Biallelic loss-of-function variants of ZFTRAF1 cause neurodevelopmental disorder with microcephaly and hypotonia.

PURPOSE: Neurodevelopmental disorders exhibit clinical and genetic heterogeneity, ergo manifest dysfunction in components of diverse cellular pathways; the precise pathomechanism for the majority remains elusive. METHODS: We studied 5 affected individuals from 3 unrelated families manifesting global developmental delay, postnatal microcephaly, and hypotonia. We used exome sequencing and prioritized variants that were subsequently characterized using immunofluorescence, immunoblotting, pulldown assays, and RNA sequencing. RESULTS: We identified biallelic variants in ZFTRAF1, encoding a protein of yet unknown function. Four affected individuals from 2 unrelated families segregated 2 homozygous frameshift variants in ZFTRAF1, whereas, in the third family, an intronic splice site variant was detected. We investigated ZFTRAF1 at the cellular level and signified it as a nucleocytoplasmic protein in different human cell lines. ZFTRAF1 was completely absent in the fibroblasts of 2 affected individuals. We also identified 110 interacting proteins enriched in mRNA processing and autophagy-related pathways. Based on profiling of autophagy markers, patient-derived fibroblasts show irregularities in the protein degradation process. CONCLUSION: Thus, our findings suggest that biallelic variants of ZFTRAF1 cause a severe neurodevelopmental disorder.

Leveraging shape screening and molecular dynamics simulations to optimize PARP1-Specific chemo/radio-potentiators for antitumor drug design.

PARP1 plays a pivotal role in DNA repair within the base excision pathway, making it a promising therapeutic target for cancers involving BRCA mutations. Current study is focused on the discovery of PARP inhibitors with enhanced selectivity for PARP1. Concurrent inhibition of PARP1 with PARP2 and PARP3 affects cellular functions, potentially causing DNA damage accumulation and disrupting immune responses. In step 1, a virtual library of 593 million compounds has been screened using a shape-based screening approach to narrow down the promising scaffolds. In step 2, hierarchical docking approach embedded in Schrödinger suite was employed to select compounds with good dock score, drug-likeness and MMGBSA score. Analysis supplemented with decomposition energy, molecular dynamics (MD) simulations and hydrogen bond frequency analysis, pinpointed that active site residues; H862, G863, R878, M890, Y896 and F897 are crucial for specific binding of ZINC001258189808 and ZINC000092332196 with PARP1 as compared to PARP2 and PARP3. The binding of ZINC000656130962, ZINC000762230673, ZINC001332491123, and ZINC000579446675 also revealed interaction involving two additional active site residues of PARP1, namely N767 and E988. Weaker or no interaction was observed for these residues with PARP2 and PARP3. This approach advances our understanding of PARP-1 specific inhibitors and their mechanisms of action, facilitating the development of targeted therapeutics.

Tobacco smoke condensate-induced senescence in endothelial cells was ameliorated by colchicine treatment via suppression of NF-κB and MAPKs P38 and ERK pathways activation.

Smoking is the major cause of cardiovascular diseases and cancer. It induces oxidative stress, leading to DNA damage and cellular senescence. Senescent cells increase the expression and release of pro-inflammatory molecules and matrix metalloproteinase, which are known to play a vital role in the initiation and progression of cardiovascular diseases and metastasis in cancer. The current study investigated the smoking induced cellular senescence and employed colchicine that blocked senescence in endothelial cells exposed to tobacco smoke condensate. Colchicine prevented oxidative stress and DNA damage in tobacco smoke-condensate-treated endothelial cells. Colchicin reduced ß-gal activity, improved Lamin B1, and attenuated cell growth arrest markers P21 and P53. Colchicine also ameliorated the expression of SASP factors and inhibited the activation of NF-kB and MAPKs P38 and ERK. In summary, colchicine inhibited tobacco smoke condensate-induced senescence in endothelial cells by blocking the activation of NF-kB and MAPKs P38 and ERK.

Surgical repair of torn base of ruptured middle cerebral artery trifurcation aneurysm.

BACKGROUND: Treating complex middle cerebral artery (MCA) trifurcation aneurysms requires a delicate balance between achieving aneurysm obliteration and preserving vascular integrity. Various cerebral revascularization techniques, including bypass, and clip reconstruction are considered individually or in combination. METHODS: This case report outlines a successful repair of a ruptured neck and base of MCA trifurcation aneurysm using a suturing-clip reconstruction technique. Temporary aneurysm trapping was implemented, with maintained elevated blood pressure to ensure collateral perfusion during repair of ruptured base and neck of MCA aneurysm. CONCLUSION: The suturing-clip reconstruction exhibited long-term radiological stability, emerging as a valuable alternative for managing challenging MCA trifurcation aneurysms.

Surgical and endovascular cerebral revascularization for cerebral vasculitis with inflammatory vessel stenosis: a case series.

Autoimmune vasculitides affect the cerebral vasculature significantly in a considerable number of cases. When immunosuppressive treatments fail to prevent stenosis in cerebral vessels, treatment options for affected patients become limited. In this case series, we present four cases of pharmacoresistant vasculitis with recurrent transient ischemic attacks (TIAs) or stroke successfully treated with either extracranial-intracranial (EC-IC) bypass surgery or endovascular stenting. Both rescue treatments were effective and safe in the selected cases. Our experience suggests that cases of pharmacoresistant cerebral vasculitis with recurrent stroke may benefit from rescue revascularization in combination with maximum medical management.

Trans-lateral ventricular approach for surgical treatment of high-located P2-P3 junction posterior cerebral artery aneurysms: from anatomical research to clinical application.

BACKGROUND: Posterior cerebral artery (PCA) aneurysms, though rare, pose treatment challenges. Endovascular therapy is the preferred option, but microsurgery becomes necessary in certain cases. Various microsurgical approaches have been suggested for PCA aneurysms, particularly those at the P2-P3 junction. This study highlights the trans-lateral ventricular approach (TVA) for addressing these complex aneurysms. This study aims to assess the feasibility and safety of the trans-lateral ventricular approach (TVA) for treating high-located complex PCA aneurysms at the P2-P3 junction. The study evaluates both clinical outcomes and anatomical considerations. METHODS: Two cases of PCA aneurysms at the P2-P3 junction were treated using TVA in 2019. Navigation-guided entry via the interparietal sulcus was planned. Ventriculostomy was performed from the cortex to the lateral ventricle's atrium. Medial atrial floor dissection exposed PCA's P2-P3 segments. Neuronavigation and ultrasound-aided guidance was used. Anatomical studies on fixed and contrast-perfused specimens refined the approach. RESULTS: Both cases saw successful aneurysm clipping. The unruptured aneurysm patient was discharged in 6 days. The poor-grade SAH patient required extended ICU care, moving to rehabilitation with mRS = 4. The unruptured complex aneurysm case exhibited no deficits, returning to work in 3 months. Anatomical dissections validated TVA for high-located P2-P3 junction PCA aneurysms. CONCLUSION: While endovascular therapy remains primary, this study demonstrates the viability of navigation-guided TVA for select high-located P2-P3 junction PCA aneurysms. Successes and challenges underscore the importance of patient selection and anatomical awareness.

Evaluation of FRESH scores in predicting outcome and quality of life after aneurysmal subarachnoid haemorrhage in a European patient cohort.

BACKGROUND: Despite aneurysmal subarachnoid haemorrhage (aSAH) patients often experiencing physical and mental disabilities impacting their quality of life (QoL), routine assessment of long-term QoL data and predictive tools are limited. This study evaluates the newly developed "functional recovery expected after subarachnoid haemorrhage" (FRESH) scores with long-term outcomes and QoL in European aSAH patients. METHODS: FRESH, FRESH-cog, and FRESH-quol scores were retrospectively obtained from aSAH patients. Patients were contacted, and the modified Rankin Scale (mRS), extended short form-36 (SF-36), and telephone interview for cognitive status (TICS) were collected and performed. The prognostic and empirical outcomes were compared. RESULTS: Out of 374 patients, 171 patients (54.1%) completed the SF-36, and 154 patients completed the TICS. The SF-36 analysis showed that 32.7% had below-average physical component summary (PCS) scores, and 39.8% had below-average mental component summary (MCS) scores. There was no significant correlation between the FRESH score and PCS (p = 0.09736), MCS (p = 0.1796), TICS (p = 0.7484), or mRS 10-82 months (average 46 months) post bleeding (p = 0.024), respectively. There was also no significant correlation found for "FRESH-cog vs. TICS" (p = 0.0311), "FRESH-quol vs. PCS" (p = 0.0204), "FRESH-quol vs. MCS" (p = 0.1361) and "FRESH-quol vs. TICS" (p = 0.1608). CONCLUSIONS: This study found no correlation between FRESH scores and validated QoL tools in a European population of aSAH patients. The study highlights the complexity of reliable long-term QoL prognostication in aSAH patients and emphasises the need for further prospective research to also focus on QoL as an important outcome parameter.

Clinical Outcome Prediction of Early Brain Injury in Aneurysmal Subarachnoid Hemorrhage: the SHELTER-Score.

BACKGROUND: Despite intensive research on preventing and treating vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage (aSAH), mortality and morbidity rates remain high. Early brain injury (EBI) has emerged as possibly the major significant factor in aSAH pathophysiology, emphasizing the need to investigate EBI-associated clinical events for improved patient management and decision-making. This study aimed to identify early clinical and radiological events within 72 h after aSAH to develop a conclusive predictive EBI score for clinical practice. METHODS: This retrospective analysis included 561 consecutive patients with aSAH admitted to our neurovascular center between 01/2014 and 09/2022. Fourteen potential predictors occurring within the initial 72 h after hemorrhage were analyzed. The modified Rankin Scale (mRS) score at 6 months, discretized to three levels (0-2, favorable; 3-5, poor; 6, dead), was used as the outcome variable. Univariate ordinal regression ranked predictors by significance, and forward selection with McFadden's pseudo-R2 determined the optimal set of predictors for multivariate proportional odds logistic regression. Collinear parameters were excluded, and fivefold cross-validation was used to avoid overfitting. RESULTS: The analysis resulted in the Subarachnoid Hemorrhage Associated Early Brain Injury Outcome Prediction score (SHELTER-score), comprising seven clinical and radiological events: age (0-4 points), World Federation of Neurosurgical Societies (0-2.5 points), cardiopulmonary resuscitation (CPR) (2 points), mydriasis (1-2 points), midline shift (0.5-1 points), early deterioration (1 point), and early ischemic lesion (2 points). McFadden's pseudo-R2 = 0.339, area under the curve for death or disability 0.899 and 0.877 for death. A SHELTER-score below 5 indicated a favorable outcome (mRS 0-2), 5-6.5 predicted a poor outcome (mRS 3-5), and ≥ 7 correlated with death (mRS 6) at 6 months. CONCLUSIONS: The novel SHELTER-score, incorporating seven clinical and radiological features of EBI, demonstrated strong predictive performance in determining clinical outcomes. This scoring system serves as a valuable tool for neurointensivists to identify patients with poor outcomes and guide treatment decisions, reflecting the great impact of EBI on the overall outcome of patients with aSAH.

Flavonoids: a review on biosynthesis and transportation mechanism in plants.

In recent years, significant progress has been made in understanding the biosynthetic pathway and regulation of flavonoids through forward genetic approaches. However, there remains a notable gap in knowledge regarding the functional characterization and underlying processes of the transport framework responsible for flavonoid transport. This aspect requires further investigation and clarification to achieve a comprehensive understanding. Presently, there are a total of four proposed transport models associated with flavonoids, namely glutathione S-transferase (GST), multidrug and toxic compound extrusion (MATE), multidrug resistance-associated protein (MRPs), and bilitranslocase-homolog (BTL). Extensive research has been conducted on the proteins and genes related to these transport models. However, despite these efforts, numerous challenges still exist, leaving much to be explored in the future. Gaining a deeper understanding of the mechanisms underlying these transport models holds immense potential for various fields such as metabolic engineering, biotechnological approaches, plant protection, and human health. Therefore, this review aims to provide a comprehensive overview of recent advancements in the understanding of flavonoid transport mechanisms. By doing so, we aim to paint a clear and coherent picture of the dynamic trafficking of flavonoids.

Microvascular anastomosis of the human lacrimal gland: a concept study towards transplantation of the human lacrimal gland.

INTRODUCTION: Severe aqueous tear deficiency is caused by primary or secondary main lacrimal gland insufficiency. The transplantation of a human lacrimal gland could become a potential treatment option to provide physiological tears with optimal properties. To this end, we performed an ex vivo study to develop a surgical strategy that would ensure a vascular supply for a lacrimal gland transplant using microvascular techniques. MATERIAL AND METHODS: Five cadaver heads were used to perform a lateral orbitotomy in order to identify the vascular pedicle and the lacrimal gland itself. The principal feasibility and the time of the required surgical steps for an intraorbital microvascular re-anastomosis of the human lacrimal gland were documented. Patency and potential leakage of the anastomosis were tested with hematoxylin intraoperatively. Postoperatively, routine histological, as well as scanning electron microscopy (SEM) of the gland and vascular anastomosis, were performed. RESULTS: The vascular pedicle of all five glands could be isolated over a minimum stretch of at least 1 cm, severed, and successfully reanastmosed microsurgically. Time for arterial anatomization (n = 4) was 23 ± 7 min and 22 ± 3 min for the vein (p = 0.62). The total time for the entire microvascular anastomosis was 46 ± 9 min. All anastomosis were patent upon testing. SEM revealed well-aligned edges of the anastomosis with tight sutures in place. CONCLUSION: Our study demonstrates as proof of principle the feasibility of intraorbital microvascular re-anastomosis of a human lacrimal gland within the presumed window of ischemia of this tissue. This should encourage orbital surgeons to attempt lacrimal gland transplantation in humans in vivo.

Exploring dynamics of plant-herbivore interactions: bifurcation analysis and chaos control with Holling type-II functional response.

In this study, we examine the plant-herbivore discrete model of apple twig borer and grape vine interaction, with a particular emphasis on the extended weak-predator response to Holling type-II response. We explore the dynamical and qualitative analysis of this model and investigate the conditions for stability and bifurcation. Our study demonstrates the presence of the Neimark-Sacker bifurcation at the interior equilibrium and the transcritical bifurcation at the trivial equilibrium, both of which have biological feasibility. To avoid unpredictable outcomes due to bifurcation, we employ chaos control methods. Furthermore, to support our theoretical and mathematical findings, we develop numerical simulation techniques with examples. In summary, our research enhances the comprehension of the dynamics pertaining to interactions between plants and herbivores in the context of discrete-time population models.

Clustering of serum biomarkers involved in post-aneurysmal subarachnoid hemorrhage (aSAH) complications.

Post-aSAH sequela is characterized by the onset of life-threatening complications along with the upregulated underlying inflammation. Cerebral vasospasm (CVS) is one of the most frequent complication after aSAH, which contributes majorly to delayed cerebral ischemia and poor clinical outcome. The objective of this study was to identify the clusters of serum biomarkers that are associated with cerebral vasospasm (CVS) after suffering from aneurysmal subarachnoid hemorrhage (aSAH). In this single-center study, serum concentrations of 10 potential biomarkers, together with clinical and demographic parameters, for 66 aSAH patients were recorded within 24 h after aSAH. The dataset was split into a training set (43 patients) and a validation set. Correlation heatmaps for both datasets were computed. Variables with inconsistent correlations on the two subsets were excluded. Clusters of relevant biomarkers were identified on the complete set, separately for patients who developed post-aSAH CVS and those who did not. Two clusters were found to be specific for patients who suffered from CVS: mitochondrial gene fragments (cytochrome B (Cyt-B), cytochrome C oxidase subunit-1 (Cox-1), displacement loop (D-loop), and IL-23, and the other one, containing IL-6, IL-10, age, and Hunt and Hess score. Clusters of serum biomarkers, analyzed within 24 h of the onset of aSAH, days before the CVS development, are expressed differently in patients suffering from post-aSAH CVS, compared to patients without CVS. This suggests that these biomarkers may be involved in the pathophysiological processes leading to CVS and may be used as its early predictors. These interesting findings are potentially highly relevant for the management of CVS and call for validation on a larger sample of patients.

Phytosterol: nutritional significance, health benefits, and its uses in poultry and livestock nutrition.

Medicinal plants with active ingredients have shown great potential as natural and sustainable additives in livestock and poultry diets as growth promoters, performance, feed conversion ratio, digestibility of nutrient enhancers, and antioxidants and immune system modulators. Among active ingredients, phytosterols, which are plant-based bio-factors that may be found in seeds, fruits, grains, vegetables and legumes, are thought to be involved in the aforementioned activities but are also widely known in human medicine due to their efficacy in treating diabetes, coronary heart disease, and tumors. Nevertheless, phytosterols can also promote carcinogens production, angiogenesis inhibition, metastasis, infiltration, and cancer cells proliferation. This review focuses on the deepening of the biological role and health benefits of phytosterols and their new potential application in poultry and livestock nutrition.

Blood Pressure Affects the Early CT Perfusion Imaging in Patients with aSAH Reflecting Early Disturbed Autoregulation.

BACKGROUND: Early computed tomography perfusion (CTP) is frequently used to predict delayed cerebral ischemia following aneurysmatic subarachnoid hemorrhage (aSAH). However, the influence of blood pressure on CTP is currently controversial (HIMALAIA trial), which differs from our clinical observations. Therefore, we aimed to investigate the influence of blood pressure on early CTP imaging in patients with aSAH. METHODS: We retrospectively analyzed the mean transit time (MTT) of early CTP imaging within 24 h after bleeding prior to aneurysm occlusion with respect to blood pressure shortly before or after the examination in 134 patients. We correlated the cerebral blood flow with the cerebral perfusion pressure in the case of patients with intracranial pressure measurement. We performed a subgroup analysis of good-grade (World Federation of Neurosurgical Societies [WFNS] I-III), poor-grade (WFNS IV-V), and solely WFNS grade V aSAH patients. RESULTS: Mean arterial pressure (MAP) significantly correlated inversely with the mean MTT in early CTP imaging (R = - 0.18, 95% confidence interval [CI] - 0.34 to - 0.01, p = 0.042). Lower mean blood pressure was significantly associated with a higher mean MTT. Subgroup analysis revealed an increasing inverse correlation when comparing WFNS I-III (R = - 0.08, 95% CI - 0.31 to 0.16, p = 0.53) patients with WFNS IV-V (R = - 0.2, 95% CI - 0.42 to 0.05, p = 0.12) patients, without reaching statistical significance. However, if only patients with WFNS V are considered, a significant and even stronger correlation between MAP and MTT (R = - 0.4, 95% CI - 0.65 to 0.07, p = 0.02) is observed. In patients with intracranial pressure monitoring, a stronger dependency of cerebral blood flow on cerebral perfusion pressure is observed for poor-grade patients compared with good-grade patients. CONCLUSIONS: The inverse correlation between MAP and MTT in early CTP imaging, increasing with the severity of aSAH, suggests an increasing disturbance of cerebral autoregulation with the severity of early brain injury. Our results emphasize the importance of maintaining physiological blood pressure values in the early phase of aSAH and preventing hypotension, especially in patients with poor-grade aSAH.

Effect of ascorbic acid on metabolic status, lipid peroxidation, antioxidant activity and quality of frozen Indian red jungle fowl (Gallus gallus murghi) semen.

The Indian red jungle fowl population is decreasing in its natural habitat. Its conservation through semen cryopreservation with sufficient live sperm recovery rate is requisite where ascorbic acid could play significant role to mitigate cryo-incited injuries. The objective was to elucidate the effect of ascorbic acid on freezability of Indian red jungle fowl sperm. Pooled semen was aliquoted and diluted (1:5) with red fowl extender having ascorbic acid: 0.0 (control), 1.0, 2.0 and 4.0 mM. Diluted samples were cryopreserved and semen quality was assessed at post-dilution, cooling, equilibration and freeze-thawing stages. Sperm metabolic status, antioxidant potential and lipid peroxidation were studied at post-dilution and freeze-thawing. Sperm motility did not differ (p > .05) in experimental extenders and control at post-dilution and cooling; however, it was recorded higher (p < .05) with ascorbic acid at 2.0 mM compared with other levels at post-equilibration and post-thawing stage. Sperm viability, plasma membrane and acrosome intactness were recorded higher (p < .05) with 2.0 mM ascorbic acid compared with other concentrations of ascorbic acid at all stages of cryopreservation. Sperm metabolic status and antioxidant potential were recorded higher (p < .05), while lipid peroxidation was recorded lowest (p < .05) with 2.0 mM ascorbic acid compared with 1.0, 4.0 mM and control. In conclusion, ascorbic acid at 2.0 mM in red fowl extender improves quality, metabolic status and antioxidant potential of frozen Indian red jungle fowl semen through ameliorating lipid peroxidation.

The Role of NF-κB in Intracranial Aneurysm Pathogenesis: A Systematic Review.

Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute to IA development. The nuclear factor "kappa-light-chain-enhancer" of activated B-cells (NF-κB) is the major driver of inflammation. It increases the expression of inflammatory markers and matrix metalloproteinases (MMPs), which contribute heavily to the pathogenesis of IAs. NF-κB activation has been linked to IA rupture and resulting subarachnoid hemorrhage. Moreover, NF-κB activation can result in endothelial dysfunction, smooth muscle cell phenotypic switching, and infiltration of inflammatory cells in the arterial wall, which subsequently leads to the initiation and progression of IAs and consequently results in rupture. After a systematic search, abstract screening, and full-text screening, 30 research articles were included in the review. In this systematic review, we summarized the scientific literature reporting findings on NF-κB's role in the pathogenesis of IAs. In conclusion, the activation of the NF-κB pathway was associated with IA formation, progression, and rupture.

Pharmacophore-Based Virtual Screening and In-Silico Explorations of Biomolecules (Curcumin Derivatives) of Curcuma longa as Potential Lead Inhibitors of ERBB and VEGFR-2 for the Treatment of Colorectal Cancer.

The newly FDA-approved drug, Axitinib, is an effective therapy against RTKs, but it possesses severe adverse effects like hypertension, stomatitis, and dose-dependent toxicity. In order to ameliorate Axitinib's downsides, the current study is expedited to search for energetically stable and optimized pharmacophore features of 14 curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) derivatives. The rationale behind the selection of curcumin derivatives is their reported anti-angiogenic and anti-cancer properties. Furthermore, they possessed a low molecular weight and a low toxicity profile. In the current investigation, the pharmacophore model-based drug design, facilitates the filtering of curcumin derivatives as VEGFR2 interfacial inhibitors. Initially, the Axitinib scaffold was used to build a pharmacophore query model against which curcumin derivatives were screened. Then, top hits from pharmacophore virtual screening were subjected to in-depth computational studies such as molecular docking, density functional theory (DFT) studies, molecular dynamics (MD) simulations, and ADMET property prediction. The findings of the current investigation revealed the substantial chemical reactivity of the compounds. Specifically, compounds S8, S11, and S14 produced potential molecular interactions against all four selected protein kinases. Docking scores of -41.48 and -29.88 kJ/mol for compounds S8 against VEGFR1 and VEGFR3, respectively, were excellent. Whereas compounds S11 and S14 demonstrated the highest inhibitory potential against ERBB and VEGFR2, with docking scores of -37.92 and -38.5 kJ/mol against ERBB and -41.2 and -46.5 kJ/mol against VEGFR-2, respectively. The results of the molecular docking studies were further correlated with the molecular dynamics simulation studies. Moreover, HYDE energy was calculated through SeeSAR analysis, and the safety profile of the compounds was predicted through ADME studies.

Effects of Different Aquafeed Sources on Growth Performance, Oxidative Capacity, and Fatty Acid Profile of Three Carps Reared in the Semi-Intensive Composite Culture System.

The current experiment is designed to evaluate the effect of different aquafeeds (farm-made versus commercial) on growth, body composition, oxidative capacity, and fatty acid profile in the semi-intensive composite culture system. For this, 1,100 fingerlings/acre having initial body weight and length, Labeo rohita (61.34 g, 171 mm), Catla catla (71.45 g, 181 mm), and Cyprinus carpio (30.80 g, 91 mm) were randomly distributed to 16 ponds and randomly fed on eight different diets (n = 2 pond/diet) in a completely randomized research design. Aquafeed were farm-based diets (D1-D2) and commercial aquafeed (D3-D8). The farm-made diets contained various crude protein levels of maize gluten (24.9%) and rice polish (7.3%), whereas commercial diets were procured from commercial feed plants (AMG, Supreme, Aqua, Star Floating, Hi-Pro, and Punjab feed). The growth performance of carps (L. rohita and C. catla) was significantly improved (p < 0.05) by feeding D3 as compared to other diets. Similarly, white blood cell concentration was greater (p < 0.05) in all species fed by D3 than in those fed on D7, D8, D5, D6, D1, and D2 fed groups, respectively. Alanine transaminase, aspartate transaminase, and alanine phosphatase activities were significantly lower (p < 0.05) in the D3-fed L. rohita, C. catla, and C. carpio compared with those fed on the rest of the treatments. The activities of glutathione peroxidase and superoxide dismutase were also higher (p < 0.05) for the D3 fed L. rohita, C. catla, and C. carpio than those fed on the rest diets. The groups fed on D3 and D4 had greater (p < 0.05) concentrations of myristic (14), palmitic acid (16), and stearic (18) acids than those fed on the rest of the commercial diets. However, meat chemical composition was similar (p > 0.05) across the treatments. These results also prove that the increase in the dietary protein level and lipid content can improve the fish's body's crude protein and fat levels. Feeding D3 improved the production performance, oxidative status, and fatty acid profile in composite major carps culture systems. Thus, based on growth, survival, and body composition, it is concluded that D3 and D4 may be recommended for a commercial culture of major carps. Dietary treatments had no significant impact (p > 0.05) on water's physical-chemical properties. Calcium content and alkalinity varied (p < 0.05), with D5 showing the lowest calcium and the highest alkalinity.

Outcomes of Radioactive Iodine (131I) Therapy among Hyperthyroid patients.

Objective: The present study aimed to assess the thyroid outcomes six-months after radioactive Iodine-131 therapy (RIT) among hyperthyroid patients and identify the factors associated with them. Methods: This retrospective observational study was conducted at the department of Nuclear Medicine and Molecular Imaging, Northwest General Hospital & Research Centre during 2013 to 2019. For the study purpose, the thyroid outcomes of 153 hyperthyroid patients were studied retrospectively for six months after RIT. The data was obtained from the medical records. Patient baseline characteristics, clinical features, laboratory investigations, results of thyroid imaging, and therapeutic investigations were acquired and recorded in a structured questionnaire. Results: Out of the 153 screened records of hyperthyroid patients, 19.6% became euthyroid, 9.2% remained hyperthyroid, and 25.5% developed hypothyroidism after six months of RIT. The observed remission rate by the end of six months was 80.95%. Three months post-RIT, gender and RAI doses had a significant effect on thyroid function. The frequency of hypothyroidism was higher among those treated with an RAI dose of ≤ 20 mCi (83.0%) than those treated with a higher dose > 20 mCi (17%). Moreover, most patients receiving > 20 mCi radioiodine became euthyroid (64.5%). Similar outcomes were observed after six months of the therapy, except gender was replaced by etiologies of hyperthyroidism (p=0.009). Conclusion: Radioactive iodine (131-I) therapy is effective for the treatment of hyperthyroidism. However, the appropriate dose is still debatable, as there was a high incidence of hypothyroidism post-therapy.

Large-scale genomic analysis reveals the genetic cost of chicken domestication.

BACKGROUND: Species domestication is generally characterized by the exploitation of high-impact mutations through processes that involve complex shifting demographics of domesticated species. These include not only inbreeding and artificial selection that may lead to the emergence of evolutionary bottlenecks, but also post-divergence gene flow and introgression. Although domestication potentially affects the occurrence of both desired and undesired mutations, the way wild relatives of domesticated species evolve and how expensive the genetic cost underlying domestication is remain poorly understood. Here, we investigated the demographic history and genetic load of chicken domestication. RESULTS: We analyzed a dataset comprising over 800 whole genomes from both indigenous chickens and wild jungle fowls. We show that despite having a higher genetic diversity than their wild counterparts (average π, 0.00326 vs. 0.00316), the red jungle fowls, the present-day domestic chickens experienced a dramatic population size decline during their early domestication. Our analyses suggest that the concomitant bottleneck induced 2.95% more deleterious mutations across chicken genomes compared with red jungle fowls, supporting the "cost of domestication" hypothesis. Particularly, we find that 62.4% of deleterious SNPs in domestic chickens are maintained in heterozygous states and masked as recessive alleles, challenging the power of modern breeding programs to effectively eliminate these genetic loads. Finally, we suggest that positive selection decreases the incidence but increases the frequency of deleterious SNPs in domestic chicken genomes. CONCLUSION: This study reveals a new landscape of demographic history and genomic changes associated with chicken domestication and provides insight into the evolutionary genomic profiles of domesticated animals managed under modern human selection.