Impaired Intracellular Calcium Buffering Contributes to the Arrhythmogenic Substrate in Atrial Myocytes From Patients With Atrial Fibrillation.

BACKGROUND: Alterations in the buffering of intracellular Ca2+, for which myofilament proteins play a key role, have been shown to promote cardiac arrhythmia. It is interesting that although studies report atrial myofibrillar degradation in patients with persistent atrial fibrillation (persAF), the intracellular Ca2+ buffering profile in persAF remains obscure. Therefore, we aimed to investigate the intracellular buffering of Ca2+ and its potential arrhythmogenic role in persAF. METHODS: Transmembrane Ca2+ fluxes (patch-clamp) and intracellular Ca2+ signaling (fluo-3-acetoxymethyl ester) were recorded simultaneously in myocytes from right atrial biopsies of sinus rhythm (Ctrl) and patients with persAF, alongside human atrial subtype induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs). Protein levels were quantified by immunoblotting of human atrial tissue and induced pluripotent stem cell-derived cardiac myocytes. Mouse whole heart and atrial electrophysiology were measured on a Langendorff system. RESULTS: Cytosolic Ca2+ buffering was decreased in atrial myocytes of patients with persAF because of a depleted amount of Ca2+ buffers. In agreement, protein levels of selected Ca2+ binding myofilament proteins, including cTnC (cardiac troponin C), a major cytosolic Ca2+ buffer, were significantly lower in patients with persAF. Small interfering RNA (siRNA)-mediated knockdown of cTnC (si-cTNC) in atrial iPSC-CM phenocopied the reduced cytosolic Ca2+ buffering observed in persAF. Si-cTnC treated atrial iPSC-CM exhibited a higher predisposition to spontaneous Ca2+ release events and developed action potential alternans at low stimulation frequencies. Last, indirect reduction of cytosolic Ca2+ buffering using blebbistatin in an ex vivo mouse whole heart model increased vulnerability to tachypacing-induced atrial arrhythmia, validating the direct mechanistic link between impaired cytosolic Ca2+ buffering and atrial arrhythmogenesis. CONCLUSIONS: Our findings suggest that loss of myofilament proteins, particularly reduced cTnC protein levels, causes diminished cytosolic Ca2+ buffering in persAF, thereby potentiating the occurrence of spontaneous Ca2+ release events and atrial fibrillation susceptibility. Strategies targeting intracellular buffering may represent a promising therapeutic lead in persAF management.

Transmural myocardial repair with engineered heart muscle in a rat model of heterotopic heart transplantation - A proof-of-concept study.

Engineered heart muscle (EHM) can be implanted epicardially to remuscularize the failing heart. In case of a severely scarred ventricle, excision of scar followed by transmural heart wall replacement may be a more desirable application. Accordingly, we tested the hypothesis that allograft (rat) and xenograft (human) EHM can also be administered as transmural heart wall replacement in a heterotopic, volume-loaded heart transplantation model. We first established a novel rat model model to test surgical transmural left heart wall repair. Subsequently and in continuation of our previous allograft studies, we tested outcome after implantation of contractile engineered heart muscle (EHM) and non-contractile engineered connective tissue (ECT) as well as engineered mesenchymal tissue (EMT) allografts as transmural heart wall replacement. Finally, proof-of-concept for the application of human EHM was obtained in an athymic nude rat model. Only in case of EHM implantation, remuscularization of the surgically created transmural defect was observed with palpable graft vascularization. Taken together, feasibility of transmural heart repair using bioengineered myocardial grafts could be demonstrated in a novel rat model of heterotopic heart transplantation.

Identification and analysis of iron transporters from the fission yeast Schizosaccharomyces pombe.

Iron is an essential trace metal ion required for all living organisms, and is taken up by iron transporters. Here, we identified and characterized three-candidate high-affinity (Fio1, Frp1 and Frp2) and two-candidate low-affinity iron transporters (Fet4 and Pdt1) from the fission yeast Schizosaccharomyces pombe. Protein sequence analyses revealed that Fio1 is a multicopper oxidase that contains three cupredoxin domains with eleven candidate iron-binding ligands, whereas Frp1 harbors a ferric reductase domain with three-candidate heme-binding ligands. Protein sequence analyses also revealed that Fet4 and Pdt1 are integral membrane proteins with 10 and 11 transmembrane regions, respectively. Deletion of fio1 and, to a lesser extent, frp1 impaired growth under iron-depleted conditions, whereas deletion of frp1 and, to a lesser extent, frp2 inhibited growth under iron-replete conditions. Deletion of fet4 and pdt1 did not affect the growth of cells under iron-depleted and iron-replete conditions. Deletion of fio1 or frp1 also increased the sensitivity of cells to other transition metals. The copper sensitivity of Δfio1 cells could be rescued by iron, suggesting that the addition of iron might decrease the uptake of potentially toxic copper in Δfio1 cells. The copper sensitivity of Δfio1 cells could also be rescued by deletion of frp1, suggesting that Fio1 and Frp1 may function together in iron and copper uptakes in S. pombe. Our results revealed that iron and copper uptake systems may be partially overlapped in S. pombe.

Schizosaccharomyces pombe Fzo1 is subjected to the ubiquitin-proteasome-mediated degradation during the stationary phase.

Mitochondria are highly dynamic organelles that undergo fission and fusion to adapt to the metabolic needs of the cell. Mitofusins are dynamin-like GTPases that play a key role in the regulation of mitochondrial fusion and metabolism. In Saccharomyces cerevisiae, mitofusin Fzo1 levels are controlled by post-translational ubiquitination and degradation. However, it is not clear whether the levels of the Schizosaccharomyces pombe mitofusin Fzo1 are similarly regulated. In this study, we examined the expression S. pombe Fzo1 during normal growth. We showed that Fzo1 protein levels but not mRNA expression levels were reduced during the stationary phase. The protein was stabilized by the proteasome inhibitor bortezomib. Disruption of ubc8 encoding a ubiquitin-conjugating enzyme and rsv2 encoding an S. pombe homolog of S. cerevisiae RPN4 known for activating the expression of genes required for proteasomal biogenesis suppresses the proteasomal degradation of Fzo1 during the stationary phase. Overexpression of fzo1 prevents its degradation. Our results suggest that like S. pombe Fzo1 expression is not regulated by transcription but rather by proteolytic degradation during the stationary phase. Our findings also suggest that although S. cerevisiae and S. pombe Fzo1 proteins are regulated by ubiquitin-proteasomal degradation, different ubiquitin-conjugating enzymes (E2) and ubiquitin ligases (E3) are involved in their degradation.

Proactive Caching in D2D Assisted Multitier Cellular Network.

Cache-enabled networks suffer hugely from the challenge of content caching and content delivery. In this regard, cache-enabled device-to-device (D2D) assisted multitier cellular networks are expected to relieve the network data pressure and effectively solve the problem of content placement and content delivery. Consequently, the user can have a better opportunity to get their favored contents from nearby cache-enabled transmitters (CETs) through reliable and good-quality links; however, as expected, designing an effective caching policy is a challenging task due to the limited cache memory of CETs and uncertainty in user preferences. In this article, we introduce a joint content placement and content delivery technique for D2D assisted multitier cellular networks (D2DMCN). A support vector machine (SVM) is employed to predict the content popularity to determine which content is to be cached and where it is to be cached, thereby increasing the overall cache hit ratio (CHR). The content request is satisfied either by the neighboring node through the D2D link or by the cache-enabled base stations (BSs) of the multitier cellular networks (MCNs). Similarly, to solve the problem of optimal content delivery, the Hungarian algorithm is employed aiming to improve the quality of satisfaction. The simulation results indicate that the proposed content placement strategy effectively optimizes the overall cache hit ratio of the system. Similarly, an effective content delivery approach reduces the request content delivery delay and power consumption.

Diagnostic Value of Cholinesterase Activity for the Development of Postoperative Delirium after Cardiac Surgery.

BACKGROUND: Depression of cholinesterase (CHE) activity has been reported to lead to an amplified neuroinflammatory response, which clinically manifests as postoperative delirium (PD). This observational study investigates the association between CHE activity and the development of PD following elective cardiac surgery. METHODS: Patients with preexisting neurologic deficits or carotid artery disease as well as patients undergoing reoperations or procedures under circulatory arrest have been excluded from this study. The Mini-Mental State Examination, the Confusion Assessment Method for the Intensive Care Unit, and the Intensive Care Delirium Screening Checklist were performed at regular intervals. CHE activity was estimated pre- and postoperatively until postoperative day (POD) 5 and at discharge. RESULTS: A total of 107 patients were included. PD was diagnosed in 34 (31.8%) patients, who have been compared with those without PD. Time on ventilator, length of ICU, and hospital stay were longer in patients with PD (p = 0.001, p < 0.001, and p = 0.004, respectively). MMSE scores were lower in patients with PD (p < 0.001; p = 0.015). CHE activity on POD 1 to 4 as well as at discharge were lower in the delirium group (p = 0.041; p = 0.029; p = 0.015; p = 0.035; p = 0.028, respectively). A perioperative drop of CHE activity of more than 50% and a postoperative CHE activity below 4,800 U/L (on POD 0) were independently associated with an increased risk of development of PD (p = 0.038; p = 0.008, respectively). CONCLUSION: In addition to the established functional tests, routine estimation of CHE activity may serve as an additional diagnostic tool allowing for the timely diagnosis and treatment of PD in cardiac surgery patients.

Atomic-Level Construction of Tensile-Strained PdFe Alloy Surface toward Highly Efficient Oxygen Reduction Electrocatalysis.

Exploring the high-performance non-Pt electrocatalysts for oxygen reduction reaction (ORR), the bottleneck process in fuel cells, is desirable but challenging. Here, we report the Pd@PdFe core-shell icosahedra as an active and durable electrocatalyst toward ORR in alkaline conditions, which feature a three-atomic-layer tensile-strained PdFe overlayer on Pd icosahedra. Our optimized catalyst shows 2.8-fold enhancement in mass activity and 6.9-fold enhancement in specific activity than commercial Pt/C catalyst toward ORR, representing one of the best non-Pt electrocatalysts. Moreover, the boosted ORR catalysis is strongly supported by the assembled fuel cell performance using Pd@PdFe core-shell icosahedra as the cathode electrocatalyst. The density functional theory calculations reveal that the synergistic coupling of tensile strain and alloy effects enables the optimum binding strength for intermediates, thus causing the maximum activity. The present work suggests the coupling between multiple surface modulations endows larger room for the rational design of remarkable catalysts.

Synthesis of New Naphthyl Aceto Hydrazone-Based Metal Complexes: Micellar Interactions, DNA Binding, Antimicrobial, and Cancer Inhibition Studies.

In the present study, naphthyl acetohydrazide (HL) ligand was prepared and used for the synthesis of new six amorphous transition metal (Co(II), Ni(II), Cu(II), Zn(II), Pb(II), Cd(II)) complexes. All the compounds were characterized by elemental analysis, UV-vis, FT-IR, 1H- and 13C-NMR, and Matrix-Assisted Laser Desorption Ionization (MALDI). The solubilization study was carried out by estimating the interaction between the metal complexes with surfactants viz. sodium stearate (SS) and Cetyltrimethylammonium bromide (CTAB). UV-Visible spectroscopy was employed to determine partitioning and binding parameters, whereas electrical conductivity measurements were employed to estimate critical micellar concentration (CMC), the extent of dissociation, and free energy of micellization. The CT-DNA interaction of synthesized compounds with DNA represents the major groove binding. The synthesized ligand and metal complexes were also tested against bacterial and fungal strains and it has been observed that Cu(II) complex is active against all the strains except Candida albicans, while Cd(II) complex is active against all bacterial and fungal strains except Pseudomonas. Among all compounds, only the Pd(II) complex shows reasonable activity against cervical cancer HeLa cell lines, representing 97% inhibition.

Complex Valve Surgery in Elderly Patients: Increasingly Necessary and Surprisingly Feasible.

OBJECTIVES: The increasing proportion of elderly patients in cardiac surgery poses additional challenges for the clinical management and leads to a higher operative risk due to multiple comorbidities of these patients. We reviewed the outcome of patients who were 75 years and older and underwent complex multiple valve surgery at our institution. METHODS: A retrospective review was performed to identify patients who were 75 years and older and underwent multiple valve surgery between January 2011 and May 2016 at our institution. Patients were assigned to one out of four subgroups: combined aortic and mitral valve surgery (group AM), aortic and tricuspid valve surgery (group AT), mitral and tricuspid valve surgery (group MT), and aortic, mitral, and tricuspid valve surgery (group AMT). RESULTS: A total of 311 patients underwent multiple valve surgery, of whom 119 (38.3%) were 75 years and older (median: 78 [25th-75th quartile: 76-80]). The estimated operative mortality (EuroSCORE II) in the overall cohort was 10.7%. The observed 30-day mortality was 4.2% (7% in group AM, 0% in group AT, 2.2% in group MT, 3.8% in group AMT; p = 0.685). Main complications were reexplorative surgery in 16%, adverse cerebrovascular events in 6.7%, prolonged mechanical ventilation in 10.1%, renal replacement therapy in 15.1%, nosocomial pneumonia in 15.1%, and pacemaker implantation in 18.5%. CONCLUSIONS: This study demonstrates the feasibility of complex multiple valve surgery in elderly patients. The observed perioperative mortality was lower than predicted. However, we observed a substantial rate of adverse events; therefore, careful patient selection is required in this high-risk patient population.

Turning Things Around: The Role of Prone Positioning in the Management of Acute Respiratory Failure After Cardiac Surgery.

OBJECTIVES: The aim of this study was to determine the benefit of prone positioning (PP) in patients developing acute respiratory failure (ARF) after cardiac surgery. DESIGN: A retrospective analysis. SETTING: Review of the institutional database between October 2016 and October 2018 revealed 24 patients who underwent PP for the treatment of ARF after cardiac surgery. PARTICIPANTS: The authors found 24 patients who underwent PP for the treatment of ARF after cardiac surgery. This included 10 patients who required extracorporeal membrane oxygenation (ECMO) therapy. Among them, 6 patients with simultaneous PP and ECMO therapy. INTERVENTIONS: Data were collected at the time of PP, 6 hours after PP, at the end of PP, and 6 hours after return to supine position (SP). MEASUREMENTS AND MAIN RESULTS: The median duration of postoperative mechanical ventilation was 281 hours (183-528 hours). Prone positioning was carried out on the fourth postoperative day (POD), with a total of 5 patients undergoing PP within 24 hours following surgery. The median duration of PP before return to SP was 12 hours (12-16 hours), with the maximal duration of PP being 22 hours in this cohort. The authors observed an increase in Horowitz index (HI) at the end of PP (p < 0.001) as well as 6 hours after supine positioning. In the subgroup of patients who underwent PP on ECMO (v-a ECLS = 3, v-v ECMO = 3), a significant reduction of ECMO support was achieved from 3.0 (2.2-5.6) liters/min to 2.5 (2.0-4.6) liters/min (p = 0.023). No adverse events occurred during the positioning of the patients. CONCLUSIONS: Prone positioning can be considered for the treatment of ARF after cardiac surgery to improve short-term respiratory conditions and possibly facilitate ECMO weaning.

Enhanced Electrocatalytic Reduction of CO2 via Chemical Coupling between Indium Oxide and Reduced Graphene Oxide.

The chemical coupling interaction has been explored extensively to boost heterogeneous catalysis, but the insight into how chemical coupling interaction works on CO2 electroreduction remains unclear. Herein we demonstrate how the chemical coupling interaction between porous In2O3 nanobelts and reduced graphene oxide (rGO) could substantially improve the electrocatalytic activity toward CO2 electroreduction. Such an In2O3-rGO hybrid catalyst showed 1.4-fold and 3.6-fold enhancements in Faradaic efficiency and specific current density for the formation of formate at -1.2 V versus reversible hydrogen electrode relative to the catalyst prepared by physically loading of In2O3 nanobelts onto rGO, respectively. The density functional theory calculations and electrochemical analysis together revealed that the chemical coupling interaction boosted CO2 electroreduction activity by improving electrical conductivity and stabilizing key intermediate HCOO-*. The present work not only deepens an understanding of chemical coupling effect but also provides an effective lever to optimize the catalytic performance toward CO2 electroreduction.

Effects of water shortage in Kabul River network on the plain areas of Khyber Pakhtunkhwa, Pakistan.

Kabul River is a shared resource of Pakistan and Afghanistan and is a major source of economy for both countries. It is used for irrigation, power generation, fishery, hunting, and recreation. This study explored human-induced impact on Kabul River and its associated wetlands. For an in-depth study, the area situated between the two tributaries of Kabul River, i.e., Shalam and Naguman Rivers, was selected. The focus of the study was to find out reduction in the wetland areas, its causes, and associated impacts. For this purpose, a survey was conducted in 10 villages selected randomly in 10 union councils. The study revealed that anthropogenic activities, such as wetland farming, grazing residential encroachment, and industrial development, have caused severe alteration in the wetland of the study areas. The results revealed that before the 1990s, 33.55% area of the study area was wetland. Due to regular decrease in the flow of the Kabul River System and human encroachment, it has engulfed 68.40% of the total wetland leaving behind only 10.60% wetland. This can be termed as a big ecological disturbance. In the long run, this will have negative effects on both the countries. It is therefore recommended to give proper attention to this important wetland, positioning between Shalam and Naguman Rivers and to conserve it. One of the solutions is to regulate the natural flow of Kabul River.

Antibacterial and antifungal potentials of the solvents extracts from Eryngium caeruleum, Notholirion thomsonianum and Allium consanguineum.

BACKGROUND: Herbal medicines have long been used for various ailments in various societies and natural bioactive compounds are gaining more and more importance due to various factors. In this context, three plant species i.e., Eryngium caeruleum, Notholirion thomsonianum and Allium consanguineum have been aimed for the scientific verification of their purported traditional uses against various infectious diseases. METHODS: In this study, three plants were assayed for antibacterial and antifungal potentials. The antibacterial investigations were performed via well diffusion method and nutrient broth dilution method. The bacterial strains used in the study were Enterococcus faecalis, Proteus mirabilis, Escherichia coli, Salmonella typhi, Klebsiella pneumonia and Pseudomonas aeruginosa. The antifungal potential was investigated by dilution method of Muller-Hinton agar media of the plants' samples. The fungal strains used were Aspergillis fumigatus, Aspergillis flavus and Aspergillis niger. Ceftriaxone and nystatin were used as standard drugs in antibacterial and antifungal assays respectively. RESULTS: Different fractions from N. thomsonianum were tested against five bacterial strains while the samples from A. consanguineum and E. caeruleum were tested against six bacterial strains. All the samples exhibited prominent antibacterial activity against the tested strains. Overall, chloroform and ethyl acetate fractions were found most potent among the three plants' samples. N. thomsonianum excelled among the three plants in antibacterial activity. Similarly, in antifungal assay, N. thomsonianum exhibited strong antifungal activity against the fungal strains. The chloroform fraction displayed MFCs of 175.67 ± 5.20***, 29.33 ± 5.48*** and 63.00 ± 4.93*** µg/ml against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger respectively. The whole study demonstrates that all the three plant species were active against tested bacterial and fungal strains. CONCLUSION: It can be concluded from our findings that N. thomsonianum, A. consanguineum and E. caeruleum have broad antibacterial and antifungal potentials. In all of the plants' samples, chloroform and ethyl acetate fractions were more active. Furthermore, being the potent samples, the chloroform and ethyl acetate fractions of these plants can be subjected to column chromatography for the isolation of more effective antimicrobial drugs.

Characterization of Shy1, the Schizosaccharomyces pombe homolog of human SURF1.

Cytochrome c oxidase (complex IV) is the terminal enzyme in the mitochondrial respiratory chain. As a rare neurometabolic disorder caused by mutations in the human complex IV assembly factor SURF1, Leigh Syndrome (LS) is associated with complex IV deficiency. In this study, we comprehensively characterized Schizosaccharomyces pombe Shy1, the homolog of human SURF1. Bioinformatics analysis revealed that Shy1 contains a conserved SURF1 domain that links to the biogenesis of complex IV and shares high structural similarity with its homologs in Saccharomyces cerevisiae and humans. Our study showed that Shy1 is required for the expression of mtDNA-encoded genes and physically interacts with structural subunits and assembly factors of complex IV. Interestingly, Rip1, the subunit of ubiquinone-cytochrome c oxidoreductase or cytochrome bc1 complex (complex III), can also co-immunoprecipitate with Shy1, suggesting Shy1 may be involved in the assembly of the mitochondrial respiratory chain supercomplexes. This conclusion is further corroborated by our BN-PAGE analysis. Unlike its homologs, deletion of shy1 does not critically disrupt respiratory chain assembly, indicating the presence of the compensatory mechanism(s) within S. pombe that ensure mitochondrial functionality. Collectively, our investigation elucidates that Shy1 plays a pivotal role in the sustainability of the regular function of mitochondria by participating in the assembly of complex IV in S. pombe.

Effect of citrus peeling (Citrus sinensis) on production performance, humoral immunity, nutrients, and energy utilization of broiler quails.

Citrus citrus peeling has a wide range of vitamins and trace minerals that have antioxidant and antimicrobial properties. It is hypothesized that the addition of citrus peeling to broiler quail diets can improve their production performance, humoral immunity, nutrients, and energy utilization. A trial was performed to study the impact of a methanolic extract of citrus peeling (Citrus sinensis) on production performance, humoral immunity, nutrients, and energy utilization of broiler quails. A healthy day-old 300 quails were randomly assigned with 5 replicates each replicate had 15 birds and used CRD for the trial. Different dietary supplementations were presented to different groups. The control group was not supplemented with any supplementation in their feed. While, the 3 other groups were supplemented by 0.5 mL/kg, 1 mL/kg, and 1.5 mL/kg of methanolic extract of dried Citrus sinensis peel (DCSP) in the basal diet (DCSP0.5, DCSP1, and DCSP1.5 groups, respectively). All the birds were allowed ad libitum feeding and water. The feed intake and FCR were significantly higher in the control group, followed by DCSP0.5, and then DCSP1. The significantly lowest feed intake and FCR were observed in the DCSP1.5 group. The weight gain and dressing % were significantly improved with the increasing level of methanolic extract of Citrus sinensis. The significantly highest weights of thymus, spleen, and bursa were recorded in the DCSP1.5 group, followed by the DCSP1. The antibody titers against infectious bursal disease, New Castle disease, and infectious bronchitis disease were significantly higher in the DCSP1.5, DCSP1, and DCSP0.5 groups than in the control group. It was concluded from the study that supplementation of quails with methanolic extract of citrus at a dose rate of 0.5 to 1.5 mL/kg of feed can improve feed intake, weight gain, FCR, dressing percentage, relative weight of lymphoid organs, and digestibility coefficient. Supplementation of Citrus sinensis has also concluded positive impacts on antibody titers against various viral diseases. The best improvement in the evaluated parameters was observed at a dose of extract of citrus was 1.5 mL/kg of feed.

Prevalence of Anxiety, Depression, and Distress and Their Association With Problems Encountered by Advanced Cancer Patients in a Tertiary Hospital in Saudi Arabia.

BACKGROUND: Patients with advanced cancer often suffer from significant psychological distress, anxiety, and depression, which can profoundly influence their quality of life. This study aimed to evaluate the prevalence and severity of these psychological factors in advanced cancer patients. Additionally, it sought to identify related psychosocial, practical, emotional, and physical problems and their association with the psychological factors. Furthermore, this study provides interventions and strategies to help mitigate the psychological burden experienced by these patients. METHODS: A cross-sectional survey involving 180 patients with advanced cancer was conducted at a tertiary hospital in Saudi Arabia. Participants were assessed using the Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS). Data analysis included descriptive statistics, chi-square tests for categorical variables, and multivariate regression to explore the factors associated with distress, anxiety, and depression. RESULTS: The prevalence of distress, anxiety, and depression among patients was 40.6%, 46.1%, and 52.2%, respectively. Patients who experienced 'changes in urination' which is an item in DT had a 2.86 times higher risk of developing distress. Patients experiencing sadness (item in DT) and fatigue (item in DT) were at a 3.91 and 2.29 times higher risk of developing anxiety, respectively. Practical problems, such as childcare and treatment decisions, emotional problems, and physical problems, such as appearance, bathing/dressing, and eating difficulties, were significantly associated with distress. There was no significant association between patients' demographics and psychological factors. CONCLUSION: The findings underscore the complex interplay of psychosocial, practical, emotional, and physical problems faced by advanced cancer patients receiving palliative care. These patients exhibit a high percentage of distress, anxiety, and depression. Addressing these multifaceted problems through targeted psychological and social interventions can significantly enhance the overall care and quality of life for this vulnerable population. This study advocates routine psychological screenings and tailored interventions to mitigate the psychological burden in this group.

A case report of coexisting multinodular goiter with carotid body tumor.

INTRODUCTION: Carotid body tumor (CBT), a neuroendocrine neoplasm, and benign multinodular goiter (BMNG) are distinct pathologies affecting the neck region. Although rare, they can occur concurrently. This case contributes to the limited evidence regarding the association between these distinct pathologies and their operative management. CASE PRESENTATION: The patient was a 45-year-old female with a palpable mass on the right side of her neck. She was diagnosed with Shamblin type III non-secretory CBT alongside BMNG. The surgical intervention included resection of the CBT, carotid artery bypass, and Dunhill thyroidectomy. DISCUSSION: This case is the third reported instance of coexisting CBT and BMNG. Their causative relationship is evident in the literature without a clear explanation of the underlying mechanism. Both conditions are treated surgically. Dunhill thyroidectomy for BMNG is a safer option, offering more flexibility and advantages over other thyroidectomies. CONCLUSION: This case highlights the complexity of managing such dual pathologies and may provide further evidence of their association.

A comparative assessment of uncrushed-river concrete mix of Hari-River, and Kamar-Kalaq: the two widely used concrete mix in Herat, Afghanistan.

Concrete, as a cornerstone of modern construction, heavily relies on the quality of its constituent materials, particularly aggregates. Among the critical factors contributing to high-quality concrete are proper gradation, absence of clay particles, and angular shape of aggregates. Adhering to these standards typically results in concrete with superior strength. However, aggregates sourced from riverbeds often possess a natural gradation, contain clay particles, and have rounded shapes. This study delves into a comparative analysis of aggregates sourced from two widely utilized riverbed regions, namely Hari-River and Kamar-Kalaq, situated within Herat province, Afghanistan. Given that over 90% of concrete in Herat province is sourced from these two riverbeds, the findings of this study carry immense significance. The research meticulously examines key parameters, including clay content, gradation, aggregate shape, and compressive strength, to determine the optimal choice for concrete production. Methodologically, samples were acquired following ASTM standards, and rigorous testing procedures were conducted, encompassing clay particle analysis, sieve analysis, and strength testing. The results reveal significant disparities between the two regions, with Hari-River demonstrating superior characteristics across various metrics. Particularly noteworthy is Hari-River's lower clay content of 2.7% compared to Kamar-Kalaq's 3.7%. The gradation of Hari-River for both coarse and fine aggregates is superior to that of Kamar-Kalaq when compared to size 67 aggregate range. Additionally, the average 28 days concrete compressive strength of Hari-River aggregates is 27.8 MPa, while that of Kamar-Kalaq is 23.4 MPa.

The Current State of Neurosurgery in Afghanistan.

BACKGROUND: Afghanistan has suffered through conflicts that have detrimentally impacted its health care systems. The countries' neurosurgeons have worked through wars and political upheavals to build solid practices and handle large caseloads with minimal supplies and almost no modern tools. Understanding the current state of neurosurgery in Afghanistan and the challenges faced by Afghan physicians and patients is critical to improving the country's healthcare capacity. METHODS: To assess neurosurgery research in Afghanistan, searches were conducted in databases for articles originating from Afghanistan neurosurgeons and/or neurosurgery departments. We developed a 30-question English-language survey to assess the current state of neurosurgical capacity. Surveys were distributed to neurosurgeons throughout Afghanistan via email with the assistance of our English-speaking Afghan neurosurgical colleagues. RESULTS: The neurosurgical disease burden of Afghanistan is poorly understood due to the lack of centralized and accessible databases. There are an estimated 124 neurosurgeons in the country based on modeled data. Surveys showed that government hospitals are poorly equipped, with private and military hospitals having access to slightly more modernized equipment but less accessible to the general population. The country lacks neurosurgery research with only 15 papers discovered through database searches deemed relevant to neurosurgery with Afghan affiliations. CONCLUSIONS: Afghanistan is facing existential humanitarian threats. Developing the country's neurosurgical capacity and general health care capabilities is crucial. Emphasis on training physicians and establishing communication routes, and aid deliverance with the country and its leaders is key to overcoming the many crises it faces.

The DZHK research platform: maximisation of scientific value by enabling access to health data and biological samples collected in cardiovascular clinical studies.

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for.