Discovery and Synthesis of Heterobifunctional Degraders of Rearranged during Transfection (RET) Kinase.

We describe the design, synthesis, and structure-activity relationship (SAR) of heterobifunctional RET ligand-directed degraders (LDDs) derived from three different second-generation RET inhibitors. These LDDs are composed of a target binding motif (TBM) that binds to the RET protein, a linker, and a cereblon binding motif (CBM) as the E3 ligase recognition unit. This led to the identification of a series of pyrazolopyridine-based heterobifunctional LDDs, as exemplified by compound .

Young People Talk About Digital Support for Mental Health: An Online Survey of 15-30-Year Olds in New Zealand.

Background: Mental distress is on the rise for young people, and there are high levels of unmet need for support. Increasingly, young people are engaging with online mechanisms of support to avoid cost and wait times; however, online support does have its limitations. We surveyed young people, 15-30 years of age, in Aotearoa New Zealand to explore their views of digital support for mental health.

Synthesis of diversely substituted quinazoline-2,4(1,3)-diones by cyclization of -butyl (2-cyanoaryl)carbamates.

The synthesis of diversely substituted quinazoline-2,4(1,3)-diones by cyclization of -butyl (2-cyanoaryl)carbamates using readily accessible Boc protected -amino nitriles is reported. The reaction proceeds smoothly at room temperature using 1 equiv. of HO under basic conditions.

Organic Photoredox-Catalyzed -Trifluoromethylation of Aromatic and Heteroaromatic Thiols.

A visible-light-mediated trifluoromethylation protocol was developed for the conversion of (hetero)aromatic thiols to their respective -trifluoromethylated derivatives employing trifluoromethanesulfonyl chloride (CFSOCl) as a cost-effective source of trifluoromethyl radical (CF·) and a highly reducing organophotocatalyst, 3DPA2FBN. The developed methodology is operationally simple, providing access to a diverse range of products in up to 92% yield. A plausible mechanism has been postulated based on preliminary mechanistic studies, including irradiation on/off, UV-vis studies, and radical trapping experiments.

Evaluating Success and Challenges of a Primary Care Youth Mental Health Programme Using Complexity, Implementation Science, and Appreciative Inquiry.

Background Using an innovative framework of complexity and implementation science, with underpinning core values of appreciative inquiry (CIS-A), this paper describes the evaluation of a pilot service in New Zealand aiming to deliver integrated psychological therapy services within primary care, to young people (aged 18-24) experiencing mild to moderate mental distress. Method Using mixed quantitative and qualitative methods and multiple data sources, there was a strong focus on local innovation and co-design with service users, young people and multiple care providers. Data is drawn from service users, stakeholders and providers of the service in three areas of the lower North Island of New Zealand.

Savory Cracker Development for Blood Glucose Control and Management: Glycogen Storage Diseases.

The blood glucose response of savory slow energy-release crackers (GLY-HYP) were evaluated in volunteers carrying glycogen storage diseases (GSDs), Types I (Ia) and IV. The crackers have been shown previously to provide a "flat" slow glucose response in healthy volunteers, for up to 4 h. On average for the mixed-sex volunteer group aged 53 to 70 for Type I, the blood glucose concentration increased from baseline to a maximum of 9.

Therapist Voices on a Youth Mental Health Pilot: Responsiveness to Diversity and Therapy Modality.

This article explores therapists' views on a large youth mental health pilot project (for 18-25-year-olds), which included an individual cognitive behavior therapy (CBT)-informed individual therapy component. Therapists' views on cultural responsiveness, therapy (delivery, modality and duration) and working with LGBTQIA+ youth were explored using two surveys, individual interviews and focus groups at various stages of the life of the pilot. Some therapists saw the CBT approach as imposed on them, preferring familiar therapy modalities.

Single-session Mentalization-based Treatment Group for Law Enforcement Officers.

Law enforcement violence has emerged as a leading public health concern, and law enforcement officers are themselves at greater risk for a range of psychiatric disorders. Drawing on the significant empirical support for mentalization-based treatment (MBT), this paper explores the use of MBT as a transdiagnostic psychotherapy for law enforcement professionals. By helping patients to mentalize-that is, to "read," access, and reflect on mental states in oneself and other people-MBT could be useful as a dual-focus treatment, able to simultaneously impact psychiatric illness among law enforcement officers while also indirectly impacting the problem of law enforcement violence in the broader society.

Is sugar extracted from plants less healthy than sugar consumed within plant tissues? The sugar anomaly.

There are dilemmas in the minds of consumers with respect to sugar consumption - they would like to consume sugars for sweetness, but in a healthy (and perhaps guilt free!) way. In a sense, consumers believe that if sugar does not appear as an ingredient on the product label, but is intrinsic in the food (and will appear as a nutrient), it is 'good'. As an ingredient, however, it is viewed as a 'bad chemical' associated with tooth decay and obesity.

Lactose, Maltose, and Sucrose in Health and Disease.

Scope: This review represents a focus on the structure and properties of the common nutritional disaccharides (lactose, maltose, and sucrose) in health and disease. The aim is to provide a comprehensive reference source related to the role of disaccharides in human nutrition.

Methods And Results: Key reference sources are searched, including Web of Science, PubMed, Science Direct, and Wiley Online, and key reference works are selected to support the factual basis of the text where interpretations and relevance of the works are discussed in the review.

Fructose, galactose and glucose - In health and disease.

Background And Aims: Monosaccharides are important components of the diet, where the sweetness of these common sugars draw animals to eat the tissue within which they are located - especially fruits. Higher (larger) saccharides, within which they are constituents, are ubiquitous throughout nature too - and include disaccharides, oligosaccharides and polysaccharides. These may be converted (hydrolysed) to monosaccharides by the plant tissue enzymes during ripening and stimulate consumption by a predator (whereupon seeds within the fruit are dispersed).

The 'epileptic diet'- ketogenic and/or slow release of glucose intervention: A review.

Background & Aims: The ketogenic diet is high in fat content, adequate with respect to protein but low in carbohydrate and designed to provide brain energy as ketone bodies rather than glucose. The consequence is that epilepsy can be managed and endurance (sport) related energy be derived from fat rather than ingested or stored (glycogen) carbohydrate. This review aims to set the diet in context for seizure related intervention, sport and potential modern variants with respect to glucose management - which have many medical (including epilepsy potentially) and activity related applications.

Cluster randomised controlled trial of a guided self-help mental health intervention in primary care.

Objectives: To ascertain whether an ultrabrief intervention (UBI) improves mental health outcomes for patients in general practice with mild-to-moderate mental health concerns.

Trial Design: Two-arm cluster randomised controlled trial.

Methods: Participants: general practitioners (GPs) were invited based on working in a participating general practice.

Utilisation of dietary fibre (non-starch polysaccharide and resistant starch) molecules for diarrhoea therapy: A mini-review.

Within the last ten years the utilisation of dietary fibre formats (non-starch polysaccharide and resistant starch) for diarrhoea therapy, have been evaluated. These polysaccharides ferment within the colon and generate short chain fatty acids which facilitate sodium absorption. Comparisons between polysaccharide structure/physico-chemical properties and fermentation capacity in the large intestine are presented.

Starch containing formulations for diarrhoea therapy.

Diarrhoea therapies in general include a number of approaches (depending on local practise and the cause of the diarrhoea) aimed at: (i) removing the cause (e.g. lactose in the diet); (ii) treating the cause of infection if present (e.

Starch granules as active guest molecules or microorganism delivery systems.

Starch granules contain an internal channel structure that can be used to encapsulate and deliver active ingredients such as nutrients, drugs, chemicals and microorganisms. Nature creates a broad range of starch granule sizes and compositions in different plants and this range of encapsulation matrices provides a great deal of commercial opportunity. Starch granules can be utilised for encapsulation in their native form or treated with amylases/amyloglucosidase to facilitate the entry of active ingredients into the granules.

A taboo topic? How General Practitioners talk about overweight and obesity in New Zealand.

INTRODUCTION Obesity is overtaking tobacco smoking in New Zealand as the leading potentially modifiable risk to health. International obesity guidelines recommend that health professionals opportunistically encourage weight management with their patients. However, research shows consistently low rates of weight management discussion, suggesting that health professionals may not be realising their full potential to address obesity.

Intrinsic and extrinsic carbohydrates in the vagina: A short review on vaginal glycogen.

The reasons for (i) the presence and (ii) mechanisms of utilisation of glycogen by the lactic acid bacteria in the human vaginal tract are not well understood. It is probable that the vaginal epithelia produce both glycogen and α-amylase where the enzyme depolymerises the polysaccharide within the vagina itself. Only these depolymerised residues are then utilised for growth by the lactic acid bacteria.

A Longitudinal Study of Interactions Between Health Professionals and People With Newly Diagnosed Diabetes.

Purpose: We undertook a study to observe in detail the primary care interactions and communications of patients with newly diagnosed diabetes over time. In addition, we sought to identify key points in the process where miscommunication might occur.

Methods: All health interactions of 32 patients with newly diagnosed type 2 diabetes were recorded and tracked as they moved through the New Zealand health care system for a period of approximately 6 months.

Role of Glucomannans in Immunology.

Glucomannans play a much broader role in human health then providing dietary fibre. They are biologically active molecules and can when added to the body imitate innate molecules found in different organs including surface carbohydrates on cells. This review considers the immunological role of exogenous glucomannans within animals and man.

Immediate Postoperative Intraocular Pressure Adjustment Reduces Risk of Cystoid Macular Edema after Uncomplicated Micro Incision Coaxial Phacoemulsification Cataract Surgery.

Purpose: To determine the accuracy of visual estimation of immediate postoperative intraocular pressure (IOP) following microincision cataract surgery (MICS) and the effect of immediate postoperative IOP adjustment on prevention of cystoid macular edema (CME).

Setting: Ambulatory surgical center.

Methods: Prospective, randomized analysis of 170 eyes in 135 patients with MICS, performed in a Medicare approved outpatient ambulatory surgery center.

'It depends on the consultation': revisiting use of family members as interpreters for general practice consultations - when and why?

Family members continue to be used as interpreters in medical consultations despite the well-known risks. This paper examines participant perceptions of this practice in three New Zealand clinics chosen for their frequent use of interpreters and their skill in using them. It is based on a detailed study of 17 video-recorded interpreted consultations and 48 post-consultation interviews with participants (5 doctors, 16 patients and 12 interpreters, including 6 family members).

Non-physiological mechanisms influencing disulfiram treatment of alcohol use disorder: A grounded theory study.

Background: The mechanism of action of disulfiram is not clear and recent systematic reviews have reached differing conclusions. The purpose of this research was to develop a conceptual model of the mechanisms that underpin the effective use of disulfiram in management of alcohol used disorder.

Methods: Grounded theory was used, based on anonymized transcripts of in-depth interviews with 14 individual clients who experienced taking disulfiram for alcohol use disorder within the context of a specialized clinic setting from New Zealand.

Patient resistance as a resource: candidate obstacles in diabetes consultations.

This study uses conversation analysis to explore 'candidate obstacles', a practice observed in sequences of patient resistance to lifestyle advice within health professional consultations. This article presents illustrative analyses of selected data excerpts drawn from audio-visual recordings of 116 tracked consultations between health professionals and 34 patients newly diagnosed with type 2 diabetes mellitus in New Zealand. The analysis shows that in consultations where health promotion activities are central, patient resistance can provide space for patients to identify obstacles to their compliance with lifestyle advice.