Association of hormone receptors and human epidermal growth factor receptor-2/neu expressions with clinicopathologic factors of breast carcinoma: a cross-sectional study in a tertiary care hospital, Kabul, Afghanistan.

BACKGROUND: Breast cancer (BC) is one of the major causes of death worldwide. It is the most common cause of death before the age of 70 years. The incidence and mortality of BC are rapidly increasing, posing great challenges to the health system and economy of every nation. METHODOLOGY: A cross-sectional analytical study was conducted at the Department of Pathology and Clinical Laboratory of the French Medical Institute for Mothers and Children (FMIC) to demonstrate the association of human epidermal growth factor receptor 2 (Her2/Neu) and estrogen receptor (ER)/ progesterone receptor (PR) with clinical as well as pathological parameters among women with BC. A consecutive nonprobability sampling method was used for this study over a span of one and a half years. RESULTS: One hundred twenty participants diagnosed with breast cancer were included in the study. The mean age at diagnosis was 44.58 ± 11.16 years. Out of the total patients, 68 (56.7%) were above 40 years old, 108 (90%) were married, 94 (78.3%) were multiparous, and 88 (73.3%) had a history of breastfeeding. 33.3% of cases were within the age range of menopause (40-50 years). The positive expression rates of ER, PR, and Her2/neu were found to be 48.8%, 44.6%, and 44.6%, respectively, and Her2/neu overexpression was found to be higher among ER/PR-negative cases. CONCLUSION: In our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.

Letter to editor: Beyond nimodipine: advanced neuroprotection strategies for aneurysmal subarachnoid hemorrhage vasospasm and delayed cerebral ischemia.

This critique discusses neuroprotective strategies for aneurysmal subarachnoid hemorrhage (SAH), excluding Nimodipine, emphasizing alternatives like verapamil, albumin, and cilostazol. While these options show potential, their efficacy lacks robust confirmation from randomized controlled trials (RCTs), relying mainly on observational studies and small trials. The letter underscores the need for comprehensive safety assessments and long-term outcome studies to enhance practical application. Highlighting ongoing trials and emerging therapies like clazosentan and TAK-044, it advocates for future research directions focused on large-scale RCTs and combination therapies, such as cilostazol and Nimodipine, which have demonstrated synergistic benefits in reducing delayed cerebral ischemia (DCI) and improving patient outcomes.

Pulmonary barotrauma as a complication of mechanical ventilation for management of COVID-19 associated acute respiratory distress syndrome (CARDS).

Objectives: To identify that incidence of pulmonary barotrauma secondary to mechanical ventilation for the management of acute respiratory distress syndrome associated with coronavirus-disease-2019, and to compare it with the incidence of pulmonary barotrauma trauma secondary to mechanical ventilation associated with all the other causes. METHODS: The retrospective case-control study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from October 2020 to March 2021 of patients who underwent mechanical ventilation. The data was divided into two groups. Data of acute respiratory distress syndrome associated with coronavirus-disease-2019 was in group 1, and that of acute respiratory distress syndrome associated with any other cause in control group 2. Medical records were reviewed to obtain demographic and clinical data, while the institutional picture archiving and communication system was used to review radiological images. Data was analysed using SPSS 24. RESULTS: Of the 261 cases, 115(44%) were in group 1; 87(75.6%) males and 28(24.3%) females. There were 146(56%) controls in group 2; 96(65.7%) males and 50(34.2%) females. There were 142(54.4%) subjects aged >60 years; 61(43%) in group 1 and 81(57%) in group 2. The incidence of pulmonary barotrauma in group 1 was 39(34%) and 8(5.5%) in group 2 (p<0.0001). CONCLUSIONS: Mechanical ventilation in the management of acute respiratory distress syndrome associated with coronavirusdisease- 2019 was found to be associated with a significantly higher incidence of pulmonary barotrauma than acute respiratory distress syndrome associated with any other cause.

Pulmonary hypertension screening in children with sickle cell disease.

BACKGROUND: Screening for pulmonary hypertension (PHT) is recommended in children with sickle cell disease (SCD). However, best approaches are poorly described. We examined the utility of PHT symptoms, echocardiogram (ECHO), N-terminal-pro hormone brain natriuretic peptide (NT-proBNP), and BNP to screen for PHT in the SCD pediatric population. METHODS: Children (8-18 years old) with SCD-HbSS and HbSthal° were prospectively included and underwent PHT screening. The screening consisted of a comprehensive PHT symptoms evaluation, ECHO measurement, and NT-proBNP and BNP levels. RESULTS: A total of 73 patients were included (mean age 12 ± 5.7 years; >80% on hydroxyurea), of which 37% had a symptom consistent with PHT, including exertional dyspnea (26.5%), fatigue (17.6%), palpitation (14.7%), and chest pain (10.3%). ECHO was obtained in 53 (72.6%) patients, with only ECHO of 48 patients included in the final analysis. Elevated ECHO peak tricuspid regurgitant jet velocity (TRV) >2.5 m/s or indirect findings to suggest PHT were seen in only two of 48 (4.2%). No significant differences were seen between those with and without PHT symptoms when compared for NT-proBNP, BNP, hemoglobin, pulmonary function testing, fractional exhaled nitric oxide, asthma, oxygen saturation, and sleep apnea. CONCLUSION: PHT symptoms are not consistent with ECHO, NT-proBNP nor BNP findings in children with SCD. PHT prevalence based on TRV was low in children on hydroxyurea, therefore screening may not be warranted for this group.

Lysosomal Potassium Channels.

Lysosomes are acidic membrane-bound organelles that use hydrolytic enzymes to break down material through pathways such as endocytosis, phagocytosis, mitophagy, and autophagy. To function properly, intralysosomal environments are strictly controlled by a set of integral membrane proteins such as ion channels and transporters. Potassium ion (K+) channels are a large and diverse family of membrane proteins that control K+ flux across both the plasma membrane and intracellular membranes. In the plasma membrane, they are essential in both excitable and non-excitable cells for the control of membrane potential and cell signaling. However, our understanding of intracellular K+ channels is very limited. In this review, we summarize the recent development in studies of K+ channels in the lysosome. We focus on their characterization, potential roles in maintaining lysosomal membrane potential and lysosomal function, and pathological implications.

Role of hesperidin and fresh orange juice in altering the bioavailability of beta-blocker, metoprolol tartrate. An in vivo model.

The aim of my study was to find the effect of co-administrating orange juice and hesperidin on the bioavailability of metoprolol tartrate in rabbits.Metoprolol tartrate (10 mg/kg) was given orally to rabbits with hesperidin (10 mg/kg) and with orange juice (6 mL/kg) separately.The plasma concentrations of metoprolol tartrate were determined using reverse phase-high performance liquid chromatography at 1.5, 1, 2, 4, and 6 h, and the pharmacokinetic parameters were studied.In comparison to the control group, the AUC of metoprolol tartrate was increased significantly by 68.32% with hesperidin while orange juice substantially reduced the AUC by 37.08%. However, no significant change was observed in Tmax, Kel, and Vd in both groups. The relative bioavailability of metoprolol tartrate with hesperidin was 168.3% as compared to orange juice, that is, 62.9%.The present study revealed that the concurrent intake of hesperidin with metoprolol tartrate increased its bioavailability while orange juice administration suppressed its bioavailability. The change in bioavailability of metoprolol tartrate might be due to alterations in the activity of cytochrome P450 enzymes involved in the metabolism of metoprolol tartrate. However, the exact mechanism is still not known. These interactions may be of clinical significance.

Clustering of countries for COVID-19 cases based on disease prevalence, health systems and environmental indicators.

The coronavirus has a high basic reproduction number ( R 0 ) and has caused the global COVID-19 pandemic. Governments are implementing lockdowns that are leading to economic fallout in many countries. Policy makers can take better decisions if provided with the indicators connected with the disease spread. This study is aimed to cluster the countries using social, economic, health and environmental related metrics affecting the disease spread so as to implement the policies to control the widespread of disease. Thus, countries with similar factors can take proactive steps to fight against the pandemic. The data is acquired for 79 countries and 18 different feature variables (the factors that are associated with COVID-19 spread) are selected. Pearson Product Moment Correlation Analysis is performed between all the feature variables with cumulative death cases and cumulative confirmed cases individually to get an insight of relation of these factors with the spread of COVID-19. Unsupervised k-means algorithm is used and the feature set includes economic, environmental indicators and disease prevalence along with COVID-19 variables. The learning model is able to group the countries into 4 clusters on the basis of relation with all 18 feature variables. We also present an analysis of correlation between the selected feature variables, and COVID-19 confirmed cases and deaths. Prevalence of underlying diseases shows strong correlation with COVID-19 whereas environmental health indicators are weakly correlated with COVID-19.

Formulation and evaluation of natural antitussive cough syrups.

Among respiratory complications, cough is an important defensive pulmonary reflex that removes fluids, irritants or foreign substances from the respiratory tract. Rosa damascene Mill, petal extract is a traditional medicine and reported to use in the management of cough. In the present study rose petals extract samples were used to prepare natural antitussive cough syrups containing ivy leaf extract to observe synergistic effect of rose water in managing coughing in rats. Four cough formulations (A1, A2, A3 and A4) were prepared. The antitussive activity was observed at three dosage levels; 5ml, 10ml and 15ml. Cough was induced by the standard procedure using sulfur dioxide gas and ammonia. The antitussive activity was recorded by observing the coughing bouts. The result indicated that all formulations had a good effect on cough reduction at 90min but comparing the effect of formulations in all doses formulations, A2 followed by A3 and A4 at 30 minute time interval which is good in comparison with standard Diphenhydramine HCL and Dextromethorphan HBr 10ml in sulfur dioxide gas and ammonia induced cough. Hence, the results of the present study indicated the synergistic effect of rose water in the management of cough ailments.

Patients' and Caregivers' Views on Communication in the Referral-Consultation Process: A Qualitative Study.

This qualitative study aimed to describe patients' and caregivers' views on referral-consultation communication, how communication impacted their care and their perspectives on the components required in high-quality communication. Purposeful and convenience sampling was used to recruit participants from urban and rural areas who had been referred to Alberta specialists. Twenty participants joined one of four focus groups - two in-person and two teleconferences. Thematic analysis was conducted on the transcripts and field notes using NVivo 12 Pro. Participants reported inadequate communication between patients, family physicians and specialists. They discussed how incomplete information impacted their continuity of care, led to inappropriate referrals and caused delays in timely diagnosis or follow-up, all of which resulted in health consequences. They wanted physicians and healthcare professionals to engage them using a person-centred approach and provide a point of contact and timely updates of their referral statuses. This article includes participant feedback that can be used to improve closed-loop communications for referrals.

Schizosaccharomyces pombe kinesin-5 switches direction using a steric blocking mechanism.

Cut7, the sole kinesin-5 in Schizosaccharomyces pombe, is essential for mitosis. Like other yeast kinesin-5 motors, Cut7 can reverse its stepping direction, by mechanisms that are currently unclear. Here we show that for full-length Cut7, the key determinant of stepping direction is the degree of motor crowding on the microtubule lattice, with greater crowding converting the motor from minus end-directed to plus end-directed stepping. To explain how high Cut7 occupancy causes this reversal, we postulate a simple proximity sensing mechanism that operates via steric blocking. We propose that the minus end-directed stepping action of Cut7 is selectively inhibited by collisions with neighbors under crowded conditions, whereas its plus end-directed action, being less space-hungry, is not. In support of this idea, we show that the direction of Cut7-driven microtubule sliding can be reversed by crowding it with non-Cut7 proteins. Thus, crowding by either dynein microtubule binding domain or Klp2, a kinesin-14, converts Cut7 from net minus end-directed to net plus end-directed stepping. Biochemical assays confirm that the Cut7 N terminus increases Cut7 occupancy by binding directly to microtubules. Direct observation by cryoEM reveals that this occupancy-enhancing N-terminal domain is partially ordered. Overall, our data point to a steric blocking mechanism for directional reversal through which collisions of Cut7 motor domains with their neighbors inhibit their minus end-directed stepping action, but not their plus end-directed stepping action. Our model can potentially reconcile a number of previous, apparently conflicting, observations and proposals for the reversal mechanism of yeast kinesins-5.

TNF gene promoter region polymorphisms and association with young-onset rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that shares a major global economic burden due to disabilities and mortality risk. It affects all age groups with a female predominance. Tumor Necrosis Factor (TNF) a proinflammatory cytokine is one of the key players in etiology of autoimmune diseases such as RA. TNF gene promoter polymorphisms predict disease susceptibility, severity and therapeutic response. Therefore, the current case-control study was designed to evaluate the possible association of TNF gene promoter polymorphisms (-238 and -308) with susceptibility to young-onset RA. The study involves 102 individuals (50 young-onset RA patients, 52 healthy individuals). Genomic DNA was extracted using a standard phenol-chloroform method followed by PCR-RFLP for the screening of TNF gene promoter polymorphisms (-238 and -308). The study resulted in the association of TNF -238G/A polymorphism with susceptibility to young-onset RA in the homozygous form GG (Odds Ratio = 3.23, p-value= <0.05), though no significant difference was observed for -308G/A polymorphism among young-onset RA patients and controls. Thus concludes; TNF -238/G/A contributes to the risk of susceptibility to young-onset RA, conversely, TNF -308 G/A protects against the disease. Consequently, the study has demonstrated a possible relationship of studied TNF polymorphism with young-onset RA.

Humanization of fibroblast growth factor 1 single-chain antibody and validation for its antitumorigenic efficacy in breast cancer and glioma cells.

Single-chain variable fragment (scFv) antibodies are the smallest immunoglobulins with high antigen-binding affinity. We have previously reported that fibroblast growth factor 1 played pivotal roles in cancer development and generated a mouse scFv (mscFv1C9) could effectively prohibit cancer cell proliferation in vitro and in vivo. Here, we further humanized this scFv (hscFv1C9) using a structure-guided complementarity determining region grafting strategy. The purified hscFv1C9 maintained similar antigen-binding affinity and specificity as mscFv1C9, and it was capable of inhibiting growth of different tumours in vitro and in vivo. These data strongly suggested that hscFv1C9 has antitumour potentials.

Molecular epidemiology of bovine anaplasmosis in Khyber Pakhtunkhwa, Pakistan.

Bovine anaplasmosis is endemic in Pakistan where it reduces livestock productivity and leads to high mortality, especially in young animals. This study was aimed to identify the potential risk factors responsible for the occurrence and spread of anaplasmosis in cattle and buffaloes for the first time in Pakistan. A total of 900 (cattle = 479, buffalo = 421) blood samples were collected irrespective of age and sex from three distinct zones of Khyber Pakhtunkhhwa (KP) province of Pakistan. Polymerase chain reaction (PCR) technique was used for the molecular detection of anaplasmosis. Data collected on a piloted questionnaire including 11 predicting variables which were analyzed using R-statistical software, and association between the dependent and independent variables was assessed using univariable analysis. Automated and manual approaches were exercised, producing comparable models. Key risk factors identified in all the approaches included species of the animal, breed of animal, sex of animal, tick infestation status, previous tick history, tick control status, and acaricides used (odds ratio > 1). The 611 bp DNA fragment specific for 16S rRNA gene of Anaplasma spp. was produced from 165 samples. The samples were confirmed for anaplasmosis through sequencing and BLAST queries. The findings of the current study conclude that by enhancing the protective measures to control the identified risk factors can reduce the spread of anaplasmosis in Pakistan.

Systemic therapies in the treatment of non-small-cell lung cancer brain metastases.

Non-small-cell lung cancer (NSCLC) brain metastases are common. Even though there are various subsets of NSCLC with molecular alterations, there is a common theme of brain metastases. Current treatment modalities are suboptimal. Systemic therapies for the treatment of NSCLC brain metastases have been explored and recent advances may pave the way for their successful employment in this patient population. While no specific agents have been associated with a marked benefit, stability of disease as well as radiographic responses have been noted in some patients. Biological activity of systemic therapies in some patients with NSCLC brain metastases raises hope for future advances and supports further investigation for this patient population with limited treatment options.

Parental Psychological Abuse toward children and Mental Health Problems in adolescence.

OBJECTIVE: Present study was conducted to explore the relationship between parental psychological abuse toward their children and mental health problems in adolescence. METHOD: Three hundred participants age range 13-17 years, (57% boys and 43% girls) participated in the study from both public and private high schools of Lahore. Psychological maltreatment experience scale (PMES) and Youth Self-Report(YSR) were used for assessment and diagnosis. RESULTS: Findings revealed that psychological abuse by parents significantly related with mental health problems in adolescents, for mother abuse (r= .24 to.67, p< .05) and father abuse (r= .20 to.70, p< .05). Adolescents who perceived their parents as more abusive exhibited greater problems. Regression analysis indicated that hypothesized factors of parental psychological abuse predicted the mental health problems in adolescents (contributed from 10% to 49% of variance). CONCLUSION: Psychological abuse by parents is related with mental health problems in adolescents. These findings will contribute to a better understanding of non-injurious psychological abuse and its impact on adolescents. Findings of the study can be used to bring the attention of parents, public and professionals' towards damaging effects of psychological abuse on adolescents.

Bilateral renal lymphangiectasia: Literature review of a rare entity.

Renal lymphangiectasia (RL) is a rare condition in which lymphatic vessels are dilated giving rise to cyst formation in peripelvic, perirenal and intrarenal locations. Knowledge about RL is limited and based upon individual case reports. This can be genetic or acquired. There is no significant association with any gender or age. It can be manifested as focal or diffuse forms and can be unilateral or bilateral. Most of the cases present with abdominal or flank pain. The diagnosis is based on radiological imaging. Due to rarity of diseases, it has potential to be misdiagnosed as other cystic disease of kidneys. The treatment is mainly conservative but prolonged follow up for associated complications like hypertension and renal vein thrombosis is required. We have presented a case of bilateral renal lymphangiectasia with the review of available literature.

The Role of Pro-Inflammatory Chemokines CCL-1, 2, 4, and 5 in the Etiopathogenesis of Type 2 Diabetes Mellitus in Subjects from the Asir Region of Saudi Arabia: Correlation with Different Degrees of Obesity.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in developing nations. The high prevalence of obesity and related diabetes cases are attributed to rapid economic progress, physical inactivity, the consumption of high-calorie foods, and changing lifestyles. OBJECTIVES: We investigated the roles of pro-inflammatory chemokines CCL1, 2, 4, and 5 in T2DM with varying levels of obesity in the Asir region of Saudi Arabia. MATERIALS AND METHODS: In total, 170 confirmed T2DM subjects and a normal control group were enrolled. Demographic data, serum levels of CCL-1, 2, 4, and 5, and biochemical indices were assessed in the subjects and control groups by standard procedures. RESULTS: T2DM subjects were divided into four groups: A (normal body weight), B (overweight), C (obese), and D (highly obese). We observed that male and female control subjects had similar mean serum concentrations of pro-inflammatory chemokines CCL-1, 2, 4, and 5. T2DM subjects in all the four groups showed significantly higher levels of all the four chemokines compared to the controls, regardless of gender. In T2DM subjects with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL-1, 2, and 4 in T2DM subjects with increasing BMI. Serum CCL5 levels increased significantly in all T2DM subject groups. The increase in CCL5 was more predominant in normal-weight people, compared to overweight and obese T2DM subjects. CONCLUSIONS: Male and female control subjects had similar serum levels of pro-inflammatory chemokines CCL-1, 2, 4, and 5. The progressive rise in blood concentrations of three pro-inflammatory chemokines CCL-1, 2, and 4 in T2DM subjects with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM subject groups. The selective and more pronounced increase in CCL5 in the T2DM group with normal BMI, compared to subjects with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 underexpression in overweight and obese T2DM subjects is due to some unexplained counterbalancing processes.

Agreement Between Mucicarmine-Stained Bronchial Brushing and Bronchial Biopsy in Subtyping Non-small Cell Lung Carcinoma.

Background Bronchial brushing and biopsy are used for the diagnosis of lung carcinoma as most of these tumors are unresectable. Recently, the subclassification of non-small cell lung carcinoma (NSCLC) into adenocarcinoma (ADC) and squamous cell carcinoma (SCC) has become mandatory due to the emergence of targeted therapies. Due to the inherent limitations of small samples, subcategorization of a tumor is not always possible. Immunohistochemical and mucin stains are being used for this purpose, especially for tumors with poorly differentiated features. In our study, we utilized mucicarmine mucin stain to refine the differentiation of SCC and ADC on bronchial brushing and determine its agreement with bronchial biopsy. This study aimed to measure the degree of agreement between mucicarmine-stained bronchial brushing and bronchial biopsy for subtyping NSCLC into SCC and ADC. Methodology This descriptive, cross-sectional study was conducted in the pathology department of Allama Iqbal Medical College. Samples were collected by the pulmonology department of Jinnah Hospital Lahore. The study was conducted for 10 months from June 2020 to April 2021. A total of 60 cases diagnosed as NSCLC, aged between 35 and 80 years, were included in this study. After cytohistological evaluation of bronchial brushing and bronchial biopsy specimens, the agreement was deduced using kappa statistics. Results The strength of agreement between mucicarmine-stained bronchial brushing and bronchial biopsy for subtyping NSCLC into SCC and ADC was found to be substantial. Conclusions As significant agreement exists between the two modalities, mucicarmine-stained bronchial brushing can be used for a reliable and rapid categorization of NSCLC.