ORBIT for E. coli: kilobase-scale oligonucleotide recombineering at high throughput and high efficiency.

Microbiology and synthetic biology depend on reverse genetic approaches to manipulate bacterial genomes; however, existing methods require molecular biology to generate genomic homology, suffer from low efficiency, and are not easily scaled to high throughput. To overcome these limitations, we developed a system for creating kilobase-scale genomic modifications that uses DNA oligonucleotides to direct the integration of a non-replicating plasmid. This method, Oligonucleotide Recombineering followed by Bxb-1 Integrase Targeting (ORBIT) was pioneered in Mycobacteria, and here we adapt and expand it for Escherichia coli. Our redesigned plasmid toolkit for oligonucleotide recombineering achieved significantly higher efficiency than λ Red double-stranded DNA recombineering and enabled precise, stable knockouts (≤134 kb) and integrations (≤11 kb) of various sizes. Additionally, we constructed multi-mutants in a single transformation, using orthogonal attachment sites. At high throughput, we used pools of targeting oligonucleotides to knock out nearly all known transcription factor and small RNA genes, yielding accurate, genome-wide, single mutant libraries. By counting genomic barcodes, we also show ORBIT libraries can scale to thousands of unique members (>30k). This work demonstrates that ORBIT for E. coli is a flexible reverse genetic system that facilitates rapid construction of complex strains and readily scales to create sophisticated mutant libraries.

Advances in molecular pathogenesis of hidradenitis suppurativa: Dysregulated keratins and ECM signaling.

Hidradenitis suppurativa (HS) is characterized by deep-seated, highly inflamed, and painful lumps/abscesses, fistulae, and sinus tracts that grow extensively deep in the dermis and are highly immunogenic in nature. In about one-third of the HS patients there is strong evidence for the role of γ-secretase mutations along with dysregulated Notch signaling. However, the contribution of dysregulated Notch signaling in HS pathogenesis in relation to hair follicle alterations and hyper-activation of the immune system remains undefined. A genome-wide association study (GWAS), proteomic data and functional investigations of identified sequence variants in HS pathology are not fully revealing. The disease initiation or progression may involve bacterial infection besides intrinsic functional defects in keratinocytes, which may be key to further exacerbate immune cell infiltration and cytokine production in and around the lesional tissue. The absence of a suitable animal model that could fully recapitulate the pathogenesis of HS is a major impediment for proper understanding the underlying mechanisms and development of effective treatments. The presence of extracellular matrix (ECM) degradation products along with dysregulation in keratinocytes and, dermal fibroblasts ultimately affect immune regulation and are various components of HS pathogenesis. Bacterial infection further exacerbates the complexity of the disease progression. While anti-TNFα therapy shows partial efficacy, treatment to cure HS is absent. Multiple clinical trials targeting various cytokines, complement C5a and ECM products are in progress. This review provides state-of-the-art information on these aspects with a focus on dysregulated keratinocyte and immune cells; and role of ECM, and Keratin functions in this regard.

Efficacy of Faricimab vs Aflibercept in Diabetic Macular Edema in the 20/50 or Worse Vision Subgroup in Phase 3 YOSEMITE/RHINE Trials.

PURPOSE: DRCR.net Protocol T data suggest the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME enrolled in faricimab phase 3 trials with baseline Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA ≤20/50. DESIGN: YOSEMITE/RHINE were identically designed, multicenter, randomized, double-masked, active comparator-controlled, noninferiority trials. PARTICIPANTS: Adults aged ≥18 years with center-involving macular edema secondary to type 1 or 2 diabetes. METHODS: Patients were randomized to faricimab every 8 weeks (Q8W), faricimab per a personalized treat-and-extend-based regimen (T&E), or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intent-to-treat population with baseline BCVA ≤20/50 (ETDRS letters <69). MAIN OUTCOME MEASURES: Changes in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses. RESULTS: In YOSEMITE/RHINE, 220/217 patients in the faricimab Q8W; 220/219, faricimab T&E; and 219/214, aflibercept Q8W arms had baseline BCVA ≤20/50. In both trials, mean change in ETDRS BCVA was comparable between treatments at years 1 and 2. In YOSEMITE, adjusted mean (95% CI) change from baseline in CST (µm) at year 1 was greater with faricimab Q8W (-232.8 [-243.5, -222.1]) and faricimab T&E (-217.4 [-227.9, -206.9]) versus aflibercept Q8W (-190.4 [-200.9, -179.8]; P<0.0001 and P=0.0004, respectively). The pattern was similar in RHINE: faricimab Q8W, -214.2 (-225.3, -203.1); faricimab T&E, -206.6 (-217.4, -195.7); aflibercept Q8W, -186.6 (-197.7, -175.5); P=0.0006 and P=0.0116 for faricimab arms versus aflibercept, respectively. In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. Median time to first CST <325 µm and first absence of intraretinal fluid was shorter in the faricimab arms versus aflibercept, with fewer injections on average. CONCLUSIONS: In patients with DME and baseline ETDRS BCVA ≤20/50, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept over 2 years of treatment.

Biocontrol of plant pathogens in omics era-with special focus on endophytic bacilli.

Nearly all plants and their organs are inhabited by endophytic microbes which play a crucial role in plant fitness and stress resilience. Harnessing endophytic services can provide effective solutions for a sustainable increase in agriculture productivity and can be used as a complement or alternative to agrochemicals. Shifting agriculture practices toward the use of nature-based solutions can contribute directly to the global challenges of food security and environmental sustainability. However, microbial inoculants have been used in agriculture for several decades with inconsistent efficacy. Key reasons of this inconsistent efficacy are linked to competition with indigenous soil microflora and inability to colonize plants. Endophytic microbes provide solutions to both of these issues which potentially make them better candidates for microbial inoculants. This article outlines the current advancements in endophytic research with special focus on endophytic bacilli. A better understanding of diverse mechanisms of disease control by bacilli is essential to achieve maximum biocontrol efficacy against multiple phytopathogens. Furthermore, we argue that integration of emerging technologies with strong theoretical frameworks have the potential to revolutionize biocontrol approaches based on endophytic microbes.

First report of Aloe root and stem rot caused by Phytophthora palmivora in Yunnan Province, China.

Aloe genus plants are perennial evergreen herb belonging to Liliaceae family which is widely used in food, medicine, beauty, and health care (Kumar et al. 2019). In August 2021, symptoms of root and stem rot was observed in approximately 20% of Aloe vera plantings in Yuanjiang County, Yunnan Province, China (23° 64' 53" N, 101° 99' 84" E). The most typical symptoms were stem and root rot, browning and necrosis of vascular tissues, gradual greening, and reddish-browning of leaves from bottom to top, abscission, and eventual plant death (Fig. S1). Therefore, to isolate and identify the pathogen, the plants showing the above symptoms were collected. The plant tissues were cut from the edges of root and stem lesions, followed by disinfection with 75% ethanol for 1 min, rinsed three times with sterilized distilled water, and cut into 3 × 3 mm small squares after excision of marginal tissues. The tissues were transferred to the oomycetes selective medium (Liu et al. 2022) and incubated at 28 °C in the dark for 3~5 days, and suspected colonies were purified. The colonies were then inoculated onto potato dextrose agar (PDA), V8-juice agar (V8), and oatmeal agar (OA) medium plates for morphological characteristics. Finally, 18 isolates with the same colonial and morphological characteristics were obtained from 30 lesioned tissue and one of them was named as ARP1. On PDA, V8 and OA medium plates, the ARP1 colonies were white. On PDA plate, the mycelia were dense and the colonies were petal-like; on V8 plate, the mycelia were cashmere and the colonies were radial or star-like. Whereas, on OA plate, the mycelia were cotton-like and the colonies were fluffy and radial (Fig. S2 A~C). Mycelium did not have septum with high branching and swelling. Sporangia were abundant, semi-papillate, varying in shape from ovoid-ellipsoid to long-ellipsoid, 18-26 × 45-63 µm (average: 22 × 54 µm, n = 30), sporangia released numerous zoospores from the papillate after maturation. The chlamydospores were spherical, 20-35 µm in diameter (average: 27.5 µm, n = 30) (Fig. S2 D~F). These morphological features were like those of the pathogenic species of the oomycetes (Chen et al. 2022). For the molecular characterization, the genomic DNA of the isolate was extracted using the cetyl trimethyl ammonium bromide method, and the translation elongation factor 1α (tef-1α) (Stielow et al. 2015), ß-tubulin (ß-tub) (Kroon et al. 2004) and internal transcribed spacer (ITS) (White et al. 1990) of isolated strain ARP1 were amplified using primer pairs EF1-1018F/EF1-1620R, TUBUF2/TUBUR1 and ITS1/ITS4, respectively. The tef-1α, ß-tub genes and ITS region of ARP1 were directly sequenced and their sequence information was deposited in GenBank under accession numbers OQ506129, OQ506127 and OQ449628. ARP1 was clustered on the same evolutionary branch with Phytophthora palmivora (Fig. S3). To confirm the pathogenicity of ARP1, the main root of A. vera was wounded to 1 cm long and 2 mm deep with a scalpel blade followed by inoculation with 50 ml suspension of ARP1 zoospores at a concentration of 1 × 106 spores / ml per potted plant, and an equal volume of water as control. All inoculated plants were placed in the greenhouse at 28°C, 12 h / 12 h light / dark. After 15 dpi, the inoculated plants showed typical symptoms of wilted and drooping leaves and stem and root rot, same as observed in the field condition (Fig. S4). After inoculation with ARP1, a strain with the same morphological and molecular characteristics as the original isolate was re-isolated, confirming Koch's postulates. To our knowledge, this is the first report of P. palmivora causing root and stem rot of A. vera in the study region. This disease could be a potential risk for aloe production and therefore appropriate management measures should be taken.

Bacillus amyloliquefaciens AK-12 Helps Rapeseed Establish a Protection against Brevicoryne brassicae.

Aphids are a serious threat to rapeseed (Brassica napus L.) production, and cause unmanageable loss. Therefore, effective prevention and management strategies are urgently required to avoid losses. Bacillus amyloliquefaciens AK-12 isolated from a dead aphid with aphicidal activity was tagged with a green fluorescent protein through a natural transformation. The transformed strains were checked for stability and growth, and the best-performing strain was tested for its colonization inside and outside the rapeseed plant. The stability of AK-12-GFP reached more than 95%, and the growth curve was consistent with that of AK-12. After 30 days of treatment, the colonization of 1 × 106 CFU/g was recorded in rapeseed leaves. Interestingly, AK-12 reduced the aphid transmission rate compared with the control and improved the growth of the rapeseed seedlings. Meanwhile, the AK-12 strain also exhibited phosphorus, potassium-solubilizing, and nitrogen-fixing activity, and produced 2.61 µg/mL of IAA at 24 h. Regulation in the activity of four enzymes was detected after the AK-12 treatment. Phenylalanine ammonia lyase (PAL) was recorded at a maximum of 86.84 U/g after 36 h, and catalase (CAT) decreased after 48 h; however, peroxidase (POD) and polyphenol oxidase (PPO) reached the maximum within 12 h of AK-12 application. Additionally, important resistance genes related to these enzymes were upregulated, indicating the activation of a defense response in the rapeseed against aphids. In conclusion, defense enzymes and defense-related gene activation could improve the pest resistance in rapeseed, which has good application prospects for the future to be developed into biopesticide.

A lightweight CORONA-NET for COVID-19 detection in X-ray images.

Since December 2019, COVID-19 has posed the most serious threat to living beings. With the advancement of vaccination programs around the globe, the need to quickly diagnose COVID-19 in general with little logistics is fore important. As a consequence, the fastest diagnostic option to stop COVID-19 from spreading, especially among senior patients, should be the development of an automated detection system. This study aims to provide a lightweight deep learning method that incorporates a convolutional neural network (CNN), discrete wavelet transform (DWT), and a long short-term memory (LSTM), called CORONA-NET for diagnosing COVID-19 from chest X-ray images. In this system, deep feature extraction is performed by CNN, the feature vector is reduced yet strengthened by DWT, and the extracted feature is detected by LSTM for prediction. The dataset included 3000 X-rays, 1000 of which were COVID-19 obtained locally. Within minutes of the test, the proposed test platform's prototype can accurately detect COVID-19 patients. The proposed method achieves state-of-the-art performance in comparison with the existing deep learning methods. We hope that the suggested method will hasten clinical diagnosis and may be used for patients in remote areas where clinical labs are not easily accessible due to a lack of resources, location, or other factors.

The hidden treasures of citrus: finding Huanglongbing cure where it was lost.

Huanglongbing (HLB), a deadly citrus disease which has significantly downsized the entire industry worldwide. The intractable and incurable disease has brought the citriculture an enormous loss of productivity. With no resistant varieties available, failure of chemical treatments despite repeated applications, and hazardous consequences to environmental health, have led to large-scale research to find a sustainable cure. Inside plants, the key determinants of health and safety, live the endophytic microbes. Endophytes possess unrivaled plant benefiting properties. The progression of HLB is known to cause disturbance in endophytic bacterial communities. Given the importance of the plant endophytic microbiome in disease progression, the notion of engineering microbiomes through indigenous endophytes is attracting scientific attention which is considered revolutionary as it precludes the incompatibility concerns associated with the use of alien (microbes from other plant species) endophytes. In this review, we briefly discuss the transformation of the plant-pathogen-environment to the plant-pathogen-microbial system in a disease triangle. We also argue the employment of indigenous endophytes isolated from a healthy state to engineer the diseased citrus endophytic microbiomes that can provide sustainable solution for vascular pathogens. We evaluated the plethora of microbiomes responses to the re-introduction of endophytes which leads to disease resistance in the citrus host. The idea is not merely confined to citrus-HLB, but it is globally applicable for tailoring a customized cure for general plant-pathogen systems particularly for the diseases caused by the vascular system-restricted pathogens.

An examination of how to engage migrants in the research process: building trust through an 'insider' perspective.

Introduction: Ensuring all members of society can equally participate in research and the provision of services is a challenging goal. Increased migration has been mirrored by media narratives of social threat, leaving many migrants feeling differentiated and distrustful of mainstream society.Objectives: We explore how migrant and ethnic minority populations can be given the opportunity to participate in the research process. In this work, we iteratively and jointly developed a range of engagement strategies that adopt an 'insider' approach; seeking to eliminate feelings of differentiation and 'otherness' by establishing mutual trust.Design: Recruitment activities were carried out with 8 focus groups of first-generation South Asian migrants (the largest ethnic minority group in England). Our analysis was grounded in the broad principles of action research with reflective evaluation of our recruitment process using field observations and relevant focus group data; asking whether we tackled barriers to engagement.Results: Our findings show that 'otherness' can be reduced by establishing a trustworthy researcher-community relationship, but also that this relationship is complex, and needs to acknowledge residual mistrust. Alongside, researchers need to enable opportunities for empowered interaction, with flexible strategies to negotiate potential power divides.Conclusions: We can successfully create opportunities for engagement but there is no 'one size fits all'. Engagement requires tailored approaches that embrace flexibility, and position both engagement and non-engagement as positive and empowered choices.

Is Glyceryl Trinitrate, a Nitric Oxide Donor Responsible for Ameliorating the Chemical-Induced Tissue Injury In Vivo?

Oxidative stress induced by well-known toxins including ferric nitrilotriacetate (Fe-NTA), carbon tetrachloride (CCl4) and thioacetamide (TAA) has been attributed to causing tissue injury in the liver and kidney. In this study, the effect of glyceryl trinitrate (GTN), a donor of nitric oxide and NG-nitroarginine methyl ester (l-NAME), a nitric oxide inhibitor on TAA-induced hepatic oxidative stress, GSH and GSH-dependent enzymes, serum transaminases and tumor promotion markers such as ornithine decarboxylase (ODC) activity and [3H]-thymidine incorporation in rats were examined. The animals were divided into seven groups consisting of six healthy rats per group. The six rats were injected intraperitoneally with TAA to evaluate its toxic effect, improvement in its toxic effect if any, or worsening in its toxic effect if any, when given in combination with GTN or l-NAME. The single necrogenic dose of TAA administration caused a significant change in the levels of both hepatic and serum enzymes such as glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), γ-glutamyl transpeptidase (GGT), glucose 6-phosphate dehydrogenase (G6PD), alanine aminotransferase (AST) and aspartate aminotransferase (ALT). In addition, treatment with TAA also augmented malondialdehyde (MDA), ornithine decarboxylase (ODC) activity and [3H]-thymidine incorporation in rats liver. Concomitantly, TAA treatment depleted the levels of GSH. However, most of these changes were alleviated by the treatment of animals with GTN dose-dependently. The protective effect of GTN against TAA was also confirmed histopathologically. The present data confirmed our earlier findings with other oxidants including Fe-NTA and CCl4. The GTN showed no change whatsoever when administered alone, however when it was given along with TAA then it showed protection thereby contributing towards defending the role against oxidants-induced organ toxicity. Overall, GTN may contribute to protection against TAA-induced oxidative stress, toxicity, and proliferative response in the liver, according to our findings.

Explosions, Burn Injuries and Adverse Health Effects of Electronic Nicotine Delivery Systems: A Review of Current Regulations and Future Perspectives.

PURPOSE: While there is a declining trend in the use of traditional methods of smoking tobacco, electronic nicotine delivery systems (ENDS) have gained popularity worldwide. ENDS are marketed as safe for the primary reason that they do not contain the well-established toxic ingredients found in traditional cigarettes. However, growing concerns over incidences of fire and explosion with specific types of ENDS, as well as their short and long-term effects, remain unaddressed. This review examines the under studied role of customized components such as batteries, e-liquid compositions, and methods of nicotine delivery that result in physical injuries and adverse health effects of ENDS. METHODS: Using online reference databases (Web of Science, PubMed, Medline other, Google scholar, FDA website, FDA register), we analyzed the mechanisms through which ENDS may pose significant risk to human health. RESULTS: An increase in the use and popularity of ENDS has been observed among youth and adults in the United States since 2007. The ENDS devices available to the public allow for custom alterations which can introduce incompatible components, resulting in overheating and explosion related injuries. Heavy metals have been found to leach from some devices into the e-liquid, and the heating of e-liquid ingredients can produce toxic byproducts. CONCLUSIONS: Overall, the current literature demonstrates that ENDS are not a safe alternative to traditional cigarettes due to explosion risks and negative health effects including addiction, adverse respiratory and cardiovascular effects, heavy metal leaching, and toxic byproducts exposure. These risks warrant regulation of ENDS devices and formulations, with urgency underscored by their increasing popularity among youth and adults.

Cardiac output monitoring in paediatric cardiac surgery: a review.

The aim of this review is to present the current options for cardiac output (CO) monitoring in children undergoing cardiac surgery. Current technologies for monitoring identified were a range of invasive, minimally invasive, and non-invasive technologies. These include pulmonary artery catheter, transoesophageal echocardiography, pulse contour analysis, electrical cardiography, and thoracic bioreactance. A literature search was conducted using evidence databases which identified two current guidelines; the NHS Greater Glasgow and Clyde guideline and Royal College of Anaesthetics Guideline. These were appraised using the AGREE II tool and the evidence identified was used to create an overview summary of each technological option for CO monitoring. There is limited evidence regarding the accuracy of modalities available for CO monitoring in paediatric patients during cardiac surgery. Each technology has advantages and disadvantages; however, none could be championed as the most beneficial. Furthermore, a gold standard for CO monitoring has not yet been identified for paediatric populations, nor is it apparent whether one modality is preferable based on the available evidence. Additional evidence using a standardised method for comparing CO measurements should be conducted in order to determine the best option for CO monitoring in paediatrics. Furthermore, cost-effectiveness assessment of each modality should be conducted. Only then will it be possible for clear, evidence-based guidance to be written.

Cardiovascular Health and Stroke in Older British Men: Prospective Findings From the British Regional Heart Study.

BACKGROUND AND PURPOSE: Research exploring the utility of cardiovascular health (CVH) and its Life's Simple 7 (LS7) components (body mass index, blood pressure [BP], glucose, cholesterol, physical activity, smoking, and diet) for prevention of stroke in older adults is limited. In the British Regional Heart Study, we explored (1) prospective associations of LS7 metrics and composite CVH scores with, and their impact on, stroke in middle and older age; and (2) if change in CVH was associated with subsequent stroke. METHODS: Men without cardiovascular disease were followed from baseline recruitment (1978-1980), and again from re-examination 20 years later, for stroke over a median period of 20 years and 16 years, respectively. LS7 were measured at each time point except baseline diet. Cox models estimated hazard ratios (95% CI) of stroke for (1) ideal and intermediate versus poor levels of LS7; (2) composite CVH scores; and (3) 4 CVH trajectory groups (low-low, low-high, high-low, high-high) derived by dichotomising CVH scores from each time point across the median value. Population attributable fractions measured impact of LS7. RESULTS: At baseline (n=7274, mean age 50 years), healthier levels of BP, physical activity, and smoking were associated with reduced stroke risk. At 20-year follow-up (n=3798, mean age 69 years) only BP displayed an association. Hazard ratios for intermediate and ideal (versus poor) levels of BP 0.65 (0.52-0.81) and 0.40 (0.24-0.65) at baseline; and 0.84 (0.67-1.05) and 0.57 (0.36-0.90) at 20-year follow-up. With reference to low-low trajectory, the low-high trajectory was associated with 40% reduced risk, hazard ratio 0.60 (0.44-0.83). Associations of CVH scores weakened, and population attributable fractions of LS7 reduced, from middle to old age; population attributable fraction of nonideal BP from 53% to 39%. CONCLUSIONS: Except for BP, CVH is weakly associated with stroke at older ages. Prevention strategies for older adults should prioritize BP control but also enhance focus beyond traditional risk factors.

Interventions to improve the uptake of screening across a range of conditions in Ethnic Minority Groups: a systematic review.

BACKGROUND: Screening programmes are well established in cancer, and are now being implemented in other conditions. An effective screening programme leads to early disease detection and improved outcomes but its impact is dependent on the quality of the test and the proportion of the target population participating. A further consideration is that uptake of screening by minority groups is low. PURPOSE: To determine which interventions have successfully increased screening uptake amongst minorities. DATA SOURCES: Medline, Cochrane database and the grey literature were searched from 1990 to 1st March 2016. STUDY SELECTION: Fifty-five English language studies that assessed uptake of screening in any minority population in the country of study aged over 18 years and that included a comparison arm. DATA EXTRACTION: Independent data extraction was undertaken by two researchers (CK and MP), using a predesigned data extraction form (DEF) which assisted retrieval of the core contents of each study and the organisation of material. DATA SYNTHESIS: Evidence was organised by screening test and type of intervention. Two authors (CK and MP) extracted data into evidence tables to enable comparison of study characteristics and findings. The heterogeneity of methods precluded a meta-analysis thus results are descriptive. Evidence was also assessed, using the Cochrane Collaboration risk of bias tables. RESULTS: This systematic review appraises data from international studies on a variety of minority groups, interventions and screening programmes providing a narrative review of their success and limitations.

Gastric volvulus through Morgagni hernia and intestinal diverticulosis in an adult patient: a case report.

BACKGROUND: Morgagni's hernia (MH) is a rare type of congenital diaphragmatic hernia with limited available literature. Late presentations are infrequent and the ones complicated due to gastric volvulus are even rarer. Another uncommon association of MH is with small bowel diverticulosis. We herein discussed a case of gastric volvulus as the content of MH, and small bowel diverticulosis present in a patient concomitantly. CASE PRESENTATION: A 30 year old woman, who presented with a one year history of epigastric burning and indigestion, occasionally associated with pain and vomiting. On clinical examination, no clue to the diagnosis could be ascertained. Her chest and abdominal x-ray indicated an abnormal air-fluid level at right hemithorax, which prompted a Computed Tomography (CT) scan, showing organo-axial gastric volvulus. MH with gastric volvulus was observed during laparotomy and trans-thoracic reduction of the contents was performed, along with repair of the defect. Multiple intestinal diverticuli were also found and the largest diverticulum was excised. CONCLUSIONS: Gastric volvulus through MH is a rare but potentially life-threatening condition. Non-specific symptoms like epigastric pain and vomiting can delay the diagnosis and management, however, advanced imaging techniques like CT scan can speed up this process. After the diagnosis is made, surgical repair should be attempted regardless of symptoms.

The Telemedicine Landscape in Pakistan- Why are we falling behind?

Telemedicine is the provision of healthcare using information and communication technology-based methods. In the past decade, the sector has grown exponentially and become a billion-dollar industry in the developed world. While telemedicine holds the promise to transcend many of the barriers impeding healthcare delivery in emerging markets, unfortunately Pakistan has not been able to obtain any significant benefit from these advancements. The lack of a regulatory framework and lack of interest from the government makes it difficult for new companies to set up projects in Pakistan which will deliver healthcare in innovative, cost-effective ways. A survey conducted across different levels of the medical community showed that only a small minority of the medical community is familiar with the concept and applications of telemedicine. From a business perspective, the landscape is ripe in Pakistan. Since other developing countries have been able to use telemedicine effectively, Pakistan should also look into the options available and catch up soon.

Hyperenhancement of the Pericardium on Cardiac Magnetic Resonance Imaging: A Marker of Acute Inflammation and Neovascularization or a Chronic Fibrotic State.

In cardiac magnetic resonance imaging, hyperenhancement of the pericardium post gadolinium administration in acute chest pain often signifies pericarditis with an acute inflammatory response and neovascularization. In the context of constrictive pericarditis, case series have indicated that the intensity of hyperenhancement and the thickness of the pericardium imply reversibility of the physiology of the constrictive pericarditis. We present a case of intense hyperenhancement and marked thickening of the pericardium in a patient with constrictive pericarditis with antecedent chest pain. Surgical resection of the pericardium and microscopy revealed a chronic fibrotic state with no evidence of inflammation or neovascularization, thus clarifying the failure of initial medical/anti-inflammatory treatment. Our case highlights the fact that hyperenhancement of the pericardium post gadolinium is non-specific for histology and does not necessarily imply the reversibility of pericardial constriction.

Understanding of elder abuse and neglect among health care professionals in Malaysia: An exploratory survey.

Elder abuse and neglect (EAN) is a hidden public health challenge for Malaysia. This cross-sectional survey studied the awareness of EAN among 148 doctors and nurses from two neighboring states in Malaysia using a self-administered questionnaire exploring their knowledge, perceptions, practices, and experience concerning EAN. Both doctors and nurses demonstrated poor understanding of signs of EAN and exhibited misperceptions on reporting requirements. Both groups perceived EAN as a national burden and reporting it as their responsibility; but most felt they had not been trained to diagnose it. Many were unsure of procedures and whether their own intervention could be effective. Only four (nurses) of 41 participants who suspected abuse during the past year reported the cases. Targeted education and uniform protocols are mandatory to ensure best practice with regards to EAN. Further research is crucial to extend this inquiry into the broader health care workforce.

Effects of resveratrol on polycystic ovarian syndrome: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Polycystic ovarian syndrome (PCOS) is the heightened ovarian dysfunction associated with excessive androgen production, manifesting with hirsutism, abnormal menstrual cycle, and polycystic ovaries. In this systematic review and meta-analysis, the effect of resveratrol on laboratory parameters of PCOS women will be assessed. METHODS: An electronic search via PubMed, Cochrane Library, and Scopus was performed up to February 2023 for randomized controlled trials conforming to our pre-specified outcomes. A random-effects model was utilized, with cohorts compared using mean differences. RESULTS: Three randomized controlled trials (RCTs) were included, reporting 84 patients receiving resveratrol, and 85 patients receiving placebo. It was observed that resveratrol significantly improved prolactin levels (P = 0.02), acne scores (P = 0.008), and total cholesterol (P = 0.02). However, there were no significant improvements observed with respect to total testosterone, follicle stimulating hormone (FSH), lutenizing hormone (LH), body mass index (BMI), hirsutism scores, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). CONCLUSION: As per the results of our analysis, resveratrol demonstrates mild therapeutic potential for the sufferers of PCOS, and cannot replace the current established treatment guidelines. However, further comprehensive RCTs are required in order to assess the efficacy in long-term dosing and the safety profile of the use of resveratrol.