Tumour mutation burden and other exome-wide biomarkers are used to determine which patients will benefit from immunotherapy. However, the cost of whole exome sequencing limits the widespread use of such biomarkers. Here, we introduce a data-driven framework for the design of targeted gene panels for estimating a broad class of biomarkers including tumour mutation burden and tumour indel burden. Our first goal is to develop a generative model for the profile of mutation across the exome, which allows for gene- and variant type-dependent mutation rates. Based on this model, we then propose a procedure for constructing biomarker estimators. Our approach allows the practitioner to select a targeted gene panel of prespecified size and construct an estimator that only depends on the selected genes. Alternatively, our method may be applied to make predictions based on an existing gene panel, or to augment a gene panel to a given size. We demonstrate the excellent performance of our proposal using data from three non small-cell lung cancer studies, as well as data from six other cancer types.

The pathogenesis of malaria is associated with blood-stage infection and there is strong evidence that antibodies specific to parasite blood-stage antigens can control parasitemia. This provides a strong rational for applying blood-stage antigen components in a multivalent vaccine, as the induced antibodies in combination can enhance protection. The Plasmodium falciparum rhoptry-associated membrane antigen (PfRAMA) is a promising vaccine target, due to its fundamental role in merozoite invasion and low level of polymorphism. Polyclonal antibodies against PfRAMA are able to inhibit P. falciparum growth and interact synergistically when combined with antibodies against P. falciparum reticulocyte-binding protein 5 (PfRh5) or cysteine-rich protective antigen (PfCyRPA). In this study, we identified a novel PfRAMA-specific mAb with neutralizing activity, which in combination with PfRh5- or PfCyRPA-specific mAbs potentiated the neutralizing effect. By applying phage display technology, we mapped the protective epitope to be in the C-terminal region of PfRAMA. Our results confirmed previous finding of synergy between PfRAMA-, PfRh5- and PfCyRPA-specific antibodies, thereby paving the way of testing these antigens (or fragments of these antigens) in combination to improve the efficacy of blood-stage malaria vaccines. The results emphasize the importance of directing antibody responses towards protective epitopes, as the majority of anti-PfRAMA mAbs were unable to inhibit merozoite invasion of erythrocytes.

This study aimed to investigate the effect of a video-assisted discharge education program on activities of daily living, functionality, and patient satisfaction following total hip replacement (THR) surgery. This study included 31 patients who were randomly divided into the physiotherapy group (n = 18), and the video-assisted discharge education (VADE) group (n = 13). Both groups received a physiotherapy program. The VADE group was also received the VADE program. Face-to-face instruction was used in all of the educational programs. There was a significant difference in favor of the VADE group in Harris Hip Score, Nottingham Extended Activities of Daily Living Scale's movement score, Tampa Scale of Kinesiophobia, Patient Satisfaction Questionnaire (p < 0.05). There was a significant difference between groups on resting pain levels in the first week and on resting and activity pain levels in the third month in favor of the VADE group (p < 0.05). The results of this study demonstrated that VADE can be effective in improving patient satisfaction and functionality, reducing pain and kinesiophobia following THR.

Behavioural research requires the use of sampling methods to document the occurrence of responses observed. Sampling/recording methods include ad libitum, continuous, pinpoint (instantaneous), and one-zero (interval) sampling. Researchers have questioned the utility of each sampling method under different contexts. Our study compared computerized simulations of both pinpoint and one-zero sampling to continuous recordings. Two separate computer simulations were generated, one for response frequency and one for response duration, with three different response frequencies (high, medium, or low) and response durations (short, medium, and long) in each simulation, respectively. Similarly, three different observation intervals (5, 50, and 500 s) were used to record responses as both pinpoint and one-zero sampling methods in the simulations. Under both simulations, pinpoint sampling outperformed one-zero sampling, with pinpoint sampling producing less statistical bias in error rates under all frequencies, durations, and observation intervals. As observation intervals increased, both mean error rates and variability in error rates increased for one-zero sampling, while only variability in error rate increased for pinpoint sampling. The results suggest that pinpoint sampling techniques are effective for measuring both frequency (event) and duration (state) behaviours, and that pinpoint sampling is a less statistically biased behavioural observation method than one-zero sampling.

Dyslipidemia is a risk factor for atherosclerotic cardiovascular disease and requires proactive management. This study aimed to investigate the association between care continuity and the outcomes of patients with dyslipidemia. We conducted a retrospective cohort study on patients with dyslipidemia by employing the Korea National Health Insurance claims database during the period 2007-2018. The Continuity of Care Index (COCI) was used to measure continuity of care. We considered incidence of atherosclerotic cardiovascular disease as a primary outcome. A Cox's proportional hazards regression model was used to quantify risks of primary outcome. There were 236,486 patients newly diagnosed with dyslipidemia in 2008 who were categorized into the high and low COC groups depending on their COCI. The adjusted hazard ratio for the primary outcome was 1.09 times higher (95% confidence interval: 1.06-1.12) in the low COC group than in the high COC group. The study shows that improved continuity of care for newly-diagnosed dyslipidemic patients might reduce the risk of atherosclerotic cardiovascular disease.

One of the complications of esophageal endoscopic submucosal dissection (ESD) is postoperative stricture formation. Stenosis formation is associated with inflammation and fibrosis in the healing process. We hypothesized that the degree of thermal damage caused by the device is related to stricture formation. We aimed to reveal the relationship between thermal damage and setting value of the device. We energized a resected porcine esophagus using the ESD device (Flush Knife 1.5). We performed 10 energization points for 1 s, 3 s, and 5 s at four setting values of the device. We measured the amount of current flowing to the conducted points and the temperature and evaluated the effects of thermal damage pathologically. As results, the mean highest temperatures for 1 s were I (SWIFT Effect3 Wat20): 61.19 °C, II (SWIFT Effect3 Wat30): 77.28 °C, III (SWIFT Effect4 Wat20): 94.50 °C, and IV (SWIFT Effect4 Wat30): 94.29 °C. The mean heat denaturation areas were I: 0.84 mm², II: 1.00 mm², III: 1.91 mm², and IV: 1.54 mm². The mean highest temperature and mean heat denaturation area were significantly correlated (P < 0.001). In conclusion, Low-current ESD can suppress the actual temperature and thermal damage in the ESD wound.

Aims: The pathogenesis of osteoarthritis (OA) is characterized by oxidative stress (OS) and sustained inflammation that are substantially associated with epigenetic DNA methylation alterations of osteogenic gene expression. Diacerein as an anthraquinone anti-OA drug exhibits multiple chondroprotective properties, but less clarified pharmacological actions. Since anthraquinone contain epigenetic modulating property, in this study we investigate whether the anti-OA functions of diacerein involve DNA methylation modulation and antioxidant signaling.

Results: OA mice incurred by DMM (destabilization of medial meniscus) exhibited marked suppression of PPARγ (peroxisome proliferator-activated receptor-gamma), a chondroprotective transcription factor with anti-inflammation and OS-balancing properties, aberrant upregulations of DNA methyltransferase (DNMT)1/3a and PPARγ promoter hypermethylation in knee joint cartilage. Diacerein treatment mitigated the cartilage damage and significantly inhibited the DNMT1/3a upregulations, the PPARγ promoter hypermethylation and the PPARγ loss, and effectively corrected the adverse expression of antioxidant enzymes and inflammatory cytokines. In cultured chondrocytes, diacerein reduced the IL-1β-induced PPARγ suppression and the abnormal expression of its downstream antioxidant enzymes in a gain of DNMT and PPARγ inhibition-sensitive manner, and in PPARγ knockout mice, the anti-OA effects of diacerein were significantly reduced.

Innovation: Our work reveals a novel anti-OA pharmacological property of diacerein, and identifies the aberrant DNMT elevations and the resultant PPARγ suppression as an important epigenetic pathway that mediates diacerein's anti-OA activities.

Conclusion: DNA methylation aberration and the resultant PPARγ suppression contribute significantly to epigenetic OA pathogenesis, and targeting PPARγ suppression via DNA demethylation is an important component of diacersin's anti-OA functions.

Introduction Breast cancer is the most common cancer among women worldwide and one of the main causes of death in the female sex. Genetic polymorphisms in the mu-opioid receptor (OPRM1) and catechol-o-methyltransferase (COMT) genes have been shown to increase breast cancer risk. Variants in these genes may carry a prognostic impact in breast cancer. Long follow-up intervals are critical to adequately analyze prognosis in diseases with prolonged survival times and late relapses. Objective To analyze the impact of genetic polymorphisms on the survival of a cohort of breast cancer patients with very long follow-up. Methods This was a retrospective study of patients treated at Portuguese Oncology Institute of Porto (IPO Porto), a Portuguese comprehensive cancer center, with invasive carcinoma of the breast with very long follow-up, with analysis of genetic polymorphisms OPMR1 rs1799971 (AA vs. G allele) and COMT rs4680 (CC vs T allele) on biological samples. Statistical analysis of survival was performed using the Kaplan-Meier method, log-rank test, and Cox regression method. Results A total of 143 patients with invasive breast cancer were included, with a median follow-up of 21.5 years. There was a statistically significant difference in overall survival (OS) at 30 years according to the OPMR1 polymorphism, with lower survival in patients with the AA genotype (p<0.05). The difference in OS according to the COMT polymorphism was also statistically significant, with worse survival in patients with genotype T allele (p<0.05). The genetic variants were not associated with patient age, stage at diagnosis, or tumor grade. Discussion The genetic polymorphisms of OPRM1 and COMT affected the overall survival of breast cancer patients, in concordance with previous research. Further investigation is needed in order to clarify the prognostic impact of these genetic alterations on breast cancer.

Keywords: breast cancer outcomes; breast cancer research; comt genotype polymorphism; genetic polymorphism; oprm1 genotype polymorphism.

Background: Ovarian cancer (OC) is the main cause of cancer-related death in women, and drug resistance is a leading cause of treatment failure. Recently, the involvement of circular RNAs (circRNAs) in cancer progression has become an area of increased investigation. The objective of this study is to uncover the function and regulatory mechanism of circ_0025033 in paclitaxel (PTX)-resistant OC cells.

Methods: The expression of circ_0025033, FOXM1 and miR-532-3p was investigated using quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expression of FOXM1 was quantified by western blot. Cell biological functions, including cell viability, migration/invasion and apoptosis, were explored using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays, transwell assays and flow cytometry assays. The interaction between miR-532-3p and circ_0025033 or FOXM1 predicted by bioinformatics analysis was validated by pull-down assay and dual-luciferase reporter assay. Exosomes were isolated to determine the further function of circ_0025033.

Result: Circ_0025033 and FOXM1 were highly expressed, while miR-532-3p was poorly expressed in OC tissues and cells, and the expression pattern was greater in PTX-resistant OC cells. Circ_0025033 knockdown lessened PTX resistance, suppressed migration/invasion and promoted apoptosis of PTX-resistant cells. With respect to mechanism, circ_0025033 upregulated the expression of FOXM1 by targeting miR-532-3p, and circ_0025033 knockdown blocked the malignant activities of PTX-resistant OC cells by enriching miR-532-3p and suppressing FOXM1. Exosomes derived from PTX-resistant cells with circ_0025033 knockdown also could repress the malignant actions of PTX-resistant OC cells.

Conclusion: Circ_0025033 downregulation impaired PTX resistance and malignant activities of PTX-resistant OC cells by regulating the miR-532-3p/FOXM1 network.

Keywords: FOXM1; circ_0025033; miR-532-3p; ovarian cancer; paclitaxel.

Sexual violence affects millions of Americans, and approximately one out of every three women and one out of every four men have experienced sexual violence during their lifetime. While prevention efforts have focused on implementing specific programmatic approaches, there has been relatively little focus on developing comprehensive and effective approaches to reduce sexual assault prevention across an organization. This study describes the development of the Prevention Evaluation Framework, an assessment targeting organizational best practices for comprehensive sexual assault prevention across multiple domains including human resources, collaborative relationships and infrastructure, use of evidence-informed approaches, quality implementation and continuous evaluation of programs/policies. Using the structured RAND/University of California, Los Angeles appropriateness method to develop the assessment, we conducted a literature review and solicited expert feedback about what a comprehensive organizational approach to sexual assault prevention should entail. We then pilot tested the assessment with 3 United States military service academies; and continued to improve and adapt the assessment to a range of organizations with input from 6 Department of Defense headquarters organizations, and 9 universities across the country. Given the nascent state of the evidence about what makes an effective organizational approach to sexual assault prevention, the assessment reflects one way of promoting quality in this evolving field. The consistency between the experts' ratings and the literature, and the relevance of the items across organizations suggest that the assessment provides important guidance to inform the development of comprehensive organizational approaches to sexual assault prevention and to the evaluation of ongoing efforts.

Cauda equina syndrome (CES) rarely occurs in upper lumbar spinal pathologies above L2. Osteoporosis is a consideration in determining the operative approach. We report a case of CES as a result of an L1 burst fracture in an osteoporotic lady with schizophrenia. A 74-year-old schizophrenic lady presented with traumatic lower back pain with no neurological deficit. Due to her psychiatric condition, the clinical assessment was challenging. On day 3 of admission, there was an acute total loss of motor function over bilateral L2-L3 myotomes to MRC grade 0/5, progressively involving bilateral L2-S1 myotomes symmetrically. There was associated symmetrical bilateral lower limb hypotonia, areflexia, acute urinary retention, and absence of anal tone and bulbocavernosus reflex. Magnetic resonance imaging (MRI) reported a severe L1 compression fracture with retropulsion and cauda equina compression. Conus medullaris terminated at T12. An L1 anterior corpectomy and decompression with T11-L3 posterior instrumentation and stabilization were performed. Intraoperatively noted osteoporotic bone. Postoperatively, motor function improved to MRC grade 4/5 over bilateral L4-S1 myotomes by postoperative day 15 with rehabilitation. A variant in anatomy may result in a high differentiation of the conus medullaris into the cauda equina. Thus, an L1 burst fracture may, on rare occasions, result in CES instead of conus medullaris syndrome. Special attention needs to be given to psychiatric patients who are unable to provide a good history and comply with a physical examination. MRI remains the diagnostic gold standard for CES. Early diagnosis and early surgical decompression are recommended for maximum functional recovery. Osteoporosis further complicates the operative intervention as both the anterior and posterior approaches must be adapted for better stabilization and surgical outcome. Early initiation of rehabilitation is crucial for postoperative functional recovery.

Keywords: cauda equina compression; l1 burst fracture; osteoporosis; rare presentation; variant anatomy.

Introduction In this study, we evaluated the scope of acute non-specific back pain (ANSBP) content available on TikTok (ByteDance Ltd, Beijing, China) in 2021. It is plausible that TikTok's popularity among teenagers, adolescents, and young adults may influence decision-making about what constitutes appropriate ANSBP self-care among a younger age cohort. Methods We examined 157 of the most viewed videos available through the hashtag #backpain available on TikTok in September 2021. We examined the following research questions: (1) What are the metadata characteristics of the videos in the final data set?, (2) What are the creator identities reflected in the final data set in this study?, (3) What are the ANSBP self-care content themes in the final data set?, and (4) What are the characteristics of the data set based on a low back pain reference checklist based on consensus guidelines?. Results We identified clear differences based on TikTok creator identity in our data set of most popular videos. We examined videos created by chiropractors, fitness professionals, influencers, physicians, physiotherapists, and other creator identities. We found that the TikTok videos created by chiropractors were consistently among the most viewed, most commented, and most shared. Conversely, chiropractic TikTok videos consistently had the lowest self-care reference checklist scores relative to all other disciplines. That is, TikTok videos created by chiropractors were least likely to reflect the scientific consensus on treating ANSBP. Discussion TikTok is an increasingly popular medium for disseminating short health messages. The main cohort using TikTok is young and at risk of ANSBP. However, we postulate that the messages reaching young TikTok users overall do not generally reflect the self-care advice described in consensus guidelines. Conclusion TikTok is a popular social media channel among young people. However, the most viewed TikTok videos about ANSBP are not produced by mainstream health professionals and the videos featuring the #backpain hashtag do not generally reflect contemporary evidence-based practice. There is considerable scope for mainstream health professionals to provide evidence-informed self-management and self-care content for ANSBP on TikTok.

Keywords: lower back pain (lbp); public health informatics; research methods and design; social media analytics; tiktok.

Glomus tympanicum is a slow-growing benign tumor that can be locally destructive, spreading along the path of least resistance. Conventionally seen as soft tissue mass in the middle ear, it is difficult to distinguish glomus tympanicum from other soft tissue masses of the tympanic cavity, especially as it hides behind an intact tympanic membrane. The primary diagnostic modalities are CT scan and MRI for evaluation of the exact anatomical extent and size of the glomus tumors. Embolization following an angiographic study helps to identify the feeding arteries with subsequent blocking of the same, thus helping in the reduction of intraoperative hemorrhage. The currently available modalities of treatment are mainly surgery and radiotherapy. Here, we report a case of a 40-year-old female who presented with unilateral deafness and tinnitus, with no co-morbidities. She showed a red bulging mass behind an intact tympanic membrane on otoscopy and otomicroscopy with mild conductive hearing loss. MRI showed an intensely enhancing lesion in the mesotympanum and hypotympanum along the cochlear promontory. A diagnosis of glomus tympanicum was made based on clinical, audiological, and radiological findings. Pre-operative embolization was carried out 48 hours before the surgery. Complete resection of the tumor was achieved by microsurgery.

Keywords: glasscock-jackson classification; glomus tympanicum; paraganglioma; pre-operative embolization; pulsatile tinnitus.

We present a case of a 39-year-old male patient who was previously diagnosed with myasthenia gravis. He presented in a myasthenic crisis secondary to a lower respiratory tract infection, with the implicated organism being Raoultella planticola. He was referred to the intensive care unit (ICU) and required ventilatory support due to respiratory insufficiency. Early broad-spectrum antibiotics for a suspected bacterial infection were provided in combination with management specific to the myasthenic crisis. The patient made a full recovery and has displayed a good clinical response. This case report explores his presentation and aims to provide further literature on the incidence and description of R. planticola.

Keywords: gram negative bacteria; lower respiratory tract infection; myasthenia gravis; myasthenic crisis; neuromuscular junction; raoultella planticola.

Background: Surgical management of periacetabular bone metastases is challenging. The Harrington Plus reconstruction is a modification of the original Harrington rod technique. An intrapelvic suprapectineal plate is used, with the aim of reconstructing a disrupted anterior column and reducing the risk of failure in cases where there is extensive medial bone loss.

Methods: A retrospective review of the 13 patients who have undergone the Harrington Plus procedure to date was performed. Mobility status, EQ5D and Oxford Hip scores were assessed.

Results: There was a significant improvement in mobility status, EQ5D and Oxford Hip Scores at 6 months postoperatively (p < 0.05). Two patients returned to theatre for debridement of infection. There were no postoperative dislocations, cup medialisation or cases of loosening of the prosthesis. No patient required revision arthroplasty surgery.

Conclusion: The Harrington Plus procedure produces a reliable construct that allows patients with extensive periacetabular metastatic defects to fully weight-bear. Careful patient selection and multidisciplinary management is essential.

Keywords: Harrington procedure; Pelvic and acetabular metastases; Suprapectineal plate.

Interleukin-12 RB1 (IL12RB1) deficiency falls under the Mendelian susceptibility to mycobacterial disease. It is a rare genetic disease with autosomal recessive inheritance. It is characterized by recurrent infections with otherwise weak bacteria, such as mycobacteria and Salmonella. Often, when encountering a maculopapular eruption, a drug-related cause comes to mind. However, we report a case of IL12RB1 deficiency presenting with a maculopapular eruption, proven by a skin biopsy to be leukocytoclastic vasculitis. The patient was given antibiotics, which improved her skin lesions. Vasculitis should be considered in the differential diagnosis in patients with IL12RB1 deficiency presenting with a cutaneous eruption.

Keywords: bcg; interleukin 12; leukocytoclastic vasculitis; maculopapular rash; mycobacterium; salmonella.

A cross-sectional study was conducted from November 2018 to May 2019 in Bishoftu and Dukem in central part of Ethiopia. The objectives of the present study were to isolate and identify <i>S. aureus, E. coli,</i> and <i>Salmonella</i> from dairy cattle, personnel, and equipment at farms. In addition to this, antimicrobial resistance profiles of the isolates were determined. A total of 607 samples consisting of fresh cow milk (125), fecal sample (211), nasal swab (211), pooled milkers' hand swabs (20), pooled floor swabs (20), and tank milk (20) samples were collected from 20 dairy farms, which included 211 animals. Structured questionnaire was designed and administered to dairy farm owners and dairy food consumers to assess their consumption behavior and antibiotics usage. The samples were examined for the presence of <i>S. aureus, E. coli,</i> and <i>Salmonella</i> following standard techniques and procedures outlined by the International Organization for Standardization. Subsequently, 62 (15.7%) of <i>S. aureus</i> were isolated from 396 of the totals analyzed samples for <i>S. aureus</i>. Out of the 62 isolated <i>S. aureus</i>, 35/211(16.7%), 19/125(15.2%), 6/20(30%), 2/20(10%), and 0/20(0%) were from nasal swabs, udder milk, bulk milk, pooled hand swab, and floor swabs, respectively. On the other hand, 30 (<i>7.6</i>%) of <i>E. coli</i> were isolated from 396 of the totals analyzed samples for <i>E. coli</i>. Out of the 30 isolated <i>E. coli</i>, 17/211(8.1%), 12/125(9.6%), 0/20(0%), 0/20(0%), and 1/20(5%) were from faeces, udder milk, bulk milk, pooled hand swab, and floor swabs, respectively. In line with this, 13 (4.8%) of <i>Salmonella</i> were isolated from 271 of the totals analyzed samples for <i>Salmonella</i>. Out of the 13 isolated <i>Salmonella</i>, 10/211(4.7%), 2/20(10%), 0/20(0%), and 1/20(5%) were from faeces, bulk milk, pooled hand swab, and floor swabs, respectively. Subsequently, 62 of <i>S. aureus</i>, 30 of <i>E. coli,</i> and 13 of <i>Salmonella</i> isolates were subjected to antimicrobial susceptibility testing, and all isolates were resistant to at least one or more antimicrobials tested. Penicillin, methicillin, and trimethoprim/sulfamethoxazole are drugs to which a large proportion of isolated <i>S. aureus</i> were highly resistant, which range from 90% to 100%. From 30 tested <i>E. coli,</i> they showed (83%) resistance to Tetracycline and 80% to Vancomycin. The resistance level of 13 isolated <i>Salmonella</i> was 69% to Nalidixic acid and 54% to Vancomycin. Multiple drug resistance was detected in high (98.4%) for <i>S. aureus</i>, (56.7%) for <i>E. coli,</i> and (53.9%) for <i>Salmonella</i>. High proportion of multiple drug resistant in the dairy farm alerts concern for animal and public health as these drugs are used widely for treatment and prophylaxis in animals and humans.

In December 2019, the emergence of the new coronavirus disease 2019 (COVID-19) began in Wuhan, China. Thereafter, the disease has been spreading rapidly across the world, with about 300 million registered cases worldwide, and the numbers are also exponentially increasing in India, with about 34 million registered cases by the end of 2021. Among the comorbidities, obesity may increase the risk of hospitalization due to COVID-19 infection as it is related to immune system dysfunction. Since the epidemiological picture of COVID-19 is changing very rapidly. Therefore, it is very important to discuss the pattern of clinical manifestation and association with comorbidities. Hence, we have conducted this observational study in one of the tertiary care centers in North India. Methods and Materials: We conducted a hospital-based prospective observational study in dedicated COVID-19 wards and ICU of a tertiary care center in North India with a sample size of 400 positive patients (males: 260, females: 140). We divided the patients in this study into three different age groups (less than 40 years, 40-60 years, and more than 60 years). The patients with age ≤ 18 years and BMI 18.5 kg/m2 were excluded from the study. Results: Out of these 400 patients, 55 (13.8%) developed severe COVID-19. There was a fewer number of patients who developed severe COVID-19 in the normal and over-weight group. Moreover, obese patients progressed to more severe cases (34.5%). This also shows that after adjusting for age, compared to the normal-weight group, those who were overweight had a 1.48-fold chance of developing severe COVID-19 (OR 1.48, P 0.0455), while those who were obese had a 1.73-fold chance of developing the disease (ORs 1.73, P 5 0.0652). Regarding gender distribution, the association appeared to be stronger in men than in women. After similar adjustment, the ORs for overweight and obese patients compared to normal-weight patients were 1.39 (p 0.5870) and 3.55 (p 0.0113) in females and 1.36 (0.5115) and 6.19 (0.0001) in males, respectively. Conclusion: Our study shows that obese patients with a BMI of greater than or equal to 27.5 are at higher risk of developing COVID-19 severity, especially in the male population. Moreover, severity may be related to other comorbid conditions. However, in our study, patients with chronic obstructive pulmonary disease (COPD) and GI/liver diseases were less obese, and severity was relatively low. So, the conclusion is that obese male patients with comorbidities are more likely to develop severe COVID-19 infection.

Keywords: bmi; covid 19; marker; multiple co-morbidities; obesity.

Hypertension and chronic kidney disease (CKD) are among the most common comorbidities associated with coronavirus disease 2019 (COVID-19) severity and mortality risk. Renin-angiotensin system (RAS) blockers are cornerstones in the treatment of both hypertension and proteinuric CKD. In the early months of the COVID-19 pandemic, a hypothesis emerged suggesting that the use of RAS blockers may increase susceptibility for COVID-19 infection and disease severity in these populations. This hypothesis was based on the fact that angiotensin-converting enzyme 2 (ACE2), a counter regulatory component of the RAS, acts as the receptor for severe acute respiratory syndrome coronavirus 2 cell entry. Extrapolations from preliminary animal studies led to speculation that upregulation of ACE2 by RAS blockers may increase the risk of COVID-19-related adverse outcomes. However, these hypotheses were not supported by emerging evidence from observational and randomized clinical trials in humans, suggesting no such association. Herein we describe the physiological role of ACE2 as part of the RAS, discuss its central role in COVID-19 infection and present original and updated evidence from human studies on the association between RAS blockade and COVID-19 infection or related outcomes, with a particular focus on hypertension and CKD.

Keywords: COVID-19; angiotensin-converting enzyme 2; chronic kidney disease; hypertension; renin–angiotensin system.

Background: Low-quality diets contribute to the burden of malnutrition and increase the risk of children not achieving their developmental potential. Nutrition-sensitive agriculture programs address the underlying determinants of malnutrition, though their contributions to improving diets do not factor into current nutrition impact modeling tools.

Objective: To synthesize the evidence on the effectiveness of nutrition-sensitive agriculture programs in improving dietary diversity in young children (6-23.9 months and 6-60 months).

Methods: A literature search was conducted for published trials through existing systematic reviews and individual database search of the ISI Web of Science. All dietary diversity measures in the studies selected to be in the analysis were extracted. Estimation of main pooled effects were conducted on outcomes of minimum diet diversity (MDD) and diet diversity score (DDS) using random-effects meta-regression models. We report pooled effect sizes as standardized mean differences (SMDs) or odds ratios (ORs).

Results: Nutrition-sensitive agricultural interventions have a significant positive impact on the diet diversity scores of children aged 6-23.9 months (SMD = 0.22, 95% confidence interval (CI) = 0.09-0.36) and on the odds of reaching minimum diet diversity (OR = 1.45, 95% CI = 1.20, 1.76). Similar impacts are found when analyses are expanded to include studies for children aged 6-60 months (DDS SMD = 0.22, 95% CI = 0.12-0.32) (MDD OR = 1.64, 95% CI: = 1.38-1.94).

Conclusion: Nutrition-sensitive agriculture interventions consistently have a positive impact on child dietary diversity. Incorporating this evidence in nutrition modeling tools can contribute to decision-making on the relative benefits of nutrition-sensitive interventions as compared with other maternal, newborn, child health and nutrition (MNCHN) interventions.

Neimeier, in 1934, proposed a classification for gallbladder perforation. The first type is fistulation between the gallbladder and adjacent viscerae. The second type is a subacute perforation surrounded by an abscess walled off by adhesions from the general peritoneal cavity; and the third type is a peritonitis due to free biliary spillage into the peritoneal cavity without protective adhesions. We will analyze a Neimeier's type 1 perforation. The patient is a 72-year-old male diagnosed with a cholecystolithiasis and empyema due to a cholecystopleural fistula. Was operated by laparoscopic surgery because its low rate of complications, and lower days at hospital staying. Everything went as planned with no complications. Even though it is not a common presentation, it sets a precedent for it to be furthermore researched, and for it to be used as a literary option in a discussion to know which type of surgery is better for these cases.