PET Imaging of Differentiated Thyroid Cancer with TSHR-Targeted [89Zr]Zr-TR1402.

Thyroid cancer is the most common endocrine cancer, with differentiated thyroid cancers (DTCs) accounting for 95% of diagnoses. While most DTC patients are diagnosed and treated with radioiodine (RAI), up to 20% of DTC patients become RAI refractory (RAI-R). RAI-R patients have significantly reduced survival rates compared to patients who remain RAI-avid. This study explores [89Zr]Zr-TR1402 as a thyroid-stimulating hormone receptor (TSHR)-targeted PET radiopharmaceutical for DTC. [89Zr]Zr-TR1402 was synthesized with a molar activity of 25.9 MBq/nmol by conjugating recombinant human TSH (rhTSH) analogue TR1402 to chelator p-SCN-Bn-deferoxamine (DFO) in a molar ratio of 3:1 (DFO/TR1402) and radiolabeling with 89Zr (t1/2 = 78.4 h, ß+ = 22.7%). As TSHR is absent in commonly available DTC-derived cell lines, TSHR was reintroduced via stable transduction by delivering a lentivirus containing the full-length coding region of the human TSHR gene. Receptor-mediated uptake of [89Zr]Zr-TR1402 was evaluated in vitro in stably transduced TSHR+ and wild-type TSHR- DTC cell lines. In vivo PET imaging was performed on Days 1-3 postinjection in male and female athymic nude mice bearing TSHR+ and TSHR- xenografts, along with ex vivo biodistribution on Day 3 postinjection. In vitro uptake of 1 nM [89Zr]Zr-TR1402 was significantly higher in TSHR+ THJ529T (P < 0.0001) and FTC133 (P < 0.01) cells than in TSHR- THJ529T and FTC133 cells. This uptake was shown to be specific in both TSHR+ THJ529T (P < 0.0001) and TSHR+ FTC133 (P < 0.0001) cells by blocking uptake with 250 nm DFO-TR1402. In vivo PET imaging showed accumulation of [89Zr]Zr-TR1402 in TSHR+ tumors, which was the highest on Day 1. In the male FTC133 xenograft model, ex vivo biodistribution confirmed a significant difference (P < 0.001) in uptake between FTC133+ (1.3 ± 0.1%ID/g) and FTC133- (0.8 ± 0.1%ID/g) tumors. A significant difference (P < 0.05) in uptake was also seen in the male THJ529T xenograft model between THJ529T+ (1.8 ± 0.6%ID/g) and THJ529T- (0.8 ± 0.4%ID/g) tumors. The in vitro and in vivo accumulation of [89Zr]Zr-TR1402 in TSHR-expressing DTC cell lines support the continued preclinical optimization of this approach.

Distortions to the passage of time for annual events: Exploring why Christmas and Ramadan feel like they come around more quickly each year.

BACKGROUND: Commonly heard statements such as "Christmas comes around more quickly each year" suggest that the passage of time between annual events can become distorted, leading to the sensation of time passing more quickly than normal. At present however, it is unclear how prevalent such beliefs are and, what factors are predictive of it. AIM: To explore the prevalence of beliefs that annual events such as Christmas (Study 1 UK sample) and Ramadan (Study 2 Iraqi sample) feel like they come around more quickly each year. To establish the association between distortions to the passage of time between annual events and emotional wellbeing, event specific enjoyment, memory function and self-reported attention to time. METHODS: Participants completed an online questionnaire exploring their subjective experience of time in relation to Christmas and Ramadan. In addition, measures of attention to time, memory function, quality of life and event specific emotion were also taken. FINDINGS: There was widespread agreement that Christmas and Ramadan appeared to come around more quickly each year. In both countries, this belief was associated with greater prospective memory errors, greater attention to time and greater enjoyment of the event. Furthermore, in the UK greater belief that Christmas comes around more quickly was associated with lower social quality of life and in Iraq, greater belief that Ramadan comes around more quickly each year was associated with lower age and female gender. CONCLUSIONS: Distortions to the passage of time for annual events are widespread, occur across multiple cultures and are consistently predicted by prospective function, event enjoyment and attention to time. The absence of an association between older age (above 55 years) and a faster passage of time suggests that caution should be taken when concluding that time passes more quickly with increasing age.

Mg/S@g-C3N4 nanosheets: A promising fluorescence sensor for selective Cu2+ detection in water.

This work describes the development of a novel fluorescence sensor based on magnesium/S@g-C3N4 nanosheets for selective detection of copper (Cu2+) ions in water. Mg/S@g-C3N4 nanosheets were prepared by the polycondensation technique and investigated by X-ray diffraction (XRD), ATR-FTIR spectroscopy, scanning electron microscopy (SEM), surface area (BET), and UV-Vis optical absorption measurements. XRD and ATR-FTIR analysis showed the characteristic peaks for S@g-C3N4. The broad full width at half maximum (0.056 radians) implies a smaller crystallite size, representing smaller Mg/S@g-C3N4 sheets. SEM micrograph showed non-exfoliated nanosheets with flake-like structures. The EDS mapping confirmed the presence of magnesium, carbon, nitrogen, and sulfur throughout the nanosheets. The Mg/S@g-C3N4 nanosheets possess a high surface area of 40 m2/g and mesopores within the nanosheets, with a size of 1.57 nm. The band gap of the Mg/S@g-C3N4 nanosheet was estimated to be 3.0 eV. The sensor exhibits a strong quenching response towards Cu2+ ions, with a decrease in fluorescence intensity as the concentration of Cu2+ increased from 1 µM to 20 µM. The Stern-Volmer quenching constant (KSV) showed a relatively high value of 185053 M-1. The estimated value of LOD by the Mg/S@g-C3N4 sensor for Cu2+ was 16.2 nM. The sensor offered high sensitivity and selectivity for Cu2+ detection over other heavy metals.

Novel paper-based potentiometric combined sensors using coumarin derivatives modified with vanadium pentoxide nanoparticles for the selective determination of trace levels of lead ions.

Novel miniaturized Pb(II) paper-based potentiometric sensors are described using coumarin derivatives I and II as electroactive ionophores and nano vanadium pentoxide as a solid contact material for the sensitive and selective monitoring of trace lead ions. Density functional theory (DFT) confirms optimum geometries, electronic properties, and charge transfer behaviors of 1:2 Pb(II): coumarin complexes. The sensors are prepared by using two strips of 20 × 5 mm filter paper with two circular orifices. One orifice is coated with vanadium pentoxide (V2O5) nanoparticles in colloidal conductive carbon as a solid-contact, covered by a PVC membrane containing coumarin ionophore to act as a sensing probe. The other orifice is treated with Ag/AgCl in a polyvinyl butyral (PVB) film, to act as a reference electrode. Sensors with ionophores (I) and (II) exhibit Nernstian slopes of 27.7 ± 0.2 and 30.2 ± 0.2 mV/decade over the linear concentration range 4.5 × 10-7 to 6.2 × 10-3 M and 8.5 × 10-8 to 6.2 × 10-3 M, with detection limits of 1.3 × 10-7 M (26.9 ppb) and 2.1 × 10-8 M (4.4 ppb), respectively. The sensors are satisfactorily used for accurate determination of lead ions in drinking water, lead-acid battery wastewater, and electronic waste leachates. The results compare favourably well with data obtained by flameless atomic absorption spectrometry.

Slow touch and ultrafast pain fibres: Revisiting peripheral nerve classification.

One hundred years ago, Erlanger and Gasser demonstrated that conduction velocity is correlated with the diameter of a peripheral nerve axon. Later, they also demonstrated that the functional role of the axon is related to its diameter: touch is signalled by large-diameter axons, whereas pain and temperature are signalled by small-diameter axons. Certain discoveries in recent decades prompt a modification of this canonical classification. Here, we review the evidence for unmyelinated (C) fibres signalling touch at a slow conduction velocity and likely contributing to affective aspects of tactile information. We also review the evidence for large-diameter Aß afferents signalling pain at ultrafast conduction velocity and likely contributing to the rapid nociceptive withdrawal reflex. These discoveries imply that conduction velocity is not as clear-cut an indication of the functional role of the axon as previously thought. We finally suggest that a future taxonomy of the peripheral afferent nervous system might be based on the combination of the axons molecular expression and electrophysiological response properties.

The Saudi Gastroenterology Association consensus on the clinical care pathway for the diagnosis and treatment of GERD.

ABSTRACT: Gastroesophageal reflux disease (GERD) is one of the most common problems encountered in outpatient general medicine and gastroenterology clinics. GERD may present with classic esophageal symptoms, extraesophageal symptoms, or mixed symptoms. The diagnosis and treatment of GERD are challenging due to the variety of symptoms and multifactorial pathophysiology. Since there is no consensus on the diagnosis and treatment of GERD in Saudi Arabia, the Saudi Gastroenterology Association established an expert group to formulate a consensus on the clinical care pathway for the diagnosis and treatment of GERD to update health-care providers in Saudi Arabia. The expert group reviewed the literature including recently published international guidelines, clinical trials, and expert opinion and conducted virtual and in-person meetings. A total of 22 statements on the definition, diagnosis, and treatment of GERD were formulated, and three algorithms for the clinical care of GERD were developed with a detailed description for each step. The expert group endorsed the new definition of GERD, the practical principles of interpretation of the diagnostic GERD evaluation, and the practical guidance for GERD treatment including medical, surgical, and endoscopic therapy. The expert group recommends further studies to investigate local data on the diagnosis and treatment of GERD.

A novel potentiometric screen-printed electrode based on crown ethers/nano manganese oxide/Nafion composite for trace level determination of copper ion in biological fluids.

Copper levels in biological fluids are associated with Wilson's, Alzheimer's, Menke's, and Parkinson's diseases, making them good biochemical markers for these diseases. This study introduces a miniaturized screen-printed electrode (SPE) for the potentiometric determination of copper(II) in some biological fluids. Manganese(III) oxide nanoparticles (Mn2O3-NPs), dispersed in Nafion, are drop-casted onto a graphite/PET substrate, serving as the ion-to-electron transducer material. The solid-contact material is then covered by a selective polyvinyl chloride (PVC) membrane incorporated with 18-crown-6 as a neutral ion carrier for the selective determination of copper(II) ions. The proposed electrode exhibits a Nernstian response with a slope of 30.2 ± 0.3 mV/decade (R2 = 0.999) over the linear concentration range 5.2 × 10-9 - 6.2 × 10-3 mol/l and a detection limit of 1.1 × 10-9 mol/l (69.9 ng/l). Short-term potential stability is evaluated using constant current chronopotentiometry (CP) and electrochemical impedance spectroscopy (EIS). A significant improvement in the electrode capacitance (91.5 µF) is displayed due to the use of Mn2O3-NPs as a solid contact. The presence of Nafion, with its high hydrophobicity properties, eliminates the formation of the thin water layer, facilitating the ion-to-electron transduction between the sensing membrane and the conducting substrate. Additionally, it enhances the adhesion of the polymeric sensing membrane to the solid-contact material, preventing membrane delamination and increasing the electrode's lifespan. The high selectivity, sensitivity, and potential stability of the proposed miniaturized electrode suggests its use for the determination of copper(II) ions in human blood serum and milk samples. The results obtained agree fairly well with data obtained by flameless atomic absorption spectrometry.

Assessment of Paracetamol Usage Practices and Perceptions among Caregivers for Children Post-COVID-19 in Saudi Arabia: A Cross-Sectional Analysis.

Caregivers often use paracetamol in the management of pediatric illnesses without a clear rationale. This study evaluated the perception and practices of caregivers regarding the use of paracetamol in children in Southwestern Saudi Arabia. This study involved a cross-sectional design involving 373 caregivers of children under twelve. The questionnaire elucidated the reasons, usage frequency, and safe usage practices. Data were analyzed using SPSS, applying Chi-square tests and logistic regression. Most caregivers were in the age range of 31-40 years, and with intermediate education. Paracetamol was mainly used for fever, generalized pain and, diarrhea, with fewer opting for other self-care measures. Caregivers with primary or less education were more likely to perceive paracetamol as safe (AOR = 2.98 (1.3-6.73), p = 0.009) and less inclined to check warning labels (AOR: 0.11 (0.05-0.25), p < 0.001) and expiry dates (AOR: 0.063 (0.027-0.14), p < 0.001). The caregiver's education level significantly influenced the determination of treatment duration (χ2 = 21.58 (4), p < 0.001), dosage (χ2 = 30.70 (4), p < 0.001), and frequency of administration (χ2 = 17.77 (4), p = 0.001). In conclusion, inadequate health literacy can result in a lack of attention towards crucial safety information about pediatric paracetamol use. Hence, counselling initiatives should be undertaken to ensure the safe and effective use of paracetamol in children.

Artificial Intelligence Electrocardiography to Predict Atrial Fibrillation in Patients With Chronic Lymphocytic Leukemia.

Background: The use of an artificial intelligence electrocardiography (AI-ECG) algorithm has demonstrated its reliability in predicting the risk of atrial fibrillation (AF) within the general population. Objectives: This study aimed to determine the effectiveness of the AI-ECG score in identifying patients with chronic lymphocytic leukemia (CLL) who are at high risk of developing AF. Methods: We estimated the probability of AF based on AI-ECG among patients with CLL extracted from the Mayo Clinic CLL database. Additionally, we computed the Mayo Clinic CLL AF risk score and determined its ability to predict AF. Results: Among 754 newly diagnosed patients with CLL, 71.4% were male (median age = 69 years). The median baseline AI-ECG score was 0.02 (range = 0-0.93), with a value ≥0.1 indicating high risk. Over a median follow-up of 5.8 years, the estimated 10-year cumulative risk of AF was 26.1%. Patients with an AI-ECG score of ≥0.1 had a significantly higher risk of AF (HR: 3.9; 95% CI: 2.6-5.7; P < 0.001). This heightened risk remained significant (HR: 2.5; 95% CI: 1.6-3.9; P < 0.001) even after adjusting for the Mayo CLL AF risk score, heart failure, chronic kidney disease, and CLL therapy. In a second cohort of CLL patients treated with a Bruton tyrosine kinase inhibitor (n = 220), a pretreatment AI-ECG score ≥0.1 showed a nonsignificant increase in the risk of AF (HR: 1.7; 95% CI: 0.8-3.6; P = 0.19). Conclusions: An AI-ECG algorithm, in conjunction with the Mayo CLL AF risk score, can predict the risk of AF in patients with newly diagnosed CLL. Additional studies are needed to determine the role of AI-ECG in predicting AF risk in CLL patients treated with a Bruton tyrosine kinase inhibitor.

Pharmaceutical applications of therapeutic deep eutectic systems (THEDES) in maximising drug delivery.

The issue of poor solubility of active pharmaceutical ingredients (APIs) has been a salient area of investigation and novel drug delivery systems are being developed to improve the solubility of drugs, enhance their permeability and thereby their efficacy. Several techniques for solubilization enhancement of poorly soluble drugs are often employed at various stages of pharmaceutical drug product development. One such delivery system is the therapeutic deep eutectic system (THEDES), which showed great potential in the enhancement of solubility and permeability of drugs and ultimately augmenting their bioavailability. THEDES are made by mixing drugs with deep eutectic solvents (DESs) in a definite molar ratio by the hit and trial method. The DESs are a new class of green solvents which are non-toxic, cheap, easy to prepare, biodegradable and have multiple applications in the pharmaceutical industry. The terminologies such as ionic liquids (ILs), DES, THEDES, and therapeutic liquid eutectic systems (THELES) have been very much in use recently, and it is important to highlight the pharmaceutical applications of these unexplored reservoirs in drug solubilization enhancement, drug delivery routes, and in the management of various diseases. This review is aimed at discussing the components, formulation strategies, and routes of administration of THEDES that are used in developing the formulation. Also, the major pharmaceutical applications of THEDES in the treatment of various metabolic and non-metabolic diseases are reviewed.

The Effect of Obesity on Severity of Asthma: An Observational Prospective Study from Pakistan.

Objective: The current research study aimed to access the relationship between obesity and asthma exacerbations and severity among adult patients at the outpatient section of a federal hospital (PIMS) in Islamabad, Pakistan. Methods: A cross-sectional research study was carried out on 207 asthma adult patients belonging to different areas and ethnic groups from the country. The study setting was the PIMS hospital, which attracts patients from all over the country due to its facilities and cost-effective treatments. The body mass index (BMI) of asthma patients was calculated using the heights and weights of the study subjects. However, the pulmonary functions were calculated using a computerized spirometer i-e Spirolab III S/N 303681 in line with Winspiro PRO 7.1.version software. It presents the patient's forced vital capacity that expires in the first second of expiration to full (FEV1) in comparison to forced vital capacity (FVC) ratio, that is, Tiffeneau-Pinelli index was also recorded to determine the asthma severity. Results: According to recent surveys, the overall prevalence of patients with overweight and obesity was 29.0% and 23.7%, respectively. A Chi-square test was used, and a statistically significant relationship was observed between BMI and asthma severity (P < 0.001). The adult obese female patients presented poor pulmonary functions. The average FEV1/FVC ratio presented significant variance among four different categories of BMI with P < 0.05. This difference was due to the normal BMI category as the Tiffeneau-Pinelli index, that is, FEV1/FVC in the normal BMI group was significantly lower as compared to that in underweight and obese patients. Conclusion: The study subjects presented raised asthma severity in accordance with the raised BMI. Obese patients presented comparatively raised asthma exacerbations. Moreover, a statistically significant association of gender difference was observed between obesity and asthma severity. It was concluded that adult asthmatic women with obesity presented raised asthma severity as compared to adult asthmatic males.

The Effectiveness of Denosumab in Middle Eastern Patients With Giant Cell Tumor of the Bone: A Single-Center, Retrospective Study.

BACKGROUND: Giant cell tumor of the bone (GCTB) is an aggressive benign tumor, which constitutes 5% of all primary bone tumors. Denosumab, a receptor activator of nuclear factor κB ligand monoclonal antibody, inhibits osteoclast-induced bone destruction and has demonstrated promising results in patients with GCTB. However, the long-term efficacy of the drug has not been extensively studied, especially in the Middle East. METHODOLOGY: In this study, we retrospectively analyzed the five-year progression-free survival (PFS) in patients with GCTB at a single Saudi center. PFS was defined as the time from diagnosis until disease progression, relapse, or death. Events were censored after five years from diagnosis. RESULTS: Sixty-two patients with GCTB were included in the study. The median age at diagnosis was 31.16 years, and 38 (61.3%) patients were female. Twenty-nine patients (46.8%) received denosumab during the study period. The median duration of denosumab treatment was 5.06 months, and the median number of cycles was 6. The median PFS was not reached, and the five-year PFS rate was 60.3%. Age, gender, body mass index, performance status at presentation, and tumor location had no impact on five-year PFS. Denosumab treatment prolonged PFS; however, this was not statistically significant compared to non-denosumab patients (P = 0.603). CONCLUSIONS: Denosumab does not seem to provide superior long-term outcomes compared to surgery alone. Although our findings are generally consistent with other studies in the literature, larger long-term studies are needed to confirm our findings.

Mesenchymal stromal cells with chimaeric antigen receptors for enhanced immunosuppression.

Allogeneic mesenchymal stromal cells (MSCs) are a safe treatment option for many disorders of the immune system. However, clinical trials using MSCs have shown inconsistent therapeutic efficacy, mostly owing to MSCs providing insufficient immunosuppression in target tissues. Here we show that antigen-specific immunosuppression can be enhanced by genetically modifying MSCs with chimaeric antigen receptors (CARs), as we show for E-cadherin-targeted CAR-MSCs for the treatment of graft-versus-host disease in mice. CAR-MSCs led to superior T-cell suppression and localization to E-cadherin+ colonic cells, ameliorating the animals' symptoms and survival rates. On antigen-specific stimulation, CAR-MSCs upregulated the expression of immunosuppressive genes and receptors for T-cell inhibition as well as the production of immunosuppressive cytokines while maintaining their stem cell phenotype and safety profile in the animal models. CAR-MSCs may represent a widely applicable therapeutic technology for enhancing immunosuppression.

Assessment of some toxic elements (Co, Cr, Mn, Se, and As) in muscle, offal, hair, and blood of camels (Camelus dromedaries) and their risk assessment.

Background: Camel meat tainted with heavy metals or trace elements may pose a health risk to consumers. Heavy metal contamination poses a severe danger due to both their toxicity and bioaccumulation in the food chain. Aim: To estimate the residual levels of heavy metals (Co, Cr, Mn, Se, and As) in muscle, liver, kidney, hair, and serum of three camel breeds (Magaheem, Maghateer, and Wadha) collected from Al-Omran abattoir, Al-Ahsa, Saudi Arabia. Methods: A total of 225 tissue samples (muscles, liver, kidney, serum, and hair) were taken and analyzed using an Atomic Absorption Spectrophotometer. Health risk assessment was assessed using the guidelines set by the US Environmental Protection Agency. Results: Camel breed significantly (p < 0.05) influences Co, Cr, Mn, and Se accumulation and distribution in organs and muscle; however, arsenic accumulation was not significantly affected (p < 0.05) by camel breeds. The highest values of Co, Cr, Se, and Mn in all examined samples were detected in the liver samples of Maghateer and Magaheem breeds. Furthermore, significant strong positive correlation between serum and liver cobalt, chromium, manganese, and arsenic. The estimated daily intake owing to camel meat consumption was less than the tolerated daily intake. Conclusion: Heavy metals were distributed among different breeds of camel. Trace elements (Pb and Cd) in meat and offal were below the international maximum permissible limit. The correlation between samples reflects the role of hair as a good tool for the identification of heavy metal pollution.

Sex estimation in the South-East Asian population: A systematic review.

INTRODUCTION: Sex estimation is crucial in forensic anthropology. In situations such as mass disasters, and forensic anthropology cases, sex estimation is a very important initial step in the disaster victim identification process. Literature has acknowledged that sex estimation is population-specific. However, sex estimation standards in South-East Asian populations are limited, leading to the usage of most Thais discriminant function equations on sex estimation by other South-East Asian countries including Malaysia. This systematic review was conducted to summarise the findings of sex estimation studies in South-East Asian countries. MATERIALS AND METHODS: A systematic literature search was performed through the SCOPUS database and Web of Science (WOS) database for relevant studies between 2014 and 2022. All published articles that are related to sex estimation from different types of bone, methods, landmarks, and sample sources (i.e., photographs, dry bones, and CT images) were included in this review. The main inclusion criteria were studies on (i) sex estimation; (ii) in South-East Asian populations; (iii) between the years 2014 and 2022; and (iv) in English. RESULTS: The literature search identified 30 potentially relevant studies, of which 15 publications met all the inclusion criteria. From those research, 13 studies were related to the Thai population and two to the Malaysian population. Only one study was based on morphological traits, while the rest were based on a morphometric approach. CONCLUSION: All studies found that sex estimation is populationspecific. Therefore, further research is recommended to explore more on population-specific sex estimation using different parts of bone.

The use and perceived value of electronic health information resources by health care professionals in the field of medicine, pharmacy, and nursing in Jazan province, Saudi Arabia.

Background: Healthcare workers increasingly use Electronic Health Information Resources (EHIRs) to make evidence-based decisions. Our study was intended to assess the perception, attitude, and practice of healthcare professionals in medicine, pharmacy, and nursing regarding their perceived value and use of EHIRs. Methods: We conducted an observational cross-sectional study using a pre-validated questionnaire among healthcare professionals in Jazan province from September 2022 to February 2023. We included healthcare professionals and interns with medical, pharmacy, or nursing degrees and excluded those who refused informed consent. Results: We included fully completed data from 294 participants, with an actual response rate of just 80.1 %. Almost 87.41 % utilized the health information resources at their workplace, with UpToDate [39.45 %] and Medscape [67.01 %] being the most frequently used medical databases. The health facilities' access to electronic health resources significantly impacted healthcare professionals' [p = 0.04] and medical interns' [p = 0.02] roles. Faculty members felt the need to access electronic health information at their workplace [p = 0.00]. Lack of time to access electronic health information due to a busy schedule was a significant reason that impacted the attitude of medical professionals [p = 0.008] and nursing staff [p = 0.025]. An excessive amount of clinically unrelated data was the primary obstacle (181/294, p < 0.0001) in using electronic health information resources. Conclusion: Our study showed the pattern of healthcare professionals using EHIRs in the Jazan province, Saudi Arabia. We believe the study's outcome can help increase the calibre of electronic health information services available to healthcare professionals and raise awareness of different EHIRs in improving clinical care.

Pediatric Anesthesia Exposure: Decoding Its Neurodevelopmental Implications and Navigating the Nuances.

General anesthesia is fundamental in pediatric medical interventions, but its potential neurodevelopmental impact on children has raised concerns, necessitating a thorough investigation. This systematic review aimed to assess the association between pediatric anesthesia exposure and neurodevelopmental outcomes, focusing on dosage effects and identifying high-risk groups. The study involved an extensive literature search across PubMed, Medline, and Google Scholar, selecting 40 relevant studies from an initial pool of 2,000, based on inclusion criteria that focused on children under 18 years exposed to anesthesia, excluding those with major comorbidities or perioperative physiological insults. It was observed that while a single exposure to anesthesia had minimal impact on general neurodevelopment, repeated or prolonged exposures posed greater concerns. Despite these findings, the study identified gaps in certain areas like adaptive behavior and sensory cognition due to limited data. The conclusion drawn is that although the evidence on anesthesia-induced neurotoxicity in children remains inconclusive, the implications of pediatric anesthesia exposure are significant enough to warrant careful consideration by healthcare professionals, who should balance the procedural benefits against the risks. This study also calls for future research to standardize methodologies and employ consistent, validated neurodevelopmental measurement tools.

Awareness and prevalence of self-reported benign prostatic hyperplasia: a cross-sectional study in Saudi Arabia.

Background: Benign prostatic hyperplasia (BPH) is a prevalent condition in older men, causing significant morbidity. Despite recent progress, essential concerns of the disease remain under-researched. This study aims to assess knowledge and estimate self-reported prevalence of BPH in Saudi Arabian men. Understanding BPH prevalence in Saudi Arabia is essential for healthcare planning, resource allocation, public awareness, early detection, intervention, research, and addressing regional variations. Method: A cross-sectional study was conducted from February to May 2022 using a validated questionnaire. Univariate and multivariate statistical methods assessed knowledge of BPH among 559 adult Saudi men (mean age: 47.2 years) and its association with demographic variables. Results: The self-reported prevalence rate of BPH for Saudi Arabian men was 12.0%. Most adults (74.2%) were aware that BPH is a risk factor for prostate cancer and 75% were aware of the increased risk of BPH in older people. Furthermore, 44.5% of participants associated nocturia with BPH, while 76.6% related urinary tract infection (UTI) with BPH. The study demonstrated a significant association between BPH awareness and marital status (p = 0.02), level of education (p = 0.02), and employment status (p = 0.04). Conclusion: While men in Saudi Arabia generally had sufficient knowledge about BPH, there was a knowledge gap regarding certain risk factors like obesity and cardiac diseases. To address this, an educational program should be developed for both the general population and those at high risk of BPH.

A multicenter study of venetoclax-based treatment for patients with Richter transformation of chronic lymphocytic leukemia.

ABSTRACT: Patients with chronic lymphocytic leukemia (CLL) who develop Richter transformation (RT) have a poor prognosis when treated with chemoimmunotherapy regimens used for de novo diffuse large B-cell lymphoma. Venetoclax, a BCL2 inhibitor, has single-agent efficacy in patients with RT and is potentially synergistic with chemoimmunotherapy. In this multicenter, retrospective study, we evaluated 62 patients with RT who received venetoclax-based treatment outside of a clinical trial, in combination with a Bruton tyrosine kinase inhibitor (BTKi; n=28), rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) (n=13), or intensive chemoimmunotherapy other than R-CHOP (n=21). The best overall and complete response rates were 36%/25%, 54%/46%, and 52%/38%, respectively. The median progression-free and overall survival estimates for the same treatment groups were 4.9/14.3 months, 14.9 months/not reached, and 3.3/9 months, respectively. CLL with del(17p) was associated with a lower complete response rate in the total cohort (odds ratio [OR] 0.15; 95% confidence interval [CI] 0.04-0.6; p=0.01) and venetoclax-naïve subgroup (OR 0.13; 95%CI 0.02-0.66; p=0.01). TP53 mutated CLL was associated with a lower complete response rate (OR 0.15; 95%CI 0.03-0.74; p=0.02) and shorter progression-free survival (hazard ratio 3.1; 95%CI 1.21-7.95; p=0.02) only in venetoclax-naïve subgroup. No other clinical or baseline characteristics, including prior venetoclax treatment for CLL, showed statistically significant association with outcomes. Grade 3-4 neutropenia and thrombocytopenia events were most frequent with intensive chemoimmunotherapy + venetoclax; grade 3-4 infection rates were similar across treatment groups. In this difficult-to-treat RT patient population, venetoclax-based combination regimens achieved high response rates, with durable remission and survival observed in a subset of patients.