 (DWPOD1) and after POD1 (DAPOD1) following lung resection. Meta-analysis was performed using a random-effects model.Results: We included eight retrospective cohort studies with a total of 216,887 patients, of which 22,250 (10.3%) patients were DWPOD1. Our meta-analysis showed that younger patients, those without cardiovascular and respiratory comorbidities, and those with better preoperative pulmonary function are more likely to qualify for DWPOD1. Certain operative factors, such as a minimally invasive approach, shorter operations, and sublobar resections, also favor DWPOD1. DWPOD1 appears to be safe, with comparable 30-day mortality and readmission rates, and significantly less postoperative morbidity than DAPOD1.Conclusions: In select patients with a favorable preoperative profile, DWPOD1 after lung resection can be achieved successfully and without increased risk of adverse outcomes such as postoperative morbidity, mortality, or readmissions

Left atrial appendage thrombus with severe mitral stenosis: Responders and non-responders to anticoagulation

Introduction and objective: Mitral stenosis (MS) is one of the most frequently observed valvular heart lesions in developing countries and is due to different etiologies. The effects of anticoagulation in different types of left atrial appendage (LAA) are unknown. The current study aimed to determine the resolution of LAA thrombus on transesophageal echocardiography (TEE) after three months of optimal anticoagulation in patients with different types of LAA at baseline cardiac computed tomography of patients with severe MS.Methods: This prospective cohort study observed the frequency of LAA thrombus resolution after three months of anticoagulation therapy in patients with severe MS. The response rate in different morphologies of LAA and locations was also assessed. Thrombus resolution after three months of warfarin therapy was assessed on repeat TEE.Results: A total of 88 patients were included, mean age 37.95±11.87 years. Repeat TEE showed thrombus resolution in only 27.3% of patients. The rate of thrombus resolution was 8/12 (66.7%), 4/28 (14.3%), 8/36 (22.2%), and 4/12 (33.3%) for patients with cactus, cauliflower, chicken wing, and windsock LAA type, respectively. The resolution rate was 0/12 (0%), 4/44 (9.1%), and 20/32 (62.5%) for patients with thrombus in the base, body, and tip of the LAA, respectively.Conclusion: The cactus type of LAA morphology and thrombus at the LAA tip responded well to three months of anticoagulation, however, patients with thrombus in the LAA base and body and cauliflower and chicken wing morphology were non-responders and could benefit from early referral for surgical management

Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: An international replication repair deficiency consortium cohort study

Background: Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.Methods: In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions.Findings: We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank pInterpretation: The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD.Funding: The Canadian Institutes for Health Research, Stand Up to Cancer, Children\u27s Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan\u27s Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold\u27em for Life, and Garron Family Cancer Center