Prevalence and Associations of Depression in Parents of Children With Congenital Talipes Equinovarus: A Single-Centre Study.

INTRODUCTION: Congenital talipes equinovarus (CTEV) is a congenital deformity that requires weekly visits to the hospital for manipulation and corrective cast application, followed by an intensive bracing regimen requiring multiple visits to the hospital spread over the years. Parents of children with clubfoot are known to undergo a range of negative emotions. The objective of this study was to identify the prevalence of depression and the factors associated with depression in parents of children with idiopathic CTEV. METHODS: This cross-sectional study consecutively enrolled 190 parents of children with idiopathic CTEV undergoing treatment at King George Medical University. Parents with conditions that preclude the assessment of mental status were not included. These conditions include a history of head injury or psychiatric illness, parents with ongoing treatment of psychiatric illness, ongoing chronic illness, chronic neurological disease, and parents with clinically established intellectual disability. Information was recorded on certain parent-related characteristics and certain child-related characteristics. Parent-related information included age and sex of the parent, religion, area of residence, number of children in the family, degree of perceived social support (using the Multidimensional Scale of Perceived Social Support, MSPSS), level of education, socio-economic status, depression subscale score of DASS 21 (Depression, Depression Anxiety, and Stress Scale -21), chronic pain (visual analogue scale, VAS), family history of clubfoot or depression, and level of stress caused by a major life event during the past year using the Presumptive Stressful Life Event Scale (PSLES). Child-related information included the sex of the child, phase of treatment (casting or bracing), limb involvement (unilateral or bilateral), relapse of the deformity, and Pirani score of the deformity. Bivariate analysis and logistic regression were used to identify factors associated with a score ≥10 on the depression subscale of DASS 21. RESULTS: One hundred forty-five subjects were males (76.3%). The mean age of the enrolled parents was 28.47±4.89 years. The mean score on the depression subscale of DASS-21 was 4.87±6.3. Thirty-two parents (16.8%) had a score of ≥10 on the depression subscale of the DASS-21. On bivariate analysis, female sex, being Hindu, having studied up to class 12th, relapse, MSPSS score, and PSLES score were found to be associated with a score ≥10 on the depression subscale of the DASS-21. On logistic regression, female sex, lack of graduate education and above, and MSPSS scores were found to be significantly associated with a score of ≥10 on the depression subscale of the DASS 21 score. CONCLUSION: The prevalence of depression in parents of children with idiopathic clubfoot was 16.8%. Female gender, lack of college education, and the level of perceived social support (MSPSS) are independently associated with a score ≥10 on the depression subscale of DASS 21. We recommend screening parents of children with clubfoot and referring those with abnormal scores to a psychiatrist for a confirmed diagnosis.

pH-Sensitive Hydrogels Fabricated with Hyaluronic Acid as a Polymer for Site-Specific Delivery of Mesalamine.

Hydrogels with the main objective of releasing mesalamine (5-aminosalicylic acid) in the colon in a modified manner were formulated in the present work using a free-radical polymerization approach. Different ratios of hyaluronic acid were cross-linked with methacrylic and acrylic acids using methylenebis(acrylamide). The development of a new polymeric network and the successful loading of drug were revealed by Fourier transform infrared spectroscopy. Thermogravimetric analysis demonstrated that the hydrogel was more thermally stable than the pure polymer and drug. Scanning electron microscopy (SEM) revealed a rough and hard surface which was relatively suitable for efficient loading of drug and significant penetration of dissolution medium inside the polymeric system. Studies on swelling and drug release were conducted at 37 °C in acidic and basic conditions (pH 1.2, 4.5, 6.8, and 7.4, respectively). Significant swelling and drug release occurred at pH 7.4. Swelling, drug loading, drug release, and gel fraction of the hydrogels increased with increasing hyaluronic acid, methacrylic acid, and acrylic acid concentrations, while the sol fraction decreased. Results obtained from the toxicity study proved the formulated system to be safe for biological systems. The pH-sensitive hydrogels have the potential to be beneficial for colon targeting due to their pH sensitivity and biodegradability. Inflammatory bowel disease may respond better to hydrogel treatment as compared to conventional dosage forms. Specific amount of drug is released from hydrogels at specific intervals to maintain its therapeutic concentration at the required level.

Human Immunodeficiency Virus Type-1 Genetic Diversity and Drugs Resistance Mutations among People Living with HIV in Karachi, Pakistan.

The human immunodeficiency virus type-1 epidemic in Pakistan has significantly increased over the last two decades. In Karachi, Pakistan, there is a lack of updated information on the complexity of HIV-1 genetic diversity and the burden of drug resistance mutations (DRMs) that can contribute to ART failure and poor treatment outcomes. This study aimed to determine HIV-1 genetic diversity and identify drug-resistance mutations among people living with HIV in Karachi. A total of 364 HIV-positive individuals, with a median age of 36 years, were enrolled in the study. The HIV-1 partial pol gene was successfully sequenced from 268 individuals. The sequences were used to generate phylogenetic trees to determine clade diversity and also to assess the burden of DRMs. Based on the partial pol sequences, 13 distinct HIV-1 subtypes and recombinant forms were identified. Subtype A1 was the most common clade (40%), followed by CRF02_AG (33.2%). Acquired DRMs were found in 30.6% of the ART-experienced patients, of whom 70.7%, 20.7%, and 8.5% were associated with resistance to NNRTIs, NRTIs, and PIs, respectively. Transmitted DRMs were found in 5.6% of the ART-naïve patients, of whom 93% were associated with resistance against NNRTIs and 7% to PIs. The high prevalence of DRMs in ART-experienced patients poses significant challenges to the long-term benefits and sustainability of the ART program. This study emphasizes the importance of continuous HIV molecular epidemiology and drug resistance surveillance to support evidence-based HIV prevention, precise ART, and targeted AIDS care.

Advancing Cardiovascular Risk Assessment with Artificial Intelligence: Opportunities and Implications in North Carolina.

Cardiovascular disease mortality is increasing in North Carolina with persistent inequality by race, income, and location. Artificial intelligence (AI) can repurpose the widely available electrocardiogram (ECG) for enhanced assessment of cardiac dysfunction. By identifying accelerated cardiac aging from the ECG, AI offers novel insights into risk assessment and prevention.

Prevalence and predictors of mitral annular disjunction and ventricular ectopy in mitral valve prolapse.

BACKGROUND: Mitral annular disjunction (MAD) is associated with ventricular arrhythmia in mitral valve prolapse (MVP). The proportional risk from MAD and other predictors of ventricular arrhythmia in MVP has not been well characterized. OBJECTIVE: This study aimed to identify predictors of complex or frequent ventricular ectopy (cfVE) in MVP and to quantify risk of cfVE and mortality in MVP with MAD. METHODS: We studied 632 adult patients with MVP on transthoracic echocardiography at the University of North Carolina Medical Center from 2016 to 2019 (median age, 64 [interquartile range, 52-74] years; 52.7% female; 16.3% African American). Resting and ambulatory electrocardiograms were used to identify cfVE. RESULTS: MAD was present in 94 (14.9%) patients. Independent associations of MAD were bileaflet prolapse (odds ratio [95% CI], 4.25 [2.47-7.33]; P < .0001), myxomatous valve (2.17 [1.27-3.71]; P = .005), absence of hypertension (2.00 [1.21-3.32]; P = .007), electrocardiogram inferior or lateral lead T-wave inversion (2.07 [1.23-3.48]; P = .006), and female sex (1.99 [1.21-3.25]; P = .006). cfVE was frequent with MAD (39 [41.5%] vs 93 [17.3%] without; P < .0001). Independent cfVE predictors were MAD (hazard ratio [95% CI], 2.23 [1.47-3.36]; P = .0001), bileaflet prolapse (1.86 [1.25-2.76]; P = .002), heart failure (1.79 [1.16-2.77]; P = .009), lower left ventricular ejection fraction (0.14 [0.03-0.61]; P = .009), coronary artery disease (1.60 [1.05-2.43]; P = .03), and inferior or lateral lead T-wave inversion (1.51 [1.03-2.22]; P = .03). After a median of 40 (33-48) months, there was increased mortality with MAD (P = .04). CONCLUSION: MAD in MVP is associated with bileaflet or myxomatous MVP, absence of hypertension, T-wave inversion, and female sex. There is increased cfVE and mortality with MAD, highlighting the need for closer follow-up of these patients.

Shift in SARS-CoV-2 variants of concern from Delta to Omicron was associated with reduced hospitalizations, increased risk of breakthrough infections but lesser disease severity.

BACKGROUND: COVID-19 epidemiology changed with the emergence of SARS-CoV-2 variants of concern (VOC). Pakistan administered mostly inactivated vaccines. We investigated the association between VOC and breakthrough infections in a mixed-vaccination-status population of Karachi. METHODS: We investigated SARS-CoV-2 VOC tested in 392 respiratory specimens collected between May and December 2021. Data for age, sex, hospital admission, vaccinations, together with CT values of the diagnostic PCR test were analyzed. RESULTS: The median age of COVID-19 cases tested was 40 (27-57) years and 43.4% were female. Delta variants were most common (56.4%) followed by Alpha (15.9%), Omicron (12.2%), Beta/Gamma (11.3%), and others (4.3%). Eighteen percent of cases were hospitalized whereby, predominant VOC were Beta/Gamma (40.8%), Alpha (35.2%) and Delta (22.5%). Overall, 55.4% of individuals were fully vaccinated, 7.4% were partially vaccinated and 37.2% were unvaccinated. Most (74.6%) inpatients were unvaccinated. Vaccines comprised inactivated (85.34%), single-shot vector (8.62%), two-shot vector (3.02%) and mRNA (3.02%) types. Omicron variants showed lower viral loads as compared to Alpha, Beta/Gamma, and Delta (p = 0.017). The risk of infection with Delta and Omicron variants was higher, 8 weeks after vaccination. The majority of those with breakthrough infections after receiving inactivated vaccines acquired COVID-19 within 4 months of vaccination. CONCLUSION: Our data highlights the shifting of VOC from Delta to Omicron during 2021 and that COVID-19 vaccinations reduced both hospitalizations and viral transmission. It informs on the increased risk of breakthrough infection within 8 weeks of vaccination, indicating the need for booster vaccinations.

Isolated Bilateral Upper Limb Amelia - A Rare Case Report.

Introduction: Congenital upper limb amelia is one of the extremely rare conditions. It is defined as a complete absence of upper limbs. It may present as isolated or with other associated anomalies. Case Report: We present a case of a 2-year-old male child with congenital complete absence of bilateral upper limb. This male child was born after four female children. With the advancement in modern-era prenatal diagnostic facilities and a better understanding of fetal-maternal drug pharmacology, such cases are rare entity. Conclusion: Amelia is a very rare and challenging situation for clinicians. Regular prenatal checkup and knowledge of maternal and fetal drug interactions during pregnancy are key factors for prevention.

Unraveling the role of cloud computing in health care system and biomedical sciences.

Cloud computing has emerged as a transformative force in healthcare and biomedical sciences, offering scalable, on-demand resources for managing vast amounts of data. This review explores the integration of cloud computing within these fields, highlighting its pivotal role in enhancing data management, security, and accessibility. We examine the application of cloud computing in various healthcare domains, including electronic medical records, telemedicine, and personalized patient care, as well as its impact on bioinformatics research, particularly in genomics, proteomics, and metabolomics. The review also addresses the challenges and ethical considerations associated with cloud-based healthcare solutions, such as data privacy and cybersecurity. By providing a comprehensive overview, we aim to assist readers in understanding the significance of cloud computing in modern medical applications and its potential to revolutionize both patient care and biomedical research.

A Novel Approach of Polyvinyl Alcohol/Acrylic Acid Based Hydrogels for Controlled Delivery of Diclofenac Sodium.

AIM AND OBJECTIVE: The aim of this study was to prepare polyvinyl alcohol/acrylic acid (PVA/AA) hydrogels for the controlled release of diclofenac sodium and to develop PVA/AA hydrogels as controlled release carriers to overcome not only the side effects of diclofenac sodium but also sustain its release for an extended period. BACKGROUND: Diclofenac sodium is employed for relieving pain and fever. The half-life of diclofenac sodium is very short (1-2 h). Hence, multiple intakes of diclofenac sodium are required to maintain a constant pharmacological action. Multiple GI adverse effects are produced as a result of diclofenac sodium intake. METHOD: A free radical polymerization technique was used for crosslinking PVA with AA in the presence of APS. EGDMA was used as a cross-linker. FTIR and XRD confirmed the preparation and loading of the drug by prepared hydrogels. An increase in the thermal stability of PVA was shown by TGA and DSC analysis. Surface morphology was investigated by SEM. Similarly, water penetration and drug loading were demonstrated by porosity and drug loading studies. The pH-sensitive nature of PVA/AA hydrogels was investigated at different pH values by swelling and drug release studies. RESULTS: The development and drug loading of PVA/AA hydrogels were confirmed by FTIR and XRD analysis. TGA and DSC indicated high thermal stability of prepared hydrogels as compared to unreacted PVA. SEM indicated a hard and compact network of developed hydrogels. The swelling and drug release studies indicated maximum swelling and drug release at high pH as compared to low pH values, indicating the pH-sensitive nature of prepared hydrogels. Moreover, we demonstrated that drug release was sustained for a prolonged time in a controlled pattern by prepared hydrogels by comparing the drug release of the developed hydrogels with the commercial product Cataflam. CONCLUSION: The results indicated that prepared PVA/AA hydrogels can be used as an alternative approach for the controlled delivery of diclofenac sodium.

The Effect of Vitamin D Deficiency as a Risk Factor of Early Fragmentation in Legg-Calve-Perthes Disease: A Prospective Study.

INTRODUCTION: Legg-Calve-Perthes disease (LCPD) is a disorder involving the hips in young children of preschool and school-going age groups, more common in 4-8 years. The insufficient blood supply to the femoral head is the main reason behind various etiologic theories. Multiple factors affect the natural progression of the disease. The natural progression of the disease involves early avascular necrosis, fragmentation, reconstitution, and healed stages. In the fragmentation stage, the bony epiphysis begins to fragment, and the subchondral radiolucent zone (crescent sign) is the result of a subchondral stress fracture, which later on determines the extent of a necrotic fragment of the femoral head. These changes later contribute to changes in the shape of the femur head and the extent of deformity. As vitamin D plays a vital role in the onset of the fragmentation stage, we conducted a study to assess the effect of vitamin D deficiency as a risk factor for early fragmentation in Legg-Calve-Perthes disease. METHODS: In our study, 50 patients aged 4-12 years were examined over three years and classified according to Catterall and Herring's lateral pillar classification; the length of the fragmentation stage and the vitamin D level were considered. A vitamin D level of less than 20 ng/mL was labeled as the deficient group, 20-30 ng/mL as the insufficient group, and more than 30 ng/mL as the sufficient (normal) group. RESULTS: The critical fragmentation stage was significantly longer (more than 12 months) in vitamin D deficiency (34%), leading to a higher risk of deformity and extrusion of the femoral head, which led to higher rates of surgical intervention and containment procedures. CONCLUSION: The fragmentation stage is critical in the course of LCPD. Vitamin D levels play a vital role in predicting the prognostic of LCPD, and it should be measured in all patients of LCPD. Patients with normal vitamin D levels have a comparatively shorter fragmentation stage duration than patients with insufficient or deficient levels, leading to a lesser duration of femoral head damage.

Bilateral Van Neck-Odelberg Disease: A Case Report.

Van Neck-Odelberg disease, also known as ischiopubic osteochondritis, is a rare cause of buttock or groin pain in the pediatric age group. The challenge in its diagnosis is due to its radiologic similarity. Ischiopubic synchondrosis occurs in childhood and is seen before the fusion of the pubis and ischium. With the advancement of age toward skeletal maturity, ischiopubic synchondrosis reduces in size and gradually vanishes due to synostosis or bony union. Here, we report the case of a 13-year-old girl who came to our outpatient department with complaints of bilateral groin pain for one year. After a thorough evaluation, she was diagnosed with a case of bilateral Van Neck-Odelberg disease, or ischiopubic osteochondritis, and conservative management was planned. Closure of ischiopubic synchondrosis varies with age and is usually finished before puberty. In a typical scenario, such fusion of the pubis and ischium does not lead to any clinical symptoms. However, in a few instances, children may experience some pain in the groin, hip, or gluteal region, which results in restricted movements at the hip joint and can lead to limping while walking. Van Neck-Odelberg disease is rare in children, causing pain in the groin region. As it is a rare condition, diagnosis is often missed. The radiological appearance suggests many differential diagnoses, such as a stress fracture, neoplasm, or infection. Prompt diagnosis and treatment can relieve the symptoms.

A Rare Case of Fungal Osteomyelitis of the Distal Tibia in a Pediatric Patient.

Staphylococcus aureus infection is the most common cause of osteomyelitis. Over 100,000 fungal species have been described; only 150 are pathogenic to humans. These opportunistic infections frequently enter the body due to a decrease in host defense or through an invasive gateway, such as a dental extraction or skin discontinuity due to trauma. Symptoms and radiological examination often mimic those of other etiologies, which can lead to substantial delays in treatment. Our case is a 13-year-old healthy boy with no history of immune incompetency who presented to us with complaints of pain and swelling over his left ankle and leg with an on-and-off history of fever for 15 days. Based on his history and examination, he is diagnosed as having sub-acute osteomyelitis of the distal tibia with septic arthritis. The bacterial culture has no growth; however, the potassium hydroxide mount came positive for fungal elements having hyphae and pseudohyphae, and the fungal culture came positive for Candida. Management of fungal infections is challenging as they have infrequent involvement in bones. Fungal osteomyelitis is considered a rare entity in the literature, and the current case is studied for the management and diagnosis of a rare variant of osteomyelitis in the pediatric population. The treatment guidelines vary based on the identified organism and the duration of treatment. Debridement of fungal osteomyelitis or septic arthritis includes removing sinus tracts, evaluation for squamous cell carcinoma, bony and soft-tissue debridement, and antibiotic or antifungal bead placement. The spectrum of osteomyelitis ranges from Staphylococcus aureus organisms to tumors; therefore, it is necessary to investigate every spectrum of the disease, and fungal infections should be considered differential even though they are a rare entity. Early diagnosis, surgical debridement, and proper antifungal treatment based on fungal species lead to better clinical outcomes and results.

Covid-19 related isolation and risk of post-traumatic stress disorder in patients presenting to tele-clinics at a private tertiary care hospital in Karachi.

The objective of this study was to assess the psychological impact of isolation on individuals with Covid-19 and determine the experiences of people in isolation. All adults with Covid-19 who reported to the infectious disease tele-clinic were included in the study; participants were sent the survey form via email. The email was sent to 146 people and 47 responses were received. IES-R questionnaire was submitted to all individuals on Day 7 of quarantine, along with a qualitative questionnaire. The mean score on IES-R for all the respondents was 18.77. Out of 47 participants, for 6 (12.8%) PTSD was a clinical concern, 3 (6.4%) participants had a probable diagnosis of PTSD, and 6 (12.8%) participants scored high enough to suppress immune function. The majority of participants reported stress due to confinement in an isolated space and interruption in daily routine, specifically work-related routine. Praying, meditation, and having social support helped the participants cope with the isolation.

Health-Related Quality of Life in Children and Adolescents With Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis.

OBJECTIVE: To conduct a systematic review (SR) and meta-analysis (MA) on health-related quality-of-life (QoL) and associated factors among children/adolescents with congenital adrenal hyperplasia (CAH). METHOD: Following registration in the PROSPERO International Prospective Register of Systematic Reviews(reg no: CRD42022313389), Google Scholar, PubMed, LILACS, Cochrane, and Scopus databases were searched up to March 5, 2022, using predefined search strategy/MESH terms to identify original studies describing/assessing self-reported/parent-reported health-related QoL in patients with CAH ≤21 years. Methodological quality was assessed by Newcastle-Ottawa Quality Assessment Scale (NOS), and heterogeneity by I2 statistics. MA assessed mean difference (MD) in QoL between children/adolescents with CAH and healthy children/adolescents. RESULTS: Among 1308 publications, the 12 studies eligible for the SR (CAH n = 781) showed NOS scales of 3 to 7/9, and the 6 eligible for MA (CAH n = 227) showed moderate-considerable heterogeneity. MA showed that parent-reported psychosocial QoL (MD 9.9 [-12.6,7.3], P ≤ .001) {consisting of school (MD 7.4[-12.2, -2.5], P = .003), emotional (MD 5.6 [-10.2, -0.9], P = .02) and social domains (MD 4.3 [-8.1, -0.5], P = .03), and self-reported school domain QoL (MD 8.5 [-15.9, -1.2], P = .02) was lower in children/adolescents with CAH while parent-reported and self-reported physical QoL were similar to controls.Factors associated with lower QoL among children/ adolescents with CAH included poor disease control, poor medication compliance, and complications including hyperpigmentation, virilization, hypertension, hospital admission, and urinary incontinence. CONCLUSION: Based on available data, children/adolescents with CAH had preserved physical QoL but impaired psychosocial QoL, especially in the school domain. Factors associated with lower QoL included poor disease control and disease/treatment-related complications. There is a need for further high-quality research that investigates the relationship between disease control, provision of psychosocial support, and improvement in QoL in children/adolescents with CAH.

A large abdominal cyst as a manifestation of pelviureteric junction obstruction in a neonate.

Intraabdominal cystic lesions diagnosed during antenatal period are uncommon. They are found to have varying origins, with renal tract being the most common site. Rarely, a large unilateral cystic lesion of renal origin is caused by Pelviureteric junction obstruction, crossing the midline, leading to compression of the contralateral kidney. We present a case of a neonate who was diagnosed with a large abdominal cyst in the antenatal period. The cyst persisted and crossed the midline causing hydronephrosis on the contralateral side. This is an unusual presentation of a commonly occurring condition, usually such large cyst at birth origins from alimentary tract rather renal system. It is important to understand unusual presentations of intraabdominal lesions and the associated pathology. It is mandatory to rule out renal obstruction, if there is any decompression of renal function, it is mandatory to save renal function till the time of definitive surgery.

Exploring the relationship between SARS-CoV-2 variants, illness severity at presentation, in-hospital mortality and COVID-19 vaccination in a low middle-income country: A retrospective cross-sectional study.

Background and Aims: COVID-19 morbidity and mortality varied globally through the pandemic. We studied the relationship of SARS-CoV-2 variants of concern (VOC) with COVID-19 severity and mortality among hospitalized patients in Pakistan. Methods: A retrospective review of clinical, laboratory, and vaccination data of 197 COVID-19 adult patients at the Aga Khan University Hospital, Karachi between April 2021, and February 2022 was performed. SARS-CoV-2 VOC identified in respiratory samples were analyzed. Univariate and multivariate analysis was conducted to identify factors associated with COVID-19 outcomes. Results: The median age of cases was 55 years and 51.8% were males. Twenty-four percent of females were pregnant. Of COVID-19 cases, 48.2% had nonsevere disease, while 52.8% had severe/critical disease. Hypertension (48%) and diabetes mellitus (41%) were common comorbids. SARS-CoV-2 VOC identified comprised; Omicron (55.3%), Beta (14.7%), Alpha (13.7%), Delta (12.7%), and Gamma (3.6%) variants. Most (59.7%) study subjects were unvaccinated. Of vaccines, 88% had received inactivated virus COVID-19 vaccines. Increased risk of severe disease was associated with age ≥50 years (odds ratio [OR]: 5.73; 95% confidence interval [CI]: [2.45-13.7]), as well as with diabetes mellitus (OR: 4.24; 95% CI: [1.82-9.85]). Full vaccination (OR: 0.25; 95% CI: [0.11-0.58]) or infection with Omicron (OR: 0.42; 95% CI: [0.23-0.74]) was associated with reduced disease severity. The risk of mortality increased with age ≥50 years (OR: 5.07; 95% CI: [1.92-13.42]) and a history of myocardial infarction (OR: 5.11; 95% CI: [1.45-17.93]) whilst, infection with Omicron was found to reduce the risk (OR: 0.22; 95% CI: [0.10-0.53]). Conclusion: Our study describes the relationship between the severity of COVID-19, in-hospital mortality in relation to SARS-CoV-2 variants, and the impact of COVID-19 vaccination in Pakistan. Outcomes were more favorable in younger individuals, after vaccinations and with Omicron variant infections. Most cases received inactivated virus vaccines therefore these data highlight the protection provided against severe COVID-19.

Humoral and T cell responses to SARS-CoV-2 reveal insights into immunity during the early pandemic period in Pakistan.

BACKGROUND: Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP). METHODS: HG and COVID-19 participants were recruited between October 2020 and May 2021. Pre-pandemic sera was collected before 2018. IgG antibodies against Spike and its Receptor Binding Domain (RBD) were determined by ELISA. Virus neutralization activity was determined using a PCR-based micro-neutralization assay. T cell - IFN-γ activation was assessed by ELISpot. RESULTS: Overall, the magnitude of anti-Spike IgG antibody levels as well as seropositivity was greatest in COVID-19 cases (90%) as compared with HG (39.8%) and PP (12.2%). During the study period, Pakistan experienced three COVID-19 waves. We observed that IgG seropositivity to Spike in HG increased from 10.3 to 83.5% during the study, whilst seropositivity to RBD increased from 7.5 to 33.3%. IgG antibodies to Spike and RBD were correlated positively in all three study groups. Virus neutralizing activity was identified in sera of COVID-19, HG and PP. Spike reactive T cells were present in COVID-19, HG and PP groups. Individuals with reactive T cells included those with and without IgG antibodies to Spike. CONCLUSIONS: Antibody and T cell responses to Spike protein in individuals from the pre-pandemic period suggest prior immunity against SARS-CoV-2, most likely from cross-reactive responses. The rising seroprevalence observed in healthy individuals through the pandemic without known COVID-19 may be due to the activation of adaptive immunity from cross-reactive memory B and T cells. This may explain the more favourable COVID-19 outcomes observed in this population.

Old drug, new tricks: polymer-based nanoscale systems for effective cytarabine delivery.

Cytarabine, an antimetabolite antineoplastic agent, has been utilized to treat various cancers. However, because of its short half-life, low stability, and limited bioavailability, achieving an optimal plasma concentration requires continuous intravenous administration, which can lead to toxicity in normal cells and tissues. Addressing these limitations is crucial to optimize the therapeutic efficacy of cytarabine while minimizing its adverse effects. The use of novel drug delivery systems, such as polymer-based nanocarriers have emerged as promising vehicles for targeted drug delivery due to their unique properties, including high stability, biocompatibility, and tunable release kinetics. In this review, we examine the application of various polymer-based nanocarriers, including polymeric nanoparticles, polymeric micelles, dendrimers, polymer-drug conjugates, and nano-hydrogels, for the delivery of cytarabine. The article highlights the limitations of conventional cytarabine administration which often lead to suboptimal therapeutic outcomes and systemic toxicity. The rationale for using polymer-based nanocarriers is discussed, highlighting their ability to overcome challenges by providing controlled drug release, improved stability, and enhanced targeting capabilities. In summary, this review offers a valuable resource for drug delivery scientists by providing insights into the design principles, formulation strategies, and potential applications of polymer-based nanocarriers that can enhance the therapeutic efficacy of cytarabine.

Late-Presenting Septic Arthritis of the Hip in Children: Variations in Presentation and a Review of 25 Hips After Surgical Debridement.

INTRODUCTION: The septic arthritis of the hip (SAH) is one of the most common musculoskeletal infections occurring in pediatric populations requiring urgent intervention. This study discusses the myriad of clinical and radiological presentations of late-presenting SAH in children and the outcomes of surgical management. METHODS: After ethical approval, we did retrospective reviews of children treated for late-presenting SAH (after five days of symptoms). We excluded late cases with established sequelae. We recorded age, duration of symptoms, clinical evaluation, and radiographs. We evaluated the final results clinically and radiologically. RESULTS: Twenty-four patients with 25 hips were eligible for evaluation. At presentation, all had decreased or painful hip movements, but none had a fever. Radiographs revealed the following changes: hip dislocation (four), capital femoral slip (seven), proximal femur/neck osteomyelitis (six), pathological fractured neck femur (two), iliac osteomyelitis (two), and early arthritic changes (two). Hip arthrotomy was done in all cases. Frank pus was found in 21 (84%) cases. Cases with capital slip and fractured neck femur required fixation with two smooth K-wires. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated in three patients and tuberculosis in two cases. Clinical outcomes showed 14 patients with poor outcomes, eight with fair, and two with good. Avascular necrosis (AVN) of the femoral head was noted in 14 hips and complete femoral head resorption in nine. CONCLUSIONS: The late-presenting SAH in children has a myriad of presentations including dislocation and capital slip with unsatisfactory outcome. However, ongoing local infective processes may necessitate debridement. With limited salvage options available at the sequelae stage, awareness and training for early diagnosis and treatment may be the best way to improve the scenario. We recommend future multicenter randomized studies of predictive factors and indications of arthrotomy in late presenters.

General Public Knowledge, Attitude, and Practice Regarding the Impact of Air Pollution and Cardiopulmonary Diseases in Jeddah, Saudi Arabia.

Introduction Air pollution is a critical public health issue associated with various respiratory and cardiovascular diseases. The lungs and heart are the organs most affected by air pollution, and damage to these organs is strongly associated with inhaled particulate matter produced by burning fossil fuels. Household and ambient air pollution have been closely linked to lower respiratory infections, with ambient air pollution alone estimated to be responsible for millions of deaths globally each year. Therefore, this study aimed to assess the general public knowledge attitude and practice regarding air pollution and cardiopulmonary morbidity in Jeddah, Saudi Arabia. Methods The study was conducted in Saudi Arabia using a self-administered questionnaire distributed through popular social media apps. A snowball sampling technique was used, including only Saudi citizens aged 18 or older. The questionnaire consisted of 30 questions derived from a comprehensive literature review on the subject matter. Questions were validated through face validity, pilot testing, and Cronbach's alpha reliability measurement. The questionnaire included questions on demographic data, knowledge of air pollution, the relationship between air pollution and cardiopulmonary diseases, and attitudes and practices toward lowering exposure to air pollution. Results The study included 649 participants, with a mean age of 32.11 ± 13.47 years, and over half were females (54.7%). Most participants were aware of outdoor and indoor air pollution, but only a tiny percentage recognized cooking as a primary indoor source of pollution. However, the majority believed that indoor pollution could contribute to outdoor pollution. Participants associated air pollution with cardiopulmonary diseases, mainly secondhand tobacco smoke and outdoor air pollution caused by factories and industrial facilities. Knowledge and practice levels varied, with older individuals, females, and those in non-health-related occupations having higher levels of knowledge. Positive attitudes, particularly believing that moving to a less polluted area improves health, were associated with better knowledge. Females exhibited better air pollution-related practices, and there was a positive correlation between knowledge and practice scores. Conclusion The study highlighted the need for targeted public health campaigns to improve awareness and promote healthier practices, particularly among young adults, to mitigate the potential health impacts of air pollution, especially cardiopulmonary health.