Successful medical management of a pituitary macroadenoma with features of resistant acromegaly and hyperprolactinemia using pasireotide.

BACKGROUND: The somatostatin analog, pasireotide, is used for the treatment of acromegaly after the failure of surgery and/or first-line medical treatment. CASE PRESENTATION: A 48-year-old male reported that during a workup for obesity in his home country, hyperprolactinemia was diagnosed and a 3.5 × 3.5 cm pituitary macroadenoma was identified on pituitary MRI. He received cabergoline for 6 months; then he was lost to follow-up. He presented at our Endocrine clinic 2 years later for treatment of obesity (BMI 49.5 kg/m2). Biochemical workup revealed that in addition to hyperprolactinemia (7,237 [normal: 85-323 mIU/L), he had acromegaly, evident by elevated insulin-like growth factor 1 (IGF-1) level (450 [normal: 88-210 µg/L]), and a positive growth hormone suppression test, secondary hypothyroidism, and secondary hypogonadism. Pituitary MRI showed that the adenoma encased parts of the left and right internal carotid arteries and encroached on the optic chiasm. Surgical excision was therefore not feasible. He was treated with cabergoline and later, long-acting release (LAR) octreotide. Prolactin levels were reduced with cabergoline, but IGF-1 levels did not respond to octreotide, and it was discontinued. The patient abandoned radiotherapy after two sessions. He was started on LAR pasireotide 40 mg every 4 weeks and continued on cabergoline 0.5 mg per week. His biochemical response was dramatic, with a near normalization of IGF-1 levels in 3 months. After 6 months from starting pasireotide, we increased cabergoline dose from 0.5 mg/week to 3 mg/week. Three months later, IGF-1 level was normalized. The patient developed type 2 diabetes as a side effect of pasireotide; however, this was well-controlled with medications. CONCLUSIONS: The case suggests that pasireotide can provide marked biochemical improvement in acromegaly after the failure of both cabergoline monotherapy and cabergoline plus octreotide. This further confirms a potentially efficacious treatment regimen in treatment-resistant acromegaly with hyperprolactinemia.

Improvement of adult female acne with a novel weekly estradiol loaded peel off mask. A split face, placebo controlled study.

BACKGROUND: Adult female acne is characterized by a relapsing eruption of acne in individuals who are 25 years or older. It usually shows slower response to the traditional adolescent acne treatments. Usually, androgens promote acne by stimulating sebum production, while estrogens have the opposite effect by reducing sebum output when present in adequate quantities. Estradiol is the female sex hormone with the highest absolute serum levels and the highest estrogenic activity during a woman's reproductive years. Peel-off facial masks were suggested to intensify the effect of the added active ingredient through forming an occlusive film after drying. OBJECTIVES: to study the safety and efficacy of weekly topical estradiol 0.05% in the treatment of adult acne in females. METHODS: Twenty female patients with adult acne were subjected to once weekly application of estradiol 0.05% and placebo masks to either side of the face for 8 weeks. Acne lesion count was performed at baseline, at each visit and 8 weeks after end of treatment. RESULTS: At the end of the treatment period, the treated side showed significant improvement of comedones, papules and pustules. Although, lesions count increased 2 months after stopping treatment, they were still significantly less on the estradiol side compared to placebo. No side effects were reported. LIMITATIONS: The limited number of patients studied and the limited follow-up period. The estradiol effect was not studied on cellular and molecular levels. CONCLUSIONS: Topical estradiol peel off mask can be a promising convenient, safe and effective treatment for adult acne in women.

Artificial intelligence in the detection and classification of dental caries.

STATEMENT OF PROBLEM: Automated detection of dental caries could enhance early detection, save clinician time, and enrich treatment decisions. However, a reliable system is lacking. PURPOSE: The purpose of this study was to train a deep learning model and to assess its ability to detect and classify dental caries. MATERIAL AND METHODS: Bitewings radiographs with a 1876×1402-pixel resolution were collected, segmented, and anonymized with a radiographic image analysis software program and were identified and classified according to the modified King Abdulaziz University (KAU) classification for dental caries. The method was based on supervised learning algorithms trained on semantic segmentation tasks. RESULTS: The mean score for the intersection-over-union of the model was 0.55 for proximal carious lesions on a 5-category segmentation assignment and a mean F1 score of 0.535 using 554 training samples. CONCLUSIONS: The study validated the high potential for developing an accurate caries detection model that will expedite caries identification, assess clinician decision-making, and improve the quality of patient care.

AR visualizations in laparoscopy: surgeon preferences and depth assessment of vascular anatomy.

Introduction: This study compares five augmented reality (AR) vasculature visualization techniques in a mixed-reality laparoscopy simulator with 50 medical professionals and analyzes their impact on the surgeon. Material and methods: ​​The different visualization techniques' abilities to convey depth were measured using the participant's accuracy in an objective depth sorting task. Demographic data and subjective measures, such as the preference of each AR visualization technique and potential application areas, were collected with questionnaires. Results: Despite measuring differences in objective measurements across the visualization techniques, they were not statistically significant. In the subjective measures, however, 55% of the participants rated visualization technique II, 'Opaque with single-color Fresnel highlights', as their favorite. Participants felt that AR could be useful for various surgeries, especially complex surgeries (100%). Almost all participants agreed that AR could potentially improve surgical parameters, such as patient safety (88%), complication rate (84%), and identifying risk structures (96%). Conclusions: More studies are needed on the effect of different visualizations on task performance, as well as more sophisticated and effective visualization techniques for the operating room. With the findings of this study, we encourage the development of new study setups to advance surgical AR.

The respiratory and hemodynamic effects of alveolar recruitment in cirrhotic patients undergoing liver resection surgery: A randomized controlled trial.

Background and Aims: Extensive surgical retraction combined with general anesthesia increase alveolar collapse. The primary aim of our study was to investigate the effect of alveolar recruitment maneuver (ARM) on arterial oxygenation tension (PaO2). The secondary aim was to observe its effect on hemodynamics parameters in hepatic patients during liver resection, to investigate its impact on blood loss, postoperative pulmonary complications (PPC), remnant liver function tests, and on the outcome. Material and Methods: Adult patients scheduled for liver resection were randomized into two groups: ARM (n = 21) and control (C) (n = 21). Stepwise ARM was initiated after intubation and was repeated post-retraction. Pressure-control ventilation mode was adjusted to deliver a tidal volume (Vt) of 6 mL/kg and an inspiratory-to-expiratory time (I:E) ratio of 1:2 with an optimal positive end-expiratory pressure (PEEP) for the ARM group. In the C group, a fixed PEEP (5 cmH2O) was applied. Invasive intra-arterial blood pressure (IBP), central venous pressure (CVP), electrical cardiometry (EC), alanine transaminase (ALT, U/L), and aspartate aminotransferase (AST, U/L) blood levels were monitored. Results: ARM increased PEEP, dynamic compliances, and arterial oxygenation, but reduced ventilator driving pressure compared to group C (P < 0.01). IBP, cardiac output (CO), and stroke volume variation were not affected by the higher PEEP in the ARM group (P > 0.05) but the CVP increased significantly (P = 0.001). Blood loss was not different between the ARM and C groups (1700 (1150-2000) mL vs 1110 (900-2400) mL, respectively and P = 0.57). ARM reduced postoperative oxygen desaturation; however, it did not affect the increase in remnant liver enzymes and was comparable to group C (ALT, P = 0.54, AST, P = 0.41). Conclusions: ARM improved intraoperative lung mechanics and reduced oxygen desaturation episodes in recovery, but not PPC or ICU stay. ARM was tolerated with minimal cardiac and systemic hemodynamic effects.

Safety, pharmacokinetic, pharmacodynamic and clinical activity of molibresib for the treatment of nuclear protein in testis carcinoma and other cancers: Results of a Phase I/II open-label, dose escalation study.

Molibresib is an orally bioavailable, selective, small molecule BET protein inhibitor. Results from a first time in human study in solid tumors resulted in the selection of a 75 mg once daily dose of the besylate formulation of molibresib as the recommended Phase 2 dose (RP2D). Here we present the results of Part 2 of our study, investigating safety, pharmacokinetics, pharmacodynamics and clinical activity of molibresib at the RP2D for nuclear protein in testis carcinoma (NC), small cell lung cancer, castration-resistant prostate cancer (CRPC), triple-negative breast cancer, estrogen receptor-positive breast cancer and gastrointestinal stromal tumor. The primary safety endpoints were incidence of adverse events (AEs) and serious AEs; the primary efficacy endpoint was overall response rate. Secondary endpoints included plasma concentrations and gene set enrichment analysis (GSEA). Molibresib 75 mg once daily demonstrated no unexpected toxicities. The most common treatment-related AEs (any grade) were thrombocytopenia (64%), nausea (43%) and decreased appetite (37%); 83% of patients required dose interruptions and 29% required dose reductions due to AEs. Antitumor activity was observed in NC and CRPC (one confirmed partial response each, with observed reductions in tumor size), although predefined clinically meaningful response rates were not met for any tumor type. Total active moiety median plasma concentrations after single and repeated administration were similar across tumor cohorts. GSEA revealed that gene expression changes with molibresib varied by patient, response status and tumor type. Investigations into combinatorial approaches that use BET inhibition to eliminate resistance to other targeted therapies are warranted.

An Electrostatic MEMS Roll-Pitch Rotation Rate Sensor with In-Plane Drive Mode.

In this paper, we presented a novel electrostatic Roll/Pitch MEMS gyroscope with in-plane drive mode and out-of-plane sense mode. The proposed structure is developed based on a tuning fork gyroscope with decoupled sense mass on each tine that control the sense out-of-plane frequency. A multi-height deep reactive ion etching (DRIE) fabrication process was utilized to achieve and enhance decoupling between the drive and sense modes. We presented our design methodology followed by an analytical and finite element (FEM) model. Our experimental results showed a good match between the analytical model and those obtained experimentally, from the drive and sense oscillation frequencies. Our characterization setup used a custom made application specific integrated circuit (ASIC) for characterization and was able to achieve ARW of 0.2 deg/rt-h, a bias instability 5.5 deg/h, and scale factor non-linearity (SFNL) 156 ppm FS.

The Impact of Therapeutic Exercises on the Quality of Life and Shoulder Range of Motion in Women After a Mastectomy, an RCT.

Breast cancer ranks highest in incidence and mortality among females and second among both genders. Lebanon has the second highest rate of breast cancer worldwide for those 35-39 years old and the highest for those 40-49. Mastectomy often results in deceased shoulder and arm mobility and decreased quality of life. The objective of this study was to assess the effect of an educational program of therapeutic exercises on the quality of life and functional ability in women after a mastectomy. Sixty women undergoing a mastectomy were randomly assigned to either an intervention or control group. The intervention group received extensive pre-surgery education as well as training on therapeutic exercises. Follow-up phone calls to the intervention group were made to ensure that the exercises were being done. Both groups were visited at home at two and four weeks to obtain the outcome variables. The Breast Cancer Patient Version was used to assess quality of life, and the "Goniometer" was used to assess the range of motion of the affected shoulder. At two and four weeks after surgery, women in the intervention group had significant improvements in their shoulder range of motion: flexion, extension, and abduction were significantly different between the control and intervention group at p = 0.04-0.00. For quality of life, physical, psychological, psychological, social, and spiritual well-being were significantly higher for the intervention group at both two and four weeks after surgery, p < 0.001. In a middle-income country, one-to-one education provided by a nurse, which included demonstrations, back demonstrations, and weekly phone calls had a positive impact on women's shoulder range of motion and quality of life. NCT04184102.

Nanoemulsions of Jasminum humile L. and Jasminum grandiflorum L. Essential Oils: An Approach to Enhance Their Cytotoxic and Antiviral Effects.

Unprecedented nanoemulsion formulations (NE) of Jasminum humile and Jasminum grandiflorum essential oils (EO) were prepared, and examined for their cytotoxic and antiviral activities. NE characterization and stability examination tests were performed to ensure formula stability. The antiviral activity was determined against hepatitis A (HAV) and herpes simplex type-1 (HSV-1) viruses using MTT assay, while the cytotoxic potential was determined against liver (HepG-2), breast (MCF-7), leukemia (THP-1) cancer cell lines and normal Vero cells. Statistical significance was determined in comparison with doxorubicin as cytotoxic and acyclovir as antiviral standard drugs. GC-MS analysis indicated twenty four compounds in the EO of J. humile and seventeen compounds in the EO of J. grandiflorum. Biological investigations of pure EOs revealed weak cytotoxic and antiviral effects. Nevertheless, their NE formulations exhibited high biological value as cytotoxic and antiviral agents. NE formulations also showed feasible selectivity index for the viral-infected and cancer cells (especially HepG-2) than normal Vero cells. Both nanoemulsions showed lower IC50 than standard doxorubicin against HepG-2 (26.65 and 22.58 vs. 33.96 µg/mL) and MCF-7 (36.09 and 36.19 vs. 52.73 µg/mL), respectively. The study results showed the dramatic effect of nanoemulsion preparation on the biological activity of EOs and other liposoluble phytopharmaceuticals.

Cytotoxic effects of extracts obtained from plants of the Oleaceae family: bio-guided isolation and molecular docking of new secoiridoids from Jasminum humile.

CONTEXT: Traditionally, Oleaceae plants are used to treat many diseases, such as rheumatism, hypercholesterolaemia, or ulcers. OBJECTIVES: To investigate the cytotoxic potential of Jasminum humile L., Jasminum grandiflorum L., and Olea europaea L. (Oleaceae) extracts against selected human cancer cells lines, followed by a phytochemical investigation of the most potent one. MATERIALS AND METHODS: The 95% ethanol extracts of aerial parts of three oleaceous plants were examined for their cytotoxicity against HepG-2, MCF-7, and THP-1 cell lines using MTT assay and doxorubicin (positive control). J. humile was bio-selected and submitted to bio-guided fractionation. Chromatographic workup of ethyl acetate and n-butanol fractions afforded two new compounds; 1-methoxyjasmigenin (1) and 1-methyl-9-aldojasmigenin (2), along with five known ones (3-7). Structures were unambiguously elucidated using 1D/2D NMR and ESI-HRMS. Isolated compounds were assessed for their anti-proliferative potential, and both selectivity index and statistical significance were determined. Molecular docking was conducted against the Mcl-1 receptor using (AZD5991) as a standard. RESULTS: Jasmoside (5) was the most potent anticancer compound showing IC50 values of 66.47, 41.32, and 27.59 µg/mL against HepG-2, MCF-7, and THP-1 cell lines, respectively. Moreover, isojasminin (4) exhibited IC50 values of 33.49, 43.12, and 51.07 µg/mL against the same cell lines, respectively. Interestingly, 5 exhibited the highest selectivity index towards MCF-7 and THP-1, even greater than doxorubicin. Molecular docking results were in full agreement with the MTT assay and the proposed SAR. CONCLUSION: In this study, two new compounds were purified. The biological activity highlighted jasmoside (5) as a lead anticancer drug for further future investigation.

High-Resolution UPLC-MS Profiling of Anthocyanins and Flavonols of Red Cabbage (Brassica oleracea L. var. capitata f. rubra DC.) Cultivated in Egypt and Evaluation of Their Biological Activity.

In this paper, biological investigations and a high-resolution UPLC-PDA-ESI-qTOF-HRMS technique were employed for Brassica oleracea L. var. capitata f. rubra DC. (red cabbage) of the family Brassicaceae (Cruciferae), cultivated in Egypt, for the first time. The positive ionization mode is usually performed to identify anthocyanins. However, this technique cannot differentiate between anthocyanins and corresponding non-anthocyanin polyphenols. Thus, the negative ionization mode was also used, as it provided a series of characteristic ions for the MS analysis of anthocyanins. This helped in identifying five kaempferol derivatives for the first time in red cabbage, as well as nine-previously reported-anthocyanins. For the biological investigations, the acidified methanolic extract of fresh leaves and the methanolic extract of air-dried powdered leaves were examined for their antioxidant, antimicrobial, and anticancer activities. The freshly prepared phenolic extract was proven to be more biologically potent. Statistical significance was determined for its anticancer activity in comparison with standard doxorubicin.

Profile of sexuality and symptoms of lower urinary tract in non-institutionalized elderly.

INTRODUCTION: Urinary or sexual dysfunction in the elderly are underreported. However, they are highly prevalent. This study aims to identify the prevalence of these conditions. OBJECTIVE: The aim is to carry out an investigation in non-institutionalized individuals over 60 years of age, to obtain data on its sexual and urinary health in São Paulo, Campinas, Santo André and Londrina. RESULTS: 6.000 questionnaires were distributed, and 3425 were included in the study, for the analysis of the questionnaires separately. In relation to ADAM, 92% of the 1385 evaluated were suspicious of androgen deficiency (ADAM). As for the male sexual function, it was observed 37% of premature ejaculation. As for the female sexual function, 1300 (74%) did not practice sexual intercourse and the main reasons were: lack of partner and lack of sexual desire. In addition, 988 (78%) of women who had no sexual intercourse responded that they didn't want sex and, more importantly, about 22% of them would like to have sexual intercourse. International prostate symptom score (IPSS) showed gradual worsening of urinary symptoms with increasing age, being the most prevalent: nocturia and urinary urgency. As for the female IPSS, we noted that even after 80 years, the majority have mild symptoms related to voiding dysfunction; with increasing age there is a gradual increase in the result of the IPSS. CONCLUSION: Due to the large number of sexual and urinary disorders found, we recommend the improve-ment in health conditions, promoting a better quality of life in the elderly.

Routine office hysteroscopy prior to ICSI vs. ICSI alone in patients with normal transvaginal ultrasound: a randomized controlled trial.

BACKGROUND: Implantation failure represents a major cause of stress to both clinician and patient undergoing ICSI cycle. Even minor uterine cavity abnormalities, such as endometrial polyps, small submucous myomas, adhesions, and septa are considered to have a negative impact on the chance to conceive through ICSI. AIM: This study aimed at assessing the role of using the office hysteroscopy as a routine investigation in improving ICSI pregnancy rates. METHODOLOGY: ICSI was performed in two groups of infertile women with no abnormality detected in transvaginal ultrasonographic examination, group I: n = 97 and group II: n = 96, women in group I were subjected to hysteroscopic examination before ICSI while group II underwent ICSI without hysteroscopy. Then, ICSI was performed for all subjects of the two study groups with no statistically significant difference (p > 0.05) regarding the number of oocytes retrieved and the number of embryo transfer. Then, all subjects were followed up for 3 weeks after embryo transfer for detection of pregnancy by ultrasound. RESULTS: 43.3 % of group I showed abnormal hysteroscopic findings. Group I showed a significantly higher pregnancy rate (70.1 %) than that of group II (45.8 %) (p = 0.001). There is statistically significant association between the use of hysteroscopy prior to ICSI and the rate of pregnancy (OR 2.77, 95 % CI [1.53-5.00]). In addition, hysteroscopy had detected abnormalities in near half of cases whose ultrasound was normal. CONCLUSION: Routine office hysteroscopy is an essential step for infertility workup before ICSI even in patients with normal TV/US.

Analysis of the effect of renal excretory system cooling during thermal radiofrequency ablation in an animal model.

OBJECTIVE: Analysis of renal excretory system integrity and efficacy of radiofrequency ablation with and without irrigation with saline at 2°C (SF2). MATERIALS AND METHODS: The median third of sixteen kidneys were submitted to radiofrequency (exposition of 1 cm) controlled by intra-surgical ultrasound, with eight minutes cycles and median temperature of 90°C in eight female pigs. One excretory renal system was cooled with SF2, at a 30mL/min rate, and the other kidney was not. After 14 days of post-operatory, the biggest diameters of the lesions and the radiological aspects of the excretory system were compared by bilateral ascending pyelogram and the animals were sacrificed in order to perform histological analysis. RESULTS: There were no significant differences between the diameters of the kidney lesions whether or not exposed to cooling of the excretory system. Median diameter of the cooled kidneys and not cooled kidneys were respectively (in mm): anteroposterior: 11.46 vs. 12.5 (p = 0.23); longitudinal: 17.94 vs. 18.84 (p = 0.62); depth: 11.38 vs. 12.25 (p = 0.47). There was no lesion of the excretory system or signs of leakage of contrast media or hydronephrosis at ascending pyelogram. CONCLUSION: Cooling of excretory system during radiofrequency ablation does not sig¬nificantly alter generated coagulation necrosis or affect the integrity of the excretory system in the studied model.

Phytochemical analysis and evaluation of its antioxidant, antimicrobial, and cytotoxic activities for different extracts of Casuarina equisetifolia.

BACKGROUND: Casuarina equisetifolia belongs to the Casuarina species with the most extensive natural distribution, which contain various phytochemicals with potential health benefits. This study aimed to investigate the chemical composition and biological activities of different extracts of Casuarina equisetifolia. METHODS: The n-hexane extract was analyzed for its unsaponifiable and fatty acid methyl esters fractions, while chloroform, ethyl acetate, and butanol extracts were studied for their phenolic components. Six different extracts of C. equisetifolia needles were evaluated for their total phenolic content, total flavonoid content, and their antioxidant, antimicrobial, and cytotoxic activities. RESULTS: The n-hexane extract contained mainly hydrocarbons and fatty acid methyl esters, while ten phenolic compounds were isolated and identified in the chloroform, ethyl acetate, and butanol extracts. The methanolic extract exhibited the highest total phenolic and flavonoid content, highest antioxidant activity, and most potent cytotoxic activity against HepG-2 and HCT-116 cancer cell lines. The ethyl acetate extract showed the most significant inhibition zone against Staphylococcus aureus and Bacillus subtilis. CONCLUSION: Casuarina equisetifolia extracts showed promising antioxidant, antimicrobial, and cytotoxic activities. Overall, Casuarina equisetifolia is a versatile tree with a variety of uses, and its plant material can be used for many different purposes.

Effect of phosphodiesterase type 5 inhibitors on surgical outcome of ventricular septal defect and pulmonary hypertension patients.

BACKGROUND: Children with ventricular septal defect (VSD) and large systemic-to-pulmonary shunts eventually develop pulmonary hypertension (PH). The perioperative management of patients with VSD and PH is quite troublesome and still debatable, especially in developing countries where the different management options and standardization of treatment is not available. Oral phosphodiesterase type 5 (PDE-5) inhibitors are good treatment options being widely available, cheap, easy administration and do not require extensive monitoring. The aim of our study was to evaluate the effect of the PDE-5 inhibitors when given orally, early preoperative and continued for 3 months postoperative on controlling postoperative PH with its effect on right ventricle (RV) functions. Fifty-one patients were randomly assigned to either sildenafil or tadalafil, 1 week before and continued for 3 months after corrective surgery. The control group received a placebo. RESULTS: There was no significant difference in the improvement in the right ventricle systolic pressure (RVSP) between both groups, early in the postoperative period (P = 0.255) and in follow-up (P = 0.259). There was also no significant difference in the changes in mean pulmonary artery pressure (mPAP), postoperatively and on follow-up (P = 0.788 and 0.059, respectively). There was a drop in RV functions in both groups postoperatively which improved on follow-up; however, it was not significant between both groups. The length of intensive care unit (ICU) stay was similar between both groups (P = 0.143). CONCLUSION: Perioperative administration of PDE-5 inhibitors does not have an impact on the clinical course as regards improvement in pulmonary artery (PA) pressure, ventricular functions and ICU stay.

Ameliorative effect of Nyctanthes arbor-tristis L. by suppression of pentylenetetrazole-induced kindling in mice: An insight from EEG, neurobehavioral and in-silico studies.

Epilepsy is an abiding condition associated with recurrent seizure attacks along with associated neurological and psychological emanation owing to disparity of excitatory and inhibitory neurotransmission. The current study encompasses the assessment of the Nyctanthes arbor-tristis L. methanolic extract (Na.Cr) in the management of convulsive state and concomitant conditions owing to epilepsy. The latency of seizure incidence was assessed using pentylenetetrazol (PTZ) kindling models along with EEG in Na.Cr pretreated mice, trailed by behavior assessment (anxiety and memory), biochemical assay, histopathological alterations, chemical profiling through GCMS, and molecular docking. The chronic assessment of PTZ-induced kindled mice depicted salvation in a dose-related pattern and outcomes were noticeable with extract at 400 mg/kg. The extract at 400 mg/kg defends the progress of kindling seizures and associated EEG. Co-morbid conditions in mice emanating owing to epileptic outbreaks were validated by behavioral testing and the outcome depicted a noticeable defense related to anxiety (P<0.001) and cognitive deficit (P<0.001) at 400 mg/kg. The isolated brains were evaluated for oxidative stress and the outcome demonstrated a noticeable effect in a dose-dependent pattern. Treatment with Na.Cr. also preserved the brain from PTZ induced neuronal damage as indicated by histopathological analysis. Furthermore, the GCMS outcome predicted 28 compounds abundantly found in the plant. The results congregated in the current experiments deliver valued evidence about the defensive response apportioned by Na.Cr which might be due to decline in oxidative stress, AChE level, and GABAergic modulation. These activities may contribute to fundamental pharmacology and elucidate some mechanisms behind the activities of Nyctanthes arbor-tristis.

A Phase I/II Study of GSK525762 Combined with Fulvestrant in Patients with Hormone Receptor-positive/HER2-negative Advanced or Metastatic Breast Cancer.

PURPOSE: Endocrine-based therapy is the initial primary treatment option for hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). However, patients eventually experience disease progression due to resistance to endocrine therapy. Molibresib (GSK525762) is a small-molecule inhibitor of bromodomain and extraterminal (BET) family proteins (BRD2, BRD3, BRD4, and BRDT). Preclinical data suggested that the combination of molibresib with endocrine therapy might overcome endocrine resistance. This study aimed to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy [objective response rate (ORR)] of molibresib combined with fulvestrant in women with HR+/HER2- mBC. PATIENTS AND METHODS: In this phase I/II dose-escalation and dose-expansion study, patients received oral molibresib 60 or 80 mg once daily in combination with intramuscular fulvestrant. Patients enrolled had relapsed/refractory, advanced/metastatic HR+/HER2- breast cancer with disease progression on prior treatment with an aromatase inhibitor, with or without a cyclin-dependent kinase 4/6 inhibitor. RESULTS: The study included 123 patients. The most common treatment-related adverse events (AE) were nausea (52%), dysgeusia (49%), and fatigue (45%). At a 60-mg dosage of molibresib, >90% of patients experienced treatment-related AE. Grade 3 or 4 treatment-related AE were observed in 47% and 48% of patients treated with molibresib 60 mg and molibresib 80 mg, respectively. The ORR was 13% [95% confidence interval (CI), 8-20], not meeting the 25% threshold for proceeding to phase II. Among 82 patients with detected circulating tumor DNA and clinical outcome at study enrollment, a strong association was observed between the detection of copy-number amplification and poor progression-free survival (HR, 2.89; 95% CI, 1.73-4.83; P < 0.0001). CONCLUSIONS: Molibresib in combination with fulvestrant did not demonstrate clinically meaningful activity in this study.

Tricuspid valve and right-heart chamber remodelling in elderly subjects with secondary tricuspid regurgitation.

BACKGROUND: The prevalence of secondary tricuspid regurgitation (TR) increases with ageing, but the exact mechanisms and the pattern of tricuspid valve (TV) remodelling are yet to be defined. This knowledge is needed to guide patient selection for the evolving therapeutic options. We sought to explore the prevalence and predictors of secondary TR in the elderly, as well as the associated pattern of right-heart chamber and TV remodelling. METHODS: Consecutive older subjects (60-year-old or older) were prospectively enrolled and detailed analysis of right-heart chambers and TV was conducted (ClinicalTrials.gov ID: NCT05784883). TR severity was defined based on a multiparametric approach. RESULTS: Out of 213 patients (age, 67.1 ± 5.9 years, 52.6% female), 48.8% had mild and 15.5% had moderate-severe TR. The frequency of moderate-severe TR increased from 4.5% in those without to 32.9% in those with underlying abnormalities of the left/right heart. There was a significant trend of worsening right-heart chamber and TV remodelling across the three grades of TR severity (none-trace, mild, and moderate-severe; p-value for linear trend < 0.001). ROC curve-defined cut-points of TV remodelling parameters predicting moderate-severe TR were annular dilatation ≥3.75 cm (AUC: 0.74), tenting area ≥1.45 cm2 (AUC: 0.67), and leaflet length ≥2.25 cm (AUC: 0.61) with increasing frequency of moderate-severe TR from 7.2% through 64.7%, in those with none vs. all three criteria (p < 0.001). The most important correlate of the three TV remodelling parameters was right ventricular and atrial (RV and RA) dilatation. CONCLUSION: Rather than ageing per se, the presence of underlying cardiac abnormalities determines the frequency of moderate-severe TR. Progressive remodelling of right-heart chambers and TV geometry starts with the development of mild TR. TA dilatation, increased tenting, and leaflet elongation are three important correlates of the development of TR that parallel progressive RV and RA dilatation.Study Registration: ClinicalTrials.gov ID: NCT05784883.

Factors Affecting the Satisfaction of Women Employees in Health Sector: A Perception Study in Saudi Arabia.

Purpose: Broad evidence points out that women workers in Saudi Arabia face a range of inequitable work practices despite continued efforts for gender equality. The study aims to assess the satisfaction of Saudi women working in the health sector among certain factors in the work environment, factors that enable them to gain opportunities and benefits and make decisions. Patients and Methods: This is a cross-sectional study, which involved the use of closed-ended surveys on 261 Saudi women working in the healthcare sector. Results: Most of the females were aged between 25 and 34 years (59%) and more than half of them worked in the governmental sector (53%). Fifty-eight percent of the females hold clinical jobs, 25% of the administrative jobs were 37% of them have more than 19 years of working experience. The finding showed a significant association between female workers in health sector satisfaction with factors related to the workplace environment, training, and development, and their involvement in decision-making. Conclusion: Most women felt empowered when they received equitable tasks and were able to reach managerial-level positions in their organizations. Establishing a positive work environment characterized by opportunities has the potential to enhance women workers' satisfaction.