mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice.

OBJECTIVE: Elastin deficiency because of heterozygous loss of an ELN allele in Williams syndrome causes obstructive aortopathy characterized by medial thickening and fibrosis and consequent aortic stiffening. Previous work in Eln-null mice with a severe arterial phenotype showed that inhibition of mTOR (mechanistic target of rapamycin), a key regulator of cell growth, lessened the aortic obstruction but did not prevent early postnatal death. We investigated the effects of mTOR inhibition in Eln-null mice partially rescued by human ELN that manifest a less severe arterial phenotype and survive long term. APPROACH AND RESULTS: Thoracic aortas of neonatal and juvenile mice with graded elastin deficiency exhibited increased signaling through both mTOR complex 1 and 2. Despite lower predicted wall stress, there was increased phosphorylation of focal adhesion kinase, suggestive of greater integrin activation, and increased transforming growth factor-ß-signaling mediators, associated with increased collagen expression. Pharmacological blockade of mTOR by rapalogs did not improve luminal stenosis but reduced mechanosignaling (in delayed fashion after mTOR complex 1 inhibition), medial collagen accumulation, and stiffening of the aorta. Rapalog administration also retarded somatic growth, however, and precipitated neonatal deaths. Complementary, less-toxic strategies to inhibit mTOR via altered growth factor and nutrient responses were not effective. CONCLUSIONS: In addition to previously demonstrated therapeutic benefits of rapalogs decreasing smooth muscle cell proliferation in the absence of elastin, we find that rapalogs also prevent aortic fibrosis and stiffening attributable to partial elastin deficiency. Our findings suggest that mTOR-sensitive perturbation of smooth muscle cell mechanosensing contributes to elastin aortopathy.

Interferon-γ-mediated allograft rejection exacerbates cardiovascular disease of hyperlipidemic murine transplant recipients.

RATIONALE: Transplantation, the most effective therapy for end-stage organ failure, is markedly limited by early-onset cardiovascular disease (CVD) and premature death of the host. The mechanistic basis of this increased CVD is not fully explained by known risk factors. OBJECTIVE: To investigate the role of alloimmune responses in promoting CVD of organ transplant recipients. METHODS AND RESULTS: We established an animal model of graft-exacerbated host CVD by combining murine models of atherosclerosis (apolipoprotein E-deficient recipients on standard diet) and of intra-abdominal graft rejection (heterotopic cardiac transplantation without immunosuppression). CVD was absent in normolipidemic hosts receiving allogeneic grafts and varied in severity among hyperlipidemic grafted hosts according to recipient-donor genetic disparities, most strikingly across an isolated major histocompatibility complex class II antigen barrier. Host disease manifested as increased atherosclerosis of the aorta that also involved the native coronary arteries and new findings of decreased cardiac contractility, ventricular dilatation, and diminished aortic compliance. Exacerbated CVD was accompanied by greater levels of circulating cytokines, especially interferon-γ and other Th1-type cytokines, and showed both systemic and intralesional activation of leukocytes, particularly T-helper cells. Serological neutralization of interferon-γ after allotransplantation prevented graft-related atherosclerosis, cardiomyopathy, and aortic stiffening in the host. CONCLUSIONS: Our study reveals that sustained activation of the immune system because of chronic allorecognition exacerbates the atherogenic diathesis of hyperlipidemia and results in de novo cardiovascular dysfunction in organ transplant recipients.

Antibacterial and antifungal potentials of the solvents extracts from Eryngium caeruleum, Notholirion thomsonianum and Allium consanguineum.

BACKGROUND: Herbal medicines have long been used for various ailments in various societies and natural bioactive compounds are gaining more and more importance due to various factors. In this context, three plant species i.e., Eryngium caeruleum, Notholirion thomsonianum and Allium consanguineum have been aimed for the scientific verification of their purported traditional uses against various infectious diseases. METHODS: In this study, three plants were assayed for antibacterial and antifungal potentials. The antibacterial investigations were performed via well diffusion method and nutrient broth dilution method. The bacterial strains used in the study were Enterococcus faecalis, Proteus mirabilis, Escherichia coli, Salmonella typhi, Klebsiella pneumonia and Pseudomonas aeruginosa. The antifungal potential was investigated by dilution method of Muller-Hinton agar media of the plants' samples. The fungal strains used were Aspergillis fumigatus, Aspergillis flavus and Aspergillis niger. Ceftriaxone and nystatin were used as standard drugs in antibacterial and antifungal assays respectively. RESULTS: Different fractions from N. thomsonianum were tested against five bacterial strains while the samples from A. consanguineum and E. caeruleum were tested against six bacterial strains. All the samples exhibited prominent antibacterial activity against the tested strains. Overall, chloroform and ethyl acetate fractions were found most potent among the three plants' samples. N. thomsonianum excelled among the three plants in antibacterial activity. Similarly, in antifungal assay, N. thomsonianum exhibited strong antifungal activity against the fungal strains. The chloroform fraction displayed MFCs of 175.67 ± 5.20***, 29.33 ± 5.48*** and 63.00 ± 4.93*** µg/ml against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger respectively. The whole study demonstrates that all the three plant species were active against tested bacterial and fungal strains. CONCLUSION: It can be concluded from our findings that N. thomsonianum, A. consanguineum and E. caeruleum have broad antibacterial and antifungal potentials. In all of the plants' samples, chloroform and ethyl acetate fractions were more active. Furthermore, being the potent samples, the chloroform and ethyl acetate fractions of these plants can be subjected to column chromatography for the isolation of more effective antimicrobial drugs.

Rapamycin inhibits smooth muscle cell proliferation and obstructive arteriopathy attributable to elastin deficiency.

OBJECTIVE: Patients with elastin deficiency attributable to gene mutation (supravalvular aortic stenosis) or chromosomal microdeletion (Williams syndrome) are characterized by obstructive arteriopathy resulting from excessive smooth muscle cell (SMC) proliferation, mural expansion, and inadequate vessel size. We investigated whether rapamycin, an inhibitor of the cell growth regulator mammalian target of rapamycin (mTOR) and effective against other SMC proliferative disorders, is of therapeutic benefit in experimental models of elastin deficiency. APPROACH AND RESULTS: As previously reported, Eln(-/-) mice demonstrated SMC hyperplasia and severe stenosis of the aorta, whereas Eln(+/-) mice exhibited a smaller diameter aorta with more numerous but thinner elastic lamellae. Increased mTOR signaling was detected in elastin-deficient aortas of newborn pups that was inhibited by maternal administration of rapamycin. mTOR inhibition reduced SMC proliferation and aortic obstruction in Eln(-/-) pups and prevented medial hyperlamellation in Eln(+/-) weanlings without compromising aortic size. However, rapamycin did not prolong the survival of Eln(-/-) pups, and it retarded the somatic growth of juvenile Eln(+/-) and Eln(+/+) mice. In cell cultures, rapamycin inhibited prolonged mTOR activation and enhanced proliferation of SMC derived from patients with supravalvular aortic stenosis and with Williams syndrome. CONCLUSIONS: mTOR inhibition may represent a pharmacological strategy to treat diffuse arteriopathy resulting from elastin deficiency.

Modulation of transforming growth factor-ß signaling and extracellular matrix production in myxomatous mitral valves by angiotensin II receptor blockers.

BACKGROUND: Little is known about the pathophysiology of myxomatous degeneration of the mitral valve, the pathological hallmark of mitral valve prolapse, associated with symptomatic mitral regurgitation, heart failure, and death. Excess transforming growth factor (TGF)-ß signaling is known to cause mitral valve degeneration and regurgitation in a mouse model of Marfan syndrome. We examined if TGF-ß signaling is dysregulated in clinical specimens of sporadic mitral valve prolapse compared with explanted nondiseased mitral valves and we tested the effects of angiotensin II receptor blockers on TGF-ß signaling in cultured human mitral valve cells. METHODS AND RESULTS: Operative specimens, cultured valve tissues, and cultured valvular interstitial cells were obtained from patients with mitral valve prolapse undergoing mitral valve repair or from organ donors without mitral valve disease. Increased extracellular matrix in diseased valve tissue correlated with an upregulation of TGF-ß expression and signaling as evidenced by SMAD2/3 phosphorylation. Both TGF-ß ligand and signaling mediators colocalized primarily to valvular interstitial cells suggesting autocrine/paracrine activation. In cultured valve tissue, exogenous TGF-ß increased basal extracellular matrix production, whereas serological neutralization of TGF-ß inhibited disease-driven extracellular matrix overproduction. TGF-ß-induced extracellular matrix production in cultured valvular interstitial cells was dependent on SMAD2/3 and p38 signaling and was inhibited by angiotensin II receptor blockers. CONCLUSIONS: TGF-ß has a profibrotic role in the pathogenesis of sporadic mitral valve prolapse. Attenuation of TGF-ß signaling by angiotensin II receptor blockers may represent a mechanistically based strategy to modulate the pathological progression of mitral valve prolapse in patients.

Research progress in the role and mechanism of Leucine in regulating animal growth and development.

Leucine, a branched-chain amino acid, is essential in regulating animal growth and development. Recent research has uncovered the mechanisms underlying Leucine's anabolic effects on muscle and other tissues, including its ability to stimulate protein synthesis by activating the mTORC1 signaling pathway. The co-ingestion of carbohydrates and essential amino acids enhances Leucine's anabolic effects. Moreover, Leucine has been shown to benefit lipid metabolism, and insulin sensitivity, making it a promising strategy for preventing and treating metabolic diseases, including type 2 diabetes and obesity. While emerging evidence indicates that epigenetic mechanisms may mediate Leucine's effects on growth and development, more research is needed to elucidate its mechanisms of action fully. Specific studies have demonstrated that Leucine promotes muscle growth and metabolic health in animals and humans, making it a promising therapeutic agent. However, it is essential to note that Leucine supplementation may cause digestive issues or interact with certain medications, and More study is required to determine definitively optimal dosages. Therefore, it is important to understand how Leucine interacts with other nutrients, dietary factors, and lifestyle habits to maximize its benefits. Overall, Leucine's importance in human nutrition is far-reaching, and its potential to prevent muscle loss and enhance athletic performance warrants further investigation.

Methicillin-Resistant Staphylococcus Aureus And Its Antibiotic Sensitivity Pattern In Patients With Vesiculobullous Disorders.

BACKGROUND: Vesiculobullous disorders are among the leading causes of admission to dermatology. These are characterized by distinct mucocutaneous involvement and by the development of vesicles and bullae (i.e. blisters). Methicillin-resistant Staphylococcus aureus (MRSA) is a group of gram-positive bacteria distinct from other strains of Staph aureus. As the susceptibility of bacteria to antibiotics varies from region to region and from time to time, this study will determine the pattern of antimicrobial susceptibility of MRSA isolates to the commonly prescribed antibiotics in our population. The objective is to determine the frequency of methicillin-resistant Staphylococcus aureus and its antibiotic sensitivity pattern in patients with vesiculobullous disorders admitted to the Dermatology unit of Lady Reading Hospital (LRH), Peshawar. It was Cross-sectional and carried out in study Department of Dermatology, Lady Reading Hospital, Peshawar from Oct 23, 2020, to Apr 22, 2021. METHODS: This study was carried out over 132 patients. After consent, Swabs of pus from the Vesiculobullous disorders were taken from all the patients and sent to a laboratory for culture. Staphylococcus aureus (MRSA) was labelled as Staphylococcus aureus bacteria by Kirby-Bauer disc diffusion method using oxacillin (1 µ gm.) disc on Mueller-Hinton agar (HiMedia Labs, Mumbai) with 24 hours incubation at 35 °C. RESULTS: In this study, 132 patients were observed. The average age was 44.44 years ±13.74 SD. Male to female ratio was 1.30:1. There were 44(33.33%) patients who showed Methicillin Resistant Staphylococcus aureus (MRSA) in vesiculobullous disorders patients. CONCLUSIONS: In our population, the frequency of staphylococcus aureus bacteria in vesiculobullous disorders is high so it will be considered while treating such patients.

Uncertainty in Medical and Dental Students of Pakistan Regarding Their Future Career and Its Major Causes: A Cross-Sectional Study.

OBJECTIVES: This study aimed to evaluate the extent of confidence in medical and dental students regarding their careers after being enrolled in their germane institutes and to identify the magnitude of uncertainty in medical and dental students about their careers and the important causes of this uncertainty. METHODS: This study was conducted among enrolled students in different medical and dental colleges and universities of Pakistan, including the public and private sectors, from March 1 to March 15, 2023. The level of confidence in their career was evaluated using a close-ended questionnaire of a three-point Likert scale developed and tested by the investigators and approved by the Ethical Review Board (ERB) along with the synopsis. Data were managed and analyzed using Microsoft Excel 19 (Microsoft Corporation, USA) and IBM SPSS Statistics for Windows, version 27 (released 2020; IBM Corp., Armonk, New York, United States). RESULTS: This study included 1,126 students from public and private medical and dental institutes. The majority of participants 965(85.7%) were satisfied with their chosen profession, and 1,042 (92.5%) students believed they could make a positive contribution to society. Out of the total participants, 246 (21.8%) students showed their intention of changing careers if provided with a comparable/alternative opportunity. A very small proportion, 154 (13.7%), were dissatisfied with their current clinical training and studies. The study also revealed that extra and unjustified academic pressure from institutions is the leading cause of uncertainty among students. Moreover, the lack of psychological support and counseling provided during the academic years adds to the magnitude of uncertainty. CONCLUSION: In Pakistan, a staggering number of medical and dental students are unsure of their future careers and career prospects. The main causes of this uncertainty are the extra, unwarranted academic pressure that institutions place on students and the dearth of psychological support and counseling offered during the course of studies. This study not only highlights the prevailing uncertainty among medical students but also identifies the causes behind it. Addressing these causes can alleviate the prevailing uncertainty and bring about satisfactory and productive academic achievements without suffering from worries about the future.

miR-1 mediated suppression of Sorcin regulates myocardial contractility through modulation of Ca2+ signaling.

MicroRNAs are negative gene regulators and play important roles in cardiac development and disease. As evident by cardiomyopathy following cardiac-specific Dicer knockdown they also are required for maintaining normal cardiac contractile function but the specific role of miR-1 in the process is poorly understood. To characterize the role of miR-1 in particular and to identify its specific targets we created a tamoxifen-inducible, cardiac-specific Dicer knockdown mouse and demonstrated that Dicer downregulation results in a dramatic and rapid decline in cardiac function concurrent with significantly reduced levels of miR-1. The importance of miR-1 was established by miR-1 antagomir treatment of wild-type mice, which replicated the cardiac-specific Dicer knockdown phenotype. Down-regulation of miR-1 was associated with up-regulation of its predicted target Sorcin, an established modulator of calcium signaling and excitation-contraction coupling, subsequently verified as a miR-1 target with luciferase constructs. siRNA-mediated knockdown of Sorcin effectively rescued the cardiac phenotypes after Dicer or miR-1 knockdown affirming Sorcin as a critical mediator of the acute cardiomyopathy observed. The regulatory relationship between miR-1 and Sorcin was further confirmed in cultured mouse cardiomyocytes where modulation of miR-1 was associated with discordant Sorcin levels and dysregulation of calcium signaling. Pathological relevance of our findings included decreased miR-1 and increased Sorcin expression in end-stage cardiomyopathy. These findings demonstrate the importance of miR-1 in cardiac function and in the pathogenesis of heart failure via Sorcin-dependent calcium homeostasis.

IFN-gamma primes intact human coronary arteries and cultured coronary smooth muscle cells to double-stranded RNA- and self-RNA-induced inflammatory responses by upregulating TLR3 and melanoma differentiation-associated gene 5.

Atherosclerosis of native coronary arteries and graft arteriosclerosis in transplanted hearts are characterized by activation of innate and adaptive immune responses. Nucleic acids generated by infections or cell death have been detected within arteriosclerotic lesions, and it is known that microbial and synthetic nucleic acids evoke inflammatory responses in cultured vascular cells. In this study, we report that model RNA, but not DNA, instigated robust cytokine and chemokine production from intact human coronary arteries containing both intrinsic vascular cells and resident/infiltrating leukocytes. An ssRNA analog induced TNF-alpha and IFN-gamma-induced protein of 10 kDa secretion by isolated human PBMCs, but not vascular cells. Conversely, synthetic dsRNA induced these inflammatory mediators by vascular cells, but not PBMCs. IFN-gamma, a cytokine linked to atherosclerosis and graft arteriosclerosis, potentiated the inflammatory responses of intact arteries and cultured vascular smooth muscle cells (VSMCs) to polyinosinic:polycytidylic acid [poly(I:C)] and was necessary for inflammatory responses of VSMC to self-RNA derived from autologous cells. IFN-gamma also induced the expression of TLR3, melanoma differentiation-associated gene 5, and retinoic acid-inducible gene I dsRNA receptors. Small interfering RNA knockdown revealed that TLR3 mediated VSMC activation by poly(I:C), whereas melanoma differentiation-associated gene 5 was more important for VSMC stimulation by self-RNA. IFN-gamma-mediated induction of dsRNA receptors and priming for inflammatory responses to poly(I:C) was confirmed in vivo using immunodeficient mice bearing human coronary artery grafts. These findings suggest that IFN-gamma, and by inference adaptive immunity, sensitizes the vasculature to innate immune activators, such as RNA, and activation of IFN-gamma-primed vascular cells by exogenous or endogenous sources of RNA may contribute to the inflammatory milieu of arteriosclerosis.

Anti-inflammatory and antimicrobial activity of 4,5-dihydropyrimidine-5-carbonitrile derivatives: their synthesis and spectral elucidation.

Thirteen new 6-(1-H-indole-2-yl)-4-oxo-2-[2-(substituted-benzylidene)-hydrazinyl]-4,5-dihydropy-rimidine-5-carbonitrile derivatives were synthesized. The title compounds, hydrazones, were synthesized by reaction of hydrazine group of 2-hydrazinyl-4-(1-H-indole-2-yl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (2) with different substituted aromatic aldehydes using a mixture (2:8, v/v) of glacial acetic acid and alcohol. The required intermediate compound 2 was synthesized from 2-mercapto-4-(1-H-indole-2-yl)-6-oxo-1,6-dihy-dropyrimidine-5-carbonitrile 1 upon nucleophilic attack by the hydrazine hydrate. Compound 1 was synthesized by modified Biginelli condensation method using indole-3-carbaldehyde, ethyl cyanoacetate and thiourea. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and antimicrobial actions. Among the newer derivatives, one compound i.e., 6-(1-H-indole-2-yl)-4-oxo-2-[2-(2,6-dichlorobenzylidene)-hydrazinyl]-4,5-dihydropyrimidine-5-carbonitrile (7) emerged as lead compound having 71.14% inhibition of edema and 12.5 microg/mL MIC against both bacterial and fungal strains.

Systematic human rights violations, traumatic events, daily stressors and mental health of Rohingya refugees in Bangladesh.

BACKGROUND: Almost 900,000 Rohingya refugees currently reside in refugee camps in Southeastern Bangladesh. Prior to fleeing Myanmar, Rohingya experienced years of systematic human rights violations, in addition to other historical and more recent traumatic events such as the burning of their villages and murder of family members, friends and neighbors. Currently, many Rohingya struggle to meet basic needs in refugee camps in Bangladesh and face mental health-related concerns that appear linked to such challenges. The purpose of this study is to describe systematic human rights violations, traumatic events, daily stressors, and mental health symptoms and to examine relationships between these factors. METHODS: Cross-sectional data was collected from a representative sample of 495 Rohingya refugee adults residing in camps in Bangladesh in July and August of 2018. RESULTS: Respondents reported high levels of systematic human rights violations in Myanmar, including restrictions related to expressing thoughts, meeting in groups, travel, religious practices, education, marriage, childbirth, healthcare, and more. Events experienced in Myanmar included exposure to gunfire (99%), destruction of their homes (93%), witnessing dead bodies (92%), torture (56%), forced labor (49%), sexual assault (33%), and other events. More than half (61%) of participants endorsed mental health symptom levels typically indicative of PTSD, and more than two thirds (84%) endorsed levels indicative of emotional distress (symptoms of anxiety and depression). Historic systematic human rights violations, traumatic events, and daily stressors were associated with symptoms of posttraumatic stress, as well as depression and anxiety. Respondents reported numerous stressors associated with current life in the camps in Bangladesh as well as previous stressors, such as harassment, encountered in Myanmar. CONCLUSIONS: Findings underscore the impact of systematic human rights violations, targeted violence, and daily stressors on the mental health of Rohingya in Bangladesh. Those working with Rohingya should consider the role of such factors in contributing to poor mental health. This research has the potential to inform interventions targeting such elements. Future research should examine the relationships between mental health and human rights violations over time.

Procedural complications of inferior vena cava filter retrieval, an illustrated review.

Annually, approximately 65,000 inferior vena cava (IVC) filters are placed in the United States (Ahmed et al., J Am Coll Radiol 15:1553-1557, 2018). Approximately 35% of filters are eventually retrieved (Angel et al., J Vasc Interv Radiol 22: 1522-1530 e1523, 2011). Complications during filter retrieval depend heavily on technique and filter position. In this paper, we review risk factors and incidence of complications during IVC filter removal. We also discuss ways these complications could be avoided and the appropriate management if they occur.

Paraphenylenediamine (Kala Pathar) Poisoning at the National Poison Control Center in Karachi: A Prospective Study.

Introduction Suicide by self-poisoning is a common cause of death, especially in the younger population. More specifically, hair-dye poisoning is being increasingly used for suicide. Paraphenylenediamine (PPD), also known as "Kala pathar", is a highly toxic ingredient present in hair-dye that can cause death. Therefore, this study is designed to assess the demographics, clinical features, laboratory findings, and outcomes of PPD poisoning in patients admitted to the National Poison Control Center in Karachi, Pakistan. Materials and methods We conducted a prospective study for a period of six months at the National Poison Control Center, Karachi, Pakistan. A total of eight patients with PPD poisoning with no cardiac, liver, or renal co-morbidities were included in this study. The demographic characteristics, clinical features, laboratory findings, mode of intoxication, and route of intoxication were noted in a proforma. Furthermore, hospitalization time, tracheostomy status, mechanical ventilation status, and mortality rates were also recorded. For continuous variables, the means and SDs were calculated. Whereas for categorical data, percentages were calculated. Results In our study, the mean age of the patients was estimated at 25.38 ± 3.77 years. It was deemed that the majority of poisoning cases were intentional in nature (75%). These suicide cases were more commonly observed in young females (75%) who belonged to a low socioeconomic class (87.5%). The preferred route of administration was oral (87.5%). In 87.5% of the patients, the characteristic clinical features such as cervicofacial edema, dysphagia, dysphonia, and stridor were noted. During the later clinical stages of poisoning, clinical features such as rhabdomyolysis (62.5%), chocolate-colored urine (87.5%), hepatitis (75%), and acute renal failure (12.5%) were noteworthy. The mean ± SD of total leukocyte count (TLC), creatine phosphokinase (CPK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine and serum potassium were, respectively, noted at 10,500 ± 3,854.4 cells/mm3, 32.87 ± 11.36 IU/L, 1,239.1 ± 1,106.2 IU/L, 776.8 ± 1,149.8 IU/L, 2.125 ± 2.275 mg/dL, and 4.9 ± 1.094 mmol/L. In our patients, the mean intensive care unit stay was 8.25 ± 3.99 days. Emergency tracheostomy was performed in 25% of patients. Mechanical ventilation was required for 50% of our patients. Overall, the mortality rate observed in our study stands at 25%. Conclusion PPD poisoning is associated with a high rate of morbidity and mortality. Therefore, it is imperative for physicians to be mindful of the clinical characteristics and treatment options in order to optimally manage such cases of poisoning. In addition, the use of hair-dyes composed of highly lethal PPD should also be banned.

Frequency of Human Immunodeficiency Virus in Patients Admitted with Acute Stroke.

Introduction Stroke is a leading cause of chronic disability and death in both developing and developed countries. A significant proportion of stroke patients are human immunodeficiency virus (HIV) positive. About half of the HIV patients experience some sort of neurological deficit in their lifetimes. The exact reason for the occurrence of stroke in HIV infected patients is poorly understood. The purpose of our study is to determine the frequency of HIV among patients admitted with acute stroke. Materials and methods This cross-sectional study is conducted at a major metropolitan hospital in Karachi for six months. A total of 130 patients of stroke between the ages of 30 and 70 years of either gender were included in this study. A complete history was taken and a physical examination was performed. Each patient underwent a battery of tests that included HIV serology, lipid profile, electrocardiography (ECG), chest X-ray (posteroanterior (PA) view), and computed tomography (CT) scan of the brain. Carotid Doppler ultrasonography to assess carotid artery stenosis was also ordered. The means and standard deviations of age and cluster of differentiation 4 (CD4) cell count were calculated. The frequencies and proportions of gender, diabetes mellitus (DM), hypertension (HTN), smoking, obesity, dyslipidemia, carotid artery stenosis, and HIV status were calculated. Stratification was done by applying the chi-square test and assuming p-value ≤0.05 as significant. This helped analyze the association of age, gender, DM, HTN, smoking, obesity, dyslipidemia, and carotid artery stenosis to the frequency of HIV. Results The mean age of the study population was 55.54 ± 11.166 years. There were 39 (30%) patients <50 years of age while 91 (70%) patients were ≥50 years of age. Gender distribution showed that 86 (66.15%) patients were male, and 44 (33.85%) patients were female. Furthermore, 71 (54.62%) patients were hypertensive, 53 (40.77%) were diabetic, 62 (47.69%) were smokers, 49 (37.69%) were obese, 52 (40%) had dyslipidemia, and 77 (59.23%) had carotid artery stenosis. The frequency of HIV was noted at 24 (18.46%). The mean CD4 count was estimated at 241 ± 103.295 cells/mm3. Stratification showed a significant relationship between the frequency of HIV with only gender (p=0.01) and dyslipidemia (p=0.037). Conclusion HIV infection in patients with stroke is not uncommon. Patients who are male, younger in age, have dyslipidemia, belong to a low socioeconomic class, or have a bad sexual history are more likely to have HIV as an underlying cause of stroke. The exact pathogenesis of such a stroke and the role of antiretroviral therapy in the prevention and treatment of this group of stroke are not completely understood and need further analysis.

Tuberculous and cryptococcal meningitis in a setting with high TB and low HIV prevalence.

OBJECTIVE: To compare the differences in presentation and outcome of patients with tuberculous meningitis (TBM) and cryptococcal meningitis (CCM). STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from December 1995 to December 2005. METHODOLOGY: Patients with a confirmed diagnosis of TBM or CCM were included in this study. The signs and symptoms, laboratory findings and other variables of patients were entered and analyzed by Statistical Package for Social Sciences (SPSS) Software version 14. RESULTS: We compared 16 patients of TBM with 11 of CCM. None of the patients with TBM were Human Immunodeficiency Virus (HIV) positive while 4 patients with CCM had HIV. The common initial signs and symptoms in patients with TBM were fever, altered mental status and headache; and in patients with CCM were fever, headache and cough. The mean CSF glucose level decreased according to the Medical Research Council (MRC) stage in TBM. The mean CSF RBCs, WBCs, glucose and protein in TBM were 2010/mm3, 228/mm3, 52.32 mg/dL and 289.48 mg/dl respectively and in CCM were 178.54/mm3, 529.54/mm3, 32.63 mg/dL and 432.18 mg/dL respectively. CONCLUSION: TBM and CCM should be suspected in all cases that present with symptoms of chronic meningitis. Patients with TBM are more likely to have altered mental status and higher CSF RBCs; those with CCM are more likely to have headache, cough and higher CSF WBCs.

Right Atrial and Massive Pulmonary Artery Mechanical Thrombectomy Under Echocardiography Guidance Using the FlowTriever System.

INTRODUCTION: Management of clot in transit in patients with pulmonary embolism, who are candidates for percutaneous intervention, can be challenging. This is a case report of simultaneous right atrial mechanical thrombectomy under echocardiography guidance and pulmonary artery embolectomy under fluoroscopy guidance, using the recently introduced FlowTriever system (Inari Medical Inc., Irvine, CA, USA). REPORT: An 88 year old female, resuscitated from cardiopulmonary arrest near the end of a total right hip arthroplasty, presented for management of suspected massive pulmonary embolism. Her right atrial thrombus was removed under transthoracic echocardiography guidance, and her pulmonary arterial thrombus was subsequently successfully treated under fluoroscopy. DISCUSSION: The FlowTriever system can be safely and effectively used under real time transthoracic echocardiography guidance to retrieve clot in transit from the cardiac chambers, in addition to its standard application for the pulmonary artery under fluoroscopy guidance.

Latest approaches to the diagnosis and management of food allergies in children.

Adverse food reactions are a challenge for physicians. As the prevalence of this condition rises, it is important that paediatricians and other health care professionals adeptly diagnose this condition. We begin by discussing the relevant points in history and physical examination, then we discuss the recent effective diagnostic tests and techniques available for doctors and patients, along with several management options. Over the last decade, there have been major advancements in this field and novel mechanisms have been proposed which efficiently modulate immune mechanisms involved. Although results are only preliminary, they do however, indicate a promising future for patients with food allergies.