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The detection of genetic alterations in patients with acute leukemias is essential for the targeting of more specific and effective therapies. Therefore, the aim of this study was to compare the sensitivity of Nested-PCR and RT-qPCR techniques in the detection of genetic alterations in patients with acute leukemias. This study included samples from 117 patients treated at the Fortaleza General Hospital. All samples were submitted to analysis using the Nested-PCR and the RT-qPCR techniques. Acute Myeloid Leukemia (AML) patients’ samples were submitted to the analysis of the following alterations: FLT3-ITD, RUNX1::RUNX1T1, CBFB::MYH11 and PML::RARA; meanwhile, BCR::ABL1, TCF3::PBX1, KMT2A::AFF1, ETV6::RUNX1, and STIL::TAL1 fusions were investigated in the Acute Lymphoblastic Leukemia (ALL) patients’ samples. Throughout the study, 77 patients were diagnosed with AML and 40 with ALL. Among the 77 AML patients, FLT3-ITD, RUNX1::RUNX1T1, PML::RARA, and CBFB::MYH11 were detected in 4, 7, 10 and 8 patients, respectively. Among the 40 ALL patients, the presence of 23 patients with BCR::ABL1 translocation and 9 patients with TCF3::PBX1 translocation was observed through the RT-qPCR methodology. Overall, the present study demonstrated that the RT-qPCR technique presented a higher sensitivity when compared to the Nested-PCR technique at the time of diagnosis of the acute leukemia samples studied.

The importance of Model Predictive Control (MPC) has significant applications in the agricultural industry, more specifically for greenhouse’s control tasks. However, the complexity of the greenhouse and its limited prior knowledge prevent an exact mathematical description of the system. Subspace methods provide a promising solution to this issue through their capacity to identify the system’s comportment using the fit between model output and observed data. In this paper, we introduce an application of Constrained Model Predictive Control (CMPC) for a greenhouse temperature and relative humidity. For this purpose, two Multi Input Single Output (MISO) systems, using Numerical Subspace State Space System Identification (N4SID) algorithm, are firstly suggested to identify the temperature and the relative humidity comportment to heating and ventilation actions. In this sense, linear state space models were adopted in order to evaluate the robustness of the control strategy. Once the system is identified, the MPC technique is applied for the temperature and the humidity regulation. Simulation results show that the regulation of the temperature and the relative humidity under constraints was guaranteed, both parameters respect the ranges 15 °C ≤ Tint ≤ 30 °C and 50 % ≤ Hint ≤ 70 % respectively. On the other hand, the control signals uf and uh applied to the fan and the heater, respect the hard constraints notion, the control signals for the fan and the heater did not exceed 0 ≤ uf ≤ 4.3 Volts and 0 ≤ uh ≤ 5 Volts, respectively, which proves the effectiveness of the MPC and the tracking tasks. Moreover, we show that with the proposed technique, using a new optimization toolbox, the computational complexity has been significantly reduced. The greenhouse in question is devoted to Schefflera Arboricola cultivation.

Abstract Labial necrosis is a rare condition with diverse causes, posing challenges for diagnosis and treatment. Methicillin‐resistant Staphylococcus aureus (MRSA) strains, particularly those positive for Panton‐Valentine leukocidin (PVL), further complicate management due to antibiotic resistance and heightened virulence. We present three cases of labial necrosis caused by MRSA, two of which resulted positive for PVL. The first case involved a 35‐year‐old male with persistent lip edema and inflammation, which progressed despite various treatments. MRSA was isolated, and the patient responded to daptomycin and clindamycin therapy. The second case featured a 38‐year‐old male with intense lip pain and swelling, initially misdiagnosed as angioedema. The patient improved after treatment with daptomycin and clindamycin, along with nasal decolonization. The third case involved a 19‐year‐old male with rapid upper lip swelling following manipulation of a boil. Prompt drainage and antibiotic treatment led to complete resolution. These cases underscore the importance of considering MRSA and PVL‐positive S. aureus as potential etiologies in labial necrosis, especially in young individuals without underlying medical conditions. Effective management involves incision and drainage, complemented by antibiotic therapy tailored to drug resistance and virulence factors.

Abstract Background Philip Morris International’s IQOS, with its heatsticks (HEETS), is the heated tobacco product with the largest global market share. IQOS and/or electronic cigarettes use rate is higher among Arabs vs. Jews in Israel. This paper aims to compare IQOS point-of-sale marketing strategies, and regulatory compliance in Arab vs. Jewish neighborhoods in Israel. Methods We integrated data from two separate studies including a cross-sectional survey with IQOS retailers (December 2020–April 2021) and audits of points-of-sale that sold IQOS/HEETS (April 2021–July 2021) in 5 large cities in Israel, after marketing restrictions including a points-of-sale display ban and plain packaging became effective in Israel (January 2020). The survey included 69 points-of-sale (21 Arab, 48 Jewish neighborhoods) and the audits included 129 points-of-sale (48 Arab, 81 Jewish neighborhoods). Comparisons of IQOS marketing strategies between points-of-sale in Arab and Jewish neighborhoods were conducted using Chi-Square test, Fisher’s exact test or Mann–Whitney test, as appropriate. Thematic analysis was used to analyze open-ended questions. Results The survey showed that most marketing strategies, such as promotions to customers, were uniform across points-of-sale in Arab and Jewish neighborhoods. The most noteworthy differences were that a higher proportion of retailers from Arab neighborhoods were invited to IQOS parties (47.6% vs. 21.7%, p

Municipal solid waste (MSW) is accumulating over elapsed time across the world, and it is observed in many projects associated with weak soils, such as marl. Therefore, effective solutions to the environmental problem are essential. Conventional techniques for stabilizing marl generally use substances such as lime and cement, which could exacerbate pollution. For this, some new stabilizers, e.g. nano-MgO, are used. There are large quantities of marls and MSW in Shiraz City, Iran. The present study aims to evaluate the feasibility of using nano-MgO as a green low-carbon binder to remove MSW from the environment and make construction projects more cost-effective. Consolidated drained shear tests were conducted to evaluate the mechanical behaviors of the nano-MgO treated marl specimens at high normal stresses. The marl specimens containing MSW percentages of 15%, 25%, 35%, and 45% and nano-MgO percentages of 0.25%, 0.5%, 0.75%, and 1%, were used. It is found that the marl containing 15% and 25% MSW and 0.5% nano-MgO at 28-d curing can perform cation exchange and form new cementitious products. The soils with merely MSW show good performance due to the removal of the kaolinite and the formation of brucite. However, the soil with 25% MSW and 0.5% nano-MgO shows the same strength enhancement as the specimen with the optimal nano-MgO (0.75%) through the formation of dolomite, with a 20.59% increase in strain energy (SE).

Abstract Background Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system characterized by a clonal expansion of abnormal lymphocyte precursor cells. ALL is the most common form of cancer in children, but despite advances in treatment, it can still be fatal. Ethnic differences influence survival rates, and genomic ancestry plays an important role, especially in mixed-race populations such as Latin America. This study aims to analyze the influence of genomic ancestry on toxicity in children with ALL in the Amazon region. Methods The study included 171 patients (protocol number 119,649/2012—Ethics Committee) with ALL treated at a pediatric treatment center in Belém do Pará, in the Brazilian Amazon. The patients were submitted to the BFM protocol of induction therapy for ALL. Toxicity was assessed based on laboratory tests and adverse events, classified according to the CTC-NCI guide. Genomic ancestry was determined using autosomal informative markers. Results The majority of children (94.74%) developed some type of toxicity during treatment, 87.04% of which were severe. Infectious toxicity was the most common, present in 84.8% of cases, 77.24% of which were severe. Amerindian ancestry showed an association with the risk of severe general toxicity and severe infectious toxicity, with a contribution of 35.0% demonstrating a significant increase in risk. In addition, post-induction refractoriness and relapse were also associated with an increased risk of death. Conclusion This study highlights the influence of Amerindian genomic ancestry on response to therapy and toxicity in children with ALL in the Amazon region. Understanding these associations can contribute to personalizing treatment and improving clinical outcomes.

BACKGROUND: Central sleep apnea (CSA) is associated with increased mortality and morbidity in patients with heart failure with reduced ejection fraction (HFrEF). Treatment of CSA with a certain type of adaptive servo-ventilation (ASV) device that targets minute ventilation (ASVmv) was found to be harmful in these patients. A newer generation of ASV devices that target peak flow (ASVpf) is presumed to have different effects on ventilation and airway patency. We analyzed our registry of patients with HFrEF-CSA to examine the effect of exposure to ASV and role of each type of ASV device on mortality. METHODS: This is a retrospective cohort study in patients with HFrEF and CSA who were treated with ASV devices between 2008 and 2015 at a single institution. Mortality data were collected through the institutional data honest broker. Usage data were obtained from vendors and manufacturers servers. Median follow-up was 64 months. RESULTS: The registry included 90 patients with HFrEF-CSA who were prescribed ASV devices. Applying a 3-h-per-night usage cutoff, we found a survival advantage at 64 months for those who used the ASV device above the cutoff (n = 59; survival 76%) compared to those who did not (n = 31; survival 49%; hazard ratio 0.44; CI 95%, 0.20 to 0.97; P = 0.04). The majority (n = 77) of patients received ASVpf devices with automatically adjusting end-expiratory pressure (EPAP) and the remainder (n = 13) received ASVmv devices mostly with fixed EPAP (n = 12). There was a trend towards a negative correlation between ASVmv with fixed EPAP and survival. CONCLUSION: In this population of patients with HFrEF and CSA, there was no evidence that usage of ASV devices was associated with increased mortality. However, there was evidence of differential effects of type of ASV technology on mortality.

BACKGROUND: The impact of sleep disordered breathing (SDB) on heart failure (HF) is increasingly recognized. However, limited data exist in support of quantification of the clinical and financial impact of SDB on HF hospitalizations. METHODS: A sleep-heart registry included all patients who underwent inpatient sleep testing during hospitalization for HF at a single cardiac center. Readmission data and actual costs of readmissions were obtained from the institutional honest broker. Patients were classified based on the inpatient sleep study as having no SDB, obstructive sleep apnea (OSA), or central sleep apnea (CSA). Cumulative cardiac readmission rates and costs through 3 and 6 months post-discharge were calculated. Unadjusted and adjusted (age, sex, body mass index, and left ventricular ejection fraction) modeling of cost was performed. RESULTS: The cohort consisted of 1547 patients, 393 (25%) had no SDB, 438 (28%) had CSA, and 716 (46%) had OSA. Within 6 months of discharge, 195 CSA patients (45%), 264 OSA patients (37%), and 109 no SDB patients (28%) required cardiovascular readmissions. Similarly, 3- and 6-month mortality rates were higher in both SDB groups than those with no SDB. Both unadjusted and adjusted readmission costs were higher in the OSA and CSA groups compared to no SDB group at 3 and 6 months post-discharge with the CSA and OSA group costs nearly double (~ $16,000) the no SDB group (~ $9000) through 6 months. INTERPRETATION: Previously undiagnosed OSA and CSA are common in patients hospitalized with HF and are associated with increased readmissions rate and mortality.

This research is a comparative study of the views of Qur'anic jurisprudence of Mohaghegh Ardabili and Dr. Sadeghi Tehrani.In order to understand the rulings of the religion, the jurists must first know the interpretation of the verses because those who are obliged to understand their religious issues get help from the Qur'an and the jurists. On the other hand, the human intellect is limited and does not have the power to understand all the knowledge. Therefore, it is necessary that the jurists, commentators and common people learn the verses of Ahkam each in turn and according to their understanding, so that they do not fall into mistakes in their daily life and religious matters. Therefore, in order to be safe from mistakes, one should try to make the interpretation based on the correct principles and firm rules that are in harmony with the purpose of the Qur'an, which is to guide mankind. In this study, the opinions of both commentators and their points of commonality and difference were identified. It can be said that there are differences of opinion in about three cases in ghusl and ablution, seven cases in prayer, two cases in fasting and seven cases in Hajj.

RATIONALE: The prognosis of patients with lung cancer admitted to the intensive care unit (ICU) is often perceived as poor. We described the characteristics, management, and outcomes of critically ill patients with lung cancer and determined the predictors of mortality. METHODS: We retrospectively studied patients with lung cancer who were admitted to the ICU of a tertiary care hospital between 1999 and 2021 for the reasons other than routine postoperative care. We noted their characteristics, ICU management, and outcomes. We performed the multivariable logistic regression analysis to determine the predictors of hospital mortality. RESULTS: In the 23-year period, 306 patients with lung cancer were admitted to the ICU (median age = 63.0 years, 68.3% males, 45.6% with moderate/severe functional disability, most had advanced lung cancer, and median Acute Physiology and Chronic Health Evaluation II score = 24.0). Life support measures included invasive mechanical ventilation (47.1%), vasopressors (34.0%), and new renal replacement therapy (8.8%). Do-Not-Resuscitate orders were implemented during ICU stay in 30.1%. The hospital mortality was 43.8% with a significantly lower rate in patients admitted after 2015 (28.0%). The predictors of mortality were moderate/severe baseline disability (odds ratio [OR] 2.65, 95% confidence interval [CI] 1.22, 5.78), advanced lung cancer (OR 8.36, 95% CI 1.81, 38.58), lactate level (OR 1.45, 95% CI 1.12, 1.88, invasive mechanical ventilation (OR 10.92, 95% CI 4.98, 23.95), and admission period after 2015 (OR 0.37, 95% CI 0.16, 0.85). CONCLUSIONS: The mortality rates in patients with lung cancer admitted to the ICU during a 23-year period decreased after 2015. Functional disability, advanced lung cancer stage, vasopressor use, and invasive mechanical ventilation predicted mortality.

Abstract Zinc oxide nanoparticles (ZnO NPs) are one of the most abundantly used nanomaterials in cosmetics and topical products, and nowadays, they are explored in drug delivery and tissue engineering. Some recent data evidenced that they are responsible for cardiotoxic effects and systemic toxicity. The present study aimed to investigate the toxic effect of ZnO NPs (39 nm) on the heart of Wistar rats and to perform a dose–response relationship using three different dose levels (25, 50, 100 mg/kg bw) of ZnO NPs on the electrocardiogram (ECG) readings, the levels of biochemical function parameters of heart, and the oxidative stress and antioxidant biomarkers. Furthermore, zinc concentration level and histopathological examination of heart tissues were determined. ZnO NPs showed a dose-dependent effect, as the 100 mg/kg bw ZnO NPs treated group showed the most significant changes in ECGs parameters: R–R distance, P–R interval, R and T amplitudes, and increased levels of heart enzymes Creatine Kinase- MB (CK-MB) and Lactate dehydrogenase (LDH). On the other hand, elevated zinc concentration levels, oxidative stress biomarkers MDA and NO, and decreased GSH levels were found also in a dose-dependent manner, the results were supported by impairment in the histopathological structure of heart tissues. While the dose of 100 mg/kg bw of ZnO bulk group showed no significant effects on heart function. The present study concluded that ZnO NPs could induce cardiac dysfunctions and pathological lesions mainly in the high dose.

The development of microchannel manufacturing technology has led to a growing interest in using them as heat exchangers. Microchannels are used to control the temperature of equipment and components that generate a high amount of heat flux. Heat transfer can be further increased by dispersing particles (nano-sized particles) with a low volume fraction into the base fluid (nanofluid). A nanofluid can change the thermophysical properties of a base fluid and improve its thermal performance. The purpose of this study was to examine the heat transfer characteristics of oil-based nanofluid within wavy microchannels in series and parallel arrangements of microchannels. In order to examine the performance of each microchannel separately and to make it easier to draw their diagrams, they are named 1 and 2. Experiments were performed on TiO2 and SiO2 oil-based nanofluids in volume fractions of 0.05 and 0.1, flow rates of 0.5, 1.0, and 1.5 lit/min, and inlet temperatures of 40°C, 45°C, 50°C, 55°C. The results show an increase in the Nusselt number of the base fluid up to 41.8% in the series arrangement and also a decrease in the surface temperature in the series arrangement compared to the parallel arrangement. Also, TiO2 and SiO2 nanofluids with a volume fraction of 0.1 caused the highest increase in heat transfer, up to 56% and 52.7% in parallel arrangement and up to 45.8% and 42% in series arrangement compared to the base fluid, respectively. The pressure drop of the test section in series arrangement was up to 82.1% higher than parallel.

Abstract Background Spinal muscular atrophy (SMA) is a fatal autosomal recessive disorder for which several treatment options, including a gene therapy, have become available. SMA incidence has not been well-characterized in most Arab countries where rates of consanguinity are high. Understanding SMA disease epidemiology has important implications for screening, prevention, and treatment in those populations. Methods We perform SMA diagnostic testing in a clinical multi-national patient cohort (N = 171) referred for hypotonia and/or muscle weakness. In addition, we carry out genetic newborn screening for SMA on 1502 healthy Emirati newborns to estimate the carrier frequency and incidence of the disease in the United Arab Emirates. Results Patients referred for SMA genetic testing are mostly Arabs (82%) representing 18 countries. The overall diagnostic yield is 33.9%, which is higher (>50%) for certain nationalities. Most patients (71%) has two SMN2 copies and earlier disease onset. For the first time, we estimate SMA carrier frequency (1.3%) and incidence of the disease (1 in 7122 live births) in the United Arab Emirates. Using birth and marriage rates in two Arab populations (United Arab Emirates and Saudi Arabia), as well as disease incidence in both countries, we show that, besides preventing new cases, premarital genetic screening could potentially result in around $8 to $324 million annual cost savings, respectively, relative to postnatal treatment. Conclusions The SMA carrier frequency and incidence we document suggests high potential benefit for universal implementation of premarital genomic screening for a wide range of recessive disorders in Arab populations.

Summary: Introduction: Excessive gestational weight gain (EGWG) is associated with adverse effects on the life of the mother and the neonate. Spexin (SPX) is considered as a new factor involved in glucose homeostasis, body weight and fat metabolism. This study aimed to evaluate the relationship between blood SPX concentration and the nutritional status of mothers with EGWG, Apgar score and the weight of the neonates. Methods: This cross-sectional study was conducted in Zahedan, Iran in 2021. The study sample includes 30 pregnant mothers with normal weight gain and 30 pregnant mothers with EGWG. Demographic questionnaire and 24-hour dietary recall (24-hr) were completed. The mothers' weight was recorded, and the birth weight and Apgar scores of the neonates were measured. The concentration of SPX in the blood sample of the pregnant mother and the umbilical cord blood of the newborn at the time of delivery was measured by a SPX kit with the ELISA method. Statistical analysis was performed using SPSS; 21. P 0.05). Weight gain during pregnancy, energy, carbohydrate and protein intake in EGWG mothers were significantly higher than the control group (P

There are well-established relationships among self-efficacy, group effectiveness, extrinsic and intrinsic motivation, and work performance in employees. However, little is known about these relationships among employees with disabilities. The purpose of this study was to examine the mediation roles of extrinsic and intrinsic motivation in the association between self-efficacy and individual work performance and between group effectiveness and individual work performance in Saudi employees with disabilities. A sample of 176 employees (59.1% female) with disabilities (visual, auditory, mobility, and learning disabilities) participated in the study. A set of structural equation models was built to establish the relationships. There were positive relationships between self-efficacy and both task and contextual performance. Furthermore, intrinsic and integrated regulation mediated the relationship between self-efficacy and task performance, and identified integrated regulation mediated the relationship between self-efficacy and contextual performance. Group effectiveness was related to work performance only through motivational regulations. Therefore, it is crucial for organizations to design psychological training to increase self-efficacy beliefs in employees with disabilities and to teach them how to internalize external forces in the workplace to promote individual work performance and organizational progress.

This research investigates an AC microgrid interconnected with the utility grid, comprising a 5.2 kW wind power system using a Permanent Magnet Synchronous Generator (PMSG), a 6.1 kW photovoltaic system (PVS), and integrated electric vehicles (EVs) with 600 V, 10Ah batteries operating in V2G and G2V modes. Bidirectional back-to-back converters, controlled via a voltage-oriented control (VOC) strategy, facilitate the interconnections. The PMSG system is controlled using vector control methodology, while the PVS employs a double-stage configuration with a perturb and observe algorithm for maximum power point tracking (MPPT). Advanced controllers based on Active Disturbance Rejection Control (ADRC) regulate generator speed and the DC link voltage of the grid-connected converters. The backstepping technique is utilized for internal loop control of PMSG currents and coupling filter currents for the grid-connected converters. A comparative study between the ADRC-Backstepping controller and the PI controller was conducted, demonstrating the superior efficacy of the ADRC-Backstepping approach. Simulation results show accurate regulation of DC link voltage at reference levels, operation with unit power factor, with a current THD below 4 %, demonstrating the effectiveness and robustness of the proposed control strategies under varying conditions.

This study addresses competences of the Open Scholar. It draws on a theoretical framework reaching out to sustainability education, responsibility and activity theory to describe competences. Competences of the Open Scholar are understood within the context of Higher Education institutions’ three missions: teaching, research and service to the community. The systematic literature review of three key concepts, Open Educator, Open Researcher and Open Scholar performed on a total of 811 articles between 2011 and 2023 as well as the content analysis performed on 10 competence frameworks highlight a dearth in epistemic competences. To fill this gap, the study raises awareness of the importance of initiating the development of scholars’ capabilities in areas that can enable them to ask questions at the level of purpose and paradigm. Capabilities to address these deeper levels are presented as a way of enhancing the responsibility of scholars. Responsibility is framed in-line with its Latin root, respondere, i.e., providing a response and drawing on a semantics of care, respect and concern (instead of the foregrounded framing of responsibility in terms of subjectivity, power and causality). Furthermore, identifying not-yetness and addressing uncertainty are presented as key competences of the Open Scholar.

Prospective teachers' attitudes towards teaching are grounded in their experiences of successes and failures as students. Thus, addressing their attitudes towards teaching before starting their profession is strategic. To this aim, this study explored Jordanian prospective kindergarten teachers' attitudes towards the teaching profession. Furthermore, the study investigated the relative influence of participants' self-esteem, communication skills, and interest in the teaching process on these attitudes. A total of 234 university students who were pursuing their bachelor degree in kindergarten education participated in the study. These were selected from the six universities offering bachelor programs in childhood education in Jordan. Three scales were administered through the internet to collect data from students. The results showed that the behavioral component of communication skills was significantly associated with attitudes. Neither cognitive nor emotional communication skills were significant predictors. Undergraduate curricula should aim to cultivate positive attitudes while addressing and improving negative ones. Fostering prospective teachers' communication skills seemed to be a promising pathway to help promote positive attitudes and interest in teaching. Kindergarten education curriculum should help students improve, learn and use communication skills effectively.

Background: Acetaminophen overdose is a common clinical condition, often leading to liver toxicity. Current treatments involve the three-infusion N-Acetylcysteine (NAC) regimen (FDA-labeled), which may be complex, time-consuming, and need to be changed. An alternative uses two infusions instead, which offers possible advantages regarding simplicity and administration errors. This study sought to compare the respective efficacies and safety outcomes when treating acute acetaminophen overdose among children and adolescents. Methods: At Montreal Children’s Hospital, a retrospective study was conducted comparing pre-2003 FDA-labelled three-infusion NAC therapy with a two-infusion regimen. Information was collected regarding patient demographics, NAC administration details, errors, rates of hepatotoxicity, and adverse reactions, and the statistical test Chi-square test was employed to obtain the results. Results: A total of 126 patients met the inclusion criteria. Of these patients, 65 received a two-infusion regimen, and 61 patients received the FDA-labeled regimen. The two-infusion group experienced significantly fewer administration errors (4 errors vs. 23 errors; p < 0.001), while the rates of hepatotoxicity between them were similar. There were no instances of liver transplantation or mortality due to either regimen. Adverse reactions occurred equally frequently between both regimens with no discernible difference—the meantime to administer NAC was 9 h for the two-infusion regimen and 8.5 h for FDA-labeled regimen groups, respectively. Three cases of hepatitis were successfully treated with timely NAC therapy, and no liver transplantation or mortality occurred. Adverse reactions, including anaphylactoid reactions, were observed in both groups but were resolved when temporarily stopped and restarted at a slower infusion rate. Conclusions: The two-infusion NAC regimen proved similar efficacy at protecting liver damage and improving patient outcomes compared to its FDA-labeled three-stage counterpart, with significantly fewer administration errors for this version of NAC treatment, suggesting potential advantages in terms of safety and simplicity. Future research should investigate larger cohorts and more variables to validate these results further and optimize the management of acetaminophen overdose cases; further investigation should focus on dosing strategies, personalized approaches, and long-term patient care in this context.

Abstract The hyperarid mangrove in the Middle East is characterised by the absence of rivers or freshwater inputs and is one of the most extreme settings of this ecosystem on Earth. Endemic to Qatar’s hyperarid mangroves, a Palaemon shrimp is uniquely confined to a sole mangrove site in the Arabian Gulf. Within these mangrove channels, we unveiled brine groundwater sources exceeding 70 ppt salinity, contrasting the local marine standard of 42 ppt. Concurrently, a mysid species typically linked to salt pans and groundwater coexists. Stable isotopic analysis implied the existence of a predator–prey dynamic between this mysid species and the studied shrimp. Then, investigating the endemic shrimp’s adaptation to extreme salinity, we conducted osmolarity experiments and phylogenetic studies. Our findings demonstrate that this shrimp transitions from hypo- to hyper-osmoregulation, tolerating salinities from 18 to 68 ppt—an unprecedented osmoregulatory capacity among caridean shrimps. This speciation pattern likely arises from the species osmolarity adaptation, as suggested for other Palaemon congeners. Phylogenetic analysis of the studied Palaemon, along with the mangrove’s geological history, suggests a profound evolutionary interplay between the ecosystem and the shrimp since the Eocene. This study proposes the hyperarid mangrove enclave as an Athalassic mangrove oasis—a distinctive, isolated ecosystem within the desert landscape.

Abstract Background Congenital disorders of the mitochondrial respiratory chain are a heterogeneous group of inborn errors of metabolism. Among them, NADH:ubiquinone oxidoreductase (complex I, CI) deficiency is the most common. Biallelic pathogenic variants in NDUFAF2, encoding the nuclear assembly CI factor NDUFAF2, were initially reported to cause progressive encephalopathy beginning in infancy. Since the initial report in 2005, less than a dozen patients with NDUFAF2-related disease have been reported. Methods Clinical, biochemical, and neuroradiological features of four new patients residing in Northern Israel were collected during 2016–2022 at Emek Medical Center. Enzymatic activities of the five respiratory-chain complexes were determined in isolated fibroblast mitochondria by spectrophotometric methods. Western blot analyses were conducted with anti-human NDUFAF2 antibody; antibody against the mitochondrial marker VDAC1 was used as a loading control. Genetic studies were performed by chromosome microarray analysis using Affymetrix CytoScan 750 K arrays. Results All four patients presented with infantile-onset growth retardation, ophthalmological impairments with nystagmus, strabismus (starting between 5 and 9 months), and further progressed to life-threatening episodes of apnea usually triggered by trivial febrile illnesses (between 10 and 18 months) with gradual loss of acquired developmental milestones (3 of 4 patients). Serial magnetic-resonance imaging studies in two of the four patients showed a progressive pattern of abnormal T2-weighted hyperintense signals involving primarily the brainstem, the upper cervical cord, and later, the basal ganglia and thalami. Magnetic-resonance spectroscopy in one patient showed an increased lactate peak. Disease progression was marked by ventilatory dependency and early lethality. 3 of the 4 patients tested, harbored a homozygous 142-kb partial interstitial deletion that omits exons 2–4 of NDUFAF2. Mitochondrial CI activity was significantly decreased in the only patient tested. Western blot analysis disclosed the absence of NDUFAF2 protein compared to normal controls. In addition, we reviewed all 10 previously reported NDUFAF2-deficient cases to better characterize the disease. Conclusions Biallelic loss-of-function mutations in NDUFAF2 result in a distinctive phenotype in the spectrum of Leigh syndrome with clinical and neuroradiological features that are primarily attributed to progressive brainstem damage.

Objective: Morphine exposure during pregnancy has detrimental effects on both the mother and her offspring, both during and after childbirth. This study aimed to investigate the impact of prenatal morphine exposure on rat pups and dams, specifically focusing on changes in Neuregulin-1 (Nrg-1)/ErbB4 gene expression, inflammation, and brain-derived neurotrophic factor (BDNF) levels. Materials and methods: Twenty female rats were randomized into two experimental groups:1-Morphine Group: Dams received morphine throughout pregnancy. 2-Control Group: Dams received no interventions.At the end of gestation, blood samples were collected from the dams. Subsequently, dams and their pups underwent tissue collection from the cortical area of the brain to evaluate the following parameters: Interleukin-6 (IL-6), Interleukin-10 (IL-10), total antioxidant capacity (TAC), Malondialdehyde (MDA), and Brain-derived neurotrophic factor (BDNF).Additionally, RNA was extracted from the pup's cortical brain tissue for the assessment of gene expression levels of Neuregulin-1 (NRG-1) and ErbB-4 using quantitative real-time polymerase chain reaction (qrt-PCR). Results: The molecular investigation revealed a decrease in NRG-1 and ErbB-4 expressions in the brain cortex of offspring exposed to morphine during prenatal development. Additionally, the levels of IL-6 and IL-10 in both the serum and brain of both the mothers and their offspring in the morphine group were significantly higher compared to the control group. The morphine-exposed group also exhibited significantly lower levels of TAC and higher levels of MDA, indicating increased oxidative stress. Furthermore, the levels of BDNF in the morphine group were significantly lower compared to the control group. Conclusion: Prenatal morphine exposure in rats has detrimental effects on both the dams and their offspring. This study demonstrates that prenatal morphine exposure disrupts critical molecular pathways involved in neurodevelopment, inflammation, oxidative stress, and neurotrophic signaling. These findings suggest that prenatal morphine exposure can have long-lasting consequences for the offspring, potentially contributing to neurodevelopmental disorders and other health issues later in life.

Obstructive sleep apnea (OSA) is a sleep disorder caused by periodic airway obstructions and has been associated with numerous health consequences, which are thought to result from tissue hypoxia. However, challenges in the direct measurement of tissue-level oxygenation make it difficult to analyze the hypoxia exposure pattern in patients. Furthermore, current clinical practice relies on the apnea-hypopnea index (AHI) and pulse oximetry to assess OSA severity, both of which have limitations. To overcome this, we developed a clinically deployable mathematical model, which outputs tissue-level oxygenation. The model incorporates spatial pulmonary oxygen uptake, considers dissolved oxygen, and can use time-dependent patient inputs. It was applied to explore a series of breathing patterns that are clinically differentiated. Supporting previous studies, the result of this analysis indicated that the AHI is an unreliable indicator of hypoxia burden. As a proof of principle, polysomnography data from two patients was analyzed with this model. The model showed greater sensitivity to breathing in comparison with pulse oximetry and provided systemic venous oxygenation, which is absent from clinical measurements. In addition, the dissolved oxygen output was used to calculate hypoxia burden scores for each patient and compared to the clinical assessment, highlighting the importance of event length and cumulative impact of obstructions. Furthermore, an intra-patient statistical analysis was used to underscore the significance of closely occurring obstructive events and to highlight the utility of the model for quantitative data processing. Looking ahead, our model can be used with polysomnography data to predict hypoxic burden on the tissues and help guide patient treatment decisions.

PurposeLimited research exists on the time course of long-term retinal and cerebral deficits in diabetic rodents. Previously, we examined short term (4-8 weeks) deficits in the Goto-Kakizaki (GK) rat model of Type II diabetes. Here, we investigated the long-term (1-8 months) temporal appearance of functional deficits (retinal, cognitive, and motor), retinal vascular pathology, and retinal dopamine levels in the GK rat.MethodsIn GK rats and Wistar controls, retinal neuronal function (electroretinogram), cognitive function (Y-maze), and motor function (rotarod) were measured at 1, 2, 4, 6, and 8 months of age. In addition, we evaluated retinal vascular function (functional hyperemia) and glucose and insulin tolerance. Retinas from rats euthanized at ≥8 months were assessed for vascular pathology. Dopamine and DOPAC levels were measured via HPLC in retinas from rats euthanized at 1, 2, 8, and 12 months.ResultsGoto-Kakizaki rats exhibited significant glucose intolerance beginning at 4 weeks and worsening over time (p < 0.001). GK rats also showed significant delays in flicker and oscillatory potential implicit times (p < 0.05 to p < 0.001) beginning at 1 month. Cognitive deficits were observed beginning at 6 months (p < 0.05), but no motor deficits. GK rats showed no deficits in functional hyperemia and no increase in acellular retinal capillaries. Dopamine levels were twice as high in GK vs. Wistar retinas at 1, 2, 8, and 12 months (p < 0.001).ConclusionAs shown previously, retinal deficits were detectable prior to cognitive deficits in GK rats. While retinal neuronal function was compromised, retinal vascular pathology was not observed, even at 12+ months. High endogenous levels of dopamine in the GK rat may be acting as an anti-angiogenic and providing protection against vascular pathology.

Globozoospermia is a form of male infertility characterized by spermatozoa with spherical heads lacking acrosomes. The aim of this study was to evaluate ultrastructural and molecular defects in different types of globozoospermia. Semen samples from 12 infertile patients (9 with complete globozoospermia and 3 with partial globozoospermia) and 10 normozoospermic men (control) were examined by transmission electron microscopy and immunocytochemistry with antibodies against lamin B1. The presence of lamin A and progerin was assessed by reverse transcription-PCR. Whole exome sequencing was performed in three patients. In semen samples with complete and partial globozoospermia, lamin B1 was observed at the periphery of sperm nuclei, whereas lamin A and progerin were absent. Nuclear envelope pores were found in spermatozoa from both patient groups, regardless of morphology and chromatin condensation, in contrast to the control group. Non-condensed chromatin was present in 51%–81% of cases of complete globozoospermia and in 36%–79% of cases of partial globozoospermia. Homozygous DPY19L2 and SPATA16 variants were identified in two patients with partial globozoospermia and one patient with complete globozoospermia. An atypical nuclear membrane with abnormal nuclear pore distribution and lamin B1 localization was observed in spermatozoa from patients with both complete and partial globozoospermia. The genetic defects in the DPY19L2 and SPATA16 genes detected in patients from both globozoospermic groups suggest a generalized disruption of nuclear structure in globozoospermia, highlighting the genetic and phenotypic similarities between complete and partial globozoospermia.