ECHO "Bootcamp": An Innovative Training Model to Onboard Providers in the Care of Gender Diverse Patients.

Extension for Community Health Outcomes (ECHO) is a model of continuing medical education meant to connect academic medical center-based specialists with community providers to increase capacity in managing complex health conditions. The purpose of this study was to evaluate the effectiveness of a shortened "bootcamp" ECHO model in increasing participant competence with topics related to transgender and gender diverse (TGD) health care and the impact of "bootcamp" participation on enrollment in an ongoing ECHO series. An ongoing monthly ECHO series was instituted on topics of TGD health.

Gender-affirming hormone therapy, mental health, and surgical considerations for aging transgender and gender diverse adults.

As the transgender and gender diverse (TGD) population ages, more transfeminine and transmasculine individuals present to clinic to initiate or continue their gender-affirming care at older ages. Currently available guidelines on gender-affirming care are excellent resources for the provision of gender-affirming hormone therapy (GAHT), primary care, surgery, and mental health care but are limited in their scope as to whether recommendations require tailoring to older TGD adults. Data that inform guideline-recommended management considerations, while informative and increasingly evidence-based, mainly come from studies of younger TGD populations.

The (Slow) Depathologizing of Gender Incongruence.

Psychiatric nosology has at times mirrored cultural mores and societal values, pathologizing behaviors seen at the time to be either immoral or outside the norm. This has been particularly true when it comes to issues related to sexuality and gender. Such pathologizing has resulted in further stigmatization and discrimination in society.

Gender-Affirming Hormone Use in Transgender Individuals: Impact on Behavioral Health and Cognition.

Purpose Of Review: With increasing numbers of transgender and gender non-binary individuals presenting for care, knowing how to elucidate the mental health and cognitive outcomes of gender-affirming hormone therapy (GAHT) is necessary. This article reviews the present literature covering GAHT effects on mood, behavioral health, and cognition in these individuals and offers research priorities to address knowledge gaps.

Recent Findings: Although there are some conflicting data, GAHT overwhelmingly seems to have positive psychological effects in both adolescents and adults.

A Four-Week Reflective Writing Program in the Psychiatry Clerkship: Testing Effects on Reflective Capacity.

Objective: Reflective capacity is the ability to review and reconstruct the importance, emotional impact, and outcomes of an experience to give it added meaning and context. In medicine, greater reflective capacity is associated with greater empathy and diagnostic accuracy. This project implemented a four-week reflective writing curriculum for third-year medical students during their psychiatric clerkship.

Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat.

A series of tetrahydroisoquinoline phenols was modified to give an estrogen receptor downregulator-antagonist profile. Optimization around the core, alkyl side chain, and pendant aryl ring resulted in compounds with subnanomolar levels of potency. The phenol functionality was shown to be required to achieve highly potent compounds, but unusually this was compatible with obtaining high oral bioavailabilities in rat.

Cubanes in medicinal chemistry: synthesis of functionalized building blocks.

A collection of novel, pharmaceutically relevant cubane-containing molecules has been prepared from the commercially available cubane-1,4-dimethylester. A range of synthetic methods have been applied to prepare these cubane building blocks with one or two functional handles to allow easy incorporation into existing medicinal chemistry programs.

Identification, optimization, and pharmacology of acylurea GHS-R1a inverse agonists.

Ghrelin plays a major physiological role in the control of food intake, and inverse agonists of the ghrelin receptor (GHS-R1a) are widely considered to offer utility as antiobesity agents by lowering the set-point for hunger between meals. We identified an acylurea series of ghrelin modulators from high throughput screening and optimized binding affinity through structure-activity relationship studies. Furthermore, we identified specific substructural changes, which switched partial agonist activity to inverse agonist activity, and optimized physicochemical and DMPK properties to afford the non-CNS penetrant inverse agonist 22 (AZ-GHS-22) and the CNS penetrant inverse agonist 38 (AZ-GHS-38).

The first intramolecular silene Diels-Alder reactions.

The synthesis of silaheterocycles through the first examples of an intramolecular silene Diels-Alder reaction is described.

Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687).

A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.

Formal synthesis of merrilactone A using a domino cyanide 1,4-addition-aldol cyclization.

A formal synthesis of merrilactone A has been completed using a domino 1,4-addition-aldol process as the key step. Both iodo- and cyano-1,4-addition-aldol cyclizations were productive in forming the highly hindered C1-C9 bond linking vic-quaternary and tertiary stereocenters. The latter method was used to complete a formal total synthesis of the natural product.

Identification, optimisation and in vivo evaluation of oxadiazole DGAT-1 inhibitors for the treatment of obesity and diabetes.

A novel series of DGAT-1 inhibitors was discovered from an oxadiazole amide high throughput screening (HTS) hit. Optimisation of potency and ligand lipophilicity efficiency (LLE) resulted in a carboxylic acid containing clinical candidate 53 (AZD3988), which demonstrated excellent DGAT-1 potency (0.6 nM), good pharmacokinetics and pre-clinical in vivo efficacy that could be rationalised through a PK/PD relationship.

Subjective effects, misuse, and adverse effects of osmotic-release methylphenidate treatment in adolescent substance abusers with attention-deficit/hyperactivity disorder.

Objective: Psychostimulants are effective treatments for attention-deficit/hyperactivity disorder (ADHD) but may be associated with euphoric effects, misuse/diversion, and adverse effects. These risks are perceived by some clinicians to be greater in substance-abusing adolescents relative to non-substance-abusing adults. The present study evaluates the subjective effects, misuse/diversion, and adverse effects associated with the use of osmotic-release oral system methylphenidate (OROS-MPH), relative to placebo, for treating ADHD in adolescents with a substance use disorder (SUD) as a function of substance use severity and compared these risks with those associated with the treatment of ADHD in adults without a non-nicotine SUD.

Randomized controlled trial of osmotic-release methylphenidate with cognitive-behavioral therapy in adolescents with attention-deficit/hyperactivity disorder and substance use disorders.

Objective: To evaluate the efficacy and safety of osmotic-release methylphenidate (OROS-MPH) compared with placebo for attention-deficit/hyperactivity disorder (ADHD), and the impact on substance treatment outcomes in adolescents concurrently receiving cognitive-behavioral therapy (CBT) for substance use disorders (SUD).

Method: This was a 16-week, randomized, controlled, multi-site trial of OROS-MPH + CBT versus placebo + CBT in 303 adolescents (aged 13 through 18 years) meeting DSM-IV diagnostic criteria for ADHD and SUD. Primary outcome measures included the following: for ADHD, clinician-administered ADHD Rating Scale (ADHD-RS), adolescent informant; for substance use, adolescent-reported days of use in the past 28 days.

A randomized controlled trial of fluoxetine and cognitive behavioral therapy in adolescents with major depression, behavior problems, and substance use disorders.

Objective: To evaluate the effect of fluoxetine hydrochloride vs placebo on major depressive disorder, substance use disorder (SUD), and conduct disorder (CD) in adolescents receiving cognitive behavioral therapy (CBT) for SUD.

Design: Randomized controlled trial.

Setting: A single-site study conducted between May 2001 and August 2004.

Substance Use Disorders and Neurologic Illness.

Because of the high rates of substance use disorders among the general and clinical populations, and the abuse potential of many medications commonly used in the treatment of neurologic illnesses, the treating neurologist must deal with drug misuse and abuse in practice. The most important tool neurologists must have in their arsenal is the ability to assess for and recognize substance use disorders in their patients. Any treatment plan developed for such patients must include ongoing management of substance abuse issues.

Stereocontrolled total synthesis of (-)-callipeltoside A.

[structure: see text] A highly stereocontrolled total synthesis of the cytotoxic macrolide (-)-callipeltoside A has been achieved in 23 steps (4.8% overall). Notable features include a novel asymmetric vinylogous aldol reaction to install the C13 stereocenter and (E)-trisubstituted alkene, an anti-selective aldol addition, a Sonogashira coupling, and, last, a Schmidt-type glycosylation to attach the sugar unit.

Anxiety Disorders in Neurologic Illness.

Anxiety disorders frequently occur in individuals with neurologic illness. Anxiety may be a symptom of or a reaction to the neurologic disorder, a medication side effect, or a comorbid condition. The most common anxiety disorders seen in neurologic patients are panic disorder, generalized anxiety disorder, social phobia, and obsessive-compulsive disorder (OCD).