The Dynamic Interplay between Puberty and Structural Brain Development as a Predictor of Mental Health Difficulties in Adolescence: a systematic review.

Puberty is a time of intense reorganization of brain structure and a high-risk period for the onset of mental health problems, with variations in pubertal timing and tempo intensifying this risk. We conducted two systematic reviews of papers published up to 1st February 2024 focusing on (1) the role of brain structure in the relationship between puberty and mental health, and (2) precision psychiatry research evaluating the utility of puberty in making individualized predictions of mental health in young people. The first review provides inconsistent evidence on whether and how pubertal and psychopathological processes could interact in relation to brain development. While most studies found an association between early puberty and mental health difficulties in adolescents, evidence on whether brain structure mediates this relationship is mixed. The pituitary gland was found to be associated with mental health status during this time, possibly through its central role in regulating puberty and its function in the hypothalamic- pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes. In the second review, the design of studies that have explored puberty in predictive models did not allow for a quantification of its predictive power. However, when puberty was evaluated through physically observable characteristics rather than hormonal measures, it was more commonly identified as a predictor of depression, anxiety, and suicidality in adolescence. Social processes might be more relevant than biological ones in the link between puberty and mental health problems, and represent an important target for educational strategies.

Maturation of the Female Pharyngeal Airway from Adolescence to Adulthood.

BACKGROUND: The present study aimed to investigate developmental changes in the female pharyngeal airway from adolescence to adulthood, considering variations in the anatomical structures related to the airway dimensions. METHODS: Lateral cephalograms of 214 females were analyzed and categorized into five developmental stages: early adolescence (10-13 years), middle adolescence (14-17 years), late adolescence (18-21 years), early adulthood (22-30 years), and middle adulthood (31-50 years). The focus of the analysis included the point A-Nasion-point B (ANB) angle, tongue pharyngeal airway space (TPS), epiglottis pharyngeal airway space (EPS), soft palate airway space (SPS), and the horizontal and vertical positions of the hyoid bone. RESULTS: The ANB angle exhibited significant variation across groups, being significantly larger in the early-adolescence group (4.22°) compared to the middle-adolescence, late-adolescence, and early-adulthood groups. The TPS and EPS were significantly shorter in the early-adolescence group. Negative correlations were observed between the ANB angle and the lengths of the pharyngeal airway spaces (SPS, TPS, and EPS). The horizontal and vertical positions of the hyoid bone remained stable after middle adolescence. CONCLUSION: The maturation of the ANB angle and pharyngeal airway in females seems nearly completed during middle adolescence (14-17 years). Additionally, a significant and negative correlation was identified between the ANB angle and the lengths of various pharyngeal airway spaces (SPS, TPS, and EPS). The horizontal and vertical positions of the hyoid bone showed stability after middle adolescence.

Exploring camouflaging by the Chinese version Camouflaging Autistic Traits Questionnaire in Taiwanese autistic and non-autistic adolescents: An initial development.

LAY ABSTRACT: Camouflaging is a coping strategy used by some autistic and other neurodivergent people to fit in neurotypical social contexts. The self-reported Camouflaging Autistic Traits Questionnaire has been validated for use in research with adults in some Western societies, but not in non-Western cultural-ethnic groups. We translated Camouflaging Autistic Traits Questionnaire into traditional Chinese and examined the use of this measure in Taiwanese adolescents via both self-report and caregiver-report in 100 autistic and 105 non-autistic adolescents. Both self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire were composed of two factors (i.e. a "compensation-masking" subscale and an "assimilation" subscale). Both adolescent self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire total score and subscales were reliable in measurement, and they highly correlated with each other. Taiwanese autistic adolescents were more likely to camouflage than non-autistic adolescents, especially on assimilation. Female autistic adolescents showed higher assimilation than male autistic adolescents. Higher camouflaging, especially assimilation, was associated with higher stress in autistic and non-autistic adolescents alike. Both self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire were reliable and offered meaningful information to help us understand the social coping experiences of autistic and non-autistic adolescents.

NAD(P)H:quinone Oxidoreductase 1 Is Involved in AZ-1-induced Apoptotic Effects in Nasopharyngeal Carcinoma TW01 Cells.

BACKGROUND/AIM: Current NPC treatment methods have improved the 5-year survival rates of patients; however, some patients do not benefit from the treatments. Therefore, the existing treatment methods or new drugs must be developed to improve the patient's prognosis. NAD (P)H:quinone oxidoreductase 1 (NQO1), an electron reductase highly expressed in various cancers, can convert aziridinyl-substituted quinone-derived compound into an alkylating agent, resulting in cell apoptosis. Therefore, a di-aziridinyl-substituted quinone-derived compound, AZ-1, was designed previously. The present study investigated whether AZ-1 has anticancer activities in NPC cells and explored the underlying mechanism. MATERIALS AND METHODS: NPC-TW01 cells were used in the study, and 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide, colony formation, terminal deoxynucleotidyl transferase dUTP nick end labeling, and immunoblotting assays were performed to assess the cell viability, cell survival, DNA fragmentation, and protein expression, respectively. RESULTS: The results show that AZ-1 significantly inhibited the viability and survival of NPC-TW01 cells. AZ-1 also induced the expression of cleaved PARP, cleaved caspase-8, cleaved caspase-9, and cleaved caspase-3, and triggered DNA fragmentation in NPC-TW01 cells. In addition, AZ-1 induced γH2AX expression, a DNA damage marker, in NPC-TW01 cells. Treatment with dicoumarol, an NQO1 activity inhibitor, not only reversed AZ-1-induced cell viability inhibition but also decreased AZ-1-induced expression of γH2AX, cleaved caspase-8, cleaved caspase-9, and cleaved caspase-3. CONCLUSION: NQO1 reverses AZ-1-triggered cell viability inhibition, DNA damage, and apoptosis. The findings of this study may provide a basis for the possible clinical application of AZ-1 in the treatment of NPC to improve the prognosis of patients with NPC.

Rational design of the genetic code expansion toolkit for in vivo encoding of D-amino acids.

Once thought to be non-naturally occurring, D-amino acids (DAAs) have in recent years been revealed to play a wide range of physiological roles across the tree of life, including in human systems. Synthetic biologists have since exploited DAAs' unique biophysical properties to generate peptides and proteins with novel or enhanced functions. However, while peptides and small proteins containing DAAs can be efficiently prepared in vitro, producing large-sized heterochiral proteins poses as a major challenge mainly due to absence of pre-existing DAA translational machinery and presence of endogenous chiral discriminators. Based on our previous work demonstrating pyrrolysyl-tRNA synthetase's (PylRS') remarkable substrate polyspecificity, this work attempts to increase PylRS' ability in directly charging tRNAPyl with D-phenylalanine analogs (DFAs). We here report a novel, polyspecific Methanosarcina mazei PylRS mutant, DFRS2, capable of incorporating DFAs into proteins via ribosomal synthesis in vivo. To validate its utility, in vivo translational DAA substitution were performed in superfolder green fluorescent protein and human heavy chain ferritin, successfully altering both proteins' physiochemical properties. Furthermore, aminoacylation kinetic assays further demonstrated aminoacylation of DFAs by DFRS2 in vitro.

Depression, postburn disability & quality of life: The moderating roles of burn specific coping strategies.

Depression has been associated with poorer postburn functional outcomes. However, whether or not certain burn specific coping strategies moderate the relationships remains unknown. Burn survivors from 2015 Formosa Fun Coast Water Park explosion were recruited in a 3-year follow-up study. Using Wave 1 data collected 1 year after discharge, we conducted multivariate regression analysis to assess the associations between depression and postburn disability and quality of life. We also performed moderation analysis to determine moderating effects of burn specific coping strategies on the associations. Our results found depression was significantly associated with worsening postburn disability and poorer quality of life. When demographic and burn related variables were accounted for, we found avoidance coping moderated the depression-disability relationship. Depression was significantly and positively correlated with disability at low and medium levels of avoidance but not high. Optimism/problem solving moderated the depression-quality of life relationship. Depression was significantly and negatively correlated with quality of life at low and medium levels of optimism/problem solving but not high. Our study provided evidence supporting early identification and intervention of depression in burn survivors to optimize functional outcomes. Such knowledge may provide insights into potential targets in rehabilitation in depressed burn survivors.

Using Hypothesis-Led Machine Learning and Hierarchical Cluster Analysis to Identify Disease Pathways Prior to Dementia: Longitudinal Cohort Study.

BACKGROUND: Dementia development is a complex process in which the occurrence and sequential relationships of different diseases or conditions may construct specific patterns leading to incident dementia. OBJECTIVE: This study aimed to identify patterns of disease or symptom clusters and their sequences prior to incident dementia using a novel approach incorporating machine learning methods. METHODS: Using Taiwan's National Health Insurance Research Database, data from 15,700 older people with dementia and 15,700 nondementia controls matched on age, sex, and index year (n=10,466, 67% for the training data set and n=5234, 33% for the testing data set) were retrieved for analysis. Using machine learning methods to capture specific hierarchical disease triplet clusters prior to dementia, we designed a study algorithm with four steps: (1) data preprocessing, (2) disease or symptom pathway selection, (3) model construction and optimization, and (4) data visualization. RESULTS: Among 15,700 identified older people with dementia, 10,466 and 5234 subjects were randomly assigned to the training and testing data sets, and 6215 hierarchical disease triplet clusters with positive correlations with dementia onset were identified. We subsequently generated 19,438 features to construct prediction models, and the model with the best performance was support vector machine (SVM) with the by-group LASSO (least absolute shrinkage and selection operator) regression method (total corresponding features=2513; accuracy=0.615; sensitivity=0.607; specificity=0.622; positive predictive value=0.612; negative predictive value=0.619; area under the curve=0.639). In total, this study captured 49 hierarchical disease triplet clusters related to dementia development, and the most characteristic patterns leading to incident dementia started with cardiovascular conditions (mainly hypertension), cerebrovascular disease, mobility disorders, or infections, followed by neuropsychiatric conditions. CONCLUSIONS: Dementia development in the real world is an intricate process involving various diseases or conditions, their co-occurrence, and sequential relationships. Using a machine learning approach, we identified 49 hierarchical disease triplet clusters with leading roles (cardio- or cerebrovascular disease) and supporting roles (mental conditions, locomotion difficulties, infections, and nonspecific neurological conditions) in dementia development. Further studies using data from other countries are needed to validate the prediction algorithms for dementia development, allowing the development of comprehensive strategies to prevent or care for dementia in the real world.

Enhanced Superconductivity and Rashba Effect in a Buckled Plumbene-Au Kagome Superstructure.

Plumbene, with a structure similar to graphene, is expected to possess a strong spin-orbit coupling and thus enhances its superconducting critical temperature (Tc ). In this work, a buckled plumbene-Au Kagome superstructure grown by depositing Au on Pb(111) is investigated. The superconducting gap monitored by temperature-dependent scanning tunneling microscopy/spectroscopy shows that the buckled plumbene-Au Kagome superstructure not only has an enhanced Tc with respect to that of a monolayer Pb but also possesses a higher value than what owned by a bulk Pb substrate. By combining angle-resolved photoemission spectroscopy with density functional theory, the monolayer Au-intercalated low-buckled plumbene sandwiched between the top Au Kagome layer and the bottom Pb(111) substrate is confirmed and the electron-phonon coupling-enhanced superconductivity is revealed. This work demonstrates that a buckled plumbene-Au Kagome superstructure can enhance superconducting Tc and Rashba effect, effectively triggering the novel properties of a plumbene.

Changes in Preexisting Temporomandibular Joint Clicking after Orthognathic Surgery in Patients with Mandibular Prognathism.

This study aimed to investigate the changes in preexisting temporomandibular joint (TMJ) clicking and the new incidence of TMJ clicking after orthognathic surgery. A total of 60 patients (30 men and 30 women) with mandibular prognathism underwent intraoral vertical ramus osteotomy (IVRO) for a mandibular setback. The setback amount and TMJ clicking symptoms (preoperative and one year postoperative) were recorded. To assess the risk of new incidence of TMJ clicking in asymptomatic patients, the cutoff value for postoperative mandibular setback was set at 8 mm. The left and right mandibular setbacks were 11.1 and 10.9 mm in men, respectively, and 10.7 and 10.0 mm in women, respectively. Thus, no difference in setback amount on either side was observed between the sexes. The improvement rate in patients with preexisting TMJ clicking was 69.2% (18 of 26 sides); the postoperative improvement rates were 71.4% (setback amount > 8 mm) and 60% (setback amount ≤ 8 mm). IVRO may reduce the severity of preexisting TMJ clicking. A high setback amount (>8 mm) may not be associated with a considerable increase in the risk of postoperative TMJ clicking.

The eBRAIN study: The impact of early adversity on trajectories of brain maturation and mental health in young adolescents - A prospective cohort study.

Introduction: More than 1 in 10 people are thought to experience a mental health problem during adolescence, with most adult psychopathology beginning during this time. Experiences of stress or adversity during childhood are important risk factors for poorer mental health outcomes and are also associated with alterations in neurodevelopment. There is evidence to suggest that this relationship is mediated by inflammation and the immune system. The eBRAIN study (The Impact of Early Adversity on Trajectories of Brain Maturation and Mental Health in Young Adolescents) will assess how early life adversity might affect trajectories of brain development throughout adolescence, whether these neurobiological changes are associated with psychopathology, and if they can potentially be explained by an activation of the immune system. Methods: A cohort of 220 adolescents between the ages of 11-14 will be recruited into this study. Each participant will complete three study visits, each one year apart, at the Institute of Psychiatry, Psychology and Neuroscience, King's College London, London (UK). At each study visit, they will be assessed with structural and functional MRI scans, biological sample collection as well as questionnaires and interviews to collect demographic information, assess experiences of adversity, and details of psychopathology. The study will also collect information about factors such as diet and nutrition, physical exercise, and cognition. Ethics and dissemination: Ethical approval for this study has been received by King's College London Research Ethics Committee (REC reference: HR-18/19-9033). Findings from the study will be published in peer-reviewed journals and disseminated at national and international conferences. Patient and public involvement (PPI) is an important component of the study, 'Study Champions' recruited from participants, their parents and teachers at collaborating schools have been invited to take an active role in study governance and dissemination.

Mediators and moderators in the relationship between maternal childhood adversity and children's emotional and behavioural development: a systematic review and meta-analysis.

Maternal experiences of childhood adversity can increase the risk of emotional and behavioural problems in their children. This systematic review and meta-analysis provide the first narrative and quantitative synthesis of the mediators and moderators involved in the link between maternal childhood adversity and children's emotional and behavioural development. We searched EMBASE, PsycINFO, Medline, Cochrane Library, grey literature and reference lists. Studies published up to February 2021 were included if they explored mediators or moderators between maternal childhood adversity and their children's emotional and behavioural development. Data were synthesised narratively and quantitatively by meta-analytic approaches. The search yielded 781 articles, with 74 full-text articles reviewed, and 41 studies meeting inclusion criteria. Maternal mental health was a significant individual-level mediator, while child traumatic experiences and insecure maternal-child attachment were consistent family-level mediators. However, the evidence for community-level mediators was limited. A meta-analysis of nine single-mediating analyses from five studies indicated three mediating pathways: maternal depression, negative parenting practices and maternal insecure attachment, with pooled indirect standardised effects of 0.10 [95% CI (0.03-0.17)), 0.01 (95% CI (-0.02 to 0.04)] and 0.07 [95% CI (0.01-0.12)], respectively. Research studies on moderators were few and identified some individual-level factors, such as child sex (e.g. the mediating role of parenting practices being only significant in girls), biological factors (e.g. maternal cortisol level) and genetic factors (e.g. child's serotonin-transporter genotype). In conclusion, maternal depression and maternal insecure attachment are two established mediating pathways that can explain the link between maternal childhood adversity and their children's emotional and behavioural development and offer opportunities for intervention.

Ferritin Conjugates With Multiple Clickable Amino Acids Encoded by C-Terminal Engineered Pyrrolysyl-tRNA Synthetase.

This study reports the application of expanding genetic codes in developing protein cage-based delivery systems. The evolved Methanosarcina mazei pyrrolysyl-tRNA synthetase (PylRS)•tRNAPyl pairs derived from directed evolution are examined to probe their recognition for para-substituted phenylalanine analogs. The evolved MmPylRS, AzFRS, harboring a wide range of substrates, is further engineered at the C-terminal region into another variant, AzFRS-MS. AzFRS-MS shows suppression of the elevated sfGFP protein amount up to 10 TAG stop codons when charging p-azido-l-phenylalanine (AzF, 4), which allows the occurrence of click chemistry. Since protein nanocages used as drug delivery systems that encompass multiple drugs through a site-specific loading approach remain largely unexplored, as a proof of concept, the application of AzFRS-MS for the site-specific incorporation of AzF on human heavy chain ferritin (Ftn) is developed. The Ftn-4 conjugate is shown to be able to load multiple fluorescence dyes or a therapeutic agent, doxorubicin (Dox), through the strain-promoted azide-alkyne cycloaddition (SPAAC) click reaction. Aiming to selectively target Her2+ breast cancer cells, Ftn-4-DOX conjugates fused with a HER2 receptor recognition peptide, anti-Her2/neu peptide (AHNP), is developed and demonstrated to be able to deliver Dox into the cell and to prolong the drug release. This work presents another application of evolved MmPylRS systems, whose potential in developing a variety of protein conjugates is noteworthy.

Prenatal Bisphenol a Exposure, DNA Methylation, and Low Birth Weight: A Pilot Study in Taiwan.

Prenatal exposure to bisphenol A (BPA) may increase the risk of abnormal birth outcomes, and DNA methylation might mediate these adverse effects. This study aimed to investigate the effects of maternal BPA exposure on maternal and fetal DNA methylation levels and explore whether epigenetic changes are related to the associations between BPA and low birth weight. We collected urine and blood samples originating from 162 mother-infant pairs in a Taiwanese cohort study. We measured DNA methylation using the Illumina Infinium HumanMethylation 450 BeadChip in 34 maternal blood samples with high and low BPA levels based on the 75th percentile level (9.5 µg/g creatinine). Eighty-seven CpGs with the most differentially methylated probes possibly interacting with BPA exposure or birth weight were selected using two multiple regression models. Ingenuity pathway analysis (IPA) was utilized to narrow down 18 candidate CpGs related to disease categories, including developmental disorders, skeletal and muscular disorders, skeletal and muscular system development, metabolic diseases, and lipid metabolism. We then validated these genes by pyrosequencing, and 8 CpGs met the primer design score requirements in 82 cord blood samples. The associations among low birth weight, BPA exposure, and DNA methylation were analyzed. Exposure to BPA was associated with low birth weight. Analysis of the epigenome-wide findings did not show significant associations between BPA and DNA methylation in cord blood of the 8 CpGs. However, the adjusted odds ratio for the dehydrogenase/reductase member 9 (DHRS9) gene, at the 2nd CG site, in the hypermethylated group was significantly associated with low birth weight. These results support a role of BPA, and possibly DHRS9 methylation, in fetal growth. However, additional studies with larger sample sizes are warranted.

Revealing USP7 Deubiquitinase Substrate Specificity by Unbiased Synthesis of Ubiquitin Tagged SUMO2.

Ubiquitination and SUMOylation of protein are crucial for various biological responses. The recent unraveling of cross-talk between SUMO and ubiquitin (Ub) has shown the pressing needs to develop the platform for the synthesis of Ub tagged SUMO2 dimers to decipher its biological functions. Still, the platforms for facile synthesis of dimers under native condition are less explored and remain major challenges. Here, we have developed the platform that can expeditiously synthesize all eight Ub tagged SUMO2 and SUMOylated proteins under native condition. Expanding genetic code (EGC) method was employed to incorporate Se-alkylselenocysteine at lysine positions. Oxidative selenoxide elimination generates the electrophilic center, dehydroalanine, which upon Michael addition with C-terminal modified ubiquitin, a nucleophile, yield Ub tagged SUMO2. The dimers were further interrogated with USP7, a SUMO2 deubiquitinase, which is involved in DNA repair, to understand specificity toward the Ub tagged SUMO2 dimer. Our results have shown that the C-terminal domain of USP7 is crucial for USP7 efficiency and selectivity for the Ub tagged SUMO2 dimer.

Probing the Active Site of Deubiquitinase USP30 with Noncanonical Tryptophan Analogues.

Methanosarcina mazei pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA have been evolved to generate genetically encoded noncanonical amino acids (ncAAs). Use of tryptophan (Trp) analogues with pyrrole ring modification for their spatial and polarity tuning in enzyme activity and substrate specificity is still limited. Herein, we report the application of an evolved PylRS, FOWRS2, for efficient incorporation of five Trp analogues into the deubiquitinase USP30 to decipher the role of W475 for diubiquitin selectivity. Structures of the five FOWRS-C/Trp analogue complexes at 1.7-2.5 Å resolution showed multiple ncAA binding modes. The W475 near the USP30 active site was replaced with Trp analogues, and the effect on the activity as well as the selectivity toward diubiquitin linkage types was examined. It was found that the Trp analogue with a formyl group attached to the nitrogen atom of the indole ring led to an improved activity of USP30 likely due to enhanced polar interactions and that another Trp analogue, 3-benzothienyl-l-alanine, induced a unique K6-specificity. Collectively, genetically encoded noncanonical Trp analogues by evolved PylRS·tRNACUAPyl pair unravel the spatial role of USP30-W475 in its diubiquitin selectivity.

Hospitalized burn injury risk associated with benzodiazepines and Z-drugs in elders: A population-based case-control study.

OBJECTIVE: To examine the association between benzodiazepines (BZDs) and Z-drugs treatment and risk of burn injury in elders. METHODS: We designed a nested case-control study. All subjects were aged 65 and older and enrolled in the National Health Insurance program in Taiwan, 2003 to 2012; 813 cases were identified with burn injury for the first time in their inpatient claims, and they were individually matched to 4879 controls based on age, gender, and index year. Benzodiazepines and Z-drugs usage (doses, duration, half-life) and the other covariates including comorbidities, health care utilization, and psychotropic medications used in the 365 days before index events were examined. RESULTS: A significant increased risk of burn injury hospitalization in elders was observed among current Z-drugs users compared with nonusers (adjusted odds ratio [AOR] = 1.59, 95% confidence interval [CI] [1.23, 2.07]). BZDs at high (AOR = 1.81, 95% CI [1.12, 2.94] and medium dosage (AOR = 1.53, 95% CI [1.15, 2.04] and Z-drugs at medium dosage (AOR = 1.60, 95% CI [1.20, 2.12]) were all significantly increased the burn-related injury requiring hospitalization. Polypharmacy of anxiolytic and hypnotic BZDs, long- and short-acting BZDs, and more than one BZD with or without Z-drugs also increased the risk. CONCLUSIONS: BZDs and Z-drugs prescriptions in elders may be associated with increased risk of burn injury hospitalization. When prescribing BZDs and Z-drugs, clinicians should exercise caution with the elderly to minimize risks.

Trends and factors in antipsychotic use of outpatients with anxiety disorders in Taiwan, 2005-2013: A population-based study.

AIM: Antipsychotics off-label use is common in clinical practice but information is limited in regards to the trends of antipsychotic use in specific mental disorders in Taiwan. This study aimed to examine the trends and associated factors of antipsychotic use among outpatients with anxiety disorders in Taiwan during 2005-2013. METHODS: We assessed the annual prescriptions of antipsychotic use in nine consecutive years (2005-2013) using the National Health Insurance Research Database among adults (aged ≥18 years) with anxiety disorders in outpatient visits in Taiwan. We applied logistic regression to examine the trends and associated factors of antipsychotic use. RESULTS: The proportion of antipsychotic medication use for anxiety disorder increased from 8.4% in 2005 to 9.1% in 2013. First-generation antipsychotics (FGA) use was more than that of second-generation antipsychotics (SGA) use in patients with anxiety disorder through the 9-year period. Sulpiride and flupentixol were the two most common FGA in the treatment of anxiety disorder. Patients with specific anxiety disorder (post-traumatic stress disorder, panic disorder/agoraphobia, generalized anxiety disorder, and obsessive-compulsive disorder), female sex, younger age (age < 65 years), comorbidity with major depression or minor depression, antidepressants concurrent use, and visits to psychiatrists, medical centers and primary care were significantly more likely to take prescribed antipsychotics. CONCLUSION: Antipsychotic off-label use significantly increased among patients with anxiety disorder in this national representative cohort. Such increased use of antipsychotics could be driven by augmentation of their prescription for major depression. As their efficacy and safety remain uncertain, further study is warranted.

Association of benzodiazepine and Z-drug use with the risk of hospitalisation for fall-related injuries among older people: a nationwide nested case-control study in Taiwan.

BACKGROUND: Non-benzodiazepine hypnotics (Z-drugs) are advocated to be safer than benzodiazepines (BZDs). This study comprehensively investigated the association of BZD and Z-drug usage with the risk of hospitalisation for fall-related injuries in older people. METHODS: This study used the Taiwan National Health Insurance Database with a nested matched case-control design. We identified 2238 elderly patients who had been hospitalised for fall-related injuries between 2003 and 2012. They were individually matched (1:4) with a comparison group by age, sex, and index year. Conditional logistic regression was used to determine independent effects of drug characteristics (type of exposure, dosage, half-life, and polypharmacy) on older people. RESULTS: Older people hospitalisation for fall-related injuries were significantly associated with current use of BZDs (adjusted odds ratio [AOR] = 1.32, 95% confidential interval [CI] = 1.17-1.50) and Z-drugs (AOR = 1.24, 95%CI = 1.05-1.48). At all dose levels of BZDs, high dose levels of Z-drugs, long-acting BZD, and short-acting BZD use were all significantly increased the risk of fall-related injuries requiring hospitalisation. Polypharmacy, the use of two or more kinds of BZDs, one kind of BZD plus Z-drugs and two or more kinds of BZDs plus Z-drugs, also significantly increased the risk (AOR = 1.61, 95% CI = 1.38-1.89; AOR = 1.65, 95% CI = 1.08-2.50, and AOR = 1.58, 95% CI = 1.21-2.07). CONCLUSIONS: Different dose levels and half-lives of BZDs, a high dose of Z-drugs, and polypharmacy with BZDs and Z-drugs were associated with an increased risk of fall-related injury requiring hospitalisation in older people. Physicians should balance the risks and benefits when prescribing these drug regimens to older people considering the risk of falls.

Concurrent exposures to nonylphenol, bisphenol A, phthalates, and organophosphate pesticides on birth outcomes: A cohort study in Taipei, Taiwan.

Prenatal exposure to phenols, phthalates (PAEs), and organophosphate (OP) pesticides may increase the risk of abnormal birth outcomes. However, many previous studies have examined exposure to a limited number of chemical classes or exposure profiles limited to a specific stage of pregnancy. This study aims to characterize the concurrent exposure scenario throughout pregnancy by simultaneously monitoring internal doses of several endocrine-disrupting compounds (EDCs), including 2 phenols (nonylphenol (NP) and bisphenol A (BPA)), 9 PAEs, and 6 OP pesticide metabolites and to assess the relationships between concurrent exposure to EDCs and infant birth weight, length, and head and chest circumference. One hundred and sixty two women provided three spot urine samples at approximately 11 and 26weeks gestation and at delivery. We applied multivariable linear regression and ridge regression models to estimate the effects of separate and correlated exposures. Multivariable linear regression models revealed that women with short birth-length infants had significantly higher urinary second-trimester NP levels (50th percentile, 5.03µg/g creatinine) (ß=-0.47cm; 95% CI=-0.93 to -0.01). Similarly significant relationships were observed between second-trimester mono-methyl phthalate (MMP) exposure and short birth length, second-trimester ΣPAEs and short birth length, second-trimester ΣPAEs exposure and reduced head and chest circumference, second-trimester diethylphosphate (DEP) exposure and reduced birth weight and length, and second-trimester ΣDEPs exposure and short birth length. Women with urinary BPA above the 75th percentile or ΣPAEs levels above the 50th percentile in the third trimester had infants with significantly reduced head circumference. These observations suggest that the second trimester may be the critical stage of susceptibility for fetal development. In ridge regression models, for which women with fewer measures for exposure to NP, BPA, MMP, ΣPAEs, DEP and ΣDEPs simultaneously were available, no relationships were found with infant size at birth. Additional studies with larger sample sizes are warranted.

Trends and factors associated with antipsychotic use among elderly patients with dementia in Taiwan from 2005 to 2013: a population-based study.

This study aimed to examine the trends and factors associated with antipsychotic prescriptions for elderly outpatients with dementia in Taiwan from 2005 to 2013. We assessed the annual prescription patterns of antipsychotic medications among elderly patients attending outpatient visits for dementia between 2005 and 2013 using the National Health Insurance Research Database in Taiwan. We also carried out logistic regression analyses to test the trends and associated factors. We found that any antipsychotic prescriptions for elderly patients making visits for dementia increased slightly, from 25.5 to 26.5%, over the 9-year period. From 2005 to 2013, prescriptions for first-generation antipsychotics only decreased from 7.8 to 3.3%, whereas second-generation antipsychotic prescriptions only increased from 17.0 to 22.2%. Elderly dementia patients who were female, older, concomitantly using other psychotropic drugs (antidepressants, benzodiazepines, and Z-drugs), and treated by psychiatrists and at regional/local hospitals were prescribed significantly more antipsychotics, whereas patients with comorbid hypertension, hyperlipidemia, diabetes, and stroke used antipsychotics significantly less. Although physicians seemed to avoid prescribing antipsychotics for elderly outpatients with dementia and certain comorbid physical disorders, second-generation antipsychotic use increased during the study period. Physicians should balance the benefits and risks of antipsychotic use to ensure the safety of dementia patients.