Search

PurposeEntinostat is an oral isoform selective histone deacetylase inhibitor that targets resistance to hormonal therapies in estrogen receptor-positive (ER+) breast cancer. This randomized, placebo-controlled, phase II study evaluated entinostat combined with the aromatase inhibitor exemestane versus exemestane alone.Patients and methodsPostmenopausal women with ER+ advanced breast cancer progressing on a nonsteroidal aromatase inhibitor were randomly assigned to exemestane 25 mg daily plus entinostat 5 mg once per week (EE) or exemestane plus placebo (EP). The primary end point was progression-free survival (PFS). Blood was collected in a subset of patients for evaluation of protein lysine acetylation as a biomarker of entinostat activity.ResultsOne hundred thirty patients were randomly assigned (EE group, n = 64; EP group, n = 66). Based on intent-to-treat analysis, treatment with EE improved median PFS to 4.3 months versus 2.3 months with EP (hazard ratio [HR], 0.73; 95% CI, 0.50 to 1.07; one-sided P = .055; two-sided P = .11 [predefined significance level of .10, one-sided]). Median overall survival was an exploratory end point and improved to 28.1 months with EE versus 19.8 months with EP (HR, 0.59; 95% CI, 0.36 to 0.97; P = .036). Fatigue and neutropenia were the most frequent grade 3/4 toxicities. Treatment discontinuation because of adverse events was higher in the EE group versus the EP group (11% v 2%). Protein lysine hyperacetylation in the EE biomarker subset was associated with prolonged PFS.ConclusionEntinostat added to exemestane is generally well tolerated and demonstrated activity in patients with ER+ advanced breast cancer in this signal-finding phase II study. Acetylation changes may provide an opportunity to maximize clinical benefit with entinostat. Plans for a confirmatory study are underway.

A structure and growth pattern of Squalius cephalus (Linnaeus, 1758) in Tuji tributary of Talar River, Mazandaran Province, was studied during the period from August 2008 till August 2009. In total, 298 fish were caught by electrofishing and fixed in 10% formalin. The weight and length of fish were measured and the age was determinated by scallometric method. The age data showed that fishes were between 0+ to 4+ age groups. Pauli`s applied growth pattern showed a positive alometric for male and female and total fish and a negative isometric for unmature fishes. The average instantaneous growth rate of European Chub showed that the age groups 2+ and 3+ with 1.1 had the fastest growth compare to 3+ and 4+ age groups with 0.89. Condition factor of specimens showed that the highest one with 1.58 (r2 = 0.983) belong to females and the lowest with 1.17 (r2 = 0.901) belong to unmature fishes. The total sex ratio (123 males to 115 females) showed no significant differences between them.

BACKGROUND AND OBJECTIVE: Identification of cancer risk factors in the community and prevention planning in high-risk groups can be helpful in cancer prevention program. Hence, the aim of this study was to investigate the relationship between reproductive factors and breast cancer in the Tabari population-based cohort study in a case-control design. METHODS: This case-control study was performed on the enrolment phase of the Tabari population-based cohort. Patients with breast cancer were considered as case group (51) and non-cancerous individuals (204) as a control group. The two groups were matched based on age category and oral contraceptive pill (OCP) intake. The studied variables included breast cancer history, demographic and reproductive factors. FINDINGS: Mean age of first pregnancy (22.76±4.99 vs. 20.8±4.16, p=0.005), mean age at first birth (23.57±4.94 vs. 21.66±4.07, p=0.006) and age of marriage (22.24±5.75 vs. 19.54±4.92, p=0.001) in the case group were significantly higher than the control group and the number of pregnancies (3.76±2.22 vs. 4.67±2.76, p=0.032) and number of children (3.27±1.97 vs. 4.16±2.44, p=0.019) in the case group was significantly less than the control group. According to multivariate analysis, the odds of incidence of breast cancer in people with first pregnancy over 22 years was 2.76 times more than (p= 0.027) those with first pregnancy age below 22 years. CONCLUSION: "Age at first full-term pregnancy" is one of the major risk factors for breast cancer in the area. [ABSTRACT FROM AUTHOR]

Introduction: Hypothyroidism is a known consequence of external-beam radiotherapy to the neck encompassing a part or whole of the thyroid gland. In this non-randomized prospective study, we have tried to evaluate the response of the thyroid gland to radiation by assessing thyroid function before irradiation and at regular intervals after irradiation. Aims and Objectives: The aim of this study were to assess in the cancer patients, who were exposed to the therapeutic external beam radiation, where radiation portals include a part or whole of the thyroid gland: the incidence of primary hypothyroidism, the time required to become hypothyroid, any relation between the total dose for the development of hypothyroidism, and whether there are any patient or treatment-related factors that are predictive for the development of hypothyroidism, including the use of concurrent chemotherapy. Materials and Methods: This non-randomized, prospective study was conducted for a period of 2 years in which thyroid function was assessed in 59 patients (cases) of head and neck cancer, breast cancer, lymphoma patients and other malignancies, who had received radiotherapy to the neck region. 59 euthyroid healthy patients (controls) were also taken, who had not received the neck irradiation. These patients/controls were assessed periodically for 2 years. Results: The incidence of hypothyroidism after external beam radiation therapy (EBRT) to neck where radiation portals include part or whole of the thyroid gland was 16.94%, seven cases had subclinical hypothyroidism (11.86%) and three cases had clinical hypothyroidism (5.08%). Mean time for development of hypothyroidism was 4.5 months. There was no effect of age, gender, primary tumor site, radiation dose and chemotherapy, whether neoadjuvant or concurrent with the development of hypothyroidism. Conclusion: In summary, we found that thyroid dysfunction is a prevalent, yet easily treatable source of morbidity in patients undergoing radiation therapy to neck where radiation portals include a part or whole of the thyroid gland. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the effect of thermosonication (TS; 37 KHz, 300 W; 30, 40, 50, and 60 °C for 10 min) and NaCl (12 % w/v) on the inactivation of Staphylococcus aureus and Shigella flexneri in lettuce, as well as to examine the kinetics of inactivation and the thermodynamic behaviors of the process. Computational Fluid Dynamics (CFD) simulations were employed to analyze the acoustic pressure field, velocity contours, and streamlines. The results showed that NaCl addition had the least impact on inactivation compared to TS and combined NaCl + TS. Increasing the temperature led to higher inactivation of both bacteria, with a more significant effect at 60 °C. Thermosonication treatment had a more consistent effect on inactivation compared to the addition of NaCl. When exposed to thermosonication, the population of S. aureus and S. flexneri could be reduced by 5.1 to 6.9 log CFU/g and 5.5 to 7.4 log CFU/g, respectively, at temperature levels of 30 and 60 °C. Additionally, no significant relationship between entropy reduction and type of microorganisms was observed. The samples that were treated only with NaCl had higher energy absorption than the other samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: The interferon regulatory factor 7 (IRF7), a member of the IRF family of transcription factors, plays a major role in the regulation of numerous aspects of an immune response and has increasingly been surveyed to determine the aetiology and pathogenesis of systemic sclerosis (SSc). Objective: This study aimed to investigate the transcriptional levels of IRF7 mRNA in peripheral blood mononuclear cells (PBMCs) and the impact of promoter methylation on IRF7 mRNA expression in SSc patients compared to healthy controls., Methods: PBMCs were obtained from confirmed 40 naïve SSc cases and 20 healthy controls for IRF-7 expression and methylation analysis. mRNA expression was performed using the quantitative real-time polymerase chain reaction (SYBR green method) concerning the housekeeping gene. A promoter methylation profile study was carried out by bisulfite treatment of DNA, followed by methylation-specific polymerase chain reaction (MS-PCR) in SSc cases against controls., Results: The relative expression analysis revealed that the selected IRF7 gene was upregulated in the patient group compared to healthy controls (p=0.003). In addition, mRNA expression of IRF7 was significantly increased in the limited cutaneous group compared to the diffuse cutaneous group. Moreover, SSc cases had hypomethylated IRF7 promoters compared to controls, and the significant impact of IRF7 promoter methylation on mRNA expression was observed (p=0.001)., Conclusion: IRF7 overexpression in PBMCs from SSc patients may be caused by IRF7 promoter demethylation, and this aberrant expression of IRF7 in SSc might provide a link between the prominent IFN signature and the development of SSc., Competing Interests: The authors declare no conflict of interest., (© The Author(s).)

Background: As a master immune system regulator, transforming growth factor β1 (TGF-β1) is closely linked to the complicated pathophysiology and development of systemic sclerosis (SSc), a multisystem fibrotic disease., Objective: We aim to evaluate the transcriptional levels of TGF-β1 mRNA in PBMCs, assess the TGF-β1 serum levels of SSc patients, and compare them with those of healthy subjects., Methods: PBMCs were isolated from whole blood of 50 SSc patients and in 30 healthy controls. After total RNA was extracted from isolated PBMCs, complementary DNA (cDNA) synthesis was performed. Afterward, the expression of TGF-β1 mRNA was assessed using quantitative real-time PCR using the SYBR Green, GAPDH, and TGF-β1 specific primers. The serum levels of TGF-β1 were determined using a commercially available ELISA kit., Results: There was a significant upregulation of TGF-β1 relative expression (p < 0.0001), when SSc patients were compared to the control group. The diffuse subgroup was more common in patients with elevated TGF-β1 mRNA expression (p < 0.0001). However, an insignificant difference was observed between the disease subsets of SSc. Serum TGF- β1 levels were upregulated in SSc patients (78.35 ± 23.16) compared to healthy subjects (61.06 ± 15.90), and were considerably higher in SSc patients with ILD (p < 0.01) and positive anti-topo-Isomerase antibody (p < 0.0001)., Conclusion: In patients with SSc, elevated levels of TGF-β1 in serum and their correlation with clinical symptoms imply that this cytokine may serve as a marker for fibrotic and vascular involvement in SSc., Competing Interests: Declarations. Ethical approval: The Institutional Ethics Committee (IEC-SKIMS) approved the study vide protocol number #RP77/2019. Consent to participate: After giving their informed consent and having the right to withdraw at any moment, participants willingly decided to participate in this study. Consent for publication: The patients who participated in this study gave written informed consent for participation and publication of this study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The latest strain of Oreochromis niloticus is an altered ecological adaptation for sustainable aquaculture and is necessary to sustain stocking density and reduce physiological stress of the new strain. The present study aimed to determine the optimum stocking density, biological performance, and economic efficiency of the Nile tilapia. The 14,000 healthy seeds and uniform weight (40 ± 2.4 g) sex-reversed Oreochromis niloticus were stocked in four cages, which are cage (1) 20 fish/m 3 , cage (2) 30 fish/m 3 , cage (3) 40 fish/m 3 , and cage (4) 50 fish/m 3 . The fish were fed 30% dietary protein and feeding frequency three times per day and the feeding rate adjusted according to the fish body weight. Results showed a significantly higher growth, weight gain, and specific growth rate in Nile tilapia stocking density on cage (1), 20 fish/m 3 and cage (2), 30 fish/m 3 compared to cage (3), 40 fish/m 3 and cage (4), 50 fish/m 3 ( p < .05). The survival and growth rate showed an inverse relationship with stocking density. The feed conversion ratio (FCR) is the lowest in cage (1) and cage (2), which is significantly different from those of other cages ( p < .05). The profit index (%) was significantly higher at low density. There was no significant variation in the HSI, VSI and CF. The digestive enzymes such as lipase and amylase were secreted highly in the cages (3) and (4) but high protease was secreted in cage (1). The lipid, ash, and protein of the whole fish were reduced to a lower density, but the moisture levels in the fish bodies raised significantly ( p < .05) with increasing stocking density. The phenomenal regression indicates that 25-35 fish/m 3 are optimum stocking density for Nile tilapia in the cage culture system. The current study has made significant step toward optimizing the stocking density of a new strain and developing cage culture in Pakistan., Competing Interests: All authors declare no conflicts of interest., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

Targeting of the estrogen receptor (ER) by anti-estrogens is the standard-of-care for patients with ER+ HER2- advanced/metastatic breast cancer. While anti-estrogens that degrade ERα (fulvestrant) or block estrogen production (aromatase inhibitors) have improved patient outcomes, clinically important challenges remain related to drug administration, limited bioavailability, lack of brain exposure, and acquired resistance due to ESR1 mutations. These limitations indicate a need for more robust ER-targeted therapies. Here, we discovered and characterized imlunestrant, a next-generation potent, brain-penetrant oral selective estrogen receptor degrader (SERD). Imlunestrant degraded ERα and decreased ERα-mediated gene expression both in vitro and in vivo. Cell proliferation and tumor growth in ESR1 wildtype and mutant models were significantly inhibited by imlunestrant. Combining imlunestrant with abemaciclib (CDK4/6 inhibitor), alpelisib (PI3K inhibitor), or everolimus (mTOR inhibitor) further enhanced tumor growth inhibition, regardless of ESR1 mutational status. In an ER+ breast cancer intracranial tumor model, imlunestrant prolonged survival compared to vehicle or alternative SERD therapies. Together, these finding support the potential of imlunestrant to degrade ERα and suppress the growth of ESR1 wildtype and mutant breast cancer, including brain metastatic tumors.

With buildings representing a substantial portion of global energy consumption, exploring alternatives to traditional fossil fuel-based heating and cooling systems is critical. Thermoelectricity offers a promising solution by converting temperature differentials into electrical voltage or vice versa, enabling efficient indoor thermal regulation. This paper presents a comprehensive investigation into the integration of thermoelectric wall systems for sustainable building climate control through numerical simulations and experimental analyses. Numerical simulations using computational fluid dynamics (CFD) techniques were conducted to model fluid flow and heat transfer within the thermoelectric wall systems under various operating conditions. These simulations provided insights into the system's thermal behavior, which were validated through experimental setups designed to measure temperature differentials, airflow rates, and power consumption. The results showed that power consumption is directly correlated with electrical current, ranging from 0.19 W to 77.4 W as the current increased from 0.1 A to 2 A. Additionally, the heat absorbed by the system increased significantly with electrical current, by 706-1044%, depending on the air velocity. The thermal energy released from the hot side of the thermoelectric modules also rose substantially, ranging from 9850 to 5285% with increasing electrical current, and from 275 to 51% with higher air velocities. Moreover, increasing air velocity led to a 6.78-9.37% reduction in power consumption for currents between 0.1 A and 2 A. The coefficient of performance (COP) analysis revealed that optimizing both electrical current and air velocity is essential for maximizing system efficiency. While fan power consumption reduces COP at higher air velocities, neglecting fan power consumption results in COP improvements ranging from 6.5 × 10⁻⁴ to 49.0%. These findings highlight the potential of thermoelectric wall systems to enhance indoor comfort and energy efficiency in buildings., (© 2024. The Author(s).)

Background/objectives: Adherence to pediatric obesity treatment can be challenging. Monetary incentives improve adherence to lifestyle interventions, with incentives framed as loss often more effective than those framed as gain. The objectives of this study were to determine if monetary incentives in the form of gift cards would improve adherence to an obesity treatment intervention and whether framing the incentive as either loss or gain affected adherence., Methods: Sixty adolescents with obesity (body mass index of ≥95th percentile for age and sex) were recruited from our pediatric obesity treatment program. They were randomized into one of three groups and given a monthly adherence score (AS) of up to 100 points. These points were based on completing a medical visit, reporting on diet intake, and measuring daily steps on a wearable tracker. The Gain Group (GG), N = 20, started each month with USD 0 in a virtual account and increased their monetary reward up to USD 100 depending on AS. The Loss Group (LG), N = 21, began each month with USD 100 in their virtual account, which decreased based on adherence. The Control Group (CG), N = 19, received USD 10 monthly., Results: Adherence was highest in the GG, with 66.0 points, compared to the LG, with 54.9 points, and CG, with 40.6 points, with p < 0.01. The GG had greater adherence to their step goal (14.6) and dietary reporting (18.7) compared to the LG (10.0 and 13.9) and the CG (3.9 and 8.1), p < 0.005., Conclusions: Gain-framed incentives are superior to loss-framed ones in improving adherence to pediatric obesity treatments.

Vitamin D deficiency is widespread and poses a significant health concern, as emerging research links it to allergic diseases owing to its immunomodulatory functions. The optimal functioning of vitamin D and its activation depend on its nuclear receptor, vitamin D receptor (VDR). Genetic variants of VDR have been explored as potential factors in autoimmune and allergic diseases, with limited studies on their association with allergic rhinitis (AR). The present investigation aims to analyse the role of three VDR genetic variants - TaqI, FokI and BsmI - in AR susceptibility and their impact on VDR mRNA and serum vitamin D levels. A total of 550 subjects, consisting of 250 AR cases and 300 age- and gender-matched controls, underwent genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). VDR mRNA and vitamin D levels were determined by quantitative real-time PCR and chemiluminescence, respectively. Although TaqI did not exhibit significant differences, FokI demonstrated a noteworthy association with AR, particularly with the CC genotype (odds ratio [OR]: 3.34; confidence interval [CI]: 1.79-6.23). Similarly, BsmI revealed an increased risk for AR, with the GA + AA genotypes showing a 2.2-fold elevated risk (OR: 2.20; CI: 1.53-3.16). VDR mRNA expression was threefold lower in AR patients (p < .0001), accompanied by reduced serum vitamin D levels (p < .0001). In addition, CC (p = .01) and AA (p = .02) genotypes of FokI and BsmI were associated with reduced VDR mRNA levels, whereas TaqI showed no such association. Similarly, heterozygous genotypes of TaqI and FokI, as well as homozygous AA of BsmI, correlated with lower serum vitamin D levels (p < .001). This study emphasizes the intricate relationship among VDR genetic variations, altered VDR activity, immune modulation and vitamin D metabolism in AR. Further research involving diverse populations is crucial for confirming and generalizing these findings, paving the way for personalized therapeutic interventions in vitamin D-related disorders., (© 2024 John Wiley & Sons Ltd.)

Present study investigates the effects of probe size geometry on thermodynamic kinetics, rheology, and microstructure of wheat and tapioca starch. Ultrasound treatment using different probe diameters (20 mm and 100 mm) significantly influenced the gelatinization process. Results showed reduced enthalpy (ΔH) and Gibbs energy (ΔG), indicating enhanced gelatinization efficiency. According to the results, using a 20 mm and 100 mm probe leads to a reduction of 52.7 % and 68.6 % in reaction enthalpy for wheat starch compared to native starch, respectively. Microstructure analysis revealed structural changes, with ultrasound treatment leading to granular fractures and a sheet-like structure with air bubbles. The rheological behavior of the starches is found to exhibit shear thinning behavior, with the Casson model providing the best fit for the experimental data. Moreover, rheology modeling using Herschel-Bulkley and power law models showed increased viscosity and shear stress in larger probes. Numerical simulation data demonstrated that probe size influenced ultrasonic pressure, sound pressure level, and thermal power dissipation density, affecting fluid motion and velocity field components. Moreover, the maximum dissipated power decreases from 8.43 to 0.655 mW/m 3 with an increase in probe diameter from 20 to 100 mm. The average yield shear stress values are calculated as 3.36 and 3.14 for wheat and tapioca starches, respectively. The larger probe diameter leads to greater entropy increases, with tapioca starch showing a 4.72 % increase and wheat starch a 4.97 % increase, compared to 2.56 % and 3.11 %, respectively, with the smaller probe. Additionally, the Keller-Miksis model provided insights into bubble dynamics, revealing increased pressure and temperature with higher pressure amplitudes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details assessment and management of the child with overweight or obesity. The term "child" is defined as the child between 2 and 12 years of age. Because children are in a continual state of development during this age range, we will specify when our discussion applies to subsets within this age range. For the purposes of this CPS, we will use the following definitions: overweight in the child is a body mass index (BMI) ≥ 85th and <95th percentile, obesity in the child is a BMI ≥95th percentile, and severe obesity is a BMI ≥120% of the 95th percentile., Methods: The information and clinical guidance in this OMA Clinical Practice Statement are based on scientific evidence, supported by medical literature, and derived from the clinical perspectives of the authors., Results: This OMA Clinical Practice Statement provides an overview of prevalence of disease in this population, reviews precocious puberty in the child with obesity, discusses the current and evolving landscape of the use of anti-obesity medications in children in this age range, discusses the child with obesity and special health care needs, and reviews hypothalamic obesity in the child., Conclusions: This OMA Clinical Practice Statement on the child with obesity is an evidence based review of the literature and an overview of current recommendations. This CPS is intended to provide a roadmap to the improvement of the health of children with obesity, especially those with metabolic, physiological, psychological complications and/or special healthcare needs. This CPS addresses treatment recommendations and is designed to help the clinician with clinical decision making., Competing Interests: Authors of this Clinical Practice Statement received no payment for their writing, editing, and publishing work. While listed journal Editors received payment for their roles as Editors, they did not receive payment for their participation as authors.Suzanne Cuda: Rhythm Gold panel, Rhythm Advisory Board. Marisa Censani: none. Valerie O'Hara: Novo Nordisk speaker: telehealth conference 2023. Jennifer Paisley: Rhythm Pharmaceuticals speakers bureau. Roohi Kharofa: Rhythm Pharmaceuticals: EMANATE trial. Rushika Conroy: GOLD academy faculty for Rhythm Pharmaceuticals. Brooke Sweeney: Rhythm Pharmaceutical: Speaker, Consultant, BEAM Project, and Research support; no financial support; Consulting Novo Nordisk, past consultant Nestle Corp. and Eli Lilly. Cristina Fernandez: Rhythm Pharmaceutical: Council HPS and BEAM Project, No financial compensation. Meredith Dryer: none. Nancy T. Browne: none., (© 2024 The Authors.)

In this study, thermosonication (37 KHz, 300 W; 50, 60, and 70 °C) of celery juice was performed to inactivate Escherichia coli and Salmonella Typhi in 6 min. The inactivation of pathogens and the process were modeled using mathematical, thermodynamic, and computational fluid dynamics models. The findings indicated that the distribution of power dissipation density was not uniform across the entire domain, including the beaker area, with a maximum value of 27.8 × 10 3  W/m 3 . At lower temperatures, E. coli showed a 9.4 % higher resistance to sonication, while at higher temperatures, S. Typhi had a 5.4 % higher durability than E. coli. Increasing the temperature decreased the maximum inactivation rate of both S. Typhi and E. coli by 15.5 % and 20.5 % respectively, while increasing the thermal level by 20 °C reduced the log time to achieve the maximum inactivation rate by 20.3 % and 34.9 % for S. Typhi and E. coli respectively, highlighting the stronger effect of sonication at higher temperatures. According to the results, the positive magnitudes of ΔG were observed in both E. coli and S. Typhi, indicating a similar range of variations. Additionally, the magnitude of ΔG increased by approximately 5.2 to 5.5 % for both microorganisms which suggested the inactivation process was not spontaneous., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The study aimed to optimize the ultrasonic-assisted modification (UAM) of corn and potato starch by assessing the influence of ultrasound geometry, power, and frequency on the fluid flow for sonicated starch to achieve porous starch with a higher degree of hydrolyzing by α-amylase. This assessment was conducted through mathematical modeling and 3D computational fluid dynamics (CFD) simulations. The ultrasonic pressure field is determined by the solution of the non-linear Westervelt equation in the frequency domain. Then, the obtained field is utilized to simulate the dissipated power and flow field characteristics. According to the results obtained from the Rapid Visco Analyzer (RVA), it was observed that the peak and final viscosity of hydrolyzed sonicated starch were less than hydrolyzed native starch. This decrease in viscosity indicates a breakdown of the starch structure, leading to a more fluid-like consistency. The shear rate and shear stress data are used for rheology modeling. The fluid's viscosity is represented based on three models of Herschel-Bulkley, Casson, and Power law (Ostwald-de Waele). The magnitude of yield shear stress at low shear rates, the shear-thinning behavior, and the nearly Newtonian fluid nature at high shear rates are extracted from the viscosity models. The surfaces of the starch granules were analyzed using scanning electron microscopy (SEM) revealed that sonication treatments caused damage, cracks, and porosity on the surfaces of the starch granules which were prone to amylolytic enzymes. This indicates that the structural integrity of the granules was compromised and facilitated enzyme penetration. This study proposes that ultrasonication can be utilized to produce damaged starch, which is susceptible to hydrolysis by α-amylase. This approach holds the potential for reducing enzyme consumption in various industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The COVID-19 pandemic has resulted in significant financial losses globally, increasing the volatility of financial assets. Thus, this study models the stock market volatility of developed economies during the COVID-19 pandemic. For this purpose, we used the GJR-GARCH (Albulescu, 2020; Albulescu, 2020) [1,1] econometric model on the daily time series returns data ranging from 01 st -July-2019 to 18th-November-2020. The entire dataset was equally divided into two subsets; before COVID-19, and after the COVID-19. The empirical results of this study showed the presence of volatility clustering, leverage effect, and excess kurtosis indicating leptokurtic phenomena in all stock indices returns. In addition to this, it can be noted that compared to before COVID-19, the stock markets showed negative returns, and increased volatility during the COVID-19. Hence, based on these findings, this study provides significant insights for global stock market investors and economic policymakers regarding financial portfolio construction particularly during crises times., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background and Objectives: In the United States, many child neurologists (CNs) and neurodevelopmental disability (NDD) specialists who read EEGs in clinical practice had no additional EEG training other than what was received during residency. This practice highlights the importance of ensuring that CN/NDD residents achieve EEG competence before graduation. However, prior survey-based evidence showed that roughly a third of graduating CN residents in the United States do not feel confident interpreting EEGs independently. As part of a needs assessment, we conducted a descriptive study characterizing EEG practices in CN and NDD residency programs in the United States and Canada., Methods: A 30-question e-survey focused on characteristics of residency programs and their EEG teaching practices was sent to all 88 CN and NDD residency program directors listed in the Accreditation Council for Graduate Medical Education, Child Neurology Society, and Canadian Residency Matching Service websites., Results: Twenty-nine (n = 29/88; 33%) residency programs completed the survey, most of which were CN (90%), academic (90%), and located in the United States (83%). The mean number of weeks dedicated to EEG training required to graduate was 7.3 ± 4 (mean ± SD). EEG rotations involved the clinic/outpatient setting (83%), epilepsy monitoring unit (EMU) (76%), and inpatient setting (excluding EMU) (72%). During a 4-week EEG rotation, residents typically read 16-45 EEGs (62%). The most common methods of EEG teaching in CN/NDD programs were teaching during EEG rotation and yearly didactics. The mean number of EEGs read per rotation had a significant positive correlation with the average percentage of residents who reportedly achieve EEG competence by graduation (coefficient 0.461; p = 0.007). Barriers to EEG education were reported by 28% of the programs; the most common barrier identified was insufficient EEG exposure. Possible solutions were primarily related to increasing quality and quantity of EEG exposure. Almost two-thirds of programs reported not using objective measures to assess EEG competence., Discussion: Our results characterize resident EEG education in a third of CN/NDD residency programs in the United States and Canada. We suggest that residency leaderships consider standardization of EEG learning along with establishment and implementation of objective measures in training requirements and competence assessment., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NE for full disclosures., (© 2024 American Academy of Neurology.)

Cholesterol mediates membrane compartmentalization, affecting signaling via differential distribution of receptors and signaling mediators. While excessive cholesterol and aberrant transforming growth factor-β (TGF-β) signaling characterize multiple liver diseases, their linkage to canonical vs. non-canonical TGF-β signaling remained unclear. Here, we subjected murine hepatocytes to cholesterol depletion (CD) or enrichment (CE), followed by biophysical studies on TGF-β receptor heterocomplex formation, and output to Smad2/3 vs. Akt pathways. Prior to ligand addition, raft-dependent preformed heteromeric receptor complexes were observed. Smad2/3 phosphorylation persisted following CD or CE. CD enhanced phospho-Akt (pAkt) formation by TGF-β or epidermal growth factor (EGF) at 5 min, while reducing it at later time points. Conversely, pAkt formation by TGF-β or EGF was inhibited by CE, suggesting a direct effect on the Akt pathway. The modulation of the balance between TGF-β signaling to Smad2/3 vs. pAkt (by TGF-β or EGF) has potential implications for hepatic diseases and malignancies., (© 2024. The Author(s).)

To achieve wheat starch acetylation (AC) with a high degree of substitution (DS), the acetylation process was carried out using various ultrasonication frequencies, including 25 kHz, 40 kHz, and 25 + 40 kHz. In the second step, wheat starch's ultrasound-assisted acetylation (UAA) is simulated using various approaches including the rheology models, non-isothermal reaction kinetics, and flow/acoustic modelling. The computational fluid dynamics (CFD) simulation solves the non-linear acoustic governing equation to determine the flow field and the amount of delivered ultrasound energy. The acetylated starch increased peak and final viscosity, with the highest values observed for the 25 + 40 kHz frequency than other single frequencies (25 kHz and 40 kHz). The viscosity of the starch is specified based on the experimental data using Herschel-Bulkley, power law, and Casson rheology models. According to differential scanning calorimetry (DSC) analysis, the gelatinization parameters and enthalpy of gelatinization (ΔH gel ), were found to be lower in acetylated starches at the frequency of 25 + 40 kHz compared to those at frequencies of 25 kHz and 40 kHz, as well as native starches (NS). Moreover, the gelatinization process is examined by implementing the non-isothermal reaction kinetics to obtain the activation energy and reaction order. Based on the results obtained, implementing sonication at 25 kHz reduces the activation energy by 70.3 % compared to native starch. However, the same parameter is obtained to be 69.9 % and 67.1 % for the application of 40 and 25 + 40 kHz transducers, respectively. Additionally, during the sonication treatment, the yield shear stress increases between 24.1 and 31.8 %, based on the applied frequency. Morphology analysis determined by scanning electron microscopy (SEM) revealed that the surfaces and small granules underwent more damage in acetylated starches at frequencies of 25 kHz and 40 kHz. However, in acetylated starches at 25 + 40 kHz, the larger granules were more affected than the smaller ones., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background & Aims: Transforming growth factor-β1 (TGF-β1) plays important roles in chronic liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD involves various biological processes including dysfunctional cholesterol metabolism and contributes to progression to metabolic dysfunction-associated steatohepatitis and hepatocellular carcinoma. However, the reciprocal regulation of TGF-β1 signaling and cholesterol metabolism in MASLD is yet unknown., Methods: Changes in transcription of genes associated with cholesterol metabolism were assessed by RNA sequencing of murine hepatocyte cell line (alpha mouse liver 12/AML12) and mouse primary hepatocytes treated with TGF-β1. Functional assays were performed on AML12 cells (untreated, TGF-β1 treated, or subjected to cholesterol enrichment [CE] or cholesterol depletion [CD]), and on mice injected with adenovirus-associated virus 8-control/TGF-β1., Results: TGF-β1 inhibited messenger RNA expression of several cholesterol metabolism regulatory genes, including rate-limiting enzymes of cholesterol biosynthesis in AML12 cells, mouse primary hepatocytes, and adenovirus-associated virus-TGF-β1-treated mice. Total cholesterol levels and lipid droplet accumulation in AML12 cells and liver tissue also were reduced upon TGF-β1 treatment. Smad2/3 phosphorylation after 2 hours of TGF-β1 treatment persisted after CE or CD and was mildly increased after CD, whereas TGF-β1-mediated AKT phosphorylation (30 min) was inhibited by CE. Furthermore, CE protected AML12 cells from several effects mediated by 72 hours of incubation with TGF-β1, including epithelial-mesenchymal transition, actin polymerization, and apoptosis. CD mimicked the outcome of long-term TGF-β1 administration, an effect that was blocked by an inhibitor of the type I TGF-β receptor. In addition, the supernatant of CE- or CD-treated AML12 cells inhibited or promoted, respectively, the activation of LX-2 hepatic stellate cells., Conclusions: TGF-β1 inhibits cholesterol metabolism whereas cholesterol attenuates TGF-β1 downstream effects in hepatocytes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

PhoP-PhoR, one of the 12 two-component systems (TCSs) that empower M. tuberculosis to sense and adapt to diverse environmental conditions, remains essential for virulence, and therefore, represents a major target to develop novel anti-TB therapies. Although both PhoP and PhoR have been structurally characterized, the signal(s) that this TCS responds to remains unknown. Here, we show that PhoR is a sensor of acidic pH/high salt conditions, which subsequently activate PhoP via phosphorylation. In keeping with this, transcriptomic data uncover that acidic pH- inducible expression of PhoP regulon is significantly inhibited in a PhoR-deleted M. tuberculosis. Strikingly, a set of PhoP regulon genes displayed a low pH-dependent activation even in the absence of PhoR, suggesting the presence of non-canonical mechanism(s) of PhoP activation. Using genome-wide interaction-based screening coupled with phosphorylation assays, we identify a non-canonical mechanism of PhoP phosphorylation by the sensor kinase PrrB. To investigate how level of P~PhoP is regulated, we discovered that in addition to its kinase activity PhoR functions as a phosphatase of P~PhoP. Our subsequent results identify the motif/residues responsible for kinase/phosphatase dual functioning of PhoR. Collectively, these results uncover that contrasting kinase and phosphatase functions of PhoR determine the homeostatic mechanism of regulation of intra-mycobacterial P~PhoP which controls the final output of the PhoP regulon. Together, these results connect PhoR to pH-dependent activation of PhoP with downstream functioning of the regulator. Thus, PhoR plays a central role in mycobacterial adaptation to low pH conditions within the host macrophage phagosome, and a PhoR-deleted M. tuberculosis remains significantly attenuated in macrophages and animal models., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Physicians and medical students who desire to build families face significant barriers due to the structure and culture of medicine., Objective: To understand the barriers and facilitators to family building for all people in medicine-not only individuals who can become pregnant-through an open-ended, qualitative analysis of survey responses., Design, Setting, and Participants: This qualitative study used a survey conducted in April and May 2021 with a broad sample of physicians and medical students. Participants were recruited through social media, targeting physician and medical student communities. Physicians (residents, fellows, and physicians in independent practice) and medical students of all gender identities and sexual orientations were included. Informed by a postpositivist approach, coding reliability thematic analysis was performed on 3 open-ended survey questions on family-building experiences (what they would do differently, what advice they have for others, and anything else they wished to share)., Main Outcomes and Measures: Identified themes were mapped to the social-ecological model, a model used in public health to examine how a spectrum of factors is associated with health outcomes., Results: A total of 2025 people (1860 [92%] women; 299 [15%] Asian, 151 [8%] Black, and 1303 [64%] White; 1730 [85%] heterosexual; and 1200 [59%] physicians who had completed training) responded to at least 1 of 3 open-ended questions. Themes mapped to social-ecological model levels included: (1) cultural, eg, medical training being at odds with family building; (2) organizational, eg, lack of institutional support for the range of family-building routes; (3) interpersonal, eg, impact of social support on family building; and (4) individual, eg, socioeconomic status and other individual factors that facilitate or inhibit family building. Recommendations to improve family-building experiences include implementing family-building curricula at medical schools, providing adequate parental leave for all physicians and medical students who become parents, and providing insurance coverage for all family-building routes., Conclusions and Relevance: In this qualitative study of physicians and medical students, self-reported barriers to family building were identified at each level of the social-ecological model. Addressing these barriers is critical to creating a more equitable family-building environment for physicians and medical students.

Background and Objectives: Management of hepatic abscesses has traditionally been performed by image-guided percutaneous techniques. More recently, EUS drainage has been shown to be efficacious and safe. The aim of this study is to compare EUS-guided versus percutaneous catheter drainage (PCD) of hepatic abscesses., Methods: Patients who underwent EUS-guided drainage or PCD of hepatic abscesses from January 2018 through November 2021 from 4 international academic centers were included in a dedicated registry. Demographics, clinical data preprocedure and postprocedure, abscess characteristics, procedural data, adverse events, and postprocedure care were collected., Results: Seventy-four patients were included (mean age, 63.9 years; 45% male): EUS-guided ( n = 30), PCD ( n = 44). Preprocedure Charlson Comorbidity Index scores were 4.3 for the EUS group and 4.3 for the PCD group. The median abscess size was 8.45 × 6 cm (length × width) in the EUS group versus 7.3 × 5.5 cm in the PCD group. All of the abscesses in the EUS group were left-sided, whereas the PCD group contained both left- and right-sided abscesses (29 and 15, respectively). Technical success was 100% in both groups. Ten-millimeter-diameter stents were used in most cases in the EUS group, and 10F catheters were used in the PCD group. The duration to resolution of symptoms from the initial procedure was 10.9 days less in the EUS group compared with the PCD group ( P < 0.00001). Hospital length of stay was shorter in the EUS group by 5.2 days ( P = 0.000126). The EUS group had significantly fewer number of repeat sessions: mean of 2 versus 7.7 ( P < 0.00001) and trended toward fewer number of procedure-related readmissions: 10% versus 34%. The PCD group had a significantly higher number of adverse events ( n = 27 [61%]) when compared with the EUS group ( n = 5 [17%]; P = 0.0001)., Conclusions: EUS-guided drainage is an efficacious and safe intervention for the management of hepatic abscesses. EUS-guided drainage allows for quicker resolution of symptoms, shorter length of hospital stay, fewer adverse events, and fewer procedural sessions needed when compared with the PCD technique. However, EUS-guided drainage may not be feasible in right-sided lesions., Competing Interests: Amy Tyberg is consultant for Ninepoint Medical, Endogastric Solutions, Obalon Therapeutics. Avik Sarkar has done consulting work for US Endoscopy and Obalon Therapeutics. Haroon Shahid has done consulting work for US Endoscopy. Michel Kahaleh has received grants support from Boston Scientific, Fujinon, W. L. Gore, Apollo Endosurgery, Cook Endoscopy, GI Dynamics, Merit Medical, Interscope Med, Olympus, ERBE, and MI Tech. He is a consultant for Boston Scientific and Laboratories Inc, AbbVie. None of this funding was related to this article. Monica Gaidhane is consultant for 3D Matrix. The other authors declare that they have no financial conflict of interest with regard to the content of this report. Everson L. Artifon and Michel Kahaleh are Assocated Editors of the journal. This article was subject to the journal's standard procedures, with peer review handled independently of the editors and their research groups., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Scholar Media Publishing.)

Background and Objectives: We recently published expert consensus-based curricular objectives for routine EEG (rEEG) interpretation for adult and child neurology residents. In this study, we used this curriculum framework to develop and validate an online, competency-based, formative and summative rEEG examination for neurology residents., Methods: We developed an online rEEG examination consisting of a brief survey and 30 multiple-choice questions covering EEG learning objectives for neurology residents in 4 domains: normal, abnormal, normal variants, and artifacts. Each question contained a deidentified EEG image, displayed in 2 montages (bipolar and average), reviewed and optimized by the authors to address the learning objectives. Respondents reported their level of confidence (LOC, 5-point Likert scale) with identifying 4 categories of EEG findings independently: states of wakefulness/sleep, sleep structures, normal variants, and artifacts. Accuracy and item discrimination were calculated for each question and LOC for each category. The test was disseminated by the International League Against Epilepsy and shared on social media., Results: Of 2,080 responses, 922 were complete. Respondents comprised clinical neurophysiologists/experts (n = 41), EEG/epilepsy clinical fellows (n = 211), EEG technologists (n = 128), attending neurologists (n = 111), adult neurology residents (n = 227), child neurology residents (n = 108), medical students (n = 24), attending non-neurologists (n = 18), and others (n = 54). Mean overall scores (95% CI) were 82% (77-86) (clinical neurophysiologists), 81% (79-83) (clinical fellows), and 72% (70-73) (adult and child neurology residents). Experts were more confident than clinical fellows in all categories but sleep structures. Experts and clinical fellows were more confident than residents in all 4 categories. Among residents, accuracy and LOC increased as a function of prior EEG weeks of training. Accuracy improved from 67% (baseline/no prior EEG training) to 77% (>12 prior EEG weeks). More than 8 weeks of EEG training was needed to reach accuracy comparable with clinical neurophysiologists on this rEEG examination. Increase in LOC was slower and less robust than increase in accuracy. All but 3 questions had a high discrimination index (>0.25)., Discussion: This online, competency-based rEEG examination, mapped to a published EEG curriculum, has excellent psychometrics and differentiates experienced EEG readers from adult and child neurology residents. This online tool has the potential to improve resident EEG education worldwide., Competing Interests: F. Nascimento, H. Gao, R. Katyal, R. Matthews, S. Yap, S. Rampp, W. Tatum, S. Beniczky report no disclosures relevant to the manuscript. R.E. Strowd is the Editor-in-Chief of Neurology® Education. Go to Neurology.org/NE for full disclosures., (© 2023 American Academy of Neurology.)

Background: Health-related quality of life is rapidly becoming recognized as an important indicator of how a disease affects patient lives and for evaluating the quality of care, especially for chronic conditions such as chronic kidney disease (CKD). Objectives: This study is an attempt to assess the quality of life in patients with chronic kidney disease at MMIMSR and also identify characteristics that may be associated with their worsening quality of life. Materials and Methods: This cross-sectional investigation was conducted at the in-patient department (IPD) of the MMIMSR hospital. This study included 105 CKD patients and used a systematic random sampling method for quantitative analysis. This study utilized a 36-item short-form SF-36 (v1.3) questionnaire to assess HRQoL in CKD patients. Descriptive statistics were employed at the baseline. Chi square and ANOVA were used to draw comparisons between two groups or more than two groups, respectively. Logistic regression analysis was utilized to identify the potential QoL determinants. A p value of 0.05 or lower was used to determine statistical significance. Results: Among a total of 105 participants, the mean (±standard deviation) age was found to be 54.53 ± 13.47 years; 48 were male patients, and 57 were female patients. Diabetes Mellitus (61.9%), hypertension (56.2%), chronic glomerulonephritis (7.6%), chronic pyelonephritis (6.7%), and polycystic kidney disease (5.7%) were identified to be the most frequent disorders associated with CKD. The current study also demonstrated that the HRQoL score domains such as symptom problem list, the effect of kidney disease, and the burden of kidney disease decline significantly and progressively as the patient advances into higher stages of CKD ( p = 0.005). A similar pattern was observed in work status, sleep, and general health ( p < 0.005). Additionally, a statistically significant difference was noted for cognitive function, quality of social interaction, overall health, dialysis staff encouragement, patient satisfaction, social support, physical functioning, role of physical health, pain, emotional well-being, role of emotional health, social functioning, and energy fatigue ( p < 0.005). The mean difference for PCS and MCS based on CKD stages was found to be statistically significant ( p < 0.005). The PCS and MCS showed a positive correlation with GFR (r = 0.521), and Hb (r = 0.378), GFR (r = 0.836), and Hb (r = 0.488), respectively. Conclusions: The findings of this study demonstrated that a significant decrease in HRQoL was observed among CKD patients, with a progressive deterioration of HRQoL dimensions as the patient advances to end-stage renal disease. This study also revealed that CKD imposes various restrictions on patients' day-to-day lives, particularly in terms of their physical and mental functioning, even in the initial stages of the disease.

Background: COVID-19, caused by the SARS-CoV-2 virus, swiftly disseminated and was declared a pandemic. Variations in the ACE2 gene can impact the virus's ability to bind to ACE2 receptor, potentially influencing an individual's susceptibility and its association with COVID-19 severity across various populations., Methods: In total, 200 individuals were sequenced for the ACE2 gene and potential impact of the found variants on the ACE2 protein was assessed using in-silico tools., Results: Eight variations in the ACE2 gene were identified in 27 COVID-19 patients, of which four were missense and four were intronic variants. Three variants had a MAF of < 0.01 (c.251C > T, p.Pro86Leu; 15C > G, p.S5S; and c. 91 A > G, p.Lys31Glu). A missense variant, p.Pro86Leu, C > T, TT genotype, was found in 9 out of 200 individuals with an allele frequency of 0.045 and showed a significant association with COVID-19 (P = 0.003). The heterozygous allele of 15C > G, p.S5S, was found with a frequency of 0.02 (8/400) in eight patients, and its CG genotype showed a significant association with COVID-19 (P = 0.0068). The remaining identified variants were not associated with COVID-19 susceptibility., Conclusion: The ACE2 gene sequence in Pakistani individuals exhibited a low frequency of identified variants in COVID-19 patients. Overall, only two variants were associated with susceptibility to the disease, possibly contributing to Pakistan's lower COVID-19 mortality and infection rates. However, individuals carrying the mutant variant experienced more severe symptoms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Thrombosis of the umbilical vein/artery is a rare complication and is highly associated with fetal mortality. Varix of the fetal umbilical vein is a very rare anomaly and refers to the focal dilatation of the umbilical vein of the fetus. It appears as a round or fusiform cystic structure in the fetal abdomen. Here, in this case report, we hereby discuss a 28-year-old pregnant female with a gestational age of 26 weeks from last menstrual period, who on antenatal ultrasound had findings suggestive of umbilical vein varix with thrombosis and hydrops fetalis., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Medical Ultrasound.)

Cancer poses a significant global health challenge, with predictions of increasing prevalence in the coming years due to limited prevention, late diagnosis, and inadequate success with current therapies. In addition, the high cost of new anti-cancer drugs creates barriers in meeting the medical needs of cancer patients, especially in developing countries. The lengthy and costly process of developing novel drugs further hinders drug discovery and clinical implementation. Therefore, there has been a growing interest in repurposing approved drugs for other diseases to address the urgent need for effective cancer treatments. The aim of this comprehensive review is to provide an overview of the potential of approved non-oncology drugs as therapeutic options for cancer treatment. These drugs come from various chemotherapeutic classes, including antimalarials, antibiotics, antivirals, anti-inflammatory drugs, and antifungals, and have demonstrated significant antiproliferative, pro-apoptotic, immunomodulatory, and antimetastatic properties. A systematic review of the literature was conducted to identify relevant studies on the repurposing of approved non-oncology drugs for cancer therapy. Various electronic databases, such as PubMed, Scopus, and Google Scholar, were searched using appropriate keywords. Studies focusing on the therapeutic potential, mechanisms of action, efficacy, and clinical prospects of repurposed drugs in cancer treatment were included in the analysis. The review highlights the promising outcomes of repurposing approved non-oncology drugs for cancer therapy. Drugs belonging to different therapeutic classes have demonstrated notable antitumor effects, including inhibiting cell proliferation, promoting apoptosis, modulating the immune response, and suppressing metastasis. These findings suggest the potential of these repurposed drugs as effective therapeutic approaches in cancer treatment. Repurposing approved non-oncology drugs provides a promising strategy for addressing the urgent need for effective and accessible cancer treatments. The diverse classes of repurposed drugs, with their demonstrated antiproliferative, pro-apoptotic, immunomodulatory, and antimetastatic properties, offer new avenues for cancer therapy. Further research and clinical trials are warranted to explore the full potential of these repurposed drugs and optimize their use in treating various cancer types. Repurposing approved drugs can significantly expedite the process of identifying effective treatments and improve patient outcomes in a cost-effective manner., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This study examined the effect of beef fermentation with Lactiplantibacillus paraplantarum ( L ) PTCC 1965, Lactiplantibacillus ( L ) plantarum subsp. plantarum PTCC 1745, and Lactiplantibacillus ( L ) pentosus PTCC 1872 bacteria on the growth of pathogenic bacteria, including Salmonella (S) Typhi PTCC 1609 and Staphylococcus ( S ) aureus PTCC 1826. The growth of lactic acid bacteria (LAB) and the effect of fermentation on pathogenic bacteria were studied using Weibull: biphasic linear and competitive models. The results showed that the rate of pH reduction was lower in the early stages and increased as the microbial population grew. The α parameter was lower for L. plantarum subsp. plantarum compared to L. paraplantarum and L. pentosus . The comparison of the α parameter for bacterial growth and pH data showed that the time interval required to initiate the rapid growth phase of the bacteria was much shorter than that for the rapid pH reduction phase. The pH value had a 50% greater effect on the inactivation of S. Typhi when compared to the samples containing L. plantarum subsp. plantarum and L. pentosus . The same parameter was reported to be 72% for the inactivation of St. aureus . In general, during the fermentation process, LAB strains caused a decrease in pH, and as a result, reduced the growth of pathogens, which improves consumer health and increases the food safety of fermented meat.

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited., Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF., Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated., Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p <0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], p interaction <0.001)., Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701)., Competing Interests: R.M reports research funding from Bayer, Pfizer, and Tempus; and 18 personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, 19 Caris, Dendreon, Exelixis, Janssen, Johnson and Johnson, Merck & Co, Myovant, Novartis, Pfizer, Sanofi, Sorrento Therapeutics, Tempus, and Vividion. A.N. reports consulting fees from AstraZeneca, Takeda Oncology and Bantam Pharmaceuticals. B.B. reports research support to institution from Amgen, Bicycle Therapeutics, Boehringer Ingelheim, Ikena Oncology, Kahr Medical, Merck, Syros, Tarveda Therapeutics. Z.B. receives research support from 10.13039/100004328Genentech/imCORE and Bristol Myers Squibb. Personal fees from UpToDate. L.A.F reports clinical trial funding from BMS, EMDserono, Pfizer, Merck, Array, Kartos, Incyte, personal fees from Elsevier, ViaOncology, outside the submitted work. J.L.W. reports research funding from NIH/NCI during the conduct of the work, research funding from AACR, consulting fees from Westat, Roche, Flatiron Health, Melax Tech, other from HemOnc.org LLC (ownership), outside the submitted work. C.H reports stock holdings in Johnson and Johnson; research funding to institution from Merck, Bausch Health, Genentech, Bayer, and AstraZeneca, consultant fees from Tempus, Genzyme, and EMD Sorono, speaking fees from OncLive/MJH Life Sciences, travel fees from Merck, all outside the submitted work. The remaining authors have nothing to disclose., (© 2023 Published by Elsevier Inc.)

Tamoxifen is the drug of choice as hormonal therapy for hormone receptor-positive breast cancers and can reduce the risk of breast cancer recurrence. However, oral tamoxifen has a low bioavailability due to liver and intestinal metabolic passes. To overcome this problem and utilize the potential of this drug to its maximum, inorganic nanoparticle carriers have been exploited and tested to increase its bioavailability. Biocompatibility and unique magnetic properties make iron oxide nanoparticles an excellent choice as a drug delivery system. In this study, we developed and tested a "green synthesis" approach to synthesize iron nanoparticles from green tea extract and coated them with agar for longer stability (AG-INPs). Later, these hybrid nanoparticles were conjugated with tamoxifen (TMX). By using this approach, we synthesized stable agar-coated tamoxifen-conjugated iron nanoparticles (TMX-AG-INPs) and characterized them with Fourier-transform infrared (FTIR) spectroscopy. The average particle size of AG-INPs was 26.8 nm, while the average particle size of tamoxifen-loaded iron nanoparticles, TMX-AG-INPs, was 32.1 nm, as measured by transmission and scanning electron microscopy. The entrapment efficiency of TMX-AG-INPs obtained by the drug release profile was 88%, with a drug loading capacity of 43.5%. TMX-AG-INPs were significantly ( p < 0.001) efficient in killing breast cancer cells when tested in vitro on the established breast cancer cell line MCF-7 by cell viability assay, indicating their potential to control cell proliferation., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Purpose: Our primary aim was to analyze bilateral epileptic tonic seizures (ETS) and bilateral non-epileptic tonic events (NTE) in critically ill patients. Our secondary aim was to analyze ETS per their epileptogenic zone., Methods: We performed a retrospective analysis of clinical signs in patients with bilateral ETS and NTE. Two authors independently reviewed 34 videos of ETS in 34 patients and 15 videos of NTEs in 15 patients. Initial screening and review was performed in an unblinded manner. Subsequently, the semiology was characterized independently and blindly by a co-author. Statistical analysis was conducted using Bonferroni correction and two-tailed Fischer exact test. Positive predictive value (PPV) was calculated for all signs. Cluster analysis of signs with a PPV >80% was performed to evaluate co-occurring semiological features in the two groups., Results: Compared to patients with ETS, those with NTEs more frequently had predominant involvement of proximal upper extremities (UE) (67% vs. 21%), internal rotation of UE (67% vs. 3%), adduction of UE (80% vs. 6%) and bilateral elbow extension (80% vs. 6%). In contrast, those with ETS more frequently had abduction of UE (82% vs 0%), elevation of UE (91% vs. 33%), open eyelids (74% vs. 20%), and involvement of both proximal and distal UE (79% vs. 27%). In addition, seizures that remained symmetrical throughout were more likely to have a generalized onset than focal (38% vs. 6%), p = 0.032, PPV 86%., Conclusions: A careful analysis of semiology can often help differentiate between ETS and NTE in the ICU. The combination of eyelids open, upper extremity abduction, and elevation reached a PPV of 100% for ETS. The combination of bilateral arms extension, internal rotation, and adduction reached a PPV of 90.9% for NTE., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Plants require copper for normal growth and development and have evolved an efficient system for copper management based on transport proteins such as P 1B -ATPases, also known as heavy metal ATPases (HMAs). Here, we report HMAs in eleven different Poaceae species, including wheat. Furthermore, the possible role of wheat HMAs in copper stress was investigated. BlastP searches identified 27 HMAs in wheat, and phylogenetic analysis based on the Maximum Likelihood method demonstrated a separation into four distinct clades. Conserved motif analysis, domain identification, gene structure, and transmembrane helices number were also identified for wheat HMAs using computational tools. Wheat seedlings grown hydroponically were subjected to elevated copper and demonstrated toxicity symptoms with effects on fresh weight and changes in expression of selected HMAs TaHMA7, TaHMA8, and TaHMA9 were upregulated in response to elevated copper, suggesting a role in wheat copper homeostasis. Further investigations on these heavy metal pumps can provide insight into strategies for enhancing crop heavy metal tolerance in the face of heavy metal pollution., (© 2023. The Author(s).)