Conjugated Polymer/Recombinant Escherichia coli Biohybrid Systems for Photobiocatalytic Hydrogen Production.

Biohybrid photocatalysts are composite materials that combine the efficient light-absorbing properties of synthetic materials with the highly evolved metabolic pathways and self-repair mechanisms of biological systems. Here, we show the potential of conjugated polymers as photosensitizers in biohybrid systems by combining a series of polymer nanoparticles with engineered Escherichia coli cells. Under simulated solar light irradiation, the biohybrid system consisting of fluorene/dibenzo [b,d]thiophene sulfone copolymer (LP41) and recombinant E. coli (i.e., a LP41/HydA BL21 biohybrid) shows a sacrificial hydrogen evolution rate of 3.442 mmol g-1 h-1 (normalized to polymer amount). It is over 30 times higher than the polymer photocatalyst alone (0.105 mmol g-1 h-1), while no detectable hydrogen was generated from the E. coli cells alone, demonstrating the strong synergy between the polymer nanoparticles and bacterial cells. The differences in the physical interactions between synthetic materials and microorganisms, as well as redox energy level alignment, elucidate the trends in photochemical activity. Our results suggest that organic semiconductors may offer advantages, such as solution processability, low toxicity, and more tunable surface interactions with the biological components over inorganic materials.

Clinical Impacts of Omalizumab on the Psychiatric Comorbidities of Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis.

Individuals with chronic spontaneous urticaria (CSU) experience significant sleep disturbances and are at risk of anxiety and depression.

The cytokine receptor Fn14 is a molecular brake on neuronal activity that mediates circadian function in vivo.

To survive, organisms must adapt to a staggering diversity of environmental signals, ranging from sensory information to pathogenic infection, across the lifespan. At the same time, organisms intrinsically generate biological oscillations, such as circadian rhythms, without input from the environment. While the nervous system is well-suited to integrate extrinsic and intrinsic cues, how the brain balances these influences to shape biological function system-wide is not well understood at the molecular level. Here, we demonstrate that the cytokine receptor Fn14, previously identified as a mediator of sensory experience-dependent synaptic refinement during brain development, regulates neuronal activity and function in adult mice in a time-of-day-dependent manner. We show that a subset of excitatory pyramidal (PYR) neurons in the CA1 subregion of the hippocampus increase Fn14 expression when neuronal activity is heightened. Once expressed, Fn14 constrains the activity of these same PYR neurons, suggesting that Fn14 operates as a molecular brake on neuronal activity. Strikingly, differences in PYR neuron activity between mice lacking or expressing Fn14 were most robust at daily transitions between light and dark, and genetic ablation of Fn14 caused aberrations in circadian rhythms, sleep-wake states, and sensory-cued and spatial memory. At the cellular level, microglia contacted fewer, but larger, excitatory synapses in CA1 in the absence of Fn14, suggesting that these brain-resident immune cells may dampen neuronal activity by modifying synaptic inputs onto PYR neurons. Finally, mice lacking Fn14 exhibited heightened susceptibility to chemically induced seizures, implicating Fn14 in disorders characterized by hyperexcitation, such as epilepsy. Altogether, these findings reveal that cytokine receptors that mediates inflammation in the periphery, such as Fn14, can also play major roles in healthy neurological function in the adult brain downstream of both extrinsic and intrinsic cues.

Spirulina-based carbon materials as adsorbents for drinking water taste and odor control: Removal efficiency and assessment of cyto-genotoxic effects.

The sensory quality of drinking water, and particularly its taste and odor (T&O) is a key determinant of consumer acceptability, as consumers evaluate water by their senses. Some of the conventional treatment processes to control compounds which impart unpleasant T&O have limitations because of their low efficiency and/or high costs. Therefore, there is a great need to develop an effective process for removing T&O compounds without secondary concerns. The primary objective of this study was to assess for the first time the effectiveness of spirulina-based carbon materials in removing geosmin (GSM) and 2-methylisoborneol (2-MIB) from water, two commonly occurring natural T&O compounds. The efficiency of the materials to remove environmentally relevant concentrations of GSM and 2-MIB (ng L-1) from ultrapure and raw water was investigated using a sensitive headspace solid-phase microextraction coupled with gas chromatography mass spectrometry (HS-SPME-GC/MS) method. Moreover, the genotoxic and cytotoxic effects of the spirulina-based materials were assessed for the first time to evaluate their safety and their potential in the treatment of water for human consumption. Based on the results, spirulina-based materials were found to be promising for drinking water treatment applications, as they did not exert geno-cytotoxic effects on human cells, while presenting high efficiency in removing GSM and 2-MIB from water.

A design for life: Predicting cognitive performance from lifestyle choices.

Maintaining cognitive capacity through adulthood has been the target of many recent studies that have examined the influence of lifestyle choices such as exercise, diet, and sleeping habits. Many of these studies have focused on a single factor (e.g., diet) and its effect on cognitive abilities; however, humans make numerous lifestyle choices every single day, many of which interact and influence each other. Here, we investigated whether combinations of lifestyle choices can predict better or worse cognitive performance in the general population, and whether optimal combinations of choices existed depending on the cognitive domain. Specifically, we examined 20 self-reported lifestyle choices, such as playing video games, drinking alcohol, and amount of exercise taken, in a sample of almost 10,000 participants. All participants also completed 12 cognitive tests that have been shown to generate three composite cognitive domain scores pertaining to short-term memory, verbal abilities, and reasoning. Using recursive feature elimination and random forest regression, we were able to explain 9% of the variance in short-term memory scores, 8% of the variance in reasoning scores, and 7% of the variance in verbal ability scores. While the regression model provided predictive power in all three domains, these levels indicate that even when considering a large number of lifestyle choices, there remains a considerable degree of variability in predicting short-term memory, reasoning and verbal abilities. Thus, while some modifiable lifestyle factors may have an impact on cognitive capacity, there likely exists no single optimal design for life.

Liver specification of human iPSC-derived endothelial cells transplanted into mouse liver.

Background & Aims: Liver sinusoidal endothelial cells (LSECs) are important in liver development, regeneration, and pathophysiology, but the differentiation process underlying their tissue-specific phenotype is poorly understood and difficult to study because primary human cells are scarce. The aim of this study was to use human induced pluripotent stem cell (hiPSC)-derived LSEC-like cells to investigate the differentiation process of LSECs. Methods: hiPSC-derived endothelial cells (iECs) were transplanted into the livers of Fah-/-/Rag2-/-/Il2rg-/- mice and assessed over a 12-week period. Lineage tracing, immunofluorescence, flow cytometry, plasma human factor VIII measurement, and bulk and single cell transcriptomic analysis were used to assess the molecular and functional changes that occurred following transplantation. Results: Progressive and long-term repopulation of the liver vasculature occurred as iECs expanded along the sinusoids between hepatocytes and increasingly produced human factor VIII, indicating differentiation into LSEC-like cells. To chart the developmental profile associated with LSEC specification, the bulk transcriptomes of transplanted cells between 1 and 12 weeks after transplantation were compared against primary human adult LSECs. This demonstrated a chronological increase in LSEC markers, LSEC differentiation pathways, and zonation. Bulk transcriptome analysis suggested that the transcription factors NOTCH1, GATA4, and FOS have a central role in LSEC specification, interacting with a network of 27 transcription factors. Novel markers associated with this process included EMCN and CLEC14A. Additionally, single cell transcriptomic analysis demonstrated that transplanted iECs at 4 weeks contained zonal subpopulations with a region-specific phenotype. Conclusions: Collectively, this study confirms that hiPSCs can adopt LSEC-like features and provides insight into LSEC specification. This humanised xenograft system can be applied to further interrogate LSEC developmental biology and pathophysiology, bypassing current logistical obstacles associated with primary human LSECs. Impact and implications: Liver sinusoidal endothelial cells (LSECs) are important cells for liver biology, but better model systems are required to study them. We present a pluripotent stem cell xenografting model that produces human LSEC-like cells. A detailed and longitudinal transcriptomic analysis of the development of LSEC-like cells is included, which will guide future studies to interrogate LSEC biology and produce LSEC-like cells that could be used for regenerative medicine.

Discrimination of ivory from extant and extinct elephant species using Raman spectroscopy: A potential non-destructive technique for combating illegal wildlife trade.

The use of elephant ivory as a commodity is a factor in declining elephant populations. Despite recent worldwide elephant ivory trade bans, mammoth ivory trade remains unregulated. This complicates law enforcement efforts, as distinguishing between ivory from extant and extinct species requires costly, destructive and time consuming methods. Elephant and mammoth ivory mainly consists of dentine, a mineralized connective tissue that contains an organic collagenous component and an inorganic component of calcium phosphate minerals, similar in structure to hydroxyapatite crystals. Raman spectroscopy is a non-invasive laser-based technique that has previously been used for the study of bone and mineral chemistry. Ivory and bone have similar biochemical properties, making Raman spectroscopy a promising method for species identification based on ivory. This study aimed to test the hypothesis that it is possible to identify differences in the chemistry of mammoth and elephant ivory using Raman spectroscopy. Mammoth and elephant tusks were obtained from the Natural History Museum in London, UK. Included in this study were eight samples of ivory from Mammuthus primigenius, two samples of carved ivory bangles from Africa (Loxodonta species), and one cross section of a tusk from Elephas maximus. The ivory was scanned using an inVia Raman micro spectrometer equipped with a x50 objective lens and a 785nm laser. Spectra were acquired using line maps and individual spectral points were acquired randomly or at points of interest on all samples. The data was then analysed using principal component analysis (PCA) with use of an in-house MATLAB script. Univariate analysis of peak intensity ratios of phosphate to amide I and III peaks, and carbonate to phosphate peaks showed statistical differences (p<0.0001) in the average peak intensity ratios between Mammuthus primigenius, Loxodonta spp. and Elephas maximus. Full width at half maximum hight (FWHM)analysis of the phosphate peak demonstrated higher crystal maturity of Mammuthus primigenius compared to living elephant species. The results of the study have established that spectra acquired by Raman spectroscopy can be separated into distinct classes through PCA. In conclusion, this study has shown that well-preserved mammoth and elephant ivory has the potential to be characterized using Raman spectroscopy, providing a promising method for species identification. The results of this study will be valuable in developing quick and non-destructive methods for the identification of ivory, which will have direct applications in archaeology and the regulation of international trade.

Metabolic effects of testosterone added to intensive lifestyle intervention in older men with obesity and hypogonadism.

BACKGROUND: Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear. OBJECTIVE: To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism. DESIGN: Secondary analysis of a randomized, double-blind, placebo-controlled trial. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: 83 older (age ≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and persistently low AM testosterone (< 10.4 nmol/L) associated with frailty. INTERVENTIONS: LT (weight management and exercise training) plus either testosterone (LT+TRT) or placebo (LT+Pbo) for six months. OUTCOME MEASURES: Primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure, and metabolic syndrome score. RESULTS: HbA1c decreased similarly in LT+TRT and LT+Pbo groups (-0.5% vs. -0.6%, respectively; p= 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in LT+Pbo group vs. 0.2 ± 1.1 mg/dL in LT+TRT group, p= 0.01) and adiponectin levels (-408 ± 489 ng/mL in TRT+LT group vs 1832 ± 468 ng/mL in LT+Pbo group, p= 0.02). CONCLUSION: In older men with obesity and hypogonadism, adding TRT for six months to LT does not result in further improved cardiometabolic profiles, and could potentially blunt some of the metabolic benefits induced by LT.

Toxicity of butylone and its enantiomers to Daphnia magna and its degradation/toxicity potential using advanced oxidation technologies.

Butylone (BTL) is a chiral synthetic cathinone available as a racemate and reported as contaminant in wastewater effluents. However, there are no studies on its impact on ecosystems and possible enantioselectivity in ecotoxicity. This work aimed to evaluate: (i) the possible ecotoxicity of BTL as racemate or its isolated (R)- and (S)- enantiomers using Daphnia magna; and (ii) the efficiency of advanced oxidation technologies (AOTs) in the removal of BTL and reduction of toxic effects caused by wastewaters. Enantiomers of BTL were obtained by liquid chromatography (LC) using a chiral semi-preparative column. Enantiomeric purity of each enantiomer was > 97 %. For toxicity assessment, a 9-day sub-chronic assay was performed with the racemate (at 0.10, 1.0 or 10 µg L-1) or each enantiomer (at 0.10 or 1.0 µg L-1). Changes in morphophysiological, behavioural, biochemical and reproductive endpoints were observed, which were dependent on the form of the substance and life stage of the organism (juvenile or adult). Removal rates of BTL in spiked wastewater (10 µg L-1) treated with different AOTs (ultraviolet, UV; ozonation, O3; and UV/O3) were similar and lower than 29 %. The 48 h D. magna acute toxicity assays demonstrated a reduction in the toxicity of the treated spiked effluents, but no differences were found amongst AOTs treatments. These results warn for the contamination and negative impact of BTL on ecosystems and highlight the need for efficient removal processes.

Fragility of overactive bladder medication clinical trials: A systematic review.

PURPOSE: Overactive bladder (OAB) syndrome significantly impairs quality of life, often necessitating pharmacological interventions with associated risks. The fragility of OAB trial outcomes, as measured by the fragility index (FI: smallest number of event changes to reverse statistical significance) and quotient (FQ: FI divided by total sample size expressed as a percentage), is critical yet unstudied. MATERIALS AND METHODS: We conducted a systematic search for randomized controlled trials on OAB medications published between January 2000 and August 2023. Inclusion criteria were trials with two parallel arms reporting binary outcomes related to OAB medications. We extracted trial details, outcomes, and statistical tests employed. We calculated FI and FQ, analyzing associations with trial characteristics through linear regression. RESULTS: We included 57 trials with a median sample size of 211 participants and a 12% median lost to follow-up. Most studies investigated anticholinergics (37/57, 65%). The median FI/FQ was 5/3.5%. Larger trials were less fragile (median FI 8; FQ 1.0%) compared to medium (FI: 4; FQ 2.5%) and small trials (FI: 4; FQ 8.3%). Double-blinded studies exhibited higher FQs (median 2.9%) than unblinded trials (6.7%). Primary and secondary outcomes had higher FIs (median 5 and 6, respectively) than adverse events (FI: 4). Each increase in 10 participants was associated with a +0.19 increase in FI (p < 0.001). CONCLUSIONS: A change in outcome for a median of five participants, or 3.5% of the total sample size, could reverse the direction of statistical significance in OAB trials. Studies with larger sample sizes and efficacy outcomes from blinded trials were less fragile.

Organelle-targeted Laurdans measure heterogeneity in subcellular membranes and their responses to saturated lipid stress.

Cell organelles feature characteristic lipid compositions that lead to differences in membrane properties. In living cells, membrane ordering and fluidity are commonly measured using the solvatochromic dye Laurdan, whose fluorescence is sensitive to membrane packing. As a general lipophilic dye, Laurdan stains all hydrophobic environments in cells, so it is challenging to characterize membrane properties in specific organelles or assess their responses to pharmacological treatments in intact cells. Here, we describe the synthesis and application of Laurdan-derived probes that read out membrane packing of individual cellular organelles. The set of Organelle-targeted Laurdans (OTL) localizes to the ER, mitochondria, lysosomes and Golgi compartments with high specificity, while retaining the spectral resolution needed to detect biological changes in membrane packing. We show that ratiometric imaging with OTL can resolve membrane heterogeneity within organelles, as well as changes in membrane packing resulting from inhibition of lipid trafficking or bioenergetic processes. We apply these probes to characterize organelle-specific responses to saturated lipid stress. While ER and lysosomal membrane fluidity is sensitive to exogenous saturated fatty acids, that of mitochondrial membranes is protected. We then use differences in ER membrane fluidity to sort populations of cells based on their fatty acid diet, highlighting the ability of organelle-localized solvatochromic probes to distinguish between cells based on their metabolic state. These results expand the repertoire of targeted membrane probes and demonstrate their application to interrogating lipid dysregulation.

The long term effects of uncoupling interventions as a therapy for dementia in humans.

In this paper we use simulation methods to study a hypothetical uncoupling agent as a therapy for dementia. We simulate the proliferation of mitochondrial deletion mutants amongst a population of wild-type in human neurons. Mitochondria play a key role in ATP generation. Clonal expansion can lead to the wild-type being overwhelmed by deletions such that a diminished population can no longer fulfil a cell's energy requirement, eventually leading to its demise. The intention of uncoupling is to reduce the formation of deletion mutants by reducing mutation rate. However, a consequence of uncoupling is that the energy production efficacy is also reduced which in turn increases wild-type copy number in order to compensate for the energy deficit. The results of this paper showed that uncoupling reduced the severity of dementia, however, there was some increase in cognitive dysfunction pre-onset of dementia. The effectiveness of uncoupling was dependent upon the timing of intervention relative to the onset of dementia and would necessitate predicting its onset many years in advance.

Tests for consciousness in humans and beyond.

Which systems/organisms are conscious? New tests for consciousness ('C-tests') are urgently needed. There is persisting uncertainty about when consciousness arises in human development, when it is lost due to neurological disorders and brain injury, and how it is distributed in nonhuman species. This need is amplified by recent and rapid developments in artificial intelligence (AI), neural organoids, and xenobot technology. Although a number of C-tests have been proposed in recent years, most are of limited use, and currently we have no C-tests for many of the populations for which they are most critical. Here, we identify challenges facing any attempt to develop C-tests, propose a multidimensional classification of such tests, and identify strategies that might be used to validate them.

Obesity Disparities Among Adult Single-Race and Multiracial Asian and Pacific Islander Populations.

Importance: Despite increasing numbers of multiracial individuals, they are often excluded in studies or aggregated within larger race and ethnicity groups due to small sample sizes. Objective: To examine disparities in the prevalence of obesity among single-race and multiracial Asian and Pacific Islander individuals compared with non-Hispanic White (hereafter, White) individuals. Design, Setting, and Participants: This cross-sectional study used electronic health record (EHR) data linked to social determinants of health and health behavior data for adult (age ≥18 years) members of 2 large health care systems in California and Hawai'i who had at least 1 ambulatory visit to a primary care practitioner between January 1, 2006, and December 31, 2018. Data were analyzed from October 31, 2022, to July 31, 2023. Exposure: Self-identified race and ethnicity provided in the EHR as a single-race category (Asian Indian, Chinese, Filipino, Japanese, Native Hawaiian only, Other Pacific Islander, or White) or a multiracial category (Asian and Pacific Islander; Asian, Pacific Islander, and White; Asian and White; or Pacific Islander and White). Main Outcomes and Measures: The main outcome was obesity (body mass index [BMI] ≥30.0), based on last measured height and weight from the EHR. Logistic regression was used to examine the association between race and ethnicity and odds of obesity. Results: A total of 5229 individuals (3055 [58.4%] male; mean [SD] age, 70.73 [11.51] years) were examined, of whom 444 (8.5%) were Asian Indian; 1091 (20.9%), Chinese; 483 (9.2%), Filipino; 666 (12.7%), Japanese; 91 (1.7%), Native Hawaiian; 95 (1.8%), Other Pacific Islander; and 888 (17.0%), White. The percentages of individuals who identified as multiracial were as follows: 417 (8.0%) were Asian and Pacific Islander; 392 (7.5%), Asian, Pacific Islander, and White; 248 (4.7%), Asian and White; and 414 (7.9%), Pacific Islander and White. A total of 1333 participants (25.5%) were classified as having obesity based on standard BMI criteria. Obesity was highest among people who identified as Asian, Pacific Islander, and White (204 of 392 [52.0%]) followed by those who identified as Other Pacific Islander (47 of 95 [49.5%]), Native Hawaiian (44 of 91 [48.4%]), and Pacific Islander and White (186 of 414 [44.9%]). After accounting for demographic, socioeconomic, and health behavior factors, people who identified as Asian, Pacific Islander, and White (odds ratio [OR], 1.80; 95% CI, 1.37-2.38) or Pacific Islander and White (OR, 1.55; 95% CI, 1.18-2.04) had increased odds of obesity compared with White individuals. All single-race Asian groups had lower odds of obesity compared with White individuals: Asian Indian (OR, 0.29; 95% CI, 0.20-0.40), Chinese (OR, 0.22; 95% CI, 0.17-0.29), Filipino (OR, 0.46; 95% CI, 0.35-0.62), and Japanese (OR, 0.38, 95% CI, 0.29-0.50). Conclusions and Relevance: In this study, multiracial Asian and Pacific Islander individuals had an increased prevalence of obesity compared with many of their single-race counterparts. As the number of multiracial individuals increases, it will be important for clinical and public health systems to track disparities in these populations.

Potential Dependent Reorientation Controlling Activity of a Molecular Electrocatalyst.

The activity of molecular electrocatalysts depends on the interplay of electrolyte composition near the electrode surface, the composition and morphology of the electrode surface, and the electric field at the electrode-electrolyte interface. This interplay is challenging to study and often overlooked when assessing molecular catalyst activity. Here, we use surface specific vibrational sum frequency generation (VSFG) spectroscopy to study the solvent and potential dependent activation of Mo(bpy)(CO)4, a CO2 reduction catalyst, at a polycrystalline Au electrode. We find that the parent complex undergoes potential dependent reorientation at the electrode surface when a small amount of N-methyl-2-pyrrolidone (NMP) is present. This preactivates the complex, resulting in greater yields at less negative potentials, of the active electrocatalyst for CO2 reduction.

Characterisation of experimental flowable composites containing fluoride-doped calcium phosphates as promising remineralising materials.

OBJECTIVE: Remineralising composites with antibacterial properties may seal the cavity and prevent secondary caries. This study aimed at developing experimental flowable composites containing different concentrations of fluoride-doped calcium phosphate fillers and evaluating their remineralising and antibacterial properties. METHODS: Experimental resin-based composites containing different concentrations (0-20 %) of fluoride-doped calcium phosphate fillers (VS10/VS20) were formulated. The release of calcium (Ca), phosphate (PO) and fluoride (F) ions was assessed for 30 days. Remineralisation properties were evaluated through ATR-FTIR and SEM/EDX after storage in simulated body fluid (SBF). The metabolic activity and viability of Streptococcus gordonii was also evaluated through ATP, CFU and live/dead confocal microscopy. The evaluation of specific monomer elution from the experimental composites was conducted using high-performance liquid chromatography (HPLC). RESULTS: The composites containing VS10 showed the highest release of Ca, those containing VS20 released more F over time (p < 0.05), while there was no significant difference in terms of PO ions release between the groups (p > 0.05). A quick 7-day mineral precipitation was observed in the tested composites containing VS10 or VS20 at 10 %; these materials also showed the greatest antibacterial activity (p < 0.05). Moreover, the tested composites containing VS10 presented the lowest elution of monomers (p < 0.05). CONCLUSIONS: Innovative composites were developed with low monomers elution, evident antibacterial activity against S. gordonii and important remineralisation properties due to specific ions release. CLINICAL SIGNIFICANCE: Novel composites containing fluoride-doped calcium phosphates may be promising to modulate bacteria growth, promote remineralisation and reduce the risk of cytotoxicity related to monomers' elution.

Musculoskeletal Morphology and Joint Flexibility-Associated Functional Characteristics across Three Time Points during the Menstrual Cycle in Female Contemporary Dancers.

Findings are inconsistent with regards to whether menstrual cycle phase-associated changes in physical functioning exist. It is possible that such discrepancies are due to varying rigour in experimental approaches. The current study aimed to systematically evaluate any effect of carefully tracked menstrual cycle phase on precisely measured muscle structure and function in a physically active group (contemporary dancers). Eleven women aged (M [SD]) 23.5 [2.94] years, undergoing 10.5 [1.73] hours of contemporary dance practice and 6.12 [2.36] hours of other physical activity per week, were recruited. Sex hormone level (enzyme-linked immunosorbent assays (ELISA), skin temperature and ovulation kits), physical pain assessments (Ice Water Test, Visual Analogue Scale, The Physical Activity Readiness Questionnaire, Self-Estimated Functional Inability Because of Pain Questionnaire, and Pain Anxiety Symptoms Scale), muscle architecture measurement (B-mode ultrasonography), and physical functioning (dynamometry, force-platform and electromyography) on both lower limbs were measured at three time points during one cycle, following three months of menstrual cycle monitoring. There was no difference in musculoskeletal flexibility variables between follicular, ovulatory, or luteal phases. Nonetheless, oestrogen change was associated with variability in 11 musculoskeletal variables, progesterone change was associated with variability in 7, and relaxin change was associated with variability in 15. Negative correlations existed between progesterone and flexibility and between oestrogen and jump variables. Moreover, oestrogen and relaxin were associated with increased musculoskeletal compliance, whilst progesterone was associated with increased muscle stiffness. In short, in absolute sex hormone levels, 'inter-individual' variances appear more impactful than 'intra-individual' variances. Not only are oestrogen and progesterone associated with differing musculoskeletal outcomes, but relaxin is also associated with musculoskeletal compliance changes. These effects are anticipated to impact jump height and flexibility, and hence, they could be expected to affect overall physical performance, including dance.

Screening for Delirium During Pediatric Brain Injury Rehabilitation.

OBJECTIVE: To assess feasibility of routine delirium screening using the Cornell Assessment of Pediatric Delirium (CAPD) in children admitted for rehabilitation with acquired brain injury (ABI), report on the prevalence of positive delirium screens in this population, and explore longitudinal trends in CAPD scores and their association with rehabilitation outcomes. DESIGN: Retrospective study. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: 144 children (median 10.8 years) with ABI (N=144). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Percent compliance with twice daily delirium screening; prevalence of positive delirium screens; trajectories in CAPD scores and their relation with FIM for Children (WeeFIM) scores. RESULTS: Screening was feasible (mean 75% compliance for each of 144 children). Of 16,136 delirium screens, 29% were positive. 62% of children had ≥1 positive screen. Four primary patterns of CAPD trajectories were identified: Static Encephalopathy (10%), Episodic Delirium (10%), Improving (32%), and No Delirium (48%). Validity of these trajectories was demonstrated through association with WeeFIM and CALS outcomes. Younger age at admission was associated with positive delirium screens, and rehabilitation length of stay was significantly longer for the Improving group. CONCLUSIONS: Delirium occurs frequently in children with ABI during inpatient rehabilitation. Routine delirium screening provides clinically relevant information including the potential to facilitate early detection and intervention for medical complications. Longitudinal ratings of delirium symptoms may also have a role in developing a standardized definition for Post Traumatic Confusional State (PTCS) stage of recovery in children.

A Case of Diffuse Thyroid Lipomatosis With Amyloid Deposits Presenting With Thyrotoxicosis.

Diffuse thyroid lipomatosis (DTL) is a rare entity of unknown etiology that can be associated with amyloidosis and rarely, thyrotoxicosis. Here, we present a case of DTL with amyloid deposits and concurrent thyrotoxicosis. A 64-year-old South-Asian woman with a several-year history of an enlarging goiter, unintentional weight loss, and work-up 10 months prior suggestive of thyroiditis presented with a viral syndrome in setting of several weeks of progressive fatigue. Her examination was notable for resting sinus tachycardia and massive painless goiter. Initial work-up revealed nephrotic range proteinuria with hypoalbuminemia, which progressed to end-stage-renal disease, elevated inflammatory markers, and elevated free thyroxine (FT4) with a suppressed thyrotropin. Hemodialysis was initiated. Further testing revealed a negative antithyroid antibody panel, an enlarged fatty thyroid per thyroid ultrasound and neck computed tomography, and normal 24-hour uptake on radioactive iodine uptake scan. Both renal and thyroid core biopsies showed amyloid deposits, with the latter confirming benign adipose tissue with entrapped thyroid follicles. Given her rising FT4 levels and persistent tachycardia, methimazole and atenolol were initiated. FT4 levels nearly normalized after uptitration of methimazole and dosing after dialysis. Although the etiopathogenesis and natural history of DTL remain unclear, we discuss the possible mechanisms of thyrotoxicosis in our patient.