Bone Mineral Density in Transgender Adolescents Treated With Puberty Suppression and Subsequent Gender-Affirming Hormones.

Importance: Bone mineral density (BMD) z scores in transgender adolescents decrease during puberty suppression with a gonadotropin-releasing hormone (GnRH) agonist. Previous research found that after short-term use of gender-affirming hormones (GAH), pretreatment z scores were not restored. Long-term follow-up studies are lacking.

Metabolic activity organizes olfactory representations.

Hearing and vision sensory systems are tuned to the natural statistics of acoustic and electromagnetic energy on earth and are evolved to be sensitive in ethologically relevant ranges. But what are the natural statistics of , and how do olfactory systems exploit them? Dissecting an accurate machine learning model (Lee et al., 2022) for human odor perception, we find a computable representation for odor at the molecular level that can predict the odor-evoked receptor, neural, and behavioral responses of nearly all terrestrial organisms studied in olfactory neuroscience.

Development of Hip Bone Geometry During Gender-Affirming Hormone Therapy in Transgender Adolescents Resembles That of the Experienced Gender When Pubertal Suspension Is Started in Early Puberty.

Bone geometry can be described in terms of periosteal and endocortical growth and is partly determined by sex steroids. Periosteal and endocortical apposition are thought to be regulated by testosterone and estrogen, respectively. Gender-affirming hormone (GAH) treatment with sex steroids in transgender people might affect bone geometry.

Direct Visualization of Native CRISPR Target Search in Live Bacteria Reveals Cascade DNA Surveillance Mechanism.

CRISPR-Cas systems encode RNA-guided surveillance complexes to find and cleave invading DNA elements. While it is thought that invaders are neutralized minutes after cell entry, the mechanism and kinetics of target search and its impact on CRISPR protection levels have remained unknown. Here, we visualize individual Cascade complexes in a native type I CRISPR-Cas system.

Multiple Sclerosis Patients Show Lower Bioavailable 25(OH)D and 1,25(OH)D, but No Difference in Ratio of 25(OH)D/24,25(OH)D and FGF23 Concentrations.

Vitamin D (VitD) insufficiency is common in multiple sclerosis (MS). VitD has possible anti-inflammatory effects on the immune system. The ratio between VitD metabolites in MS patients and the severity of the disease are suggested to be related.

Fracture Risk in Trans Women and Trans Men Using Long-Term Gender-Affirming Hormonal Treatment: A Nationwide Cohort Study.

Concerns about bone health in transgender people using gender-affirming hormonal treatment (HT) exist, but the fracture risk is not known. In this nationwide cohort study, we aimed to compare the fracture incidence in transgender people using long-term HT with an age-matched reference population. All adult transgender people who started HT before 2016 at our gender-identity clinic were included and were linked to a random population-based sample of 5 age-matched reference men and 5 age-matched reference women per person.

Bone geometry and trabecular bone score in transgender people before and after short- and long-term hormonal treatment.

Background: Gender-affirming hormonal treatment (HT) in adult transgender people influences bone mineral density (BMD). Besides BMD, bone geometry and trabecular bone score are associated with fracture risk. However, it is not known whether bone geometry and TBS changes during HT.

Gender-Affirming Hormone Treatment Decreases Bone Turnover in Transwomen and Older Transmen.

Sex steroids play a key role in bone turnover and preserving BMD; hence, gender-affirming hormone treatment (HT) in transgender people affects bone metabolism. Most studies have looked into the effect of HT on changes in BMD; however, they do not provide insights into changes in bone metabolism caused by HT. This study investigated changes in bone turnover markers (BTMs) and sclerostin, as well as their correlations with change in BMD in transwomen and transmen during the first year of HT.

Systematic analysis of Type I-E Escherichia coli CRISPR-Cas PAM sequences ability to promote interference and primed adaptation.

CRISPR interference occurs when a protospacer recognized by the CRISPR RNA is destroyed by Cas effectors. In Type I CRISPR-Cas systems, protospacer recognition can lead to «primed adaptation» - acquisition of new spacers from in cis located sequences. Type I CRISPR-Cas systems require the presence of a trinucleotide protospacer adjacent motif (PAM) for efficient interference.

Peripheral Insulin Extraction in Non-Diabetic Subjects and Type 2 Diabetes Mellitus Patients.

Background: Insulin has to be transported across the capillary endothelium to stimulate muscle glucose uptake. We investigated insulin uptake from the peripheral circulation in non-diabetic (ND) individuals and in type 2 diabetes (T2D) patients.

Methods: Single-center cross-sectional study involving 40 ND (age 65±11 years) and 30 T2D patients (age 67±8 years).

Bone Safety During the First Ten Years of Gender-Affirming Hormonal Treatment in Transwomen and Transmen.

Concerns about the effects of gender-affirming hormonal treatment (HT) on bone mineral density (BMD) in transgender people exist, particularly regarding the decrease in estrogen concentrations in transmen. Although it is known that HT is safe for BMD in the short term, long-term follow-up studies are lacking. Therefore this study aimed to investigate the change in BMD during the first 10 years of HT, to determine whether HT is safe and if assessing BMD during HT is necessary.

Targeting mechanisms of tailed bacteriophages.

Phages differ substantially in the bacterial hosts that they infect. Their host range is determined by the specific structures that they use to target bacterial cells. Tailed phages use a broad range of receptor-binding proteins, such as tail fibres, tail spikes and the central tail spike, to target their cognate bacterial cell surface receptors.

Secondary Surgery following Initial Replantation/Revascularization or Completion Amputation in the Hand or Digits.

Background: The authors studied the rate of secondary surgery following replantation/revascularization or completion amputation in patients with traumatic upper extremity injuries. The authors hypothesized that there are no factors associated with secondary surgery after initial treatment and that travel distance to the authors' hospital does not influence the number of secondary operations.

Methods: A multi-institutional retrospective study was performed including patients presenting from 2006 to 2014.

Clinical utility of bone markers in various diseases.

Measurements of bone markers (BMs) in peripheral blood or urine are a pivotal part of bone research within modern clinical medicine. In recent years the use of BMs increased substantially as they can be useful either to diagnose bone (related) disease and to follow its natural history, but also to monitor the effects of interventions. However, the use of BMs is still complicated mainly due to (pre)analytical variability of these substances, limited accessibility of assays, variable cut-off values in different countries and laboratories and heterogeneous results with regard to clinical implications of measuring BMs in several studies.

The relationship between serum IGF-1, handgrip strength, physical performance and falls in elderly men and women.

Objective: Human aging is accompanied by a decrease in growth hormone secretion and serum insulin-like growth factor (IGF)-1 levels. Also, loss of muscle mass and strength and impairment of physical performance, ending in a state of frailty, are seen in elderly. We aimed to investigate whether handgrip strength, physical performance and recurrent falls are related to serum IGF-1 levels in community-dwelling elderly.

Shooting the messenger: RNA-targetting CRISPR-Cas systems.

Since the discovery of CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-associated genes) immune systems, astonishing progress has been made on revealing their mechanistic foundations. Due to the immense potential as genome engineering tools, research has mainly focussed on a subset of Cas nucleases that target DNA. In addition, however, distinct types of RNA-targetting CRISPR-Cas systems have been identified.

Effect of antiretroviral therapy on bone turnover and bone mineral density in men with primary HIV-1 infection.

Introduction: Previous studies indicate that human immunodeficiency virus (HIV)-infection and combination antiretroviral therapy (cART) can affect bone turnover. Furthermore, HIV-infected patients have lower bone mineral density (BMD) compared to a healthy reference population.

Objective: To evaluate the longitudinal effect of HIV-infection and cART on bone turnover markers (BTMs) and BMD in men with primary HIV-infection (PHI).

Complete Genome Sequence of the Phage Ayreon.

We report the whole-genome sequence of a new temperate phage, Ayreon, comprising a linear double-stranded DNA (dsDNA) genome of 44,708 bp.

Bacteriophage DNA glucosylation impairs target DNA binding by type I and II but not by type V CRISPR-Cas effector complexes.

Prokaryotes encode various host defense systems that provide protection against mobile genetic elements. Restriction-modification (R-M) and CRISPR-Cas systems mediate host defense by sequence specific targeting of invasive DNA. T-even bacteriophages employ covalent modifications of nucleobases to avoid binding and therefore cleavage of their DNA by restriction endonucleases.

Symptomatic Neuroma Following Initial Amputation for Traumatic Digital Amputation.

Purpose: We tested the null hypothesis that no factors are independently associated with the development of symptomatic neuroma after traumatic digital amputation.

Methods: We performed a retrospective review of 1,083 patients who underwent revision amputation for traumatic digital amputation; we excluded those undergoing replantation or revascularization. Patients who developed a painful neuroma during follow-up were identified with a minimum follow-up of 1 week and a median of 3.

Bone Mineral Density Increases in Trans Persons After 1 Year of Hormonal Treatment: A Multicenter Prospective Observational Study.

Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross-sex hormonal treatment (CHT) in transgender persons can affect bone mineral density (BMD). The aim of this study was to investigate in a prospective observational multicenter study the first-year effects of CHT on BMD in transgender persons.

Effect of pubertal suppression and cross-sex hormone therapy on bone turnover markers and bone mineral apparent density (BMAD) in transgender adolescents.

Puberty is highly important for the accumulation of bone mass. Bone turnover and bone mineral density (BMD) can be affected in transgender adolescents when puberty is suppressed by gonadotropin-releasing hormone analogues (GnRHa), followed by treatment with cross-sex hormone therapy (CSHT). We aimed to investigate the effect of GnRHa and CSHT on bone turnover markers (BTMs) and bone mineral apparent density (BMAD) in transgender adolescents.

Two distinct DNA binding modes guide dual roles of a CRISPR-Cas protein complex.

Small RNA-guided protein complexes play an essential role in CRISPR-mediated immunity in prokaryotes. While these complexes initiate interference by flagging cognate invader DNA for destruction, recent evidence has implicated their involvement in new CRISPR memory formation, called priming, against mutated invader sequences. The mechanism by which the target recognition complex mediates these disparate responses-interference and priming-remains poorly understood.

RNA targeting by the type III-A CRISPR-Cas Csm complex of Thermus thermophilus.

CRISPR-Cas is a prokaryotic adaptive immune system that provides sequence-specific defense against foreign nucleic acids. Here we report the structure and function of the effector complex of the Type III-A CRISPR-Cas system of Thermus thermophilus: the Csm complex (TtCsm). TtCsm is composed of five different protein subunits (Csm1-Csm5) with an uneven stoichiometry and a single crRNA of variable size (35-53 nt).