Fentanyl and xylazine crisis: Crafting coherent strategies for opioid overdose prevention.

The United States is in the throes of a severe opioid overdose epidemic, primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine, a veterinary sedative often mixed with fentanyl. The high potency and long duration of fentanyl is compounded by the added risks from xylazine, heightening the lethal danger faced by opioid users. Measures such as enhanced surveillance, public awareness campaigns, and the distribution of fentanyl-xylazine test kits, and naloxone have been undertaken to mitigate this crisis. Fentanyl-related overdose deaths persist despite these efforts, partly due to inconsistent policies across states and resistance towards adopting harm reduction strategies. A multifaceted approach is imperative in effectively combating the opioid overdose epidemic. This approach should include expansion of treatment access, broadening the availability of medications for opioid use disorder, implementation of harm reduction strategies, and enaction of legislative reforms and diminishing stigma associated with opioid use disorder.

Isolated left ventricular non-compaction: Clinical characterisation of a teenage male.

Isolated Left Ventricular Non-compaction (LVNC) is a type of cardiomyopathy that usually has a genetic origin. Its diagnosis is based on finding such as deep intertrabecular recesses or sinusoids and ventricular trabeculations communicating with the left ventricular cavity. LVNC was first clinically recognised almost four decades ago, yet its diagnostic and management challenges persist. In this report, we present the case of an 18-year-old boy, who presented at the National Institute of Cardiovascular Diseases, Karachi, in March 2023, with complaints of dizziness, pedal oedema, and shortness of breath. Echocardiography revealed signs suggestive of LVNC, which were confirmed conclusively on Cardiovascular Magnetic Resonance (CMR) (NC/C ratio>2.4). The patient underwent implantable cardioverter defibrillator (ICD) placement, was discharged after a smooth post-procedure recovery, and is doing well on follow-ups. Hence, ICD and guideline-directed medical therapy as a combination have turned out to have satisfactory outcomes in decreasing morbidity and providing mortality benefits for such patients.

Feasibility and safety of cryoballoon ablation for atrial fibrillation and closing patent foramen ovale without implantation：A pilot study.

BACKGROUND: Patent foramen ovale (PFO) affects 20%-34% of adults and is associated with strokes and other disorders. The conventional treatment of PFO-related strokes is a closure procedure. The metal device is associated with some adverse events. OBJECTIVE: Our aim was to investigate the efficacy and safety of PFO closure using cryoablation without implantation in patients with atrial fibrillation (AF) who underwent pulmonary vein isolation (PVI). METHODS: We divided the 22 patients with both PFO and AF who underwent PVI via cryoablation into 2 groups: standard PVI + atrial septal (AS) cryoablation group (group 1, n = 11) and standard PVI group (group 2, n = 11). The guidewire accesses the left atrium through the PFO without AS puncture during the procedure. Standard PVI via cryoablation was performed. The cryoballoon was retracted to the right atrium and inflated against the AS post-PVI. Patients in group 1 had cryoablation for 120-150 seconds, whereas patients in group 2 received sham ablation. The co-primary end points were the PFO closure rate and a composite of AF recurrence and stroke/transient ischemic attack (TIA) events. RESULTS: There were no differences in procedure-related adverse events between the 2 groups. Neither group had an ischemic stroke report at 1-year follow-up. The PFO closure rate at 6 months in group 1 was significantly higher than that in group 2 (7 [63.6%] vs 1 [9.1%]; P = .002). AF recurrence post ablation was comparable in both groups at 3 months (3 [27.3%] vs 1 [9.1%]; P = .269), 6 months (0 vs 0), and 12 months (2 [18.2%%] vs 1 [9.1%]; P = .534) of follow-up. CONCLUSION: Cryoablation is a safe and effective approach to close PFO in patients with AF undergoing PVI in a single procedure.

A novel fusion of genetic grey wolf optimization and kernel extreme learning machines for precise diabetic eye disease classification.

In response to the growing number of diabetes cases worldwide, Our study addresses the escalating issue of diabetic eye disease (DED), a significant contributor to vision loss globally, through a pioneering approach. We propose a novel integration of a Genetic Grey Wolf Optimization (G-GWO) algorithm with a Fully Convolutional Encoder-Decoder Network (FCEDN), further enhanced by a Kernel Extreme Learning Machine (KELM) for refined image segmentation and disease classification. This innovative combination leverages the genetic algorithm and grey wolf optimization to boost the FCEDN's efficiency, enabling precise detection of DED stages and differentiation among disease types. Tested across diverse datasets, including IDRiD, DR-HAGIS, and ODIR, our model showcased superior performance, achieving classification accuracies between 98.5% to 98.8%, surpassing existing methods. This advancement sets a new standard in DED detection and offers significant potential for automating fundus image analysis, reducing reliance on manual examination, and improving patient care efficiency. Our findings are crucial to enhancing diagnostic accuracy and patient outcomes in DED management.

Mavacamten: A Review of a Novel Therapeutic Approach for Hypertrophic Cardiomyopathy.

Hypertrophic Cardiomyopathy (HCM) is a heart disease that can cause left ventricular hypertrophy, arrhythmias, heart failure, and sudden cardiac death. Currently, pharmacological treatment is limited and ineffective. Mavacamten (CamzyosTM) is a cardiac myosin inhibitor developed as a therapeutic option to reduce myocardial contractility and restoration of myocardial function. The Food and Drug Administration (FDA) approved the use of Mavacamten in 2022 for HCM symptoms. Clinical studies have proven that Mavacamten can reduce Left Ventricular Outflow Tract (LVOT) involvement, cardiac hypercontraction, and hypertrophy. This review provides an overview of HCM, its pathophysiology, current treatments, synthesis of Mavacamten, and the clinical trials of Mavacamten.

Arachnoid cyst in the quadrigeminal cistern: A case from Afghanistan.

Arachnoid cysts, fluid-filled lesions within the central nervous system, pose diagnostic challenges. This study examines a unique case of a quadrigeminal arachnoid cyst in a 13-year-old girl, emphasizing accurate identification and treatment. The patient's symptoms of blurred vision and headaches led to the discovery of papilledema and imaging revealing a sizable cyst causing obstructive hydrocephalus. Urgent surgical intervention involved suboccipital craniectomy and infratentorial-supracerebellar cyst drainage, resulting in favorable postoperative outcomes. Further analysis of anatomical variations, age-related factors, and etiological debates deepens understanding. Diagnostic advancements, notably MRI, are crucial for noninvasive characterization. This case offers nuanced insights into managing arachnoid cysts, highlighting the success of tailored surgical strategies. Recognizing clinical subtleties, utilizing diagnostic innovations, and customizing surgical techniques are essential for navigating complexities. This study underscores the importance of a comprehensive approach in addressing the challenges of arachnoid cysts within the central nervous system.

Soybean-mediated suppression of BjaI/BjaR1 quorum sensing in Bradyrhizobium diazoefficiens impacts symbiotic nitrogen fixation.

The acyl-homoserine lactones (AHLs)-mediated LuxI/LuxR quorum sensing (QS) system orchestrates diverse bacterial behaviors in response to changes in population density. The role of the BjaI/BjaR1 QS system in Bradyrhizobium diazoefficiens USDA 110, which shares homology with LuxI/LuxR, remains elusive during symbiotic interaction with soybean. Here this genetic system in wild-type (WT) bacteria residing inside nodules exhibited significantly reduced activity compared to free-living cells, potentially attributed to soybean-mediated suppression. The deletion mutant strain ΔbjaR1 showed significantly enhanced nodulation induction and nitrogen fixation ability. Nevertheless, its ultimate symbiotic outcome (plant dry weight) in soybeans was compromised. Furthermore, comparative analysis of the transcriptome, proteome, and promoter activity revealed that the inactivation of BjaR1 systematically activated and inhibited genomic modules associated with nodulation and nitrogen metabolism. The former appeared to be linked to a significant decrease in the expression of NodD2, a key cell-density-dependent repressor of nodulation genes, while the latter conferred bacterial growth and nitrogen fixation insensitivity to environmental nitrogen. In addition, BjaR1 exerted a positive influence on the transcription of multiple genes involved in a so-called central intermediate metabolism within the nodule. In conclusion, our findings highlight the crucial role of the BjaI/BjaR1 QS circuit in positively regulating bacterial nitrogen metabolism and emphasize the significance of the soybean-mediated suppression of this genetic system for promoting efficient symbiotic nitrogen fixation by B. diazoefficiens.IMPORTANCEThe present study demonstrates, for the first time, that the BjaI/BjaR1 QS system of Bradyrhizobium diazoefficiens has a significant impact on its nodulation and nitrogen fixation capability in soybean by positively regulating NodD2 expression and bacterial nitrogen metabolism. Moreover, it provides novel insights into the importance of suppressing the activity of this QS circuit by the soybean host plant in establishing an efficient mutual relationship between the two symbiotic partners. This research expands our understanding of legumes' role in modulating symbiotic nitrogen fixation through rhizobial QS-mediated metabolic functioning, thereby deepening our comprehension of symbiotic coevolution theory. In addition, these findings may hold great promise for developing quorum quenching technology in agriculture.

Exploring the Potential of New Benzamide-Acetamide Pharmacophore Containing Sulfonamide as Urease Inhibitors: Structure-Activity Relationship, Kinetics Mechanism, and In Silico Studies.

The search for novel drug scaffolds that can improve effectiveness and safety through drug conjugates is a promising approach. Consequently, drug conjugates constitute a dynamic field of study and advancement within medicinal chemistry. This research demonstrates the conjugation of diclofenac and mefenamic acid with sulfa drugs and their screening for urease inhibition. These conjugates' structural confirmation was performed using elemental analysis and spectroscopic methods, including IR, 1H NMR, and 13C NMR. Diclofenac conjugated with sulfanilamide (4), sulfacetamide (10), and mefenamic acid conjugated with sulfanilamide (12), and sulfamethoxazole (17) was found potent and demonstrated urease inhibition competitively, with IC50 (µM) values 3.59 ± 0.07, 5.49 ± 0.34, 7.92 ± 0.27, and 8.35 ± 0.26, respectively. Diclofenac conjugated with sulfathiazole (6), sulfamerazine (8), and sulfaguanidine (11), while mefenamic acid conjugated with sulfisoxazole (13), sulfathiazole (14), and sulfadiazine (15) exhibited a mixed mode of urease inhibition. The IC50 (µM) values were 16.19 ± 0.21, 9.50 ± 0.28, 4.35 ± 0.23, 15.86 ± 0.25, 14.80 ± 0.27, and 7.92 ± 0.27, respectively. Furthermore, molecular docking studies were employed to predict the binding pose of competitive inhibitors at the urease active site. These conjugates generated stable complexes with the urease protein observed through molecular dynamics (MD) simulations, where no conformational changes occurred throughout the simulations. These results highlight the potential for approved therapeutic molecule conjugates to give rise to new categories of pharmacological agents for urease inhibition. The structural similarity of sulfonamides with urea allows them to compete with urea for binding to the active site of the urease enzyme. Sulfonamides and nonsteroidal anti-inflammatory drugs (NSAIDs) can interact hydrophobically with the active site of the urease enzyme, which may disturb its structure and catalytic activity. Therefore, these conjugates may be helpful in the development of novel pharmacological agents for the treatment of a variety of illnesses in which the urease enzyme is involved.

Prevalence of Variants of Uncertain Significance in Patients Undergoing Genetic Testing for Hereditary Breast and Ovarian Cancer and Lynch Syndrome.

Hereditary Breast and Ovarian Cancer (HBOC) and Lynch Syndrome (LS) are the most common inherited cancer syndromes identified with genetic testing. Testing, though, commonly reveals variants of uncertain significance (VUSs). This is a retrospective observational study designed to determine the prevalence of pathogenic mutations and VUSs in patients tested for HBOC and/or LS and to explore the characteristics of the VUS population. Patients 18-80 years old that met NCCN criteria for HBOC and/or LS genetic screening were tested between 2006 and 2020 at Mount Auburn Hospital in Cambridge, Massachusetts. A total of 663 patients were included in the study, with a mean age of 50 years old and 90% being females. Pathogenic mutations were identified in 12.5% and VUSs in 28.3%. VUS prevalence was associated with race (p-value = 0.019), being particularly higher in Asian populations. Patients with a personal history of breast cancer or family history of breast or ovarian cancer were more likely to have a VUS (personal breast: OR: 1.55; CI: 1.08-2.25; family breast: OR: 1.68; CI: 1.08-2.60, family ovarian OR: 2.29; CI: 1.04-5.45). In conclusion, VUSs appear to be detected in almost one third patients tested for cancer genetic syndromes, and thus future work is warranted to determine their significance in cancer development.

Osteoarthritis knee and modifiable cardiovascular risk factors: play in tandem.

Objective: To know the frequency of modifiable cardiovascular risk factors in knee osteoarthritis patients. Method: Cross sectional study was done at Department of Rheumatology Indus Medical College, Tando Mohammad Khan from March 25, 2022 to November 24, 2022. Total 246 Osteoarthritis of knee cases with (Kellgren-Lawrence grad-II and above) on x-ray, were selected after demographic details, blood pressure, body mass index and physical examination was done, 5ml of venous blood was drawn by phlebotomist, sent for fasting blood sugar, serum lipids analysis and Framingham 10years risk score was calculated afterward for each participant. Results: In this study males (126) and females (120). Overall (78%) had risk factors, Patients having one CVD risk factor were (22.8%), two risk factors in (21.1%), three in (21.5%), four (9.8%) and five factors in (1.6%) while frequency of modifiable cardiovascular risk shows obesity (45.5%) hypertension (40.2%) intermediate to high risk of framingham score (40%) diabetes mellitus (25%), smoking (17%), high low density lipoproteins (8.1%). In males obesity(54.2%), hypertension (47.5% ) and (45.8%) were on medication, diabetes mellitus(31.7%), smoker(31%), high risk FRS(39.2%), K-L grade-IV(58.4%) and in females: obesity (42%), hypertension (43.7%) and (40.5%) were on medication, diabetes mellitus in (19%), smoking (4%), high risk FRS (13.5%), K-L Grade-4 (42%), significant association of diabetes mellitus, smoking, FRS and K-L grades with gender (p<0.05). Conclusion: In OA knee there is high prevalence of modifiable cardiovascular risk factors and together these imposes a major health risk for future cardiac events and disability.

A study on the effect of bioactive glass and hydroxyapatite-loaded Xanthan dialdehyde-based composite coatings for potential orthopedic applications.

The most important challenge faced in designing orthopedic devices is to control the leaching of ions from the substrate material, and to prevent biofilm formation. Accordingly, the surgical grade stainless steel (316L SS) was electrophoretically deposited with functional composition of biopolymers and bioceramics. The composite coating consisted of: Bioglass (BG), hydroxyapatite (HA), and lawsone, that were loaded into a polymeric matrix of Xanthan Dialdehyde/Chondroitin Sulfate (XDA/CS). The parameters and final composition for electrophoretic deposition were optimized through trial-and-error approach. The composite coating exhibited significant adhesion strength of "4B" (ASTM D3359) with the substrate, suitable wettability of contact angle 48°, and an optimum average surface roughness of 0.32 µm. Thus, promoting proliferation and attachment of bone-forming cells, transcription factors, and proteins. Fourier transformed infrared spectroscopic analysis revealed a strong polymeric network formation between XDA and CS. scanning electron microscopy and energy dispersive X-ray spectroscopy analysis displayed a homogenous surface with invariable dispersion of HA and BG particles. The adhesion, hydrant behavior, and topography of said coatings was optimal to design orthopedic implant devices. The said coatings exhibited a clear inhibition zone of 21.65 mm and 21.04 mm with no bacterial growth against Staphylococcus aureus (S. Aureus) and Escherichia coli (E. Coli) respectively, confirming the antibacterial potential. Furthermore, the crystals related to calcium (Ca) and HA were seen after 28 days of submersion in simulated body fluid. The corrosion current density, of the above-mentioned coating was minimal as compared to the bare 316L SS substrate. The results infer that XDA/CS/BG/HA/lawsone based composite coating can be a candidate to design coatings for orthopedic implant devices.

Acetylsalicylic acid-sulfa drugs conjugates as potential urease inhibitors and anti-inflammatory agents: bio-oriented drug synthesis, molecular docking, and dynamics simulation studies.

To explore the new mode of action and reduce side effects, making conjugates of existing drugs is becoming an attractive tool in the realm of medicinal chemistry. In this work, we exploited this approach and synthesized new conjugates to assess their activities against the enzymes involved in different pathological conditions. Specifically, we design and synthesized conjugates involving acetylsalicylic acid and sulfa drugs, validating the newly crafted conjugates using techniques like IR, 1HNMR, 13CNMR, and elemental analysis. These conjugates underwent assessment for their ability to inhibit cyclooxygenase-2 (COX-2), urease enzymes, and their anti-inflammatory potential. A competitive mode of urease inhibition was observed for acetylsalicylic acid conjugated with sulfanilamide, sulfacetamide, and sulfadiazine with IC50 of 2.49 ± 0.35 µM, 6.21 ± 0.28 µM, and 6.57 ± 0.44 µM, respectively. Remarkably, the acetylsalicylic acid-sulfamethoxazole conjugate exhibited exceptional anti-inflammatory activity, effectively curtailing induced edema by 83.7%, a result akin to the reference anti-inflammatory drug indomethacin's performance (86.8%). Additionally, it demonstrated comparable COX-2 inhibition (75.8%) to the reference selective COX-2 inhibitor celecoxib that exhibited 77.1% inhibition at 10 µM concentration. To deepen our understanding, we employed molecular docking techniques to predict the binding interactions of competitive inhibitors with COX-2 and urease receptors. Additionally, MD simulations were carried out, confirming the stability of inhibitor-target complexes throughout the simulation period, devoid of significant conformational changes. Collectively, our research underscores the potential of coupling approved medicinal compounds to usher in novel categories of pharmacological agents, holding promise for addressing a wide spectrum of pathological disorders involving COX-2 and urease enzymes.Communicated by Ramaswamy H. Sarma.

Exploring the potential of propanamide-sulfonamide based drug conjugates as dual inhibitors of urease and cyclooxygenase-2: biological and their in silico studies.

Derivative synthesis has been a crucial method for altering the effects of already-approved medications, especially to lessen adverse effects and enhance results. Making use of this multi-target approach, a series of naproxen-sulfa drug conjugates was designed and synthesized. The newly designed conjugates were confirmed by spectroscopic techniques like IR, 1HNMR, 13CNMR, and elemental analysis. The conjugates were screened for anti-inflammatory, urease, and cyclooxygenase-2 (COX-2) inhibition. Naproxen conjugated with sulfanilamide, sulfathiazole, and sulfaguanidine was found potent and showed a competitive mode of urease inhibition, with IC50 (µM) values 6.69 ± 0.11, 5.82 ± 0.28, 5.06 ± 0.29, respectively. When compared to other screened conjugates, the naproxen-sulfamethoxazole conjugation showed better anti-inflammatory action by inhibiting induced edema by 82.8%, which is comparable to the medication indomethacin (86.8% inhibition). Whereas it exhibited 75.4% inhibition of COX-2 at 10 µM concentration which is comparable with the reference drug (celecoxib, 77.1% inhibition). Moreover, the binding modes of competitive inhibitors with the urease and COX-2 receptor were predicted through molecular docking studies and their stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and there were no conformational changes that occurred during simulation. The obtained results showed that the conjugates of approved therapeutic molecules may lead to the development of novel types of pharmacological agents in the treatment of several pathological disorders where urease and COX-2 enzymes are involved.

New Acetamide-Sulfonamide-Containing Scaffolds: Antiurease Activity Screening, Structure-Activity Relationship, Kinetics Mechanism, Molecular Docking, and MD Simulation Studies.

The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a result, drug conjugates are an active area of research and development in medicinal chemistry. This research demonstrates acetamide-sulfonamide scaffold preparation after conjugation of ibuprofen and flurbiprofen with sulfa drugs, and these scaffolds were then screened for urease inhibition. The newly designed conjugates were confirmed by spectroscopic techniques such as IR, 1HNMR, 13CNMR, and elemental analysis. Ibuprofen conjugated with sulfathiazole, flurbiprofen conjugated with sulfadiazine, and sulfamethoxazole were found to be potent and demonstrated a competitive mode of urease inhibition, with IC50 (µM) values of 9.95 ± 0.14, 16.74 ± 0.23, and 13.39 ± 0.11, respectively, and urease inhibition of 90.6, 84.1, and 86.1% respectively. Ibuprofen conjugated with sulfanilamide, sulfamerazine, and sulfacetamide, whereas flurbiprofen conjugated with sulfamerazine, and sulfacetamide exhibited a mixed mode of urease inhibition. Moreover, through molecular docking experiments, the urease receptor-binding mechanisms of competitive inhibitors were anticipated, and stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and that no conformational changes occurred during the simulation. The findings demonstrate that conjugates of approved therapeutic molecules may result in the development of novel classes of pharmacological agents for the treatment of various pathological conditions involving the urease enzyme.

International cooperation to fight cancer's late-stage presentation in low- and middle-income countries.

Cancer is becoming a massive public health burden in low- and middle-income countries (LMIC). 70% of all cancer deaths globally are attributed to LMIC while the incidence proportion is below 60%. The main reason for the higher mortality rate is "late-stage presentation" of patients with stage III or IV diseases when being diagnosed. Main reasons for this are limited (financial) resources, poor knowledge of health service provider about cancer, misbelieves and fear among patients as well as low health literacy rate. During the 1st International Conference on Hospital Partnerships, conducted by the German Agency for International Cooperation (GIZ), cancer specialists from seven LMIC and Germany discussed opportunities, challenges and solutions of the development of cancer services. Two days of in-depths discussion identified five topics to be playing a key role in the effort to reduce the cancer burden in LMIC: Health Policy & Financing, Barriers to Access, Capacity Building, Cancer Registries and Adapted Treatment Guidelines. By using mind-mapping technique, stakeholders, core topics, main and important topics were visualized and interconnections displayed. Many topics can be addressed through international cooperations but political willingness and commitment in the respective countries plays the crucial role. An essential contribution will be to assist policy makers in formulating and endorsing affordable and effective health policies. Another lesson learned from this workshop is the similarity of challenges among the participating representatives from different LMIC. The authors of this letter emphasize on the importance of building international long-term cooperations to advance oncology care on a global scale.

Influence of solvent selection and extraction methods on the determination of polyphenols, antioxidant, lipoxygenase and tyrosinase inhibition activities of Opuntia ficus-indica fruits peel and pulp collected from the Kingdom of Saudi Arabia (KSA).

The effect of extracting solvents used by two methods on the TPC, TFC, antioxidant as well as lipoxygenase, and tyrosinase inhibition activities of O. ficus-indica fruit (peel and pulp) were studied. The results manifest that extracts with solvent polarities showed different levels of polyphenols contents and antioxidant activities. The extracts acquired by the Soxhlet method were the most fascinating. Interestingly, peel extracts contain more polyphenols than pulp and showed activities. Lipoxygenase and tyrosinase inhibitory activity of the fruit peel and pulp extracts was reported for the first time. The promising results obtained prompted to the formulation of a stable phytocosmetic emulsion system loaded with 1% pre-concentrated peel extract, aiming to revive facial skin properties. The efficacy of the formulations was determined through SPF and UVA protection factors. To the in vitro safety assessment CAM-TBS, HET-CAM, and red blood cell tests were achieved. Importantly, the formulation did not induce any toxicity.

Level of patient satisfaction with online psychiatric outdoor services.

BACKGROUND: The COVID-19 global pandemic exposed gaps in the treatment of common physical and mental disorders that had to do with things like lockdowns, poor convenience, fear of contracting COVID, and economic constraints. Hence, to address these treatment gaps while also limiting exposure to the COVID-19 infection, telemedicine in the form of telephone and internet consultations has increasingly become the recourse around the world. Our center adopted this trend and also launched a telepsychiatry initiative in order to better cater to the needs of patients with pre-existing mental health disorders and to ensure regular follow-ups and compliance with prescription regiments. AIM: The present study aimed to assess the level of patient satisfaction with the online psychiatric services/telepsychiatry. METHODS: The sample consisted of 100 patients with pre-existing mental health disorders. This was a cross-sectional study lasting 6 months. The DigiDoc app by Hospital Information Software (HIS) software, which is used to manage a patients appointment schedule, relevant clinical and lab details, along with follow-up prescriptions, was used to follow the selected patients for the purpose of this study. This software also provides a digital platform for video calls for online consultation. The Client Satisfaction Questionnaires-8 (CSQ-8) was employed to collect patient data for analysis. RESULTS: The mean total CSQ-8 score of the study sample was 21.015.80 (832), which corresponds to a low-to-moderate level of satisfaction with online psychiatric services/telepsychiatry. Most patients (45%) reported low satisfaction levels, followed by 37% who reported moderate levels of satisfaction. Only 18% of patients reported higher satisfaction with telepsychiatry. CONCLUSION: Despite the psychiatrists ability to provide adequate professional advice and psychoeducation through online psychiatric services, patients level of satisfaction proved moderate-to-low. This suggests a need to design standard protocols and guidelines in the search and provision of consultation services on online psychiatric service platforms that could help enhance patients levels of satisfaction.

Awake Surgery for Lesional Epilepsy in Resource-Limited Settings: Case Report and Review of Literature

Epilepsy surgery is a well-established treatment for drug-resistant epilepsy, with awake craniotomy being used in certain cases to remove epileptogenic foci while preserving crucial brain functions. We are presenting the first reported case from Pakistan of a 19-year-old woman who underwent awake epilepsy surgery to treat cortical dysplasia. She had a history of generalized tonic-clonic seizures since her childhood and was referred to our clinic due to an increase in seizure frequency. EEG and MRI identified the epileptogenic focus in the right parieto-temporal region. The patient underwent a neuro-navigation guided awake craniotomy and an excision of the epileptogenic focus in the right parieto-temporal region. The procedure was carried out using a scalp block and dexmedetomidine for conscious sedation, enabling the patient to remain awake throughout the surgery. Intraoperative mapping and electrocorticography were used for complex multidisciplinary care. Post-resection corticography showed no spikes along the resected margins. The patient was discharged without any complications and remained free of symptoms a year after the surgery. Awake epilepsy surgery is a viable option for removing epileptogenic foci while preserving vital cognitive functions. However, it is seldom used in low- and middle-income countries such as Pakistan. The successful outcome of this case underscores the need for greater awareness and availability of epilepsy surgery in resource-limited settings. Cost-effective measures, such as using small subdural strips for intraoperative localization, can be implemented.

MF-Storm: a maximum flow-based job scheduler for stream processing engines on computational clusters to increase throughput.

Background: A scheduling algorithm tries to schedule multiple computational tasks on a cluster of multiple computing nodes to maximize throughput with optimal utilization of computational and communicational resources. A Stream Processing Engine (SPE) is deployed to run streaming applications (computational tasks) on a computational cluster which helps execution and coordination of these applications. It is observed that there is a gap in the optimal mapping of a computational and communicational load of a streaming application on the underlying computational and communication power of the resources (cluster). Frequently communicated tasks are scheduled at different processing nodes with relatively slow communicating links. This increases network latency with a decrease in resource utilization. Hence, reduces the achieved throughput of the cluster significantly. Methods: MF-Storm, a max-flow min-cut based job scheduler is presented to achieve a near-optimum schedule to maximize throughput. It schedules a streaming application by considering the processing, communication demands, available computational and communicational resources in a heterogeneous cluster, dynamically with minimized scheduling cost. To keep the scheduling cost minimum, the scheduler is built in a pipeline with two major stages: in the first stage, the application's tasks graph is partitioned using the max-flow min-cut algorithm to minimize inter-partition traffic, and in the second stage, these partitions are assigned to computing nodes according to the computational power of the cluster's nodes. Results: Extensive experiments were done to evaluate the performance of MF-Storm using different topologies with multiple scenarios on a physical cluster implementation. Results showed on average 148% improvement in throughput with 30% less computational resources as compared to different state-of-the-art schedulers.

The Role of High-output His-bundle Pacing During Atrioventricular Node Ablation.

Atrioventricular (AV) junction ablation (AVJA) is an acceptable strategy to control the heart rate in atrial fibrillation (AF) with a high procedural success rate. However, a small subset of patients pose a technical challenge with the standard right-sided approach. High-output His-bundle pacing has been shown to help localize the His bundle in a difficult-to-ablate AV junction. We report a case series of patients with difficult-to-ablate AVJA and present strategies to troubleshoot them. In this small series of patients, we found that high-output His pacing can be an effective alternative for successfully localizing the AVJA site. In this series, we also observed that an inability to achieve His capture from the right side can predict failure of ablation using the standard right-sided approach and the consequent need for a left-sided approach.