Antiangiogenic-immune-checkpoint inhibitor combinations: lessons from phase III clinical trials.

Antiangiogenic agents, generally antibodies or tyrosine-kinase inhibitors that target the VEGF-VEGFR pathway, are currently among the few combination partners clinically proven to improve the efficacy of immune-checkpoint inhibitors (ICIs). This benefit has been demonstrated in pivotal phase III trials across different cancer types, some with practice-changing results; however, numerous phase III trials have also had negative results. The rationale for using antiangiogenic drugs as partners for ICIs relies primarily on blocking the multiple immunosuppressive effects of VEGF and inducing several different vascular-modulating effects that can stimulate immunity, such as vascular normalization leading to increased intratumoural blood perfusion and flow, and inhibition of pro-apoptotic effects of endothelial cells on T cells, among others. Conversely, VEGF blockade can also cause changes that suppress antitumour immunity, such as increased tumour hypoxia, and reduced intratumoural ingress of co-administered ICIs. As a result, the net clinical benefits from antiangiogenic-ICI combinations will be determined by the balance between the opposing effects of VEGF signalling and its inhibition on the antitumour immune response. In this Perspective, we summarize the results from the currently completed phase III trials evaluating antiangiogenic agent-ICI combinations. We also discuss strategies to improve the efficacy of these combinations, focusing on aspects that include the deleterious functions of VEGF-VEGFR inhibition on antitumour immunity, vessel co-option as a driver of non-angiogenic tumour growth, clinical trial design, or the rationale for drug selection, dosing and scheduling.

Vitamin D [Serum 25(OH) cholecalciferol] Insufficiency is Associated With Childhood Asthma: Recent Case-Control Findings From Bangladesh.

Objectives. To evaluate the interaction between childhood asthma and S. 25(OH) cholecalciferol among Bangladeshi children. Methods. This case control study was conducted in child asthma clinic, Bangladesh Shishu Hospital Institute during March-August 2021. Comparison was made between clinically-diagnosed (following GINA guideline) asthmatic children (2-12 years-old) (cases = 87) and age and sex-matched children having no respiratory illness (controls = 90) using SPSS' (Statistical Package for Social Science, V.23.0 Windows) software. Results. Serum 25(OH) cholecalciferol was found to be significantly lower among the cases than the controls (P < .01). The cases had 3.4 times higher likelihood of having low vitamin D (combined deficient + insufficient) than the controls (P < .01). Conclusions. The results of the study demonstrate an association of Serum 25 (OH) cholecalciferol with asthma which underscores the importance of potential future trial to evaluate the efficacy of Vitamin-D supplementation for understanding the outcomes of asthmatic Bangladeshi children.

Pattern and Predictors of Infection Among Patients With Rheumatological Disease on Immunosuppressive Medications: A Retrospective Study in a Tertiary Care Hospital in Bangladesh.

Background Immunomodulatory therapy for chronic rheumatic disease carries a risk for infectious complications. In Bangladesh, there is limited information regarding patterns and factors associated with infections among patients receiving immunosuppressive medications. Objective The present study aimed to find out patterns and predictors associated with infection among patients who were on different immunosuppressive medications due to chronic rheumatological disease. Methodology This was a retrospective study; all confirmed cases of (new and old) different rheumatological diseases on disease-modifying agents attended at the rheumatology clinic of Dhaka Medical College Hospital from January 2019 to December 2021 were enrolled. Result Among 489 cases, 90 (18.4%) patients had documented infections. The most common rheumatological diseases were systemic lupus erythematosus (28, 31.1%), ankylosing spondylitis (26, 28.8%), and rheumatoid arthritis (20, 22.2%). COVID-19 (28, 31.1%) was the most commonly occurring infection followed by urinary tract infection (14, 15.6%), fungal infection (12, 13.3%), herpes zoster (10, 11.1%), pulmonary tuberculosis (TB) (eight, 8.8%), latent TB (seven, 7.7%), community-acquired pneumonia (six, 6.6%), and sepsis (three, 3.3%). Infection was most prevalent among patients who received steroids of more than 10 mg per day (17, 18.8%) than those less than 10 mg steroid per day (six, 6.7%), Factors associated with infections were (odds ratio, 95% CI, p-value) underweight (2.3, [1.3-2.7], 0.001), anemia (1.8, [1.1-5.7], 0.01), neutropenia (1.6, [1.1-2.9], <0.002), hypoalbuminemia (3.1, [1.6-4.9], 0.001), hypovitaminosis D (1.9, [1.3-4.5], 0.001), high blood sugar (1.5, [1.1-5.3], 0.02), inadequate counseling of steroid side effect (1.7, [1.1-3.9], 0.03), prednisolone >10mg/day (2.2, [1.19-4.10], 0.001). Conclusion COVID-19 pneumonia, urinary tract infections, fungal infection, tuberculosis, herpes zoster, and community-acquired pneumonia were commonly occurring infections among patients receiving different immunosuppressive medications. Factors like poor nutritional status, presence of anemia, leucopenia, hypoalbuminemia, hyperglycemia, and hypovitaminosis D had a significant association with infection. Moreover, inadequate counseling of steroid side effects and history of daily intake of prednisolone (>10mg/day) were also significant factors associated with infection.

Variation of Acromiocoracoid and Acromioglenoid Distance in Bangladeshi People.

This cross-sectional descriptive purposive study was done on 150 (70 right and 80 left) fully ossified dry human scapulae of Bangladeshi people to find out the variation in length of acromiocoracoid and acromioglenoid distance. Sample collection was carried out in the Department of Anatomy, Mymensingh Medical College, Bangladesh from January to December 2019. Any kind of damaged or broken scapulae were excluded to maintain standard measurement. Length of these distances was measured with the help of digital Vernier slide calipers. The mean±SD acromiocoracoid distance were 35.8±4.64 mm and 36.32±5.55 mm on right and left sided scapulae respectively and the mean±SD acromioglenoid distance were 27.69±3.43 mm on right sided scapulae and 28.18±3.26 mm on left sided scapulae. These data are important to compare Bangladeshi scapulae to those from various other races that could contribute to demographic studies of shoulder disease probability and management in Bangladeshi population.

Sexual exposure, awareness, and knowledge of long-acting reversible contraceptives among female university students in Ekiti State, Nigeria.

Unplanned and unintended pregnancies have become major medical, social and public health issues worldwide. The objective of this study was to determine sexual exposure, awareness and knowledge of long active reversible contraceptives (LARC) among female undergraduate students in public and private universities in Ekiti State, Southwest Nigeria. A comparative cross-sectional study was carried out among 428 female university undergraduates in Ekiti State (208 students in public and 210 students in private) using a multi-stage sampling technique. Data were obtained using a semi-structured questionnaire and analyzed using IBM SPSS version 23. P-value <0.05 was taken as significant. The mean age of respondents was 21.1±2.5years in public and 19.3±2.1years in private university. 53% of public university students and 30% of private university students have had sexual intercourse. While 41.3% of public university students were aware of LARC, 37.1% of the private university students were aware. The knowledge of LARC among the public university students was lower (23.6%) as compared to those in private university (33.3%). We conclude that while sexual exposure is higher among public university students than in private, the awareness of LARC was higher in public than private universities. Continuous campaign programmes to university students on the benefit of LARC is recommended.

Wastewater treatment plants elevating microplastic abundances, ecological risks, and loads in Japanese rivers: a source-to-sink perspective.

Little were certain about how wastewater treatment plants (WWTPs) affected the Japanese riverine microplastic contamination. This study explored the influences of WWTPs on microplastic pollution, assessed ecological risks, and looked at the sources-to-sinks phenomenon (WWTPs-to-rivers-to-marine) in riverine settings in Japan's Yamaguchi prefecture. Fifty surface water samples from the five selected rivers (Koya, Saba, Shimaji, and Fushino, Nishiki) and 11 effluent samples from WWTPs in the rivers' catchment were examined. Microplastics were analyzed using filtration, wet-peroxidation, density-separation, and attenuated reflectance-Fourier transform infrared spectroscopy techniques. Results suggested that the less populated and rural river (Nishiki) was less contaminated compared to the WWTPs and urban areas affected rivers (Koya, Saba, Shimaji, and Fushino). The WWTPs increased microplastic abundance twofold in the downstream regions compared to upstream stations. Microplastic characterization showed that the smaller microplastics < 500 µm, fiber-shaped, transparent, blue, and green color particles were major. Polymer identification demonstrated that the polyethylene, polypropylene, and polyethylene terephthalate were prevalent both for the rivers and WWTP effluents. There was a significant emission of microplastics from WWTPs to rivers (4.671 billion pieces per day; 71.8 kg per day) and rivers to Seto Inland Sea (0.13/billion pieces per day/km2; 7.1 kg per day). The per capita MP emissions to the rivers via WWTPs ranged from 0.02 to 6.49 g per day, which was approximately 2% of per capita single-use plastic wastes in Japan. An assessment of ecological risks showed that the WWTPs posed high ecological risks to rivers, and built up the pollution hotspots to their downstream areas by releasing higher number of microplastics and highly toxic polymers. Overall, the WWTPs influenced the rivers through both abundances and characteristics (shapes-size-color-polymers), increased the complexity of microplastic compositions as well as elevated ecological risks in the rivers. This study contributed to bridging the knowledge gaps about microplastic sources-to-sinks, ecological risks, and pollution management in Japan and beyond.

Prevalence of haemoglobin A1c based dysglycaemia among adult community dwellers in selected states in Nigeria: a descriptive cross-sectional study.

Background: Type 2 diabetes mellitus (T2DM) is a disease of public health importance globally with an increasing burden of undiagnosed pre-diabetes and diabetes in low- and middle-income countries, Nigeria in particular. Pre-diabetes and diabetes are established risk factors for cardiovascular complications. However, data are scanty on the current prevalence of these conditions in Nigeria, based on haemoglobin A1c (HbA1c) diagnosis as recommended by the WHO in 2009. We aimed to determine the prevalence of pre-diabetes, diabetes, and undiagnosed diabetes among the adult population of Nigeria using HbA1c. Methodology: A cross-sectional, multi-site population study was carried out in selected states in Nigeria (namely, Ekiti, Lagos, Osun, Oyo, and Kwara states) involving 2,708 adults (≥18 years) in rural and urban community dwellers, without prior diagnosis of pre-diabetes or diabetes. Participants with ongoing acute or debilitating illnesses were excluded. Data were collected using an interviewer-administered pretested, semi-structured questionnaire. Socio-demographic, clinical (weight, height, blood pressure, etc.), and laboratory characteristics of participants including HbA1c were obtained. Data were analysed using STATA version 16. Results: The mean age of participants was 48.1 ± 15.8 years, and 65.5% were female. The overall prevalence of pre-diabetes and undiagnosed diabetes was 40.5% and 10.7%, respectively, while the prevalence of high blood pressure was 36.7%. The prevalence of pre-diabetes was the highest in Lagos (48.1%) and the lowest in Ekiti (36.7%), while the prevalence of diabetes was the highest in Kwara (14.2%) and the lowest in Ekiti (10%). There was a significant association between age of the participants (p< 0.001), gender (p = 0.009), educational status (p = 0.008), occupation (p< 0.001), tribe (p = 0.004), marital status (p< 0.001), blood pressure (p< 0.001), and their diabetic or pre-diabetic status. Independent predictors of diabetes and pre-diabetes include excess weight gain, sedentary living, and ageing. Participants within the age group 45-54 years had the highest total prevalence (26.6%) of pre-diabetes and diabetes. Conclusion: Over half of the respondents had pre-diabetes and diabetes, with a high prevalence of undiagnosed diabetes. A nationwide screening campaign will promote early detection of pre-diabetes and undiagnosed diabetes among adult Nigerians. Health education campaigns could be an effective tool in community settings to improve knowledge of the risk factors for diabetes to reduce the prevalence of dysglycaemia.

University female students' perception and prospective practice of female genital mutilation in Umudike, Southeast Nigeria.

Female genital mutilation (FGM) under the guise of female circumcision is still practiced across wider communities in Nigeria despite various dangers associated with it and several efforts to curtail the practice. This study investigated the prevalence of and personal disposition towards female genital mutilation in 345 university undergraduate students of Michael Okpara University of Agriculture, Umudike (MOUAU), South east Nigeria using a pre-tested structured questionnaire. The major inclusion criteria for the face-to-face interview were being a female student of MOUAU and consented approval. Associations between various variable were tested with Chi square and statistical significance was established at P < 0.05. There was no association (P = 0.165) between place of birth and circumcision status, whereas state of circumcision had a significant association (P = 0.00001) with willingness to carry out circumcision in daughter in the future. Also, the belief that non-circumcised girls are prone to prone to promiscuity in adulthood had a significant (P = 0.00001) association with prospective circumcision of daughters. The prevalence of circumcision is high in this population (30.1%) with a reasonable number (16.8%) seeing no ills in the practice and expressed willingness to sustain it. Therefore, a strategy to curtail this practice has to focus on creating awareness at correcting this misconception as a learning theme at the tertiary level of education system rather than an assumption of passive knowledge. Further studies involving many universities in the study area and South-eastern Nigeria in particular are suggested to validate the results of this study.

Evaluation of instrumental variable method using Cox proportional hazard model in epidemiological studies.

The instrumental variable (IV) method with a Cox proportional hazard (PH) model has been used to evaluate treatment effects in epidemiological studies involving survival data. The effectiveness of the IV methods in these circumstances has yet to be fully understood, though. The study aimed to evaluate the performance of IV methods using a Cox model. We evaluated the validity of treatment effects estimated by two-stage IV models using simulated scenarios with varying confounder strengths and baseline hazards. Our simulation demonstrated that when observed confounders were not taken into account in the IV models, and the confounder strength was moderate, the treatment effects based on the two-stage IV models were similar to the true value. However, the effect estimates diverged from the true value when observed confounders were taken into account in the IV models. In the case of a null treatment effect (i.e., hazard ratio=1), the estimates from the unadjusted and adjusted IV models (only two-stage) were close to the true value. The implication of our study findings is that the treatment effects obtained through IV analyses using the Cox PH model remain valid if the estimates are reported from unadjusted IV models with moderate confounding effects or if the treatment does not impact the outcome.•For every simulation, we utilized a sample size of 10,000 and performed 1,000 replications.•The true treatment effects (HR) of 3, 2, and 1 (null effect) were evaluated.•The 95% confidence intervals (CI) were calculated as the range between the 2.5 and 97.5 percentiles of the 1000 estimates.

Abundance, characteristics, and ecological risks of microplastics in the riverbed sediments around Dhaka city.

Microplastic (MP) pollution has become an escalating problem in Bangladesh due to its rapid urbanization, economic growth, and excessive use of plastics; however, data on MP pollution from fresh water resources in this country are limited. This study investigated microplastics pollution in riverbed sediments in the peripheral rivers of Dhaka, the capital of Bangladesh. Twenty-eight sediment samples were collected from the selected stations of the Buriganga, Turag, and Balu Rivers. Density separation and wet-peroxidation methods were employed to extract MP particles. Attenuated total reflectance-Fourier transform infrared spectroscopy was used to identify the polymers. The results indicated a medium-level abundance of MPs in riverbed sediment in comparison with the findings of other studies in freshwater sediments worldwide. Film shape, white and transparent color, and large-size (1-5 mm) MPs were dominant in the riverbed sediment. The most abundant polymers were polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET). Pollution load index (PLI) values greater than 1 were observed, indicating that all sampling sites were polluted with MPs. An assessment of ecological risks, using the abundance, polymer types, and toxicity of MPs in the sediment samples, suggested a medium to very high ecological risk of MP pollution of the rivers. The increased abundance of MPs and the presence of highly hazardous polymers, namely; polyurethane, acrylonitrile butadiene styrene, polyvinyl chloride, epoxy resin, and polyphenylene sulfide, were associated with higher ecological risks. Scanning electron microscopy (SEM) analysis indicated that the MPs were subjected to weathering actions, reducing the size of MPs, which caused additional potential ecological hazards in these river ecosystems. This investigation provides baseline information on MP pollution in riverine freshwater ecosystems for further in-depth studies of risk assessment and developing strategies for controlling MP pollution in Bangladesh.

Decision-making in the treatment of radial head fractures: Delphi methodology.

BACKGROUND: The treatment of partially displaced radial head fractures is determined not only by the type of fracture but also by patient characteristics such as age, occupation, hand dominance, mechanism of injury, and concomitant injuries and comorbidities. The goal of this study was to employ the Delphi method to achieve consensus on the management of patients with radial head fractures, utilizing the experience of the ASES Elbow Fracture-Dislocation Multicenter Study Group and Mayo Elbow Club surgeons. METHODS: The initial survey was sent to participants, which included consent to participate in the study and questions about their experience, knowledge, and interest in participating in the Delphi method. We used both open-ended and category-based questions. The second questionnaire generated 76 variables, and individual questions with mean Likert ratings of <2.0 or >4.0 were deemed significant and merged to form multifactorial clinical scenarios relating to both nonoperative and operative management, respectively. RESULTS: Of the surgeons who responded to the questionnaire, 64% were from the United States, while the remainder were from overseas practices. Years in practice on average were 12.4 years (range, 1-40). Seven of the 76 factors met the criteria of a mean Likert score of <2.0 or >4.0. These factors were as follows: age, block to the range of motion (ROM) after aspiration/injection, crepitation with ROM, tenderness over the distal radioulnar joint and/or interosseous membrane (dorsal forearm), gap and/or displacement >2 mm on imaging, complete loss of contact of the head with the rest of the radius on imaging, and fracture head involvement 30% on imaging. Twenty-two (46%) of the 96 clinical scenarios gained >90% consensus in favor of surgical treatment, whereas 8 (17%) reached >90% consensus in favor of nonoperative treatment. CONCLUSION: Obtaining expert consensus on the treatment of radial head fractures remains challenging. Certain factors such as gap/displacement ≥2 mm without complete loss of contact, ≥30% head involvement with a block to an ROM regardless of tenderness over distal radioulnar joint or interosseous membrane (dorsal forearm), or crepitation when the patient was <80 years of age led to a recommendation of operative treatment in 100% of the surveyed surgeons. Patients older than 80 years with no block to ROM after aspiration/injection, no crepitation with ROM, and no tenderness on distal radioulnar joint/interosseous membrane (dorsal forearm) were recommended for nonoperative treatment regardless of the size of the radial head involvement on imaging.

Prevalence and associated risk factors for mental health problems among young adults in Fiji Island during COVID-19: a cross-sectional study.

Introduction: The COVID-19 pandemic has had a significant impact on mental health globally. To understand the impact of the pandemic on mental health in Fiji, this study aimed to investigate the prevalence of anxiety disorder and depression among the young adults. Method: An online survey was conducted to assess the prevalence of anxiety disorder and depression among the general population in Suva, Fiji during the COVID-19 pandemic. A total of 1,119 Fiji adults participated in the study. The study was conducted between May 20 to June 30, 2022, using a snowball sampling via social media platforms. The Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) scales were used to measure anxiety and depression, respectively. The COVID-19 related stressors was evaluated using the adapted SARS stressors assessment. Univariate and multivariate logistic regression analysis was performed to determine the factors influencing mental health among respondents. Results: The result shows that a significant portion of individuals experienced each of the stressors, with the highest prevalence seen for hearing information about the severity of COVID-19. The prevalence of anxiety and depression was found to be 45% and 49%, respectively. Being female, having pre-existing illness and COVID-19 stressors were a risk factor to develop anxiety and depression. On the other hand, employed individuals and having high BMI was a protective factor against developing depression during COVID-19 lockdown. Conclusion: These findings highlight the importance of addressing the mental health needs of the Fijian population during the COVID-19 pandemic and beyond.

Capsule phase microextraction of six bisphenols from human breast milk using a monolithic polyethylene glycol sorbent-based platform prior to high performance liquid chromatography-photo-diode array detection determination.

The determination of bisphenols in human breast milk is a matter of ongoing interest since it reveals the exposure levels in both lactating mothers, fetuses, and infants. Herein, capsule phase microextraction (CPME) is applied for the first time for the extraction of a mixture of bisphenols from human breast milk followed by their subsequent determination by high-performance liquid chromatography-photodiode array detection (HPLC-DAD). CPME is a recently introduced as an advanced micro preparative technique that meets the principles of Green Analytical Chemistry. Moreover, it integrates filtration, extraction and stirring mechanism into one single device, a composite attribute that allows selective extraction of analytes without any sample cleanup and facilitates faster extraction kinetics, resulting in enhancing the performance of the equilibrium-based extraction techniques that ensure better reproducibility and operational simplicity. Among four tested CPME devices, the sol-gel poly(ethylene glycol) capsules showed the best extraction efficiency. Critical factors of the extraction performance were investigated and optimized. The developed CPME-HPLC-PDA method was validated. Limits of detection and quantification were 7.58 ng/mL and 25 ng/mL, respectively. Relative recoveries were estimated between 89.7 and 110.5%, while the RSD values were <11% in all cases. CPME is poised to be a useful tool both for routine bioanalysis and research purposes.

Implementation status of non-communicable disease control program at primary health care level in Bangladesh: Findings from a qualitative research.

Objective: Bangladesh has 67% of estimated deaths caused by non-communicable diseases (NCDs). The country aimed to reduce NCD-related premature deaths by one-third by 2030. This study aimed to explore the overall implementation status of the NCD control program at the primary health care (PHC) level in Bangladesh, explore the challenges, and identify the way forward for better implementation. Study design: Qualitative study. Methods: Key informant interviews and observations of NCD service delivery at Upazila Health Complexes (UzHC) were conducted. Data were analyzed using framework analysis. Results: NCD is prioritized in policy documents however, implementation remains weak. The operational plan indicators focus mostly on the process, which is hampering the quality of care. The primary health care (PHC) facilities are not yet fully ready to deliver all ranges of NCD care including mental health. The national NCD management protocol for PHC addressed health workforce scarcity through task shifting and team-based care which is yet to be scaled up nationwide. Record-keeping is poor as it is done manually. District health information software (DHIS2) is not yet capturing NCD monthly service provision data and not tracking indicators. Awareness for NCD screening at community clinics, and referral to the NCD corner of UzHC is operational in around 66 Upazilas of 31 districts, which needs to scale up nationwide. Conclusions: NCD management protocol implementation, availability of drugs, diagnostics, electronic database development, updated DHIS2 to track indicators, and engagement of stakeholders to influence public policies on shared risk factors are important to achieve universal primary care for NCDs.

Sexual Debut, Sexual Education, Abortion, Awareness and Prevalence of Contraceptive Among Female Undergraduates Students in Public and Private Universities in Ekiti State, Nigeria.

Introduction Of the 182 million annual pregnancies in developing countries, 76 million are unintended and 66% of these are among non-users of contraception. Unintended pregnancy is a risk factor for abortion, disruption of education, future unemployment, and poor socio-economic status. This study aimed to determine the age of sexual debut, sexual education, abortion, awareness, and prevalence of contraceptives among female undergraduate students in public and private universities in Ekiti State. Methods A comparative cross-sectional study was carried out among 418 [public (208) and private (210)] female university undergraduate students in Ekiti State using a multi-stage sampling technique. Data was gathered using a semi-structured questionnaire and analyzed using SPSS (IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp). Chi-square was used to assess the association between dependent and independent variables at the bivariate level of analysis. P-value<0.05 was taken as significant. Results The mean age of respondents was 21.1±2.5 years in the public univeristy and 19.3±2.1 years in the private university. About 53.8% of students in the public university have been engaged in sexual intercourse as against 30% of students in the private university. The mean age at first sexual debut was lower in the public university (14.2±4.1 years) than in the private university (16.9±3.3 years) while more public university students (87.5%) had access to sexual education than their counterparts at the private university (79.0%). Of those who had ever been pregnant in public university (18.8%), about four-fifth (81.1%) of them had an abortion while all those who ever got pregnant (15.9%) in private university had an abortion. All the respondents in both universities were aware of contraception with the majority getting to know through social media. The prevalence of contraceptive use was lower among public university students (39.3%) than those in the private university (60.3%). Conclusion Mean age at sexual debut and rate of abortion were lower in public university students than in private. While access to sexual education was higher in the public university than in the private university, the prevalence of contraceptive use was lower in the public university. Therefore it is recommended that the government and other relevant stakeholders need to institute continuous awareness campaign programs to increase contraception uptake and reduce the prevalence and effect of unwanted pregnancy as a result of unprotected sexual activities.

Irrigation techniques used in spine surgery for surgical site infection prophylaxis: a systematic review and meta-analysis.

BACKGROUND: The greater likelihood of morbidity, mortality, length of hospital stays and poorer long-term outcomes as a result of surgical site infections secondary to spinal surgery makes prophylactic measures an imperative focus. Therefore, the aim of this review was to evaluate the available research related to the efficacy of different intraoperative irrigation techniques used in spinal surgery for surgical site infection (SSI) prophylaxis. METHODS: We performed a comprehensive search using Ovid Medline, EMBASE, Web of Science and the Cochrane library pertaining to this topic. Our meta-analysis was conducted according to PRISMA guidelines. The inclusion criteria consist of spine surgeries with intraoperative use of any wound irrigation technique, comparison groups with a different intraoperative irrigation technique or no irrigation, SSI identified with bacterial cultures or clinically in the postoperative period, reported SSI rates. Data extracted from eligible studies included, but was not limited to, SSI rates, irrigation technique and control technique. Exclusion criteria consist of articles with no human subjects, reviews, meta-analyses and case control studies and no details about SSI identification or rates. Pooled risk ratios were calculated. A meta-analysis was performed with a forest plot to determine risk estimates' heterogeneity with I2 index, Q-statistic, and p value under a random-effects model. Funnel plot was used to assess publication bias. All databases were last checked on January, 2022. PROBAST tool was used to assess both risk of bias and applicability concerns. RESULTS: After reviewing 1494 titles and abstracts, 18 articles met inclusion criteria. They included three prospective randomized-controlled trials, 13 retrospective cohort studies, two prospective cohort studies. There were 54 (1.8%) cases of SSIs in the povidone-iodine irrigation group (N = 2944) compared to 159 (4.6%) in the control group (N = 3408). Using intraoperative povidone-iodine wound irrigation produced an absolute risk reduction of 2.8%. Overall risk ratio was 0.32 (95% CI 0.20-0.53, p < 0.00001). In a global analysis, study heterogeneity and synthesizing mostly retrospective data were primary limitations. CONCLUSION: The most evidence exists for povidone-iodine and has Level 2 evidence supporting SSI reduction during spinal surgery. Other antiseptic solutions such as dilute chlorhexidine lack published evidence in this patient population which limits the ability to draw conclusions related to its use in spinal surgery. LEVEL OF EVIDENCE: II - Systematic Review with Meta-Analysis.

A transition copula model for analyzing multivariate longitudinal data with missing responses.

In multivariate longitudinal studies, several outcomes are repeatedly measured for each subject over time. The data structure of these studies creates two types of associations which should take into account by the model: association of outcomes at a given time point and association among repeated measurements over time for a specific outcome. In our approach, because of some advantageous arisen from features like flexibility of marginal distributions, a copula-based approach is used for joint modeling of multivariate outcomes at each time points, also a transition model is used for considering the association of longitudinal measurements over time. For the problem of incomplete data, missingness mechanism is assumed to be ignorable. Some simulation results are reported in different scenarios using the Gaussian, t and several commonly used copulas of the family of Archimedean copulas. Akaike information criterion (AIC) is used to select the best copula function. The proposed approach is also used for analyzing a real obesity data set.

A Bayesian shared parameter model for joint modeling of longitudinal continuous and binary outcomes.

Joint modeling of associated mixed biomarkers in longitudinal studies leads to a better clinical decision by improving the efficiency of parameter estimates. In many clinical studies, the observed time for two biomarkers may not be equivalent and one of the longitudinal responses may have recorded in a longer time than the other one. In addition, the response variables may have different missing patterns. In this paper, we propose a new joint model of associated continuous and binary responses by accounting different missing patterns for two longitudinal outcomes. A conditional model for joint modeling of the two responses is used and two shared random effects models are considered for intermittent missingness of two responses. A Bayesian approach using Markov Chain Monte Carlo (MCMC) is adopted for parameter estimation and model implementation. The validation and performance of the proposed model are investigated using some simulation studies. The proposed model is also applied for analyzing a real data set of bariatric surgery.

Cooperative cargo transportation by a swarm of molecular machines.

Cooperation is a strategy that has been adopted by groups of organisms to execute complex tasks more efficiently than single entities. Cooperation increases the robustness and flexibility of the working groups and permits sharing of the workload among individuals. However, the utilization of this strategy in artificial systems at the molecular level, which could enable substantial advances in microrobotics and nanotechnology, remains highly challenging. Here, we demonstrate molecular transportation through the cooperative action of a large number of artificial molecular machines, photoresponsive DNA-conjugated microtubules driven by kinesin motor proteins. Mechanical communication via conjugated photoresponsive DNA enables these microtubules to organize into groups upon photoirradiation. The groups of transporters load and transport cargo, and cargo unloading is achieved by dissociating the groups into single microtubules. The group formation permits the loading and transport of cargoes with larger sizes and in larger numbers over long distances compared with single transporters. We also demonstrate that cargo can be collected at user-determined locations defined by ultraviolet light exposure. This work demonstrates cooperative task performance by molecular machines, which will help to construct molecular robots with advanced functionalities in the future.

Age Related Changes in the Purkinje Cells in Human Cerebellar Cortex in Bangladeshi People.

This study was done to see the changes in the number of Purkinje cells per square mm in different age groups of Bangladeshi people. This cross-sectional descriptive type of study was done on total 40 postmortem human cerebellums, in the Department of Anatomy, Mymensingh Medical College, Bangladesh from July 2016 to June 2017. The specimens were collected from morgue in the department of Forensic Medicine, Mymensingh Medical College, by purposive sampling technique. All the specimens were grouped into four categories: Group A (20 to 29 years), Group B (30 to 39 years), Group C (40 to 49 years) and Group D (50 to 59 years). Paraffin blocks of cerebellum were cut at 4-5µm thickness and stained with routine "Haematoxylin and Eosin" (H & E) stain. Estimation of number of Purkinje cell was done by using the counting circle and examined under the light microscope. In the present study, the mean±SD number of Purkinje cell was found 128.67±25.15 per sq mm in Group A, 136.53±34.45 in Group B per sq mm, 135.55±29.44 per sq mm in Group C, 127.69±35.31 per sq mm in Group D.