Exploring the Interplay of the CRISPR-CAS System with Antibiotic Resistance in Staphylococcus aureus: A Poultry Meat Study from Lahore, Pakistan.

Staphylococcus aureus is one of the major pathogens responsible for causing food poisoning worldwide. The emergence of antibiotic resistance in this bacterium is influenced by various factors. Among them, bacterial acquired defense systems described as clustered regularly interspaced short palindromic repeats (CRISPR)-cas system might be involved in antibiotic resistance development in bacteria. The current study was designed to assess the prevalence of S. aureus and its antibiotic resistance profile and identify the relationship of the CRISPR-cas system with antimicrobial resistance, followed by phylogenetic analysis. Total samples (n = 188) of poultry meat were collected from the poultry bird market of Lahore, Punjab, Pakistan. We used both phenotypic (antibiotic disc diffusion) and genotypic methods (PCR) to identify multi-drug resistant (MDR) strains of S. aureus. Additionally, the role of the CRISPR-Cas system in the isolated MDR S. aureus was also assessed. In addition, real-time quantitative PCR (qRT-PCR) was used to evaluate the association of the CRISPR-cas system with antimicrobial resistance. All of the S. aureus isolates showed 100% resistance against erythromycin, 97.5% were resistant to tetracycline, and 75% were resistant to methicillin. Eleven isolates were MDR in the current study. The CRISPR system was found in all MDR isolates, and fifteen spacers were identified within the CRISPR locus. Furthermore, MDR S. aureus isolates and the standard strain showed higher expression levels of CRISPR-associated genes. The correlation of said system with MDR isolates points to foreign gene acquisition by horizontal transfer. Current knowledge could be utilized to tackle antibiotic-resistant bacteria, mainly S. aureus.

Biomass fly ash as nanofiller to improve the dielectric properties of low-density polyethylene for possible high-voltage applications.

Flexible capacitive energy storage applications require polymer nanocomposites with high dielectric properties, which can be accomplished by addition of inorganic nanofillers to the polymer matrix. Low-density polyethylene (LDPE), known for its good dielectric characteristics and wide use in electrical insulation have been investigated for the desired applications. However, the improvement of its breakdown strength still continues with the use of various nanomaterials employed as nanofillers. In this study, a waste-derived material known as biomass fly ash (BFA) as a nanofiller to improve the dielectric properties of LDPE has been explored. BFA exhibits versatility in its composition with various metal oxides, making it an attractive choice as a nanofiller. The BFA-LDPE sheets were prepared using a conventional solvent mixing and subsequent hot-pressing process, incorporating BFA loadings ranging from 1 % to 4 wt%. The effects of different BFA loadings were carefully examined, and the synthesized nanocomposites were extensively characterized using various characterization methods, such as XRD, SEM, FTIR, TGA and dielectric constant measurements, to investigate the crystallographic properties, morphology, chemical composition, and thermal stability. Among all the nanocomposites, 4 wt%BFA-LDPE exhibited the highest dielectric constant, with a value of 11.58, compared to simple LDPE that had a dielectric constant of 8.33. This improvement is ascribed to the synergistic effects of different inorganic metal oxides (SiO2, MgO, and Fe2O3) present in BFA. The results showed a significant enhancement in dielectric properties, indicating that the waste-derived BFA can be purposefully applied as an effective nanofiller in the LDPE-based composites with even less than 4% loading for electrical insulating applications in future studies.

Novel echocardiographic markers for left ventricular filling pressure prediction in heart failure with preserved ejection fraction (ECHO-PREDICT): a prospective cross-sectional study.

Heart failure with preserved ejection fraction is a complex clinical syndrome associated with a high level of morbidity and mortality, constituting 56% of heart failure cases and showing an increasing prevalence. The E/Ea ratio, used for echocardiographic assessment of left ventricular (LV) filling pressure, has been commonly recommended as a noninvasive measure. However, its validity lacks robust prospective validation in patients with preserved LV ejection fraction, and its accuracy has been questioned in comparison to patients with reduced LV ejection fraction. The objective of this study was to evaluate the accuracy of novel echocardiographic markers incorporating peak E velocity, left atrial volume index (LAVi), and pulmonary artery systolic pressure (PAP) for noninvasive estimation of LV end-diastolic pressure (LVEDP) against invasive measurement. In this cross-sectional study conducted at a tertiary care hospital, a sample size of 122 participants was utilized. Statistical analyses including independent samples t-test, χ2 test, and linear regression analysis were employed to explore correlations and predict outcomes. The results indicated that Group 1 (LVEDP <20 mmHg) had a mean age of 59.25 years, while Group 2 (LVEDP >20 mmHg) had a mean age of 56.93 years. Mitral E velocity positively predicted LVEDP, while Mitral E/A ratio showed a negative association. Notably, (E+PAP)/2, (E+LAVi)/2, and Mitral E exhibited good discriminative ability, with respective area under the curve values of 0.840, 0.900, and 0.854. (E+LAVi)/2 demonstrated the highest discriminatory power, with a threshold of 40.100, yielding high sensitivity (0.971) but relatively low specificity (0.302) in predicting LVEDP greater than 20. These findings emphasize the accuracy and utility of combining diastolic variables and peak E velocity as markers for left ventricular filling pressure in patients with a high burden of cardiac disease. Additionally, the study highlights the importance of these parameters in assessing cardiac abnormalities and supports the potential of novel echocardiographic parameters, particularly (E+LAVi)/2, in predicting LVEDP greater than 20. Further research is warranted to validate and explore the prognostic implications of these parameters in larger patient populations, ultimately improving the diagnosis and management of cardiac disease and enhancing clinical outcomes.

Cervical Pott's Disease Presenting As Quadriplegia in a Young Patient: A Case Report.

Cervical Pott's disease, a form of spinal tuberculosis (TB), is a significant concern in low- and middle-income countries (LMICs). Early detection and treatment are critical to preventing complications like vertebral collapse. Clinical and radiological features of cervical Pott's disease can resemble other spinal conditions, posing diagnostic challenges. We present a case of a 28-year-old female who initially presented with quadriplegia, cervical instability, and high-grade fever. Through multidisciplinary collaboration and prompt intervention, the patient was diagnosed with cord compression syndrome secondary to a cervical abscess and probable cervical Pott's disease. Anti-tuberculosis treatment (ATT) and steroids were initiated, leading to significant improvement in symptoms and disease resolution. In summary, this case underscores the diagnostic challenge of cervical Pott's disease and the importance of imaging in TB diagnosis in resource-limited settings. The positive treatment response emphasizes early intervention's significance.

Prevalence and Risk Factors of Delirium in Patients Admitted to Intensive Care Units: A Multicentric Cross-Sectional Study.

Background Delirium is a common and serious complication among critically ill patients in the intensive care unit. Knowledge of the risk factors of delirium can help tremendously in the diagnosis of delirium. Methods In April of 2023, a cross-sectional multicenter study was conducted in eight intensive care units (ICUs) across Pakistan. Delirium was assessed using the intensive care delirium screening checklist. Demographic and clinical data were collected, and multivariable logistic regression analysis was performed to identify predictors of delirium. A total of 256 patients were enrolled in the study. Results The mean age of participants was 56 (S.D. 12) years. The point prevalence of delirium was 39%, and the point prevalence did not vary significantly among the participating intensive care units. Advanced age, higher Acute Physiology and Chronic Health Evaluation - IV (APACHE IV) scores, and higher Richmond Agitation-Sedation Scale (RASS) scores at enrollment were identified as significant predictors of delirium. Conclusion The high prevalence of delirium, observed at 39.0%, emphasizes the importance of proactive screening and effective management strategies in the ICU setting. Healthcare providers in Pakistan should be mindful of these risk factors and implement preventive measures to minimize the occurrence of delirium in critically ill patients. Further research and implementation of targeted interventions are warranted to improve patient outcomes and enhance the overall quality of care in this population.

Lansoprazole plus levosulpiride versus esomeprazole in participants with gastroesophageal reflux disease and erosive esophagitis: a double blinded randomized control trial.

Aim: The aim was to compare the efficacy and safety of lansoprazole plus levosulpiride over esomeprazole. Methodology: This randomized control trial recruited 1000 participants having symptomatic gastroesophageal reflux disease (GERD) and erosive esophagitis and they were blindly randomized into two groups in a 1:1 ratio with appropriate concealment. Group 1 was given lansoprazole plus levosulpiride combination twice daily whereas group 2 was prescribed only esomeprazole twice daily. The primary efficacy endpoint was the healing of erosive esophagitis and GERD at week 49. Secondary assessments included improvement in quality of life. Participants' quality of life was assessed before starting the treatment and post-treatment using a short-form health survey questionnaire (SF-36). Results: The lansoprazole plus levosulpiride group had significantly lower rates of positive postintervention GERD and erosive esophagitis status, and higher rates of sustained resolution of heartburn compared to the esomeprazole alone group. However, the lansoprazole plus levosulpiride group also had a higher risk of nausea. Conclusion: Lansoprazole plus levosulpiride is a more effective and safe treatment for GERD than esomeprazole alone. Participants in the lansoprazole plus levosulpiride group showed a significantly higher rate of sustained resolution of GERD, lower rates of postintervention GERD and erosive esophagitis status, and a higher incidence of nausea compared to the esomeprazole alone group. Although quality of life worsened in both groups, adverse effects did not significantly differ. These findings strongly support the use of lansoprazole plus levosulpiride as a preferred treatment option for GERD and erosive esophagitis, which could have significant clinical implications for managing this common condition.

Conservative Management of Splenic Injury in Blunt Abdominal Trauma: A Single Center Experience.

BACKGROUND: Road traffic accidents are the greatest cause of death worldwide. Most intra-abdominal injuries caused by blunt abdominal trauma have been treated surgically for a very long period. Over the past few decades, conservative care has gained in popularity and effectiveness as a treatment choice for blunt abdominal trauma. OBJECTIVE: To determine the efficacy of conservative management in patients suffering from splenic injury in blunt abdominal trauma. METHODS: The study included 62 cases of blunt abdominal trauma treated non-operatively in the general surgery department of the Hayatabad Medical Complex Peshawar between June 2021 and December 2022. RESULTS: Minimal hemoperitoneum was observed in 47 (75.8%) cases, moderate hemoperitoneum was noted in 11 (17.7%) cases, and 4 (6.4%) patients didn't have free fluid in the abdomen. There was no massive hemoperitoneum among the study patients. No major complications were observed during the study period. Only 7 (11.3%) cases develop minimal pleural effusion while 2 (3.2%) patients developed splenic abscess. Mortality was observed in only 1 (1.6%) case. CONCLUSIONS: Conservative management is a safe and efficient strategy and should be considered as a first line of treatment for all hemodynamically stable patients who suffered blunt splenic injury.

Assessing Thrombocytopenia and Chronic Liver Disease in Southeast Asia: A Multicentric Cross-Sectional Study.

Background This multicentric cross-sectional study aimed to examine the prevalence of thrombocytopenia (TCP) and investigate the various causes of chronic liver disease (CLD) across 15 Southeast Asian (India, Pakistan, and Bangladesh) tertiary care centers over a three-month period. The study focused on assessing the fibrosis index (FI) and Model for End-Stage Liver Disease (MELD)-sodium (Na) score's capacity to grade and predict the progression and outcomes of patients with already diagnosed CLD. Methods The cross-sectional study enrolled 377 CLD patients. The study utilized admission registries from 15 tertiary care hospitals in Southeast Asia, spanning from April 2023 to June 2023. Various descriptive variables were collected, including gender, tobacco use (specifically, chewed tobacco), underlying etiology, presence of anemia, leukopenia, pancytopenia, infectious state, and liver cirrhosis diagnosed via traditional ultrasonography. This study examined liver failure indicators, including alanine transaminase levels, compensation status, TCP, and liver transplant (LT) listing. The MELD-Na score was the focus of frequency and percentage analysis. MELD-Na and FI medians and standard deviations were provided. Results The study of 377 patients with CLD found that TCP was present in 4% of patients and leukopenia was present in 12% of patients. The risk of TCP was significantly higher in leukopenic patients (89.5%) than in non-leukopenic patients (52.5%) (p = 0.003). The most common CLD cause was undiagnosable (31%), followed by autoimmune (26%), hepatitis C virus (21%), hepatitis B virus (14%), and schistosomiasis (8%). The majority of patients (98%) had decompensated liver disease. Of the patients, 64% had TCP, while 36% did not. The illness severity indicators MELD score and FI had mean ± SD values of 16.89 ± 6.42 and 4.1 ± 1.06, respectively. Similarly, the prevalence of LT needs among traditional ultrasonography-diagnosed cirrhotic patients was 83.1%, compared to 59.6% among non-cirrhotic patients (p = 0.001). Conclusion Leukopenia and TCP may be linked, which may affect CLD treatment and prognosis in this population. Non-invasive indicators like the FI and MELD-Na score can detect liver fibrosis and severity without invasive procedures, enhancing patient management. These findings highlight the need to improve early diagnosis methods for CLD in Southeast Asia and raise awareness among clinicians about effective diagnostic strategies for non-infectious causes of CLD.

Imaging phenotypes predict overall survival in glioma more accurate than basic demographic and cell mutation profiles.

BACKGROUND: Magnetic resonance imaging (MRI), digital pathology imaging (PATH), demographics, and IDH mutation status predict overall survival (OS) in glioma. Identifying and characterizing predictive features in the different modalities may improve OS prediction accuracy. PURPOSE: To evaluate the OS prediction accuracy of combinations of prognostic markers in glioma patients. MATERIALS AND METHODS: Multi-contrast MRI, comprising T1-weighted, T1-weighted post-contrast, T2-weighted, T2 fluid-attenuated-inversion-recovery, and pathology images from glioma patients (n = 160) were retrospectively collected (1983-2008) from TCGA alongside age and sex. Phenotypic profiling of tumors was performed by quantifying the radiographic and histopathologic descriptors extracted from the delineated region-of-interest in MRI and PATH images. A Cox proportional hazard model was trained with the MRI and PATH features, IDH mutation status, and basic demographic variables (age and sex) to predict OS. The performance was evaluated in a split-train-test configuration using the concordance-index, computed between the predicted risk score and observed OS. RESULTS: The average age of patients was 51.2years (women: n = 77, age-range=18-84years; men: n = 83, age-range=21-80years). The median OS of the participants was 494.5 (range,3-4752), 481 (range,7-4752), and 524.5 days (range,3-2869), respectively, in complete dataset, training, and test datasets. The addition of MRI or PATH features improved prediction of OS when compared to models based on age, sex, and mutation status alone or their combination (p < 0.001). The full multi-omics model integrated MRI, PATH, clinical, and genetic profiles and predicted the OS best (c-index= 0.87). CONCLUSION: The combination of imaging, genetic, and clinical profiles leads to a more accurate prognosis than the clinical and/or mutation status.

Automated Video-Based Capture of Crustacean Fisheries Data Using Low-Power Hardware.

This work investigates the application of Computer Vision to the problem of the automated counting and measuring of crabs and lobsters onboard fishing boats. The aim is to provide catch count and measurement data for these key commercial crustacean species. This can provide vital input data for stock assessment models, to enable the sustainable management of these species. The hardware system is required to be low-cost, have low-power usage, be waterproof, available (given current chip shortages), and able to avoid over-heating. The selected hardware is based on a Raspberry Pi 3A+ contained in a custom waterproof housing. This hardware places challenging limitations on the options for processing the incoming video, with many popular deep learning frameworks (even light-weight versions) unable to load or run given the limited computational resources. The problem can be broken into several steps: (1) Identifying the portions of the video that contain each individual animal; (2) Selecting a set of representative frames for each animal, e.g, lobsters must be viewed from the top and underside; (3) Detecting the animal within the frame so that the image can be cropped to the region of interest; (4) Detecting keypoints on each animal; and (5) Inferring measurements from the keypoint data. In this work, we develop a pipeline that addresses these steps, including a key novel solution to frame selection in video streams that uses classification, temporal segmentation, smoothing techniques and frame quality estimation. The developed pipeline is able to operate on the target low-power hardware and the experiments show that, given sufficient training data, reasonable performance is achieved.

Achieving Critical View of Safety via a New Technique: The Triple One (111) Technique.

BACKGROUND: Misidentification of anatomical structures is one of the most common causes of bile duct injury following laparoscopic cholecystectomy. Achieving Critical View of Safety (CVS) is a standard step in conducting safe cholecystectomy all over the world. In our institute, we achieve CVS via a unique technique called Triple One or 111 and find it very helpful and easy to achieve CVS. Moreover, the rate of conversion has also decreased while achieving CVS via this technique. The unique aspect of the Triple One technique is that by following this method, even new laparoscopic surgeons can achieve CVS very easily in difficult cases and, hence, it decreases the chances of vasculobiliary injury (VBI). OBJECTIVE: This study aimed to determine how effective the Triple One technique is in achieving CVS as well as in lessening the chances of VBI. MATERIAL AND METHODS: A total of 545 patients were admitted through the outpatient department, ranging in age from 30 to 70 years, with a mean of 50 years. The study comprised patients with American Society of Anaesthesiologists (ASA) I & II, acute and chronic cholecystitis, and symptomatic cholelithiasis. The study excluded patients with co-morbidities, prior abdominal procedures, and suspected complications. On the second postoperative day, all patients received their discharge papers and on the seventh postoperative day, follow-up was completed. RESULTS: Successful gallbladder extraction using the Triple One technique was achieved in 540 (99%) cases. The other five (1%) cases converted to open cholecystectomy because of the difficult gallbladder anatomy and extensive scarring. No VBI or bile duct injury was noted. No mortality was recorded during the study period. CONCLUSION: By incorporating CVS using the Triple One technique into our policies and curriculum, we may encourage safe cholecystectomy practices and prevent bile duct injuries.

Current status and future of cardio-obstetrics-review.

Cardio-obstetrics refers to an approach to maternal care that is based upon teamwork with specialists from maternal-foetal medicine, cardiology, anaesthesiology, neonatology, nursing, social work, and pharmacy that work together to achieve appropriate outcomes for the pregnant patient. The aim of this paper is to highlight and provide a narrative review on the currently published research on the current status and future of cardio-obstetrics. A short review on the hemodynamic physiology in pregnancy has also been described in this paper. The authors have discussed the major risk factors associated with exacerbation of pregnancy and the possible remedies that are currently available in this paper in accordance to the updated research. The cardio-obstetrics team provides advice about healthy pregnancy planning before conception. Proper cardio-obstetric care is associated with better outcomes in women with a high cardiovascular risk with decreased adverse maternal and foetal outcomes. Such care should be given to underserved and marginalized communities with great care as they have largely lacked such care in the past. The authors conclude the paper by recommendations to advance this newly emerging field by way of further scientific research and public awareness. This review can serve helpful to any physician working in the healthcare as well as the public that are interested in awareness about the multidisciplinary needs of pregnant women with cardiovascular disease.

Artificial intelligence in critical illness and its impact on patient care: a comprehensive review.

Artificial intelligence (AI) has great potential to improve the field of critical care and enhance patient outcomes. This paper provides an overview of current and future applications of AI in critical illness and its impact on patient care, including its use in perceiving disease, predicting changes in pathological processes, and assisting in clinical decision-making. To achieve this, it is important to ensure that the reasoning behind AI-generated recommendations is comprehensible and transparent and that AI systems are designed to be reliable and robust in the care of critically ill patients. These challenges must be addressed through research and the development of quality control measures to ensure that AI is used in a safe and effective manner. In conclusion, this paper highlights the numerous opportunities and potential applications of AI in critical care and provides guidance for future research and development in this field. By enabling the perception of disease, predicting changes in pathological processes, and assisting in the resolution of clinical decisions, AI has the potential to revolutionize patient care for critically ill patients and improve the efficiency of health systems.

Early Outcomes of Laparoscopic Transabdominal Preperitoneal (TAPP) Repair.

Background Inguinal hernia repair is one of the commonest general surgical procedures performed all over the world. The introduction of synthetic mesh and laparoscopic repair has revolutionized inguinal hernia surgery in the recent past. Laparoscopic transabdominal preperitoneal (TAPP) repair is now considered a well-established procedure with minimal complications and short hospital stay and less recurrence. The TAPP approach gives a good view of the inguinal anatomy and a better understanding of the sac contents. The learning curve associated with TAPP repair is much less as compared to total extraperitoneal (TEP) repair. The aim of this study was to assess the effectiveness of TAPP repair for inguinal hernia in terms of the duration of surgery, hospital stay, complications, and recurrence rate. Method From March 1, 2019, to February 28, 2021, a total of 60 patients with inguinal hernias between ages 25 and 70 years were included in the study. A preoperative anesthesia assessment was done, and informed written consent was taken from all patients. The TAPP procedure was performed with polypropylene mesh in all cases, and surgery was performed by a surgeon with more than five years of laparoscopic experience. Results The total number of patients included in the study was 60. All patients were male. The mean±standard deviation (SD) age of the patients was 54.6±11.4 years. Unilateral primary inguinal hernia was present in 46 (76.6%) cases, recurrent in eight (13.3%) cases, and primary bilateral in six (10%) cases. The mean±SD duration of surgery for unilateral inguinal hernia was 59.1±15.7 minutes, and for bilateral hernia, it was 83.5±12.6 minutes. The mean hospital stay was 3.6±1.5 days. Scrotal swelling was noted as a common complication in seven (11.6%) cases, surgical site infection (SSI) in three (5%), mesh infection in two (3.3%), urinary retention in two (3.3%), and chronic pain in one (1.6%). No recurrence was noted. Conclusion Transabdominal preperitoneal repair for inguinal hernia is a very effective procedure with a short learning curve and minimal complication rate. The hospital stay is less, and recurrence is very low.

Feature Transformation for Efficient Blood Glucose Prediction in Type 1 Diabetes Mellitus Patients.

Diabetes Mellitus, a metabolic disease, causes the body to lose control over blood glucose regulation. With recent advances in self-monitoring systems, a patient can access their personalized glycemic profile and may utilize it for efficient prediction of future blood glucose levels. An efficient diabetes management system demands the accurate estimation of blood glucose levels, which, apart from using an appropriate prediction algorithm, depends on discriminative data representation. In this research work, a transformation of event-based data into discriminative continuous features is proposed. Moreover, a multi-layered long short-term memory (LSTM)-based recurrent neural network is developed for the prediction of blood glucose levels in patients with type 1 diabetes. The proposed method is used to forecast the blood glucose level on a prediction horizon of 30 and 60 min. The results are evaluated for three patients using the Ohio T1DM dataset. The proposed scheme achieves the lowest RMSE score of 14.76 mg/dL and 25.48 mg/dL for prediction horizons of 30 min and 60 min, respectively. The suggested methodology can be utilized in closed-loop systems for precise insulin delivery to type 1 patients for better glycemic control.

Levofloxacin Cocrystal/Salt with Phthalimide and Caffeic Acid as Promising Solid-State Approach to Improve Antimicrobial Efficiency.

To overcome the issue of multidrug resistant (MDR) microbes, the exploration of ways to improve the antimicrobial efficiency of existing antibiotics is one of the promising approaches. In search of synthons with higher efficiency, in current investigations, cocrystal and amorphous salt of levofloxacin hemihydrate (LEV) were developed with phthalimide (PTH) and caffeic acid (CFA). New materials were characterized with the help of FT-IR, Raman spectroscopy, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Shifting, attenuation, appearance/disappearance and broadening of bands were observed in the FT-IR and Raman spectra of the materials as evidence of the required product. The PXRD diffraction pattern observed for LEV-PTH indicated cocrystal while halo diffractogram of LEV-CFA revealed amorphous nature. DSC/TG analysis confirmed the hydrated nature of the cocrystal/salt. The dissolution rate and antimicrobial activity against selected strains, K.pneumonia, E. coli and S. typhi of parent drug and the new material were compared. The zone of inhibition (ZI) observed for 5 µg LEV-PTH was 30.4 + 0.36 (K. pneumonia), 26.33 + 0.35 (E. coli) and 30.03 + 0.25 mm (S. typhi) while LEV-CFA salt (5 µg) against the same strains inhibited 33.96 ± 0.25, 31.66 ± 0.35 and 27.93 ± 0.40 mm, respectively. These novel formulations enhance the dissolution rate as well as antibacterial efficiency and are expected to be potent against MDR bacterial strains.

Combining Biocontrol Agent With Plant Nutrients for Integrated Control of Tomato Early Blight Through the Modulation of Physio-Chemical Attributes and Key Antioxidants.

Early blight (EB) is one of the major fungal diseases caused by Alternaria solani that is responsible for destructive tomato production around the globe. Biocontrol agent/s can be adequately implemented in an integrated management framework by using it in combination with vital plant nutrients, e.g., nitrogen, phosphorus, and potassium (NPK) and zinc (Zn). The current study was aimed to assess the integrated effect of a biocontrol agent Bacillus subtilis (BS-01) and the selective plant nutrients (NPK and Zn) on EB disease management and tomato crop performance. A field experiment was conducted for the off-season tomato production (under walk-in tunnels) in Punjab, Pakistan. The trial was set in a randomized complete block design (RCBD) and comprised nine treatments of a biocontrol agent (BS-01) either alone or in combination with the plant nutrients, viz., NPK (64:46:50 kg acre-1) and Zn (10 kg acre-1) as sustainable disease managing approach against EB. In addition, the biocontrol efficacy of B. subtilis (BS-01) on a fungal load of A. solani was estimated by quantitative PCR assays, where the foliar application of BS-01 on tomato plants either alone or in combination with the plant nutrients was done as a preventive measure. Our results revealed that the interactive effect of BS-01 with plant nutrients conferred significantly a varying degree of resilience in the infected tomato plants against EB by effectively modifying the content of total chlorophyll, carotenoids, and total phenolics along with the activities of antioxidant enzymes (SOD, CAT, POX, PPO, and PAL). In addition, the integrative effect of BS-01 and plant nutrients proved significantly effective in reducing pathogen load on inoculated tomato foliage, displaying the desired level of protection against A. solani infection. Besides, the complementary interaction of BS-01 + Zn + NPK worked synergistically to improve crop productivity by providing the highest marketable yield (21.61 tons acre-1) and net profit (361,363 Pakistani rupees acre-1). This integrated approach is put forward as a way to reduce the fungicide doses to control EB that would act as a sustainable plant protection strategy to generate profitable tomato production.

Effect of MHC Linked 7-Gene Signature on Delayed Hepatocellular Carcinoma Recurrence.

Dysregulated immune response significantly affects hepatocellular carcinoma's (HCC) prognosis. Human Leukocyte Antigens are key in devising immune responses against HCC. Here, we investigated how HLAs modulate HCC development at the transcriptomic level. RNA-seq data of 576 patients from two independent cohorts was retrieved. The clinicopathological relevance of all HLA genes was investigated using Fisher-Exact, correlation, and Kaplan-Meier and cox regression survival tests. Clustering of ~800 immune-related genes against HLAs was completed using a ward-agglomerative method. Networks were generated using 40 HLA associated unique genes and hub genes were investigated. HLAs including HLA-DMA, HLA-DMB, HLA-DOA and HLA-DRB6 were associated with delayed recurrence in both discovery (204 HCC cases) and validation (372 HCC cases) cohorts. Clustering analyses revealed 40 genes associated with these four HLAs in both cohorts. A set of seven genes (NCF4, TYROBP, LCP2, ZAP70, PTPRC, FYN and WAS) was found co-expressed at gene-gene interaction level in both cohorts. Furthermore, survival analysis revealed seven HLA-linked genes as predictors of delayed recurrence. Multivariate analysis also predicted that mean expression of 7-gene is an independent predictor of delayed recurrence in both cohorts. We conclude that the expression of 7-gene signature may lead to improved patient prognosis. Further studies are required for consideration in clinical practice.

Ventricular Septal Defect in Delayed Presentation of ST-Elevation Myocardial Infarction (STEMI) Secondary to COVID-19 Pandemic.

Like many other countries at the moment, the United Kingdom (UK) is currently under national lockdown due to the coronavirus disease 2019 (COVID-19) pandemic. An unfortunate consequence of such social isolation measures is that patients with genuine acute medical emergencies may not present to a hospital in a timely manner. We present such a scenario, whereby a patient had a delayed presentation of ST-elevation myocardial infarction (STEMI) due to fear of breaching COVID-19 lockdown rules. As a result of the patient presenting well outside the optimal treatment window, her STEMI was complicated by a severe ventricular septal defect (VSD). We discuss how the COVID-19 pandemic has influenced the nature and management of STEMIs and associated issues.