Approach to the patient : pharmacological management of trans and gender-diverse adolescents

Internationally, increasing numbers of children and adolescents with gender dysphoria are presenting for care. In response, gender-affirming therapeutic interventions that seek to align bodily characteristics with an individual's gender identity are more commonly being used. Depending on a young person's circumstances and goals, hormonal interventions may aim to achieve full pubertal suppression, modulation of endogenous pubertal sex hormone effects, and/or development of secondary sex characteristics congruent with their affirmed gender. This is a relatively novel therapeutic area and, although short-term outcomes are encouraging, longer term data from prospective longitudinal adolescent cohorts are still lacking, which may create clinical and ethical decision-making challenges. Here, we review current treatment options, reported outcomes, and clinical challenges in the pharmacological management of trans and gender-diverse adolescents

Selective Estrogen Receptor Modulators: A Potential Option For Non-Binary Gender-Affirming Hormonal Care?

Gender dysphoria describes the distress associated with having a gender identity that differs from one’s birth-assigned sex. To relieve this distress, transgender, and gender diverse (henceforth, trans) individuals commonly undergo medical transition involving hormonal treatments. Current hormonal treatment guidelines cater almost exclusively for those who wish to transition from male to female or vice versa. In contrast, there is a dearth of hormonal options for those trans individuals who identify as non-binary and seek an androgynous appearance that is neither overtly male nor female. Though prolonged puberty suppression with gonadotrophin releasing hormone agonists (GnRHa) could in theory be gender-affirming by preventing the development of unwanted secondary sex characteristics, this treatment option would be limited to pre- or peri-pubertal adolescents and likely have harmful effects. Here, we discuss the theoretical use of Selective Estrogen Receptor Modulators (SERMs) for non-binary people assigned male at birth (AMAB) who are seeking an androgynous appearance through partial feminization without breast growth. Given their unique range of pharmacodynamic effects, SERMs may represent a potential gender-affirming treatment for this population, but there is a lack of knowledge regarding their use and potentially adverse effects in this context

Acrometastasis from an epidermal-growth-factor-receptor (EGFR) mutation-positive lung adenocarcinoma

AbstractWe report the first case of epidermal-growth-factor-receptor (EGFR) mutation-positive lung adenocarcinoma with acrometastasis in a 51-year-old woman who presented with a swelling on her right hand. Magnetic resonance imaging revealed an expansile lesion at the base of the 5th metacarpal bone of her right hand with cortical erosion and patchy enhancement suggestive of a malignant transformation of a giant-cell tumor. A core needle biopsy of this lesion showed a metastatic adenocarcinoma on histopathological examination which was immunoreactive to cytokeratin (CK) 7 and thyroid transcription factor (TTF)-1 but not to CK20 suggesting a lung primary. A chest radiograph and computed tomography (CT) scan revealed a right upper lobe lung mass. Fluoro-deoxyglucose hypermetabolism was noted in the lung mass and the right 5th metacarpal bone lesion but not elsewhere on positron-emission-tomography/CT scan. Needle biopsy of the lung mass showed adenocarcinoma with histopathological and immunohistochemical features similar to that of the right 5th metacarpal bone lesion. Both the primary lung adenocarcinoma and the acrometastatic lesion were tested positive for EGFR mutation in exon 21 (L858R substitution). She underwent R0 resection of her right upper and middle lobes with systematic mediastinal lymph nodes resection and wide excision of the metacarpal metastasis followed by cytotoxic chemotherapy. A curative approach with complete resection of the primary tumor and oligometastastic site in Stage IV non-small cell lung carcinoma (NSCLC) followed by additive cytotoxic chemotherapy has not been reported to date and as such there is still no data on disease-free survival with this approach

Conversion of Sago (Metroxylon sagu) Pith Waste to Fermentable Sugars via a Facile Depolymerization Process

The conversion of starchy sago (Metroxylon sagu) pith waste (SPW), a lignocellulosic biomass waste, to fermentable sugars under mild conditions had been successfully demonstrated. The optimum depolymerization of SPW was achieved at 2 wt% sample loading which was catalyzed by 100 mM of oxalic acid in the presence of 25 wt% NaCl solution at 110 °C for 3 h. Up to 97% SPW sample was being converted into fermentable sugars with limited formation of by-products after two sequential depolymerization cycles. Both reaction temperature and concentration of oxalic acid were crucial parameters for the depolymerization of SPW which exhibited a high selectivity for the production of glucose over other reducing sugars. © 2017, Springer Science+Business Media, LLC

Porous Cellulose Beads Fabricated from Regenerated Cellulose as Potential Drug Delivery Carriers

Highly porous cellulose beads (CBs) of various mean sizes were successfully prepared from regenerated cellulose of paper wastes. The drug delivery characteristics of CBs with different mean sizes were investigated using curcumin as the model drug under controlled conditions. The loading capacity and efficiency of curcumin onto CBs were substantially influenced by factors such as their morphological characteristics, curcumin concentration, and duration of loading.The release kinetic profiles of curcumin from CBs of different mean sizes were investigated in media of pH values resembling digestive juices and intestinal fluids. Release kinetic models were used to simulate and elucidate release kinetics and mechanisms of curcumin from CBs under specific conditions. The loading capacity and efficiency of curcumin onto CBs could be enhanced via the optimization of curcumin solution concentration and the morphological characteristics of CBs, whereas the release kinetic profiles of curcumin from CBs could be modulated by varying the mean diameter of CBs. Optimized CBs derived from regenerated cellulose of paper wastes are potentially useful as cost-effective drug delivery carriers

Regeneration of cello-oligomers via selective depolymerization of cellulose fibers derived from printed paper wastes

tCellulose extracted from printed paper wastes were selectively depolymerized under controlledconditions into cello-oligomers of controllable chain lengths via dissolution in an ionic liquid, 1-allyl-3-methylimidazolium chloride (AMIMCl), and in the presence of an acid catalyst, Amberlyst 15DRY. Thedepolymerization process was optimized against reaction temperature, concentration of acid catalyst,and reaction time. Despite rapid initial depolymerization process, the rate of cellulose depolymerizationslowed down gradually upon prolonged reaction time, with 75.0 wt% yield of regenerated cello-oligomers(mean Viscosimetric Degree of Polymerization value of 81) obtained after 40 min. The depolymeriza-tion of cellulose fibers at 80◦C appeared to proceed via a second-order kinetic reaction with respect tothe catalyst concentration of 0.23 mmol H3O+. As such, the cellulose depolymerization process couldafford some degree of control on the degree of polymerization or chain lengths of cello-oligomersformed

Effective fertility counselling for transgender adolescents : a qualitative study of clinician attitudes and practices

OBJECTIVE: Fertility counselling for trans and gender diverse (TGD) adolescents has many complexities, but there is currently little guidance for clinicians working in this area. This study aimed to identify effective strategies for-and qualities of-fertility counselling for TGD adolescents based on clinicians' experiences. DESIGN: We conducted qualitative semi-structured individual interviews in 2019 which explored clinician experiences and fertility counselling practices, perspectives of the young person's experience and barriers and facilitators to fertility preservation access. Data were analysed using thematic analysis. SETTING: This qualitative study examined experiences of clinicians at the Royal Children's Hospital-a tertiary, hospital-based, referral centre and the main provider of paediatric TGD healthcare in Victoria, Australia. PARTICIPANTS: We interviewed 12 clinicians from a range of disciplines (paediatrics, psychology, psychiatry and gynaecology), all of whom were involved with fertility counselling for TGD adolescents. RESULTS: Based on clinician experiences, we identified five elements that can contribute to an effective approach for fertility counselling for TGD adolescents: a multidisciplinary team approach; shared decision-making between adolescents, their parents and clinicians; specific efforts to facilitate patient engagement; flexible personalised care; and reflective practice. CONCLUSIONS: Identification of these different elements can inform and hopefully improve future fertility counselling practices for TGD adolescents, but further studies examining TGD adolescents' experiences of fertility counselling are also required

A Framework for Diagnosing Dyscalculia

This paper outlines the development of mathematical items which evolves from making sense of mathematics through perception, operation, and reason. There are three main constructs in this framework, and it involves seven tests namely simple reaction time, short term memory, number sense, matching Items, dot enumeration, number comparison and arithmetic. This study is concerned with how a group of students struggle with basic numerical skills which may be caused by dyscalculia. One of the most important contributions of this study, in addition to its wider theoretical and practical applications, is that it has come out with a set of standardized instruments which is called the Malaysian Dyscalculia Instrument (MDI) for primary school students. This tool could be further used widely in the fields of psychology and education, especially special education and particularly research studies related to education

Clusters of internally primed transcripts reveal novel long noncoding RNAs

Non- protein- coding RNAs ( ncRNAs) are increasingly being recognized as having important regulatory roles. Although much recent attention has focused on tiny 22- to 25- nucleotide microRNAs, several functional ncRNAs are orders of magnitude larger in size. Examples of such macro ncRNAs include Xist and Air, which in mouse are 18 and 108 kilobases ( Kb), respectively. We surveyed the 102,801 FANTOM3 mouse cDNA clones and found that Air and Xist were present not as single, full- length transcripts but as a cluster of multiple, shorter cDNAs, which were unspliced, had little coding potential, and were most likely primed from internal adenine- rich regions within longer parental transcripts. We therefore conducted a genome- wide search for regional clusters of such cDNAs to find novel macro ncRNA candidates. Sixty- six regions were identified, each of which mapped outside known protein- coding loci and which had a mean length of 92 Kb. We detected several known long ncRNAs within these regions, supporting the basic rationale of our approach. In silico analysis showed that many regions had evidence of imprinting and/ or antisense transcription. These regions were significantly associated with microRNAs and transcripts from the central nervous system. We selected eight novel regions for experimental validation by northern blot and RT- PCR and found that the majority represent previously unrecognized noncoding transcripts that are at least 10 Kb in size and predominantly localized in the nucleus. Taken together, the data not only identify multiple new ncRNAs but also suggest the existence of many more macro ncRNAs like Xist and Air