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Background: Tuberculosis (TB), a global infectious threat, has seen a concerning rise in aminoglycoside-resistant Mycobacterium tuberculosis (M.tb) strains. The potential role of capsule proteins remains largely unexplored. This layer acts as the primary barrier for tubercle bacilli, attempting to infiltrate host cells and subsequent disease development. Methods: The study aims to bridge this gap by investigating the differentially expressed capsule proteins in aminoglycoside-resistant M.tb clinical isolates compared with drug-sensitive isolates employing two-dimensional gel electrophoresis, mass spectrometry, and bioinformatic approaches. Results: We identified eight proteins that exhibited significant upregulation in aminoglycoside-resistant isolates. Protein Rv3029c and Rv2110c were associated with intermediary metabolism and respiration; Rv2462c with cell wall and cell processes; Rv3804c with lipid metabolism; Rv2416c and Rv2623 with virulence and detoxification/adaptation; Rv0020c with regulatory functions; and Rv0639 with information pathways. Notably, the Group-based Prediction System for Prokaryotic Ubiquitin-like Protein (GPS-PUP) algorithm identified potential pupylation sites within all proteins except Rv3804c. Interactome analysis using the STRING 12.0 database revealed potential interactive partners for these proteins, suggesting their involvement in aminoglycoside resistance. Molecular docking studies revealed suitable binding between amikacin and kanamycin drugs with Rv2462c, Rv3804c, and Rv2623 proteins. Conclusion: As a result, our findings illustrate the multifaceted nature of aminoglycoside resistance in M.tb and the importance of understanding how capsule proteins play a role in counteracting drug efficacy. Identifying the role of these proteins in drug resistance is crucial for developing more effective treatments and diagnostics for TB.

Background: Audiovisual distraction is a potentially good technique to reduce medical treatment procedure-related fear and anxiety among children. However, few studies have assessed its effectiveness. Objective: To conduct a systematic review and meta-analysis for evaluating the effectiveness of audiovisual distraction in reducing pain anxiety in pediatrics. Methods: Randomized control trials and experimental studies that reported the use of audiovisual distraction during medical/dental treatments among children aged 3–8 years, used the Face, Legs, Activity, Cry, Consolability (FLACC) scale to assess pain, and were published between 2005–2021 and in English were retrieved from PubMed, Scopus, and Web of Science. A random-effects model was used for evidence analysis. Results: A total of four studies were included in the systematic review and meta-analysis: two were from South Asia and one each were from Africa and North America. Three of these studies were randomized control trials. The variability among the studies was high. Three of the four studies found that AV techniques were significantly effective in reducing pain during procedures compared with the control group (P < 0.00001), while one study found no difference; the cumulative evidence in the forest plot was similar. Conclusion: Cumulative evidence suggests that the use of audiovisual distraction is an effective strategy in reducing medical/dental procedures-related pain anxiety among children aged 3–8 years. However, evidence on this is currently limited, and thus further studies are required using various AD techniques and on different populations to substantiate these findings. Funding: None. Registration: PROSPERO (Ref no.: CRD42021245874).

Abstract The present paper reviews the extant literature on Earnings Management (EM) in emerging economies using the integrated ‘Antecedents Decisions Outcomes (ADO)–Theory, Context, and Methods (TCM)’ framework to identify the firm-level and country-level factors influencing EM practices in these economies. Considering the increasing share of emerging economies in global Foreign Direct Investment and their unique institutional settings and opaque reporting environment, this review seeks to identify the key perspectives of EM studies in these economies. This review analyses 96 articles from 50 journals published between the period 2003 and 2021. Concentrated ownership structures at the firm level, weak regulatory mechanisms for investor protection, low level of enforcement, and culture at the country level are identified as key determinants influencing EM practices in emerging economies. The review finds a dearth of studies integrating the agency, institutional, and organizational theories which will help in better understanding the phenomena of EM in emerging economies. The review also identifies a contextual gap in terms of the need for more multi-country studies within the emerging economies which will provide a better insight into the diverse formal and informal institutions that shape incentives for EM in these economies. Similarly, there is a need to adopt a qualitative and mixed methods approach to study this phenomenon which helps strengthen the theoretical framework for studying EM in emerging economies.

Abstract Accurate structure elucidation of biologically active molecules is crucial for designing and developing new drugs, as well as for analyzing their pharmacological activity. In this study, density functional theory calculations are applied to explore the electronic structure and properties of phenethylamine derivatives, including Amphetamine, Methamphetamine, and Methylene Dioxy Methamphetamine(MDMA). The investigation encompasses various aspects such as geometry optimization, vibrational analysis, electronic properties, Molecular Electrostatic Potential analysis, and local and global descriptor analysis. Additionally, the study utilizes Natural Bond Orbital analysis and Quantum Theory of Atoms in Molecules to investigate the chemical bonding and charge density distributions of these compounds. Experimental techniques such as Fourier transform infrared (FT-IR) and Raman spectroscopic analysis are employed in the range of 4000-400 $$cm^{-1}$$ c m - 1 and 4000-50 $$cm^{-1}$$ c m - 1 , respectively. Theoretical vibrational analysis with Potential Energy Distribution(PED) assignments is conducted, and the resulting frequencies are compared to experimental spectral data, revealing good agreement. By correlating various structural parameters with the pharmacological activity of each derivative, computational structure elucidation aids in understanding the unique actions of phenethylamine derivatives. The obtained results offer a comprehensive understanding of the molecular behavior and properties of these drugs, facilitating the development of new drugs and therapies for addiction and related disorders.

Urinary dysfunction following treatment for rectal adenocarcinoma is a common and complex complication. We present a case of a 69-year-old male who underwent laparoscopic-assisted left hemicolectomy and loop ileostomy after receiving chemotherapy and radiation therapy for rectal adenocarcinoma. Postoperatively, it was incidentally discovered the patient had urinary frequency and urgency. Cystoscopy revealed radiation changes to the bladder walls and a bladder leak was confirmed by cystogram. The patient underwent successful repair of the urinary bladder leak, with challenges posed by prior radiation therapy. Effective prevention and management strategies for urinary dysfunction require a comprehensive preoperative risk assessment, consideration of nerve-preserving surgical techniques, and prompt identification and repair of postoperative complications.

Abstract The aim of this paper is to discuss some results concerning the demiclosedness principle of generalized, nonexpansive mappings in uniformly convex spaces. Further, we present some new fixed-point theorems for generalized nonexpansive mappings in different settings of Banach spaces.

Marchiafava-Bignami Disease (MBD) is an unusual neurological illness caused by prolonged alcoholism that is distinguished by demyelination of the corpus callosum. Clinicians encounter a wide range of alcohol-related diseases in their practice, and MBD is a rare condition that requires a high clinical suspicion due to its potential to mimic withdrawal symptoms, Wernicke’s-Korsakoff’s Psychosis, and various other neurological conditions, leading to confusion in diagnosis. It is a toxic-demyelinating syndrome that typically affects chronic alcoholics, but it has been described in rare instances in chronically malnourished teetotalers. The symptoms and warning signs are diffuse, and the onset could be abrupt or gradual. This is a case of a 54-year-old chronic alcoholic who presented with neurological symptoms. Magnetic Resonance Imaging (MRI) of the brain revealed typical features of MBD. The patient was treated with high doses of thiamine along with folic acid and other symptomatic treatments, after which significant improvement was observed. This case report reviews past reported cases to shed light on the varied presentation features of the disease. It adds to the limited corpus of MBD literature and highlights the intricate diagnostic process and management complexities associated with this condition. By integrating clinical observations, neuroimaging findings, and treatment outcomes, this report underscores the importance of maintaining a high clinical suspicion in cases involving alcohol abuse and the significance of tailored therapeutic strategies. As MBD continues to present diagnostic challenges, this report contributes valuable insights into its presentation, progression, and potential pathways to recovery. Therefore, it requires a high clinical suspicion for both clinical and radiological diagnosis.

Background: Fentanyl-induced cough (FIC) is an undesirable side effect associated with intravenous injection of the opioid fentanyl, which can lead to an increase in intraocular, intrathoracic, and intraabdominal pressures. The incidence of FIC is reported to be 18–65%, more common in young females, who are also at high risk population for post-operative nausea and vomiting (PONV). FIC and PONV are both common anesthesia-related events that seem to have common risk factors. Aims and Objectives: The objectives of the study were to find out the incidence of FIC in female patients undergoing elective surgery under general anesthesia and if FIC was a risk factor for developing PONV. Materials and Methods: A randomized, prospective study was done to compare the incidence of FIC and its correlation with PONV. 263 adult female patients belonging to American Society of Anesthesiologists status I and II, aged 18–59 years, posted for elective surgery under general anesthesia were studied over a period of 2 years. Pre-operatively, fentanyl (2 mg/kg body weight) was injected intravenously over 10 s as premedication, and the occurrence of any episode of cough within 60 s of fentanyl administration was taken as FIC. The incidence and severity of PONV were assessed in the same study population for a 24-h period. The incidence of FIC during general anesthesia in the study population was noted, and its correlation with PONV was analyzed. Results: The incidence of FIC in the study population was found to be 27%. The incidence of PONV in the FIC group was found to be 38%, as compared to 29.7% in the non-FIC group. FIC group had a higher incidence of PONV than the non-FIC group, but it was statistically insignificant (P=0.254). Conclusion: The incidence of PONV was slightly higher in the FIC group than in the non-FIC group, but it was not statistically significant.

Introduction: Chronic urticaria is defined as the almost daily occurrence of wheals and pruritus for a minimum of six weeks, adversely affecting the quality of life and necessitating management with a drug with better efficacy and a high safety profile. This study was designed to determine how monotherapy with newer antihistamines benefits chronic spontaneous urticaria by producing earlier and longer periods of remission. Additionally, the study aimed to assess the adverse effects associated with the drugs. Aim: To compare the efficacy of Levocetirizine and Bilastine in chronic spontaneous urticaria. Materials and Methods: The study was a single-blinded randomised controlled trial conducted in the Department of Dermatology at Madras Medical College, Chennai, Tamil Nadu, India over 24 months from January 2020 to December 2021. A total of 163 patients with chronic urticaria were randomly divided into two groups: Group A with 82 patients and group B with 81 patients. The patients were treated with tablet Levocetirizine 5 mg and tablet Bilastine 20 mg for six months (with up-dosing to four-fold maximum) in Group A and Group B, respectively. The treatment response was assessed using the Urticaria Activity Score (UAS) at each follow-up. Patients were followed-up for an additional six months to observe the time of recurrence. Total 15 patients were lost to follow-up and were consequently excluded from the statistical analysis. Results: At the end of six months, the improvement observed in UAS was statistically similar in both groups (p-value=0.513). The time taken for remission was shorter with Levocetirizine (11.19±5.31 weeks) compared to Bilastine (14.59±5.02 weeks). Recurrence occurred earlier with Bilastine compared to Levocetirizine. Conclusion: Levocetirizine and Bilastine are equally effective in controlling urticaria at the end of six months of treatment. Patients on Levocetirizine experienced earlier remission as well as late recurrence compared to those on Bilastine.

A novel additive-manufactured antenna for stretchable sensor application is designed, simulated and measured. The fully transparent antenna has air as a substrate and a conductive aluminium metal sheet as a patch. The layers are defined with thin Thermo Poly Urethane (TPU) material, as its flexible/stretchable property doesn't disturb the actual property of air. The air substrate is locked within the flexible TPU with a thickness of 200 microns, and the conducting patch is also dimensioned with the 3D printing method. The stretchable antenna is fabricated with 3D printing technology, considered a dielectric medium, and the conducting medium is a conducting aluminium sheet. Re-configurability is achieved with the pressure level applied over the air–substrate antenna. Hence, the minimal change in shape changes the dielectric constant, thus changing the antenna parameter and radiation pattern. The antenna achieves improved size and performance with a gain of 7.2 dB, a directivity of 7.574 dB, a radiation efficiency of 95.67 %, and a 12:509 front-to-back ratio. The fabricated antenna is tested for its resonant characteristics and radiation properties. This reconfigurable antenna can be used for various applications, including Wireless Local Area Network (WLAN) communication.

IntroductionVarious studies have suggested use of socket grafting materials after dental extraction for socket preservation. However, there is no single material that has been accepted as standard for preserving the socket. The purpose of this systematic review was to analyze the evidence for the use of biphasic calcium phosphate for socket regeneration. Materials and MethodsThe team conducted a systematic literature search in accordance with the protocol registered at PROSPERO. PubMed, OVID, and EMBASE databases were used in the search. The articles were then screened using RAYYAN open-source software for the synthesis of evidence. ResultsOf the 240 articles found in the search, two studies could be included in the review. ConclusionBiphasic calcium phosphate (60% hydroxyapatite, HA and 40% beta-tricalcium phosphate, β-TCP) has a significant effect in the socket preservation and quality of bone regeneration.

AimThe current study was conducted to assess the effects of various surface treatments on the implant surface. Materials and MethodsA total of 45 dental implants measuring 16 mm in length and 5 mm in diameter were used, along with the appropriate abutments. Depending on the surface treatment used, the samples were randomly split into three groups, with 15 implants in each group: Group 1: Control, Group 2: UV light-treated, Group 3: Sandblasted and acid-etched (SLA)-treated. After surface treatment, a scanning electron microscope (SEM) was used to assess the test samples’ surface properties. All sample images were captured using a 3000× magnification. After all three groups’ surfaces were treated, the surface roughness was measured using a digital optical profilometer with a stylus speed of 0.5 mm/s that was connected to computer software. ResultsThe maximum surface roughness was found in the group treated with SLA (0.714 ± 0.12), followed by the group treated with UV light (0.692 ± 0.09) and the control group (0.516 ± 0.12). There was a significant difference found between different surface treatment methods. ConclusionThe present study concluded that the group that received the SLA treatment had the highest surface roughness when compared to the UV light and control groups.

BackgroundBioactivity refers to the ability of a material to interact with living organisms or biological systems in a way that elicits a specific response. In the context of materials science and medicine, bioactivity is particularly important because it can determine the suitability of material for various applications. ObjectiveTo evaluate and compare different commercially available calcium silicate-based materials regarding: 1. Morphological and elemental analysis at the dentin/material interface. 2. Calcium and silicon release and uptake by adjacent root canal dentine by evaluating the calcium and silicon incorporation depth in adjacent root canal dentin. Materials and MethodsThis study examined four calcium silicate-based cements: Biodentine, MTA Angelus, BioAggregate, and MTA Plus. One hundred extracted human teeth with intact apices and no cavities were selected. Root sections measuring 3 mm in length were created at the mid-root level using low-speed diamond discs. Bioactivity was evaluated at 1, 7, 30, and 90 days, respectively. ResultsThe principal composition of the interfacial dentine layer and incorporation of calcium and silicon into dentine was measured at 1, 7, 30, and 90 days. Statistical analysis was performed by multiple comparisons using post hoc Tukey HSD. ConclusionAll the materials have shown bioactivity, i.e. release of calcium, silicon, and their uptake in the adjacent dentin in the presence of phosphate-buffered saline.

BackgroundNeurodegenerative diseases induce amnesia, and effective treatment is still elusive. Aims and Objectives: The present study highlights the ameliorating effects of Manasa Mitra Vatakam (MMV) using behavioral parameters on scopolamine-induced memory loss in female Wistar rats. Materials and MethodsMMV was compared with DPZ as a standard in the present study to determine the behavioral parameters through elevated plus maze (Hebb William maze/rectangular maze)and locomotor activity in scopolamine-induced memory loss in female Wistar rats. Results and DiscussionThe results of the study illustrate the effectiveness of MMV in reversing memory dysfunction and memory-enhancing effects. ConclusionThe study paves the way for exploring research in CNS disorders and its potential application in drug-induced neurotoxicity.

BackgroundThe scientific validity of contemporary and alternative medicinal practices, such as Ayurveda and Siddha, holds significant importance in today’s context. Aim and ObjectiveThe present study employs gas chromatography-mass spectrometry (GC-MS) analysis to investigate a pain-relieving Ayurvedic oil, Dhanwantharam Thailam, aiming to establish correlations between its medicinal activity and the biomolecules it contains. Materials and MethodsProcured sample from a reputable Ayurvedic vendor in Chennai, Dhanwantharam Thailam underwent GC-MS analysis using standard procedures. Results and DiscussionThe resulting profile revealed the presence of crucial molecules like oleic acid, dodecanoic acid, 1,2,3-propanetriyl ester, ethenyl ester, and 9,12-octadecadienoyl chloride (Z, Z), aligning with the medicinal properties attributed to Dhanwantharam Thailam. ConclusionThe identification of these biomolecules supports the role of Dhanwantharam Thailamas an effective pain-relieving oil.

Introduction and AimPerforming endodontic treatment in an immature permanent tooth that has experienced trauma or carious exposure can pose challenges. The root canals in these teeth are typically open and fragile, making instrumentation and obturation difficult. Traditional apexification, which involves placing calcium hydroxide paste in the root canal for a specified period to induce the formation of a calcified barrier, has been a long-standing approach. While it is a widely used method, leaving the paste in the root for extended periods can weaken it due to the paste’s hygroscopic properties and the proteolytic activities of calcium hydroxide. As a result, researchers have been exploring alternative treatments that allow for the full development of immature teeth. Revascularization has emerged as one such alternative, with a variety of treatment protocols documented in scientific literature. Description of the CaseThis case report, for the first time, describes the use of NeoPutty MTA® and triple antibiotics paste for revascularization in a young female child on a carious, exposed lateral incisor with opex apex with success. ConclusionThe revascularization process attempted on the infected tooth met with success and closure of apex was noticed in a short period of time.

Abstract Most lung cancer patients with metastatic cancer eventually relapse with drug-resistant disease following treatment and EGFR mutant lung cancer is no exception. Genome-wide CRISPR screens, to either knock out or overexpress all protein-coding genes in cancer cell lines, revealed the landscape of pathways that cause resistance to the EGFR inhibitors osimertinib or gefitinib in EGFR mutant lung cancer. Among the most recurrent resistance genes were those that regulate the Hippo pathway. Following osimertinib treatment a subpopulation of cancer cells are able to survive and over time develop stable resistance. These ‘persister’ cells can exploit non-genetic (transcriptional) programs that enable cancer cells to survive drug treatment. Using genetic and pharmacologic tools we identified Hippo signalling as an important non-genetic mechanism of cell survival following osimertinib treatment. Further, we show that combinatorial targeting of the Hippo pathway and EGFR is highly effective in EGFR mutant lung cancer cells and patient-derived organoids, suggesting a new therapeutic strategy for EGFR mutant lung cancer patients.

Introduction: Colorectal Cancer (CRC) has been primarily considered a disease of the elderly, but recent data have shown an alarming rise among young people. It has also been suggested that young age is associated with aggressive histopathological characteristics and advanced stages of the disease at diagnosis. Aim: To assess and compare the clinical and pathological characteristics of patients with rectal cancer diagnosed at ages over and below 45 years. Materials and Method: This prospective cross-sectional study was conducted between January 2020 and August 2022 in the Departments of Surgical, Medical, Radiation Oncology, Surgical Gastroenterology, and General Surgery at All India Institute of Medical Sciences (AIIMS) Rishikesh, Uttarakand, India. All patients underwent a biopsy from the representative site for histological documentation of the disease. They then underwent treatment (surgery/chemotherapy/radiotherapy) as required. All the data were categorised into two groups: an early-onset group (age

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, was first reported in China in 2019 and later declared a pandemic. Coagulation abnormalities play the pivotal role in causing most of the symptoms related to COVId-19 infection. As the pathophysiology of COVID-19 is now being understood, it is found that these coagulation abnormalities, especially thrombosis are very well related to the severity of the disease. D-dimer is a potential biomarker for various thrombotic diseases. This study aims to determine the efficacy of D-dimer, Fibrinogen, Prothrombin time (PT), and activated partial thromboplastin time (aPTT) to determine the severity of COVID-19 infection. Aims and Objectives: The objectives of the study are as follows: (1). To determine the efficacy of D-dimer in assessing the severity of the disease in COVID-19 infection. (2). To determine the role of PT, aPTT, and Fibrinogen levels in assessing the severity of COVID-19 Infection. Materials and Methods: The study was conducted among 160 reverse transcription polymerase chain reaction confirmed COVID-19 patients admitted in Government Medical College, Kottayam. The sociodemographic profile and presenting complaints were obtained using a structured format. Blood samples were collected on the day of admission, the 5th day, and 10th day. Samples are tested for levels of D-dimer, Fibrinogen, PT, and aPTT. Based on the clinical outcome, patients were categorized into two groups: Mild group and severe group. Results: The difference between the median D-dimer at admission in the severe group (1339 ng/mL) and the mild group (390 ng/mL) was statistically significant. Area under the receiver operating characteristic (ROC) for D-dimer was 0.774 and cut-off value was found to be 569 μg/mL with a sensitivity of 83.3% and a specificity of 61.2%. The ROC curve analysis, area under the curve of PT also can be used for diagnosis with 76.3% with 76.3% sensitivity and 61.2% of specificity. Conclusion: Coagulopathy is an important complication of COVID-19 patients and is related to severity as well as prognosis of disease. D-dimer and PT can be used as reliable and convenient parameter for assessing coagulopathy and severity in COVID-19 infected patients.

The concept of energy in graphs and matrices is frequently used in all application fields. The energy of a matrix is an extended version of the energy of a graph. The neutrosophic matrix energy concept needs to be more noticeable in multi-criteria decision-making environments. This study presents the concept of the energy of a multi-valued neutrosophic matrix. The upper and lower bounds of the proposed energy were determined. The connection between the neutrosophic hesitant matrix and the multi-valued neutrosophic matrix is provided. Since the parameters of the two matrices differ in truth, indeterminacy, and false entries, the matrix is converted into a single-valued form, and then the energy was calculated. The MCDM problem was addressed with the proposed energy, which is solved by a novel decision-making method. The task is to select a machine from a group of repaired machines in a particular industry that is in good condition. The final ranking values are calculated by the ranking energy formula that decides which is preferred. Then the comparative results were given to demonstrate the accuracy of the proposed energy outcomes.

Big Science is a fertile learning environment for the transfer of knowledge and technology to suppliers since it boosts economic performance, innovation and reputation. However, despite the growing importance of this topic in the literature, empirical evidence is still limited. This paper investigates technology transfer from Big Science through procurement relationships related to the need to develop front-end technologies for Big Science research infrastructures. The results show that the benefits generated for companies include intangible dimensions, such as the acquisition of technical knowledge and improved reputation. In addition, this procurement relationship leads to organizational changes such as the introduction of new specific organizational units and improved investment in R&D. In turn companies are able enter new markets thanks to the newly acquired competencies.

Career selection in medicine is a complex and underexplored process. Most medical career studies performed in the U.S. focused on the effect of demographic variables and medical education debt on career choice. Considering ongoing U.S. physician workforce shortages and the trilateral adaptive model of career decision making, a robust assessment of professional attitudes and work-life preferences is necessary. The objective of this study was to explore and define the dominant viewpoints related to career choice selection in a cohort of U.S. IM residents. We administered an electronic Q-sort in which 218 IM residents sorted 50 statements reflecting the spectrum of opinions that influence postgraduate career choice decisions. Participants provided comments that explained the reasoning behind their individual responses. In the final year of residency training, we ascertained participating residents' chosen career. Factor analysis grouped similar sorts and revealed four distinct viewpoints. We characterized the viewpoints as "Fellowship-Bound-Academic," "Altruistic-Longitudinal-Generalist," "Inpatient-Burnout-Aware," and "Lifestyle-Focused-Consultant." There is concordance between residents who loaded significantly onto a viewpoint and their ultimate career choice. Four dominant career choice viewpoints were found among contemporary U.S. IM residents. These viewpoints reflect the intersection of competing priorities, personal interests, professional identity, socio-economic factors, and work/life satisfaction. Better appreciation of determinants of IM residents' career choices may help address workforce shortages and enhance professional satisfaction.

Purpose of reviewReferral to nutrition care providers in the USA such as registered dietitian nutritionists (RDNs) for medical nutrition therapy (MNT) remains low. We summarize research on the effectiveness of MNT provided by dietitians versus usual care in the management of adults with dyslipidemia. Improvements in lipids/lipoproteins were examined. If reported, blood pressure (BP), fasting blood glucose (FBG) glycated hemoglobin (A1c), body mass index (BMI), and cost outcomes were also examined.Recent findingsThe synthesis of three systematic reviews included thirty randomized controlled trials. Multiple MNT visits (3-6) provided by dietitians, compared with usual care, resulted in significant improvements in total cholesterol (mean range: - 4.64 to - 20.84 mg/dl), low-density lipoprotein cholesterol (mean range: - 1.55 to - 11.56 mg/dl), triglycerides (mean range: - 15.9 to - 32.55 mg/dl), SBP (mean range: - 4.7 to - 8.76 mm Hg), BMI (mean: - 0.4 kg/m2), and A1c (- 0.38%). Cost savings from MNT were attributed to a decrease in medication costs and improved quality of life years (QALY). Multiple MNT visits provided by dietitians compared with usual care improved lipids/lipoproteins, BP, A1c, weight status, and QALY with significant cost savings in adults with dyslipidemia and justify a universal nutrition policy for equitable access to MNT.

PURPOSE: Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a dont-eat-me signal overexpressed on cancer cells. Cluster of differentiation 47 blockade by magrolimab promotes macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine, which increases expression of eat-me signals. We report final phase Ib data in patients with untreated higher-risk myelodysplastic syndromes (MDS) treated with magrolimab and azacitidine (ClinicalTrials.gov identifier: NCT03248479). PATIENTS AND METHODS: Patients with previously untreated Revised International Prognostic Scoring System intermediate-/high-/very high-risk MDS received magrolimab intravenously as a priming dose (1 mg/kg) followed by ramp-up to a 30 mg/kg once-weekly or once-every-2-week maintenance dose. Azacitidine 75 mg/m2 was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle. Primary end points were safety/tolerability and complete remission (CR) rate. RESULTS: Ninety-five patients were treated. Revised International Prognostic Scoring System risk was intermediate/high/very high in 27%, 52%, and 21%, respectively. Fifty-nine (62%) had poor-risk cytogenetics and 25 (26%) had TP53 mutation. The most common treatment-emergent adverse effects included constipation (68%), thrombocytopenia (55%), and anemia (52%). Median hemoglobin change from baseline to first postdose assessment was -0.7 g/dL (range, -3.1 to +2.4). CR rate and overall response rate were 33% and 75%, respectively. Median time to response, duration of CR, duration of overall response, and progression-free survival were 1.9, 11.1, 9.8, and 11.6 months, respectively. Median overall survival (OS) was not reached with 17.1-month follow-up. In TP53-mutant patients, 40% achieved CR with median OS of 16.3 months. Thirty-four patients (36%) had allogeneic stem-cell transplant with 77% 2-year OS. CONCLUSION: Magrolimab + azacitidine was well tolerated with promising efficacy in patients with untreated higher-risk MDS, including those with TP53 mutations. A phase III trial of magrolimab/placebo + azacitidine is ongoing (ClinicalTrials.gov identifier: NCT04313881 [ENHANCE]).

PURPOSE: We examined how antecedent sexual health factors affect lower urinary tract symptoms (LUTS) in adolescent women. METHODS: We analyzed 1,941 adolescent women from the Avon Longitudinal Study of Parents and Children at age 19. At ages 15 and 17, participants reported use of oral contraceptives (OCs), history of sexual intercourse, number of sexual partners, and condom use. At age 19, The Bristol Female Lower Urinary Tract Symptoms questionnaire quantified the frequency over the past month: stress incontinence, any incontinence, urgency, sensation of incomplete emptying, bladder pain, and urinary tract infection. Multivariable regression models examined associations between sexual health behaviors reported at ages 15 and 17 and six LUTS reported at age 19, after controlling for covariates. RESULTS: Commonly reported LUTS at age 19 were past-month stress incontinence (26.8%), bladder pain (26.3%), any urine leakage (22.1%), and urinary tract infection (15.4%). OC use by age 17 was associated with urgency (odds ratio [OR] = 1.62, 95% confidence interval [CI] 1.19-2.20), incomplete emptying (OR = 1.62, 95% CI = 1.17-2.26), bladder pain (OR = 1.45, 95% CI = 1.15-1.83), and urinary tract infections (OR = 1.68, 95% CI = 1.28-2.21) at age 19 after adjustment for covariates. However, associations were attenuated after adjustment for condom use and number of sexual partners. Sexual intercourse by age 17 was associated with 1.53-2.65 increased odds of LUTs categories except incontinence, with lower confidence interval boundaries > 1.0. Associations were stronger among women with ≥ 3 sexual partners (vs. 0) by age 17. DISCUSSION: We found longitudinally assessed associations between OC use, sexual intercourse, and number of sexual partners during adolescence and LUTS at age 19.

Novel treatment strategies are needed for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in older patients. This trial evaluated the feasibility and outcomes with the anti-CD19 bispecific T-cell-engaging antibody, blinatumomab, in combination with dasatinib and steroids. Patients 65 years of age or older with Ph+ or Ph-like ALL (with dasatinib-sensitive fusions/mutations) were eligible and could be newly diagnosed or relapsed/refractory. Induction therapy consisted of dasatinib/prednisone. Patients not achieving response by day 56 proceeded to blinatumomab reinduction therapy. Patients achieving response with induction or reinduction therapy proceeded to blinatumomab/dasatinib postremission therapy for 3 cycles followed by dasatinib/prednisone maintenance. All patients received central nervous system prophylaxis with intrathecal methotrexate for a total of 8 doses. Response was assessed at days 28, 56, and 84 and at additional time points based on response parameters. Measurable residual disease was assessed centrally by 8-color flow cytometry at day 28. A total of 24 eligible patients with newly diagnosed Ph+ ALL were enrolled with a median age of 73 years (range, 65-87 years). This combination was safe and feasible. With a median of 2.7 years of follow-up, 3-year overall survival and disease-free survival were 87% (95% confidence interval [CI], 64-96) and 77% (95% CI, 54-90), respectively. Although longer follow-up is needed, these results are encouraging, and future trials are building on this backbone regimen. This trial was registered at www.clinicaltrials.gov as #NCT02143414.

Molecular oxygen levels vary during development and disease. Adaptations to decreased oxygen bioavailability (hypoxia) are mediated by hypoxia-inducible factor (HIF) transcription factors. HIFs are composed of an oxygen-dependent α subunit (HIF-α), of which there are two transcriptionally active isoforms (HIF-1α and HIF-2α), and a constitutively expressed β subunit (HIFβ). Under normoxic conditions, HIF-α is hydroxylated via prolyl hydroxylase domain (PHD) proteins and targeted for degradation via Von Hippel-Lindau (VHL). Under hypoxic conditions, hydroxylation via PHD is inhibited, allowing for HIF-α stabilization and induction of target transcriptional changes. Our previous studies showed that Vhl deletion in osteocytes (Dmp1-cre; Vhl f/f ) resulted in HIF-α stabilization and generation of a high bone mass (HBM) phenotype. The skeletal impact of HIF-1α accumulation has been well characterized; however, the unique skeletal impacts of HIF-2α remain understudied. Because osteocytes orchestrate skeletal development and homeostasis, we investigated the role of osteocytic HIF-α isoforms in driving HBM phenotypes via osteocyte-specific loss-of-function and gain-of-function HIF-1α and HIF-2α mutations in C57BL/6 female mice. Deletion of Hif1a or Hif2a in osteocytes showed no effect on skeletal microarchitecture. Constitutively stable, degradation-resistant HIF-2α (HIF-2α cDR), but not HIF-1α cDR, generated dramatic increases in bone mass, enhanced osteoclast activity, and expansion of metaphyseal marrow stromal tissue at the expense of hematopoietic tissue. Our studies reveal a novel influence of osteocytic HIF-2α in driving HBM phenotypes that can potentially be harnessed pharmacologically to improve bone mass and reduce fracture risk. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.