Erector Spinae Plane Block Decreases Narcotic Requirements in Patients Undergoing Subcutaneous Implantable Cardioverter-defibrillator Placement Under Sedation.

Providing adequate analgesia perioperatively during subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation can be a challenge. The objective of our study was to assess the efficacy and safety of the erector spinae plane (ESP) block technique in providing analgesia and minimizing the risk of opioid use in high-risk patient populations. We enrolled consecutive patients >18 years of age undergoing S-ICD implantation from February 2020 to February 2022 at our center prospectively. Patients were randomly assigned to receive the ESP block or traditional wound infiltration. A total of 24 patients were enrolled, including 13 patients randomized to ESP block and 11 patients as controls who received only wound infiltration. The primary outcome assessed was the overall use of perioperative analgesic medications in the ESP block group versus the surgical wound infiltration group. A significant reduction in intraoperative fentanyl use was observed [median ([interquartile range]) in the ESP block group (0 [0-50] µg) compared to the wound infiltration block group (75 [50-100] µg) (P = .001). The overall postoperative day (POD) 0 fentanyl use was also significantly decreased (75 [50-100] µg) in the ESP block group compared to the surgical wound infiltration group (100 [87.5-150] µg) (P = .049). There was also a trend of decreased POD 0 oxycodone-acetaminophen use. Finally, the number of days to discharge was less in the ESP block group. These results indicate that ESP block is an innovative, safe, and effective technique that decreases intraoperative and postoperative opioid consumption and may be a useful adjunct pain-management technique in these high-risk patients. Larger studies are needed to further validate its use.

Urban Churches Show an Increase in Attendance, Donations, and Finances During the COVID-19 Pandemic in the USA: Evidence from the United Methodist Church.

The COVID-19 pandemic has had a significant impact on religion and its practice. This paper aims to examine how the pandemic affects religious activities, donations, and finances over time and across regions within the United Methodist Church (UMC) in the USA. To address this question, we analyze survey data collected during the pandemic from 2963 churches in the USA by United Methodist Communications. Our analysis utilizes several quantitative techniques, including Z-tests, one-way analysis of variance (ANOVA), and multinomial logistic regressions. The results indicate a decrease in church attendance over time, with a more pronounced effect observed in non-urban areas (suburban, small town, and rural). Similarly, while church donations and finances mitigate over time across churches, churches in urban areas experience a quicker rebound compared to those in non-urban areas. Lastly, we find that church attendance and donations positively affect finances. These findings hold important implications for churches in various regions, offering insights to develop strategies for navigating the challenges posed by the COVID-19 pandemic.

A spatial analysis of TB cases and abnormal X-rays detected through active case-finding in Karachi, Pakistan.

Tuberculosis (TB) is the leading cause of avoidable deaths from an infectious disease globally and a large of number of people who develop TB each year remain undiagnosed. Active case-finding has been recommended by the World Health Organization to bridge the case-detection gap for TB in high burden countries. However, concerns remain regarding their yield and cost-effectiveness. Data from mobile chest X-ray (CXR) supported active case-finding community camps conducted in Karachi, Pakistan from July 2018 to March 2020 was retrospectively analyzed. Frequency analysis was carried out at the camp-level and outcomes of interest for the spatial analyses were mycobacterium TB positivity (MTB+) and X-ray abnormality rates. The Global Moran's I statistic was used to test for spatial autocorrelation for MTB+ and abnormal X-rays within Union Councils (UCs) in Karachi. A total of 1161 (78.1%) camps yielded no MTB+ cases, 246 (16.5%) camps yielded 1 MTB+, 52 (3.5%) camps yielded 2 MTB+ and 27 (1.8%) yielded 3 or more MTB+. A total of 79 (5.3%) camps accounted for 193 (44.0%) of MTB+ cases detected. Statistically significant clustering for MTB positivity (Global Moran's I: 0.09) and abnormal chest X-rays (Global Moran's I: 0.36) rates was identified within UCs in Karachi. Clustering of UCs with high MTB positivity were identified in Karachi West district. Statistically significant spatial variation was identified in yield of bacteriologically positive TB cases and in abnormal CXR through active case-finding in Karachi. Cost-effectiveness of active case-finding programs can be improved by identifying and focusing interventions in hotspots and avoiding locations with no known TB cases reported through routine surveillance.

A Review of Integrative Omic Approaches for Understanding Rice Salt Response Mechanisms.

Soil salinity is one of the most serious environmental challenges, posing a growing threat to agriculture across the world. Soil salinity has a significant impact on rice growth, development, and production. Hence, improving rice varieties' resistance to salt stress is a viable solution for meeting global food demand. Adaptation to salt stress is a multifaceted process that involves interacting physiological traits, biochemical or metabolic pathways, and molecular mechanisms. The integration of multi-omics approaches contributes to a better understanding of molecular mechanisms as well as the improvement of salt-resistant and tolerant rice varieties. Firstly, we present a thorough review of current knowledge about salt stress effects on rice and mechanisms behind rice salt tolerance and salt stress signalling. This review focuses on the use of multi-omics approaches to improve next-generation rice breeding for salinity resistance and tolerance, including genomics, transcriptomics, proteomics, metabolomics and phenomics. Integrating multi-omics data effectively is critical to gaining a more comprehensive and in-depth understanding of the molecular pathways, enzyme activity and interacting networks of genes controlling salinity tolerance in rice. The key data mining strategies within the artificial intelligence to analyse big and complex data sets that will allow more accurate prediction of outcomes and modernise traditional breeding programmes and also expedite precision rice breeding such as genetic engineering and genome editing.

An ensemble prediction model for COVID-19 mortality risk

BackgroundIts critical to identify COVID-19 patients with a higher death risk at early stage to give them better hospitalization or intensive care. However, thus far, none of the machine learning models has been shown to be successful in an independent cohort. We aim to develop a machine learning model which could accurately predict death risk of COVID-19 patients at an early stage in other independent cohorts. MethodsWe used a cohort containing 4711 patients whose clinical features associated with patient physiological conditions or lab test data associated with inflammation, hepatorenal function, cardiovascular function and so on to identify key features. To do so, we first developed a novel data preprocessing approach to clean up clinical features and then developed an ensemble machine learning method to identify key features. ResultsFinally, we identified 14 key clinical features whose combination reached a good predictive performance of AUC 0.907. Most importantly, we successfully validated these key features in a large independent cohort containing 15,790 patients. ConclusionsOur study shows that 14 key features are robust and useful in predicting the risk of death in patients confirmed SARS-CoV-2 infection at an early stage, and potentially useful in clinical settings to help in making clinical decisions.

Epimutations and Their Effect on Chromatin Organization: Exciting Avenues for Cancer Treatment.

The three-dimensional architecture of genomes is complex. It is organized as fibers, loops, and domains that form high-order structures. By using different chromosome conformation techniques, the complex relationship between transcription and genome organization in the three-dimensional organization of genomes has been deciphered. Epigenetic changes, such as DNA methylation and histone modification, are the hallmark of cancers. Tumor initiation, progression, and metastasis are linked to these epigenetic modifications. Epigenetic inhibitors can reverse these altered modifications. A number of epigenetic inhibitors have been approved by FDA that target DNA methylation and histone modification. This review discusses the techniques involved in studying the three-dimensional organization of genomes, DNA methylation and histone modification, epigenetic deregulation in cancer, and epigenetic therapies targeting the tumor.

Barriers to Access of Healthcare Services for Rural Women-Applying Gender Lens on TB in a Rural District of Sindh, Pakistan.

BACKGROUND: Women in the rural districts of Pakistan face numerous barriers to healthcare, rendering gender-responsive health programming important, including for the disease of tuberculosis (TB). This study was conducted to assess the general understanding of TB and for women's access to healthcare, as a first step towards implementation of a gender responsive TB program in Tando Allahyar, a rural district of Pakistan. METHODS: A total of 36 participants were interviewed for the study. The focus group discussion guide comprised of questions on: (1) family/household dynamics, (2) community norms, (3) healthcare systems, (4) women's access to healthcare, (5) TB Awareness, and (6) women's access to TB Care. RESULTS: Limited autonomy in household financial decision-making, disapproval of unassisted travel, long travel time, lack of prioritization of spending on women's health and inadequate presence of female health providers, were identified as barriers to access healthcare for women, which is even higher in younger women. Facilitators to access of TB care included a reported lack of TB-related stigma, moderate knowledge about TB disease, and broad understanding of tuberculosis as a curable disease. Other suggested facilitators include health facilities closer to the villages and the availability of higher quality services. CONCLUSION: Significant barriers are faced by women in accessing TB care in rural districts of Pakistan. Program implementers in high burden countries should shift towards improved gender-responsive TB programming.

Pain Relief in Late Preterm Neonates: A Comparative Study of Kangaroo Mother Care, Oral Dextrose 50%, and Supine Nesting Position.

OBJECTIVE: The objectrve is to compare the analgesic effect of Kangaroo Mother Care (KMC), oral dextrose 50% (D50) and supine nesting position in late preterm neonates (34 week to <37 week Gestation Age) while doing heel prick for blood glucose monitoring. MATERIALS AND METHODS: Babies were randomized into three groups; KMC, D50 and supine nesting. Premature infant pain profile (PIPP) score was used to measure pain severity following heel prick. Total crying time was also compared. RESULTS: Data of 149 eligible babies were analyzed; significant difference was noted in total PIPP scores (mean; SD) across groups; KMC (8.42 [1.99]), D50 (8.76 [1.84]) and nesting (13.08 [1.70]) (P < 0.001). Post hoc analysis revealed comparable scores among KMC and D50 groups (P = 0.638), significantly less than nesting group (P < 0.001). Significant difference in crying time (median; interquartile range) was also noted amongst three groups (P < 0.001). CONCLUSION: The analgesic effect of KMC and oral D50 is comparable and found to be superior to supine nesting position in reducing pain of heel prick.

Use of Serratus Anterior Plane and Transversus Thoracis Plane Blocks for Subcutaneous Implantable Cardioverter-Defibrillator (S-ICD) Implantation Decreases Intraoperative Opioid Requirements.

OBJECTIVES: The present study investigated whether regional anesthetic techniques, especially truncal blocks, can provide adjunct anesthesia without the additional risk of general anesthesia and neuraxial techniques for subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation. DESIGN: Single-center, prospective, randomized study. SETTING: Holding area and operating room at a single-center tertiary care hospital. PARTICIPANTS: The study comprised 22 American Society of Anesthesiologists (ASA) physical status 3 or 4 patients with severe cardiac disease undergoing S-ICD implantation. INTERVENTIONS: Patients received either a combination of serratus anterior plane block and transversus thoracis plane block or surgical infiltration of local anesthetics. MEASUREMENTS AND MAIN RESULTS: Perioperative analgesic medication in the fascial plane block group versus the surgical wound infiltration group, visual analog pain scale score (0-10), intraoperative vital signs, total procedure time, and length of stay in the intensive care unit were measured. Total intraoperative fentanyl requirements (µg) were significantly less in the truncal block group versus the surgical infiltration group (45 [25-50] v 90 [50-100]; p = 0.026), and no patients had any adverse sequelae related to the study. Median intraoperative propofol use in the surgical infiltration group was 66.48 (47.30-73.73) µg/kg/min, and 65.95 (51.86-104.86) µg/kg/min for the truncal block group. This difference between the groups was not statistically significant (p = 0.293). CONCLUSIONS: The performance of both the serratus anterior plane block and transversus thoracis plane blocks for S-ICD implantation are appropriate and may have the benefit of decreasing intraoperative opioid requirements.

Assessment of C-reactive Protein Level and Efficacy of Diclofenac Sodium and Mefenamic Acid in Relieving Pain in Mandibular Impacted Third Molar Surgery.

AIM: To compare the efficacy of diclofenac sodium and mefenamic acid in relieving pain in mandibular impacted third molar surgery and to assess the level of the C-reactive protein (CRP) level. MATERIALS AND METHODS: This study was conducted on 90 patients of impacted mandibular third molars. All patients were administered with 2% lignocaine with 1:80,000 adrenaline, and surgical removal of impacted third molar was done following the standardized surgical procedure by a single oral surgeon. Patients were divided into two groups of 45 each. In group I, patients were prescribed 50 mg diclofenac sodium and in group II patients were prescribed 500 mg mefenamic acid for three times a day for 3 days. The CRP level was again evaluated after 3 days of analgesics. Pain was assessed using the visual analog scale (VAS). RESULTS: The mean VAS was 2.58 in group I and 3.46 in group II, which was statistically considerable (p < 0.05). The mean CRP level postoperatively in group I was 15.7 and after 3 days was 27.2 in group I, whereas it was 25.1 postoperatively and 31.5 after 3 days in group II. CONCLUSION: Authors found that diclofenac sodium as useful as mefenamic acid. The CRP level was raised significantly following surgery, thus reflecting that it is an indicator of inflammation. CLINICAL SIGNIFICANCE: Diclofenac sodium can be used to relieve pain. The CRP level evaluation can be helpful to assess inflammation following surgery.

Use of Stem Cell Extracellular Vesicles as a "Holistic" Approach to CNS Repair.

Neurodegeneration is a hallmark of many diseases and disorders of the central nervous system (CNS). High levels of neuroinflammation are often associated with irreparable damage to CNS cells due to the dysregulation of signaling cascades that are unable to restore a homeostatic balance. Due to the inherent complexity of the CNS, development of CNS-related therapeutics has met limited success. While stem cell therapy has been evaluated in the context of CNS repair, the mechanisms responsible for their functional properties have not been clearly defined. In recent years, there has been growing interest in the use of stem cell extracellular vesicles (EVs) for the treatment of various CNS pathologies as these vesicles are believed to mediate many of the functional effects associated with their donor stem cells. The potency of stem cell EVs is believed to be largely driven by their biological cargo which includes various types of RNAs, proteins, and cytokines. In this review, we describe the characteristic properties of stem cell EVs and summarize their reported neuroprotective and immunomodulatory functions. A special emphasis is placed on the identification of specific biological cargo, including proteins and non-coding RNA molecules, that have been found to be associated with stem cell EVs. Collectively, this review highlights the potential of stem cell EVs as an alternative to traditional stem cell therapy for the repair of cellular damage associated with diverse CNS pathologies.

Engagement of private healthcare providers for case finding of tuberculosis and diabetes mellitus in Pakistan.

BACKGROUND: The rising co-epidemic of tuberculosis (TB) and diabetes mellitus (DM) is a challenge for constrained health systems in low and middle-income countries. Diabetes is a known risk factor for tuberculosis and associated with poor tuberculosis treatment outcomes, while tuberculosis is associated with worsening glycemic control. We investigated the performance of bi-directional TB and DM case finding approaches through a private-sector engagement model in Karachi, Pakistan. METHODS: Between July 2016 and July 2018, private health care providers were engaged to generate referrals for bi-directional TB and DM screening at private diagnostic and treatment centers in Karachi, Pakistan. Individuals diagnosed with TB underwent glycated hemoglobin (HbA1c) testing at the time of anti-tuberculous treatment initiation and at three -month follow up stage. All individuals with a history of diabetes or random blood sugar of greater than 200 mg/dl were screened for TB using a chest X-ray and Xpert MTB/RIF. RESULTS: A total of 6312 persons with tuberculosis were tested on HbA1c at treatment initiation, of whom 1516 (24%) were newly diagnosed with DM. About one third of those with HbA1c in the diabetic range (≥ 6.5%) at baseline were found to have a normal HbA1c (< 5.7%) result at 3-month follow-up. A total of 3824 individuals with DM, of whom 2396 (63%) were known cases and 1428 (37%) were newly identified with random blood sugar > 200 mg/dl, underwent chest x-ray and Xpert MTB/RIF testing, with 321 (13.4%) known and 54 (3.8%) new diabetics respectively identified with tuberculosis. CONCLUSION: This study demonstrates a high yield of TB and DM through bidirectional screening and the feasibility of engagement of private sector in finding missing cases of tuberculosis and diabetes. Given the high prevalence of undiagnosed DM in individuals with TB tuberculosis patients, there is a need to scale-up DM screening within TB programmes. Increased awareness of the high risk of TB among individuals with DM is needed among private health providers and screening for TB among diabetics should be strongly considered.

Evaluation of computer aided detection of tuberculosis on chest radiography among people with diabetes in Karachi Pakistan.

Pakistan ranks fifth among high tuberculosis (TB) burden countries and also has seventh highest burden for diabetes mellitus (DM). DM increases the risk of developing TB and contributes to adverse TB treatment outcomes hence screening and integrated management for both diseases in high burden countries is suggested. Computer-Aided Detection for TB (CAD4TB) can potentially be used as triage tool in low resource settings to pre-screen individuals for Xpert MTB/RIF testing. The aim of this study was to evaluate the diagnostic accuracy and performance of CAD4TB software in people with diabetes (PWD) enrolled in a TB screening program in Karachi, Pakistan. A total of 694 individuals with a diagnosis of DM (of whom 31.1% were newly diagnosed) were screened with CAD4TB and simultaneously provided sputum for Xpert MTB/RIF testing. Of the 74 (10.7%) participants who had bacteriologically positive (MTB+) results on Xpert testing, 54 (73%) had a CAD4TB score >70; and 155 (25%) participants who tested MTB-negative had scores >70. The area under the receiver operator curve was 0.78 (95% CI: 0.77-0.80). Our study findings indicate that CAD4TB offers good diagnostic accuracy as a triage test for TB screening among PWD using Xpert MTB/RIF as the reference standard.

Computer aided detection of tuberculosis on chest radiographs: An evaluation of the CAD4TB v6 system.

There is a growing interest in the automated analysis of chest X-Ray (CXR) as a sensitive and inexpensive means of screening susceptible populations for pulmonary tuberculosis. In this work we evaluate the latest version of CAD4TB, a commercial software platform designed for this purpose. Version 6 of CAD4TB was released in 2018 and is here tested on a fully independent dataset of 5565 CXR images with GeneXpert (Xpert) sputum test results available (854 Xpert positive subjects). A subset of 500 subjects (50% Xpert positive) was reviewed and annotated by 5 expert observers independently to obtain a radiological reference standard. The latest version of CAD4TB is found to outperform all previous versions in terms of area under receiver operating curve (ROC) with respect to both Xpert and radiological reference standards. Improvements with respect to Xpert are most apparent at high sensitivity levels with a specificity of 76% obtained at a fixed 90% sensitivity. When compared with the radiological reference standard, CAD4TB v6 also outperformed previous versions by a considerable margin and achieved 98% specificity at the 90% sensitivity setting. No substantial difference was found between the performance of CAD4TB v6 and any of the various expert observers against the Xpert reference standard. A cost and efficiency analysis on this dataset demonstrates that in a standard clinical situation, operating at 90% sensitivity, users of CAD4TB v6 can process 132 subjects per day at an average cost per screen of $5.95 per subject, while users of version 3 process only 85 subjects per day at a cost of $8.38 per subject. At all tested operating points version 6 is shown to be more efficient and cost effective than any other version.

Optimization and modelling of enzymatic polymerization of ε-caprolactone to polycaprolactone using Candida Antartica Lipase B with response surface methodology and artificial neural network.

Recently enzymatic catalysts have replaced organic and organometallic catalysts in the synthesis of bio-resorbable polymers. Enzymatic polymerization is considered as an alternative to conventional polymerization as they are less toxic, environmental friendly and can operate under mild conditions. In this research, the enzymatic ring-opening polymerization (e-ROP) of e-caprolactone (e-CL) using Candida Antartica Lipase B (CALB) as catalyst to produce the Polycaprolactone. Two modelling techniques namely response surface methodology (RSM) and artificial neural network (ANN) have been used in this work. RSM is used to optimize the parameters and to develop a model of the process. ANN is used to develop the model to predict the results obtained from the experiment. The parameters involved are time, reaction temperature, mixing speed and enzyme-solvent ratio. The experimental result is Polydispersity index (PDI) of the polymer. The experimental data obtained was adequately fitted into second-order polynomial models. Simulation was done using artificial neural network model developed with Mean absolute error (MAD) value of 1.65 in comparison with MAD value of 7.4 for RSM. The Regression value (R2) values of RSM and ANN were found to be 0.96 and 0.93 respectively. The predictive models were validated experimentally and were found to be in agreement with the experimental values.

Autophagy, EVs, and Infections: A Perfect Question for a Perfect Time.

Autophagy, a highly conserved process, serves to maintain cellular homeostasis in response to an extensive variety of internal and external stimuli. The classic, or canonical, pathway of autophagy involves the coordinated degradation and recycling of intracellular components and pathogenic material. Proper regulation of autophagy is critical to maintain cellular health, as alterations in the autophagy pathway have been linked to the progression of a variety of physiological and pathological conditions in humans, namely in aging and in viral infection. In addition to its canonical role as a degradative pathway, a more unconventional and non-degradative role for autophagy has emerged as an area of increasing interest. This process, known as secretory autophagy, is gaining widespread attention as many viruses are believed to use this pathway as a means to release and spread viral particles. Moreover, secretory autophagy has been found to intersect with other intracellular pathways, such as the biogenesis and secretion of extracellular vesicles (EVs). Here, we provide a review of the current landscape surrounding both degradative autophagy and secretory autophagy in relation to both aging and viral infection. We discuss their key features, while describing their interplay with numerous different viruses (i.e. hepatitis B and C viruses, Epstein-Barr virus, SV40, herpesviruses, HIV, chikungunya virus, dengue virus, Zika virus, Ebola virus, HTLV, Rift Valley fever virus, poliovirus, and influenza A virus), and compare secretory autophagy to other pathways of extracellular vesicle release. Lastly, we highlight the need for, and emphasize the importance of, more thorough methods to study the underlying mechanisms of these pathways to better advance our understanding of disease progression.

Evaluation of the diagnostic accuracy of Computer-Aided Detection of tuberculosis on Chest radiography among private sector patients in Pakistan.

The introduction of digital CXR with automated computer-aided interpretation, has given impetus to the role of CXR in TB screening, particularly in low resource, high-burden settings. The aim of this study was to evaluate the diagnostic accuracy of CAD4TB as a screening tool, implemented in the private sector in Karachi, Pakistan. This study analyzed retrospective data from CAD4TB and Xpert MTB/RIF testing carried out at two private TB treatment and diagnostic centers in Karachi. Sensitivity, specificity, potential Xperts saved, were computed and the receiver operator characteristic curves were constructed for four different models of CAD4TB. A total of 6,845 individuals with presumptive TB were enrolled in the study, 15.2% of which had MTB + ve result on Xpert. A high sensitivity (range 65.8-97.3%) and NPV (range 93.1-98.4%) were recorded for CAD4TB. The Area under the ROC curve (AUC) for CAD4TB was 0.79. CAD4TB with patient demographics (age and gender) gave an AUC of 0.83. CAD4TB offered high diagnostic accuracy. In low resource settings, CAD4TB, as a triage tool could minimize use of Xpert. Using CAD4TB in combination with age and gender data enhanced the performance of the software. Variations in demographic information generate different individual risk probabilities for the same CAD4TB scores.

Emergence of fluoroquinolone resistance among drug resistant tuberculosis patients at a tertiary care facility in Karachi, Pakistan.

BACKGROUND: Pakistan is classified as one of the high multi-drug resistant tuberculosis (MDR-TB) burden countries. A poorly regulated private sector, over-prescription of antibiotics and self-medication has led to augmented rates of drug-resistance in the country. Pakistan's first national anti-tuberculosis drug resistance survey identified high prevalence of fluoroquinolone resistance among MDR-TB patients. Further institutional evidence of fluoroquinolone drug-resistance can support re-evaluation of treatment regimens as well as invigorate efforts to control antibiotic resistance in the country. FINDINGS: In this study, data for drug-susceptibility testing (DST) was retrospectively analyzed for a total of 133 patients receiving MDR-TB treatment at the Chest Department of Jinnah Postgraduate Medical Center, Karachi, Pakistan. Frequency analyses for resistance patterns was carried out and association of fluoroquinolone (ofloxacin) resistance with demographics and past TB treatment category were assessed. Within first-line drugs, resistance to isoniazid was detected in 97.7% of cases, followed by rifampicin (96.9%), pyrazinamide (86.4%), ethambutol (69.2%) and streptomycin (64.6%). Within second-line drugs, ofloxacin resistance was detected in 34.6% of cases. Resistance to ethionamide and amikacin was 2.3% and 1.6%, respectively. Combined resistance of oflaxacin and isoniazid was detected in 33.9% of cases. Age, gender and past TB treatment category were not significantly associated with resistance to ofloxacin. CONCLUSION: Fluoroquinolone resistance was observed in an alarmingly high proportion of MDR-TB cases. Our results suggest caution in their use for empirical management of MDR-TB cases and recommended treatment regimens for MDR-TB may require re-evaluation. Greater engagement of private providers and stringent pharmacy regulations are urgently required.