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To obtain a more recent and comprehensive insight into the prevalence of glomerular diseases in our patient population, medical records of 200 patients with biopsy proven glomerulonephritis (GN), between January 1994 and June 1999, at the King Khalid University Hospital, Riyadh, Saudi Arabia were analyzed. Primary glomerular disease was found to be the most prevalent, accounting for 63.5% of all glomerular diseases. Among primary glomerular diseases, focal and segmental glomerulosclerosis (FSGS) was the most common histological lesion (34.6%) and was associated with a high prevalence of hypertension (86.4%), nephrotic syndrome (68.18%), hematuria (63.6%) and renal functional impairment (27.3%). Mesangioproliferative GN was the second most common lesion (25.1%) followed by mesangiocapillary GN (15.7%), IgA nephropathy (10.2%), and minimal change disease (8.5%). Amongst secondary glomerular diseases, lupus nephritis was the most prevalent (24.5%). In conclusion, primary glomerular diseases constituted the commonest group encountered and the prevalence of FSGS was quite high with male sex and young adults predominating. FSGS was also associated with a high prevalence of end-stage renal disease. Further collaborative studies are necessary to explore the predisposing factors and associations of glomerular disease, especially FSGS.

Abstract The study by Mwatenga et al. found a tuberculosis (TB) prevalence of 10.2% and an HIV prevalence of 19.1% among inmates, with all TB cases co-infected with HIV. Education level, smoking history, and substance use are key predictors of coinfections. Although informative, its single-centred design and reliance on sputum samples may be insufficient for some patient groups, potentially compromising diagnostic accuracy. Expanding the study to include several jails and employing more diagnostic procedures may increase reliability and the ability to generalize. The report also notes the lack of debate on broader socioeconomic variables and structural barriers to healthcare in jails, which are crucial to understanding inmates' health challenges. Overcrowding, malnutrition, and a poor healthcare system are examples of environmental factors that probably contribute to the spread of tuberculosis and make managing HIV more difficult. Additionally, not enough is known about the dietary habits of prisoners and other health conditions like diabetes or mental health, which may have an impact on the course of HIV and TB. Future studies should take these extra characteristics into account to create more comprehensive approaches to controlling HIV coinfections and TB in prison populations. This will help build more effective therapies.

ObjectiveThis study aims to clinically and genetically assess 30 unrelated consanguineous Pakistani families from various ethnic backgrounds, all exhibiting features of neurodevelopmental disorders (NDDs).MethodsWe conducted clinical, genetic, biochemical, and molecular analyses on 30 consanguineous families with NDDs enrolled from various regions of Pakistan. The likely molecular causes of primary microcephaly and NDDs were identified. Detailed clinical investigations and molecular diagnoses were performed using whole exome sequencing (WES) of the proband, followed by Sanger sequencing for validation and segregation in the available family members of the affected families.ResultsWES identified likely disease-causing homozygous variants in 30 unrelated consanguineous families. Six families presented newly described variants in known NDD-related genes: ABAT (c.1439 T > G; p.Phe480Cys) [OMIM613163], SLC12A6 (c.2865_2865insT; p.Glu955Asnfs*5) [OMIM 218000], SHANK3 (c.1305-3_1,305-2delTT; p.Gln29-_Gly305del) [OMIM 606232], BCKDK (c.356_356insC; p.Gly119Alafs*24) [OMIM 614923], DDHD2 (c.2065G > T; p.Asp689Tyr) [OMIM 615033], ERCC2 (c.1255G > A; p.Glu419Lys) [OMIM 610756]. Additionally, 12 families had previously reported disease-causing variants associated with different types of NDDs: ATRX (c.109C > T; p.Arg37*) [OMIM 309580], GPR56 [ADGRG1] (c.1423C > T; p.Arg475*) [OMIM 606854], NAGLU (c.1694G > A; p.Arg565Gln) [OMIM 252920], DOLK (c.3G > A; p.Met1Ile) [OMIM 610768], GPT2 (c.815C > T; p.Ser272Leu) [OMIM 616281], DYNC1I2 (c.607 + 1G > A; p.?) [OMIM 618492], FBXL3 (c.885delT; p.Leu295Phefs25*) [OMIM 606220], LINGO1 (c.869G > A; p.Arg290His) [OMIM 618103], and ASPM (c.3978G > A; Trp1326*, c.9557C > G; p.Ser3186*, c.6994C > T; p.Arg2332*) [OMIM 608716]. All the identified variants showed segregation compatible with autosomal recessive inheritance.ConclusionIn the present study, we observed a high frequency of ASPM variants in the genetic analysis of 30 consanguineous families exhibiting features of NDDs, particularly those associated with autosomal recessive primary microcephaly. These findings contribute to studies on genotype–phenotype correlation, genetic counseling for families, and a deeper understanding of human brain function and development.

Video forgery detection is a critical aspect of digital forensics, addressing the challenges posed by the manipulation of video content. This paper presents a novel approach for video forgery detection using Deep Convolutional Neural Networks (DCNN). Leveraging the power of deep learning, our method aims to improve the accuracy and efficiency of object-based forgery detection in advanced video sequences. In the proposed approach, we build upon the foundation of an existing method, which utilizes Convolutional Neural Networks, and introduce innovative modifications to the DCNN architecture. These modifications include data preprocessing, network architecture, and training strategies that enhance the model’s ability to detect tampered objects in video frames. We conduct experiments on the SYSU-OBJFORG dataset, the largest object-based forged video dataset to date, with advanced video encoding standards. Our DCNN-based approach is compared with the existing method, demonstrating superior performance. The results show increased accuracy and robustness in detecting object-based video forgery. This paper not only contributes to the field of video forgery detection but also underscores the potential of deep learning, particularly DCNN, in addressing the evolving challenges of digital video manipulation. The findings open avenues for future research in the localization of forged regions and the application of DCNN in lower bitrate or lower resolution video sequences.

Pakistan's Emergency Medical Services (EMS) are a critical component of its healthcare system, providing pre-hospital emergency care across a nation with over 220 million people. This article explores the evolutionary journey of Pakistan's EMS, highlighting both the challenges it faces and the strides it has made, with a specific emphasis on patients experiencing out-of-hospital cardiac arrest (OHCA). To extract relevant information, we searched MEDLINE & Embase data bases using MeSH terms “Emergency Medical Services” OR “EMS” AND “Out-of-Hospital-Cardiac-Arrest” OR “OHCA” AND “Pakistan”. In addition, we also retrieved information from the EMS leadership in Pakistan through e-mails. We delve into the significance of key performance indicators for OHCA, advocate for the establishment of OHCA registries to improve patient outcomes, address regional disparities in pre-hospital care, and acknowledge the gradual progress of the EMS system.

Abstract DNA can be folded into rationally designed, unique, and functional materials. To fully realise the potential of these DNA materials, a fundamental understanding of their structure and dynamics is necessary, both in simple solvents as well as more complex and diverse anisotropic environments. Here we analyse an archetypal six-duplex DNA nanoarchitecture with single-particle cryo-electron microscopy and molecular dynamics simulations in solvents of tunable ionic strength and within the anisotropic environment of biological membranes. Outside lipid bilayers, the six-duplex bundle lacks the designed symmetrical barrel-type architecture. Rather, duplexes are arranged in non-hexagonal fashion and are disorted to form a wider, less elongated structure. Insertion into lipid membranes, however, restores the anticipated barrel shape due to lateral duplex compression by the bilayer. The salt concentration has a drastic impact on the stability of the inserted barrel-shaped DNA nanopore given the tunable electrostatic repulsion between the negatively charged duplexes. By synergistically combining experiments and simulations, we increase fundamental understanding into the environment-dependent structural dynamics of a widely used nanoarchitecture. This insight will pave the way for future engineering and biosensing applications.

Abstract Sweet potato feathery mottle virus (SPFMV) and Sweet potato mild mottle virus (SPMMV) are members of the genera Potyvirus and Ipomovirus, family Potyviridae, sharing Ipomoea batatas as common host, but transmitted, respectively, by aphids and whiteflies. Virions of family members consist of flexuous rods with multiple copies of a single coat protein (CP) surrounding the RNA genome. Here we report the generation of virus-like particles (VLPs) by transient expression of the CPs of SPFMV and SPMMV in the presence of a replicating RNA in Nicotiana benthamiana. Analysis of the purified VLPs by cryo-electron microscopy, gave structures with resolutions of 2.6 and 3.0 Å, respectively, showing a similar left-handed helical arrangement of 8.8 CP subunits per turn with the C-terminus at the inner surface and a binding pocket for the encapsidated ssRNA. Despite their similar architecture, thermal stability studies reveal that SPMMV VLPs are more stable than those of SPFMV.

In the underlying work, the problems faced during message dissemination in the conventional Vehicular Energy Networks (VENs) like lack of security, breach of personal identities, absence of trust between vehicle owners, etc., are tackled. In this study, a Blockchain (BC) based announcement system is proposed for VENs to ensure secure and reliable announcement dissemination in the proposed network. The proposed system is a three-layered system comprising message dissemination layer, storage layer and BC layer. In the first layer, all the vehicles are registered through a Certificate Authority (CA), which ensures only the legitimate vehicles become part of the proposed network and interact with each other. Later, in the second layer, the data sent by the vehicles is stored at the artificial intelligence based Interplanetary File System (IPFS), which is incorporated with the Road Side Units (RSUs). This ensures reduction in storage cost and data availability. Besides, vehicle owners’ privacy is ensured by concealing the real identities of the vehicles. Moreover, the hashes of the data stored in the IPFS are stored in BC in the third layer. Also, lightweight trustworthiness verification of the vehicles, reputation based incentivization and concealing predictable trends in vehicles’ reputation scores are performed in the same layer. Overall, the novelty of the proposed work lies in the fact that the proposed system efficiently tackles different problems encountered in the existing systems simultaneously. Through extensive simulations, it is inferred that the computational time is reduced by 15–18% and the storage overhead is reduced by 80–85%, respectively when storing hash of data on the BC network as compared to storing actual data on the network.

AIM: To investigate the genetic basis of autosomal recessive retinitis pigmentosa (arRP) in two consanguineous/ endogamous Pakistani families. METHODS: Whole exome sequencing (WES) was performed on genomic DNA samples of patients with arRP to identify disease causing mutations. Sanger sequencing was performed to confirm familial segregation of identified mutations, and potential pathogenicity was determined by predictions of the mutations' functions. RESULTS: A novel homozygous frameshift mutation [NM_000440.2:c.1054delG, p. (Gln352Argfs*4); Chr5:g.149286886del (GRCh37)] in the PDE6A gene in an endogamous family and a novel homozygous splice site mutation [NM_033100.3:c.1168-1G>A, Chr10:g.85968484G>A (GRCh37)] in the CDHR1 gene in a consanguineous family were identified. The PDE6A variant p. (Gln352Argfs*4) was predicted to be deleterious or pathogenic, whilst the CDHR1 variant c.1168-1G>A was predicted to result in potential alteration of splicing. CONCLUSION: This study expands the spectrum of genetic variants for arRP in Pakistani families.

Replicative hexameric helicases are fundamental components of replisomes. Here the authors resolve a cryo-EM structure of the E1 helicase from papillomavirus bound to a DNA replication fork, providing insights into the mechanism of DNA unwinding by these hexameric enzymes.

IntroductionA subset of individuals with COVID-19 can suffer from a severe form of the disease requiring breathing support for respiratory failure and even death due to disease complications. COVID-19 disease severity can be attributed to numerous factors, where several studies have associated changes in the expression of serum pro-inflammatory cytokines with disease severity. However, very few studies have associated the changes in expression of pro-inflammatory changes in the nasopharyngeal milieu with disease severity. Therefore, in the current study, we performed differential gene expression analysis of various pro-inflammatory cytokines in the nasopharyngeal milieu of mild & severe COVID-19 cases.Material and methodFor this retrospective, cross-sectional study, a total of 118 nasopharyngeal swab samples, previously collected from mild and severe (based on the WHO criteria) COVID-19 patients were used. A real-time qPCR was performed to determine the viral loads and also evaluate the mRNA expression of eight cytokines (IL-1, IL-2, IL-4, IL-6, IL-10, IFN-γ, TGF-β1, and TNF-α). Subsequently, an unpaired T-test was applied to compare the statistical difference in mean expression of viral loads and each cytokine between the mild and severe groups, while the Pearson correlation test was applied to establish a correlation between disease severity, viral load, and cytokines expression. Similarly, a multivariable logistic regression analysis was performed to assess the relationship between different variables from the data and disease severity.ResultsOut of 118 samples, 71 were mild, while 47 were severe. The mean viral load between the mild and severe groups was comparable (mild group: 27.07± 5.22; severe group: 26.37 ±7.89). The mRNA expression of cytokines IL-2, IL-6, IFN- γ, and TNF-α was significantly different in the two groups (pConclusionThis decreased expression of certain cytokines (IL-2, IL-6, TNF-α, and IFN-γ) in the nasopharyngeal milieu may be considered early biomarkers for disease severity in COVID-19 patients.

BACKGROUND: Although tyrosine kinase inhibitors (TKIs) are the gold standard in clinical management of chronic myeloid leukemia, it is not feasible to use these drugs in at least some cases when patients are resistance to all available TKIs due to compound BCR-ABL mutations, due to patient safety profile or due to the nonavailability of drugs in developing countries on account of cost or logistic issues. We reported earlier that interferon alpha can eradicate compound BCR-ABL mutations and induce stable responses. Here, we report a follow-up of this study. PATIENTS AND METHODS: Some chronic myeloid leukemia (CML) patients did not get TKIs directly because of very high cost of imatinib and were given interferon alpha (experimental group) until the provision of imatinib free of cost through GLIVEC® International Patient Assistance Program while the other groups of patients (control group) were directly given imatinib. A very sensitive allele-specific polymerase chain reaction was employed to detect BCR-ABL compound mutations before treatment and confirmation of mutations was carried out using reliable molecular assays. Mutations were reinvestigated at all important time points during the long-term follow-up studies. RESULTS: The use of interferon-alpha for 6 months prior to TKIs eradicated compound BCR-ABL mutations (Phe311Val/Met351Thr and Thr315Ile/Phe311Val/Met351Thr) and provided deep molecular responses without any progression or mortality in CML patients (experimental group) as compared with patients who did not use interferon and was directly given TKIs (control group). CONCLUSIONS: Interferon alpha can eradicate highly resistant BCR-ABL mutations and lead to durable deep molecular responses to TKIs in CML. Therefore, interferon-alpha is recommended for CML patients with compound mutations resistant to TKIs, specifically in those scenarios where some TKIs are not available or not safe to use for CML patients. Our long-term follow-up study is well supported by recently published literature.

Ampullary cancers are rare accounting for 0.2% of all gastrointestinal cancers. Signet ring is a rare variant of adenocarcinoma, characterized by having more than 50% of mucin secreting cells and clinically having a worse prognosis. We present the case of a teenage girl with this tumor, the youngest ever reported in medical literature. An 18 years old girl with no significant past medical history presented to our clinic with symptoms of upper abdominal pain and jaundice. Her upper GI endoscopy showed an ampullary lesion which was biopsied—diagnosing it as adenocarcinoma. She underwent a pancreato-duodenectomy (Whipple’s procedure) with Child’s reconstruction and a feeding jejunostomy. Her final histopathology report was documented as infiltrating adenocarcinoma of Signet Ring variety arising from the Ampulla of Vater. Being such a rare entity, there is a lack of randomized trials advising the optimum treatment for such cases. Till then anecdotal experiences will drive the optimum management of this rare disease.

Abstract Background Parathyroid cancer is a rare cause of primary hyperparathyroidism. It presents a diagnostic and therapeutic challenge that may not be recognized preoperatively, and is often not conclusively identified during the operation. We present the case of a lady with backache and hypercalcemia, but with inadequate work-up for her condition for several years. Case presentation A middle aged lady of Asian descent presented with backache. Initial work up revealed mild hypercalcemia, negative work up for multiple myeloma, negative sestamibi scan for parathyroid pathology. A phenomenally elevated parathormone (PTH) level—2105 pg/mL (16–87 pg/mL), and rising serum calcium, 15.1 mg/dL, (8.6–10.5 mg/dL), ordered years later prompted a repeat sestamibi scan and ultrasonography of neck. Based on these investigations, a diagnosis of primary hyperparathyroidism, with high suspicion of parathyroid cancer was made. The patient underwent surgical tumour resection, with subsequent histopathological confirmation of diagnosis. Conclusion In the setting of hypercalcemia, PTH level assessment is a must. This helps to differentiate between the parathyroid dependant and independent causes of high serum calcium, thereby encouraging a comprehensive pathway to the work up of the cause of hypercalcemia. The parathyroid cancer is a very rare cause of hypercalcemia, which needs to be considered in the differentials of primary hyperparathyroidism, particularly in the setting of high PTH levels.

Widespread antibiotic resistance has returned attention to bacteriophages as a means of managing bacterial pathogenesis. Synthetic biology approaches to engineer phages have demonstrated genomic editing to broaden natural host ranges, or to optimise microbicidal action. Gram positive pathogens cause serious pastoral animal and human infections that are especially lethal in newborns. Such pathogens are targeted by the obligate lytic phages of the Salasmaviridae and Guelinviridae families. These phages have relatively small ~20 kb linear protein-capped genomes and their compact organisation, relatively few structural elements, and broad host range, are appealing from a phage-engineering standpoint. In this study, we focus on portal proteins, which are core elements for the assembly of such tailed phages. The structures of dodecameric portal complexes from Salasmaviridae phage GA1, which targets Bacillus pumilus, and Guelinviridae phage phiCPV4 that infects Clostridium perfringens, were determined at resolutions of 3.3 Å and 2.9 Å, respectively. Both are found to closely resemble the related phi29 portal protein fold. However, the portal protein of phiCPV4 exhibits interesting differences in the clip domain. These structures provide new insights on structural diversity in Caudovirales portal proteins and will be essential for considerations in phage structural engineering.

Background: Chronic myeloid leukemia (CML) is initiated in bone marrow due to chromosomal translocation t(9;22) leading to fusion oncogene BCR-ABL. Targeting BCR-ABL by tyrosine kinase inhibitors (TKIs) has changed fatal CML into an almost curable disease. Despite that, TKIs lose their effectiveness due to disease progression. Unfortunately, the mechanism of CML progression is poorly understood and common biomarkers for CML progression are unavailable. This study was conducted to find novel biomarkers of CML progression by employing whole-exome sequencing (WES). Materials and Methods: WES of accelerated phase (AP) and blast crisis (BC) CML patients was carried out, with chronic-phase CML (CP-CML) patients as control. After DNA library preparation and exome enrichment, clustering and sequencing were carried out using Illumina platforms. Statistical analysis was carried out using SAS/STAT software version 9.4, and R package was employed to find mutations shared exclusively by all AP-/BC-CML patients. Confirmation of mutations was carried out using Sanger sequencing and protein structure modeling using I-TASSER followed by mutant generation and visualization using PyMOL. Results: Three novel genes (ANKRD36, ANKRD36B and PRSS3) were mutated exclusively in all AP-/BC-CML patients. Only ANKRD36 gene mutations (c.1183_1184 delGC and c.1187_1185 dupTT) were confirmed by Sanger sequencing. Protein modeling studies showed that mutations induce structural changes in ANKRD36 protein. Conclusions: Our studies show that ANKRD36 is a potential common biomarker and drug target of early CML progression. ANKRD36 is yet uncharacterized in humans. It has the highest expression in bone marrow, specifically myeloid cells. We recommend carrying out further studies to explore the role of ANKRD36 in the biology and progression of CML.

Background: Cervical radiculopathy is a condition of pain and sensorimotor deficits due to cervical nerve root compression. The symptoms may include weakness, tingling, numbness and pain. C6, C7 nerve roots are most involved in cervical radiculopathy. Various modalities and therapeutic interventions are used and recommended for management of cervical radiculopathy including cervical collars, immobilization, manipulation, cervical traction TENS and therapeutic exercises.The aimof this study is to evaluate the efficacy of neurodynamics in comparison to manual traction in the management of cervical radiculopathy. Methods: An Interventional research was performed in the Department of Physiotherapy, Mayo hospital Lahore, Pakistan. 40 subjects aged between 18-60 years participated in the study. They were divided into two groups namely Group A and Group B with 20 subjects in each group. The duration of the study was 4 weeks with 4 sessions per week. GroupA received neurodynamics along with strengthening exercises while Group B received manual traction along with strengthening exercises. Neck Disability Index (NDI) scale was used as an outcome measure andpaired sample t-test was used for statistical analysis. Results: A significant improvement was found in both neurodynamics group and manual traction group for pain and functional status with p value< 0.05. Conclusion: This study concluded that the treatment techniques, neurodynamics and manual traction were effective in alleviating the symptoms associated with cervical radiculopathy in terms of decreasing pain intensity, increasing ranges of motion and improving functional capacity.

A 40-year-old premenopausal female presented with foul-smelling per vaginal discharge for 3 months. Diagnostic work revealed a locally advanced primary malignant melanoma of uterine cervix. The patient declined pelvic surgery and was treated with Dacarbazine. Malignant melanoma is a rare tumour of skin and has been ranked in the top ve cancers of Australia and Sweden. It is a tumour of melanocytes which forms melanin pigment in the skin. In men, the most common site is trunk while in females common site is limbs. However, melanoma can arise from mucosal surfaces where the melanocytes are present. Most common mucosal sites are head and neck followed by female genital tract. Key words: Cervix, dacarbazine, malignant melanoma

Autosomal recessive hypotrichosis is a rare genetic irreversible hair loss disorder characterized by sparse scalp hair, sparse to absent eyebrows and eyelashes, and sparse axillary and body hair. The study, presented here, established genetic linkage in four families showing similar phenotypes to lysophosphatidic acid receptor 6 (LPAR6) gene on chromosome 13q14.11-q21.32. Subsequently, sequence analysis of the gene revealed two previously reported missense mutations including p.D63V in affected members of one and p.I188F in three other families. Molecular modeling and docking analysis was performed to investigate binding of a ligand oleoyl-L-alpha-lysophosphatidic acid (LPA) to modeled protein structures of normal and mutated (D63V, G146R, I188F, N248Y, S3T, L277P) LPAR6 receptors. The mutant receptors showed a complete shift in orientation of LPA at the binding site. In addition, hydropathy analysis revealed a significant change in the membrane spanning topology of LPAR6 helical segments. The present study further substantiated involvement of LPAR6-LPA signaling in the pathogenesis of hypotrichosis/woolly hair and provided additional insight into the molecular mechanism of hair development.

BACKGROUND: BCR-ABL kinase domain mutations are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients. Recent studies indicate the presence of pre-existing BCR-ABL mutations in a higher percentage of CML patients when CD34+ stem/progenitor cells are investigated using sensitive techniques, and these mutations are associated with imatinib resistance and disease progression. However, such studies were limited to smaller number of patients. METHODS: We investigated BCR-ABL kinase domain mutations in CD34+ cells from 100 chronic-phase CML patients by multiplex allele-specific PCR and sequencing at diagnosis. Mutations were re-investigated upon manifestation of imatinib resistance using allele-specific PCR and direct sequencing of BCR-ABL kinase domain. RESULTS: Pre-existing BCR-ABL mutations were detected in 32/100 patients and included F311L, M351T, and T315I. After a median follow-up of 30 months (range 8-48), all patients with pre-existing BCR-ABL mutations exhibited imatinib resistance. Of the 68 patients without pre-existing BCR-ABL mutations, 24 developed imatinib resistance; allele-specific PCR and BCR-ABL kinase domain sequencing detected mutations in 22 of these patients. All 32 patients with pre-existing BCR-ABL mutations had the same mutations after manifestation of imatinib-resistance. In imatinib-resistant patients without pre-existing BCR-ABL mutations, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients except T315I and Y253F mutations responded to imatinib dose escalation. CONCLUSION: Pre-existing BCR-ABL mutations can be detected in a substantial number of chronic-phase CML patients by sensitive allele-specific PCR technique using CD34+ cells. These mutations are associated with imatinib resistance if affecting drug binding directly or indirectly. After the recent approval of nilotinib, dasatinib, bosutinib and ponatinib for treatment of chronic myeloid leukemia along with imatinib, all of which vary in their effectiveness against mutated BCR-ABL forms, detection of pre-existing BCR-ABL mutations can help in selection of appropriate first-line drug therapy. Thus, mutation testing using CD34+ cells may facilitate improved, patient-tailored treatment.

Understanding the structure of Ru(V)-oxo species is crucial for designing novel catalysts for sustainable energy applications, such as water splitting for green hydrogen production. This study reports the EPR detection of a Ru(V)-oxo intermediate stabilized by terpyridine and phenanthroline carboxylate ligands. The interaction between the carboxylate group and the ruthenium center, along with PCET-dependent hemilability under oxidative conditions, plays a critical role in achieving the high-valent state. Subtle changes in the coordination environment around the central metal also proved to be essential. Low-temperature NMR, high-resolution mass spectrometry, UV-Vis spectroscopy, and density functional theory calculations support these findings., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

One of the biggest public health problems globally is that of iron deficiency anemia. The present research aimed to determine the effect of prebiotics along with iron fortification on iron biomarkers in female anemic rats as some evidence suggests that prebiotics convert increase the solubility of iron, thereby enhancing its absorption. A total of 126 Sprague Dawley rats were fed with sixteen different types of fortified feed containing prebiotics (Inulin + Galacto Oligosaccharides) and Iron Fortificants (Sodium Ferric Ethylenediaminetetraacetate + Ferrous Sulphate). The duration of the trials was 3 months aimed at determining the effect of iron fortification and prebiotics on different iron biomarkers including Hemoglobin (Hb), Hematocrit, Red Blood Cell (RBC) count, Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC). The trials resulted in statistically significant improved iron biomarkers among female anemic rats (P-value < 0.05). It was concluded that iron fortification and prebiotics in combination were able to increase the levels of iron biomarkers in female anemic rats.

Vaccination provides great protection against several infections, including coronavirus disease 2019 (COVID-19). However, the endeavor faces multiple context-specific problems that affect its uptake, leading to vaccine hesitancy. Vaccine hesitancy is a focal barrier to the success of COVID-19 vaccination programs. This umbrella review aimed to present a summary of global data regarding vaccine hesitancy and acceptance rates among medical students, health professionals, and health care workers. In this regard, two databases, PubMed and Scopus, were selected for data retrieval and analysis. A search term and an inclusion/exclusion criterion were applied to summarize the findings of existing systematic reviews. A pooled prevalence of vaccine acceptance and hesitancy with 95% confidence interval (CI) was taken as a prerequisite for this review. The results found a high percentage of COVID-19 vaccination ranging from 13.1% (95% CI, 6.9%-20.9%) to 46% (95% CI, 0.38%-0.54%), while the percentage of acceptance varied from 46% (95% CI, 37%-54%) to 83.0% (95% CI, 71%-96%) among medical students, health professionals, and health care workers. This umbrella review found a high percentage of COVID-19 vaccine hesitancy among medical students, health professionals, and health care workers. Further studies analyzing the determinants of vaccine hesitancy are important predictors for successful vaccination programs at the global level., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Korean Vaccine Society.)

The current study focuses on Punica granatum L. (pomegranate) peel and peel extract and their use as functional foods, food additives, or physiologically active constituents in nutraceutical formulations. The pomegranate peel extract is a good source of bioactive substances needed for the biological activity of the fruit, including phenolic acids, minerals, flavonoids (anthocyanins), and hydrolyzable tannins (gallic acid). The macromolecules found in pomegranate peel and peel extract have been recommended as substitutes for synthetic nutraceuticals, food additives, and chemo-preventive agents because of their well-known ethno-medical significance and chemical properties. Moreover, considering the promises for both their health-promoting activities and chemical properties, the dietary and nutraceutical significance of pomegranate peel and pomegranate peel extract appears to be underestimated. The present review article details their nutritional composition, phytochemical profile, food applications, nutraceutical action, and health benefits., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Low molecular weight sulfated galactan (LMSG) supplemented with octanoyl ester (Oct-LMSG) demonstrated superior wound healing activity compared to the unsupplemented LMSG in a fibroblast wound model. To test the hypothesis that the increased bioactivity of Oct-LMSG may depend on its penetration into the plasma membrane, its cellular uptake was investigated and collagen production in fibroblast cells was assessed for the first time. The cellular uptake of Oct-LMSG was examined using indirect immunofluorescence and a confocal laser scanning microscope. In addition, the degree of fibroblast activation associated with this uptake was evaluated. The results indicated increased LMSG internalization in fibroblasts treated with Oct-LMSG. Transmission electron micrographs revealed the ultrastructure of active protein production in fibroblasts upon treatment with Oct-LMSG. In addition, Oct-LMSG upregulated the expression of type I collagen mRNA and proteins, as well as related signaling molecules involved in collagen synthesis, including collagen type I α1 chain (Col1A1), Col1A2, phosphorylated (p)-Smad2/3 and p-Smad4. The current findings support the notion that the supplementation of LMSG with octanoyl enhanced its cellular uptake into fibroblasts and, as a result, regulated the expression of type I collagen in fibroblasts via the activation of the Smad signaling pathway. This study demonstrates the therapeutic potential of Oct-LMSG in promoting tissue regeneration., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Sakaew et al.)

Twenty surface sediment samples were gathered from Chasma Lake, deciding the radionuclides 137 Cs, 226 Ra, 228 Ra, 232 Th, and 40 K and their associated hazard indices. The deliberate radionuclide activities of present research have been contrasted with earlier research, and acquired outcomes in the present study are found below the results in the world. The radiation hazard indices following the presence of natural radionuclides in sediment samples were estimated, and the results assigned the values of all the determined radiological indices found inside the worldwide suggested limits. It was concluded from the current review that the sediment of Chashma Lake is safe for construction and agriculture and does not make radiation dangerous to the nearby local area of the lake., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Iron supplementation and fortification are the well-known approaches to treat iron deficiency anemia (IDA) in women of reproductive age. The objective of the current randomized controlled trial (RCT) was to evaluate the cumulative effects of prebiotics and iron fortification among women of reproductive age. For this purpose, a total of 75 iron deficient women of childbearing age were recruited and randomly divided into 5 groups (4 treatment groups and 1 control group). Four different types of fortified wheat flour were prepared using two iron fortificants (NaFeEDTA and FeSO 4 ) and two prebiotics [inulin and galacto oligosaccharides (GOS)], while control group was treated with iron fortified flour without any prebiotics. Blood samples were collected from overnight fasted women on monthly basis up to 90 days. Hematological indices such as Hemoglobin (Hb), Hematocrit, Red Blood Cell (RBC) Count and Mean Corpuscular Volume (MCV), as well as iron biomarkers including serum iron, ferritin, transferrin, and Total Iron Binding Capacity (TIBC) were evaluated for analyses. The results showed a considerable positive improvement in all iron biomarkers as well as hematological indices among the treatment groups ( P -value < 0.05), as compared to the control group. A maximum Hb (11.86 ± 0.24 mg/dL) and hematocrit value (35.06 ± 1.32%), was reported in group G 3 which was treated with fortified wheat flour at a dose of 963 mg/kg GOS + 15 ppm FeSO 4 . On the other hand, highest mean values for RBC Count (4.73 ± 0.41 mil/mm 3 ), MCV (81.41 ± 3.21 fL), serum iron (75.62 ± 2.79 μg/dL), serum transferrin (16.82 ± 0.30 mg/dL), and TIBC (403.68 ± 7.27 μg/dL) were observed in G 4 group receiving the fortified wheat flour at a dose of 963 mg/kg GOS + 30 ppm FeSO 4 level. The study concluded that prebiotic fortification along with iron salts helps to enhance iron absorption among iron deficiency anemic women of reproductive age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Iqbal, Ahmed, Zafar, Farooq, Abid, Shah, Akram, Ghazanfar and Ahmad.)

Objective: To find out the prevalence and associated factors of undernutrition in a semi-rural setting., Methods: The community-based cross-sectional study was conducted in Tehsil Battagram of Khyber Pakhtunkhwa province, Pakistan, in January and February 2020 after approval from the ethics review committee of Nanjing Medical University, Jiangsu, China, and comprised children aged 6-59 months who had no physical or mental disability. Data was collected using a structured questionnaire. Anthropometric data was analysed using the World Health Organisation Anthro software. Multivariate logistic regression analysis was used to find out the association between dependent variables, like wasting, underweight and stunting, and independent variables, like socioeconomic, child, maternal and environmental characteristics. Data was analysed using SPSS 21., Results: Of the 504 children, 257(51%) were girls and 247(49%) were boys. The largest group was aged 36-47 months 127(25.2%), while the smallest group was aged 6-11 months 56(11.1%). Overall, 94(18.7%) children were wasted, 167(33.1%) were underweight and 248(49.2%) were stunted. Children whose family income was high had low odds for being wasted (odds ratio: 0.59, 95% confidence interval: 0.25-0.71), underweight (odds ratio: 0.30, 95% confidence interval: 0.08-0.72) and stunted (odds ratio: 0.54, 95% confidence interval: 0.30-0.80). Similarly, those children who were exclusively breastfed had low odds of being wasted were (odds ratio: 0.45, 95% confidence interval: 0.32-0.53), underweight (odds ratio: 0.56, 95% confidence interval: 0.42-0.78) and stunted (odds ratio: 0.62, 95% confidence interval: 0.51-0.97). Children who were not immunised had higher odds of wasting (odds ratio: 4.16, 95% confidence interval: 2.18-7.93), underweight (odds ratio: 4.45, 95% confidence interval: 2.77-7.14) and stunted (odds ratio: 4.36, 95% confidence interval: 2.32-8.71). Children of mothers who did not have antenatal care visits had higher odds of being wasted (odds ratio: 1.91, 95% confidence interval: 1.13-3.22), underweight (odds ratio: 1.32, 95% confidence interval: 1.22-2.13) and stunted (odds ratio: 1.48, 95% confidence interval: 1.32-2.62). Children who did not have a latrine facility had higher odds of being wasted (odds ratio: 1.63, 95% confidence interval: 1.29-1.58), underweight (odds ratio: 1.76, 95% confidence interval: 1.36-3.84) and stunted (odds ratio: 1.45, 95% confidence interval: 1.22-2.12)., Conclusion: Undernutrition among children aged 6-59 months was widespread. Nutrition awareness, interventions and multi-sectoral approaches were found to be needed to cope with the problem in the study area.

Accurate translation of genetic information into proteins is vital for cell sustainability. ProXp-ala prevents proteome-wide Pro-to-Ala mutations by hydrolyzing misacylated Ala-tRNA Pro , which is synthesized by prolyl-tRNA synthetase. Bacterial ProXp-ala was previously shown to combine a size-based exclusion mechanism with conformational and chemical selection for the recognition of the alanyl moiety, whereas tRNA Pro is selected via recognition of tRNA acceptor-stem elements G72 and A73. The identity of these critical bases changed during evolution with eukaryotic cytosolic tRNA Pro possessing a cytosine at the corresponding positions. The mechanism by which eukaryotic ProXp-ala adapted to these changes remains unknown. In this work, recognition of the aminoacyl moiety and tRNA acceptor stem by human ( Homo sapiens , or Hs ) ProXp-ala was examined. Enzymatic assays revealed that Hs ProXp-ala requires C72 and C73 in the context of Hs cytosolic tRNA Pro for efficient deacylation of mischarged Ala-tRNA Pro The strong dependence on these bases prevents cross-species deacylation of bacterial Ala-tRNA Pro or of Hs mitochondrial Ala-tRNA Pro by the human enzyme. Similar to the bacterial enzyme, Hs ProXp-ala showed strong tRNA acceptor-stem recognition but differed in its amino acid specificity profile relative to bacterial ProXp-ala. Changes at conserved residues in both the Hs and bacterial ProXp-ala substrate-binding pockets modulated this specificity. These results illustrate how the mechanism of substrate selection diverged during the evolution of the ProXp-ala family, providing the first example of a trans -editing domain whose specificity evolved to adapt to changes in its tRNA substrate., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Vargas-Rodriguez et al.)

Introduction: Diarrheal disease due to toxigenic Clostridium difficile (CD) accounts for an increased number of hospitalizations and deaths each year. Published guidelines recommend reflex testing of CD antigen-positive samples to molecular testing or testing samples directly by a molecular assay. This multicenter study was designed to compare the accuracy of two different molecular methods targeting different CD genes: Xpert C. difficile Epi RUO RT-PCR assay (XPCR) which targets toxin B (Cepheid, Sunnyvale, CA) and a laboratory-developed PCR (LDPCR) which targets mutations in the tcdC regulatory gene., Methodology: Two molecular methods for toxigenic CD detection, the Xpert C. difficile Epi RUO RT-PCR assay (XPCR) [Cepheid, Sunnyvale, CA] and a laboratory-developed PCR assay (LDPCR) were compared to a consensus gold standard (CGS) or toxigenic culture (TC) as the reference method. A subset of specimens was subjected to additional molecular characterization of toxigenic CD., Results: Both molecular methods were >90% sensitive for CD detection. Discordant results were noted when molecular test results were compared to non-molecular methods. Supplemental molecular characterization illustrated inherent difficulties in comparisons using different molecular methods for CD., Conclusion: Laboratories may consider using multiple CD detection methods or combinations of methods, including molecular detection for rapid and accurate diagnosis of CD, as driven by best practices for the respective healthcare environment. Laboratories must be aware of intrinsic differences when comparing performance characteristics of different molecular assays.

Seventeen of our 42 regular hemodialysis (HD) patients (40.5%), and six of our 16 patients on continuous ambulatory peritoneal dialysis (CAPD) (37%) were found to be positive for hepatitis C virus (HCV) antibody in June, 1992. Since the virus was considered susceptible to eradication by the available disinfection methods of the HD machines, the most likely source of transmission was considered to be incomplete application of the universal infection control techniques. These recommendations were strictly applied, but no attempt was made towards designating specific machines for anti-HCV positive patients. Review of data revealed that seven of our 25 previously negative patients (28%) turned positive in the following 12 months. Risk factors such as blood transfusions were excluded in all these patients. A strict protocol of careful chemical disinfection using Citrosteril run at 85 degrees C for 35 minutes after each dialysis session was adopted. Over the following 18 months, six of the remaining 17 negative patients (35.2%) seroconverted. They all had received blood transfusions, 7 to 14 months before (mean 10.5 months). The blood had been screened and had tested negative for anti-HCV antibody. By contrast, none of our CAPD patients who were anti-HCV negative in June 1992, and remained on CAPD, turned positive. The HD machine disinfection techniques were thoroughly reviewed and found to be as prescribed In the absence of other sources of infection with HCV we conclude that the HD machines were the most likely source of transmission of HCV infection and therefore, it is important to assign specific HD machines for anti-HCV positive patients. We have now adopted such a system.