A male steroid controls female sexual behaviour in the malaria mosquito.

Insects, unlike vertebrates, are widely believed to lack male-biased sex steroid hormones1. In the malaria mosquito Anopheles gambiae, the ecdysteroid 20-hydroxyecdysone (20E) appears to have evolved to both control egg development when synthesized by females2 and to induce mating refractoriness when sexually transferred by males3. Because egg development and mating are essential reproductive traits, understanding how Anopheles females integrate these hormonal signals can spur the design of new malaria control programs. Here we reveal that these reproductive functions are regulated by distinct sex steroids through a sophisticated network of ecdysteroid-activating/inactivating enzymes. We identify a male-specific oxidized ecdysteroid, 3-dehydro-20E (3D20E), which safeguards paternity by turning off female sexual receptivity following its sexual transfer and activation by dephosphorylation. Notably, 3D20E transfer also induces expression of a reproductive gene that preserves egg development during Plasmodium infection, ensuring fitness of infected females. Female-derived 20E does not trigger sexual refractoriness but instead licenses oviposition in mated individuals once a 20E-inhibiting kinase is repressed. Identifying this male-specific insect steroid hormone and its roles in regulating female sexual receptivity, fertility and interactions with Plasmodium parasites suggests the possibility for reducing the reproductive success of malaria-transmitting mosquitoes.

Dissecting mechanisms of chamber-specific cardiac differentiation and its perturbation following retinoic acid exposure.

The specification of distinct cardiac lineages occurs before chamber formation and acquisition of bona fide atrial or ventricular identity. However, the mechanisms underlying these early specification events remain poorly understood. Here, we performed single cell analysis at the murine cardiac crescent, primitive heart tube and heart tube stages to uncover the transcriptional mechanisms underlying formation of atrial and ventricular cells. We find that progression towards differentiated cardiomyocytes occurs primarily based on heart field progenitor identity, and that progenitors contribute to ventricular or atrial identity through distinct differentiation mechanisms. We identify new candidate markers that define such differentiation processes and examine their expression dynamics using computational lineage trajectory methods. We further show that exposure to exogenous retinoic acid causes defects in ventricular chamber size, dysregulation in FGF signaling and a shunt in differentiation towards orthogonal lineages. Retinoic acid also causes defects in cell-cycle exit resulting in formation of hypomorphic ventricles. Collectively, our data identify, at a single cell level, distinct lineage trajectories during cardiac specification and differentiation, and the precise effects of manipulating cardiac progenitor patterning via retinoic acid signaling.

Comparative Analysis of Calcium and Hydroxyl Ion Release from Pulp Dressing Materials in Pulpotomized Premolars.

BACKGROUND The aim of this study was to evaluate the time-dependent release of calcium (Ca⁺⁺) and hydroxyl (OH⁻) ions from 3 different pulp dressing materials used to cap root canal orifices in pulpotomized premolars. MATERIAL AND METHODS Freshly extracted (n=40) premolars were subjected to standardized pulpotomy procedure and finally restored in 5 groups using resin-modified glass ionmmer liner (RMGI) and bonded resin composite directly against the pulp chamber's floor (Control, G2) and over 3 different orifices' capping materials - Dycal (G3), Endo Sequence root repair material (ESRRM, G4), and mineral trioxide aggregate (MTA) Angelus (G5). Another 10 sound premolars served as the Reference group (G1). The restored teeth were incubated at 37±1°C in sealed containers filled with deionized water to assess Ca⁺⁺ and OH⁻ ions release after 24 h and at 1, 4, and 8 weeks. Two-way ANOVA and Tukey's comparisons at alpha=0.05 were used to statistically analyze the collected data. RESULTS Two-way ANOVA revealed significant differences in Ca⁺⁺ ions between test groups at different testing time intervals (P<0.05). Despite the constant (Tukey's, P<0.05) pH levels (OH⁻ release), Group 5 specimens exhibited higher Ca⁺⁺ ion release in comparison to Groups 4 and 3 at different testing timepoints (Tukey's, P<0.05). CONCLUSIONS Although all the assessed pulp dressing materials had equivalent and stable pH levels, ESRRM and MTA-Angelus had the highest Ca⁺⁺ ion release at the assessment intervals.

Detecting Cyber Attacks In-Vehicle Diagnostics Using an Intelligent Multistage Framework.

The advanced technology of vehicles makes them vulnerable to external exploitation. The current trend of research is to impose security measures to protect vehicles from different aspects. One of the main problems that counter Intrusion Detection Systems (IDSs) is the necessity to have a low false acceptance rate (FA) with high detection accuracy without major changes in the vehicle network infrastructure. Furthermore, the location of IDSs can be controversial due to the limitations and concerns of Electronic Control Units (ECUs). Thus, we propose a novel framework of multistage to detect abnormality in vehicle diagnostic data based on specifications of diagnostics and stacking ensemble for various machine learning models. The proposed framework is verified against the KIA SOUL and Seat Leon 2018 datasets. Our IDS is evaluated against point anomaly attacks and period anomaly attacks that have not been used in its training. The results show the superiority of the framework and its robustness with high accuracy of 99.21%, a low false acceptance rate of 0.003%, and a good detection rate (DR) of 99.63% for Seat Leon 2018, and an accuracy of 99.22%, a low false acceptance rate of 0.005%, and good detection rate of 98.59% for KIA SOUL.

The Mitochondrial mitoNEET Ligand NL-1 Is Protective in a Murine Model of Transient Cerebral Ischemic Stroke.

PURPOSE: Therapeutic strategies to treat ischemic stroke are limited due to the heterogeneity of cerebral ischemic injury and the mechanisms that contribute to the cell death. Since oxidative stress is one of the primary mechanisms that cause brain injury post-stroke, we hypothesized that therapeutic targets that modulate mitochondrial function could protect against reperfusion-injury after cerebral ischemia, with the focus here on a mitochondrial protein, mitoNEET, that modulates cellular bioenergetics. METHOD: In this study, we evaluated the pharmacology of the mitoNEET ligand NL-1 in an in vivo therapeutic role for NL-1 in a C57Bl/6 murine model of ischemic stroke. RESULTS: NL-1 decreased hydrogen peroxide production with an IC50 of 5.95 µM in neuronal cells (N2A). The in vivo activity of NL-1 was evaluated in a murine 1 h transient middle cerebral artery occlusion (t-MCAO) model of ischemic stroke. We found that mice treated with NL-1 (10 mg/kg, i.p.) at time of reperfusion and allowed to recover for 24 h showed a 43% reduction in infarct volume and 68% reduction in edema compared to sham-injured mice. Additionally, we found that when NL-1 was administered 15 min post-t-MCAO, the ischemia volume was reduced by 41%, and stroke-associated edema by 63%. CONCLUSION: As support of our hypothesis, as expected, NL-1 failed to reduce stroke infarct in a permanent photothrombotic occlusion model of stroke. This report demonstrates the potential therapeutic benefits of using mitoNEET ligands like NL-1 as novel mitoceuticals for treating reperfusion-injury with cerebral stroke.

Overcoming the acquired resistance to gefitinib in lung cancer brain metastasis in vitro and in vivo.

In our previous work, PC-9-Br, a PC-9 brain seeking line established via a preclinical animal model of lung cancer brain metastasis (LCBM), exhibited not only resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib in vitro, but also chemotherapy regimens of cisplatin plus etoposide in vivo. Using this cell line, we investigated novel potential targeted therapeutics for treating LCBM in vitro and in vivo to combat drug resistance. Significant increases in mRNA and protein expression levels of Bcl-2 were found in PC-9-Br compared with parental PC-9 (PC-9-P), but no significant changes of Bcl-XL were observed. A remarkable synergistic effect between EGFR-TKI gefitinib and Bcl-2 inhibitors ABT-263 (0.17 ± 0.010 µM at 48 h and 0.02 ± 0.004 µM at 72 h), or ABT-199 (0.22 ± 0.008 µM at 48 h and 0.02 ± 0.001 µM at 72 h) to overcome acquired resistance to gefitinib (> 0.5 µM at 48 h and 0.10 ± 0.007 µM at 72 h) in PC-9-Br was observed in MTT assays. AZD9291 was also shown to overcome acquired resistance to gefitinib in PC-9-Br in MTT assays (0.23 ± 0.031 µM at 48 h and 0.03 ± 0.008 µM at 72 h). Western blot showed significantly decreased phospho-Erk1/2 and increased cleaved-caspase-3 expressions were potential synergistic mechanisms for gefitinib + ABT263/ABT199 in PC-9-Br. Significantly decreased protein expressions of phospho-EGFR, phospho-Akt, p21, and survivin were specific synergistic mechanism for gefitinib + ABT199 in PC-9-Br. In vivo studies demonstrated afatinib (30 mg/kg) and AZD9291 (25 mg/kg) could significantly reduce the LCBM in vivo and increase survival percentages of treated mice compared with mice treated with vehicle and gefitinib (6.25 mg/kg). In conclusion, our study demonstrated gefitinib + ABT263/ABT199, afatinib, and AZD9291 have clinical potential to treat LCBM.

Impact of Glyphosate-Roundup® in the Ileal Structure of Male and Female Rats: A Morphological and Immunohistochemical Study.

The current study was aimed to evaluate the effects of variable doses of the weedicide glyphosate on the ileal (the final section of the small intestine) structure of rats of both sexes, using histological, histochemical, and ultrastructural methods. Forty animals were classified into four groups of 10 animals per group (five males and five females). The first group acted as a control, and the remaining groups were treated with glyphosate-Roundup® 25, 50, and 100 mg/kg body weight daily for 15 days. The results indicated extinct histopathological changes manifested in the deformation of villi, foci of leukocytic infiltration in the core of villi, and hyperplasia of goblet cells. Histochemical examination (Alcian blue and Periodic acid-Schiff stain) revealed a strong positive reaction of goblet cells and an increase in their number in all treated groups. In addition, the immunohistochemical investigation revealed the immunoreactivity of matrix metalloproteinase-9 expression. Furthermore, electron microscopic alternations were represented by the deformation of nuclei, destruction of microvilli, and deposition of lipid droplets. Collectively, the present findings indicate that treatment with glyphosate results in extensive morphological alternations to the ileal structure of rats of both sexes and that female rats are more affected than male rats are.

Knowledge, attitudes and practices of community pharmacists on generic medicines in Palestine: a cross-sectional study.

BACKGROUND: Generic substitution in several countries has become a common practice. Besides, it is considered as a major cost minimizing strategy meant to contain pharmaceutical expenditure without compromising healthcare quality. However, the safety and quality issues of generic products are of top concerns of general practitioners and health work professionals. This study aimed to investigate community pharmacist's knowledge, attitudes and practices toward generic medicines in Palestine. METHODS: This study was a cross-sectional observational study employing a self-administered questionnaire. The questionnaire was of four main sections: demographic and practice details of the participants, knowledge, attitudes and the influencing factors related to selection and dispensing of generic medicines. A convenience sampling technique was implemented in this study in which the data collection form was distributed in West Bank- Palestine among a set of practicing pharmacists. Mann-Whitney-U or Kruskal-Wallis tests were used to comparison of different issues as appropriate. P-values of <0.05 were considered significant. RESULTS: A total of 302 community pharmacists were interviewed, slightly more than half were males (52.3%). The mean knowledge score of participants regarding generic medicines was (5.91 ± 1.27) where the highest score was 8 of 10. Knowledge score was not significantly influenced by any of the socio-demographic characteristics. Our data showed that most of included pharmacists in the study (95.4%) agreed that health authorities should implement bioequivalence policies prior to marketing approval of generics, while 87.4% of participants agreed that they should be given the right to substitute generics and the majority (62.3%) support generic substitution for brand name drugs in all cases when a generic is available The main two factors affect pharmacists' selection and dispensing of generic medicines are personal faith in the product (86.1%) and cost effectiveness of generic medicines (84.1%). CONCLUSIONS: Generic medicines substitution among pharmacists is widespread and prevalent. Our data found that participant pharmacists in Palestine had basic knowledge with regards to generic medicine. However, their knowledge score pertaining the technical and regulatory aspects of bioequivalence and pharmacokinetic parameters in particular was insufficient.

Reducing unnecessary testing: an intervention to improve resident ordering practices.

PURPOSE OF THE STUDY: To reduce the number of unnecessary laboratory tests ordered through a measurement of effects of education and cost awareness on laboratory ordering behaviour by internal medicine residents for common tests, including complete blood cell count (CBC) and renal profile (RP), and to evaluate effects of cost awareness on hospitalisation, 30-day readmission rate and mortality rate. STUDY DESIGN: 567 patients admitted during February, March and April 2014 were reviewed as the control group. Total CBC, CBC with differential and RP tests were counted, along with readmission and mortality rates. Interventions were education and visual cost reminders. The same tests were reassessed for 629 patients treated during 12 months after intervention in 2015. RESULTS: Data showed a significant increase in CBCs ordered after the intervention (mean number per hospitalisation changed from 1.7 to 2.3 (p<0.001)), a decrease in CBCs with differential (mean number changed from 1.7 to 1.2 (p<0.001)) and no change in RPs ordered (mean number, 3.7 both before and after intervention (p=0.23)). No change was found in mortality rate, but the decrease in the readmission rate was significant (p=0.008). CONCLUSIONS: Education in the form of cost reminders did not significantly reduce the overall ordering of the most common daily laboratory testing in our academic teaching service. We believe further research is needed to fully evaluate the effectiveness of other education forms on the redundant ordering of tests in the hospital setting.

Adverse pregnancy outcome among teenagers: a reality?

The objective of this retrospective analysis was to evaluate maternal, fetal and neonatal outcomes in primi-adolescent pregnancies in Kuwait. Case records of primigravidae under 29 years of age, attending the antenatal clinic at our tertiary hospital, between January 2002 and December 2010, were analysed. The study group (up to 19 years of age at first pregnancy) consisted of 3,863 women and the control group (20-29 years of age at first pregnancy) comprised of 4,416 women. Maternal obstetric, fetal and neonatal complications were compared between the groups. Rates of ectopic pregnancy, pre-eclampsia, eclampsia, preterm labour, premature rupture of membrane and caesarean section were significantly higher among adolescents < 15 years of age; the risk then decreased steadily with age and became comparable with the control group after 16 years of age.

Assessing Awareness, Knowledge, and Attitude of Saudi Mothers Regarding Shaken Baby Syndrome in the Eastern Province of Saudi Arabia: A Cross-Sectional Prospective Study.

Shaken baby syndrome (SBS) is a form of traumatic brain injury. Shaking babies can cause the brain matter to bounce within the cranium causing bruising and bleeding, which can result in permanent brain injury. Understanding the attitudes and knowledge of mothers on SBS would help establish effective interventions to raise awareness and establish preventive measures and education programs to avoid debilitating sequelae from SBS in newborns and infants. This study aimed to explore the awareness and attitude regarding SBS. An observational, cross-sectional study was conducted from April 1st through July 31st, 2023. The study population is comprised of mothers who are residents of the Eastern Province of Saudi Arabia and excluded females with no children and those who refused to participate, in addition to mothers not in the Eastern Province. The final sample size included 403 participants. An online-based validated questionnaire was used in the Arabic language. The questionnaire included demographic information and questions to assess the knowledge and attitude of participants regarding SBS. The chi-square test was used to test for significant associations. The majority of the participants were married (72%), while 15.6% were divorced and 10.2% were widowed. Only 7.4% of the participants were illiterates, 30.5% had primary education only, and 15.9% had postgraduate studies. Of note, 37% of the participants said that they would shake their children to calm them if they started to cry. Only 33% of the participants said that shaking babies is harmful. The most commonly reported complications of shaking babies were intracranial bleeding (48.1%), behavioral changes (23.8%), and learning disability (23.5%). Regarding attitude toward SBS, more than two-thirds (72.5%) of the participants said that they want to know more about SBS. Only the educational level had statistically significant relationship between the awareness and the sociodemographic level of the participants. This study concludes that Saudi mothers' knowledge about SBS is inadequate despite the favorable attitude toward gaining information about it. The awareness level is significantly associated with educational status, which reflects the importance of education programs, especially during the pregnancy period, in raising awareness about SBS and its complications.

Epidemiology, microbiological, clinical characteristics, and outcome of Burkholderia cepacia complex infections in non-cystic fibrosis adult patients from Qatar.

Objectives: Burkholderia species infections are associated with diverse and challenging clinical presentations because of distinct virulence and antimicrobial resistance factors. The study aims to evaluate the epidemiology, microbiological, and clinical outcomes of Burkholderia cepacia complex (Bcc) infections in non-cystic fibrosis (CF) patients from Qatar. Methods: A retrospective study was conducted on adult patients across all hospitals at Hamad Medical Corporation between January 2012 and December 2018 to evaluate clinically relevant Bcc in non-CF adult patients. Results: Over 7 years, 72 episodes of Burkholderia species infections were recorded, 64 were secondary to Bcc primarily affecting males (78.12%) with a mean age of 53 years, from the Middle and Southeastern region (92.2%) affected predominantly by diabetes mellitus (34.4%), chronic kidney (23.4%), coronary heart (20.3%), and hypertensive diseases (17.2%) while recent hospitalization and admission to critical care were evident in 45.3% and 93.8% of cases, respectively. Main infection sites were urinary (43.8%) and respiratory (29.7%) with associated bacteremia recorded in 26.6% of cases. Microbiological characteristics demonstrated high-level resistance profiles leading to delayed microbiological clearance in case of bacteremia (61%) and management with multiple therapeutic agents (range 4-6) resulting in disease resolution in 90.6% of cases with observed 30-day mortality of 7.8%. Conclusions: B. cepacia infections are infrequent, recorded mainly in middle-aged males with chronic comorbidities presenting as urinary, respiratory, and bacteremia associated with hospitalization, admission to critical care, and invasive procedures. High-level antimicrobial resistance is observed necessitating multiple therapeutic agents and suboptimal bacteriological clearance.

Endogenous Purulent Pericarditis Due to Klebsiella aerogenes in a Patient With Traumatic Chest Injury: A Case Report.

Purulent pericarditis is a rare but serious medical condition caused by an infection that spreads to the pericardial space surrounding the heart. Gram-positive organisms are the most common pathogens associated with purulent pericarditis. However, there has been a shift in recent years toward gram-negative bacteria. Klebsiella aerogenes is a rare pathogen that has never been linked to purulent pericarditis. In this report, we describe the case of a 40-year-old male patient with chronic bronchiectasis who, two months after suffering an injury, developed purulent pericarditis due to an uncommon organism, K. aerogenes. During his stay in the hospital, the patient developed several infections caused by K. aerogenes. These included bacteremia and ventilator-associated pneumonia (VAP). Beta-lactamase-inducible K. aerogenes was grown in pericardial fluid culture following an emergency pericardiocentesis. The organism was resistant to carbapenems in a sputum culture, even though it was sensitive to meropenem in a blood culture. The patient had hypotension, requiring inotropes, and continued persistent bacteremia due to K. aerogenes. The patient had a heart attack with no pulse or electrical activity and died despite getting the best care possible. In light of this example, it is crucial to think about K. aerogenes and other rare organisms as possible pathogens in purulent pericarditis, especially in people who do not normally have known risk factors for this condition. Multidrug resistance patterns can make treatment more complicated, and aggressive care may be necessary in critically ill patients with chronic bacteremia.

Are current clinical trials in diabetes addressing important issues in diabetes care?

AIMS/HYPOTHESIS: Clinical trials assessing interventions for treating and preventing diabetes mellitus and its complications are needed to inform evidence-based practice. To examine whether current studies adequately address these needs, we conducted a descriptive analysis of diabetes-related trials registered with ClinicalTrials.gov from 2007 to 2010. METHODS: From a dataset including 96,346 studies registered in ClinicalTrials.gov downloaded on 27 September, 2010, a subset of 2,484 interventional trials was created by selecting trials with disease condition terms relevant to diabetes. RESULTS: Of the diabetes-related trials, 74.8% had a primarily therapeutic purpose while 10% were preventive. Listed interventions included drugs (63.1%) and behavioural (11.7%). Most trials were designed to enrol ≤ 500 (91.1%) or ≤ 100 (58.6%) participants, with mean/median times to completion of 1.8/1.4 years. Small percentages of trials targeted persons aged ≤ 18 years (3.7%) or ≥ 65 years (0.6%), while 30.8% excluded patients >65 years and the majority excluded those >75 years. Funding sources included industry (50.9%), NIH (7.5%) or other, with most being single-centre trials of other sponsorship (37.7%) or industry-funded multicentre studies (27.4%). A small number of trials (1.4%) listed primary outcomes including mortality or clinically significant cardiovascular complications. The distribution of trials by global region and US state does not correlate with prevalence of diabetes. CONCLUSIONS/INTERPRETATION: The majority of diabetes-related trials include small numbers of participants, exclude those at the extremes of age, are of short duration, involve drug therapy rather than preventive or non-drug interventions and do not focus upon significant cardiovascular outcomes. Recently registered diabetes trials may not sufficiently address important diabetes care issues or involve affected populations.

Bilateral, Symmetrical, Congenital Becker's Nevus Melanosis: A Rare Presentation and Review of the Literature.

Becker's nevus, also known as Becker's melanosis or Becker's pigmentary hamartoma, is a concurrent melanosis first described by S. William Becker. It is a type of acquired hyperpigmentation characterized by well-defined, unilateral lesions with regular borders. It is associated with hypertrichosis and hyperpigmented brownish patches with a mean diameter of 15 cm. The shoulder, scapular area, and upper arms are the most commonly affected areas, but it can occur on any area of the body, including the forehead, face, neck, lower trunk, extremities, and buttocks. The lesion usually appears around puberty, and males are more likely to be affected than females. A 27-year-old male of Arabic descent who was medically free presented to the dermatology clinic complaining of bilateral, symmetrical, hyperpigmented patches on the upper back. The lesions started almost at birth, gradually growing in size and darkening in color over time. On local skin examination, the lesions were bilateral, symmetrical, hyperpigmented patches on the upper back. They were both homogeneous and brown in color with irregular borders and blotchy hyperpigmented macules on both sides of the upper back associated with sparse hair development. Histopathological examination revealed epidermal hyperkeratosis, acanthosis, and focal regular elongation of rete ridges with clubbing. Increased basal layer pigmentation was noticed. The dermis showed focal areas with pigment incontinence. Based on the above clinicopathological findings, the patient was diagnosed with Becker's melanosis. He was referred to the laser clinic for further treatment.

Evaluation of the Awareness, Beliefs, and Psychological Impact of Patients with Alopecia Areata in Makkah City, Saudi Arabia.

Methods: A descriptive cross-sectional study was conducted among patients diagnosed with AA at different hospitals. A total of 211 patients were included in the investigation between November 2021 and June 2022. The participants were subjected to a well-structured, Arabic-based, validated questionnaire. Results: More than half of the patients were men (54.0%) and single (50.7%). The most common age groups were 30 to 44 years (46.9%) and 18 to 29 years (36.0%). More than two-thirds of the participants (67.8%) had heard of AA before their diagnosis. Of these, the level of knowledge was low among 36.4%, medium among 42.0%, and high among 21.7%. Most of the patients believed that AA may be caused by genetic, nutritional, or health factors (77.3%) and that it is a serious health problem that necessitates treatment (64.0%). The most common psychological attributes caused by AA are feeling ashamed in front of other individuals (63.0%), anxiety (47.9%), and depression (36.0%). Conclusion: Our results show more than two-thirds of the participants were knowledgeable about AA. Most believed that the cause of AA is genetic, nutritional, or health factors and suffered negative psychological effects. According to our study, high levels of anxiety and depression are closely associated with AA patients, which affect their quality of life.

Combined Cancer Immunotheranostic Nanomedicines: Delivery Technologies and Therapeutic Outcomes.

Cancer is among the main causes of mortality all over the world. The delayed diagnosis is directly related to the decrease in survival rate. The use of immunotherapy has dramatically changed the treatment outcomes of different types of cancers. However, many patients still do not respond to immunotherapies, and many also suffer from severe immune-related side effects. Recent advances in the fields of nanomedicine bioengineering and in particular imaging offered new approaches which can enhance not only the safety but also the efficacy of immunotherapy. Theranostics has showed great progress as a branch of medicine which integrates both diagnosis and therapy in a single system. The outcomes from animal studies demonstrated an improvement in the diagnostic and immunotherapeutic potential of nanoparticles within the theranostic framework. Herein, we discuss the most recent developments in the application of nanotheranostics for combining tumor imaging and cancer immunotherapies.

Dietary Effects of Nanopowder Eggshells on Mineral Contents, Bone Turnover Biomarkers, and Regulators of Bone Resorption in Healthy Rats and Ovariectomy-Induced Osteoporosis Rat Model.

Postmenopausal osteoporosis is a critical issue for female health worldwide. This current study was designed to evaluate the role of nanopowder eggshell (NPES) in healthy and ovariectomy-induced osteoporosis rats. Fifty-six female rats were divided into healthy rats (35) and ovariectomized rats (21). The healthy rats were subdivided into five groups (G1-G5) and received one of the following treatments: saline, 20 or 40 mg/kg of calcium carbonate, and 20 or 40 mg/kg of NPES. The 21 ovariectomized rats were divided into three groups (G6-G8) and received either saline, 40 mg/kg of calcium carbonate, or 40 mg/kg of NPES. Biochemical and histopathological assessments of bone formation and resorption were performed. Biomarkers of bone formation (calcium and osteocalcin (OCN)) and calcium content in left femur ashes were significantly higher in healthy rats given 40-mg/kg NPES than in healthy control rats and healthy rats given 40-mg/kg calcium carbonate. The ovariectomized groups had significantly lower levels of vitamin D3, OCN, and osteoprotegerin (OPG) than the healthy control. Alanine transaminase (ALT), alkaline phosphatase (ALP), and receptor activator of nuclear factor-κB ligand (RANKL) were significantly increased in the ovariectomized group than in the healthy control group. Treatment with NPES and calcium carbonate reduced liver enzymes in ovariectomized rats. NPES treatment significantly increased Vit D3, OCN, OPG, and bone ash mineral content (calcium, magnesium, zinc, and phosphorus) in ovariectomized rats. NPES also increased femur cortical thickness, osteoblast number, and collagen fiber. The current study suggests that NPES can modulate bone turnover biomarkers and increase bone trace elements. Moreover, NPES alleviates bone resorption in ovariectomy-induced osteoporosis.

The Occurrence of Depression Among Adults With Sickle Cell Disease in Saudi Arabia.

Introduction Sickle cell disease (SCD) is recognized as a widely prevalent genetic disorder that impacts individuals globally and is inherited within families. The primary cause of SCD is a singular genetic mutation that affects the globin chain of the hemoglobin protein. Depression and its symptoms are frequently observed in individuals with SCD. This observation has led to a higher probability of adverse health outcomes. Therefore, the primary objective of this study was to analyze depression among Saudi Arabian adults with sickle cell disease. Method The online survey questionnaire was administered in both Arabic and English to collect essential information regarding SCD distress among the urban adult population in Saudi Arabia, using a cross-sectional study design. Data analysis was conducted using IBM SPSS software version 25 (IBM Corp., Armonk, NY, USA) and Microsoft Excel (Microsoft Corporation, Redmond, WA, USA). The study was designed with a statistical power of 80% at a cut-off value of 0.05 and 0.2. Diverse statistical approaches have been utilized to examine the connection between independent variables, including methods such as Chi-square analysis and Pearson's statistical assessment. Result A total of 685 respondents were included in the survey for this study, with the majority of the participants from the eastern region (31%) and between the age groups of 25 and 30 years (34%) showing a lot of enthusiasm There was a clear dominance of the Saudi population (71%) who spoke Arabic (83%). Female (65%) participants showed more interest in this survey. The collected data were organized comprehensively in tables to facilitate a better understanding of the study's findings. P-values less than 0.05 were considered significant for the obtained results. Conclusion The study has shown that there were a variety of depression entanglements as a result of SCD, but they were handled well with the necessary measures by medical care professionals with much-needed psychological counseling and well-equipped medical facilities.

Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy.

Patients with metastatic breast cancer have high and continually increasing rates of brain metastases. During the course of the disease, brain metastases can occur in up to 30% of these patients. In most cases, brain metastases are diagnosed after significant disease progression. The blood-tumor barrier increases the difficulty of treating brain metastasis by preventing accumulation of chemotherapy within metastases at therapeutically effective concentrations. Traditional therapies, such as surgical resection, radiotherapy, and chemotherapy, have poor efficacy, as reflected by a low median survival rate of 5-8% after post-diagnosis. Low-intensity focused ultrasound (LiFUS) is a new treatment for enhancing drug accumulation within the brain and brain malignancies. In this study, we elucidate the effect of clinical LiFUS combined with chemotherapy on tumor survival and progression in a preclinical model of triple-negative breast cancer metastasis to the brain. LiFUS significantly increased the tumor accumulation of 14C-AIB and Texas Red compared to controls (p< 0.01). LiFUS-mediated opening of the BTB is size-dependent, which is consistent with our previous studies. Mice receiving LiFUS with combinatorial Doxil and paclitaxel showed a significant increase in median survival (60 days) compared to other groups. LiFUS plus combinatorial chemotherapy of paclitaxel and Doxil also showed the slowest progression of tumor burden compared to chemotherapy alone or individual chemotherapy and LiFUS combinations. This study shows that combining LiFUS with timed combinatorial chemotherapeutic treatment is a potential strategy for improving drug delivery to brain metastases.