THE BROWN ALGAE: SARGASSUM BINDERI SONDER SHOWS A POTENTIAL NEPHROPROTECTIVE ACTIVITY IN IN-VIVO EXPERIMENTAL MODEL.

OBJECTIVES: This study aimed to investigate the protective effect of ethanolic (EtOH) and water (H2O) extracts of brown seaweed named Sargassum binderi (S. binderi) against cisplatin (anticancer drug) - triggered nephrotoxicity. This drug is normally used for the treatment of solid tumors that causes acute kidney damage after assemblage in the renal tubules. MATERIAL AND METHODS: It was an acute study, animals were divided into different groups randomly, cisplatin (7mg/kg i.p.) and normal saline were used as positive and negative control respectively. The EtOH and H2O extracts of S. bindari were given orally in a dose of 200mg/kg for 5 days to their respective groups. Nephroprotective and antioxidants potential of extracts were investigated in term of kidney and liver biomarkers, electrolytes, glucose & lipid profile along with reduced glutathione, catalase and malondialdehyde. GC-MS was performed to evaluate the presence of important therapeutic compounds in hexane extract of S.binderi. RESULTS: The EtOH and H2O extracts were found effective in decreasing the kidney and liver biomarkers with glucose and lipid profile, normalizing electrolytes which were disturbed by cisplatin and up-grading the antioxidant parameters by reducing the oxidative stress. GC-MS evaluation of hexane extract revealed the presence of 21 new compounds from S.binderi. Of which, 8-heptadecene, methyl tetradecanoate, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, hexadecanoic acid, methyl ester were reported as antioxidant, anti-inflammatory, anti-diuretic and hypocholesterolemic compounds. CONCLUSION: S. binderi showed nephroprotective effect by stabilizing its associated biochemical parameters probably due to the antioxidant activity as confirmed by the presence of compounds.

TriClip G4: A game-changer for tricuspid valve regurgitation treatment.

Tricuspid valve regurgitation, or TR, is a difficult-to-manage condition. In addition to EVOQUE, percutaneous annuloplasty, and surgical repair, the TriClip G4 system has been added to the interventional therapeutic choices for TR. Recently, the Food and Drug Administration (FDA) approved the use of the TriClip G4 device to treat patients with symptomatic, severe TR who have received optimal medication therapy but are at intermediate or higher risk of surgery. This review attempts to offer a thorough examination of the procedural features, learning curves, results of the device and compares the TriClip G4 system to other interventional therapies for TR. TriClip G4 has shown to have promising results in pivotal clinical trials, be cost-effective, and improve the quality of life of patients. Furthermore, it has its unique advantages against other conventional techniques and devices.

Healthcare workers' knowledge and risk perception regarding the first wave of COVID-19 in Khyber Pakhtunkhwa, Pakistan: an online cross-sectional survey.

Background: Increased COVID-19 transmission among the populace may be caused by healthcare workers (HCWs) who lack knowledge, awareness, and good preventive practices. Additionally, it may cause elevated stress levels, anxiety, poor medical judgement, and situational overestimation. Objectives: The present survey aimed to assess knowledge and risk perception regarding COVID-19 among HCWs in Khyber Pakhtunkhwa (KP), Pakistan. Methodology: A web-based online, pre-tested questionnaire comprising 26 items was circulated via social media in April 2020 amongst HCWs in major tertiary care facilities in KP. Results: The study's results, revealing both the commendable knowledge levels among HCWs about COVID-19 and their heightened risk perception, highlight the critical need for targeted interventions to address the potential impact on self-protective behaviour and mental health within this vital workforce. This insight is important for designing strategies that not only enhance HCWs' well-being but also ensure the continued effectiveness of healthcare delivery during pandemics. The percentage mean score (PMS) of COVID-19 knowledge was 85.14±10.82. Male HCWs and those with an age older than or equal to 32 years demonstrated a higher knowledge score (85.62±11.08; P=0.032 and 87.59±7.33, P=0.021, respectively). About 76% of HCWs feared contracting COVID-19. Nearly 82% of respondents were mentally preoccupied with the pandemic and also terrified of it. 'Of these, 81% were nurses, 87% had a job experience of 6-8 years and 54.45% were frontline workers. Feelings of panic and concern about the pandemic were found to be more in HCWs who were physicians above the age of 32, and who had 3-5 years of work experience. HCWs' overall risk perception was found to be significantly different between males (7.04±2.26) and females (8.01±1.97), job experience of 6-10 years (8.04±177) with 3-5 years and younger than or equal to 2 years job experience (7.18±2.43,6.93±2.22), respectively, and between frontline HCWs (7.50±2.10) and non-frontline HCWs (6.84±2.40). Conclusion: HCWs demonstrated good knowledge about COVID-19. As the risk perception of COVID-19 among HCWs is high, it can raise concerns about their self-protective behaviour, and mental health. These issues need to be addressed.

Primary leiomyosarcoma of thyroid with pulmonary metastasis: A diagnostic odyssey.

The presented primary thyroid leiomyosarcoma (TL) case report underscores the importance of recognizing and addressing the diagnostic challenges and management complexities associated with this exceedingly rare malignancy. Given the limited effective therapeutic strategies available, timely intervention, thorough diagnostics, and vigilant follow-up are paramount in managing such intricate tumors. Further research focusing on molecular-based treatment modalities is imperative to improve patient outcomes in cases of primary TL.

The inhibitory effects of endophytic metabolites on glycated proteins under non-communicable disease conditions: A review.

Protein glycation in human body is closely linked to the onset/progression of diabetes associated complications. These glycated proteins are commonly known as advanced glycation end products (AGEs). Recent literature has also highlighted the involvement of AGEs in other non-communicable diseases (NCDs) such as cardiovascular, cancer, and Alzheimer's diseases and explored the impact of plant metabolites on AGEs formation. However, the significance of endophytic metabolites against AGEs has recently garnered attention but has not been thoroughly summarized thus far. Therefore, the objective of this review is to provide a comprehensive overview of the importance of endophytic metabolites in combating AGEs under NCDs conditions. Additionally, this review aims to elucidate the processes of AGEs formation, absorption, metabolism, and their harmful effects. Collectively, endophytic metabolites play a crucial role in modulating signaling pathways and enhancing the digestibility properties of gut microbiota (GM) by targeting on AGEs/RAGE (receptor for AGEs) axis. Furthermore, these metabolites exhibit anti-AGEs activities similar to those derived from host plants, but at a lower cost and higher production rate. The use of endophytes as a source of such metabolites offers a risk-free and sustainable approach that holds substantial potential for the treatment and management of NCDs.

Digital eye strain and its associated factors among radiology physicians in Pakistan: a cross-sectional survey using logistic regression analysis.

Background and aims: Increased use of digital devices in the modern era has led to the development of digital eye strain (DES) or computer vision syndrome in their users. This can result in the development of various ocular and visual symptoms among them. In this study, the authors aimed to view the prevalence of digital eye strain among radiology physicians in Pakistan and their associated risk factors. Materials and methods: A cross-sectional study was conducted to evaluate occupational DES among radiology physicians in Pakistan. The data collection was done using the convenience sampling technique, and the data were analyzed using IBM SPSS for Windows, Version 25.0. Results: Out of the 247 respondents, 33.6% were males and 66.4% were females. 41.7% of them were between 30 and 40 years of age and 51.8% of them were radiology residents. 52.2% of the participants had a refractive error and were using a corrective lens. The majority of the radiologists in our study (84.2%) preferred picture archiving and communication system (PACS) over films and 82.2% of them reported having breaks of less than 15 min. Major symptoms reported by the participants were tired or heavy eyes (69.6%) and headache (69.3%). The proportion of developing DES was higher in females [P=0.001, adjusted odds ratio (aOR)=2.94], radiology residents (P=0.031, aOR=3.29), and working hours of more than 4 h per day (P<0.001, aOR=0.04). Conclusion: With recent advances in the field of radiology in Pakistan, the frequency of developing DES among radiologists is increasing. Being a female, having long working hours, and having noticeable flickers on the digital screens were among the significant factors in developing DES among radiologists.

Eye Drop with Fas-Blocking Peptide Attenuates Age-Related Macular Degeneration.

Age-related macular degeneration (AMD), characterized by macular retinal degeneration, poses a significant health concern due to the lack of effective treatments for prevalent dry AMD. The progression of AMD is closely linked to reactive oxygen species and Fas signaling, emphasizing the need for targeted interventions. In this study, we utilized a NaIO3-induced retinal degeneration mouse model to assess the efficacy of Fas-blocking peptide (FBP). Intravitreal administration of FBP successfully suppressed Fas-mediated inflammation and apoptosis, effectively arresting AMD progression in mice. We developed a 6R-conjugated FBP (6R-FBP) for eye drop administration. 6R-FBP, administered as an eye drop, reached the retinal region, attenuating degeneration by modulating the expression of inflammatory cytokines and blocking Fas-mediated apoptosis in rodent and rabbit NaIO3-induced retinal degeneration models to address practical concerns. Intravitreal FBP and 6R-FBP eye drops effectively reduced retinal degeneration and improved retinal thickness in rodent and rabbit models. This study highlights the therapeutic potential of FBP, particularly 6R-FBP as an eye drop, in inhibiting Fas-mediated cell signaling and protecting against retinal cell death and inflammation in dry AMD. Future investigations should explore the translational prospects of this approach in primates with eye structures comparable to those of humans.

Ethnobotanical, ecological and health risk assessment of some selected wild medicinal plants collected along mafic and Ultra Mafic rocks of Northwest Pakistan.

The current study investigated wild plant resources and health risk assessment along with northern Pakistan's mafic and ultramafic regions. Ethnobotanical data was collected through field visits and semi-structured questionnaire surveys conducted from local inhabitants and healers. Six potentially toxic elements (PTEs) such as lead (Pb), cadmium (Cd), nickel (Ni), chromium (Cr), manganese (Mn), and zinc (Zn) were extracted with acids and analyzed using atomic absorption spectrophotometer (AAS, Perkin Elmer-7000) in nine selected wild medicinal plants. Contamination factor (CF), pollution load index (PLI), estimated daily intake (EDI), target hazard quotient (THQ), and hazard index (HI) were used to determine the health risk assessment of the studied medicinal plants. The results showed that the selected medicinal plants were used for the treatments of cough, joint swelling, cardiovascular disorders, toothaches, diabetes, and skin pimples by the local inhabitants due to their low-cost and easy accessibility. The concentrations of Pb (3.4-53 mg kg-1), Cd (0.03-0.39 mg kg-1), Ni (17.5-82 mg kg-1), Cr (29-315 mg kg-1), Mn (20-142 mg kg-1), and Zn (7.4-64 mg kg-1) in the studied medicinal plants were found above the safe limits (except Zn) set by WHO/FAO/USEPA (1984/2010). The Pb contamination factor was significantly (p < 0.05) higher in A. modesta (7.84) and D. viscosa (6.81), and Cd contamination factor was significantly higher in C. officinalis (26.67), followed by A. modesta (8.0) mg kg-1. Based on PTE concentrations, the studied plants are considered not suitable for human consumption purposes. Pollution load index values for A. modesta, A. barbadensis, A. caudatus, A. indica, C. procera (2.93), D. viscosa (2.79), and C. officinalis (2.83), R. hastatus (3.12), and Z. armatum were observed as 1.00, 2.80, 2.29, 2.29, 2.93, 2.79, 2.83, 3.12 and 2.19, respectively. Hazard index values were in order of R. hastatus (1.32 × 10-1) ˃ C. procera (1.21 × 10-1) ˃ D. viscosa (1.10 × 10-1) ˃ A. caudatus (9.11 × 10-2) ˃ A. barbadensis (8.66 × 10-2) ˃ Z. armatum (7.99 × 10-2) ˃ A. indica (6.87 × 10-2) ˃ A. modesta (5.6 × 10-2) ˃ C. officinalis (5.42 × 10-2). The health risk index values suggested that consumption of these plants individually or in combination would cause severe health problems in the consumers. Pearson's correlation results showed a significant correlation (p ≤ 0.001) between Zn and Mn in the studied medicinal plants. The current study suggests that wild medicinal plants should be adequately addressed for PTEs and other carcinogenic pollutants before their uses in the study area. Open dumping of mining waste should be banned and eco-friendly technology like organic amendments application should be used to mitigate PTEs in the study area.

Systemic Treatment with Fas-Blocking Peptide Attenuates Apoptosis in Brain Ischemia.

Apoptosis plays a crucial role in neuronal injury, with substantial evidence implicating Fas-mediated cell death as a key factor in ischemic strokes. To address this, inhibition of Fas-signaling has emerged as a promising strategy in preventing neuronal cell death and alleviating brain ischemia. However, the challenge of overcoming the blood-brain barrier (BBB) hampers the effective delivery of therapeutic drugs to the central nervous system (CNS). In this study, we employed a 30 amino acid-long leptin peptide to facilitate BBB penetration. By conjugating the leptin peptide with a Fas-blocking peptide (FBP) using polyethylene glycol (PEG), we achieved specific accumulation in the Fas-expressing infarction region of the brain following systemic administration. Notably, administration in leptin receptor-deficient db/db mice demonstrated that leptin facilitated the delivery of FBP peptide. We found that the systemic administration of leptin-PEG-FBP effectively inhibited Fas-mediated apoptosis in the ischemic region, resulting in a significant reduction of neuronal cell death, decreased infarct volumes, and accelerated recovery. Importantly, neither leptin nor PEG-FBP influenced apoptotic signaling in brain ischemia. Here, we demonstrate that the systemic delivery of leptin-PEG-FBP presents a promising and viable strategy for treating cerebral ischemic stroke. Our approach not only highlights the therapeutic potential but also emphasizes the importance of overcoming BBB challenges to advance treatments for neurological disorders.

Paracetamol-Mediated Synthesis of Silver Nanoparticles and Their Functionalization with Ionic Liquid for the Colorimetric Biosensing of Ascorbic Acid.

Ascorbic acid is a vital biomolecule for human beings. When the body's level of ascorbic acid is abnormal, it can lead to a number of illnesses. Its appropriate concentration is necessary for the oxidation of prostaglandins and cyclic adenosine monophosphate, the production of dopamine, norepinephrine, epinephrine, and carnitine, and the expansion and durability of the collagen triple helix in humans. In the present work, silver nanoparticle synthesis was performed through a paracetamol-mediated approach. Different characterization techniques, such as X-ray diffractometry (XRD), energy dispersive X-ray (EDX), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM), were used to confirm the prepared nanoparticles. Subsequently, the prepared Ag NPs functionalized with an ionic liquid were used as a sensing platform for ascorbic acid in blood serum samples. To achieve the best possible results, the proposed biosensor was optimized with different parameters such as TMB concentration, time, amount of capped nanoparticles (NPs), and pH. The proposed biosensor offers a sensitive and straightforward method for ascorbic acid with a linear range from 2 × 10-9 to 3.22 × 10-7 M, an LOD of 1.3 × 10-8 M, an LOQ of 4.3 × 10-8 M, and an R2 of 0.9996, Moreover, applications of the proposed biosensor were successfully used for the detection of ascorbic acid in samples of human plasma, suggesting that Ag NPs with high peroxidase-like activity, high stability, and facile synthesis exhibited promising applications in biomedical fields.

Genetic characterization of human echinococcosis in Southern Punjab, Pakistan.

Introduction: Echinococcosis is a neglected tropical zoonotic infection that affects both the human and livestock populations. In Pakistan, the infection is long-standing, but data on its molecular epidemiology and genotypic characterization in the southern Punjab region are limited. The aim of the current study was the molecular characterization of human echinococcosis in southern Punjab, Pakistan. Methods: Echinococcal cysts were obtained from a total of 28 surgically treated patients. Patients' demographic characteristics were also recorded. The cyst samples were subjected to further processing to isolate DNA in order to probe the Nad1 and Cyt-b genes, followed by DNA sequencing and phylogenetic analysis for genotypic identification. Results: The majority of the echinococcal cysts were from male patients (60.7%). The liver was the most commonly infected organ (60.71%), followed by the lungs (25%), spleen (7.14%), and the mesentery (7.14%). Molecular and genotypic identification through sequencing and phylogenetic tree analysis showed that most of the cysts (24/28, 85.7%) were caused by the species Echinococcus granulosus sensu stricto (E. granulosus s.s.) (G1 and G3), followed by Echinococcus multilocularis (E. multilocularis) and Echinococcus canadensis (E. canadensis) (G6/G7) (3/28, 10.8%, and 1/28, 3.5%, respectively). Conclusion: The current study concluded that the majority of human infections were caused by E. granulosus s.s., followed by the E. multilocularis and E. canadensis species (G6/G7). Genotypic characterization among both human and livestock populations is needed to explore the genetic diversity of echinococcosis.

Frequency of Amblyopia in strabismus patients presenting to tertiary care hospital.

Objective: The rationale of study was to find the magnitude of amblyopia with reference to type of squint among the strabismus patients visiting Hayatabad Medical Complex Peshawar, Pakistan. Materials and Methods: After ethical approval, a cross sectional study was carried out in the Department of Ophthalmology, Hayatabad Medical Complex, Peshawar, Pakistan, from April 2022 to October 2022, the total number of patients included being 237. Results: Amblyopia was observed in 113 out of 160 (70.6%) cases of uniocular squint, while in alternating squint it was found to be 11 out of 77 (14.2%). Amblyopia in patients with esotropia was seen in 73.2% (107 out of 146), while 59.3% (54 out of 91) exotropia had associated amblyopia. Conclusion: Strabismus amblyopia leads to developmental arrest of vision in early critical years of life. Permanent visual loss can be avoided with comprehensive screening and detailed examination of strabismic patient.

Unconventional but effective: breaking through IBS-D clinical practice guidelines - correspondence.

Irritable Bowel Syndrome (IBS) is a chronic, one of the commonest and persistent gastrointestinal (GI) disorder. Previously, the management plan for IBS-D included enhancing awareness; first line treatment included an increased dietary fiber intake, opioids for diarrhea and antispasmodics for pain management. A recent treatment guideline by the American Gastroenterology Association (AGA) suggests a modified approach to treating patients with IBS-D. Eight drug recommendations were made, and a set of instructions on when to employ which medication was devised. With the incorporation of these structured guidelines, a more tailored and focused approach to IBS management may become plausible.

Triple-negative breast cancer: epidemiology, molecular mechanisms, and modern vaccine-based treatment strategies.

Long-standing scarcity of efficacious treatments and tumor heterogeneity have contributed to triple-negative breast cancer (TNBC), a subtype with a poor prognosis and aggressive behavior that accounts for 10-15% of all new cases of breast cancer. TNBC is characterized by the absence of progesterone and estrogen receptor expression and lacks gene amplification or overexpression of HER2. Genomic sequencing has detected that the unique mutational profile of both the somatic and germline modifications in TNBC is staggeringly dissimilar from other breast tumor subtypes. The clinical utility of sequencing germline BRCA1/2 genes has been well established in TNBC. Nevertheless, reports regarding the penetrance and risk of other susceptibility genes are relatively scarce. Recurring mutations (e.g., TP53 and PI3KCA mutations) occur together with rare mutations in TNBC, and the shared effects of genomic modifications drive its progression. Given the heterogeneity and complexity of this disease, a clinical understanding of the genomic modifications in TNBC can pave an innovative way toward its therapy. In this review, we summarized the most recent discoveries associated with the underlying biology of developmental signaling pathways in TNBC. We also summarize the recent advancements in genetics and epidemiology and discuss state-of-the-art vaccine-based therapeutic strategies for TNBC that will enable tailored therapeutics.

Heavy migration of flood affectees in Pakistan and increased risk of autism spectrum disorder in children: a call to action.

Autism spectrum disorder (ASD) refers to various neurodevelopmental disabilities generally seen in kids. Pakistan, being vulnerable to natural disasters, faced one of the most devastating floods in July 2022 due to which many individuals were displaced. This not only affected the mental health of growing children but also the developing fetus of migrant mothers. This report establishes the link between the aftereffects of migration due to floods on children particularly associated with ASD in Pakistan. Flood affected families are devoid of basic necessities and are under a lot of psychological stress. On the other hand, Extensive treatment for autism is complicated, expensive, and provided in proper settings only which is not easily accessible to migrants. Considering all these factors, there are chances that ASD will be more prevalent in future generations of these migrants. Our study calls on respective authorities to take timely action for this growing concern.