The effects of online facial muscle training with resonance vocalization on mental health in postpartum women: A single-arm pilot study.

Background: Mental health problems among expectant and nursing mothers also affect their infants, partners, and families. While physical activity is a potential method for preventing postpartum depression (PPD), it is difficult for postpartum women to find the time for physical exercise. A recent study reported that improving communication between expectant couples can be used as a preventive intervention for PPD, and a systematic review and meta-analysis recently reported decreased facial emotional expressivity in individuals with different non-psychotic disorders.

A real-world study of persistence and adherence to prescription medications in patients with chronic idiopathic constipation in the United States.

Background: At present, 4 prescription therapies have been approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation (CIC) in adults.

Objectives: To compare persistence with and adherence to prucalopride vs 3 other prescription medications for CIC in a US population.

Methods: This retrospective, observational cohort study used data from the IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental Databases (January 2015-June 2020).

The role of neuroestrogens in the estrogen-induced gonadotropin surge in male monkeys.

Neuroestrogens locally synthesized in the brain are known to play a role in sexual behaviors. However, the question of whether neuroestrogens are involved in the regulation of the gonadotropin-releasing hormone (GnRH) release is just emerging. Because previous studies in this lab indicate that neuroestradiol is also important for the pulsatile release as well as the surge release of GnRH in female rhesus monkeys, in the present study, we examined whether neuroestradiol plays a role in the estrogen-induced LH surge in orchidectomized (ORX) male rhesus monkeys.

Clinical Outcomes Before and After Prucalopride Treatment: An Observational Study in Patients With Chronic Idiopathic Constipation in the United States.

Introduction: This real-world US-based claims study compared constipation-related symptoms and complications 6 months before and after prucalopride initiation in adults with chronic idiopathic constipation (CIC).

Methods: This observational, retrospective cohort analysis used the IBM MarketScan Commercial Claims and Encounters Database and the Medicare Supplemental Database (January 2015-June 2020). Prucalopride-treated patients (≥18 years old) who had ≥1 constipation-related International Classification of Diseases, Tenth Revision, Clinical Modification ( ICD-10-CM ) diagnosis code during the baseline or study period were included.

Journey to anticoagulant access following payer rejection of apixaban.

Objectives: To investigate the journey to oral anticoagulant (OAC) access following formulary-related rejection of apixaban (Eliquis) and evaluate characteristics associated with failure to achieve OAC access among patients with atrial fibrillation (AF).

Study Design: Retrospective study using the Optum Market Clarity Data from January 2016 through February 2020.

Methods: Patients had at least 1 claim rejection for apixaban due to prior authorization (PA), formulary exclusion (FE), or quantity limit (QL) and at least 1 AF diagnosis on or before the rejected claim.

Payer formulary tier increases of apixaban: how patients respond and potential implications.

Objective: To assess potential impacts of formulary tier increases of apixaban-an efficacious oral anticoagulant (OAC) for preventing stroke in patients with atrial fibrillation (AF)-on patients' prescription drug plan (PDP) switching and OAC treatment patterns.

Methods: Nationwide claims data for Medicare beneficiaries with Parts A, B, and D (100% sample) were used to assess apixaban-treated AF patients who faced a formulary tier increase for apixaban in 2017 by their Part D PDP. Patients' out-of-pocket (OOP) costs for apixaban were described, along with PDP switching and OAC treatment patterns.

Safety differences across androgen receptor inhibitors in nonmetastatic castration-resistant prostate cancer.

Approval of apalutamide, enzalutamide and darolutamide has transformed the treatment landscape and guideline recommendations for patients with nonmetastatic castration-resistant prostate cancer but now raises the issue of decision-making regarding treatment selection. In this perspective, we discuss the efficacy and safety of these second-generation androgen receptor inhibitors and propose that for patients with nonmetastatic castration-resistant prostate cancer, safety considerations for these treatments are especially important. We examine these considerations in the context of patient and caregiver preferences as well as patient clinical characteristics.

Long-term results of carbidopa/levodopa enteral suspension across the day in advanced Parkinson's disease: Post-hoc analyses from a large 54-week trial.

Introduction: Carbidopa/levodopa enteral suspension (CLES) previously demonstrated reduction in total daily OFF from baseline by over 4 hours in advanced Parkinson's disease patients across 54 weeks. Evidence on CLES's long-term effectiveness on patterns of motor-symptom control throughout the day remains limited.

Methods: We present post-hoc analyses of a large, open-label study of CLES monotherapy (N = 289).

Payer formulary exclusions of apixaban: how patients respond and potential implications.

In recent years, US payers have increased usage of formulary exclusions as a means to help manage costs. Earlier this year, one of the largest pharmacy benefit managers in the country added Eliquis (apixaban), the most widely used anticoagulant, to its list of excluded medicines from its formulary, raising concerns by physicians and patients. In this commentary, we examine the potential impacts of formulary exclusion of a drug like apixaban-a treatment for patients with atrial fibrillation and venous thromboembolism to help prevent stroke and clotting events and which has been demonstrated to have a strong efficacy and safety profile.

The Hospitalization-Related Costs of Adverse Events for Novel Androgen Receptor Inhibitors in Non-Metastatic Castration-Resistant Prostate Cancer: An Indirect Comparison.

Introduction: Three novel androgen receptor inhibitors are approved in the USA for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC): apalutamide, enzalutamide, and darolutamide. All three therapies have demonstrated prolonged metastasis-free survival in their respective phase III trials, with differing safety profiles. The objective of this study was to compare the mean per-patient costs of all-cause adverse events (AEs) requiring hospitalization between darolutamide versus apalutamide and enzalutamide for nmCRPC in the USA.

Ultrafast time-resolved single-shot birefringence microscopy for laser-induced anisotropy.

The interaction between ultrashort laser pulses and materials in the ultrafast time domain, especially regarding the effect of laser polarization, has attracted much attention. In this study, ultrafast time-resolved single-shot birefringence microscopy is performed to observe laser-induced anisotropy. The birefringences of the optical Kerr effect and laser-induced anisotropic nanostructures by femtosecond laser pulses in silica glass are measured, and their slow axis is confirmed to correspond to the linear polarization angle of the pump light.

The mechanism underlying the pubertal increase in pulsatile GnRH release in primates.

In primates, the gonatotropin-releasing hormone (GnRH) neurosecretory system, consisting of GnRH, kisspeptin, and neurokinin B neurons, is active during the neonatal/early infantile period. During the late infantile period, however, activity of the GnRH neurosecretory system becomes minimal as a result of gonadal steroid independent central inhibition, and this suppressed GnRH neurosecretory state continues throughout the prepubertal period. At the initiation of puberty, the GnRH neurosecretory system becomes active again because of the decrease in central inhibition.

Patterns of Daily Motor-Symptom Control with Carbidopa/Levodopa Enteral Suspension Versus Oral Carbidopa/Levodopa Therapy in Advanced Parkinson's Disease: Clinical Trial Post Hoc Analyses.

Introduction: A clinical trial in advanced Parkinson's disease (APD) has established the superiority of carbidopa/levodopa enteral suspension (CLES) in reducing total patient "off" time (OFF) and increasing total "on" time without troublesome dyskinesia (ON-woTD) over orally administered immediate-release carbidopa/levodopa tablets (IR-CL). However, temporal patterns of these improvements throughout the waking day have not been examined. In this analysis, time to ON-woTD after waking and patterns of motor-symptom control throughout the waking day were compared between CLES and IR-CL.

Physiological Characterization and Transcriptomic Properties of GnRH Neurons Derived From Human Stem Cells.

Gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus play a key role in the regulation of reproductive function. In this study, we sought an efficient method for generating GnRH neurons from human embryonic and induced pluripotent stem cells (hESC and hiPSC, respectively). First, we found that exposure of primitive neuroepithelial cells, rather than neuroprogenitor cells, to fibroblast growth factor 8 (FGF8), was more effective in generating GnRH neurons.

Indirect Comparison of Darolutamide versus Apalutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer.

Purpose: No published head-to-head randomized trials have compared the safety and efficacy of darolutamide vs apalutamide or enzalutamide in nonmetastatic castration-resistant prostate cancer. This study compares prespecified adverse events and metastasis-free survival associated with darolutamide vs apalutamide, and darolutamide vs enzalutamide, via matching-adjusted indirect comparisons.

Materials And Methods: Individual patient data from the phase III ARAMIS trial (N=553; N=943) were selected and reweighted to match the inclusion criteria and baseline characteristics published for the phase III SPARTAN (N=401; N=806) and PROSPER (N=468; N=933) trials.

Clinical Outcomes and Health-Care Resource Use Associated With Reslizumab Treatment in Adults With Severe Eosinophilic Asthma in Real-World Practice.

Background: Reslizumab, an anti-IL-5 monoclonal antibody, is indicated as add-on maintenance treatment for adults with severe eosinophilic asthma.

Research Question: What are the real-world outcomes associated with reslizumab use in patients with severe eosinophilic asthma in a US clinical practice?

Study Design And Methods: In this retrospective study, patient-level data from adults treated with reslizumab were obtained from center- and panel-based medical chart reviews. Eligible patients had available medical records and treatment history for ≥ 6 months before initiation of reslizumab treatment (index date) to ≥ 7 months after reslizumab initiation.

Neuroendocrine mechanisms of puberty in non-human primates.

An increase in pulsatile release of gonadotropin releasing hormone (GnRH) initiates puberty in mammalian species. While mutations in and and their receptors, and , respectively, result in the absence or abnormal timing of puberty, the neurocircuitry and precise role of kisspeptin and neurokinin B (NKB) in regulation of the GnRH neurosecretory system in primate puberty remain elusive. This review discusses how kisspeptin and NKB signaling contributes to the pubertal increase in GnRH release in non-human primates and how remodeling of the NKB and kisspeptin signaling circuitry controlling GnRH neurons takes place during the progress of puberty.

Role of Kisspeptin and NKB in Puberty in Nonhuman Primates: Sex Differences.

To understand the roles of kisspeptin and neurokinin B (NKB) in puberty and sex differences in their involvement, we conducted a series of experiments measuring the release of gonadotropin-releasing hormone (GnRH) and kisspeptin in the median eminence of the hypothalamus in male and female monkeys throughout sexual development. Results indicate that kisspeptin-10 and the NKB agonist, senktide, stimulated GnRH release in males and females at the prepubertal and pubertal stages, but females are much more sensitive to kisspeptin signaling than males. Moreover, throughout the progress of puberty, major remodeling of kisspeptin and NKB signaling pathways for the regulation of GnRH release takes place.

Mechanism of pulsatile GnRH release in primates: Unresolved questions.

The pulsatility of GnRH release is essential for reproductive function. The key events in reproductive function, such as puberty onset and ovulatory cycles, are regulated by the frequency and amplitude modulation of pulsatile GnRH release. Abnormal patterns of GnRH pulsatility are seen in association with disease states, such as polycystic ovarian syndrome and anorexia nervosa.

Hypothalamic Reproductive Endocrine Pulse Generator Activity Independent of Neurokinin B and Dynorphin Signaling.

Context: Kisspeptin-neurokinin B (NKB)-dynorphin neurons are critical regulators of the hypothalamic-pituitary-gonadal axis. NKB and dynorphin are hypothesized to influence the frequency of GnRH pulses, whereas kisspeptin is hypothesized to be a generator of the GnRH pulse. How these neuropeptides interact remains unclear.

Dupilumab Versus Cyclosporine for the Treatment of Moderate-to-Severe Atopic Dermatitis in Adults: Indirect Comparison Using the Eczema Area and Severity Index.

Dupilumab is approved for uncontrolled moderate-to-severe atopic dermatitis (AD); cyclosporine is approved for severe AD for ≤ 1 year. The efficacy/effectiveness of these treat-ments was compared indirectly. Regression models used pooled patient-level data to estimate response (Eczema Area and Severity Index (EASI) EASI-50/EASI-75 at weeks 12-16 and 24-30) to dupilumab 300 mg every 2 weeks (CHRONOS [NCT02260986]) or cyclosporine (University Medical Center).

The burden of tardive dyskinesia secondary to antipsychotic medication use among patients with mental disorders.

To assess the impact of developing tardive dyskinesia (TD), both with and without other pre-existing extrapyramidal symptoms (EPS), on healthcare resource utilization (HRU) among patients with mental disorders receiving antipsychotic medications. Data on patients receiving antipsychotics who had schizophrenia, major depressive disorder or bipolar disorder were extracted from a Medicaid claims database. Separate cohorts of TD patients with and without other EPS ("TD + EPS" and "TD non-EPS") were constructed and matched to patients in a non-TD/EPS control cohort at a ∼1:5 ratio.

Role of Kisspeptin and Neurokinin B Signaling in Male Rhesus Monkey Puberty.

Despite the well-established concept that an increase in pulsatile GnRH release triggers puberty, the precise signaling mechanism responsible for the pubertal increase in GnRH release remains unclear. A recent study indicates that developmental changes in the network formation between kisspeptin and neurokinin B (NKB) signaling greatly contribute to the pubertal increase in GnRH release in female monkeys. It is, however, unknown whether similar developmental changes in the kisspeptin and NKB network are involved in male puberty.

Accelerated Episodic Luteinizing Hormone Release Accompanies Blunted Progesterone Regulation in PCOS-like Female Rhesus Monkeys (Macaca Mulatta) Exposed to Testosterone during Early-to-Mid Gestation.

Background/aims: Ovarian theca cell hyperandrogenism in women with polycystic ovary syndrome (PCOS) is compounded by androgen receptor-mediated impairment of estradiol and progesterone negative feedback regulation of episodic luteinizing hormone (LH) release. The resultant LH hypersecretion, likely the product of accelerated episodic release of gonadotropin-releasing hormone (GnRH) from the median eminence of the hypothalamus, hyperstimulates ovarian theca cell steroidogenesis, enabling testosterone (T) and androstenedione excess. Prenatally androgenized (PA) female monkeys exposed to fetal male levels of T during early-to-mid gestation, when adult, demonstrate PCOS-like traits, including high T and LH levels.

Role of Kisspeptin and Neurokinin B in Puberty in Female Non-Human Primates.

In human patients, loss-of-function mutations in the genes encoding kisspeptin () and neurokinin B ( and their receptors ( and , respectively) result in an abnormal timing of puberty or the absence of puberty. To understand the neuroendocrine mechanism of puberty, we investigated the contribution of kisspeptin and NKB signaling to the pubertal increase in GnRH release using rhesus monkeys as a model. Direct measurements of GnRH and kisspeptin in the median eminence of the hypothalamus with infusion of agonists and antagonists for kisspeptin and NKB reveal that kisspeptin and NKB signaling stimulate GnRH release independently or collaboratively by forming kisspeptin and NKB neuronal networks depending on the developmental age.