Prenatal exposures and cell type proportions are main drivers of DNA methylation in maltreated and non-maltreated children.

DNA methylation in peripheral tissues may be a relevant biomarker of risk for developing mental disorders after exposure to early life adversity. Genes involved in HPA axis regulation, such as , might play a key role. In this study, we aimed to identify the main drivers of salivary methylation in a cohort of 162 maltreated and non-maltreated children aged 3-5 years at two measurement timepoints.

Best practices in the African Medicines Regulatory Harmonization initiative: Perspectives of regulators and medicines manufacturers.

In the African Medicines Regulatory Harmonization initiative, national regulatory authorities (NRAs) within each of Africa's regional economic communities coordinate their activities, rely on the work of one another and other trusted regulatory authorities, and apply other principles of smart regulation. The first regional medicines regulatory harmonization (MRH) initiative in Africa was launched in 2012, with the goal of accelerating access to quality, safe, effective medical products, and now five MRH initiatives are active on the continent. Thus, a wealth of knowledge regarding best practices and approaches to dealing with common challenges has accumulated.

Reliance: a smarter way of regulating medical products - The IPRP survey.

: A survey was conducted among national regulatory authorities' members of the International Pharmaceutical Regulators Programme (IPRP) to collect and share experiences of reliance approaches. Reliance allows formally, or informally, one regulatory authority to use assessments made by other regulatory authorities while remaining responsible for the final decision. Reliance is an essential concept to increase the efficiency of the global regulatory oversight of medical products by national regulatory authorities.

The T-type calcium channel isoform Ca3.1 is a target for the hypnotic effect of the anaesthetic neurosteroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile.

Background: The mechanisms underlying the role of T-type calcium channels (T-channels) in thalamocortical excitability and oscillations in vivo during neurosteroid-induced hypnosis are largely unknown.

Methods: We used patch-clamp electrophysiological recordings from acute brain slices ex vivo, recordings of local field potentials (LFPs) from the central medial thalamic nucleus in vivo, and wild-type (WT) and Ca3.1 knock-out mice to investigate the molecular mechanisms of hypnosis induced by the neurosteroid analogue (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH).

Eight years of the East African Community Medicines Regulatory Harmonization initiative: Implementation, progress, and lessons learned.

Jane H. Mashingia and colleagues reveal the progress made to date for the East African Community Medicines Regulatory Harmonization initiative.

Should Surgeons or Anesthesiologists Manage Perioperative Pain Protocols?

Enhanced recovery after surgery (ERAS) protocols vary by surgery type. This article examines benefits of ERAS pathways, compares ERAS pathways to traditional protocols from clinical and ethical standpoints, and discusses formal recommendations of the American College of Surgeons, the American Society of Anesthesiologists, and other groups.

What Constitutes Effective Team Communication After an Error?

Many procedures performed today involve a team of specialists with their own training histories and backgrounds. Some errors are inevitable in the course of clinical careers. Because errors tend to lead to complications, they often also lead to assignations of blame.

The value and benefits of the International Conference on Harmonisation to drug regulatory authorities: advancing harmonization for better public health.

The International Conference on Harmonisation (ICH) is an unparalleled undertaking, which has brought together drug regulatory authorities and pharmaceutical trade associations from Europe, Japan, and the United States, to discuss the scientific and technical aspects of medical product registration. Launched in 1990, the value and benefits of ICH to regulators are being realized. ICH has harmonized submission requirements and created a harmonized submission format that is relieving both companies and regulatory authorities of the burdens of assembling and reviewing separate submissions for each region.

Recurrent aphthous stomatitis.

Etiology and Epidemiology: The Greek term aphthai was initially used in relation to disorders of the mouth and is credited to Hippocrates (460-370 BC). Today, recurrent aphthous ulceration, or recurrent aphthous stomatitis (RAS), is recognized as the most common oral mucosal disease known to human beings. Considerable research attention has been devoted to elucidating the causes of RAS; local and systemic conditions, and genetic, immunologic, and infectious microbial factors all have been identified as potential etiopathogenic agents (Table 1).

Factors associated with dental anxiety.

This study assessed dental anxiety in adults living in the Detroit tricounty area and identified factors associated with it. The prevalence of dental anxiety was 10.0 percent.

The effects of in vitro cocaine exposure on human sperm motility, intracellular calcium, and oocyte penetration.

Objective: To determine if cocaine exposure affects human sperm motility, intracellular calcium level, and fertilizing capability.

Design And Methods: Human semen samples were treated with 1 to 1,000 microM cocaine hydrochloride for up to 2 hours in vitro. Sperm motion kinematics were measured by computer-assisted semen analysis (CASA).

Isolation of Mycoplasma gallopavonis from free-ranging wild turkeys in coastal North Carolina seropositive and culture-negative for Mycoplasma gallisepticum.

Serum samples and choanal cleft swabs were collected from livetrapped and hunter killed wild turkeys (Meleagris gallopavo) from Martin and Bertie counties, North Carolina (USA). Sera were tested for antibodies to Mycoplasma gallisepticum, Mycoplasma synoviae and Mycoplasma meleagridis by hemagglutination inhibition (HI). Sera from 33% (five of 15) of livetrapped turkeys were positive for antibodies to M.

Neuroendocrinological studies on depression with special reference to research at the Max-Planck-Institute of Psychiatry.

Hypercortisolism due to Cushing's syndrome or glucocorticoid therapy induces disturbances in several other endocrine systems and may also cause mental changes, predominantly depression of various degrees. On the other hand, it has repeatedly been shown that endogenous depression is often accompanied by hypercortisolemia, usually of a modest degree, and/or by changes in other hormonal systems similar to those observed in Cushing's syndrome and during treatment with glucocorticoids. Research performed at the MPIP on 327 psychiatric patients and 103 healthy subjects has demonstrated that, in contrast to Cushing's syndrome, the circadian rhythm in depression is usually well preserved, and that diurnal variation in mood is correlated with that rhythm.

Diurnal variation of mood and the cortisol rhythm in depression and normal states of mind.

A large scale chronobiological investigation was undertaken in 20 drug-free psychiatric inpatients displaying RDC major depression (endogenous subtype) in comparison to 10 healthy control subjects and 10 of the patients after clinical recovery. A series of measurements was taken 6 times a day and, in 8 of a total of 14 variables, also once a night over a period of 10 to 14 days. The following variables were assessed: mood (three different scales), performance (two tests), motor activity (three measures), salivary flow, urinary excretion of water, sodium, potassium, and free cortisol (UFC), and rectal temperature.

The nature of neuroendocrine abnormalities in depression: a controversial issue in contemporary psychiatry.

Neuroendocrine abnormalities in depression have been regarded, by many authors, as relatively specific markers of nosological subtypes of the disorder, e.g. primary vs.

Are biological rhythms disturbed in depression?

In a large-scale investigation of circadian rhythms in endogenous depression, no free-running rhythms or indications of phase-advance were found in the patients compared with themselves after clinical recovery and with healthy controls. They exhibited a reduction of the amplitude of depression scales, partially due to a "ceiling effect" of highly elevated scores. A reduction of the amplitude of body temperature was probably related to a negative masking of the temperature rhythm by e.

Circadian rhythms in endogenous depression.

A comprehensive study of circadian rhythms was carried out in 16 drug-free patients with endogenous depression, 10 of whom were reinvestigated after clinical remission, and 10 healthy controls. No free-running periods were observed in body temperature, urinary excretion of potassium and free cortisol, or any other variable. Moreover, there was little, if any, indication of phase-advance.

The limited utility of the dexamethasone suppression test for the diagnostic process in psychiatry.

In 231 psychiatric in-patients, the 1 mg or 1.5 mg DST with blood samples at 0900 h, 1600 h and 2300 h and a post-dexamethasone plasma cortisol threshold of greater than or equal to 5 micrograms/dl were tested for their differential diagnostic utility in clinical psychiatry. Neither test significantly separated endogenous depressed patients from patients with other depressive or non-depressive psychiatric disorders.

Behavior, attitude, nutrition and endocrinology in anorexia nervosa.

Twenty-four anorexia nervosa patients participated in an inpatient broad spectrum behavior therapy program. The changes in body weight, anorectic behaviors and attitudes and endocrine variables (24-h plasma cortisol, dexamethasone suppression test, 24-h plasma luteinizing hormone) were measured. Data indicate that specific anorectic behaviors and attitudes showed significant improvement during inpatient treatment, while attitudes of a more general neurotic scope such as the feeling of insufficiency, general distress, (sexual) anxieties and anancasm did not.

Efficacy and side effects of haloperidol in psychotic patients: oral versus intravenous administration.

It is a commonly held view among clinicians that intravenously administered haloperidol has a greater antipsychotic effect than oral haloperidol. To test this hypothesis, the authors carried out a double-blind study on patients with acute schizophrenia and patients with schizophreniform or schizoaffective (with manic features) psychoses. Using biologically equivalent doses, they found that intravenously administered haloperidol was slightly more effective during the first 3 hours; thereafter the route of administration did not make a difference in effectiveness.

Neuroendocrinological and neurophysiological studies in major depressive disorders: are there biological markers for the endogenous subtype?

The possibility of characterizing subgroups of depressive disorders by biological markers was studied by means of the dexamethasone suppression test (DST), the 24-hr urinary free cortisol (UFC), the growth hormone response to the insulin tolerance test (ITT), and polygraphic sleep recordings. Forty-five hospitalized patients suffering from a moderate to severe nonpsychotic major depressive disorder were clinically subdivided into three groups: endogenous (n = 20), neurotic (n = 19), and "ambiguous" (n = 6). These clinical diagnoses were supplemented by operational diagnostic tools, namely, the Research Diagnostic Criteria (RDC) and the Newcastle Scale.