Risk Factors and Scoring Systems to Predict the Mortality Risk of Afebrile Adult Patients with Monomicrobial Gram-Negative Bacteremia: A 10-Year Observational Study in the Emergency Department.

BACKGROUND: The mortality rate of afebrile bacteremia has been reported to be as high as 45%. This investigation focused on the risk factors and predictive performance of scoring systems for the clinical outcomes of afebrile patients with monomicrobial gram-negative bacteria (GNB) in the emergency department (ED). METHODS: We conducted a retrospective analysis of afebrile adult ED patients with monomicrobial GNB bacteremia from January 2012 to December 2021. We dissected the demographics, clinical pictures, and laboratory investigations. We applied five scoring systems and three revised systems to predict the clinical outcomes. RESULTS: There were 600 patients included (358 males and 242 females), with a mean age of 69.6 ± 15.4 years. The overall mortality rate was 50.17%, reaching 68.52% (74/108) in cirrhotic patients. Escherichia coli was the leading pathogen (42.83%). The non-survivors had higher scores of the original MEDS (p < 0.001), NEWS (p < 0.001), MEWS (p < 0.001), qSOFA (p < 0.001), and REMS (p = 0.030). In univariate logistic regression analyses, several risk factors had a higher odds ratio (OR) for mortality, including liver cirrhosis (OR 2.541, p < 0.001), malignancy (OR 2.259, p < 0.001), septic shock (OR 2.077, p = 0.002), and male gender (OR 0.535, p < 0.001). The MEDS demonstrated that the best predictive power with the maximum area under the curve (AUC) was measured at 0.773 at the cut-off point of 11. The AUCs of the original NEWS, MEWS, qSOFA, and REMS were 0.663, 0.584, 0.572, and 0.553, respectively. We revised the original MEDS, NEWS, and qSOFA by adding red cell distribution width, albumin, and lactate scores and found a better predictive power of the AUC of 0.797, 0.719, and 0.694 on the revised MEDS ≥11, revised qSOFA ≥ 3, and revised NEWS ≥ 6, respectively. CONCLUSIONS: The original MEDS, revised MEDS, revised qSOFA, and revised NEWS were valuable tools for predicting the mortality risk in afebrile patients with monomicrobial GNB bacteremia. We suggested that clinicians should explore patients with the risk factors mentioned above for possible severe infection, even in the absence of fever and initiate hemodynamic support and early adequate antibiotic therapy in patients with higher scores of the original MEDS (≥11), revised MEDS (≥11), revised NEWS (≥6), and revised qSOFA (≥3).

Unveiling the proteome-wide autoreactome enables enhanced evaluation of emerging CAR-T therapies in autoimmunity.

Given the global surge in autoimmune diseases, it is critical to evaluate emerging therapeutic interventions. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leveraged advances in programmable-phage immunoprecipitation (PhIP-Seq) methodology to explore the modulation, or lack thereof, of autoantibody profiles, proteome-wide, in both health and disease. Using a custom set of over 730,000 human derived peptides, we demonstrated that each individual, regardless of disease state, possesses a distinct and complex constellation of autoreactive antibodies. For each individual, the set of resulting autoreactivites constituted a unique immunological fingerprint, or "autoreactome," that was remarkably stable over years. Using the autoreactome as a primary output, we evaluated the relative effectiveness of various immunomodulatory therapies in altering autoantibody repertoires. We found that therapies targeting B-Cell Maturation Antigen (BCMA) profoundly altered an individual's autoreactome, while anti-CD19 and CD20 therapies had minimal effects. These data both confirm that the autoreactome is comprised of autoantibodies secreted by plasma cells, and strongly suggest that BCMA or other plasma cell targeting therapies may be highly effective in treating currently refractory autoantibody mediated diseases.

Traumatic terson syndrome with a peculiar mass lesion and tractional retinal detachment: a case report.

BACKGROUND: To report a case with bilateral Terson syndrome presented with a unique mushroom-like mass lesion on the optic disc along with proliferative vitreoretinopathy and tractional retinal detachment. CASE PRESENTATION: A 33-year-old man was injured during a traffic accident and had diffuse brain swelling and intraocular hemorrhage. Poor vision in both eyes was noted after the patient regained consciousness. B-scan ultrasonography showed extensive vitreous opacity with a posterior vitreous detachment and without obvious retinal detachment. Vitrectomy was performed in both eyes five months after the accident. After clearing up the vitreous opacity, a peculiar pigmented mushroom-like mass lesion was noted in the posterior pole and had severe adhesion to the underneath optic disc. Extensive multilayered peripapillary epiretinal membrane was found covering the posterior pole and led to tractional retinal detachment around the macula. The mass was presumed to be an organized vitreous hemorrhage originated from the optic disc. The extensive and adherent epiretinal membrane together with the mass lesion were removed as much as possible and silicon oil was injected for tamponade. However, in the right eye, the retina redetached under silicon oil, whereas in the left eye, his vision improved to 20/100. CONCLUSIONS: Terson syndrome usually has a favorable prognosis but may be complicated by proliferative vitreoretinopathy and tractional retinal detachment. Careful monitoring is warranted and early vitrectomy should be considered in cases suspecting additional pathologies.

The emergence of tumor-initiating cells in an advanced hypopharyngeal tumor model exhibits enhanced angiogenesis and nuclear factor erythroid 2-related factor 2 associated antioxidant effects.

Hypopharyngeal cancer (HPC) is associated with the worst prognosis of all head and neck cancers and is typically identified in an advanced stage at the time of diagnosis. While oxidative stress might contribute to the onset of HPC in patients using tobacco or alcohol, the extent of this influence and the characteristics of HPC cells in advanced stage remain to be investigated. In this study, we explored whether HPC cells survived from necrotic xenograft tumors at late stage would display increased tumor resistance along with altered tolerance to oxidative stress. The remnant living HPC cells isolated from a late-stage xenograft tumor, named FaDu Ex-vivo cells showed stronger chemo- and radio-resistance, tumorigenesis, and invasiveness compared to parental FaDu cells. FaDu Ex-vivo cells also displayed increased angiogenic ability after re-transplantation to mice visualized by in vivo near infrared-II (NIR-II) fluorescence imaging modality. Moreover, FaDu Ex-vivo cells exhibited significant tumor-initiating cells (TICs) related properties accompanied by a reduction of the level of reactive oxygen species (ROS), which was associated with up-regulation of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Interestingly, inhibition of Nrf2 by the RNA interference and the chemical inhibitor could reduce TICs related properties of FaDu Ex-vivo cells. Oxidative stress potentially initiates HPC, but elevation of Nrf2-associated antioxidant mechanisms would be essential to mitigate this effect for promoting and sustaining the stemness of HPC at the advanced stage. Current data suggest that the antioxidant potency of advanced HPC would be a therapeutic target for the design of adjuvant treatm.

GBA1 as a risk gene for osteoporosis in the specific populations and its role in the development of Gaucher disease.

BACKGROUND: Osteoporosis and its primary complication, fragility fractures, contribute to substantial global morbidity and mortality. Gaucher disease (GD) is caused by glucocerebrosidase (GBA1) deficiency, leading to skeletal complications. This study aimed to investigate the impact of the GBA1 gene on osteoporosis progression in GD patients and the specific populations. METHODS: We selected 8115 patients with osteoporosis (T-score ≤ - 2.5) and 55,942 healthy individuals (T-score > - 1) from a clinical database (N = 95,223). Monocytes from GD patients were evaluated in relation to endoplasmic reticulum (ER) stress, inflammasome activation, and osteoclastogenesis. An in vitro model of GD patient's cells treated with adeno-associated virus 9 (AAV9)-GBA1 to assess GBA1 enzyme activity, chitotriosidase activity, ER stress, and osteoclast differentiation. Longitudinal dual-energy X-ray absorptiometry (DXA) data tracking bone density in patients with Gaucher disease (GD) undergoing enzyme replacement therapy (ERT) over an extended period. RESULTS: The GBA1 gene variant rs11264345 was significantly associated [P < 0.002, Odds Ratio (OR) = 1.06] with an increased risk of bone disease. Upregulation of Calnexin, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) and Apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) was positively associated with osteoclastogenesis in patients with GD. In vitro AAV9-GBA1 treatment of GD patient cells led to enhanced GBA1 enzyme activity, reduced chitotriosidase activity, diminished ER stress, and decreased osteoclast differentiation. Long-term bone density data suggests that initiating ERT earlier in GD leads to greater improvements in bone density. CONCLUSIONS: Elevated ER stress and inflammasome activation are indicative of osteoporosis development, suggesting the need for clinical monitoring of patients with GD. Furthermore, disease-associated variant in the GBA1 gene may constitute a risk factor predisposing specific populations to osteoporosis.

Syndromic ciliopathy: a taiwanese single-center study.

BACKGROUND: Syndromic ciliopathies are a group of congenital disorders characterized by broad clinical and genetic overlap, including obesity, visual problems, skeletal anomalies, mental retardation, and renal diseases. The hallmark of the pathophysiology among these disorders is defective ciliary functions or formation. Many different genes have been implicated in the pathogenesis of these diseases, but some patients still remain unclear about their genotypes. METHODS: The aim of this study was to identify the genetic causes in patients with syndromic ciliopathy. Patients suspected of or meeting clinical diagnostic criteria for any type of syndromic ciliopathy were recruited at a single diagnostic medical center in Southern Taiwan. Whole exome sequencing (WES) was employed to identify their genotypes and elucidate the mutation spectrum in Taiwanese patients with syndromic ciliopathy. Clinical information was collected at the time of patient enrollment. RESULTS: A total of 14 cases were molecularly diagnosed with syndromic ciliopathy. Among these cases, 10 had Bardet-Biedl syndrome (BBS), comprising eight BBS2 patients and two BBS7 patients. Additionally, two cases were diagnosed with Alström syndrome, one with Oral-facial-digital syndrome type 14, and another with Joubert syndrome type 10. A total of 4 novel variants were identified. A recurrent splice site mutation, BBS2: c.534 + 1G > T, was present in all eight BBS2 patients, suggesting a founder effect. One BBS2 patient with homozygous c.534 + 1G > T mutations carried a third ciliopathic allele, TTC21B: c.264_267dupTAGA, a nonsense mutation resulting in a premature stop codon and protein truncation. CONCLUSIONS: Whole exome sequencing (WES) assists in identifying molecular pathogenic variants in ciliopathic patients, as well as the genetic hotspot mutations in specific populations. It should be considered as the first-line genetic testing for heterogeneous disorders characterized by the involvement of multiple genes and diverse clinical manifestations.

Effects of occupational exposure to metal fume PM2.5 on lung function and biomarkers among shipyard workers: a 3-year prospective cohort study.

OBJECTIVE: This study investigates the associations of α1-antitrypsin, inter-α-trypsin inhibitor heavy chain (ITIH4), and 8-isoprostane with lung function in shipyard workers exposed to occupational metal fume fine particulate matter (PM2.5), which is known to be associated with adverse respiratory outcomes. METHODS: A 3-year follow-up study was conducted on 180 shipyard workers with 262 measurements. Personal exposure to welding fume PM2.5 was collected for an 8-h working day. Pre-exposure, post-exposure, and delta (∆) levels of α1-antitrypsin, ITIH4, and 8-isoprostane were determined in urine using enzyme-linked immunosorbent assays. Post-exposure urinary metals were sampled at the beginning of the next working day and analyzed by inductively coupled plasma-mass spectrometry. Lung function measurements were also conducted the next working day for post-exposure. RESULTS: An IQR increase in PM2.5 was associated with decreases of 2.157% in FEV1, 2.806% in PEF, 4.328% in FEF25%, 5.047% in FEF50%, and 7.205% in FEF75%. An IQR increase in PM2.5 led to increases of 42.155 µg/g in ∆α1-antitrypsin and 16.273 µg/g in ∆ITIH4. Notably, IQR increases in various urinary metals were associated with increases in specific biomarkers, such as post-urinary α1-antitrypsin and ITIH4. Moreover, increases in ∆ α1-antitrypsin and ∆ITIH4 were associated with decreases in FEV1/FVC by 0.008% and 0.020%, respectively, and an increase in ∆8-isoprostane resulted in a 1.538% decline in FVC. CONCLUSION: Our study suggests that urinary α1-antitrypsin and ITIH4 could indicate early lung function decline in shipyard workers exposed to metal fume PM2.5, underscoring the need for better safety and health monitoring to reduce respiratory risks.

Prognostic value of preoperative radiographic perinephric fat features in renal cell carcinoma patients undergoing surgery.

BACKGROUND: We aimed to assess the prognostic importance of perinephric fat features in images of patients with non-metastatic renal cell carcinoma (RCC) undergoing surgery. METHODS: We enrolled RCC patients who underwent surgical treatment between 2011 and 2019. Two characteristics, including perinephric fat thickness and perinephric fat stranding, were evaluated using preoperative computed tomography or magnetic resonance images. The association between perinephric fat characteristics and disease progression was examined by Kaplan-Meier survival analysis and Cox regression model. RESULTS: In a multivariate Cox proportional hazards model adjusting for tumor stage, intratumoral necrosis, and neutrophil-to-lymphocyte ratio, we found that patients in the thin perinephric fat group (<1 cm) had a poorer progression-free survival (PFS) compared to the thick perinephric fat group (≥1 cm) (HR 2.8; 95% CI 1.175-6.674, p = 0.02). Additionally, the fat stranding group had a poorer PFS than the non-stranding group (HR 3.852; 95% CI 1.082-13.704, p = 0.037). The non-stranding with thick perinephric fat group exhibits the highest cumulative PFS while the stranding with thin perinephric fat group has the lowest cumulative PFS. In receiver operating characteristic curve analysis, combing these two perinephric fat characteristics with tumor stage can achieve a better discriminatory power than tumor stage alone. CONCLUSIONS: Our study indicates that the evaluation of image-based perinephric fat features is a simple, straightforward, reproducible tool for predicting RCC prognosis and may assist in preoperative risk stratification.

Non-homologous End-joining Genotype, mRNA Expression, and DNA Repair Capacity in Childhood Acute Lymphocytic Leukemia.

BACKGROUND/AIM: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL. MATERIALS AND METHODS: Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation was investigated by examining mRNA transcript expression and the capacity for overall and precise NHEJ repair. RESULTS: The variant genotypes of XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 were significantly associated with increased odds of childhood ALL. Further analysis based on susceptibility genotypes showed no significant differences in mRNA transcript expression levels among childhood ALL cases with various putative high-risk genotypes, except XRCC6 rs5751129. Moreover, the overall NHEJ repair capacity was similar among carriers of different XRCC4, XRCC5, and XRCC6 genotypes. However, it is worth noting that individuals carrying the variant C allele at XRCC6 rs5751129 exhibited lower precise NHEJ repair capacity compared to those with the wild-type T allele. CONCLUSION: Our study identified significant associations between XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 genotypes and childhood ALL. Notably, lower transcriptional expression and reduced precise NHEJ repair capacity were observed in patients carrying the C allele of XRCC6 rs5751129. Further investigations are required to gain deeper insights into childhood ALL development.

Concurrent Ingestion of Alkaline Water and L-Glutamine Enhanced Salivary α-Amylase Activity and Testosterone Concentration in Boxing Athletes.

Athletes often take sport supplements to reduce fatigue and immune disturbances during or after training. This study evaluated the acute effects of concurrent ingestion of alkaline water and L-glutamine on the salivary immunity and hormone responses of boxers after training. Twelve male boxing athletes were recruited in this study. During regular training, the participants were randomly divided into three groups and asked to consume 400 mL of alkaline water (Group A), 0.15 g/kg body weight of L-glutamine with 400 mL of water (Group G), and 0.15 g/kg of L-glutamine with 400 mL of alkaline water (Group A+G) at the same time each day for three consecutive weeks. Before and immediately after the training, saliva, heart rates, and the rate of perceived exertion were investigated. The activity of α-amylase and concentrations of lactoferrin, immunoglobulin A (IgA), testosterone, and cortisol in saliva were measured. The results showed that the ratio of α-amylase activity/total protein (TP) significantly increased after training in Group A+G but not in Group A or G, whereas the ratios of lactoferrin/TP and IgA/TP were unaffected in all three groups. The concentrations of salivary testosterone after training increased significantly in Group A+G but not in Group A or G, whereas the salivary cortisol concentrations were unaltered in all groups. In conclusion, concurrent ingestion of 400 mL of alkaline water and 0.15 g/kg of L-glutamine before training enhanced the salivary α-amylase activity and testosterone concentration of boxers, which would be beneficial for post-exercise recovery.

Current treatment concepts for Achilles tendon rupture.

Achilles tendon rupture is a common and primary cause of lower limb tendon injury suffered during sports-related activities. The causes of Achilles tendon rupture include the calf muscle and tendon overuse, poor tendon quality, and various medical conditions. Historically, acute Achilles tendon rupture was treated conservatively. However, historical techniques are now associated with an increased risk of rerupture. To address this problem, open repair has been proposed. Open repair is associated with a reduced risk of rerupture; however, it is also closely associated with wound complications, like wound infection, whose treatment is time-consuming and costly. Therefore, minimally invasive Achilles tendon repair has been proposed as a promising option with acceptable functional outcomes. Nevertheless, despite its benefits, minimally invasive Achilles tendon repair is associated with increased risks of sural nerve injury and rerupture. In this review, we evaluate the currently used treatment strategies for acute Achilles tendon rupture and their historical evolution to provide evidence-based recommendations for physicians.

Supplementation of L-glutamine enhanced mucosal immunity and improved hormonal status of combat-sport athletes.

BACKGROUND: Maintaining proper immune function and hormone status is important for athletes to avoid upper respiratory tract infection (URTI) and insufficient recovery, which is detrimental to sport performance and health. The aim of this study was to evaluate whether three-week supplementation of L-glutamine could benefit the mucosal immunity and hormonal status of combat-sport athletes as well as their rates of upper respiratory tract infection (URTI) and subjective feelings of well-being after intensive training. METHODS: Twenty-one combat-sport athletes from the National Taiwan University of Sport were recruited in this study. After intensive training, two groups of the participants were asked to consume powder form of 0.3 g/kg body weight of L-glutamine (GLU group) or maltodextrin (PLA group) with drinking water in a randomized design at the same time every day during 3 weeks. Saliva samples were collected to measure immunoglobulin A (IgA), nitric oxide (NO), testosterone (T) and cortisol (C) before and after three-week supplementation; moreover, Hooper's index questionnaires were completed for wellness assessment. The incidence and duration of URTI were recorded by using a health checklist throughout the entire study period. RESULTS: Supplementation of L-glutamine significantly enhanced the concentrations of IgA and NO in saliva; additionally, the incidence of URTI was significantly reduced. Regarding hormones, T concentration was significantly decreased in the PLA group, whereas C concentration was significantly increased, resulting in a significant decrease of T/C ratio. In contrast, the GLU group showed a significant increase of T/C ratio, while the mood scores of the Hooper's index questionnaire were higher in the PLA group. CONCLUSIONS: Three-week supplementation of L-glutamine after intensive training enhanced the mucosal immunity, improved hormonal status and reduced the rate of URTI of combat-sport athletes while feelings of well-being were also enhanced. Therefore, L-glutamine would be beneficial for the sports performance and recovery of athletes.

C-C chemokine receptor 4 (CCR4)-positive regulatory T cells interact with tumor-associated macrophages to facilitate metastatic potential after radiation.

PURPOSE: Our previous study revealed that elevated C-C motif chemokine ligand 2 (CCL2) secretion by irradiated cancer cells recruited C-C motif chemokine receptor 2 (CCR2)-positive myeloid cells and polarized M2-type tumor-associated macrophages (TAMs), promoting lung metastasis in an established mouse model. This study investigated the impact of CCL2 and TAMs on adaptive immunity. METHODS: We assessed the influence of CCL2 and TAMs on adaptive immunity through two ectopic allograft mouse models constructed with MB49 bladder cancer cells and Lewis lung carcinoma cells. Both models exhibited delayed primary tumor growth following radiation therapy (RT), but RT promoted the development of pulmonary metastases in C57BL/6 mice. Additionally, we employed a direct coculture system to investigate the interaction between macrophages and target cells in the context of adaptive immunity. RESULTS: C-C motif chemokine receptor 4 (CCR4)-positive regulatory T cells (Tregs) were recruited to the postirradiated tumor microenvironment (TME). Utilizing a CCR4 antagonist to inhibit CCL2-CCR4 activation reversed the infiltration of CCR4 + Tregs and reduced the incidence of pulmonary metastases. In addition, a positive feedback loop between M2-type TAMs and Tregs was observed. The combined blockade of the CCL2-CCR4 and CCL2-CCR2 signaling pathways further decreased the risk of RT-promoted lung metastasis. CONCLUSION: The recruitment of CCR4 + Tregs to the postirradiated TME increases the metastatic potential of tumor cells through increased interactions with M2-type TAMs. A significant reduction in post-RT lung metastases in ectopic mouse models was achieved by disrupting the recruitment of both CCR4 + Tregs and CCR2 + myeloid cells, which are TAM precursors.

Type 2 diabetes mellitus increases the risk of circumcision among men aged between 30 and 69 years using a nationwide population-based dataset in Taiwan: a five-year follow-up study.

BACKGROUND: Diabetes is an important factor in the development of penile inflammation. We studied whether type 2 diabetes (DM), with/without hypertension and hyperlipidemia increased the risk of circumcision among men aged between 30 and 69 using a population-based dataset in Taiwan during a 5-year follow-up period. METHODS: The research data in this study were obtained from Taiwan's National Health Insurance Research Database between 1997 and 2010. We identified 23,197 patients who had a new diagnosis of DM and randomly matched 115,985 subjects as controls. We observed whether circumcision was the treatment after a new DM diagnosis. The initial step involved analyzing the data using Poisson regression analysis. To address potential confounding factors, this study employed propensity score matching based on three variables. Additionally, a Cox regression with a Gamma frailty was utilized to compare outcomes between different groups. RESULTS: Poisson regression analysis showed that DM (RR = 1.75, 95CI = 0.10 ~ 1.22), but not hypertension (RR = 1.14, 95CI=-0.44 ~ 0.70), hyperlipidemia (RR = 0.94, 95CI=-0.66 ~ 0.53), or age (RR = 0.83, 95CI=-0.43 ~ 0.62), had an impact on circumcision treatment. Cox regression with a frailty model found that DM was a risk factor associated with circumcision (HR = 2.31, 95% CI = 1.74 ~ 3.06, p-value < 0.01), whereas no significant difference was noted between circumcision and hypertension (HR = 1.10, 95% CI = 0.80 ~ 1.51), hyperlipidemia (HR = 1.05, 95% CI = 0.79 ~ 1.40), or age (HR = 1.00, 95% CI = 0.99 ~ 1.02). CONCLUSIONS: Type 2 diabetes mellitus, but not hypertension, hyperlipidemia or age increases the risk of circumcision in men aged between 30 and 69 years.

New materials used for the synthesis of 2-chlorophenyl cyclopentyl ketone seized from an illicit ketamine manufacturing unit.

Ketamine deemed as a psychoactive substance has gained popularity for recreational use owing to its hallucinogenic and dissociative effects. Understanding the synthetic processes of ketamine can provide essential clues for law enforcement officers against illicit ketamine manufacturing. In this case report, a chemical company was being monitored by law enforcement officers due to its importation of precursors and materials that could be used for the synthesis of illicit drugs. After materials and products seized from this chemical company were employed for analyses using gas chromatography-mass spectrometry, liquid chromatography-high-resolution mass spectrometry, and nuclear magnetic resonance analyses, ketamine, hydroxylamine, 2-chlorophenyl cyclopentyl ketone, and cyclopentanone p-toluenesulfonylhydrazone were identified. In addition, a novel process for the synthesis of ketamine precursor 2-chlorophenyl cyclopentyl ketone from cyclopentanone p-toluenesulfonylhydrazone and 2-chlorobenzaldehyde was validated. This is the first report to uncover this novel process for the synthesis of 2-chlorophenyl cyclopentyl ketone and can be used to increase awareness among law enforcement officers and forensic practitioners about these novel starting materials for the synthesis of ketamine.

Prenatal to preschool exposure of nonylphenol and bisphenol A exposure and neurodevelopment in young children.

BACKGROUND: Nonylphenol (NP) and bisphenol A (BPA) are produced in large quantities worldwide as multipurpose agents. However, studies on relations between NP and BPA exposure and childhood neurodevelopment are few, and the results are inconsistent. This study aimed to investigate associations between prenatal and early childhood NP and BPA exposure and neurodevelopment in mother-child pairs. METHODS: Pregnant women at 27-38 weeks' gestation were recruited, as were children 2-3 years of age (n = 94) and 4-6 years of age (n = 56) years. Urine was collected to assess NP and BPA exposure. Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-III), Wechsler Preschool and Primary Scale of Intelligence (4th edition), and the Full Scale Intelligence Quotient (WPPSI-IV-FSIQ) were used to assess the neurodevelopment of the children. RESULTS: The detection rate and concentration of NP and BPA in the urine of children 4-6 years old were higher than in those 2-3 years old. Children were divided into a high concentration group (3rd tertile) and a reference group (1st and 2nd tertiles) based on natural log-transformed urine concentration of NP and BPA. Girls' Bayley-III motor scores in the high concentration group were higher than those of the BPA reference group of urine of mothers (ß = 6.85, 95% confidence interval [CI]: 1.58-12.13). Boys' FSIQ in the higher concentration group were significantly lower than those in children 2-3 years old in the NP reference group (ß = -11.29, 95% CI: -18.62 to -3.96) (all, p < 0.05). CONCLUSIONS: Prenatal and childhood exposure to NP and BPA may have different effects on the neurodevelopment of young children, and there are no consistent effects between boys and girls.

Trends in age at menarche from 1943 through 1989 in Taiwan: A retrospective population-based analysis.

BACKGROUND: Recent studies have demonstrated a global decline in the age at menarche. Our study aimed to determine the age at menarche of Taiwanese women born between 1943 and 1989. METHODS: Data were obtained from the Taiwan Biobank. To view the trends in age at menarche, we analyzed data from 74,799 women. The mean, standard deviation, and annual percentage change in age at menarche were calculated for birth-year cohorts. RESULTS: The mean age at menarche of Taiwanese women born in 1943 was 14.85 years. The age at menarche decreased to 12.20 years for those born in 1989. The mean age at menarche declined by 2.65 years across the 47-year study period; hence, the reduction rate was 0.56 years per decade. This study demonstrated a downward secular trend in the age at menarche of Taiwanese women born between 1943 and 1989. This trend occurred in three stages of decline: fast (1943-1953), slow (1953-1965), and moderate (1965-1989). CONCLUSION: The age at menarche decreased by 2.65 years among Taiwanese women born in 1943 compared with those born in 1989. This decline occurred in three stages: fast (1943-1953), slow (1953-1965), and moderate (1965-1989). This significant downward secular trend in age at menarche reflects Taiwan's socioeconomic development.