Realized heritability, inheritance, and mechanism of chlorfenapyr resistance in biocontrol agent, Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae): A step towards sustainable pest management.

A field population of Chrysoperla carnea was exposed for 17 generations to chlorfenapyr insecticide that resulted in 217-fold resistance compared to a susceptible strain. The overlapping of LC50 values in reciprocal crosses and their dominance values indicated that chlorfenapyr resistance was autosomal and incompletely dominant. The chi-square analysis of back-cross mortality confirmed the polygenic nature of chlorfenapyr resistance. The results of effective dominance of chlorfenapyr resistance indicated that resistance at the highest concentration was completely recessive. The realized heritability of chlorfenapyr resistance in the first 9, last 9, and a total of 18 generations was 0.28, 0.42, and 0.31, respectively. Furthermore, synergism results showed that both experimental synergists, PBO and DEF, did not synergize the toxicity of chlorfenapyr. In conclusion, C. carnea had been found to have autosomal, partially dominant, and polygenic chlorfenapyr resistance. Meaning that thereby resistance is inherited through multiple genes and is not limited to a single gene or sex-linked trait. These findings will help to develop an effective IPM model focusing on the simultaneous use of selective insecticides and resistant biocontrol agents to reduce the problem of resistance development in pest populations.

The Pathogenesis of Foot-and-Mouth Disease Virus Infection: How the Virus Escapes from Immune Recognition and Elimination.

Foot-and-mouth disease virus (FMDV) is a highly contagious and economically devastating pathogen that affects cloven-hoofed animals worldwide. FMDV infection causes vesicular lesions in the mouth, feet, and mammary glands, as well as severe systemic symptoms such as fever, salivation, and lameness. The pathogenesis of FMDV infection involves complex interactions between the virus and the host immune system, which determine the outcome of the disease. FMDV has evolved several strategies to evade immune recognition and elimination, such as antigenic variation, receptor switching, immune suppression, and subversion of innate and adaptive responses. This review paper summarizes the current knowledge on the pathogenesis of FMDV infection and the mechanisms of immune evasion employed by the virus. It also discusses the challenges and opportunities for developing effective vaccines and therapeutics against this important animal disease.

Foot-and-mouth disease seroprevalence is higher in young female crossbred sheep and goats compared to their counterparts in the border area between Pakistan and Afghanistan.

OBJECTIVE: Foot-and-mouth disease (FMD) is a highly contagious disease in ruminants that causes significant economic losses worldwide. However, the prevalence of FMD virus (FMDV) in small ruminants has been overlooked in Pakistan. This study aimed to determine the prevalence of FMD in sheep and goats in the border area between Pakistan and Afghanistan. ANIMALS: 800 sheep and goats belongs to age groups of 6 month to > 2 years. METHODS: A total of 800 serum samples were collected from sheep (n = 424) and goats (n = 376) and subjected to structural protein (SP) and 3ABC non-SP (NSP) ELISAs for the detection of antibodies against SP and NSP of the FMDV. RESULTS: For NSP, 340/800 (42.5%) of samples were positive, while SP analysis revealed that serotype O (44.5%) was the most common in sheep and goats, followed by Asia-1 (42%) and A (32%) serotypes. Sheep (39%; 95% CI, 34 to 44) had a higher (P < .05) prevalence of FMD than goats (46%; 95% CI, 41 to 51). Statistically significant (P < .05) differences in the seroprevalence of FMD-SP and FMD-NSPs were observed between various agencies (areas) of the study area. Risk factors such as age, sex, breed, season, flock size, body condition, animal movement, and production system were significantly (P < .05) associated with FMDV prevalence. CONCLUSIONS: This study showed that FMD is highly prevalent in sheep and goats in the border areas of Pakistan and Afghanistan. Therefore, outbreak investigation teams should be arranged at the border level to develop FMD risk-based surveillance and control plans for small ruminants in order to mitigate infection risks.

Navigating the Uncharted Territory of Pediatric-Onset Multiple Sclerosis in a 12-Year-Old Male: A Case Study.

This case report presents an atypical instance of pediatric-onset multiple sclerosis (MS) in a 12-year-old male, a demographic less commonly affected by this condition. The patient's clinical course was marked by severe and progressive symptoms, including lower limb weakness and loss of bowel/bladder control, diverging from the typical relapsing-remitting pattern observed in pediatric MS. Despite initial resistance to high-dose steroid treatment, his condition was ultimately stabilized through plasmapheresis, following the detection of myelin oligodendrocyte glycoprotein antibodies. Unique aspects of this case included the patient's young age, male gender, and the occurrence of osteopenia, as identified by a dual-energy X-ray absorptiometry scan. This report highlights the variability in MS presentations among pediatric patients and underscores the importance of a personalized, multidisciplinary approach to diagnosis and treatment. It contributes to the growing body of knowledge on pediatric MS, emphasizing the need for heightened clinical vigilance and tailored management strategies in young patients with this complex and lifelong disease.

A QSPR analysis of physical properties of antituberculosis drugs using neighbourhood degree-based topological indices and support vector regression.

Topological indices are molecular descriptors used in QSPR modelling to predict the physicochemical properties of molecules. Topological indices are used in numerous applications in drug design. In this work, we compute the neighbourhood degree-based topological indices of 15 antituberculosis drugs, we studied the QSPR analysis of these drugs using support vector regression. The efficiency of support vector regression is determined by comparing it with the classical linear regression. Our QSPR model further shows the superiority of the SVR model as a better predictive model in QSPR analysis of the physical properties of antituberculosis drugs. The findings in this study are a further contribution to the field of chemical graph theory and drug design, providing a deeper understanding of neighbourhood degree-based topological indices and their predictive capabilities in QSPR model.

Why do patients with DR-TB do not complete their treatment? Findings of a qualitative study from Pakistan.

BACKGROUND: One of the major reasons for unsuccessful treatment outcomes among patients with drug-resistant tuberculosis (DR-TB) is the high rate of loss to follow-up (LTFU). However, in Pakistan, no qualitative study has been conducted to explore the perceptions of LTFU patients with regard to DR-TB treatment, the problems they face and the reasons for LTFU in detail. METHODS: This was a qualitative study that involved semistructured, indepth, face-to-face interviews of 39 LTFU patients with DR-TB. All interviews were carried out in Pakistan's national language 'Urdu' using an interview guide in two phases: the first phase was from December 2020 to February 2021 among patients with extensively drug-resistant tuberculosis and the second phase from July 2021 to September 2021 among patients with multidrug-resistant tuberculosis. RESULTS: The inductive thematic analysis of audio-recorded interviews generated the following four key themes, which were the major reasons reported by the participants of the current study to have led to LTFU: (1) patient-related factors, such as lack of awareness about the total duration of DR-TB treatment, fatigue from previous multiple failed episodes, lack of belief in treatment efficacy and perception of DR-TB as a non-curable disease; (2) medication-related factors, such as use of injectables, high pill burden, longer duration and adverse events; (3) socioeconomic factors, such as gender discrimination, poor socioeconomic conditions, non-supportive family members, social isolation and unemployment; and (4) service provider-related factors, such as distant treatment centres, non-availability of a qualified person, lack of adequate counselling and poor attitude of healthcare professionals. CONCLUSION: In the current study, patients' perceptions about DR-TB treatment, socioeconomic condition, medication and service provider-related factors emerged as barriers to the successful completion of DR-TB treatment. Increasing patients' awareness about the duration of DR-TB treatment, interacting sessions with successfully treated patients, availability of rapid drug susceptibility testing facilities at treatment centres, decentralising treatment and using the recently recommended all-oral regimen may further decrease the rate of LTFU.

Foot-and-mouth disease virus dynamics in border areas of Pakistan with Afghanistan.

BACKGROUND: Foot and mouth disease (FMD) is a highly contagious disease that impacts cloven-hoofed animals globally. The illegal trade of livestock between the border regions of Pakistan and Afghanistan can contribute to the spread of this disease. This study focuses on investigating the outbreaks of FMD that occurred in this area from June 2020 to May 2021. METHODS: RESULTS: A total of 233 epithelial tissue samples were collected, and 77% were found positive for FMDV through an antigen-detection by ELISA and molecular conformation through RT-PCR. The study found three serotypes of FMDV dominating in the border area of Pakistan with Afghanistan: O, A, and Asia-1. The outbreak activity was peaked between August/September followed by July/October 2020. Phylogenetic analysis conducted using the VP1 region sequence showed that serotype O isolates belonged to the Middle East-South Asia (ME-SA) topotype, PanAsia-2 lineage, and ANT-10 sub-lineage, while serotype Asia-1 isolates belonged to a novel lineage BD-18.The highest prevalence of serotype O of FMDV was found in cattle and buffalo of 1-2 year age group, while the highest outbreak ratio of serotype O was recorded in goats of 0-1 year age group and sheep of > 2 year age group. The serotype O was more prevalent in male than female sheep. The type A was more prevalent in females of sheep and goats than their corresponding males. The serotype Asia-1 was more prevalent in females of cattle and sheep than their corresponding males. The outbreak epidemiology of FMD varied significantly between various regions, months of study, animal species, age groups, and gender. CONCLUSIONS: The study found that FMD outbreaks in the border area of Pakistan and Afghanistan were diverse and complicated, and that different types of FMDV were circulating. The study recommended effective actions to stop FMD transmission in this area.

Smoke Signals: Unraveling the Paradoxical Impact of Smoking on Stroke Prognosis and Treatment Efficacy.

Smoking is a well-established risk factor for stroke, yet its impact on stroke prognosis remains complex and multifaceted. This systematic review aims to elucidate the relationship between smoking and various stroke outcomes, including response to treatment and long-term recovery. We conducted a comprehensive analysis of four fundamental studies that examined the prognosis of stroke in smokers, focusing on clinical outcomes post-endovascular treatment, response to antiplatelet therapy, incidence of post-stroke delirium, and the effectiveness of thrombolysis treatment. The studies varied in design, including observational, retrospective, and post hoc trial analyses. The review reveals that smoking may paradoxically predict better clinical outcomes in specific treatment scenarios, such as post-endovascular treatment and when using clopidogrel. However, smokers also demonstrated higher rates of ischemic stroke and post-stroke delirium. Notably, the smoker's paradox in thrombolysis treatment was not supported. These findings highlight the need for personalized treatment approaches based on smoking status. Smoking has a complex and significant impact on stroke prognosis. While some benefits in specific treatment contexts were observed, the overall evidence strongly advises against smoking due to its adverse health consequences. This review underscores the importance of personalized stroke management in smokers and the integration of smoking cessation programs in post-stroke care. Future research should focus on larger, longitudinal studies to explore these associations further.

Navigating Neurological and Cardiac Complexities: A Case Study on Viral Meningoencephalitis in a Patient With Ischemic Heart Disease.

We present a case of viral meningoencephalitis in a 40-year-old male with ischemic heart disease, a combination that is rare and presents unique diagnostic and therapeutic challenges. The patient's symptoms included high-grade fever, severe headache, projectile vomiting, and altered consciousness. The diagnosis was supported by MRI and CSF analysis. Management, complicated by the patient's cardiac condition, required a personalized approach, including antiviral therapy, corticosteroids, and vigilant monitoring of cardiac and neurological status. Treatment adjustments were made in response to the patient's evolving condition, leading to improvement within a week. This case underscores the need for a multidisciplinary approach in such complex scenarios, highlighting the significance of tailored care for patients with neurological symptoms and concurrent cardiac comorbidities. The report contributes to the literature on managing meningoencephalitis in patients with significant cardiac histories, underscoring personalized medicine's role in successful outcomes.

Impact of SSO-ASTRO Margin Guidelines on Re-excision Rate in Breast-conserving Surgery: A Single-center Experience.

Introduction: Breast-conserving surgery (BCS) has been historically linked with a high rate of re-excision. To address this issue, the Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO) developed consensus guidelines in 2014 to standardize practices and improve clinical outcomes for BCS patients. In our tertiary cancer care hospital, we assessed the impact of these guidelines on the re-excision rate following BCS. Materials and Methods: We conducted a retrospective study on breast cancer patients who underwent BCS at the Shaukat Khanum Memorial Cancer Hospital and Research Centre in Lahore, Pakistan. The study compared the re-excision rate before the implementation of the SSO-ASTRO consensus guidelines (November 2015-July 2017) and after the implementation (January 2018-August 2019). Margins were considered positive if "ink on tumor" was present and negative if "no ink on tumor" was present. Fisher's exact test or Chi-square test was used to compare the re-excision rates between the pre- and post-guideline periods. Results: A total of 919 patients were identified, with 533 from the pre-guideline period and 386 from the post-guideline period. Of the 919 patients, 31 with ductal carcinoma in situ (DCIS) were excluded from the re-excision analysis because the guidelines were not implemented on the DCIS. Furthermore, the overall rate of re-excision in our data was 4.3%. The re-excision rate decreased from 71.1% to 28.9% (P ≤ 0.05) following the adoption of the guidelines. We observed a statistically significant decrease in the re-excision rate after implementing the SSO-ASTRO guidelines. Conclusion: Implementation of the SSO-ASTRO margin guidelines led to a notable decrease in the overall re-excision rate in our data set. These findings suggest that continued adherence to the guidelines may lead to a further reduction in the re-excision rate in the future.

Sex-specific differences in risk factors, comorbidities, diagnostic challenges, optimal management, and prognostic outcomes of heart failure with preserved ejection fraction: A comprehensive literature review.

Due to hormonal variations, heart failure with preserved ejection fraction (HFpEF) remains prevalent in women and affects almost half of the heart failure (HF) patients. Given the yearly death rate of 10-30% and the unavailability of medications targeting HFpEF, the need arises for a better understanding of the fundamental mechanisms of this syndrome. This comprehensive review explores sex-specific differences in traditional risk factors; female-specific factors that may impact HFpEF development and response to therapy, including variations in hormone levels that may occur pre- and post-menopausal or during pregnancy; and disparities in comorbidities, clinical presentation, and diagnostic challenges. Lastly, the review addresses prognostic outcomes, noting that women with HFpEF have a poor quality of life but a higher survival rate. It also discusses novel biomarkers and precision medicine, emphasizing their potential to improve early detection and personalized treatment.

Non-Coding RNA-Mediated Gene Regulation in Cardiovascular Disorders: Current Insights and Future Directions.

Cardiovascular diseases (CVDs) pose a significant burden on global health. Developing effective diagnostic, therapeutic, and prognostic indicators for CVDs is critical. This narrative review explores the role of select non-coding RNAs (ncRNAs) and provides an in-depth exploration of the roles of miRNAs, lncRNAs, and circRNAs in different aspects of CVDs, offering insights into their mechanisms and potential clinical implications. The review also sheds light on the diverse functions of ncRNAs, including their modulation of gene expression, epigenetic modifications, and signaling pathways. It comprehensively analyzes the interplay between ncRNAs and cardiovascular health, paving the way for potential novel interventions. Finally, the review provides insights into the methodologies used to investigate ncRNA-mediated gene regulation in CVDs, as well as the implications and challenges associated with translating ncRNA research into clinical applications. Considering the broader implications, this research opens avenues for interdisciplinary collaborations, enhancing our understanding of CVDs across scientific disciplines.

Development of alpha-cypermethrin resistance and its effect on biological parameters of yellow fever mosquito, Aedes aegypti (L.) (Diptera: Culicidae).

Alpha-cypermethrin interacts with the sodium channel and causes nerve blockage in insects. It is used to manage Aedes aegypti (Linnaeus) (Diptera: Culicidae), a primary vector of dengue worldwide. It not only affects both target and non-target organisms, but overuse of this insecticide increases the chances of resistance development in insect pests. In this study, resistance development, biological parameters, and stability of alpha-cypermethrin resistance were studied in a laboratory-selected strain of Ae. aegypti. The alpha-cypermethrin selected strain (Alpha Sel) developed an 11.86-fold resistance level after 12 rounds of alpha-cypermethrin selection compared to the unselected strain (Unsel). In biological parameters, Alpha Sel and Cross1 (Unsel ♂ and Alpha Sel♀) had shorter larval durations compared to Unsel and Cross2 (Unsel ♀ and Alpha Sel ♂) populations. The pupal duration of Alpha Sel and both crosses was shorter than that in the Unsel strain. The relative fitness of Alpha Sel, Cross1, and Cross2 was significantly less than that of the Unsel strain. These results indicate that alpha-cypermethrin resistance comes with fitness costs. Moreover, the frequency of alpha-cypermethrin resistance decreased when the Alpha Sel population was reared without further selection pressure for four generations. So, resistance was unstable and reversed when insecticide pressure ceased. We concluded that the judicious and rotational use of different insecticides with different modes of action and the adoption of other IPM-recommended practices would suppress resistance development for more extended periods in Ae. aegypti.

Orbital Onset: The Intricate Journey From Ear Abscess to Cavernous Sinus Thrombosis in a Diabetic Male.

Cavernous sinus thrombosis (CST) is a rare, yet severe condition often linked to infections in the nasal and facial areas. We present a case of a 43-year-old male farmer with diabetes who initially showed ear abscess symptoms that progressed to vision loss and CST-like symptoms. Self-treatment and an unidentified medication regimen may have worsened his condition. Advanced diagnostic evaluations, particularly magnetic resonance imaging with magnetic resonance venography, confirmed CST, likely originating from the ear infection spreading to the eyes, causing bilateral orbital cellulitis. Treatment with antibiotics, anticoagulants, and supportive therapy stabilized the patient's condition. This case emphasizes the importance of early detection and intervention in CST, especially in atypical presentations, and the need for comprehensive diagnostic and therapeutic approaches.

Molecular characterization of lumpy skin disease virus from recent outbreaks in Pakistan.

Lumpy skin disease (LSD) is a contagious viral transboundary disease listed as a notifiable disease by the World Organization of Animal Health (WOAH). The first case of this disease was reported in Pakistan in late 2021. Since then, numerous outbreaks have been documented in various regions and provinces across the country. The current study primarily aimed to analyze samples collected during LSD outbreaks in cattle populations in the Sindh and Punjab provinces of Pakistan. Phylogenetic analysis was conducted using partial sequences of the GPCR, p32, and RP030 genes. Collectively, the LSDV strains originating from outbreaks in Pakistan exhibited a noticeable clustering pattern with LSDV strains reported in African, Middle Eastern, and Asian countries, including Egypt, the Kingdom of Saudi Arabia, India, China, and Thailand. The precise reasons behind the origin of the virus strain and its subsequent spread to Pakistan remain unknown. This underscores the need for further investigations into outbreaks across the country. The findings of the current study can contribute to the establishment of effective disease control strategies, including the implementation of a mass vaccination campaign in disease-endemic countries such as Pakistan.

Current and Future Technologies for the Detection of Antibiotic-Resistant Bacteria.

Antibiotic resistance is a global public health concern, posing a significant threat to the effectiveness of antibiotics in treating bacterial infections. The accurate and timely detection of antibiotic-resistant bacteria is crucial for implementing appropriate treatment strategies and preventing the spread of resistant strains. This manuscript provides an overview of the current and emerging technologies used for the detection of antibiotic-resistant bacteria. We discuss traditional culture-based methods, molecular techniques, and innovative approaches, highlighting their advantages, limitations, and potential future applications. By understanding the strengths and limitations of these technologies, researchers and healthcare professionals can make informed decisions in combating antibiotic resistance and improving patient outcomes.

Orthostatic Hypotension in Benign Prostatic Hyperplasia Patients and Its Association With Alpha-1 Antagonist Use: A Comprehensive Literature Review.

Orthostatic hypotension (OH) is frequently observed in benign prostatic hyperplasia (BPH) patients undergoing alpha-1 adrenergic antagonist (A1AA) therapy. While previous studies have acknowledged the prevalence of OH in BPH patients on A1AAs, limited data exist on ranking the safety of different A1AAs. This comprehensive review explores the underlying mechanisms of OH, examines numerous factors influencing its development, and provides insights into effective treatment strategies such as hydration, gradual postural changes, leg exercises, compression stockings, and tilt-table training for BPH management. The review highlights the significance of individualized care, interdisciplinary collaboration, and further research to optimize A1AA treatment, improve patient outcomes, and enhance quality of life.

Comparative Roles of IL-1, IL-6, IL-10, IL-17, IL-18, 1L-22, IL-33, and IL-37 in Various Cardiovascular Diseases With Potential Insights for Targeted Immunotherapy.

In recent years, the study of interleukins (ILs), crucial cytokines involved in immune response and inflammation, has garnered significant attention within the sphere of cardiovascular diseases (CVDs). The research has provided insights into the involvement of ILs in diverse CVDs, including arrhythmias, myocardial infarction, atherosclerosis, and heart failure (HF). ILs have emerged as promising therapeutic targets for drug interventions through their involvement in disease development and progression. This comprehensive review provides a detailed overview of ILs, elucidating their functions within the immune system and offering insights into their specific contributions to various CVDs. Moreover, the article delves into the examination of current and potential drug therapies that selectively target ILs in the management of CVDs, presenting a comprehensive analysis of the advantages and disadvantages associated with these therapeutic approaches. A comprehensive literature review was conducted to investigate the involvement of ILs in CVDs. The relevant articles were searched on PubMed, PubMed Central, Medline, Cochrane, Google Scholar, and ScienceDirect databases. The search encompassed articles published from these databases' inception until July 12, 2023. We first examine generalized aspects of ILs, particularly CVDs. Then, we shift focus towards examining the direct impact of ILs on cardiac cells and tissue; on the immune system and inflammation; endothelial cells and vascular function; and finally, their interactions with other signaling pathways and molecules. Then, we discuss the molecular mechanisms of various ILs. Sequentially, we delve into a comprehensive analysis of the individualized role of each distinct IL in diverse CVDs, examining their specific contributions. Finally, we explore the potential for targeted drug therapy to modulate IL activity, aiming to enhance outcomes for patients burdened with CVD. The objective is the identification of gaps in current knowledge and highlight areas that require further investigation within the context of cardiovascular medicine. Through deepening our comprehension of the intricate involvement of ILs in CVDs and harnessing their potential for targeted drug therapy, novel treatment strategies can be devised, leading to improved patient outcomes in cardiovascular medicine.

Advancements in Percutaneous Coronary Intervention Techniques: A Comprehensive Literature Review of Mixed Studies and Practice Guidelines.

Percutaneous coronary intervention (PCI) is a widely used therapy for coronary artery disease (CAD), but it carries risks and complications. Adhering to evidence-based practice guidelines is crucial for optimal outcomes. This review compares the recommendations of the 2021 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) and 2018 European Society of Cardiology (ESC) guidelines for coronary artery revascularization and discusses emerging trends and novel devices in PCI. A comprehensive literature review of mixed studies, clinical trials, and guidelines was conducted. Intravascular imaging, including intravascular ultrasound and optical coherence tomography, for stent optimization, is also recommended when feasible. However, differences reflecting variations in evidence quality interpretation and applicability were identified. Furthermore, novel devices and technologies with the potential for improving outcomes were highlighted, but their safety and efficacy compared to standard-of-care techniques require further evaluation through extensive randomized trials. Clinicians should stay updated on advancements and personalize treatment decisions based on individual patient factors. Future research should address evidence gaps and barriers to adopting innovative devices and techniques. This review provides recommendations for clinical practice, emphasizing the need to remain current with the evolving landscape of PCI to optimize patient outcomes. The discoveries provide valuable counsel for the deliberation of clinical interventions and prospective inquiries within the realm of interventional cardiology. Overall, the review underscores the importance of evidence-based practice and ongoing advancements in PCI for CAD management.

Unlocking the Mysteries, Bridging the Gap, and Unveiling the Multifaceted Potential of Stem Cell Therapy for Cardiac Tissue Regeneration: A Narrative Review of Current Literature, Ethical Challenges, and Future Perspectives.

Revolutionary advancements in regenerative medicine have brought stem cell therapy to the forefront, offering promising prospects for the regeneration of ischemic cardiac tissue. Yet, its full efficacy, safety, and role in treating ischemic heart disease (IHD) remain limited. This literature review explores the intricate mechanisms underlying stem cell therapy. Furthermore, we unravel the innovative approaches employed to bolster stem cell survival, enhance differentiation, and seamlessly integrate them within the ischemic cardiac tissue microenvironment. Our comprehensive analysis uncovers how stem cells enhance cell survival, promote angiogenesis, and modulate the immune response. Stem cell therapy harnesses a multifaceted mode of action, encompassing paracrine effects and direct cell replacement. As our review progresses, we underscore the imperative for standardized protocols, comprehensive preclinical and clinical studies, and careful regulatory considerations. Lastly, we explore the integration of tissue engineering and genetic modifications, envisioning a future where stem cell therapy reigns supreme in regenerative medicine.