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Introduction Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. This genus comprises 32 unicellular species infecting various vertebrate hosts, transmitted via sand-fly bites from Phlebotomus and Lutzomyia. Leishmaniasis affects the skin, mucous membranes, and internal organs, manifesting as cutaneous, mucocutaneous, or visceral leishmaniasis. Approximately 350 million people across 98 countries are at risk, with an annual global prevalence of 0.2-0.4 million cases of visceral leishmaniasis and 0.7-1.2 million cases of cutaneous and mucocutaneous leishmaniasis. In Pakistan, both anthroponotic cutaneous leishmaniasis (ACL) and zoonotic cutaneous leishmaniasis (ZCL) are reported, with significant cases in urban centers and rural areas. Methodology This study aimed to obtain baseline data for leishmaniasis in the Khyber Pakhtunkhwa province of Pakistan, conducted at Lady Reading Hospital, Peshawar. Data from 684 patients (475 males and 208 females) over one year were analysed using SPSS version 20.0. The chi-square test was applied to assess the association between infection rates and demographic variables. Result Results indicated the highest infection rate (46.7%) in the age group 1-15 years, followed by 16-30 years (19.8%), 31-45 years (9.4%), 46-60 years (6.1%), and above 60 years (3.3%). Gender-wise, males had a higher prevalence rate (69.3%) compared to females (30.7%). Positive cases were more prevalent in males (83.9%) than females (84.8%), although the association between infection and gender was statistically non-significant (p = 0.784). Discussion The discussion highlights that younger individuals have a higher infection rate due to a less developed immune system. Cultural practices in the region, such as males sleeping outside without adequate protection, contribute to higher infection rates in males. Diagnostic techniques for cutaneous leishmaniasis include slit skin smears and skin biopsies, with slit skin smears offering a more convenient yet less accurate alternative. The findings are consistent with previous studies, emphasizing the need for confirmatory skin biopsies in cases of negative slit skin smears but with high clinical suspicion. [ABSTRACT FROM AUTHOR]

The liver, a pivotal organ in human metabolism, serves as a primary site for heme biosynthesis, alongside bone marrow. Maintaining precise control over heme production is paramount in healthy livers to meet high metabolic demands while averting potential toxicity from intermediate metabolites, notably protoporphyrin IX. Intriguingly, our recent research uncovers a disrupted heme biosynthesis process termed 'porphyrin overdrive' in cancers that fosters the accumulation of heme intermediates, potentially bolstering tumor survival. Here, we investigate heme and porphyrin metabolism in both healthy and oncogenic human livers, utilizing primary human liver transcriptomics and single-cell RNA sequencing (scRNAseq). Our investigations unveil robust gene expression patterns in heme biosynthesis in healthy livers, supporting electron transport chain (ETC) and cytochrome P450 function without intermediate accumulation. Conversely, liver cancers exhibit rewired heme biosynthesis and a massive downregulation of cytochrome P450 gene expression. Notably, despite diminished drug metabolism, gene expression analysis shows that heme supply to the ETC remains largely unaltered or even elevated with patient cancer progression, suggesting a metabolic priority shift. Liver cancers selectively accumulate intermediates, which are absent in normal tissues, implicating their role in disease advancement as inferred by expression analysis. Furthermore, our findings in genomics establish a link between the aberrant gene expression of porphyrin metabolism and inferior overall survival in aggressive cancers, indicating potential targets for clinical therapy development. We provide in vitro proof-of-concept data on targeting porphyrin overdrive with a drug synergy strategy. [ABSTRACT FROM AUTHOR]

Heme, an iron-containing tetrapyrrole, is essential in almost all organisms. Heme biosynthesis needs to be precisely regulated particularly given the potential cytotoxicity of protoporphyrin IX, the intermediate preceding heme formation. Here, we report on the porphyrin intermediate accumulation within the tumor microenvironment (TME), which we propose to result from dysregulation of heme biosynthesis concomitant with an enhanced cancer survival dependence on mid-step genes, a process we recently termed "Porphyrin Overdrive". Specifically, porphyrins build up in both lung cancer cells and stromal cells in the TME. Within the TME's stromal cells, evidence supports cancer-associated fibroblasts (CAFs) actively producing porphyrins through an imbalanced pathway. Conversely, normal tissues exhibit no porphyrin accumulation, and CAFs deprived of tumor cease porphyrin overproduction, indicating that both cancer and tumor-stromal porphyrin overproduction is confined to the cancer-specific tissue niche. The clinical relevance of our findings is implied by establishing a correlation between imbalanced porphyrin production and overall poorer survival in more aggressive cancers. These findings illuminate the anomalous porphyrin dynamics specifically within the tumor microenvironment, suggesting a potential target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Electrocatalytic water splitting is an essential hydrogen production method for resolving present energy shortage and progress toward more efficient technologies. For this purpose, a versatile and cheap electrocatalysts are the main challenge along the way. In this report, we synthesized vanadium telluride and carbon nanotube (VTe–CNT)‐based nanocomposite via facile hydrothermal route. The VTe–CNTs are characterized by X‐ray diffraction analysis, scanning electron microscopy, energy‐dispersive spectroscopy, Fourier transform infrared spectroscopy, and Brunauer–Emmett–Teller. These characterizations depict nanosphere structures, morphology, and high surface area that maintains high porosity, which are essential for inclusive water‐splitting phenomena in 1.0 M solution of KOH. Additionally, the electrochemical performance of VTe–CNTs has shown best O2 evolution reactions activity with of onset potential of 1.42 V versus reversible hydrogen electrode and required 10 mA/cm2 of current density at 278 mV overpotential, which is excellent among other electrocatalysts, VTe (342 mV@10 mA/cm−2) and CNTs (365 mV@10mA/cm−2). Moreover, VTe–CNT exhibits remarkable stability for almost 20 h. It also requires a low onset potential of 0.05 V with a small Tafel slope of 47 mV/dec for H2 evolution reactions. Hence, this research might facilitate the easy transportation of electrons and open up the new era, serving as an excellent replacement for noble metal–derived materials. [ABSTRACT FROM AUTHOR]

The presentation of Figures 1 and 2 in the published manuscript is smooth and baseline corrected, which may cause difficulty for readers of the journal. Therefore, we want to present the raw version of these figures without smoothing or baseline correction. Additionally, Figure 2 had a labeling issue which now has been corrected. We apologize for these mistakes which will not affect the scientific conclusions. [ABSTRACT FROM AUTHOR]

Objective: To determine the clinico-pathological profile in patients with megaloblastic anemia. Study Design: Cross Sectional study. Setting: Department of Pathology, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan. Study Period: June 2022 to July 2023. Material & Methods: The study subjects were 100 patients suffering from megaloblastic anemia. Using convenient sampling technique, blood samples were analyzed for complete blood count (CBC) and peripheral blood morphology followed by serum B12, serum and red cell folate levels and the bone marrow examination. SPSS version 23 was utilized to analyze the data. The results of variables including age, gender, clinical features and hematological profile were analyzed. Results: Out of 100 diagnosed patients of megaloblastic anemia, 51 (51%) were males, whereas 49 (49%) were females. Anemia alone was present in 18(18%), 11(11%) had anemia along with leucopenia, 14 (14%) faced anemia with thrombocytopenia, 57(57%) had pancytopenia while 16(16%) were pallor. Moreover, 01(01%) of the studied patients presented with fatigue and bleeding while 02 (2%) got weight loss. 10(10%) had fatigue accompanying with Pallor. 19(19%) faced pallor associated with fatigue and bleeding. 14(14%) had pallor accompanying with fatigue, Jaundice and weight loss. 37(37%) had pallor along with fatigue, bleeding, weight loss and jaundice. Conclusion: Males were more frequently affected by megaloblastic anaemia than females. The frequent clinical features appreciated were fatigue, pallor, weight loss, bleeding, and jaundice. Common cytopenia was pancytopenia, followed by bicytopenia. [ABSTRACT FROM AUTHOR]

Objectives: To find the association of breastfeeding and the risk of breast cancer in our population. Study Design: Case-control study. Place and Duration of Study: Oncology Ward-4 at Jinnah Postgraduate Medical Center, Karachi Pakistan, from Jun 2018 to Jun 2019. Methodology: All patients with diagnosed Breast Cancer visiting the outpatient department were enrolled in this study. Controls were randomly selected from the community. Demographic characteristics, reproductive history, breastfeeding pattern, and hormonal status of cancer were collected from all participants. Results: Among patients who had a positive history of breastfeeding were three times more likely to develop breast cancer than those with no history of breastfeeding [Odds Ratio 3.315 (95% Confidence Interval: 2.094-5.249)]. 69.7% of participants in our study breastfed for more than 2 years. There was also a weak inverse association between lactation amenorrhea and breast cancer risk. Women who experienced lactation amenorrhea had only half the risk of women who did not experience lactation amenorrhea [Odds Ratio 0.685 (95% of Confidence Interval: 0.397-1.182)]. Conclusion: There was a negative relationship between breast cancer and breastfeeding. Further research should explore the genetic and cultural differences and the risk of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Lower gut bleeding is an alarming sign among caregivers. Determining the etiology is of utmost importance for further management. This is the first study conducted in northernmost India. Methods: This cross-sectional study was conducted at the Department of Pediatrics, Government Medical College, Srinagar. This study aimed to describe the etiology of lower gastrointestinal bleeding in the age group of 1-18 years over the past 5 years from June 2017 to June 2022. Results: A total of 310 children presented with hematochezia (53.5%), blood mixed with loose stools for > 2 weeks (39.3%), melena (1.9%), and occult blood in stools (0.3%). The mean age was 5.12 years. The age group of 1-6 years was 73.5 %. The most common findings were rectosigmoid polyps n = 104 (33.5%), anal fissure n = 47 (15.1%), lymphoid nodular hyperplasia (LNH) n = 38 (12.2%), trichuris dysentery syndrome n = 30(9.7%), cow's milk protein allergy n = 27(8.7%), non-specific colitis n = 18(5.8%), solitary rectal ulcer syndrome n = 14(4.5%), inflammatory bowel disease n = 6 (1.9%),intestinal tuberculosis n = 3(0.9%), duodenal dieulafoy lesion 1(0.3%), and blue bleb nevus rubber syndrome n = 1(0.3%). 21 patients had a normal colonoscopy. The colonoscopy yield was 93.3 %. Among the colonoscopy-negative patients, 6(1.6%) had Meckel's diverticulum, and 1(0.3%) had a duodenal dieulafoy lesion. Conclusion: Lower GI bleeding most commonly presents as hematochezia, and the most common cause is a rectosigmoid polyp. Colonoscopy is the procedure of choice to evaluate the etiology of lower GI bleeding. Anal fissures, LNH, Trichuris trichiura, and cow's milk protein allergy are other common causes of lower gut bleeding in Kashmir, northernmost India. [ABSTRACT FROM AUTHOR]

Introduction: Temporomandibular joint (TMJ) ankylosis is a debilitating condition usually afflicting children and young adults, causing long-term functional, aesthetic, and severe psychological impacts on the lives of these patients. Objective: To compare the postoperative outcomes after using one of the most commonly employed inter-positional graft, i.e., temporalis fascia, and a recently introduced 'more suitable' graft, i.e., dermal fat. Methods: A prospective study in which 20 patients of TMJ ankylosis were randomly assigned into two groups of 10 patients each. Temporalis fascia was used as an inter-positional graft in one group, while dermal fat graft was used in the other group. Post-surgical clinical parameters were evaluated, including interincisal mouth-opening and pain. Results: Interincisal mouth opening at six months was greater in group A (32.1 ± 12.93) as compared to group B (33.8 ± 4.89), but statistically, it was not significant (P = 0.478). The mean pain score in group A was 4.60 ± 1.17, 1.50 ± 0.70, 0.20 ± 0.42 on day 1, 7, and 15, respectively. The mean pain score in group B was 4.10 ± 0.99, 1.30 ± 0.48, 0.20 ± 0.42 on day 1, 7, and 15, respectively. Conclusion: Both the graft materials work well in terms of maximum interincisal opening. For more clarification, a larger sample size with a longer duration of follow-up is needed to validate the study. [ABSTRACT FROM AUTHOR]

Study Design: Systematic Review and Meta-analysis Objectives: This systematic review and meta-analysis is aimed to assess effectiveness, safety, clinical, functional and radiological outcome of either combined anteroposterior or posterior-only approach in the surgical management of active tubercular disease of paediatric thoracolumbar spine. Methods: A systematic literature search through PubMed, Scopus, Web of Science and Cochrane Library database was performed. Data extraction was undertaken following methodological quality assessment. Results: 9 out of the 182 publications identified, were included for analysis. A total of 247 patients were analysed. Two amongst the 9 studies were retrospective comparative studies evaluating posterior approach with combined anteroposterior approach and were considered for comparative meta-analysis. Blood loss and duration of surgery was significantly higher in the anteroposterior group, as compared to the posterior-only group. There was no significant difference between the 2 groups in terms of post-operative kyphosis angles, final kyphosis angles, number of complications, functional outcome and spinal fusion time. However, all the included studies were non-randomised and retrospective. Only 2 of them had a control group with a high heterogeneity amongst these 2 studies. Conclusion: The inference from the studies included in this review suggests that equivalent results can be achieved with posterior-only approach for thoracolumbar tuberculosis in children as compared to anteroposterior approach, with much lower complexity, reduced blood loss and shorter surgical time. However, due to the high risk of bias and considerable heterogeneity among the studies included, we cannot conclude whether one approach is better than the other. [ABSTRACT FROM AUTHOR]

Medicinal plants are highly used in the ethnoveterinary practice as considerable livestock resources in remote areas. The aim of the present study is to explore the ethnoveterinary medicinal practices in three different communities and discuss the cross‐cultural consensus on the usage of medicinal plants for the treatment of animals. The field survey was conducted by the animal healers of the area during the different seasons of plant growth. A total of 83 informants were interviewed through Semi‐structured interview involving experts of traditional knowledge in 21 localities of the three regions (Zhob, D. I. Khan and Mianwali) were conducted. Findings of the study were quantitatively analyzed through the informant consensus factors to identify the homogeneity information provided by the informants. Furthermore, cross‐culture consensuses were analyzed and recorded data were represented in a tabulated and Venn diagrams. In particularly, 59 species of plants were documented in the comparative analysis. Among them, 32 plant species were recorded in Pashto community, while Punjabi and Sarakai communities exhibited nine and four plant species, respectively. Whereas cross‐cultural analysis showed 14 medicinal plants that were commonly utilized by three different ethnic communities, that indicated low interregional consensus in regard to ethnoveterinary practices of medicinal plants. The current study showed that different communities and ethnic groups sharing some traditional knowledge and cross‐culturally approaches have been reported from traditional uses of plants against livestock's diseases. Therefore, current findings are the opportunities to scrutinize the plants for the discovery of new drug sources for humans and animals. [ABSTRACT FROM AUTHOR]

This study was conducted to see the frequency of hormone receptors and Her-2/Neu positivity in different histology in breast cancer patients. Methods: It was a cross-sectional study conducted at the Department of Medical Oncology, Jinnah Postgraduate Medical Centre from June 2018- March 2019. Total 373 patients of age 22–81 years of which 360 female and 13 males, with histopathological proven diagnosis of breast cancer were included in the study using non-probability consecutive sampling technique. The immunohistochemistry (IHC) was performed on biopsy sample for the status of PR, ER and HER-2/Neu and the confirmation of Her-2/Neu was done by Fluorescent In situ Hybridization (FISH) technique if HER-2/Neu was equivocal by IHC testing. Information regarding demographics, family history, histology, grade, stage, metastatic site and other histopathological parameters were noted on predesigned proforma by the researcher. SPSS-23 was used to analyse data. Results: Total of 373 patients were included in the study. The mean patient age was 45.34±12.28 years. ER, PR, Her 2 Neu (IHC) & Her 2 Neu (FISH) were found positive in 206 (55.2%), 182 (48.8%), 121 (32.4%) & 23 (6.2%) patients, respectively. The histology with PR receptor & grade of tumour with ER & PR receptor showed statistical significance (p<0.05). Conclusion: ER, PR &HER-2/NEU expressions in breast cancer vary among different population and it is very important to find out the frequency among different histopathological types as it is of predictive and prognostic value. So, it is recommended to look for these markers and treat them accordingly. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukaemia (AML) is malignant neoplasms of myeloid cells categorized by clonal expansion of hematopoietic blasts of myeloid lineage in peripheral blood and bone marrow. The aim of current study is to identify the common cytogenetic abnormalities in AML patients presenting at a tertiary care hospital of Pakistan. Methods: It was a cross-sectional study conducted at the department of Medical oncology of the Jinnah Postgraduate Medical Center, Karachi from Jun 2017- Jan 2019. The non-probability consecutive sampling technique was used to select patients. Total 92 cases of AML of age 15–55 years of either gender were included in the study. The detection of cytogenetic abnormality was done on the bone marrow biopsy. The cytogenetic abnormalities were classified into the three cytogenetic risk groups as favourable, intermediate and unfavourable. For analysis of data SPSS 23 version was used. Results: The cytogenetic abnormalities were detected in 34 (37%) of the AML patients while 58 (63%) patients had normal cytogenetic. Thirty-two females (34.8%) had a normal cytogenetic (46; XX), and 15 females (16.3%) had various cytogenetic abnormalities. Twenty-six males (28.3%) had normal cytogenetic (46; XY) and 19 males (20.7%) had various cytogenetic abnormalities. Most of the patients were in intermediate risk group (67.4%), followed by favourable (17.4%) and unfavourable risk group (15.2%). The most frequent chromosomal abnormalities observed were complex cytogenetic which was detected in 5 AML patients. Conclusion: In the present study cytogenetic abnormalities were found in 37% of AML patients. Sixty-seven of the AML patients were in intermediate risk group and five patients had complex cytogenetic. Hence the cytogenetic analysis provides significant information regarding prognosis of AML patients and the cytogenetic abnormalities are less than international literature. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to determine the frequency of amenorrhea after chemotherapy among breast cancer patients". Methods: Total 201 premenopausal females (having menstruation during the past 6 months at the time of diagnosis) of age 15-45 years and had confirmed diagnosis of breast cancer requiring chemotherapy were included in the study using non-probability consecutive sampling technique. Amenorrhea within 6 months after the completion of chemotherapy was labelled as chemotherapy induced amenorrhea. Data was entered and analysed using SPSS-23. Results: The mean age of the patients was reported as 37.06±5.68 years. Majority of the females were married (86.6%) & multigravida (81.1%). Most of the patients (23.9%) received neoadjuvant chemotherapy followed by surgery and radiotherapy. A total of 129 patients received Adriamycin plus cyclophosphamide followed by paclitaxel as chemotherapy regimen. Out of 201 females, 184 (91.5%) experienced amenorrhea after start or completion of chemotherapy. Conclusion: The frequency of CIA was very high among breast cancer patients in our study, long term follow-up is needed to see input of CIA on future fertility. [ABSTRACT FROM AUTHOR]

Introduction: Soft-tissue chondromas are rare, benign cartilaginous tumors predominantly affecting the extremities, often diagnosed in middle-aged individuals without a clear sex predilection. Despite their benign nature, these tumors can pose significant diagnostic challenges due to their slow growth, asymptomatic nature, and potential for mimicking other soft-tissue tumors., Case Report: We report a case of a 27-year-old male with an 8-year history of a progressively enlarging mass on the dorsal aspect of the second toe of the left foot, leading to pain, difficulty in walking, and wearing shoes. Initial clinical examination revealed a firm, non-tender swelling with hypoesthesia over the affected area. Radiographic findings suggested a soft-tissue mass with stippled calcification, while magnetic resonance imaging indicated a large altered signal intensity lesion abutting but not arising from the bone. Fine needle aspiration cytology hinted at a benign mixed tumor/chondroid syringoma. An excisional biopsy was performed, revealing a well-circumscribed tumor with lobules of mature hyaline cartilage, consistent with a diagnosis of soft-tissue chondroma. Post-operative period recovery was uneventful except for local flap necrosis which was managed with skin grafting. There was no recurrence at the 1-year follow-up., Conclusion: Soft-tissue chondromas, while rare and benign, can significantly impact patients' quality of life. Correct diagnosis, involving a comprehensive evaluation and histopathological confirmation, is crucial for effective management and prevention of unnecessary interventions. This case adds valuable insight into the clinical presentation, diagnostic challenges, and management strategies for soft-tissue chondromas., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Objective: To evaluate the response rate of Cisplatin plus Docetaxel in the treatment of locally advanced head and neck squamous cell carcinomas (HNSCC) at a tertiary care hospital in Karachi, Pakistan., Materials and Methods: It was a longitudinal study, conducted at the Department of Medical Oncology, Jinnah Postgraduate Medical Center, Karachi, Pakistan from December 2018 to June 2019. One hundred patients of age 14-66 years of age of either gender with histologically proven Squamous Cell Carcinoma of Head and Neck, Stage III and IV (locally advanced) with no distant metastases were included in the study. Patients who were declared unresectable by the otolaryngologist and those with delayed appointment for radiation were given 3 cycles of Induction Chemotherapy with Cisplatin and Docetaxel, both at a dose of 75mg/m2 3 weekly. After 3 cycles, CT scan was repeated to assess the clinical response. Those patients who had partial or complete response as per RECIST criteria were re-assessed by the otolaryngologist and were planned for surgery if disease became resectable while other patients were referred for Concurrent Chemo-Radiation Therapy (CCRT). SPSS version 23 was used to analyze data., Results: The partial response was achieved in majority of the patients after Induction Chemotherapy with Docetaxel and Cisplatin (62%) with a complete response in 12 %. However, 22% showed progression of the disease, and 4% showed stable disease. The most frequent side effects observed were diarrhea (62%) and neutropenia (57%)., Conclusion: Induction chemotherapy with Cisplatin and Docetaxel is a promising regimen with good response and favorable toxicity profile and can be considered as a potentially effective outpatient regimen for locally advanced squamous cell carcinoma of head and neck.

Neuroblastoma is the most common intra-abdominal and extracranial solid tumour in children, accounting for 7%-8% of all childhood cancers. It is a malignant tumour of the autonomic nervous system derived from the neural crest. Most children with neuroblastoma have distant metastatic disease at the time of diagnosis. Pulmonary metastasis at the time of diagnosis is rare, and rarer is the presence of associated pleural effusion. We present the case of a child with recurrent empyema, who was diagnosed to have a thoracic neuroblastoma., (Copyright 2014, NMJI.)