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White matter tract integrity (WMTI) can characterize brain microstructure in areas with highly aligned fiber bundles. Several WMTI biomarkers have now been validated against microscopy and provided promising results in studies of brain development and aging, as well as in a number of brain disorders. Currently, WMTI is mostly used in dedicated animal studies and clinical studies of slowly progressing diseases, and has not yet emerged as a routine clinical tool. To this end, a less data intensive experimental method would be beneficial by enabling high resolution validation studies, and ease clinical applications by speeding up data acquisition compared with typical diffusion kurtosis imaging (DKI) protocols utilized as part of WMTI imaging. Here, we evaluate WMTI based on recently introduced axially symmetric DKI, which has lower data demand than conventional DKI. We compare WMTI parameters derived from conventional DKI with those calculated analytically from axially symmetric DKI. We employ numerical simulations, as well as data from fixed rat spinal cord (one sample) and in vivo human (three subjects) and rat brain (four animals). Our analysis shows that analytical WMTI based on axially symmetric DKI with sparse data sets (19 images) produces WMTI metrics that correlate strongly with estimates based on traditional DKI data sets (60 images or more). We demonstrate the preclinical potential of the proposed WMTI technique in in vivo rat brain (300 µm isotropic resolution with whole brain coverage in a 1 h acquisition). WMTI parameter estimates are subject to a duality leading to two solution branches dependent on a sign choice, which is currently debated. Results from both of these branches are presented and discussed throughout our analysis. The proposed fast WMTI approach may be useful for preclinical research and e.g. clinical evaluation of patients with traumatic white matter injuries or symptoms of neurovascular or neuroinflammatory disorders.
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Biomarcadores/análise , Imagem de Tensor de Difusão/métodos , Substância Branca/metabolismo , Animais , Fenômenos Biofísicos , Simulação por Computador , Humanos , Análise Numérica Assistida por Computador , Ratos Long-EvansRESUMO
In approximately one-third of individuals with schizophrenia, the illness demonstrates a poor response to standard antipsychotic treatments. Although a relatively small proportion fails to achieve remission after the initial exposure to either first- or second-generation antipsychotic drugs, the condition often becomes progressively more resistant to medication following subsequent relapses. We conducted comprehensive searches in databases such as PubMed and PubMed Central, extracting and assessing data quality using the Cochrane risk-of-bias tool for randomized clinical trials (RCTs). A random effects model was employed to calculate the pooled prevalence and explore heterogeneity, utilizing the I2 statistic. Subgroup analyses differentiated between experimental and placebo groups, while sensitivity analyses assessed the robustness of our findings, and publication bias was examined. Our meta-analysis included a sample size of 323 patients from seven studies out of the 10 selected articles. The pooled sample evaluated the effectiveness of amisulpride and clozapine in treating schizophrenia, with Positive and Negative Syndrome Scale (PANSS)-positive and PANSS-negative scores used in the subgroup analysis. The analysis revealed a heterogeneity of 78% and a statistically significant p-value of <0.05, favoring amisulpride and clozapine for treating schizophrenia either as monotherapy or in combination. These findings indicate that the effectiveness of these drugs is statistically significant. Our study underscores the necessity of conducting larger RCTs to further elucidate the optimal dosage and guideline criteria for prescribing amisulpride, clozapine, or their combination for patients resistant to first- and second-generation antipsychotics.
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This review explores the psychosocial impact of vitiligo on patients, its consequences for their quality of life, and the need for holistic support. Vitiligo's psychosocial burden, driven by the need to conceal lesions and societal beauty ideals, leads to stress, sadness, and low self-esteem. Social stigma affects self-esteem, especially in cultural contexts, exacerbating the need for culturally sensitive support. Anxiety and depression are common due to visible differences and societal pressures. Vitiligo significantly reduces the quality of life, especially in younger patients, impacting daily activities, careers, and relationships. Disease severity worsens these effects, particularly in visible areas and among individuals with darker skin tones. Long-term disease activity may improve acceptance and quality of life. Psychological support and counseling are crucial, as many patients don't seek medical help. Education plays a key role, improving understanding and reducing anxiety. Raising awareness about the impact of vitiligo can challenge perceptions and contribute to enhancing patients' well-being. In conclusion, this review highlights the interplay between psychosocial factors, quality of life, and the importance of addressing social stigma, providing psychological support, and advancing education and awareness for those with vitiligo.
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Cardiometabolic syndrome (CMS) is a complex interplay of metabolic dysregulation, cardiovascular disease (CVD), and diabetes risk factors. It encompasses obesity, insulin resistance, dyslipidemia, hyperuricemia, and hypertension, with obesity triggering metabolic disturbances. The global prevalence of CMS, driven by rising obesity rates and sedentary lifestyles, varies across regions. Underlying CMS mechanisms intertwine genetics, sedentary behaviors, poor diets, and hormonal imbalances. Genetic predisposition interacts with environmental factors, while sedentary lifestyles and poor diets amplify obesity and insulin resistance. Hormonal disruptions further complicate the syndrome's development. CMS has far-reaching clinical implications, extending beyond CVD and diabetes to conditions such as non-alcoholic fatty liver disease, cancer, and sleep apnea. Innovative CMS approaches revolve around biomarkers, personalized medicine, lifestyle interventions, and pharmacological breakthroughs. Emerging biomarkers offer early insights, while personalized medicine tailors interventions based on genetic profiles. Lifestyle modifications, encompassing dietary changes and tailored exercise, foster metabolic recalibration. The pharmaceutical frontier targets CMS facets, promising more precise treatments.
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Introduction Severe uncontrolled asthma is challenging to manage and impacts lung function and symptoms. Biologic agents targeting inflammatory pathways have transformed asthma management. This retrospective chart review aimed to assess biologic therapy in severe uncontrolled asthma patients and evaluate outcomes. Methods The study analyzed medical records of 30 patients receiving biologic therapy for severe asthma at a tertiary care center in Peshawar, Pakistan, from December 2022 to Jun 2023. Ethical approval was obtained, and patient demographics, biologic agent usage, and clinical parameters were collected. Clinical outcomes were evaluated after six months, including forced expiratory volume in the first second (FEV1), eosinophil count, IgE levels, and exacerbation rates. Results After six months, biologic treatment significantly improved FEV1 (48.7% to 62.4%), reduced eosinophils (540 cells/µL to 290 cells/µL) and IgE levels (410 IU/mL to 280 IU/mL), and decreased exacerbations (4.6 to 1.9). Subgroup analysis based on age and sex showed consistent lung function improvements. Conclusion Biologic agents effectively targeted inflammatory pathways, improving asthma control in severe uncontrolled asthma patients. This study provides valuable insights into biologic therapy for severe asthma, offering new possibilities for patient outcomes. Larger studies are needed to validate findings and optimize personalized treatment strategies.
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Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a very rare autosomal dominant genetic disorder that leads to abnormal blood vessel formation in the skin, mucus membranes (called telangiectasia), and organs such as the lung, liver, and brain. It occurs due to a mutation in one of the ACVRL1, ENG, and SMAD4 genes, which code for the formation of blood vessels. The most common symptom is recurring nosebleed (epistaxis; due to rupture of nasal mucosal telangiectasia), which begins in childhood and affects about 90-95% of people with HHT. Other common signs and symptoms include punctate, linear, or splinter-like telangiectasias on the upper body, oral mucosa, or nail beds, gastrointestinal bleeding, and iron deficiency anemia. The diagnostic criteria currently in use are the Curaçao criteria. The diagnosis is made by clinical screening (e.g., history and physical exam), baseline investigations (complete blood count, hemoglobin, hematocrit, and ferritin level), genetic testing, and detailed medical imaging to detect visceral arteriovenous malformations (AVMs) such as esophagogastroduodenoscopy, colonoscopy, multiphase contrast CT, computed tomography angiography (CTA or CT Angio), magnetic resonance angiography (MRA), chest X-ray, Doppler ultrasonography, liver biopsy, and cerebral angiography. Management includes intravenous iron therapy or blood transfusion, antifibrinolytics (e.g tranexamic acid), ablation therapies (e.g. laser treatment, radiofrequency ablation, electrosurgery, sclerotherapy, and argon plasma coagulation), and systemic anti-angiogenic agents (e.g. thalidomide, bevacizumab). In this report, we present the case of a 22-year-old man from Swabi, Pakistan, with a history of recurrent epistaxis (nosebleed) from childhood, who presented with multiple episodes of melena (blood in stool), fatigue, palpitation, and iron deficiency anemia for five years. Multiple esophagogastroduodenoscopies (OGDs) and colonoscopies were done over the years, which showed AVM in the antrum and fundus of the stomach, duodenum, and colon, and a diagnosis of HHT was made. CTA and exploratory laparotomy showed ileal loop hemangiomas. He was managed with multiple blood transfusions, argon plasma coagulation (APC) for the AVMs, oral thalidomide, and steroids. Despite therapy, the patient had intermittent episodes of blood in stool and low blood counts. During his stay in Hayatabad Medical Complex (HMC), the patient was managed with high-frequency blood transfusion and bevacizumab (systemic anti-angiogenic agent). A dramatic reduction in the number of required transfusions and improvement in the patient's bloodlines and symptoms was noted. This case highlights the importance of endoscopic methods for the timely diagnosis of HHT and its management with intravenous bevacizumab.
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Objective To determine the frequency of hepatitis A, B, C, and E viruses (HAV, HBV, HCV, HEV) in pregnant women with acute hepatitis presenting to the medical units of HMC, Peshawar. Methods This is a descriptive cross-sectional study in which 442 pregnant women, either multi or primigravida, with yellow discolouration of the sclerae of the eyes and elevated alanine aminotransferase (ALT) > 100 U/L on laboratory tests were chosen by convenience (non-probability) sampling to assess the frequency of HAV, HBV, HCV, HEV. Results The majority, i.e., 58.8%, were in the age range of >30 years and presented in the third trimester. Of the subjects, 81.90% had parity in the range of 1-5, 89.4% were multigravida, 71.3% were illiterate, and 73.1% were in the low-income category. Anti-HEV was detected in 47.3% of pregnant women, Anti-HCV in 30.3%, Hepatitis B surface antigen (HBsAg) in 11.5%, Hepatitis A-IgM in 5%, and 5.90% of the cases were virus-free. Conclusions HBV, HCV, and HEV exposure, in particular, may have a substantially larger impact on pregnancy and neonatal outcomes than HAV. As a result, at the first prenatal appointment, standard viral hepatitis screening in pregnant women may need to be reviewed.
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Brugada syndrome (BrS) is an autosomal-dominant condition mainly caused by defects in sodium channels causing ST-segment elevation in electrocardiograms (ECGs) in the V1 and V2 precordial leads, with ventricular tachyarrhythmias due to premature ventricular contractions, which increases the risk of sudden cardiac death. BrS usually presents in adulthood, with an average age of presentation of 41 years. In this article, we describe a case of BrS diagnosed in a 36-year-old male having sudden cardiac arrest with no comorbidities such as hypertension, diabetes mellitus, smoking, or any valvular disease history. We then explain the ECG-based diagnosis, signs and symptoms, presentation at the emergency department, and treatment options.
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Banti's syndrome is a chronic congestive enlargement of the spleen leading to the destruction of blood cells resulting in pancytopenia. It is also associated with cirrhosis and ascites along with symptoms of pancytopenia such as infection, bruising, weakness, and fatigue. Multiple factors such as hepatitis B infection, coagulation abnormalities and exposure to arsenic, etc. may also cause Banti's syndrome. Clinical evaluation with blood profile along with use of imaging studies such as MRI and splenic venography is utilized for the determination of Banti's syndrome. In this report, we present a 29-year-old diabetic male who presented with abdominal distention, right leg cellulitis, fever, and a past history of hematemesis and melena. On examination, distended abdomen showed marked splenomegaly with ascites (positive shifting dullness and fluid thrill). Also, the left leg was warm, swollen, and tender to the touch. Complete blood count showed decreased WBC, RBC, Hb, with peripheral smear negative for malarial parasites. Ultrasound scan of abdomen and pelvis was done illustrating massive splenomegaly with pelvic dilation and ascites.
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Protection of the brain from viral infections involves the type I IFN (IFN-I) system, defects in which render humans susceptible to herpes simplex encephalitis (HSE). However, excessive cerebral IFN-I levels lead to pathologies, suggesting the need for tight regulation of responses. Based on data from mouse models, human HSE cases, and primary cell culture systems, we showed that microglia and other immune cells undergo apoptosis in the HSV-1-infected brain through a mechanism dependent on the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway, but independent of IFN-I. HSV-1 infection of microglia induced cGAS-dependent apoptosis at high viral doses, whereas lower viral doses led to IFN-I responses. Importantly, inhibition of caspase activity prevented microglial cell death and augmented IFN-I responses. Accordingly, HSV-1-infected organotypic brain slices or mice treated with a caspase inhibitor exhibited lower viral load and an improved infection outcome. Collectively, we identify an activation-induced apoptosis program in brain immune cells that downmodulates local immune responses.
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Encéfalo/imunologia , Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Interferon Tipo I/imunologia , Proteínas de Membrana/imunologia , Nucleotidiltransferases/imunologia , Animais , Apoptose/genética , Apoptose/imunologia , Encéfalo/virologia , Herpes Simples/genética , Humanos , Interferon Tipo I/genética , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Microglia/imunologia , Microglia/virologia , Nucleotidiltransferases/genéticaRESUMO
Electroconvulsive therapy (ECT) is an effective but underutilized modality for the treatment of depression unresponsive to antidepressants. Mild to moderate cognitive impairment is a commonly encountered adverse effect but it normally resolves within hours. We report a case of post-ECT delirium lasting over a course of 14 days with succeeding sessions. Modification of ECT protocol by spacing the intervals of subsequent sessions and switching from bilateral brief pulse to unilateral ultra-brief pulse was found to be effective in reducing the confusion.
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Major depressive disorder (MDD) becomes difficult to treat when the patient has a comorbid personality disorder. For such patients, even a combination of psychotherapy and pharmacotherapy has been ineffective. Electroconvulsive therapy (ECT) has been the first line of therapy for the treatment-resistant depression. We used this mode of therapy for a patient who had MDD along with borderline personality disorder and had failed trials of multiple medications and psychotherapy. ECT was very successful in our patient.
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The war in Syria has entered the seventh year, with no sign of resolution. It is often referred as "the greatest human tragedy" since World War 2. Because of limited health facilities, we propose telepsychiatric interventions for the provision of mental healthcare services in Syria and in refugee camps to treat post-trauma patients.