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Abstract In this randomized controlled trial, we assessed the effects of three consecutive intra-silicone oil (SO) injections of methotrexate (MTX) on the outcomes of surgery for proliferative vitreoretinopathy grade C (PVR-C). Seventy-four eyes of 74 patients with PVR-C were included. Of these, 37 eyes were assigned to the MTX group and 37 eyes to the control group. Fourteen patients failed to comply with the 6-month follow-up period. All eyes underwent vitrectomy and SO injection. In the MTX group, 250 µg MTX was injected into the SO after surgery and at weeks 3 and 6 postoperatively. The primary outcome was the retinal reattachment rate at 6 months. The secondary outcomes included limited PVR recurrence and adverse events. Retinal reattachment was achieved in 22 eyes (73.3%) in the MTX group and 23 eyes (76.7%) in the control group (difference: -3.4%, 95% CI: -25.2–18.5%). Limited PVR recurrence was observed in one eye (4.5%) in the MTX group versus nine eyes (39.1%) in the control group at 6 months (P = 0.01). No adverse effects were observed. Adjunctive treatment with three consecutive applications of intra-SO MTX did not reveal a significant effect on the retinal re-detachment rate but could statistically significantly reduce limited PVR recurrence. Trial registration: http//ClinicalTrials.gov NCT04482543, 22/07/2020.

Abstract Ultramarathon running is of increasing popularity, where the time-limited 24-hour run is one of the most popular events. Although we have a high scientific knowledge about different topics for this specific race format, we do not know where the best 24-hour runners originate from and where the fastest races are held. The purpose of the present study was to investigate the origin of these runners and the fastest race locations. A machine learning model based on the XG Boost algorithm was built to predict running speed based on the athlete´s age, gender, country of origin and the country where the race takes place. Model explainability tools were used to investigate how each independent variable would influence the predicted running speed. A sample of 171,358 race records from 63,514 unique runners from 73 countries participating in 24-hour races held in 57 countries between 1807 and 2022 was analyzed. Most of the athletes originated from the USA, France, Germany, Great Britain, Italy, Japan, Russia, Australia, Austria, and Canada. Tunisian athletes achieved the fastest average running speed, followed by runners from Russia, Latvia, Lithuania, Island, Croatia, Slovenia, and Israel. Regarding the country of the event, the ranking looks quite similar to the participation by the athlete, suggesting a high correlation between the country of origin and the country of the event. The fastest 24-hour races are recorded in Israel, Romania, Korea, the Netherlands, Russia, and Taiwan. On average, men were 0.4 km/h faster than women, and the fastest runners belonged to age groups 35–39, 40–44, and 45–49 years. In summary, the 24-hour race format is spread over the world, and the fastest athletes mainly originate from Eastern Europe, while the fastest races were organized in European and Asian countries.

Abstract Background Sickle cell disease is a genetic disease with multisystem involvement. More than 300,000 children are born with sickle cell disease globally, with the majority of cases being in Sub-Saharan Africa. In Uganda, about 20,000 children are born with sickle cell disease annually, with more than three-quarters dying before the age of 5 years. Those who live beyond 5 years tend to have poor health-related quality of life, numerous complications, and recurrent hospitalizations. In developing countries, most symptomatic patients are diagnosed early in childhood. Few of those not screened in childhood tend to present in adulthood with variable symptoms. Case presentation This case reports a 22-year-old African male patient of Toro tribe who presented with paroxysms of multiple joint pain associated with generalized body malaise for about 6 months. He presented as a referral from a lower facility with an unestablished cause of symptoms. Physical examination revealed conjunctival pallor, icterus, and tenderness of joints. Cell counts showed anemia and hemoglobin electrophoresis revealed 87% of sickled hemoglobin. Conclusion This case report pinpoints the importance of considering the diagnosis of sickle cell disease even in adults presenting with symptoms of sickle cell disease. It also adds to the relevance of screening at all age groups, especially in high-endemic regions such as Africa and Asia.

Abstract Hematological changes is one of the most common complications occurred in cancer patients. Therefore, the current study aimed to assess the hematological toxicity of cervical cancer patients before and after the initiation of treatment. The retrospective cohort study was conducted from 2015 to 2022 at the University of Gondar Comprehensive Specialized Hospital. The hematological profile and sociodemographic and clinical data of the cervical cancer patients were collected using data extraction sheets. The Epidata version 3.1 and SPSS version 25 were used for data entry and analysis, respectively. Descriptive statistics were employed to summarize the data. To compare the median differences in hematological parameters before and after treatment, the Wilcoxon rank test was used. In addition, to assess the presence of an independent association between hematological abnormalities and the independent variables, logistic regression models were used. A p value less than 0.05 was considered to indicate statistical significance for all tests. In current study, the median (Interquartile range) of hemoglobin levels, white blood cell counts, and platelet counts, before treatment were 13.2 (12.1, 15) g/dl, 7.5 (5.8, 11.8) *109/L, and 330 (252, 383) *109/L, respectively. However, after treatment the median (Interquartile range) value of hemoglobin levels, white blood cell counts, and platelet counts were significantly lowered. On the other hand, red cell distribution width was significantly greater after treatment. At baseline, the magnitude of leucocytosis, anemia, and thrombocytosis were 27.9%, 24.6%, and 18.7%, respectively. After the treatment, anemia increased to 44.3%, but leucocytosis and thrombocytosis were replaced by leucopenia 18.3% and thrombocytopenia 17.8%, respectively. Hematological abnormalities such as anemia, leucopenia and thrombocytopenia were high after chemo-radiotherapy, and surgery. As the stage of cancer advances, the risk of developing anemia, leucocytosis, and thrombocytosis increased in 7.6, 6.9 and 9 times, respectively. Furthermore, being HIV patients and rural resident increased the risk of developing anemia about twofold. In conclusion hematological abnormalities were observed before and after cervical cancer treatment, with significance increment after chemo-radiotherapy and surgery. As the stage of cancer advances, the risk of developing hematological abnormalities increases. Therefore, routine monitoring of hematological changes before and after treatment and screening for major risk factors are important for improved patients’ management.

Objective: The purpose of the study was to compare the fluoride release in two conventional glass ionomer cements (Ionobond, Ketac Molar) and two resin-modified glass ionomer cements (Vitrebond, Fuji II LC) adapted with halloysite nanotubes preloaded with sodium fluoride at different concentrations. Methods: In total, 96 samples were prepared and distributed into four control groups and eight experimental groups (5 % and 10 %). Totals of 10 % and 5 % of the total weight of ionomer powder needed to prepare the samples were replaced with nanotubes, preloaded at 2,000 parts per million, respectively. The experimental groups were followed for 120 days at seven time intervals. All the samples were stored at 37 °C. Results: All the experimental groups showed significant differences compared with the control groups; likewise, differences were observed between the concentrations of 5% and 10%. Conclusion: The experimental groups (conventional and resin-modified glass ionomer cements adapted with preloaded nanotubes) released a higher and more constant amount of fluoride compared to the control groups.

Abstract The management of a food supply chain is difficult and complex because of the product's short shelf-life, time-sensitivity, and perishable nature which must be carefully considered to minimize food waste. Temperature-controlled perishable food supply chain provides the highly crucial facilities necessary to maintain the quality and safety of the product. The storage temperature is the most vital factor in maintaining both the quality and shelf-life of a perishable food. Adequate storage temperature control ensures that perishable foods are transported to the end-users in good quality and safe to consume. This paper presents perishable food storage temperature control through mathematical optimal control model where the storage temperature is regarded as the control variable and the deterioration of the perishable food’s quality follows the first-order reaction. The optimal storage temperature for a single perishable food is determined by applying the Pontryagin's maximum principle to solve the optimal control model problem. For multi-temperature commodities supply chain, an unsupervised machine learning (ML) method, called k-means clustering technique is used to determine the temperature clusters for a range of perishables. Based on descriptive analysis, it is observed that the k-means clustering technique is effective in identifying the best suitable storage temperature clusters for quality control of multi-commodity supply chain.

Abstract This study investigates the efficacy of predicting age-related macular degeneration (AMD) activity through deep neural networks (DNN) using a cross-instrument training dataset composed of Optical coherence tomography-angiography (OCTA) images from two different manufacturers. A retrospective cross-sectional study analyzed 2D vascular en-face OCTA images from Heidelberg Spectralis (1478 samples: 1102 training, 276 validation, 100 testing) and Optovue Solix (1003 samples: 754 training, 189 validation, 60 testing). OCTA scans were labeled based on clinical diagnoses and adjacent B-scan OCT fluid information, categorizing activity into normal, dry AMD, active wet AMD, and wet AMD in remission. Experiments explored cross-instrument disease classification using separate and combined datasets for training the DNN. Testing involved 100 Heidelberg and 60 Optovue samples. Training on Heidelberg data alone yielded 73% accuracy on Heidelberg images and 60% on Optovue images. Training on Optovue data alone resulted in 34% accuracy on Heidelberg and 85% on Optovue images. Combined training data from both instruments achieved 78% accuracy on Heidelberg and 76% on Optovue test sets. Results indicate that cross-instrument classifier training demonstrates high classification prediction accuracy, making cross-instrument training viable for future clinical applications. This implies that vascular morphology in OCTA can predict disease progression.

Abstract Decoding locomotor tasks is crucial in cognitive neuroscience for understanding brain responses to physical tasks. Traditional methods like EEG offer brain activity insights but may require additional modalities for enhanced interpretative precision and depth. The integration of EEG with ocular metrics, particularly eye blinks, presents a promising avenue for understanding cognitive processes by combining neural and ocular behaviors. However, synchronizing EEG and eye blink activities poses a significant challenge due to their frequently inconsistent alignment. Our study with 35 participants performing various locomotor tasks such as standing, walking, and transversing obstacles introduced a novel methodology, pcEEG+, which fuses EEG principal components (pcEEG) with aligned eye blink data (syncBlink). The results demonstrated that pcEEG+ significantly improved decoding accuracy in locomotor tasks, reaching 78% in some conditions, and surpassed standalone pcEEG and syncBlink methods by 7.6% and 22.7%, respectively. The temporal generalization matrix confirmed the consistency of pcEEG+ across tasks and times. The results were replicated using two driving simulator datasets, thereby confirming the validity of our method. This study demonstrates the efficacy of the pcEEG+ method in decoding locomotor tasks, underscoring the importance of temporal synchronization for accuracy and offering a deeper insight into brain activity during complex movements.

Abstract Background: Takotsubo syndrome is characterized by transient regional systolic dysfunction, left ventricular (LV) dilatation, and edema, often occurring without obstructive coronary artery disease. The mechanisms underlying this stress-induced condition, especially the role of mechanical dyssynchrony in affecting systolic function, remain poorly understood. Methods: In our study, we evaluated global LV function and mechanical dyssynchrony in 24 Takotsubo patients compared to 20 controls by analyzing pressure-volume loops and time-varying elastance. Additionally, we monitored changes in LV segmental volume and internal flow. Results: Here we show a significant reduction in global myocardial contractility and pronounced mechanical dyssynchrony in Takotsubo syndrome, particularly in the mid and apical LV segments, without disturbances in electrical conduction. Conclusions: Our findings reveal substantial mechanical dyssynchrony in Takotsubo patients, characterized by increased internal flow and a shortened systolic ejection time. This indicates a mechanical basis for the inefficient LV function in Takotsubo syndrome, independent of electrical conduction abnormalities.

Abstract This research proposes a day-ahead scheduling utilizing both demand side management (DSM), and Energy Management (EM) in a grid-tied nanogrid comprises of photovoltaic, battery, and diesel generator for optimizing the generation cost and the energy not supplied (at grid-outage). Wider terminology is introduced to combine both load controllability (considered in traditional DSM), and interval capability to accommodate additional loads defined as flexible, non-flexible, and semi-flexible intervals. Moreover, the user selection for EM or combined operation of EM with DSM at different degrees of interval flexibility is defined as user preference. In addition, three utility’s operations are considered denoted as fixed rate pricing (FRP), time-of-use (ToU) pricing, and FRP with grid-outage. Hence, the suggested framework utilizes the opportunities of generation diversity, the electricity pricing strategy, and the load flexibility. The obtained result show that, DSM with flexible intervals reduces the cost by 21.02%, 25.23%, and 18.15% for FRP, ToU, and FRP with grid-outage scenarios respectively. And cost reduction by 20.41%, 22.42%, and 17.81% for DSM with semi-flexible intervals and 16.24%, 21.15%, and 13.8% for DSM with non-flexible intervals. This cost reduction is associated with full utilization of renewable energy generation and reduction of the energy from/to battery which enhances its lifetime or reduces the required battery size during design stage for cost and provisions saving in flexible and semi-flexible intervals. A hybrid optimization technique of Moth-flame optimization algorithm, and Lagrange’s multiplier is proposed and confirms its effectiveness with detailed comparison with other techniques.

Abstract Background The Brazilian Policy for Comprehensive Care for People with Rare Diseases was implemented in 2014; however, national epidemiological data on rare diseases (RDs) are scarce and mainly focused on specific disorders. To address this gap, University Hospitals, Reference Services for Neonatal Screening, and Reference Services for Rare Diseases, all of which are public health institutions, established the Brazilian Rare Diseases Network (RARAS) in 2020. The objective of this study was to perform a comprehensive nationwide epidemiological investigation of individuals with RDs in Brazil. This retrospective survey collected data from patients receiving care in 34 healthcare facilities affiliated with RARAS in 2018 and 2019. Results The survey included 12,530 participants with a median age of 15.0 years, with women representing 50.5% of the cohort. Classification according to skin color demonstrated that 5044 (47.4%) participants were admixed. Most had a confirmed diagnosis (63.2%), with a predominance of phenylketonuria (PKU), cystic fibrosis (CF), and acromegaly. Common clinical manifestations included global developmental delay and seizures. The average duration of the diagnostic odyssey was 5.4 years (± 7.9 years). Among the confirmed diagnoses, 52.2% were etiological (biochemical: 42.5%; molecular: 30.9%), while 47.8% were clinical. Prenatal diagnoses accounted for 1.2%. Familial recurrence and consanguinity rates were 21.6% and 6.4%, respectively. Mainstay treatments included drug therapy (55.0%) and rehabilitation (15.6%). The Public Health System funded most diagnoses (84.2%) and treatments (86.7%). Hospitalizations were reported in 44.5% of cases, and the mortality rate was 1.5%, primarily due to motor neuron disease and CF. Conclusion This study marks a pioneering national-level data collection effort for rare diseases in Brazil, offering novel insights to advance the understanding, management, and resource allocation for RDs. It unveils an average diagnostic odyssey of 5.4 years and a higher prevalence of PKU and CF, possibly associated with the specialized services network, which included newborn screening services.

Abstract Over 50% of the original oil in place (OOIP) is immobile or trapped in the reservoir. Therefore, today, more efficient methods have been introduced in the tertiary oil recovery sector as a scheme of enhanced oil recovery (EOR). Due to the decline of conventional hydrocarbon reserves, polymers are increasingly used in EOR methods, such as surfactant-polymer (SP) and alkaline-surfactant-polymer (ASP) flooding. SP flooding has a complex formulation and design, leading to undesirable phase separation if improperly mixed. Polymeric surfactants are a promising alternative to SP flooding. They consist of hydrophobic groups attached to hydrophilic polymers, which help to improve the mobility ratio and reduce interfacial tension (IFT). This paper examines the rheological and synthesis properties of a new polymeric surfactant produced through bond co-polymerization reaction using different hydrolyzed polyacrylamide (HPAM) ratios and a zwitterion hydrophobic group. The synthesized hydrophobically modified zwitterionic polyacrylamide (HMZPAM) was characterized by FTIR and HMNR analysis. HMZPAM performed better than other substances in IFT, viscosity, wettability, oil recovery, and resistance to different one and two-valence cations. The results indicate that HPAM reduced the IFT to 13.65, while HMZPAM reduced it to 0.441 mN/m. Wettability change evaluated on a rock carbonate/crude oil/HMZPAM system that changed the water-wet state of the primary oil-wet rock carbonate to strongly water-wet state as wettability change measurements showed a decrease in contact angle from 62.76 to 21.23 degree. Comparative studies on the effectiveness of HPAM and HMZPAM were also conducted according to the measurement of viscosity and shear rate in the presence of salt, which indicates the higher shear rate and viscosity of HMZPAM. Core flooding tests revealed that HMZPAM resulted in better additional recovery due to microscopic displacement, resulting in a total oil recovery of 84%, compared to 48% of residual oil saturation for HPAM. Also, salts decreased oil recovery in HPAM injection but increased oil recovery in HMZPAM injection.

Abstract A concern in the field of autism electroencephalography (EEG) biomarker discovery is their lack of reproducibility. In the present study, we considered the problem of learning reproducible associations between multiple features of resting state (RS) neural activity and autism, using EEG data collected during a RS paradigm from 36 to 96 month-old children diagnosed with autism (N = 224) and neurotypical children (N = 69). Specifically, EEG spectral power and functional connectivity features were used as inputs to a regularized generalized linear model trained to predict diagnostic group (autism versus neurotypical). To evaluate our model, we proposed a procedure that quantified both the predictive generalization and reproducibility of learned associations produced by the model. When prioritizing both model predictive performance and reproducibility of associations, a highly reproducible profile of associations emerged. This profile revealed a distinct pattern of increased gamma power and connectivity in occipital and posterior midline regions associated with an autism diagnosis. Conversely, model selection based on predictive performance alone resulted in non-robust associations. Finally, we built a custom machine learning model that further empirically improved robustness of learned associations. Our results highlight the need for model selection criteria that maximize the scientific utility provided by reproducibility instead of predictive performance.

Abstract The armed conflict in Tigray, which spanned from November 2020 to November 2022, along with the accompanying siege, led to the near-total collapse of Tigray’s healthcare system. Type 1 Diabetes Mellitus, the most common chronic condition in children, requires significant lifestyle adjustments, including daily insulin injections, regular glucose monitoring, and dietary modifications; all of which are severely impacted by war and siege. This study compared Type 1 diabetes care for children at the Ayder Comprehensive Specialized Hospital, Tigray, during the conflict and siege period with that of the pre-war period. We conducted a retrospective cross-sectional survey, analyzing data from September 2019 to August 2020 (pre-war period) and comparing it with data from September 2021 to August 2022 (war and siege period). Descriptive statistics, including frequencies and percentages, were employed, and Pearson’s or Spearman’s correlation analyses were used to evaluate correlations where appropriate. We identified 143 pediatric patients admitted (56 during the pre-war period and 87 during the war and siege period), with a mean age of 109 months in both periods. During the war and siege, a higher proportion of diabetes admissions were due to diabetic ketoacidosis (DKA) (90%) compared to the pre-war period (75%). In the pre-war period, the most common trigger for DKA was infections (35%), while in the war and siege period, it shifted to malnutrition (47%), infections (46%), lack of access to healthcare facilities (31%), and running out of medicines (24%). Complications such as death, renal failure, cerebral edema, and shock were more prevalent during the war and siege periods. The case fatality rate was significantly higher during the war and siege (9%) compared to the pre-war period (0%), correlating strongly with the severity of DKA, the degree of hypokalemia, the presence of complications, and admission during the war and siege. Our study showed the negative impact of war and siege on diabetes care in children demonstrating a high rate of DKA admissions with increased severity, complications, malnutrition, and case fatality rates. People with diabetes especially type 1 deserve great attention during such a crisis as the lack of insulin could lead to severe complications including death.

Abstract This retrospective study aimed to assess different macular neovascular network characteristics in relation to changes in best corrected visual acuity (BCVA) over 3 and 12 months following treatment. Using optical coherence tomography angiography, we reviewed the medical records of 46 treatment-naïve patients with neovascular age-related macular degeneration (nAMD) who received intravitreal aflibercept injections. The change in BCVA from baseline to 3 months and 12 months after treatment was recorded. The mean vessels percentage area, junctions density, lacunarity, and fractal dimension were significantly correlated with the change of BCVA from baseline to month 3 (P = 0.003, 0.046, 0.007, and 0.005 respectively). Fractal dimension and vessels percentage area were correlated with the change of BCVA from baseline to month 12 (P = 0.023 and 0.023 respectively). The findings suggest that baseline characteristics of macular neovascular complexes may serve as predictors for BCVA changes following treatment with aflibercept in nAMD patients.

Abstract We demonstrate two general classes of magnetophoretic transistors, called the “trap” and the “repel-and-collect” transistors, capable of switching single magnetically labeled cells and magnetic particles between different paths in a microfluidic chamber. Compared with prior work on magnetophoretic transistors operating in a two-dimensional in-plane rotating field, the use of a tri-axial magnetic field has the fundamental advantages of preventing particle cluster formation and better syncing of single particles with the general operating clock. We use finite element methods to investigate the energy distribution on the chip surface and to predict the particle behavior at various device geometries. We then fabricate the proposed transistors and compare the experimental results with the simulation predictions. We found that with gate electrical currents of ~ 40 mA for a transistor with proper geometry, complete switching of magnetic particles with diameters in the range of 8–15 μm is achieved. We show that the device is reliable and works well at different magnetic field strengths (50–100 Oe) and frequencies (0.05–0.5 Hz). We also employed an image processing code with a trained convolutional neural network to automate the proposed transistors for identifying and sorting particles with various sizes and magnetic susceptibilities with accuracies higher than 98%. The proposed transistors can be used in designing novel magnetophoretic circuits for important applications in biomedical microdevices and single-cell biology.

Abstract Using direct numerical simulation, the primary atomization of shear-thinning liquid jets into stagnant gas is investigated. Starting from a Newtonian configuration with material properties approximately corresponding to a Diesel injection, two hypothetical shear-thinning cases using the power-law and the Carreau-Yasuda models for the calculation of the apparent viscosity are investigated. A recently developed tracking algorithm is used to identify droplets newly formed from the core jet, as well as all other droplets in the computational domain, and a number of relevant droplet characteristics, such as droplet volume, surface area and center of mass, is recorded at each time step. This allows a comparison of droplet characteristics on the basis of probability density functions. It is observed that the shear-thinning behavior of the liquid phase, which is particularly relevant at the interface, influences the droplet volumes and shapes. While the mean viscosity differs significantly for the different cases, the first- and second-order velocity and volume fraction statistics remain nearly unchanged.

Abstract The TAR DNA Binding Protein 43 (TDP-43) has been implicated in the pathogenesis of human neurodegenerative diseases and exhibits hallmark neuropathology in amyotrophic lateral sclerosis (ALS). Here, we explore its tractability as a plasma biomarker of disease and describe its localization and possible functions in the cytosol of platelets. Novel TDP-43 immunoassays were developed on three different technical platforms and qualified for specificity, signal-to-noise ratio, detection range, variation, spike recovery and dilution linearity in human plasma samples. Surprisingly, implementation of these assays demonstrated that biobank-archived plasma samples yielded considerable heterogeneity in TDP-43 levels. Importantly, subsequent investigation attributed these differences to variable platelet recovery. Fractionations of fresh blood revealed that ≥ 95% of the TDP-43 in platelet-containing plasma was compartmentalized within the platelet cytosol. We reasoned that this highly concentrated source of TDP-43 comprised an interesting substrate for biochemical analyses. Additional characterization of platelets revealed the presence of the disease-associated phosphoserine 409/410 TDP-43 proteoform and many neuron- and astrocyte-expressed TDP-43 mRNA targets. Considering these striking similarities, we propose that TDP-43 may serve analogous functional roles in platelets and synapses, and that the study of platelet TDP-43 might provide a window into disease-related TDP-43 dyshomeostasis in the central nervous system.

Abstract Steatotic liver disease has been shown to associate with cardiovascular disease independently of other risk factors. Lipoproteins have been shown to mediate some of this relationship but there remains unexplained variance. Here we investigate the plasma lipidomic changes associated with liver steatosis and the mediating effect of these lipids on coronary artery disease (CAD). In a population of 2579 Swedish participants of ages 50 to 65 years, lipids were measured by mass spectrometry, liver fat was measured using computed tomography (CT), and CAD status was defined as the presence of coronary artery calcification (CAC score > 0). Lipids associated with liver steatosis and CAD were identified and their mediating effects between the two conditions were investigated. Out of 458 lipids, 284 were found to associate with liver steatosis and 19 of them were found to also associate with CAD. Two fatty acids, docosatrienoate (22:3n6) and 2-hydroxyarachidate, presented the highest mediating effect between steatotic liver disease and CAD. Other mediators were also identified among sphingolipids and glycerophospholipids, although their mediating effects were attenuated when adjusting for circulating lipoproteins. Further research should investigate the role of docosatrienoate (22:3n6) and 2-hydroxyarachidate as mediators between steatotic liver disease and CAD alongside known risk factors.

Abstract Vitamin D deficiency is an emerging public health problem globally, with devastating health consequences. Some studies suggest that exogenous sex hormones, found in hormonal contraceptives, may enhance vitamin D levels. However, the reasons for this association are not fully understood, as women using hormonal contraception may have different lifestyle habits affecting their vitamin D status. Therefore, this study seeks to explore the relationship between hormonal contraceptive use and vitamin D levels. A Facility based comparative cross-sectional study was conducted in Gondar town from February to April 2023, involving a total of 162 women using three types of hormonal contraceptives (Norplant, DMPA, and COC) and 162 age and BMI-matched non-users as controls in a 1:1 ratio. Participants were selected using systematic random sampling. A semi-structured questionnaire was used to collected data regarding the socio-demographic, economic, obstetric, lifestyle, and clinical information. 5 milliliters of blood samples were collected from each participant for Laboratory analysis of serum vitamin D, calcium, and alkaline phosphates using a Beckman Coulter chemistry analyzer. Independent t-tests, ANOVA with post hoc Bonferroni test was used to compare statistics between the two groups, and logistic regression models to identify factors associated with Vitamin D deficiency. The mean serum Vitamin D levels of Norplant, DMPA, and COC users were 24.08 (± 5.17), 24.83 (± 5.52), and 31.90 (± 6.94) respectively; whereas control group has mean Vitamin D level of 22.00 (± 7.97). On the current study the prevalence of Vitamin D deficiency (

Abstract The study aimed to evaluate the impact of AI assistance on pulmonary nodule detection rates among radiology residents and senior radiologists, along with assessing the effectiveness of two different commercialy available AI software systems in improving detection rates and LungRADS classification in chest CT. The study cohort included 198 participants with 221 pulmonary nodules. Residents’ mean detection rate increased significantly from 64 to 77% with AI assist, while seniors’ detection rate remained largely unchanged (85% vs. 86%). Residents showed significant improvement in segmental nodule localization with AI assistance, seniors did not. Software 2 slightly outperformed software 1 in increasing detection rates (67–77% vs. 80–86%), but neither significantly affected LungRADS classification. The study suggests that clinical experience mitigates the need for additional AI software, with the combination of CAD with residents being the most beneficial approach. Both software systems performed similarly, with software 2 showing a slightly higher but non-significant increase in detection rates.

Abstract The majority of participants in Ironman triathlon races are age group athletes. We have extensive knowledge about recreational athletes’ training and competition participation. Nonetheless, Ironman age group triathletes must achieve fast race times to qualify for the Ironman World Championship in Hawaii. They can, therefore, benefit from knowing where the fastest Ironman racecourses in the world are. The aim of the present study was to investigate where the fastest Ironman racecourses for age group triathletes are located in the world. Data from 677,702 Ironman age group finishers’ records (544,963 from men and 132,739 from women) originating from 228 countries and participating in 444 events across 66 different Ironman race locations between 2002 and 2022 were analyzed. Data was analyzed through traditional descriptive statistics and with machine learning regression models. Four algorithms were tested (Random Forest Regressor, XG Boost Regressor, Cat Boot Regressor, and Decision Tree Regressor). The models used gender, age group, country of origin, environmental factors (average air and water temperatures), and the event location as independent variables to predict the final overall race time. Despite the majority of successful Ironman age group triathletes originating from the USA (274,553), followed by athletes from the United Kingdom (55,410) and Canada (38,264), these countries exhibited average overall race times that were significantly slower compared to the fastest countries. Most of the triathletes competed in Ironman Wisconsin (38,545), followed by Ironman Florida (38,157) and Ironman Lake Placid (34,341). The fastest overall race times were achieved in Ironman Copenhagen (11.68 ± 1.38 h), followed by Ironman Hawaii (11.72 ± 1.86 h), Ironman Barcelona (11.78 ± 1.43 h), Ironman Florianópolis (11.80 ± 1.52 h), Ironman Frankfurt (12.03 ± 1.38 h) and Ironman Kalmar (12.08 ± 1.47 h). The fastest athletes originated from Belgium (11.48 ± 1.47 h), followed by athletes from Denmark (11.59 ± 1.40 h), Switzerland (11.62 ± 1.49 h), Austria (11.68 ± 1.50), Finland (11.68 ± 1.40 h) and Germany (11.74 ± 15.1 h). Flat running and cycling courses were associated with faster overall race times. Three of the predictive models identified the ‘country’ and ‘age group’ variables as the most important predictors. Environmental characteristics showed the lowest influence regarding the other variables. The origin of the athlete was the most predictive variable whereas environmental characteristics showed the lowest influence. Flat cycling and flat running courses were associated with faster overall race times. The fastest overall race times were achieved mainly in European races such as Ironman Copenhagen, Ironman Hawaii, Ironman Barcelona, Ironman Florianópolis, Ironman Frankfurt and Ironman Kalmar. The fastest triathletes originated from European countries such as Belgium, Denmark, Switzerland, Austria, Finland, and Germany.

Abstract Site-specific recombinases (SSRs) are critical for achieving precise spatiotemporal control of engineered alleles. These enzymes play a key role in facilitating the deletion or inversion of loci flanked by recombination sites, resulting in the activation or repression of endogenous genes, selection markers or reporter elements. However, multiple recombination in complex alleles can be laborious. To address this, a new and efficient method using AAV vectors has been developed to simplify the conversion of systems based on Cre, FLP, Dre and Vika recombinases. In this study, we present an effective method for ex vivo allele conversion using Cre, FLP (flippase), Dre, and Vika recombinases, employing adeno-associated viruses (AAV) as delivery vectors. AAVs enable efficient allele conversion with minimal toxicity in a reporter mouse line. Moreover, AAVs facilitate sequential allele conversion, essential for fully converting alleles with multiple recombination sites, typically found in conditional knockout mouse models. While simple allele conversions show a 100% efficiency rate, complex multiple conversions consistently achieve an 80% conversion rate. Overall, this strategy markedly reduces the need for animals and significantly speeds up the process of allele conversion, representing a significant improvement in genome engineering techniques.

Abstract This study aimed to determine the effects of Saccharomyces yeast postbiotics on cell turnover, immune responses, and oxidative stress in the jejunal mucosa of pigs. Thirty-two newly weaned pigs at 6.05 ± 0.24 kg were assigned to two dietary treatments based on a randomized complete block design. The treatments were control group receiving a basal diet and a group supplemented with Saccharomyces yeast postbiotics (175 g/ton diet) in the basal diet. After 35 d of the study, pigs were euthanized and jejunal mucosa were collected to assess immune status, oxidative stress, barrier markers, cell proliferation, and apoptosis. Saccharomyces yeast postbiotics reduced (P

Abstract Tylosin, an antibiotic with a long history in treating respiratory bacterial infections, has unknown effects on the gut microbiota of healthy and infected pigs. The study aimed to investigate the effect of a therapeutic dose of tylosin on swine gut microbiota and explored the relationship between this effect and tylosin pharmacokinetics (PK). We also assessed whether changes in gut microbiota after tylosin administration differ between healthy animals (n = 7) and animals intranasally co-infected (n = 7) with Actinobacillus pleuropneumoniae and Pasteurella multocida. Both groups were intramuscularly administered with tylosin (20 mg/kg). The 16S rRNA gene analyses revealed a significantly lower species richness and diversity, after tylosin treatment, in the infected than the healthy pigs, with infected pigs having lower levels of Bacteroidetes and Firmicutes and higher levels of Proteobacteria. Greater tylosin exposure (greater area under curve (AUC) and maximum plasma concentration (Cmax), and slower elimination (longer terminal half-life, T1/2) were observed in healthy than infected pigs. Relative abundance of Lactobacillus, Oscillibacter, Prevotella, and Sporobacter was positively and significantly correlated with AUC and Cmax, whereas the abundance of Acinetobacter, Alishewanella, and Pseudomonas was positively and significantly correlated with T1/2 and mean residence time (MRT) of tylosin. Our findings, for the first time, demonstrated significant changes in swine gut microbiota after a single therapeutic dose of tylosin was administered, whereas the effect of these changes on tylosin PK was not evident.

Abstract This study aimed to assess the magnitude of hematological toxicity and associated factors in newborns with hyperbilirubinemia. A cross-sectional study was conducted from April to December 2023. A total of 247 newborns were included. The data were collected using questionnaires and a data extraction sheet. Four 4 ml of blood was collected. A Sysmex KX-21 analyzer was used for blood analysis, and a Mindray BS-240 analyzer was used for bilirubin measurement. The data were entered into Epi-data and analyzed by SPSS. The logistic regression was used. The P value was set at 0.05. Before phototherapy, the hematological toxicities, such as anemia, leucopenia, and thrombocytopenia, were 45.7%, 22.2%, and 6.1%, respectively, whereas after phototherapy, anemia and thrombocytopenia, significantly increased, but the leucopenia, significantly decreased. The risk of developing anemia increased, 3.5, 2.7, and 2.1-fold among newborns with bilirubin > 18 mg/dl, with Rh blood group incompatibility, and treated with intensive phototherapy, respectively. Both low birth weight and intensive phototherapy increased the incidence of thrombocytopenia by 2 and 3.4-fold, respectively. Hematological toxicity was found to be a severe public health issue in newborns. Thus, strict follow-up and early detection of toxicity by considering aggravation factors are necessary.

Abstract The hypothesis of this study was that evaluation of radiodensity assessment beyond a carotid stenosis in arterial and/or venous phase can be used to separate near-occlusion and conventional ≥ 50% stenosis. We prospectively included participants with ≥ 50% carotid stenosis with inclusion preference for cases with extracranial internal carotid artery (ICA) asymmetry. All participants were examined with a research biphasic computed tomography angiography (CTA) protocol (arterial and venous phase). Reference diagnosis was set by interpretation on CTA and radiodensity difference between ipsilateral and contralateral ICA (c-corrected) or vertebral (v-corrected) was compared. We included 93 participants, 62 with near-occlusion and 31 with conventional ≥ 50% stenosis. Just beyond the stenosis, median c-corrected radiodensity was − 20 Hounsfield units (HU) among near-occlusions and − 1 HU among conventional ≥ 50% stenoses (p

Abstract Background Clinical practice guidelines are crucial for enhancing healthcare quality and patient outcomes. Yet, their implementation remains inconsistent across various professions and disciplines. Previous findings on the implementation of the German guideline for schizophrenia (2019) revealed low adherence rates among healthcare professionals. Barriers to guideline adherence are multifaceted, influenced by individual, contextual, and guideline-related factors. This study aims to investigate the effectiveness of a digital guideline version compared to print/PDF formats in enhancing guideline adherence. Methods A multicenter, cluster-randomized controlled trial was conducted in South Bavaria, Germany, involving psychologists and physicians. Participants were divided into two groups: implementation of the guideline using a digital online version via the MAGICapp platform and the other using the traditional print/PDF version. The study included a baseline assessment and a post-intervention assessment following a 6-month intervention phase. The primary outcome was guideline knowledge, which was assessed using a guideline knowledge questionnaire. Results The study included 217 participants at baseline and 120 at post-intervention. Both groups showed significant improvements in guideline knowledge; however, no notable difference was found between both study groups regarding guideline knowledge at either time points. At baseline, 43.6% in the control group (CG) and 52.5% of the interventional group (IG) met the criterion. There was no significant difference in the primary outcome between the two groups at either time point (T0: Chi2 (1) = 1.65, p = 0.199, T1: Chi2 (1) = 0.34, p = 0.561). At post-intervention, both groups improved, with 58.2% in the CG and 63.5% in the IG meeting this criterion. Conclusions While the study did not include a control group without any implementation strategy, the overall improvement in guideline knowledge following an implementation strategy, independent of the format, was confirmed. The digital guideline version, while not superior in enhancing knowledge, showed potential benefits in shared decision-making skills. However, familiarity with traditional formats and various barriers to digital application may have influenced these results. The study highlights the importance of tailored implementation strategies, especially for younger healthcare providers. Trial registration https://drks.de/search/de/trial/DRKS00028895

Abstract Muscle synergy analyses are used to enhance our understanding of motor control. Spatially fixed synergy weights coordinate multiple co-active muscles through activation commands, known as activation coefficients. To gain a more comprehensive understanding of motor learning, it is essential to understand how activation coefficients vary during a learning task and at different levels of movement proficiency. Participants walked on a line, a beam, and learned to walk on a tightrope—tasks that represent different levels of proficiency. Muscle synergies were extracted from electromyography signals across all conditions and the number of synergies was determined by the knee-point of the total variance accounted for (tVAF) curve. The results indicated that the tVAF of one synergy decreased with task proficiency, with the tightrope task resulting in the highest tVAF compared to the line and beam tasks. Furthermore, with increasing proficiency and after a learning process, trial-to-trial similarity increased and temporal overlap of synergy activation coefficients decreased. Consequently, we propose that precise adjustment and refinement of synergy activation coefficients play a pivotal role in motor learning.

Abstract Suxamethonium is considered by many to be the best drug for providing ideal intubating conditions, short surgical procedures, and rapid sequence induction. However, its usefulness is limited by the frequent occurrence of adverse effects like postoperative myalgia. Therefore this study aimed to assess the prevalence and associated factors of postoperative suxamethonium-induced myalgia. An institutional-based cross-sectional study was conducted on 210 patients who underwent surgery with general anesthesia. The data was collected by using structured and pretested questionnaires and analyzed using SPSS version 20.0. Logistic regression was conducted to identify significant predictors based on a P-value of less than 0.05 with a 95% confidence level. Among 210 patients the prevalence of suxamethonium-induced postoperative myalgia in the first 48 h was 88 (41.9%). Patients having previous anesthesia and surgical exposure (AOR 5.29, 95% CI 1.86–15.05), patients having a co-existing disease (AOR 2.69, 95% CI 1.08–6.67), patients that had not taken premedication (analgesia) (AOR 4.64, 95% CI 1.69–12.74), anesthesia maintenance using halothane (AOR 4.5 95% CI 1.7–11.4) and relaxation maintained with suxamethonium (AOR 3.1, 95% CI 1.2–8.1) were significantly associated with the prevalence of postoperative myalgia. The magnitude of suxamethonium-induced postoperative myalgia was high. So it is better to do with preventive techniques. As much as possible it is better to avoid using suxamethonium and necessary to use better to Premedicate with nonsteroidal anti-inflammatory drugs and non-depolarizing neuromuscular medications.

Abstract The purpose of the present study is to evaluate whether an online reference system (ORS, STATdx Elsevier, Amsterdam, Netherlands) impacts finding the histologically confirmed diagnosis of rare or atypical abdominal tumors and lesions in radiologic imaging. In total, 101 patients with rare tumor entities or lesions and atypical manifestations of common tumors were enrolled retrospectively. Blinded readings were performed by four radiologists with varying levels of experience, who reported on: (a) correct diagnosis (CD), (b) time needed to find the diagnosis, and (c) diagnostic confidence, initially without followed by the assistance of the ORS. The experienced reader (3 years of experience post-residency, CD 49.5%), as well as the advanced reader with 1 year of experience post-residency (CD 43.6%), and a resident with 5 years of experience (CD 46.5%) made the correct diagnosis more frequently compared to the less experienced reader (CD 25.7%). A significant improvement in making the correct diagnosis was only achieved by the advanced reader, the resident with 5 years of experience (CD with ORS 58.4%; p

Abstract The study of rapid and stochastic events that involve multiple species, such as chemical reactions and plasma dynamics, requires means to capture multispectral information in two dimensions at both high temporal- and spatial resolution. Commercially available cameras that provide high temporal resolution are based on either signal intensification or rapid data acquisition. Intensified cameras provide extremely short acquisition times using intensification by means of micro channel plates, but the conversion between electrons and photons makes these cameras inherently monochrome. In contrast, high-speed cameras can achieve color-sensitivity through integrated Bayer filters but suffer from a reduced light collection efficiency and a fixed spectral composition. In this article we present a non-integrated optical arrangement for instantaneous multispectral imaging based on FRAME image multiplexing. By spectrally separating the signal using lossless dichroic mirrors, a 16-fold increase in light-collection efficiency is gained (compared to past solutions), resulting in an equivalent increase in temporal resolution. This improvement provides new avenues for multispectral imaging of rapid events. We demonstrate the system’s versatility and suitability for studies of such processes by applying it for (i) temperature mapping using a high-resolution CCD camera, (ii) high-speed videography up to 10 kHz at four spectral channels and (iii) dual-species visualization in a plasma discharge using an intensified sCMOS camera.

Abstract A circular polarized (CP) pentaband antenna based on the aperture-in-aperture (AIA) concept is presented for CubeSat applications. This AIA consists of five different bands ranging from L-band to Ka-band. Four different antennas, each operating at a specific frequency band, namely 12 GHz, 18.5 GHz, 26 GHz, and 32 GHz, were incorporated into an L-band (viz. 1.5 GHz) antenna. Notably, the five antennas can operate simultaneously for a CubeSat downlink operation with a frequency ratio of 21.3:1. The antenna structure shows a realized gain of 5–10 dBi with good CP bandwidth (

Introducción: La sedación paliativa continua (SPC) es definida como la administración de fármacos para lograr el alivio del sufrimiento físico o psicológico (síntomas refractarios), inalcanzable con otras medidas, mediante la disminución, progresiva y previsiblemente irreversible de la consciencia en un paciente cuya muerte se prevé muy próxima. Esta terapia se considera clínica, comunicativa, ética, legal y emocionalmente compleja reflejada por la inconsistencia que persiste en la literatura sobre su definición, diversidad de los síntomas refractarios, necesidades individuales y las indicaciones precisas. Objetivos: Analizar los desafíos profesionales y éticos de los médicos especialistas en el uso de SPC a través de un enfoque más personalizado y valorizando sus voces. Métodos: Investigación cualitativo, específicamente discusiones de grupos focales. Realizamos tres grupos focales (Dos con dos informantes y uno con tres de diversas especialidades, total de 7 médicos) Resultados: Se utilizó análisis fenomenológico interpretativo, usando procesos de descripción, interpretación y comparación para consolidar los datos en cuatro categorías en base a los propósitos: experiencias en el uso de SPC, abordaje clínico, entorno y el impacto profesional y ético. Conclusión: Se revela que los médicos perciben la SPC como una herramienta viable para aliviar el sufrimiento físico refractario en pacientes terminales, sin la intención de acelerar la muerte. Sin embargo, reconocen la complejidad de esta práctica a nivel multifactorial; pudiendo influir en la calidad de la sedación, por lo que es imperativo intensificar la investigación, desarrollar recursos educativos robustos y actualizar las guías clínicas para abordar los desafíos que enfrentan los equipos interprofesionales.

Objectives Scant data are available on syphilis infection within migrant populations worldwide and in the population of the Middle East and North Africa region. This study investigated the prevalence of both lifetime and recent syphilis infections among migrant craft and manual workers (MCMWs) in Qatar, a diverse demographic representing 60% of the country’s population.Methods Sera specimens collected during a nationwide cross-sectional survey of SARS-CoV-2 seroprevalence among the MCMW population, conducted between 26 July and 9 September 2020, were analysed. Treponema pallidum antibodies were detected using the Mindray CL-900i Chemiluminescence Immunoassay Analyzer. To differentiate recent infections, rapid plasma reagin (RPR) testing was performed, with an RPR titre of ≥1:8 considered indicative of recent infection. Logistic regression analyses were employed to identify factors associated with lifetime syphilis infection. Sampling weights were incorporated into all statistical analyses to obtain population-level estimates.Results T. pallidum antibodies were identified in 38 of the 2528 tested sera specimens. Prevalence of lifetime infection was estimated at 1.3% (95% CI 0.9% to 1.8%). Among the 38 treponemal-positive specimens, 15 were reactive by RPR, with three having titres ≥1:8, indicating recent infection. Prevalence of recent infection was estimated at 0.09% (95% CI 0.01 to 0.3%). Among treponemal-positive MCMWs, the estimated proportion with recent infection was 8.1% (95% CI: 1.7 to 21.4%). The adjusted OR for lifetime infection increased with age, reaching 8.68 (95% CI 2.58 to 29.23) among those aged ≥60 years compared with those ≤29 years of age. Differences in prevalence were observed by nationality and occupation, but no differences were found by educational attainment or geographic location.Conclusions Syphilis prevalence among MCMWs in Qatar is consistent with global levels, highlighting a disease burden with implications for health and social well-being. These findings underscore the need for programmes addressing both sexually transmitted infections and the broader sexual health needs of this population.

Introduction The TriAD study will assess the Xpert MTB/XDR (Xpert XDR; Cepheid) assay to detect tuberculosis (TB) drug resistance in sputum testing positive for TB to rapidly triage and treat patients with a short all-oral treatment regimen.Methods and analysis In this study, approximately 4800 Xpert MTB/RIF or Ultra MTB-positive patients (irrespective of rifampicin (RIF) resistance (RR) status) from several clinical sites across South Africa, Nigeria and Ethiopia will be enrolled over 18–24 months and followed-up for approximately 6 months post-TB treatment completion. Participants will be enrolled into one of two cohorts based on Xpert MTB/RIF and Xpert XDR results: Mycobacterium tuberculosis (M.tb) positive participants with RR in Cohort 1 (n=880) and M.tb positive RIF susceptible TB patients with isoniazid mono-resistance irrespective of presence of resistance to fluoroquinolones, second-line injectable drugs or ethionamide in Cohort 2 (n=400). Cohort 1 will be compared with historical cohorts from each implementing sites. The primary study outcomes include time to initiation of an appropriate treatment regimen by resistance profile and the proportion of patients with favourable treatment outcomes compared with historical cohorts from each of the implementing sites. Secondary outcomes include feasibility, acceptability and cost-effectiveness of this approach to inform policies and guidelines for programmatic implementation of this triage and treat model for drug-resistant tuberculosis management. Utility of the tuberculosis molecular bacterial load assay (TB-MBLA) for real-time treatment response assessment will also be evaluated.Ethics and dissemination The University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC) and local research committees have provided ethical review and approval (BREC/00002654/2021, HREC 210805, NHREC/01/01/2007 and EPHI-IRB-459–2022). The South African Health Products Regulatory Authority (SAHPRA) have granted regulatory approval for the TRiAD Study (SAHPRA MD20211001). Trial results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry.Trial registration number Clinicaltrials.gov; Trial registration number: NCT05175794; South African National Clinical Trials Register (SANCTR DOH-27-012022-4720)

Objetivo: Revisar la tendencia de la mortalidad materna ocurrida en un Hospital Nacional del ex-Instituto Peruano de Seguridad Social (ahora EsSALUD). Diseño: Estudio epidemiológico descriptivo retrospectivo de las muertes maternas registradas en los archivos del Hospital. Sujetos: Doscientos once mujeres que fallecieron durante la gestación, el parto o el puerperio. Lugar: Departamento de Obstetricia y Ginecología del Hospital Nacional Edgardo Rebagliati Martins, ex-lPSS. Resultados: La muerte obstétrica directa representó el 72,5% (153 casos), incluyendo 25, 1 % (53 casos) por hipertensión inducida por el embarazo, 24,2% (51 casos) por infecciones, 15,6% (33 casos) por hemorragias y 7,6% (16 casos) por otras causas obstétrica directas. La mortalidad obstétrica indirecta fue 27,0% (57 casos) y la no relacionada 0,5% (1 caso). La tasa de mortalidad materna resultó 40,8/1 00000nv, no habiendo variado en los últimos diez años. Conclusión: Se discute las razones probables por las que no esté disminuyendo la mortalidad materna en nuestro Hospital y se hace énfasis en medidas que puedan contribuir a disminuirla, incluyendo una atención con calidad y calidez, una mejor referencia y contrarreferencia y modernizar el equipamiento.

Se realizó el estudio retrospectivo de 116 pacientes hospitalizados con tuberculosis meníngea en el Hospital General Cayetano Heredia en el curso de los años 1977-1981. Las historias clínicas fueron seleccionadas con criterios descritos por variosautores. Se recogió información concerniente a la admisión y al ingreso, con la intención de evaluarlos aspectos clínicos de la enfermedad actual, antecedentes, examen físico y auxiliares, tratamiento y aspectos pronósticos. Se describe mayor frecuencia de varones, menores de 5 años y adultos jóvenes. El antecedente de contacto se obtuvo en 58 o/o del total y de enfermedad tuberculosa en 25 o/o. Consultas previas a la admisión se observaron en 75 o/o del total, encontrando elevada proporción de estadíos clínicos neurológicos avanzados al ingreso. Convulsiones se refirió en 83 o/o de los lactantes y 52 o/o de los preescolares. Se encontró anormales, 93 o/o de las radiografías del tórax de lactantes y preescolares, 71 o/o de las de escolares y 73 o/o de las adultas. La edad, el estado nutricional, las alteraciones del comportamiento y sensorio se asociaron al pronóstico. Cefalea, vómitos, convulsiones, enfermedad miliar, tiempo de enfermedad que motivó el ingreso, vacuna BCG, esquemas antibióticos y corticoterapiano se asociaron al pronóstico. El estadio clínico neurológico al ingreso fue el factor pronóstico más importante. Se sugiere una variante nueva para la clasificación clínica neurológica de los pacientes a la admisión que puede resultar de enorme interés práctico. Se discute los resultados en relación a los distintos aspectos epidemiológicos y patogénicos de la enfermedad, comparando los hallazgos con otros estudios nacionales y extranjeros. Agradecimiento: A la Sra. Teresa Orrego de Cancino, Secretaria del Instituto de Investigaciones dela Altura, por su trabajo mecanográfico.

Mammalian sperm delve into the female reproductive tract to fertilize the female gamete. The available information about how sperm regulate their motility during the final journey to the fertilization site is extremely limited. In this work, we investigated the structural and functional changes in the sperm flagellum after acrosomal exocytosis (AE) and during the interaction with the eggs. The evidence demonstrates that the double helix actin network surrounding the mitochondrial sheath of the midpiece undergoes structural changes prior to the motility cessation. This structural modification is accompanied by a decrease in diameter of the midpiece and is driven by intracellular calcium changes that occur concomitant with a reorganization of the actin helicoidal cortex. Midpiece contraction occurs in a subset of cells that undergo AE, and live-cell imaging during in vitro fertilization showed that the midpiece contraction is required for motility cessation after fusion is initiated. These findings provide the first evidence of the F-actin network’s role in regulating sperm motility, adapting its function to meet specific cellular requirements during fertilization, and highlighting the broader significance of understanding sperm motility.

Group therapy is a scalable and effective treatment for anxiety disorders. However, when performed online, the reduced ability to identify with group members and the reduced interactivity can limit its appeal and effectiveness. Extended reality (XR) technology, including virtual reality and augmented reality, may help address these limitations, thereby enhancing the reach of online group therapy and the benefits that can be drawn from it. To understand how the incorporation of XR technology may improve online group therapy for anxiety disorders, this viewpoint paper examines evidence related to the treatment of anxiety disorders using offline group therapy, online group therapy, and virtual reality, as well as ways to increase social identification and interactivity with the platform, the therapist, and other users. This viewpoint paper suggests ways to integrate these research streams to leverage the strengths of XR platforms and improve group therapeutic offerings.

Crohn's disease (CD) is a transmural inflammatory process that can affect any segment of the gastrointestinal tract. CD has a predilection for the colon and the small bowel, specifically the terminal ileum. Esophageal involvement of CD is exceedingly rare and there is a paucity of data regarding the disease phenotypes, course, complications and treatment. We report a case of an 18-year-old male patient presenting for intermittent dysphagia and epigastric pain. Upper endoscopy revealed esophageal ulcers in the middle esophagus surrounded by normal esophageal mucosa. Biopsies were taken from the ulcerated lesions. Histology revealed granulomatous esophagitis. The stomach and duodenum were unremarkable. An ileo-colonoscopy was performed and showed unremarkable mucosa with normal biopsies. The patient was started on proton pump inhibitors and prednisolone as induction therapy with significant symptomatic improvement within 15 days of therapy. The patient was then started on azathioprine 150 mg once daily as maintenance therapy with complete resolution of symptoms. Esophageal CD is an overlooked entity. This article underscores the need to rule out CD when physicians are confronted by esophageal ulcers on upper endoscopy.

Nebivolol is a third-generation beta-blocker known for its high selectivity for beta-1 adrenergic receptors and its unique ability to induce vasodilation via nitric oxide (NO) release. Nebivolol, despite its favourable safety profile, can lead to significant liver injury. We describe the case of a 73-year-old hypertensive patient who developed significant liver enzyme elevations following the addition of nebivolol to her treatment regimen. Comprehensive workup ruled out other causes, leading to a diagnosis of drug-induced hepatotoxicity. Discontinuation of nebivolol resulted in normalization of liver enzymes. This case underscores the importance of monitoring liver function during beta-blocker therapy, particularly with nebivolol.

As artificial intelligence (AI) technologies occupy a bigger role in psychiatric and psychological care and become the object of increased research attention, industry investment, and public scrutiny, tools for evaluating their clinical, ethical, and user-centricity standards have become essential. In this paper, we first review the history of rating systems used to evaluate AI mental health interventions. We then describe the recently introduced Framework for AI Tool Assessment in Mental Health (FAITA-Mental Health), whose scoring system allows users to grade AI mental health platforms on key domains, including credibility, user experience, crisis management, user agency, health equity, and transparency. Finally, we demonstrate the use of FAITA-Mental Health scale by systematically applying it to OCD Coach, a generative AI tool readily available on the ChatGPT store and designed to help manage the symptoms of obsessive-compulsive disorder. The results offer insights into the utility and limitations of FAITA-Mental Health when applied to “real-world” generative AI platforms in the mental health space, suggesting that the framework effectively identifies key strengths and gaps in AI-driven mental health tools, particularly in areas such as credibility, user experience, and acute crisis management. The results also highlight the need for stringent standards to guide AI integration into mental health care in a manner that is not only effective but also safe and protective of the users’ rights and welfare.

Schistosomiasis is an infectious disease caused by parasitic flatworms of the genus Schistosoma. The species Schistosoma mansoni is associated with hepatosplenic disease. Schistosomiasis involving the gallbladder alone is highly unusual, with a few cases reported. Herein, we present the case of a woman from a region with endemic schistosomiasis who presented with a painless solid lesion and wall thickening of the gallbladder. She underwent an uneventful laparoscopic cholecystectomy. Microscopic examination of the surgical specimen revealed Schistosoma mansoni eggs associated with granulomatous reaction, leading to the diagnosis of schistosomiasis of the gallbladder, prompting subsequent treatment with praziquantel and follow-up. This case illustrates the importance of suspicion for this diagnosis in endemic areas, as it can be misdiagnosed with malignancy if not examined microscopically. Complications and treatment strategies are poorly characterized for the few cases of schistosomiasis; reporting this case can serve as a helpful reminder of a rare presentation of this disease.

Objectives Methotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.Methods In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7 days and 3–6 months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.Results Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. In addition, spike-specific B cell frequencies were unaffected. Remarkably, the frequency of antigen-specific CD4 T cells was reduced in patients using MTX and correlated strongly with anti-RBD IgG antibodies. These results suggest that decreased CD4 T cell activity may result in slower vaccination antibody responses in MTX-treated patients.Conclusion Taken together, MTX treatment reduces vaccine-induced CD4 T cell activation, which correlates with lower antibody responses.Trial registration number NL8900.

Abstract Human milk oligosaccharides (HMOs) promote adequate intestinal microbiota development and favor the immune system's maturation and cognitive development. In addition to non-modifiable factors, HMOs composition can be influenced by other factors like body mass index and eating habits, but the reports are discrepant. The aim of this work was to describe the correlation between maternal factors and HMOs concentration in colostrum in 70 women from northeastern Mexico categorized into women with normal weight and women with overweight or obesity. The absolute concentration of six HMOs were significantly lower in women with overweight or obesity compared to women with normal weight (LNFPI p = 0.0021, 2’-FL p = 0.0304, LNT p = 0.0492, LNnT p = 0.00026, 3’-SL p = 0.0476, 6’-SL p = 0.00041). Another main finding was that the frequency of consumption of food groups such as vegetables, fruits and meats was positively correlated to specific HMOs (Poblano chili and 2’-FL; r s = 0.702, p = 0.0012; Orange or tangerine and 3-FL; r s = 0.428, p = 0.0022; Chicken and 2'-FL; r s = 0.615, p = 0.0039). This study contributes to the elucidation of how maternal factors influence the composition of HMOs and opens possibilities for future research aimed at mitigating overweight or obesity, consequently improving the quality of human milk.

Abstract Aim of this study was to analyse the associations of cardiovascular health and adrenal gland volume as a rather new imaging biomarker of chronic hypothalamic–pituitary–adrenal (HPA) axis activation. The study population originates from the KORA population-based cross-sectional prospective cohort. 400 participants without known cardiovascular disease underwent a whole-body MRI. Manual segmentation of adrenal glands was performed on VIBE-Dixon gradient-echo sequence. MRI based evaluation of cardiac parameters was achieved semi-automatically. Cardiometabolic risk factors were obtained through standardized interviews and medical examination. Univariate and multivariate associations were derived. Bi-directional causal mediation analysis was performed. 351 participants were eligible for analysis (56 ± 9.1 years, male 58.7%). In multivariate analysis, significant associations were observed between adrenal gland volume and hypertension (outcome hypertension: Odds Ratio = 1.11, 95% CI [1.01, 1.21], p = 0.028), left ventricular remodelling index (LVRI) (outcome LVRI: β = 0.01, 95% CI [0.00, 0.02], p = 0.011), and left ventricular (LV) wall thickness (outcome LV wall thickness: β = 0.06, 95% CI [0.02, 0.09], p = 0.005). In bi-directional causal mediation analysis adrenal gland volume had a borderline significant mediating effect on the association between hypertension and LVRI (p = 0.052) as well as wall thickness (p = 0.054). MRI-based assessment of adrenal gland enlargement is associated with hypertension and LV remodelling. Adrenal gland volume may serve as an indirect cardiovascular imaging biomarker.

Abstract This study aimed to investigate the effect of orbital wall decompression surgery and reduction of proptosis on the choroidal vascularity index (CVI) and subfoveal choroidal thickness (SFCT) in patients with thyroid eye disease (TED). Fifty-one eyes from 38 patients with controlled TED and proptosis were enrolled in this study. The majority of the patients (50.9%) had a clinical activity score (CAS) of zero, and none had a CAS greater than 2. The patients underwent a complete baseline ophthalmologic examination, and their choroidal profile alterations were monitored using enhanced depth imaging optical coherence tomography (EDI-OCT) before and during the three months after surgery. Changes in SFCT, luminance area (LA), total choroidal area (TCA), and the choroidal vascularity index (CVI) were measured as the ratio of LA to TCA in EDI-OCT images. The participants had an average age of 46.47 years, and 22 were female (57.9%). The SFCT of the patients exhibited a significant reduction over the follow-up period, decreasing from 388 ± 103 to 355 ± 95 µm in the first month (p

Despite advances in hookworm control and prevention campaigns, the prevalence remains high in sub-Saharan Africa. Iron deficiency anaemia is a major complication in those with prolonged infection, a high hookworm burden, and undernutrition, though most infected people are asymptomatic. While infected patients are commonly diagnosed by the presence of ova or cysts in the stool, gastrointestinal (GI) endoscopy is required for those with negative stool tests and chronic iron deficiency anaemia. A 48-year-old female with symptoms of anaemia for nearly two years presented to Mbarara Regional Referral Hospital with worsening palpitations, easy fatigability, and dizziness over a period of one month. She was given blood transfusions on two occasions. She lives near the lake where she also gets water for drinking and domestic use. We advise GI endoscopy for all patients with chronic iron deficiency anaemia of unexplained aetiology on standard non-invasive testing. Hookworm’s mass empirical treatment policy in endemic areas should be further emphasised.