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Congenital pituitary hormone deficiencies have been reported in approximately one in 4,000 live births, however studies reporting mutations in some widely studied transcription factors account for only a fraction of congenital hormone deficiencies in humans. Anterior pituitary hormones are required for development and function of several glands including gonads, adrenals, and thyroid. In order to identify additional factors that contribute to human congenital hormone deficiencies, we are investigating the forkhead transcription factor, FOXO1, which has been implicated in development of several organs including ovary, testis, and brain. We find that FOXO1 is present in the nuclei of non-dividing pituitary cells during embryonic development, consistent with a role in limiting proliferation and/or promoting differentiation. FOXO1 is present in a subset of differentiated cells at e18.5 and in adult with highest level of expression in somatotrope cells. We detected FOXO1 in p27Kip1-positive cells at e14.5. In the absence of p27Kip1 the number of pituitary cells containing FOXO1 is significantly increased at e14.5 suggesting that a feedback loop regulates the interplay between FOXO1 and p27Kip1. [ABSTRACT FROM AUTHOR]

Congenital pituitary hormone deficiencies have been reported in approximately one in 4,000 live births, however studies reporting mutations in some widely studied transcription factors account for only a fraction of congenital hormone deficiencies in humans. Anterior pituitary hormones are required for development and function of several glands including gonads, adrenals, and thyroid. In order to identify additional factors that contribute to human congenital hormone deficiencies, we are investigating the forkhead transcription factor, FOXO1, which has been implicated in development of several organs including ovary, testis, and brain. We find that FOXO1 is present in the nuclei of non-dividing pituitary cells during embryonic development, consistent with a role in limiting proliferation and/or promoting differentiation. FOXO1 is present in a subset of differentiated cells at e18.5 and in adult with highest level of expression in somatotrope cells. We detected FOXO1 in p27Kip1-positive cells at e14.5. In the absence of p27Kip1 the number of pituitary cells containing FOXO1 is significantly increased at e14.5 suggesting that a feedback loop regulates the interplay between FOXO1 and p27Kip1. [ABSTRACT FROM AUTHOR]

Yorkshire, red Duroc, and F1 (first-generation cross) pigs heal with normal, fibroproliferative/hypercontractile, and intermediate levels of scarring, respectively. The purpose of this study was to evaluate the healing phenotype of Yorkshire × F1 backcross animals, to address the molecular basis for genetic transmission of the red Duroc scarring phenotype. Macroscopically and histologically, full-thickness wounds on backcross animals followed the Yorkshire phenotype, with one exception; the backcross wounds exhibited contraction following re-epithelialization. The molecular expression patterns in the backcross animals generally correlated with the macroscopic and histologic findings. Compared to Yorkshire, red Duroc, and F1 wounds, the backcross wounds demonstrated a diminished initial inflammatory phase, followed by a prolonged expression of several relevant growth factors. Additionally, collagen expression was prolonged, expression of matrix metalloproteinases was increased, and alterations in tissue inhibitor of metalloproteinase expression were detected. Moreover, a subset of molecules still followed the red Duroc pattern of mRNA expression, a finding that allows for correlations between the scarring phenotype and the molecular expression patterns to be made in this model. The results indicate that a number of genes are likely involved in the red Duroc healing phenotype and that identification of the specific genes involved will require a more detailed genomic analysis.Journal of Investigative Dermatology (2007) 127, 233–244. doi:10.1038/sj.jid.5700482; published online 20 July 2006 [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is seldom considered in the evaluation of infertility, and the link between the two has been referred to many times in the literature as a 'neglected clinical association'. It is estimated that approximately 7.4-14% of women are infertile in North America, with 15% of this infertility attributed to unexplained factors after hormonal and anatomical causes have been ruled out. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by CAG trinucleotide repeat expansions in exon 1 of the HTT gene. In addition to germline CAG expansions, somatic repeat expansions in neurons also contribute to HD pathogenesis. The DNA mismatch repair gene, MSH3, identified as a genetic modifier of HD onset and progression, promotes somatic CAG expansions, and thus presents a potential therapeutic target. However, what extent of MSH3 protein reduction is needed to attenuate somatic CAG expansions and elicit therapeutic benefits in HD disease models is less clear. In our study, we employed potent di-siRNAs to silence mouse Msh3 mRNA expression in a dose-dependent manner in HdhQ111/+ mice and correlated somatic Htt CAG instability with MSH3 protein levels from simultaneously isolated DNA and protein after siRNA treatment. Our results reveal a linear correlation with a proportionality constant of ~ 1 between the prevention of somatic Htt CAG expansions and MSH3 protein expression in vivo, supporting MSH3 as a rate-limiting step in somatic expansions. Intriguingly, despite a 75% reduction in MSH3 protein levels, striatal nuclear HTT aggregates remained unchanged. We also note that evidence for nuclear Msh3 mRNA that is inaccessible to RNA interference was found, and that MSH6 protein in the striatum was upregulated following MSH3 knockdown in HdhQ111/+ mice. These results provide important clues to address critical questions for the development of therapeutic molecules targeting MSH3 as a potential therapeutic target for HD. [ABSTRACT FROM AUTHOR]

Focuses on the recommendation for patients undergoing major lower limb amputation who have a high cardiovascular risk to take statins. Assessment of the efficacy of the drug in patients; Measurement of the cholesterol of the patients; Inadequacy of the treatment for patients with peripheral arterial disease undergoing amputation.

CONTEXT: Racial/ethnic inequities are well documented in both maternal-infant health and substance use disorder treatment outcomes. OBJECTIVE: To systematically review research on maternal-infant dyads affected by opioid use disorder (OUD) to evaluate for racial/ethnic disparities in health utilization or outcomes and critically assess the reporting and inclusion of race/ethnicity data. DATA SOURCES: Peer-reviewed literature in MEDLINE, Embase, and Web of Science from 2000 to 2020. STUDY SELECTION: Research reporting health utilization and outcomes data on dyads affected by OUD during pregnancy through the infant's first birthday. DATA EXTRACTION: We extracted data on race/ethnicity, study exposures/outcomes, how race/ ethnicity data were analyzed, how authors discussed findings associated with race/ethnicity, and whether racism was mentioned as an explanation for findings. RESULTS: Of 2023 articles reviewed, 152 quantitative and 17 qualitative studies were included. Among quantitative studies, 66% examined infant outcomes (n 5 101). Three articles explicitly focused on evaluating racial/ethnic differences among dyads. Among quantitative studies, 112 mentioned race/ethnicity, 63 performed analyses assessing for differences between exposure groups, 27 identified racial/ethnic differences, 22 adjusted outcomes for race/ethnicity in multivariable analyses, and 11 presented adjusted models stratified by race/ ethnicity. None of the qualitative studies addressed the role that race, ethnicity, or racism may have had on the presented themes. CONCLUSIONS: Few studies were designed to evaluate racial/ethnic inequities among maternal-infant dyads affected by OUD. Data on race/ethnicity have been poorly reported in this literature. To achieve health equity across perinatal OUD, researchers should prioritize the inclusion of marginalized groups to better address the role that structural racism plays. [ABSTRACT FROM AUTHOR]

The purpose of this study was to: (1) examine the associations of individual-level objective socioeconomic status (OSS), subjective socioeconomic status (SSS), and area-based indicators of socioeconomic status, with 12-month DSM-IV mood, anxiety, alcohol use, and drug use disorders; and, (2) determine the extent of racial/ethnic differences in these associations across non-Latino White, non-Latino Black, Latino, and Asian participants. Data are from the Collaborative Psychiatric Epidemiology Studies dataset, a collection of three population-based surveys of mental disorders among U.S. residents aged 18 and older (n = 13,775). Among all indicators of socioeconomic status, SSS was most consistently associated with 12-month mental disorders. Income was negatively associated with mood and anxiety disorders; education was negatively associated with alcohol use and drug use disorders. Significant interactions with race/ethnicity were found for the associations of socioeconomic indicators with anxiety, alcohol use, and drug use disorders but not with mood disorders. SSS was not associated with any of the 12-month mental disorders among Blacks. Education had stronger associations with 12-month anxiety and alcohol use disorders among Whites than among other racial/ethnic groups. Among Asians, low income compared to high income was associated with a lower risk of anxiety disorders and less than high school completion compared to college or more was associated with a lower risk of alcohol use disorders. Finally, tract-level income inequality was associated with a greater risk of drug use disorders only among Blacks. The patterns and magnitudes of the associations of individual-level and area-based socioeconomic indicators differed by type of disorder and race/ethnicity. [ABSTRACT FROM AUTHOR]

Background: The prevalence of mental disorders among Black, Latino, and Asian adults is lower than among Whites. Factors that explain these differences are largely unknown. We examined whether racial/ethnic differences in exposure to traumatic events (TEs) or vulnerability to trauma-related psychopathology explained the lower rates of psychopathology among racial/ethnic minorities. Methods: We estimated the prevalence of TE exposure and associations with onset of DSM-IV depression, anxiety and substance disorders and with lifetime post-traumatic stress disorder (PTSD) in the Collaborative Psychiatric Epidemiology Surveys, a national sample (N = 13 775) with substantial proportions of Black (35.9%), Latino (18.9%), and Asian Americans (14.9%). Results: TE exposure varied across racial/ethnic groups. Asians were most likely to experience organized violence – particularly being a refugee – but had the lowest exposure to all other TEs. Blacks had the greatest exposure to participation in organized violence, sexual violence, and other TEs, Latinos had the highest exposure to physical violence, and Whites were most likely to experience accidents/injuries. Racial/ethnic minorities had lower odds ratios of depression, anxiety, and substance disorder onset relative to Whites. Neither variation in TE exposure nor vulnerability to psychopathology following TEs across racial/ethnic groups explained these differences. Vulnerability to PTSD did vary across groups, however, such that Asians were less likely and Blacks more likely to develop PTSD following TEs than Whites. Conclusions: Lower prevalence of mental disorders among racial/ethnic minorities does not appear to reflect reduced vulnerability to TEs, with the exception of PTSD among Asians. This highlights the importance of investigating other potential mechanisms underlying racial/ethnic differences in psychopathology. [ABSTRACT FROM AUTHOR]

The present research extends the use of a new scheme for classifying children's peer relationships that (a) jointly evaluates friendship and antipathy nominations and (b) includes nonreciprocated friend and antipathy nominations. Findings revealed that 12.1% of all classroom dyads (total dyads = 2,313) were unbalanced relationships, in which one child perceived a friendship but was disliked by the other child. Furthermore, having high frequencies of 'befriending but disliked' relationships was associated with poor social competence and having high frequencies of 'disliking but befriended' relationships was associated with good social competence. Results support the use of this new classification scheme by highlighting the common nature of unbalanced relationships and by establishing the association of unbalanced relationships to peer social competence outcomes. [ABSTRACT FROM AUTHOR]

Examines the room temperature reactions of VX, GB, GD, and HD with nanosize Al[sub 2]O[sub 3]. Formation of aluminophosphonates; Production of surface bound complexes of the corresponding nontoxic phosphonates.

Abstract Background Parathyroid carcinoma is a rare cause of primary hyperparathyroidism and may be associated with significant disease related morbidity and mortality. Preoperative diagnosis remains a challenge, which may jeopardize appropriate and successful patient treatment. Case presentation We report a case of parathyroid carcinoma diagnosed in a 60-year-old woman that presented with a tender nodule located at the left lower thyroid pole and had been present for several years. Ultrasound examination revealed a 2.7 × 1.6 × 2.7 cm mass within the lower left lobe of the thyroid with cystic and solid areas. Lab measurement of the intact PTH level revealed it to be three times the upper limit of normal and the serum calcium level was within normal limits. A left thyroid lobectomy and isthmusectomy was carried out. Histopathological evaluation was diagnostic for a parathyroid carcinoma. At greater than two years of follow-up, the patient has had no evidence of disease recurrence and her serum PTH and calcium levels have remained within normal. Conclusion Parathyroid carcinoma is a rare endocrine tumor which must be considered in the differential diagnosis of a nodular thyroid mass. En bloc resection remains the treatment of choice for this malignancy. Disease prognosis is influenced by the extent of the initial resection, the presence of metastases, and adequate long-term follow-up.

The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25 mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are among the leading causes of mortality worldwide. Cigarette smoking is among the main aetiologic factors for both ailments. These diseases share common pathogenetic mechanisms including inflammation, oxidative stress, and tissue remodelling. Current therapeutic approaches are limited by low efficacy and adverse effects. Consequentially, LC has a 5-year survival of < 20%, while COPD is incurable, underlining the necessity for innovative treatment strategies. Two promising emerging classes of therapy against these diseases include plant-derived molecules (phytoceuticals) and nucleic acid-based therapies. The clinical application of both is limited by issues including poor solubility, poor permeability, and, in the case of nucleic acids, susceptibility to enzymatic degradation, large size, and electrostatic charge density. Nanoparticle-based advanced drug delivery systems are currently being explored as flexible systems allowing to overcome these limitations. In this review, an updated summary of the most recent studies using nanoparticle-based advanced drug delivery systems to improve the delivery of nucleic acids and phytoceuticals for the treatment of LC and COPD is provided. This review highlights the enormous relevance of these delivery systems as tools that are set to facilitate the clinical application of novel categories of therapeutics with poor pharmacokinetic properties., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ovarian disease constitutes various types of endocrine disorders, such as polycystic ovarian syndrome (PCOS), ovarian cancer, premature ovarian failure, ovarian endometriosis, and ovarian cysts. The prevalence of ovarian-related diseases is highly vulnerable in the world. The utility of various drug delivery systems for ovarian diseases has resulted in varied success. Moreover, most of them lead to severe adverse effects and are incapable of ameliorating the signs and symptoms of the condition. Intrauterine devices (IUDs) have positioned themselves as a mechanism to deliver the drug for various ovarian-related diseases. Thereby avoiding various stability-related issues arising due to various physiological barriers of the female reproductive tract. However, the use of intrauterine devices for drug delivery to the ovaries has not been fully explored. This is attributed to the fact that they cause cysts in the ovaries and skepticism among patients and physicians. Photo-sensitive devices are an appealing approach for managing disorders affecting the ovaries. Photo-sensitive in situ forming intrauterine implants (IUIs) have several advantages, including simplicity in application, reduced invasiveness, as well as improved site-specific drug release control. Polymeric nanoparticles (PNPs) loaded with a drug may be a suitable choice to provide sustained release, alter the pharmacokinetics, and reduce the dose and dosing frequency. The current manuscript hypothesizes the utility of a PNP-loaded biodegradable photo-responsive intrauterine implantable device as an alternate novel strategy for ameliorating ovarian-related diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Parkinson's disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed., 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 Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Today, therapeutic candidates with low solubility have become increasingly common in pharmaceutical research pipelines. Several techniques such as hot melt extrusion, spray drying, supercritical fluid technology, electrospinning, KinetiSol, etc., have been devised to improve either or both the solubility and dissolution to enhance the bioavailability of these active substances belonging to BCS Class II and IV. The principle involved in all these preparation techniques is similar, where the crystal lattice of the drug is disrupted by either the application of heat or dissolving it in a solvent and the movement of the fine drug particles is arrested with the help of a polymer by either cooling or drying to remove the solvent. The dispersed drug particles in the polymer matrix have higher entropy and enthalpy and, thereby, higher free energy in comparison to the crystalline drug. Povidone, polymethaacrylate derivatives, hydroxypropyl methyl cellulose (HPMC) and hydroxypropyl methylcellulose acetate succinate derivatives are commonly used as polymers in the preparation of ASDs. Specifically, hydroxypropylmethylcellulose acetate succinate (HPMCAS)-based ASDs have become well established in commercially available products and are widely explored to improve the solubility of poorly soluble drugs. This article provides an analysis of two widely used manufacturing techniques for HPMCAS ASDs, namely, hot melt extrusion and spray drying. Additionally, details of HPMCAS-based ASD marketed products and patents have been discussed to emphasize the commercial aspect.

Polycystic Ovarian Syndrome (PCOS) comprises a set of symptoms that pose significant risk factors for various diseases, including type 2 diabetes, cardiovascular disease, and cancer. Effective and safe methods to treat all the pathological symptoms of PCOS are not available. The gut microbiota has been shown to play an essential role in PCOS incidence and progression. Many dietary plants, prebiotics, and probiotics have been reported to ameliorate PCOS. Gut microbiota shows its effects in PCOS via a number of mechanistic pathways including maintenance of homeostasis, regulation of lipid and blood glucose levels. The effect of gut microbiota on PCOS has been widely reported in animal models but there are only a few reports of human studies. Increasing the diversity of gut microbiota, and up-regulating PCOS ameliorating gut microbiota are some of the ways through which prebiotics, probiotics, and polyphenols work. We present a comprehensive review on polyphenols from natural origin, probiotics, and fecal microbiota therapy that may be used to treat PCOS by modifying the gut microbiota.

Background: Curcumin (CRM) is known to possess various therapeutic properties, such as anti-inflammatory and antidiabetic properties, and is, therefore, considered to be an effective therapeutic., Objective: A sensitive method for the estimation of CRM in plasma, as well as fecal matter-based solid self-nano emulsifying drug delivery system (S-SNEDDS), has been reported for the first time., Methods: A bioanalytical method was optimized using Box-Behnken Design having 13 runs and 3 responses. The optimized method was developed using methanol and water (70:30 v/v) with a flow rate of 1 mL/min. Quercetin was used as an internal standard. A specificity test was also performed for the developed CRM solid self-nano emulsifying drug delivery system., Results: The retention time of CRM was found to be 14.18 minutes. The developed method was validated and found to be linear in the range of 50-250 ng/mL with an R 2 of 0.999. Accuracy studies indicated that CRM had a percentage recovery of less than 105% and more than 95%, respectively. Precision studies were carried out for inter, intraday, and inter-analyst precision, and the %RSD was found to be less than 2%. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 3.37 ng/mL and 10.23 ng/mL, respectively. Stability studies for shortterm, long term and freeze-thaw cycles showed a %RSD of less than 2%, indicating the stability of CRM in the plasma matrix. Moreover, the blank fecal microbiota extract slurry did not show any peak at the retention time of CRM in a CRM-loaded solid nanoemulsifying drug delivery system containing fecal microbiota extract indicating its specificity., Conclusion: Hence, the developed method can have clinical implications as it helps estimate CRM in blood samples and also provides a simple and sensitive method for the estimation of plant-based flavonoids along with fecal microbiota extract formulations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)