Development of neonatal brain functional centrality and alterations associated with preterm birth.

Formation of the functional connectome in early life underpins future learning and behavior. However, our understanding of how the functional organization of brain regions into interconnected hubs (centrality) matures in the early postnatal period is limited, especially in response to factors associated with adverse neurodevelopmental outcomes such as preterm birth. We characterized voxel-wise functional centrality (weighted degree) in 366 neonates from the Developing Human Connectome Project. We tested the hypothesis that functional centrality matures with age at scan in term-born babies and is disrupted by preterm birth. Finally, we asked whether neonatal functional centrality predicts general neurodevelopmental outcomes at 18 months. We report an age-related increase in functional centrality predominantly within visual regions and a decrease within the motor and auditory regions in term-born infants. Preterm-born infants scanned at term equivalent age had higher functional centrality predominantly within visual regions and lower measures in motor regions. Functional centrality was not related to outcome at 18 months old. Thus, preterm birth appears to affect functional centrality in regions undergoing substantial development during the perinatal period. Our work raises the question of whether these alterations are adaptive or disruptive and whether they predict neurodevelopmental characteristics that are more subtle or emerge later in life.

The PD-1/PD-L1 Axis in the Biology of MASLD.

Metabolic Dysfunction-Associated Steatotic Liver (MASL), previously named nonalcoholic fatty liver (NAFL), is a multifactorial disease in which metabolic, genetic, and environmental risk factors play a predominant role. Obesity and type 2 diabetes act as triggers of the inflammatory response, which contributes to the progression of MASL to Metabolic Dysfunction-Associated Steatohepatitis and the development of hepatocellular carcinoma. In the liver, several parenchymal, nonparenchymal, and immune cells maintain immunological homeostasis, and different regulatory pathways balance the activation of the innate and adaptative immune system. PD-1/PD-L1 signaling acts, in the maintenance of the balance between the immune responses and the tissue immune homeostasis, promoting self-tolerance through the modulation of activated T cells. Recently, PD-1 has received much attention for its roles in inducing an exhausted T cells phenotype, promoting the tumor escape from immune responses. Indeed, in MASLD, the excessive fat accumulation dysregulates the immune system, increasing cytotoxic lymphocytes and decreasing their cytolytic activity. In this context, T cells exacerbate liver damage and promote tumor progression. The aim of this review is to illustrate the main pathogenetic mechanisms by which the immune system promotes the progression of MASLD and the transition to HCC, as well as to discuss the possible therapeutic applications of PD-1/PD-L1 target therapy to activate T cells and reinvigorate immune surveillance against cancer.

Curcumin and Andrographolide Co-Administration Safely Prevent Steatosis Induction and ROS Production in HepG2 Cell Line.

Non-alcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease worldwide. Curcumin and andrographolide are famous for improving hepatic functions, being able to reverse oxidative stress and release pro-inflammatory cytokines, and they are implicated in hepatic stellate cell activation and in liver fibrosis development. Thus, we tested curcumin and andrographolide separately and in combination to determine their effect on triglyceride accumulation and ROS production, identifying the differential expression of genes involved in fatty liver and oxidative stress development. In vitro steatosis was induced in HepG2 cells and the protective effect of curcumin, andrographolide, and their combination was observed evaluating cell viability, lipid and triglyceride content, ROS levels, and microarray differential gene expression. Curcumin, andrographolide, and their association were effective in reducing steatosis, triglyceride content, and ROS stress, downregulating the genes involved in lipid accumulation. Moreover, the treatments were able to protect the cytotoxic effect of steatosis, promoting the expression of survival and anti-inflammatory genes. The present study showed that the association of curcumin and andrographolide could be used as a therapeutic approach to counter high lipid content and ROS levels in steatosis liver, avoiding the possible hepatotoxic effect of curcumin. Furthermore, this study improved our understanding of the antisteatosis and hepatoprotective properties of a curcumin and andrographolide combination.

The journey from viral hepatitis to hypocythemia: Two case reports.

Acute viral hepatitis, including hepatitis A, B, E, D, and G, can lead to severe bone marrow suppression due to cytotoxic lymphocytes. The bone marrow suppression causes aplastic anaemia which is mostly unresponsive to immunosuppressive therapy. Such patients require bone marrow transplant for a complete cure. The pancytopenia can evolve during recovery from transaminitis. We are presenting two case reports relating aplastic anaemia with acute viral hepatitis in two young patients-23 and 16 years of age. The 23-year-old female patient had hepatitis A associated with aplastic anaemia whereas the young 16-year-old male patient was diagnosed with Hepatitis E IgG associated aplastic anaemia. Unfortunately, the first patient could not cope with the complications relating to pancytopenia and was unable to reach the bone marrow transplant stage. The second patient did not have a bone marrow transplant but showed an excellent response to immunosuppressive therapy before the transplant and survived.

Correlation between stages of breast cancer and BMI in females: a multi-centre study.

OBJECTIVE: To determine the link between breast cancer and obesity in women by using body mass index at the time of diagnosis. Methods: The cross-sectional study was conducted from October 2019 to April 2020 at Pakistan Ordinance Factories Hospital, Wah Cantt, and Islamabad Medical Complex National Engineering and Scientific Commission Hospital, Islamabad, Pakistan. The sample comprised women aged 40-70 years with a recent diagnosis of breast cancer. Patients' body mass index values were calculated after they were diagnosed and additional staging examinations were carried out. Data was analysed using SPSS 21. RESULTS: There were 100 cases with a mean age of 52.24±7.47 years. There was a significant link between obesity and breast cancer (p=0.002), with higher body mass index carrying a higher risk of advanced breast cancer. CONCLUSIONS: Obesity may contribute to postmenopausal breast cancer in women.

Exploring areas of improvement in postnatal care services in a tertiary care hospital in Lahore.

Background and Objective: Poor postnatal care can increase morbidity and mortality. This study assessed the current deficiencies in quality of postnatal care provided to mothers in Lady Aitchison hospital, Lahore when compared to WHO standards and identifies the areas for quality improvement. Methods: It is a descriptive cross-sectional study which employs quantitative method to collect and analyze the data. It was conducted to include ninety-six maternities attending the wards of Lady Aitchison Hospital, Lahore during January 2022 to February 2022. Consenting post-partum mothers were selected by random sampling and interviewed by using a structured proforma. Results: Among 96 mothers, 56% were below 25 years of age, 39% had secondary education, with more than one child (71%) and 57% visited for the first time. Majority of mothers, were given medicine timely (82%) and found the attitude (85%) and information (83%) provided by the healthcare workers helpful. Their subjective satisfaction rate with staff was 90%. The main areas of concern were lack of proper examination guidelines and facilities, limited information to mothers regarding neonatal care and substandard interior of hospitals. The statistics on the detailed maternal and neonatal examination showed that it was left out in 30% to 50% patients. Information regarding the danger signs of mothers and neonates was not given in 69% and information on family planning was provided to only 28%. Contentment with the infrastructure of the hospital was subpar and it was suggested that the sanitary conditions of washrooms and the paraphernalia of the wards i.e., ACs and beds needed improvement. Conclusions: This study suggests that in developing countries like Pakistan, majority of the patients were satisfied by the services of healthcare workers. The prime improvement area is the infra-structure of the hospital which can be upgraded to provide better quality facilities in terms of air-conditioning, washrooms and well-designed areas for extensive examination of breast, pelvis, abdomen and neonates. There is also need for introduction of standard guidelines for postnatal care.

Age-appropriate BMI cut-points for cardiometabolic health risk: a cross-sectional analysis of the Canadian Longitudinal Study on Aging.

OBJECTIVES: Body composition changes that occur with aging pose unique health risks to older adults. The current World Health Organization (WHO) body mass index (BMI) cut-points may not accurately reflect health risks in older adults (65+). Prior findings suggest those classified as overweight may be conferred survival advantages. This study aims to define age-specific BMI cut-points for adults (45-64, 65-74, and 75-85 years) associated with cardiometabolic outcomes, and compare the performance of these thresholds to the WHO BMI thresholds using cardiometabolic conditions and frailty as outcomes. METHODS: Using baseline data from the comprehensive cohort of the Canadian Longitudinal Study on Aging (N = 30,097), a classification and regression tree cross-sectional analysis was conducted to derive age-specific BMI cut-points based on cardiometabolic health risk. The area under the receiver operating curve (AUC), sensitivity, and specificity were estimated. Agreement with waist circumference was conducted. RESULTS: For older adults (65-74 and 75+ years old), the BMI threshold for identifying overweight increased to 26.9 and 26.6, respectively, from the WHO definition of 25.0 kg/m2. For obesity, the thresholds were revised to 29.0 and 30.9, respectively, from 30.0. The largest improvements to AUC occurred in older adults (65+). Across all age-sex stratifications, the new overweight threshold demonstrated lower sensitivity and higher specificity compared to the traditional threshold. Age-specific BMI thresholds demonstrated higher agreement with waist circumference for some age-sex stratifications and poor performance with hearing. CONCLUSIONS: Age-appropriate BMI thresholds for older adults may improve classification by health risk compared to standard WHO cut-points. A higher overweight threshold but lower obesity cut-points may be best suited to this demographic.

Awareness and adherence to lifestyle modifications in hypertensive patients presenting to a tertiary care setting.

OBJECTIVE: To assess the level of awareness and adherence to lifestyle modifications in hypertensive patients. METHODS: The descriptive study was conducted from January to June 2019 at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, and comprised adult patients of either gender with hypertension history of at least 1 year. Data was collected using a structured questionnaire to evaluate the subjects' awareness and adherence to lifestyle modifications for the control of hypertension. Data was analysed using SPSS 20. RESULTS: Of the 294 patients, 160(54.4%) were women. The overall mean age was 53.3±12.1 years and mean body mass index was 27.1±5.9kg/m2, and mean duration of hypertension was 8.2±7.1 years. There were 122(41.5%) obese and 97(33%) overweight patients. Overall, 201(68.4%) patients had co-morbidities and 40(13.6%) were smokers. Of the total, 205(69.7%) knew the importance of exercise, but 104(35.4%) were doing it; 270(91.8%) were aware of restriction of sodium diet, but 244(83%) were adhering to it; 222(75.5%) knew the importance of dietary approaches to stop hypertension, but 185(62.9%) were adhering to it; and 247(84%) were aware that regular blood pressure measurement and follow-ups were important, but 150(51%) were adhering to it. CONCLUSIONS: The level of awareness regarding lifestyle modifications was found to be high in hypertensive patients, but the status of adherence was not up to the mark.

Assessment of quality of life of stroke survivors and their caregivers presenting to a tertiary care hospital in Pakistan.

OBJECTIVE: To determine the quality of life of stroke survivors and their caregivers presenting to a tertiary care setup. METHODS: The descriptive study was conducted from July to December 2019 at the Neurology Department, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, and comprised patients of either gender with ischaemic or haemorrhagic stroke aged 40-70 years and their caregivers. Data was collected using the stroke-specific quality of life Scale and the caregiver quality of life questionnaire. Data was analysed using SPSS 20. RESULTS: Of the 80 patients, 50(62.5%) were males and 30(37.5%) were females. The overall mean age was 61.46±11.80 years, and 56(70%) were aged >55 years. Among the patients, speaking power, mobility and mood were more affected with mean levels of 15.51±8.63, 22.63±8.33 and 19.08±7.05, respectively. The domains of social role, self-care and upper extremity function were also affected with mean values of 19.022±7.06, 15.71±8.81 and 18.88±7.02, respectively. Among the caregivers, the levels of physical wellbeing and functional wellbeing were high 15.07±5.65 and 15.35±5.76, respectively. There were differences in terms of age and gender but the difference was not significant (p>0.05). CONCLUSIONS: The quality of life of stroke survivors was low, and that of caregivers was also quite compromised.

Unpredictability of SARS-CoV-2: Pneumoperitoneum a rare complication.

COVID-19 is a viral disease caused by a novel coronavirus that ignited the ongoing pandemic in December 2019. The infected patients may be asymptomatic, have fever and myalgias, develop mild pulmonary symptoms or go into overt respiratory failure. There is also a significant number of patients with gastrointestinal and thromboembolic disease presentation and complications. Since respiratory features predominate, physicians might miss other systemic manifestations. Here, we present the case of a 62-year-old male who was admitted with COVID-19 pneumonia and later went into septic shock and then developed acute abdomen caused by small gut perforation.

Drug-induced duodenal perforation in the paediatric patient with thalassemia major, an unreported side effect of iron- chelating agent: A case report.

Duodenal ulcer disease is uncommon in paediatric age group. Its perforation is even rarer. However, it should be kept in mind when examining children with acute abdomen especially if there are signs of shock or possibility of upper gastrointestinal bleed. We report a case of a 6 years old female child, a known case of thalassemia major and taking oral Deferasirox since two years of age. She had atypical presentation as there was no previous history of peptic ulcer disease and she only suffered epigastric pain and vomiting for a week but due to lack of proper diagnosis at a local clinic developed duodenal ulcer perforation, which was ultimately diagnosed at a tertiary care hospital and managed with Graham Patch Closure.

Wheat pill poisoning: complications and management.

Wheat pill (zinc or aluminium phosphide), also known as rice pill, is used as rodenticide in wheat and rice storage reservoirs. In developing countries such as Pakistan there has been an increase in the number of aluminium phosphide (wheat pill) poisoning with suicidal intent due to its easy accessibility. It has a high mortality rate, with no antidote available. A young female presented with classical signs and symptoms of wheat pill poisoning, although during her stay at the hospital she developed cardiac arrhythmias leading to shock, haematuria, pleural effusion, and hyperglycaemia due to acute pancreatitis. Due to the appropriate recognition and management of the complications, the patient was able to recuperate. Appropriate transfer to Intensive Care Unit and prompt recognition of complications can lead to good outcomes. We recommend that there should be a nationwide cognizance campaign regarding the lethal consequences of wheat pill consumption by humans and proper disposal of this deadly material.

Comparative analysis of Bacterial Vaginosis microbiota among pregnant and non-pregnant females and isolation of phages against Enterococcus faecalis, Enterococcus faecium, and Shigella flexneri strains.

BACKGROUND AND OBJECTIVES: Bacterial vaginosis (BV) is the most common vaginal infection in women of reproductive age. It shifts the paradigms of the vagina from healthy, beneficial microbiota to facultative and strict anaerobes. BV remains one of the most arduous and controversial challenges in modern-day clinical microbiology because of its high prevalence and relapse rates. A lot of research has been carried out on it. Still, its etiology is unknown, which gave this infection global importance. The current study was designed to investigate and compare the microbiota of pregnant and non-pregnant females suffering from BV, and phages were isolated against BV microbiota. MATERIAL AND METHODS: The samples were collected from the vagina by using a speculum, and swabs were streaked on different media to isolate bacteria. The microbiological analysis was performed by microscopy, biochemical testing, and antibiotic susceptibility was determined by using Metronidazole and Clindamycin. Furthermore, the phages were isolated and characterized against BV strains. RESULTS AND CONCLUSION: The Gram staining showed high prevalence of Staphylococcus (36% vs. 33%), followed by Streptococcus (31% vs. 14%) and Enterococcus (7% vs. 14%) in non-pregnant and pregnant females' respectively. However, the exception was observed in non-pregnant BV positive females, who had Shigella flexneri in their samples. The antibiotic sensitivity showed Metronidazole was resistant against all BV microbiota, and Clindamycin showed susceptibility against 3 strains. Phages were isolated against three bacterial strains, i.e. E. faecalis, E. faecium, and S. flexneri. Bacterial reduction assay showed bacterial growth decreases in the presence of phage suspension, pH stability showed phages' maximum lytic activity at pH 7 for E. faecalis and E. faecium and pH 9 for S. flexneri. However, the thermal stability showed phages' highest lytic activity at 55 °C for E. faecalis, 70 °C for E. faecium, and 40 °C for S. flexneri. Phage genome isolation showed that all phages nucleic acid was DNA in nature and between 15 and 20kbp. SEM analysis showed they were circular in shape and might belong to the Podoviridae family. This study provides an understanding of pathogens involved in BV and helps the doctors to treat the patients accordingly. Furthermore, this study showed that Bacterial Vaginosis and BV secondary bacteria have associations. BV secondary microbiota is also involved in the pathogenesis of this infection, whereas bacteriophage therapy has the potential to be used as an alternative treatment to antibiotics.

DAR-GRACE: Diabetes and Ramadan: glycaemic control, physician counselling and patient practices -experience from a tertiary care hospital in Pakistan.

OBJECTIVE: To identify patient practices and knowledge pertaining to Ramadan fasting and to see whether physicians were providing adequate counselling and adjusting medications accordingly. METHODS: The cross-sectional study was conducted at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from June to August 2018, and comprised diabetic patients who fasted during Ramadan. A questionnaire was designed to assess patients' knowledge, risk category, pre-Ramadan counselling, medication adjustment, lifestyle changes, pre- and post- Ramadan glycated haemoglobin levels, and complications during Ramadan. Data was analysed using SPSS 23. RESULTS: Out of 272 diabetics, 176(64.7%) were females. Mean number of fasts kept were 22±10.61. Pre-Ramadan 120(44.1%) patients consulted their physicians and 105(87.5%) of them received relevant counselling. Medications were adjusted in only 30 (25%) such cases. Overall, 41(15.1%) patients were in the high risk category, while 109(40.1%) and 122(44.9%) were in the moderate and low-risk categories. During the month, 17(6.25%) were hospitalised due to diabetes-related complications. Glycated haemoglobin levels fell significantly (p<0.0001). CONCLUSIONS: Anomalous patient behaviours and suboptimal physician practices were noticed.

Bacterial vaginosis: An insight into the prevalence, alternative treatments regimen and it's associated resistance patterns.

Bacterial Vaginosis (BV) is a complex polymicrobial infection of vagina that shifts the paradigms of vaginal flora from lactobacilli to opportunistic pathogens. BV is catagorized by greyish white discharge, pH greater than 4.5. It results in the preterm labor, abortion, pelvic inflammatory disorders, post cesarean infections. BV is associated with Sexually Transmitted Diseases (STDs) or immune deficiency disorders like Human Immunodeficiency Virus, Human Papilloma Virus, Herpes Simplex Virus 1 and 2, and Neisseria gonorrhoeae. The prevalence rate is about 21.2 million (29.2%) worldwide. BV is more frequent in black females as compared to white females, independent of geographical distribution. Globally, BV is treated with the current recommended antibiotic therapy including Metronidazole and Clindamycin. The recurrence rates are 76% and occur within 06 months of treatment due to antibiotic resistance against pathogenic bacteria and their biofilms. The antibiotic resistance is a global health issue which directs the attentions towards other treatments. One of these is the treatment of sex partners, thus helping to stop the recurrence rates in females. However, this method does not show any positive results. Probiotic therapy is an incorporation of Lactobacilli orally or intravaginally for the recolonization of healthy microbes. This therapy has exhibited promising results but some studies revealed that Probiotic therapy does not control the recurrence rate. The other methods are in trials period and none of them are used clinically or commercially available for the treatment. The thermoplastic polyurethane (TPU) intravaginal rings contain lactic acid and metronidazole showed promising results in trials of BV treatment. The vaginal acidifiers are used as an alternative method to maintain the vaginal pH but the process of douching is a major limitation. The activated charcoal is used to treat BV patients in clinical trials showed decrease in the pH with only 3.1% loss of lactobacilli. Phage therapy is a reemerging field to overcome the bacterial resistance. They are host specific and easier to handle. They can be used naturally, synthetically; phage cocktails and phage-antibiotics combination can be used. Phages show auspicious results for the treatment of bacterial infections as compared to antibiotics as they also treat biofilms. This is one of the promising therapy in future to treat infections with no side effects. Phage therapy can be used in pharmaceuticals according to Food and Drug Administration (FDA) guidelines. Taken together, it is suggested that large funding is required by pharmaceutical sector or government for further investigation of bacteriophages to be used against BV pathogenesis.

Primary angiosarcoma of neck nodes with bony metastasis - A case report.

This is a case of a 30 year old female who presented in February 2012 with a large painless left neck swelling since 5 months. Her biopsy was done but the result was inconclusive. Later on after proper staging workup it was found to be bony metastatic disease. Her repeated biopsy showed spindle cell lesion. She was advised surgery, which was done revealing poorly differentiated angiosarcoma involving 27 out of 33 lymph nodes. Angiosarcoma is an uncommon malignant neoplasm characterized by rapidly proliferating, extensively infiltrating anaplastic cells derived from blood vessels and lining irregular blood-filled spaces. Cutaneous angiosarcoma of the scalp and face is the most common form of angiosarcoma. Angiosarcoma of the cervical lymph node without a primary scalp or oral cavity lesion is a very rare presentation and has been reported only once. Thus, this case reported with bony metastasis can be labeled as the first of its kind.

The Management of Preeclampsia: A Comprehensive Review of Current Practices and Future Directions.

Preeclampsia (PE) is a disease in pregnancy that is characterized by new-onset hypertension end-organ dysfunction, often occurring after 20 weeks of gestation. Risk factors include a prior history of PE, diabetes, kidney disease, obesity, and high maternal age at pregnancy. Current treatment and management guidelines focus on the management of high blood pressure and any potential complications. The only known curative treatment is termination of pregnancy (either induction of delivery or cesarean section). However, the current guidelines and recommendations lack adequate prediction markers and are unable to prevent maternal and fetal mortality. There also exists a need for multidisciplinary collaborative action in view of the quality of life and psycho-educational counseling.

Perioperative Intravenous Lidocaine Infusion for Postlaparoscopic Cholecystectomy Pain.

OBJECTIVE: To compare intravenous lidocaine infusion adjunct to NSAID and Acetaminophen with regular analgesics for postoperative mean pain score and mean ambulation time after laparoscopic cholecystectomy. STUDY DESIGN: Randomised controlled trial. PLACE AND DURATION OF STUDY: Department of General Surgery, Islamabad Medical Complex, (IMC), from March 2020 to December 2021. METHODOLOGY: Sixty (n=60) adult patients, both males and females between the ages of 18-60 years planned for laparoscopic cholecystectomy, were selected and randomly allocated to two groups of treatment (Lidocaine and Ringer Lactate). The control group did not receive any other placebo other than Ringer Lactate infusion. Both groups received Intramuscular Diclofenac 12 hourly and intravenous acetaminophen infusion 8 hourly. Postoperative pain 2, 6, 12 and 24 hours (h) and mean ambulation time were compared in both groups. RESULTS: Mean VAS (Visual Analogue Scale) of group 1 versus group 2 at 2 h, 6 h, 12 h and 24 h were 3.47 ± 0.82 vs. 6.27 ± 0.52 (p=<0.001), 2.7 ± 0.75 vs. 4.8 ± 0.8 (p<0.001), 2.0 ± 0.49 vs. 3.93 ± 0.94 (p<0.001), 0.73 ± 0.82 vs. 2.2 ± 0.61 (p<0.001). Time for spontaneous ambulation after surgery was 5.57 ± 1.55 hours for Group 1 versus 7.3 ± 1.9 hours for Group 2 (p<0.001). CONCLUSION: Pain scores at all-time intervals were lower, and ambulation time was shorter in patients who received intravenous infusion of lidocaine as compared to patients who received only regular analgesics for laparoscopic cholecystectomy. KEY WORDS: Ambulation time, Laparoscopic cholecystectomy, Postoperative pain.

A rare case of Swyer syndrome from Pakistan in a young girl with primary amenorrhea and 46XY genotype.

Swyer syndrome is a condition where individuals with a 46XY karyotype, typically associated with males, display complete gonadal dysgenesis and lack testicular differentiation. This results from a mutation in the SRY gene, which is essential for testis development. As a consequence, affected individuals who appear phenotypically female have male chromosomes but do not develop functional testes. As a result, there is an absence of testosterone that leads to lack of masculinization and the presence of female genitalia. This article describes a 20-year-old female from Pakistan who exhibited primary amenorrhea. On examination, she possessed a typical female physique but lacked breast growth and axillary hair. She had scant pubic hair with female-type external genitalia. The pelvic imaging showed a underdeveloped uterus, along with small ovaries and fallopian tubes. Her karyotype came out to be 46XY. The examination and radiological results indicated Swyer syndrome. During laparoscopy, the patient's uterus was found to be infantile, while the fallopian tubes were healthy. Streak gonads were also present, and due to the risk of gonadoblastoma, they were surgically removed. Hormone replacement therapy was started to induce pubertal development and optimize bone mineral accumulation.