Air-conditioning adoption and electricity demand highlight climate change mitigation-adaptation tradeoffs.
We elucidate mid-century climate change impacts on electricity demand accounting for endogenous adoption of residential air-conditioning (AC) in affluent, cooler countries in Europe, and in poorer, hotter states in India. By 2050, in a high-warming scenario (SSP585) AC prevalence grows twofold in Europe and fourfold in India, reaching around 40% in both regions. We document a mitigation-adaptation tradeoff: AC expansion reduces daily heat exposures by 150 million and 3.8 billion person degree-days (PDDs), but increases annual electricity demand by 34 TWh and 168 TWh in Europe and India, respectively (corresponding to 2% and 15% of today's consumption). The increase in adoption and use of AC would result in an additional 130 MMTCO2, of which 120 MMTCO2 in India alone, if the additional electricity generated were produced with today's power mix. The tradeoff varies geographically and across income groups: a one PDD reduction in heat exposure in Europe versus India necessitates five times more electricity (0.53 kWh vs 0.1 kWh) and two times more emissions (0.16 kgCO[Formula: see text] vs 0.09 kgCO[Formula: see text]), on average. The decomposition of demand drivers offers important insights on how such tradeoff can be moderated through policies promoting technology-based and behavioral-based adaptation strategies.


Circular RNAs Interaction with MiRNAs: Emerging Roles in Breast Cancer.
Despite significant advances in cancer therapy strategies, breast cancer is one of the most common and lethal malignancies worldwide. Characterization of a new class of RNAs using next-generation sequencing opened new doors toward uncovering etiopathogenesis mechanisms of breast cancer as well as prognostic and diagnostic biomarkers. Circular RNAs (circRNAs) are a novel class of RNA with covalently closed and highly stable structures generated primarily from the back-splicing of precursor mRNAs. Although circRNAs exert their function through various mechanisms, acting as a sponge for miRNAs is their primary mechanism of function. Furthermore, growing evidence has shown that aberrant expression of circRNAs is involved in the various hallmarks of cancers. This paper reviews the biogenesis, characteristics, and mechanism of functions of circRNAs and their deregulation in various cancers. Finally, we focused on the circRNAs roles as a sponge for miRNAs in the development, metastasis, angiogenesis, drug resistance, apoptosis, and immune responses of breast cancer.


Recent Advances in Ultrathin Chiral Metasurfaces by Twisted Stacking.
Artificial chiral nanostructures have been subjected to extensive research for their unique chiroptical activities. Planarized chiral films of ultrathin thicknesses are in particular demand for easy on-chip integration and improved energy efficiency as polarization-sensitive metadevices. Recently, controlled twisted stacking of two or more layers of nanomaterials, such as 2D van der Waals materials, ultrathin films, or traditional metasurfaces, at an angle has emerged as a general strategy to introduce optical chirality into achiral solid-state systems. This method endows new degrees of freedom, e.g., the interlayer twist angle, to flexibly engineer and tune the chiroptical responses without having to change the material or the design, thus greatly facilitating the development of multifunctional metamaterials. In this review, recent exciting progress in planar chiral metasurfaces are summarized and discussed from the viewpoints of building blocks, fabrication methods, as well as circular dichroism and modulation thereof in twisted stacked nanostructures. The review further highlights the ever-growing portfolio of applications of these chiral metasurfaces, including polarization conversion, information encryption, chiral sensing, and as an engineering platform for hybrid metadevices. Finally, forward-looking prospects are provided.


Nature of hapten-modified determinants involved in induction of T cell tolerance and suppressor T cells to NDFB contact sensitivity.
Unresponsiveness to DNFB contact sensitivity induced by DNP-modified lymphoid cells (DNP-LC) is mediated by two separable pathways: a rapidly induced, long lasting inhibition of reactive T cell clones (donor tolerance), and a transient period of suppressor T cell (Ts) activity. The present report has examined the nature of the hapten-modified determinants responsible for the induction of these pathways by utilizing soluble DNP-LC cell lysate preparations as tolerogens. The results indicate that both DNP-modified MHC and non-MHC encoded determinants can mediate donor tolerance 7 days after tolerization. On the other hand, the induction of Ts requires DNP-modified MHC determinants, since DNP-LC lysates passed over lentil lectin or specific anti-H-2 immunoabsorbent columns lost their ability to induce Ts. Additional experiments showed that the injection of DNP-LC lysate compatible with the recipient strain at the H-2K and H-2D region of the MHC was sufficient for the induction of Ts. We propose that Ts induction involves the direct presentation of DNP-H-2 determinants to Ts precursors, whereas the induction of donor tolerance may involve host processing and presentation of DNP-modified membrane determinants in conjunction with host MHC structures.


A modified pseudolikelihood approach for analysis of longitudinal data.
We consider the analysis of longitudinal data when the covariance function is modeled by additional parameters to the mean parameters. In general, inconsistent estimators of the covariance (variance/correlation) parameters will be produced when the "working" correlation matrix is misspecified, which may result in great loss of efficiency of the mean parameter estimators (albeit the consistency is preserved). We consider using different "working" correlation models for the variance and the mean parameters. In particular, we find that an independence working model should be used for estimating the variance parameters to ensure their consistency in case the correlation structure is misspecified. The designated "working" correlation matrices should be used for estimating the mean and the correlation parameters to attain high efficiency for estimating the mean parameters. Simulation studies indicate that the proposed algorithm performs very well. We also applied different estimation procedures to a data set from a clinical trial for illustration.


Appearance of fibronectin in rabbit cornea after thermal burn.
The sequence of the appearance of fibronectin in the rabbit cornea after thermal burn was investigated by indirect immunofluorescent microscopy. One day after thermal burn, the keratocytes disappeared completely from the burned area, and faint fibronectin-specific fluorescence was detected beneath the epithelium and on the stromal side of the Descemet's membrane. On day 3, activated keratocytes began to migrate to the burned lesion. Fibronectin was detected in the burned area as well as in the surrounding uninjured area, and on both sides of the Descemet's membrane. One week after the burn, the keratocytes had increased in the lesion and, concomitantly, fibronectin-specific fluorescence could be observed at the locations corresponding to the keratocytes. Fibronectin in the surrounding area gradually diminished. After 4 weeks, activated keratocytes had accumulated in the lesion, and fibronectin was detected only in the central lesion and at the level of the Descemet's membrane. Thus the appearance of fibronectin was concordant with the appearance of the keratocytes, and this suggests that fibronectin may be involved in the wound-healing of thermally burned rabbit corneas.


Diarrhoeal enterotoxin production by psychrotrophic Baccillus cereus present in reconstituted milk-based infant formulae (MIF).
One hundred reconstituted milk-based infant formulae (MIF) representative of 10 leading brands available in many European Economic Community countries were examined for psychrotrophic Bacillus cereus and for the presence of diarrhoeal enterotoxin. Of the 38 B. cereus isolates recovered from MIF, one, four and 16 strains grew at 4, 6 and 8 degrees C after 15 d. One (2.6%), two (5.3%) and six (15.8%) of the isolates were identified as potential psychrotrophic food poisoning strains as they were both enterotoxigenic and exhibited good growth at 4, 6 and 8 degrees C, respectively. Enterotoxin was not detected in MIF in which less than 5.36 log10 cfu of B. cereus ml-1 had grown. While psychrotrophic enterotoxigenic B. cereus strains occur occasionally in MIF, brief storage of reconstituted MIF at the recommended refrigeration temperature of 4 degrees C will allow this product to remain safe for consumption.


Drying dissipative structures of nonionic surfactants in aqueous solution.
Macroscopic and microscopic dissipative structural patterns form in the course of drying a series of aqueous solutions of polyoxyethylenealkyl ethers. The shift from the single round hill with accumulated surfactant molecules to the broad ring patterns of the hill in a macroscopic scale occurs as the HLB (hydrophile-liophile balance) of the surfactant molecules increases. The patterns correlate intimately with the HLB values of the surfactants. Microscopic patterns of small blocks, starlike patterns, and branched strings are formed. The size and shape of the surfactant molecules themselves influence the drying patterns in part. The pattern area and the time to dryness have been discussed as a function of surfactant concentration and HLB of the surfactants. The convection flow of water accompanying the surfactant molecules, the change in the contact angles at the drying frontier between solution and substrate in the course of dryness, and interactions among the surfactants and substrate are important for the macroscopic pattern formation. Microscopic patterns are determined in part by the shape and size of the molecules, translational Brownian movement of the surfactant molecules, and the electrostatic and hydrophobic interactions between surfactants and/or between the surfactant and substrate in the course of solidification.


Factors associated with ICD-11 posttraumatic stress disorder and complex posttraumatic stress disorder among older adults during the COVID-19 pandemic.
ICD-11 posttraumatic stress disorder (PTSD) and complex PTSD have been understudied in the older population. The study focused on the associations between traumatic exposure before the pandemic, COVID-19 worries, depression, and loneliness with current PTSD and CPTSD among older adults. A random sample of five hundred and twelve Israeli older adults (Mage = 72.67 ± 3.81, range 68-87) was recruited using a Web-based survey company (Ipanel, Israel). Participants completed questionnaires of demographic details, self-rated health, COVID-19 worries, trauma exposure, depressive symptoms, level of loneliness, PTSD, and CPTSD. Univariate logistic regression revealed that trauma exposure, COVID-19 worries, depression, and loneliness were associated with PTSD. Multinomial regression revealed that only trauma exposure was associated with PTSD among older adults with PTSD compared with those not reaching the PTSD cutoff level. In the comparison between older adults suffering from CPTSD with those not reaching the PTSD cutoff level, being married, higher levels of trauma exposure, COVID-19 worries, depression, and loneliness were associated with a higher risk of CPTSD. Results suggest that specific factors may be significant psychological correlates of CPTSD symptoms among older adults during the COVID-19 pandemic. Identifying these factors could assist practitioners in tailoring more effective interventions.


Differential expression of IGF-I and IGF-II in eutopic and ectopic endometria of women with endometriosis and in women without endometriosis.
Factors regulating the development, growth, and differentiation of endometrial cells of endometriotic lesions are poorly understood. To investigate the paracrine-autocrine regulation of ectopic endometrial cell growth, the expression of IGF-I and IGF-II were studied. Tissue specimens of eutopic and ectopic endometria were obtained from eight patients with endometriosis at laparoscopy and from the endometria of 14 women without endometriosis as controls. They were tested for the expression of IGF-I and IGF-II by immunohistochemical analysis. Immunohistochemical study for IGF-I in controls showed a more intense staining during the proliferative phase both in stromal and epithelial cells. In eutopic endometria of women with endometriosis a reduction in the staining was observed, whereas in epithelial cells of fibrotic peritoneal adhesions an intense immunostaining for IGF-I was observed. Immunohistochemical study of IGF-II in controls showed a more intense staining during secretory phase both in stromal and epithelial cells. In eutopic endometria of women with endometriosis, a reduction in the staining was observed, whereas in epithelial cells of fibrotic peritoneal adhesions an intense immunostaining for IGF-I was observed. Immunohistochemical study of IGF-II in controls showed a more intense staining during secretory phase both in stromal and epithelial cells. In eutopic endometria of women with endometriosis, a reduction in the staining was observed, whereas in epithelial cells of ovarian lesions and fibrotic peritoneal adhesions, no immunostaining for IGF-II was observed. In endometriosis there is an alteration of mechanisms regulating cell proliferation and differentiation.


GP interest in teaching junior doctors - Does practice location, size and infrastructure matter?
With the influx of Australian medical graduates into the workforce, new clinical prevocational training rotations within general practice need to be developed. This study describes the relationship between general practitioner teachers' interest in hosting junior doctor rotations, and general practice characteristics including rural location, size and infrastructure. All GP teachers of registrars and medical students in the Australian Capital Territory and southeast New South Wales were sent a survey. The features of rural location, size and infrastructure of these teachers' general practices were analysed to determine their influence on teacher interest in hosting junior doctor rotations. Factors such as rural location and infrastructure did not influence willingness to host junior doctors significantly. However, those in medium sized practices were less interested than small or large practices. Rural location and teaching room infrastructure of practices need not be determinants in junior doctor teaching practice recruitment, while medium practice size is a significant determinant of lack of teacher interest in hosting junior doctors. This requires further investigation.


Isolated nerve endings (neurosecretosomes) from the posterior pituitary. Partial separation of vasopressin and oxytocin and the isolation of microvesicles.
Subcellular fractions of the bovine posterior pituitary, including one composed almost exclusively of pinched-off nerve endings (neurosecretosomes), were characterized electron microscopically, hormonally, and enzymically. 15% of the nerve terminals in the gland were isolated as neurosecretosomes, as estimated from determinations of lactic dehydrogenase, a soluble, cytoplasmic enzyme. Neurosecretosomes were subdivided into three fractions by density-gradient centrifugation. The three subfractions, each shown to be nearly homogeneous populations of neurosecretosomes by means of electron microscopic and enzymic criteria, differed from each other in their vasopressin/oxytocin (VP/OT) ratios. The VP/OT ratio increased from the lightest to the densest fraction, indicating that VP is localized to denser and OT to lighter neurosecretosomes; similar results have been obtained previously for subfractions of neurosecretory granules (NSG). No morphological differences were apparent in neurosecretosomes among the three subfractions. Although complete separation of VP and OT was not achieved, the findings suggest that VP and OT are each stored in a different species of nerve ending and support the hypothesis that a given neurosecretory cell synthesizes, stores, and secretes only one of the peptide hormones. Microvesicles, 40-80 mmicro diameter and contained in typical neurosecretory cell terminals, are believed to be degradation products of membrane ghosts of depleted NSG; electron micrographs indicative of this transformation are presented. A fraction rich in microvesicles, but containing some NSG membranes, was prepared by density-gradient centrifugation of an osmolysate of neurosecretosomes. Smaller, apparently nonneurosecretory nerve endings, lacking NSG but filled with small vesicles, are occasionally seen in sections from whole gland. The vesicles in these atypical posterior pituitary nerve endings may be true neurohumor-containing, "synaptic" vesicles.


Psilocybin-Induced Mystical-Type Experiences are Related to Persisting Positive Effects: A Quantitative and Qualitative Report.
Psychedelic drugs such as psilocybin have shown substantial promise for the treatment of several psychiatric conditions including mood and addictive disorders. They also have the remarkable property of producing persisting positive psychological changes in healthy volunteers for at least several months. In this study (NCT03289949), 35 medium-high doses of psilocybin were administered to 28 healthy volunteers (12 females). By the end of the dosing day, participants reported the intensity of their acute experience using the 30-item Mystical Experience Questionnaire (MEQ) and an open-form qualitative report from home. Persisting psychological effects attributed to the psilocybin experience were measured using the Persisting Effects Questionnaire (PEQ) 3-months after administration. Using a linear latent-variable model we show that the MEQ total score is positively associated with the later emergence of positive PEQ effects (p = 3 × 10-5). Moreover, the MEQ subscales "Positive Mood" (pcorr = 4.1 × 10-4) and "Mysticality" (pcorr = 2.0 × 10-4) are associated with positive PEQ whereas the subscales "Transcendence of Time and Space" (pcorr = 0.38) and "Ineffability" (pcorr = 0.45) are not. Using natural language pre-processing, we provide the first qualitative descriptions of the "Complete Mystical Experience" induced by orally administered psilocybin in healthy volunteers, revealing themes such as a sense of connection with the Universe, familial love, and the experience of profound beauty. Combining qualitative and quantitative methods, this paper expands understanding of the acute psilocybin induced experience in healthy volunteers and suggests an importance of the type of experience in predicting lasting positive effects.


In vivo pharmacological characterization of indiplon, a novel pyrazolopyrimidine sedative-hypnotic.
Indiplon (NBI 34060; N-methyl-N-[3-[3-(2-thienylcarbonyl)-pyrazolo[1,5-alpha]pyrimidin-7-yl]phenyl]acetamide), a novel pyrazolopyrimidine and high-affinity allosteric potentiator of GABA(A) receptor function, was profiled for its effects in rodents after oral administration. In mice, indiplon inhibited locomotor activity (ED(50) = 2.7 mg/kg p.o.) at doses lower than the nonbenzodiazepine hypnotics zolpidem (ED(50) = 6.1 mg/kg p.o.) and zaleplon (ED(50) = 24.6 mg/kg p.o.), a sedative effect that was reversed by the benzodiazepine site antagonist flumazenil. Indiplon inhibited retention in the mouse passive avoidance paradigm over a dose range and with a temporal profile that coincided with its sedative activity. Indiplon, zolpidem, and zaleplon were equally effective in inhibiting locomotor activity in the rat and produced dose-related deficits on the rotarod. In a rat vigilance paradigm, indiplon, zolpidem, and zaleplon produced performance deficits over a dose range consistent with their sedative effects, although indiplon alone showed no significant increase in response latency. Indiplon produced a small deficit in the delayed nonmatch to sample paradigm at a dose where sedative effects became apparent. Indiplon was active in the rat Vogel test of anxiety, but it showed only a sedative profile in the mouse open field test. The pharmacokinetic profile of indiplon in both rat and mouse was consistent with its pharmacodynamic properties and indicated a rapid T(max), short t(1/2), and excellent blood-brain barrier penetration. Therefore, indiplon has the in vivo profile of an efficacious sedative-hypnotic, in agreement with its in vitro receptor pharmacology as a high-affinity allosteric potentiator of GABA(A) receptor function, with selectivity for alpha1 subunit-containing GABA(A) receptors.


Assessment of citrate concentrations in citrus fruit-based juices and beverages: implications for management of hypocitraturic nephrolithiasis.
Dietary intake of citrate in the form of citrus juices (eg, lemonade, orange juice) will enhance urinary citrate excretion, a valuable benefit for patients with hypocitraturic calcium oxalate nephrolithiasis. While information on citrate concentrations in select citrus juices is available, data on citrate concentrations of commercially available beverages (juice and otherwise) are limited. Using nuclear magnetic resonance spectroscopy (1H NMR), we report citrate concentrations of several beverages to help guide dietary recommendations aimed at increasing urinary citrate excretion and correcting hypocitraturia. Citrate concentrations of a squeezed lemon, several fruit juices, and common beverages were measured using 1H NMR. Spectra for each sample were obtained in duplicate; citrate peak was identified, measured, and quantified and compared with the citrate concentration in the juice of 1 medium lemon. Quantitative analysis revealed the highest concentration of citrate was in grapefruit juice (64.7 mmol/L), followed in decreasing concentrations by lemon juice (47.66 mmol/L), orange juice (47.36 mmol/L), pineapple juice (41.57 mmol/L), reconstituted lemonade (38.65 mmol/L), lemonade flavored Crystal Light (38.39 mmol/L), ready to consume not from concentrate lemonade (38.24 mmol/L), cranberry juice (19.87 mmol/L), lemon-flavored Gatorade (19.82 mmol/L), homemade lemonade (17.42 mmol/L), Mountain Dew (8.84 mmol/L), and Diet 7Up (7.98 mmol/L), respectively. According to 1H NMR, all of the tested "natural" citrus juices have high concentrations of citrate (38.3-67.4 mmol/L), with grapefruit juice having the highest concentration of the beverages chosen. Lemonade flavored Crystal Light had the highest concentration of citrate in the nonjuice category of tested beverages. In patients with mild to moderate hypocitraturia, dietary supplementation with citrus-based juices may be an effective alternative to medical management while not requiring large serving sizes. Further prospective studies are warranted to evaluate the clinical significance of these findings.


Thalidomide for the treatment of acute myeloid leukemia.
In analogy to solid neoplasms, accumulating data suggest the requirement of angiogenesis also for the development and progression of hematopoietic malignancies including acute myeloid leukemia (AML). Inhibition of increased microvessel density in bone marrow (BM) might be a promising target for pharmacological interventions aimed at reducing disease activity. Among the putative inhibitors of angiogenesis, thalidomide has demonstrated a considerable efficacy in myelodysplastic syndromes (MDS) and AML with overall response rates up to 56% and 25%, respectively. Responders experienced hematologic improvements with increased hemoglobin and platelet counts resulting in temporary transfusion independence. In AML, partial responses--defined as reduction of the leukemic blast cell infiltration of at least 50% in BM--occurred in four of 20 patients after one month of thalidomide administration in a previous phase I/II study. Additionally, we observed a long-term response in one AML patient of more than 20 months, meanwhile fulfilling the criteria of complete remission. The decrease in leukemic blast infiltration in BM of responders was accompanied by a significant reduction of the microvessel density. Overall adverse events caused by the drug consisted mainly of fatigue, constipation, skin rash and polyneuropathy with a tolerable dose of 200-400 mg p.o. per day. In conclusion, thalidomide as a single agent has significant anti-leukemic activity with some evidence for anti-angiogenic effects in BM, although the precise mechanism of action remains to be elucidated.


Engineering yeasts as platform organisms for cannabinoid biosynthesis.
Δ9-tetrahydrocannabinolic acid (THCA) is a plant derived secondary natural product from the plant Cannabis satival. The discovery of the human endocannabinoid system in the late 1980s resulted in a growing number of known physiological functions of both synthetic and plant derived cannabinoids. Thus, manifold therapeutic indications of cannabinoids currently comprise a significant area of research. Here we reconstituted the final biosynthetic cannabinoid pathway in yeasts. The use of the soluble prenyltransferase NphB from Streptomyces sp. strain CL190 enables the replacement of the native transmembrane prenyltransferase cannabigerolic acid synthase from C. sativa. In addition to the desired product cannabigerolic acid, NphB catalyzes an O-prenylation leading to 2-O-geranyl olivetolic acid. We show for the first time that the bacterial prenyltransferase and the final enzyme of the cannabinoid pathway tetrahydrocannabinolic acid synthase can both be actively expressed in the yeasts Saccharomyces cerevisiae and Komagataella phaffii simultaneously. While enzyme activities in S. cerevisiae were insufficient to produce THCA from olivetolic acid and geranyl diphosphate, genomic multi-copy integrations of the enzyme's coding sequences in K. phaffii resulted in successful synthesis of THCA from olivetolic acid and geranyl diphosphate. This study is an important step toward total biosynthesis of valuable cannabinoids and derivatives and demonstrates the potential for developing a sustainable and secure yeast bio-manufacturing platform.


Validamycin treatment significantly inhibits the glycometabolism and chitin synthesis in the common cutworm, Spodoptera litura.
Validamycin, as a broadly applied antibiotic, has been used to control rice sheath blight disease. Furthermore, validamycin was considered as an insecticide to control agricultural pests. Insight into the mechanism of validamycin's action on insects can provide molecular targets for the control of agricultural pests. In this study, a toxicological test analysis revealed that Spodoptera litura larval growth and development was significantly inhibited and the pupation rate was significantly reduced with the increase of the concentration of validamycin. According to the NMR-based metabolomic analysis, a total of 15 metabolites involved in glycolysis and tricarboxylic acid cycle (TCA) pathways were identified. Additionally, trehalase activities, glucose and chitin contents were significantly downregulated, but the trehalose content was upregulated after exposure to validamycin. Reverse transcription quantitative PCR analysis revealed that the expression level of genes involved in glycolysis, TCA and chitin synthesis were upregulated after treating with validamycin. Further chitin staining also confirmed that chitin content was downregulated at 12 h after validamycin treatment. Our results indicated that validamycin worked via two different molecular mechanisms, one through inhibiting glycometabolism and the other by inhibiting chitin synthesis in S. litura. The information lays a theoretical foundation for further control of S. litura.


THE FUNCTIONAL BASIS OF NATURAL SELECTION FOR VERTEBRAL TRAITS OF LARVAE IN THE STICKLEBACK GASTEROSTEUS ACULEATUS.
Previous studies have demonstrated selective predation for vertebral traits of larvae in the stickleback Gasterosteus aculeatus. I tested the hypothesis that this selection results from a direct functional advantage to particular vertebral phenotypes by direct measurement of the burst swimming performance of larvae. Within a narrow window of lengths, burst speed did depend on vertebral phenotype. As in the previous predation experiments, performance was related more directly to the ratio of abdominal to caudal vertebrae (VR) than to the total number of vertebrae (VN), and the optimal VR decreased as larval length increased. Changes with length in the vertebral phenotype frequencies of wild larvae provided evidence of selection for VR and for VN in the wild. Larvae with particular VR increased in frequency in the wild at just those lengths when their relative performance was superior in the laboratory. The observed pattern of length-dependent selection for vertebral number provides an explanation for the widespread trends in vertebral number that occur among populations of related fishes.


Human BRCA1 inhibits growth in yeast: potential use in diagnostic testing.
Germline-inactivating mutations of BRCA1 result in a hereditary predisposition to breast and ovarian cancer. Truncating mutations of BRCA1 predispose to cancer and can be ascertained by protein truncation testing or sequencing. However, cancer-predisposing missense mutations of BRCA1 are difficult to distinguish from polymorphisms by genetic testing methods currently used. Here we show that expression of BRCA1 or BRCA1 fused to a GAL4 activation domain in Saccharomyces cerevesiae inhibits growth, resulting in small colonies easily distinguishable from vector-transformed controls. The growth inhibitory effect can be localized to sequences encoding the recently described BRCA1 C-terminal domains. Growth suppression by a BRCA1 fusion protein is not influenced by introduction of neutral polymorphisms but is diminished or abolished by frameshift, nonsense, or disease-associated missense mutations located in the C-terminal 305 amino acids of BRCA1. These observations may permit the functional significance of many BRCA1 sequence changes to be assessed in yeast. Additionally, the correlation of growth suppression with wild-type forms of BRCA1 suggests that the assay may be capable of detecting functionally conserved interactions between the evolutionarily conserved BRCA1 C-terminal domains and cellular elements found in both human and yeast cells.


Design and performance of a multilayered mirror monochromator in the low-energy region of the VUV.
For the energy region from tens to hundreds of electron volts, the multilayered mirror (MLM) monochromator has never been realized due to the difficulty of reducing the background noise of the total reflection component, in spite of its usefulness in synchrotron radiation experiments. In this work, a double-crystal-type MLM monochromator equipped with a thin-film filter has been designed on the basis of trial fabrication of the mirror-driving system and of Mo/Si and Mo/C MLMs; its performance has been evaluated by calculating its output photon flux. It is shown that by using the MLMs at low incident angles, combined with an appropriate thin-film filter, it is possible to make a practical monochromator with high output photon flux and low background noise.


Study Design of VESUTO®: Efficacy of Tiotropium/Olodaterol on Lung Hyperinflation, Exercise Capacity, and Physical Activity in Japanese Patients with Chronic Obstructive Pulmonary Disease.
The superiority of tiotropium/olodaterol is demonstrated in improvement of lung function, dyspnea, lung hyperinflation, and quality of life compared with either monotherapy in patients with chronic obstructive pulmonary disease (COPD). Japanese Respiratory Society Guidelines for COPD management include improvement of exercise tolerance and daily physical activity as the treatment goals; however, there is limited evidence in Japanese patients with COPD. A protocol is developed for the VESUTO® study that investigates the efficacy of tiotropium/olodaterol fixed-dose combination (FDC) compared with tiotropium alone on inspiratory capacity (IC, volume from functional residual capacity to total lung capacity), exercise capacity, and daily physical activity in Japanese patients with COPD. A total of 180 Japanese patients with COPD, aged ≥40 years will be enrolled into the double-blind, multicenter, active-controlled, crossover study (NCT02629965) and will be randomized to receive either tiotropium/olodaterol FDC or tiotropium for 6 weeks each [two puffs via RESPIMAT® (Boehringer Ingelheim, Ingelheim, Germany) inhaler in the morning]. The primary endpoint is IC at rest measured at 60 min post-dose after 6 weeks treatment. The secondary endpoints include the 6-min walk distance (6MWD) at 90 min post-dose and physical activity measured by the activity monitor in the last 2 weeks of the 6-week treatment periods. Lung function tests will also be assessed after 6 weeks treatment. A mixed-effects model repeated measures approach will be used for the primary and secondary endpoints. The VESUTO® study is the first randomized interventional study to investigate exercise capacity (6MWD) and physical activity measured by a 3-axis accelerometer in Japanese patients with COPD. The study could provide additional evidence of long-acting muscarinic antagonist (LAMA) + long-acting β2-agonist (LABA) combination therapy on patients' physical activities as well as lung function. ClinicalTrials.gov: NCT02629965 (registered on December 1, 2015). The VESUTO study was funded by Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.


Social determinants of health derived from people with opioid use disorder: Improving data collection, integration and use with cross-domain collaboration and reproducible, data-centric, notebook-style workflows.
Deriving social determinants of health from underserved populations is an important step in the process of improving the well-being of these populations and in driving policy improvements to facilitate positive change in health outcomes. Collection, integration, and effective use of clinical data for this purpose presents a variety of specific challenges. We assert that combining expertise from three distinct domains, specifically, medical, statistical, and computer and data science can be applied along with provenance-aware, self-documenting workflow tools. This combination permits data integration and facilitates the creation of reproducible workflows and usable (reproducible) results from the sensitive and disparate sources of clinical data that exist for underserved populations.


Low Rates of Psychosocial Screening and Lifestyle Counseling in Hidradenitis Suppurativa Patients in the USA.
Although hidradenitis suppurativa (HS) is associated with psychosocial comorbidities such as depression as well as modifiable comorbidities such as obesity, rates of psychosocial screening and lifestyle counseling in the USA have not been characterized. This cross-sectional study utilized publicly available data from the National Ambulatory Medical Care Survey (NAMCS) between 2008 and 2018 to identify visits with a diagnosis of HS (ICD-9 code 705.83, ICD-10 code L73.2). T tests and multivariate logistic regressions analyzed trends in rates of screening and counseling while controlling for race, sex, and age. Survey weights are applied to each visit to represent a national sample. Depression screening was completed in only 2% of reported visits. No visits reported screening for alcohol misuse, substance abuse, or domestic violence. There were low rates of counseling for weight reduction (7.8%), diet and nutrition (3.3%), exercise (2.4%), smoking (1.0%), and substance abuse (0.7%). Black patients and individuals with public health insurance received less screening and counseling overall. Rates of psychosocial screening and counseling on lifestyle modifications are low in ambulatory clinic visits for HS patients, and there are disparities based on race and insurance status. Implementing strategies to incorporate routine psychosocial screening and lifestyle counseling into visits may improve HS patient outcomes.


Endophenotype approach to developmental psychopathology: implications for autism research.
This paper discusses the utility of the endophenotype approach in the study of developmental psychopathology. It is argued that endophenotype research holds considerable promise for the study of gene-brain/cognition-behaviour pathways for developmental disorders. This paper outlines the criteria for determining useful endophenotypes. Possible endophenotypes for autism are discussed as an example of an area where endophenotype research on developmental disorders may be fruitful. It is concluded that although the endophenotype approach holds promise for the study of gene-brain/cognition-behaviour pathways, much work remains to be done in order to validate endophenotype measures. It is also noted that the changing nature of any developmental psychopathology poses a particular challenge to this type of research.


[Clinical application of supraclavicular flap for oncologic reconstruction of hypopharynx and upper esophagus].
Objective: To assess the efficacy of supraclavicular artery island flap (SCAIF) for the reconstruction of hypopharynx and upper esophagus. Methods: The SCAIF procedure on was used in 10 patients, including 8 with hypopharygeal carcinomas, 1 with esophageal carcinoma and neck skin invasion and 1 with hypopharyngeal leiomyosarcoma, at the Otorhinolaryngology Hospital, the First Affiliated Hospital, Sun Yatsen University between December 2015 and June 2017. The sizes of the flaps were measured in (4-8) cm×(5-12) cm. Clinical indexes such as harvesting time and survival were recorded. Results: Harvesting time for SCAIF ranged from 20 to 30 minutes, averaging 26 minutes. Nine flaps survived, one flap had partially necrosis. Functional outcomes were excellent and the donor sites were direct closed without complications. Conclusions: SCAIF is a versatile, reliable, and easily harvested flap, with good cosmetic and functional outcomes for reconstructing the defects of hypopharynx and upper esophagus.


Identification of Human Leukotriene A4 Hydrolase Inhibitors Using Structure-Based Pharmacophore Modeling and Molecular Docking.
Leukotriene B4 (LTB4) is a potent, proinflammatory lipid mediator implicated in the pathologies of an array of inflammatory diseases and cancer. The biosynthesis of LTB4 is regulated by the leukotriene A4 hydrolase (LTA4H). Compounds capable of limiting the formation of LTB4, through selective inhibition of LTA4H, are expected to provide potent anti-inflammatory and anti-cancer agents. The aim of the current study is to obtain potential LTA4H inhibitors using computer-aided drug design. A hybrid 3D structure-based pharmacophore model was generated based on the crystal structure of LTA4H in complex with bestatin. The generated pharmacophore was used in a virtual screen of the Maybridge database. The retrieved hits were extensively filtered, then docked into the active site of the enzyme. Finally, they were consensually scored to yield five hits as potential LTA4H inhibitors. Consequently, the selected hits were purchased and their biological activity assessed in vitro against the epoxide hydrolase activity of LTA4H. The results were very promising, with the most active compound showing 73.6% inhibition of the basal epoxide hydrolase activity of LTA4H. The results from this exploratory study provide valuable information for the design and development of more potent and selective inhibitors.


New direct method for evaluating recoilless f-factors of two iron-sites in Fe-bearing compounds using Mössbauer spectrometry.
We propose a new direct method for calculating simultaneously two recoilless f-factors of any iron-bearing compound relative to that of a reference material by collecting only a single-temperature Mössbauer spectrum. This methodology is comparatively much simpler than the usual one which requires taking Mössbauer spectra of the compound at several temperatures and subsequently fitting the temperature dependence of the subspectral area or the isomer shift data with a lattice vibrational model. We demonstrate the applicability of this new methodology in the case of three common iron-bearing compounds: magnetite, akaganeite and goethite, but of course this type of study can be extended to other materials. The two f-factors for each compound were related to iron ions located in sites of different origin: for magnetite, these were related to irons with two different oxidation states; for akaganeite to irons in two different crystallographic sites; and for goethite to irons in similar crystal sites but located in grains of different sizes. In the case of magnetite, we found that the f-factors for the Fe(3+) and Fe(2.5+) sites relative to that of metallic iron powder were of fFe (3+)∕fFe = 0.97 ± 0.05 and fFe (2.5+)∕fFe = 0.92 ± 0.05, respectively. Interestingly, the quotient of these two f-factors, i.e., fFe (2.5+)∕fFe (3+), is equal to 0.95 ± 0.05, which compares fairly well with a value reported in literature obtained using the complex methodology based on the temperature dependence of the absolute subspectral area and the Debye approximation. For akaganeite, the f-factors of the doublet 1, D1, and doublet 2, D2, sites relative to that of metallic iron powder were of fD 1∕fFe = 0.95 ± 0.08 and fD 2∕fFe = 0.98 ± 0.15, respectively. And for goethite we found that the f-factors of the sextet 1, G1, and sextet 2, G2, sites relative to that of metallic iron powder were of fG 1∕fFe = 0.80 ± 0.02 and fG 2∕fFe = 0.80 ± 0.02, respectively. The similarity of these last two factors is perhaps due to a sharp distribution of large grains.


Examining associations, moderators and mediators between childhood maltreatment, social functioning, and social cognition in psychotic disorders: a systematic review and meta-analysis.
Childhood maltreatment (CM) has been related to social functioning and social cognition impairment in people with psychotic disorders (PD); however, evidence across different CM subtypes and social domains remains less clear. We conducted a systematic review and meta-analysis to quantify associations between CM, overall and its different subtypes (physical/emotional/sexual abuse, physical/emotional neglect), and domains of social functioning and social cognition in adults with PD. We also examined moderators and mediators of these associations. A PRISMA-compliant systematic search was performed on 24 November 2022 (PROSPERO CRD42020175244). Fifty-three studies (N = 13 635 individuals with PD) were included in qualitative synthesis, of which 51 studies (N = 13 260) with 125 effects sizes were pooled in meta-analyses. We found that CM was negatively associated with global social functioning and interpersonal relations, and positively associated with aggressive behaviour, but unrelated to independent living or occupational functioning. There was no meta-analytic evidence of associations between CM and social cognition. Meta-regression analyses did not identify any consistent moderation pattern. Narrative synthesis identified sex and timing of CM as potential moderators, and depressive symptoms and maladaptive personality traits as possible mediators between CM and social outcomes. Associations were of small magnitude and limited number of studies assessing CM subtypes and social cognition are available. Nevertheless, adults with PD are at risk of social functioning problems after CM exposure, an effect observed across multiple CM subtypes, social domains, diagnoses and illness stages. Maltreated adults with PD may thus benefit from trauma-related and psychosocial interventions targeting social relationships and functioning.


Multimorbidity and survival in older persons with colorectal cancer.
To ascertain the effect of common chronic conditions on mortality in older persons with colorectal cancer. Retrospective cohort study. Population-based cancer registry. Patients in the Surveillance Epidemiology and End Results-Medicare linked database who were aged 67 and older and had a primary diagnosis of Stage 1 to 3 colorectal cancer during 1993 through 1999. Chronic conditions were identified using claims data, and vital status was determined from the Medicare enrollment files. After estimating the adjusted hazard ratios for mortality associated with each condition using a Cox model, the population attributable risk (PAR) was calculated for the full sample and by age subgroup. The study sample consisted of 29,733 patients, 88% of whom were white and 55% were female. Approximately 9% of deaths were attributable to congestive heart failure (CHF; PAR = 9.4%, 95% confidence interval (CI) = 8.4-10.5%), more than 5% were attributable to chronic obstructive pulmonary disease (COPD; PAR = 5.3%, 95% CI = 4.7-6.6%), and nearly 4% were attributable to diabetes mellitus (PAR = 3.9%, 95% CI = 3.1-4.8%). The PAR associated with CHF increased with age, from 6.3% (95% CI = 4.4-8.8%) in patients aged 67 to 70 to 14.5% (95% CI = 12.0-17.5%) in patients aged 81 to 85. Multiple conditions were common. More than half of the patients who had CHF also had diabetes mellitus or COPD. The PAR associated with CHF alone (4.29%, 95% CI = 3.68-4.94%) was similar to the PAR for CHF in combination with diabetes mellitus (3.08, 95% CI = 2.60-3.61%) or COPD (3.93, 95% CI = 3.41-4.54%). A substantial proportion of deaths in older persons with colorectal cancer can be attributed to CHF, diabetes mellitus, and COPD. Multimorbidity is common and exerts a substantial effect on colorectal cancer survival.


In vivo analysis of covering materials composed of biodegradable polymers enriched with flax fibers.
The objective of this study was to investigate the in vivo effect of bioactive composites with poly(lactic acid) (PLA) or polycaprolactone (PCL) as the matrix, reinforced with bioplastic flax fibers, on the surrounding muscle tissue. Materials of pure PLA and PCL and their composites with flax fibers from genetically modified plants producing poly-3-hydroxybutyrate (PLA-transgen, PCL-transgen) and unmodified plants (PLA-wt, PCL-wt) were placed subcutaneous on the M. latissimus dorsi for four weeks. The analysis of histological samples revealed that every tested material was differently encapsulated and the capsule thickness is much more pronounced when using the PCL composites in comparison with the PLA composites. The encapsulation by connective tissue was significantly reduced around PCL-transgen and significantly increased in the cases of PLA-transgen and PLA-wt. In the collected muscle samples, the measured protein expression of CD45, lymphocyte common antigen, was significantly increased after the use of all tested materials, with the exception of pure PCL. In contrast, the protein expression of caveolin-1 remained unchanged after treatment with the most examined materials. Only after insertion of PLA-wt, a significant increase of caveolin-1 protein expression was detected, due to the improved neovascularization. These data support the presumption that the new bioactive composites are biocompatible and they could be applicable in the medical field to support the regenerative processes.


In Situ Control of Oxygen Vacancies in TaOx Thin Films via Plasma-Enhanced Atomic Layer Deposition for Resistive Switching Memory Applications.
The plasma-enhanced atomic layer deposition (PEALD) process using Ta(OC2H5)5 as a Ta precursor and plasma-activated hydrogen as a reactant for the deposition of TaOx films with a controllable concentration of oxygen vacancies (VO) is reported herein. The VO concentration control was achieved by varying the hydrogen volume fraction of the hydrogen-argon mixture in the plasma, allowing the control of the leakage current density in the tantalum oxide films within the range of 5 orders of magnitude compared with the Ta2O5 film grown via thermal ALD using the identical Ta precursor and H2O. Temperature-dependent current-voltage measurements combined with Poole-Frenkel emission modeling demonstrated that the bulk trap depth decreases with the increasing hydrogen volume fraction, which could be attributed to the increase of the VO concentration. The possible chemical change in the PEALD TaOx films grown under different hydrogen volume fractions was confirmed by the in situ X-ray photoelectron spectroscopy (XPS) measurements of the Ta 4f core and valence band spectra. The comparison of the XPS-measured nonstoichiometry and the secondary ion mass spectrometry analysis of the hydrogen content allowed this study to conclude that the nonstoichiometry is largely related to the formation of Ta-VO sites rather than of Ta-H sites. Such oxygen-deficient TaOx layers were studied for application as an oxygen-deficient layer in a resistance switching random access memory stack (Ta2O5/TaOx) where the actual switching occurred within the stoichiometric Ta2O5 layer. The bilayer memory stack showed reliable resistance switching up to ∼106 switching cycles, whereas the single-layer Ta2O5 memory showed only several hundred switching cycles.


Association of infertility with type and timing of menopause: a prospective cohort study.
What is the association between past infertility and the type and timing of menopause in midlife women? Women with a history of infertility were more likely to experience surgical menopause overall and had elevated risk of earlier surgical menopause until age 43 years but experienced no differences in the timing of natural menopause. Infertility is experienced by 12-25% of women and is thought to reveal a propensity for poor health outcomes, such as chronic illness, later in life. However, little is known about whether infertility is linked with characteristics of the menopausal transition as women age, despite possible shared underlying pathways involving ovarian function and gynecologic disease. Secondary analysis of a prospective cohort study of 13 243 midlife females recruited in Phase 1 of the Alberta's Tomorrow Project (Alberta, Canada) and followed approximately every 4 years (2000-2022). Data were collected through standardized self-report questionnaires. History of infertility, defined as ever trying to become pregnant for more than 1 year without conceiving, was measured at baseline. Menopause characteristics were measured at each study follow-up. Menopause type was defined as premenopause, natural menopause, surgical menopause (bilateral oophorectomy), or indeterminate menopause (premenopausal hysterectomy with ovarian conservation). Timing of natural menopause was defined as the age at 1 full year after the final menstrual period, and timing of surgical and indeterminate menopause was defined as the age at the time of surgery. We used flexible parametric survival analysis for the outcome of menopause timing with age as the underlying time scale and multinomial logistic regression for the outcome of menopause type. Multivariable models controlled for race/ethnicity, education, parity, previous pregnancy loss, and smoking. Sensitivity analyses additionally accounted for birth history, menopausal hormone therapy, body mass index, chronic medical conditions, and age at baseline. Overall, 18.2% of women reported a history of infertility. Past infertility was associated with earlier timing of surgical menopause exclusively before age 43 years (age 35: adjusted hazard ratio 3.13, 95% CI 1.95-5.02; age 40: adjusted hazard ratio 1.83, 95% CI 1.40-2.40; age 45: adjusted hazard ratio 1.13, 95% CI 0.87-1.46) as well as greater odds of experiencing surgical menopause compared to natural menopause (adjusted odds ratio 1.40, 95% CI 1.18-1.66). Infertility was not associated with the timing of natural or indeterminate menopause. Information on the underlying cause of infertility and related interventions was not collected, which precluded us from disentangling whether associations differed by infertility cause and treatment. Residual confounding is possible given that some covariates were measured at baseline and may not have temporally preceded infertility. Women with a history of infertility were more likely to experience early surgical menopause and may therefore benefit from preemptive screening and treatment for gynecologic diseases to reduce bilateral oophorectomy, where clinically appropriate, and its associated health risks in midlife. Moreover, the lack of association between infertility and timing of natural menopause adds to the emerging knowledge that diminishing ovarian reserve does not appear to be a primary biological mechanism of infertility nor its downstream implications for women's health. Alberta's Tomorrow Project is only possible due to the commitment of its research participants, its staff and its funders: Alberta Health, Alberta Cancer Foundation, Canadian Partnership Against Cancer and Health Canada, and substantial in-kind funding from Alberta Health Services. The views expressed herein represent the views of the author(s) and not of Alberta's Tomorrow Project or any of its funders. This secondary analysis is funded by Project Grant Priority Funding in Women's Health Research from the Canadian Institutes of Health Research (Grant no. 491439). N.V.S. is supported by a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research. H.K.B. is supported by the Canada Research Chairs Program. E.A.B. is supported by an Early Career Investigator Award in Maternal, Reproductive, Child and Youth Health from the Canadian Institutes of Health Research. A.K.S. has received honoraria from Pfizer, Lupin, Bio-Syent, and Eisai and has received grant funding from Pfizer. N.V.S., H.K.B., and E.A.B. have no conflicts of interest to report. N/A.


Comparative Study on Crystal Structures and Synthetic Techniques of Ternary Hafnium/Zirconium Fluorides.
Mild hydrothermal synthesis was employed to grow high-quality single crystals of ternary fluoridohafnates at low temperatures. The series of new materials was characterized using single-crystal X-ray diffraction, and the crystal structures of AHfF6 (A = Mg and Sr), A2HfF8 (A = Ba and Pb), Ca5Hf3F22, and Cd2HfF8(H2O)6 are discussed herein. Although some material compositions have similar stoichiometries, all of the compositions adopt different structural motifs. A comparison of the crystal structures and synthesis techniques of ternary fluoridohafnates and ternary fluoridozirconates is also reported, and the impact of the subtle changes of synthesis conditions on overall structures is discussed.


Shear-responsive injectable supramolecular hydrogel releasing doxorubicin loaded micelles with pH-sensitivity for local tumor chemotherapy.
In this study, glycol chitosan-Pluronic F127 conjugate (GC-PF127), produced by an amidation reaction between terminal-carboxylated PF127 and glycol chitosan (GC), was used to prepare doxorubicin (DOX)-loaded micelles. The DOX/GC-PF127 micelles produced at optimal conditions had sizes of about 150nm and pH-sensitive surface charges. DOX/GC-PF127 hydrogel formed after addition of α-cyclodextrin into DOX/GC-PF127 micelle solution. The hydrogel had good shear-responsive, injectable and rapid recovery properties. In vitro release experiment confirmed that the hydrogel could sustainedly release DOX/GC-PF127 micelles via the dissociation of the hydrogel. After peritumoral injection into H22 tumor-bearing mice, the hydrogel could greatly increase DOX accumulation in tumor tissue and synchronously avoid DOX accumulation in normal tissues including heart. At similar total DOX dose administrated, the tumors of free DOX treatment group grew slowly after thrice intravenous injections, the tumors of the micelle group did not grow after twice intravenous injections, and the tumors of the hydrogel group disappeared almost after once peritumoral injection. This study demonstrates that injectable DOX/GC-PF127 hydrogel, which can sustainedly release DOX-loaded micelles with tumor-targeting function, is a promising system for local tumor chemotherapy.


The Prevalence of PTSD Symptoms and Depressive Symptoms and Related Predictors in Children and Adolescents 3 Years After the Ya'an Earthquake.
The objectives of this study were to investigate the prevalence of post-traumatic stress disorder (PTSD) symptoms and depressive symptoms in teenage survivors three years after the Ya'an earthquake to assess the differences between left-behind (LBC) and non-left-behind (non-LBC) children, and to explore predictors for PTSD symptoms and depressive symptoms. The participants were assessed using children's revised impact of event scale (CRIES) and short mood and feelings questionnaire (SMFQ), after which t tests, Chi square tests, and a multivariate logistic regression were conducted to examine the differences in the LBC and identify the associated predictors. It was found that the PTSD and depressive symptom prevalences were 13.10% and 20.75%, with the LBC having a significantly higher prevalence than the non-LBC. The PTSD and depression symptoms tended to be highly comorbid (r = .52, p < .001). Being female, being aged less than 15, having siblings, being an LBC, and having higher exposure were found to be associated with PTSD and depressive symptoms.


Does the calcification of adamantinomatous craniopharyngioma resemble the calcium deposition of osteogenesis/odontogenesis?
Calcification in adamantinomatous craniopharyngioma (ACP) is troublesome for surgical intervention. The aim of this study was to examine the osteogenic proteins that play important roles in the calcium deposition of the odontogenic/osteogenic tissues in craniopharyngioma. Craniopharyngiomas (n = 89) were investigated for the presence and expression pattern of the osteoinductive/odontoinductive factor bone morphogenetic protein-2 (Bmp2) and two osteoblastic differentiation makers, Runt-related transcription factor-2 (Runx2) and Osterix, using immunohistochemistry and Western blotting. Our results showed that Bmp2, Runx2 and Osterix levels increased in cases with high calcification and correlated positively with the degree of calcification in ACP, whereas they showed little or no expression in squamous papillary craniopharyngioma. In ACP, Bmp2 was expressed primarily in the stellate reticulum and whorl-like array cells; Runx2 and Osterix tended to be expressed in calcification-related epithelia, including whorl-like array cells and epithelia in/around wet keratin and calcification lesions. Our study indicated, for the first time, that osteogenic factor Bmp2 may play an important role in the calcification of ACP via autocrine or paracrine mechanisms. Given the presence of osteogenic markers (Runx2 and Osterix), craniopharyngioma cells could differentiate into an osteoblast-like lineage, and the process of craniopharyngioma calcification resembles that which occurs in osteogenesis/odontogenesis.


Acute Low Force Electrically Induced Exercise Modulates Post Prandial Glycemic Markers in People with Spinal Cord Injury.
Regular exercise involves daily muscle contractions helping metabolize up to 70% of daily ingested glucose. Skeletal muscle increases glucose uptake through two distinct pathways: insulin signaling pathway and muscle contraction mediated AMPK pathway. People with paralysis are unable to contract their muscles which atrophy, transform into insulin resistant glycolytic muscle, and develop osteoporosis. Our goal is to determine if low force electrically induced exercise (LFE) will modulate the post prandial insulin and glucose response in people with and without spinal cord injury (SCI). 18 people with SCI and 23 without SCI (Non-SCI) participated in an assessment of metabolic biomarkers during passive sitting (CTL) and a bout of LFE delivered to the quadriceps/hamstring muscle groups after a glucose challenge. Baseline fasting insulin (p = 0.003) and lactate (p = 0.033) levels were higher in people with SCI, but glucose levels (p = 0.888) were similar compared to the non-SCI population. After 1-h of muscle contractions using LFE, heart rate increased (p < 0.001), capillary glucose decreased (p = 0.004), insulin decreased (p < 0.001), and lactate increased (p = 0.001) in the SCI population. These findings support that LFE attenuates certain metabolic blood biomarkers during a glucose challenge and may offer a lifestyle strategy to regulate metabolic responses after eating among people with SCI.


Subcellular localization of rat Abca5, a rat ATP-binding-cassette transporter expressed in Leydig cells, and characterization of its splice variant apparently encoding a half-transporter.
Several transporters belonging to the ABCA subfamily of ABC (ATP-binding cassette) proteins are involved in lipid trafficking. Human ABCA5 and its rat orthologue, rAbca5, represent recently identified subfamily members whose substrate spectrum remains to be defined. The elucidation of (sub)cellular rAbca5 distribution would be expected to provide a basis for optimization of functional analyses. In the present study, we applied in situ hybridization to examine rAbca5 mRNA distribution within sections of rat testis, a tissue expressing high levels of rAbca5 mRNA. We found rAbca5 mRNA to be predominantly expressed in interstitial Leydig cells, which are major sites of testosterone synthesis. To investigate rAbca5 subcellular localization, we constructed expression vectors yielding rAbca5 fused either to EGFP (enhanced green fluorescent protein) or to a peptide bearing the viral V5 epitope. During rAbca5 cDNA cloning, we discovered a splice variant sequence (rAbca5 V20+16), predicted to give rise to a truncated, half-size transporter, which was highly homologous with a human splice variant described by us previously. Quantitative RT (reverse transcription)-PCR demonstrated that the rAbca5 splice variant was expressed in numerous tissues (including testis, brain and lungs), its cDNA amounting to 2.6-11.2% of total rAbca5 cDNA. Transfection of individual rAbca5-EGFP, rAbca5 splice variant-EGFP or transporter-V5 expression plasmids along with organelle marker plasmids into HEK-293 cells (human embryonic kidney 293 cells) revealed that both rAbca5 and splice variant fusion proteins co-localized with marker protein for the Golgi apparatus. Expression of rAbca5 mRNA in Leydig cells, intracellular localization of rAbca5-EGFP/rAbca5-V5 and involvement of rAbca5-related proteins in lipid transport suggest that rAbca5 may participate in intracellular sterol/steroid trafficking.


Nomogram use for the prediction of indolent prostate cancer: impact on screen-detected populations.
Screening for prostate cancer has resulted in an increased incidence-to-mortality ratio. Not all cancers deserve immediate treatment. It has therefore become more important to be able to identify those cases of screen-detected prostate cancer most likely to show indolent behavior. The Kattan-nomogram for the prediction of indolent prostate cancer was validated and recalibrated for use in a screening setting. The recalibrated nomogram was used to calculate the number of men who were predicted to have indolent cancer in a screen-detected cohort from the European Randomized study of Screening for Prostate Cancer (ERSPC), section Rotterdam. Of 1629 cancers detected in 2 subsequent screening rounds 825 were suitable for nomogram use. The remainder were very unlikely to have indolent cancer. A total of 485 men (485 of 825 = 59%) were predicted to have indolent cancer, which is 30% (485 of 1629) of all screen-detected cases. Cancers found at repeated screening after 4 years had a higher probability of indolent cancer than cases from the prevalence screening (44% vs 23%; P < .001). The current nomogram can identify substantial groups of screen-detected cancers that are likely indolent and can therefore be considered for active surveillance.


COVID-19 Vaccine Impacts in Saudi Arabia: A Cross-Sectional Study.
Background and purpose Vaccinations provide disease protection through a variety of mechanisms; however, vaccines can occasionally cause adverse effects. Therefore, the objective of this investigation was to assess the short- and long-term adverse effects of COVID-19 vaccinations in Saudi Arabia. Methods In Saudi Arabia, between October 2021 and October 2022, a cross-sectional study was conducted. A validated Arabic and English dual-language online questionnaire were utilized to collect data. Results This investigation included 492 participants who were all immunized against the COVID-19 virus. There were 152 (30.9%) male participants and 340 (69.1%) female participants, with a mean age of 35±10.7 years. About 72.2% of study participants received three doses of vaccine, with 75.6% receiving the Pfizer-BioNTech vaccine, 22.2% receiving the Oxford-AstraZeneca vaccine, and 2.2% receiving the Moderna vaccine. Fever was observed in 66.3% (326/492) of the participants following vaccination, headache in 57.3% (282/492) of the participants, fatigue in 54.7% (269/492) of the participants, and influenza-like symptoms in 51% (251/492) of the participants. Younger participants (18-29 years old) exhibited influenza-like symptoms and fever after vaccination in comparison to older participants (P=0.03, P=0.02, respectively). In contrast, older participants reported more immobilization of the hands or legs, difficulty breathing, and chest pain than younger participants (P=0.04, P=0.02, and P=0.03, respectively). There was a significant correlation between gender and injection-site pain, headache, lethargy or convulsions, and flu-like symptoms. In addition, the participants' clinical history of chronic diseases was significantly associated with the occurrence of post-vaccination adverse effects. Conclusion The majority of the documented adverse reactions are of a temporary and minimal nature. Additional research is required to assess the enduring adverse reactions and efficacy of the vaccines in preventing SARS-CoV-2 reoccurrence.


Bioactive Molecule Prediction Using Extreme Gradient Boosting.
Following the explosive growth in chemical and biological data, the shift from traditional methods of drug discovery to computer-aided means has made data mining and machine learning methods integral parts of today's drug discovery process. In this paper, extreme gradient boosting (Xgboost), which is an ensemble of Classification and Regression Tree (CART) and a variant of the Gradient Boosting Machine, was investigated for the prediction of biological activity based on quantitative description of the compound's molecular structure. Seven datasets, well known in the literature were used in this paper and experimental results show that Xgboost can outperform machine learning algorithms like Random Forest (RF), Support Vector Machines (LSVM), Radial Basis Function Neural Network (RBFN) and Naïve Bayes (NB) for the prediction of biological activities. In addition to its ability to detect minority activity classes in highly imbalanced datasets, it showed remarkable performance on both high and low diversity datasets.


Promising Mass-Productive 4-Inch Commercial SERS Sensor with Particle in Micro-Nano Porous Ag/Si/Ag Structure Using in Auxiliary Diagnosis of Early Lung Cancer.
The construction of commercial surface enhanced Raman scattering (SERS) sensors suitable for clinical applications is a pending problem, which is heavily limited by the low production of high-performance SERS bases, because they usually require fine or complicated micro/nano structures. To solve this issue, herein, a promising mass-productive 4-inch ultrasensitive SERS substrate available for early lung cancer diagnosis is proposed, which is designed with a special architecture of particle in micro-nano porous structure. Benefitting from the effective cascaded electric field coupling inside the particle-in-cavity structure and efficient Knudsen diffusion of molecules within the nanohole, the substrate exhibits remarkable SERS performance for gaseous malignancy biomarker, with the limit of detection is 0.1 ppb and the average relative standard deviation value at different scales (from cm2 to µm2 ) is ≈16.5%. In practical application, this large-sized sensor can be further divided into small ones (1 × 1 cm2 ), and more than 65 chips will be obtained from just one 4-inch wafer, greatly increasing the output of commercial SERS sensor. Further, a medical breath bag composed of this small chip is designed and studied in detail here, which suggested high-specificity recognition for lung cancer biomarker in mixed mimetic exhalation tests.


Chemical Composition of Alphitobius diaperinus (Coleoptera: Tenebrionidae) Abdominal Glands and the Influence of 1,4-benzoquinones on its Behavior.
This study aimed to identify and quantify the compounds present in the abdominal glands of Alphitobius diaperinus Panzer, 1797 (Coleoptera: Tenebrionidae) and to evaluate the influence of these compounds on its behavior. The extraction of volatiles present in the abdominal glands was made by dissection (10 individuals per sex) and by air entrainment (200 insects per sex), and they were analyzed by gas chromatography-flame ionization detector, gas chromatograph-mass spectrometer, and gas chromatograph-electroantennography detector (GC-EAD). The influence of these volatiles on the behavior of conspecifics was evaluated in a four-arm olfactometer. Twenty-three compounds were identified from male and female abdominal gland extracts, of which six were quinones: the 2-methyl-1,4-benzoquinone and the 2-ethyl-1,4-benzoquinone were the major components, and 1,4 benzoquinone and three hydroquinones were registered for the first time for this species. The GC-EAD analysis using the crude extracts from abdominal glands showed that male and female antennae responded to the three major benzoquinones. For the olfactometer bioassays, both genders were repelled either by the abdominal gland extracts or by synthetic solutions containing the three benzoquinones. The results suggest that the 1,4-benzoquinones play a role as a repellent to A. diaperinus.


[Subjective aspects of pharmacotherapy in schizophrenia during implementation of chlorpromazine in Poland--a review].
Introduction of chlorpromazine was the breakthrough in psychiatric practice. Pharmacotherapy with chlorpromazine started in Polish hospitals in the autumn and winter in 1954 and the first papers covering clinical experiences started to be published in 1955. Some of these papers are very informative about subjective aspects of pharmacotherapy, comparison of older and new method of treatment, changes of psychiatric wards atmosphere. They inform also about some social aspects of introduction of this new drug to the practice. In the example families were involved in gaining the drugs for ill family members and doctors sometimes had to win persons' in charge consent to start treatment. In this papers the hope that patients treated with the new drug are more prone to psychotherapy have been expressed. This kind of hope is now expressed in regard to the second generation of antipsychotics. The paper of a Polish author published 1969 that is the pioneering work in the field of research of subjective aspects of pharmacotherapy is presented. Conclusions and methodology of this study are very similar to the later studies that were published in psychiatric literature at the end of 1970's.


Integrative view on how erythropoietin signaling controls transcription patterns in erythroid cells.
Erythropoietin (EPO) is necessary and sufficient to trigger dynamic transcriptional patterns that drive the differentiation of erythroid precursor cells into mature, enucleated red cells. Because the molecular cloning and Food and Drug Administration approval for the therapeutic use of EPO over 30 years ago, a detailed understanding of how EPO works has advanced substantially. Yet, the precise epigenetic and transcriptional mechanisms by which EPO signaling controls erythroid expression patterns remains poorly understood. This review focuses on the current state of erythroid biology in regards to EPO signaling from human genetics and functional genomics perspectives. The goal of this review is to provide an integrative view of the gene regulatory underpinnings for erythroid expression patterns that are dynamically shaped during erythroid differentiation. Here, we highlight vignettes connecting recent insights into a genome-wide association study linking an EPO mutation to anemia, a study linking EPO-signaling to signal transducer and activator of transcription 5 (STAT5) chromatin occupancy and enhancers, and studies that examine the molecular mechanisms driving topological chromatin organization in erythroid cells. The genetic, epigenetic, and gene regulatory mechanisms underlying how hormone signal transduction influences erythroid gene expression remains only partly understood. A detailed understanding of these molecular pathways and how they intersect with one another will provide the basis for novel strategies to treat anemia and potentially other hematological diseases. As new regulators and signal transducers of EPO-signaling continue to emerge, new clinically relevant targets may be identified that improve the specificity and effectiveness of EPO therapy.


Steric and hyperconjugative contributions to rotation barriers in diboron analogs B2L4 (L = F, OH, NH2, CH3, and H).
The rotational barriers of B(2)L(4) (where L = F, OH, NH(2), CH(3), and H) were investigated with respect to the hyperconjugation and steric effects at the levels of RHF, MP2, and B3LYP using a basis set of 6-311G(d,p). At all levels of theory, the LBBL dihedral angle of the minimum energy conformation was found to increase with decreasing electronegativity of the atom bonded to boron. The L substituents that possess no lone pairs have greater steric exchange energy, destabilizing the planar conformation relative to the perpendicular. However, the planar conformation of compounds with L substituents having lone pairs on the heavy atom is counterstabilized by conjugative delocalization into the "empty" p-orbitals associated with boron. For B(2)(NH(2))(4), neither factor dominates and the optimal geometry is skewed at a dihedral angle of 37.62 degrees (MP2).


P-glycoprotein expression and in vitro reversion of doxorubicin resistance by verapamil in clinical specimens from acute leukaemia and myeloma.
The expression of the P-glycoprotein which is associated with the development of multidrug resistance in various cell lines was investigated in 87 fresh acute leukaemia and multiple myeloma samples using the specific mouse monoclonal antibody MRK16 in an indirect immunofluorescence assay. Considering a 10% positive cell cut-off value, a heterogeneous expression of P-glycoprotein was observed in 5/22 (22.7%) de novo acute leukaemias, 7/22 (31.8%) relapse or secondary acute leukaemias, 14/27 (51.8%) acute transformation of myeloproliferative or myelodysplastic syndromes and 5/16 (31.2%) multiple myelomas. This expression was not associated with specific cytogenetic abnormalities, especially alterations of chromosome 7q. Verapamil, a calcium channel blocker, has been demonstrated to circumvent the multidrug resistance in cell lines, possibly by interfering with P-glycoprotein function. Using the microculture tetrazolium assay, verapamil was demonstrated to increase the sensitivity of fresh leukaemic or myeloma cells to doxorubicin in 19/43 (43.1%) samples. The doxorubicin IC50 level and the capacity of verapamil to increase the sensitivity of blast cells to doxorubicin in vitro did not correlate with the expression of P-glycoprotein. We conclude that high non-cytotoxic concentrations of verapamil were able to increase the in vitro doxorubicin sensitivity of fresh acute leukaemia and myeloma cells without detectable expression of the P-glycoprotein.


Proposal for a unified classification system and nomenclature of lagoviruses.
Lagoviruses belong to the Caliciviridae family. They were first recognized as highly pathogenic viruses of the European rabbit (Oryctolagus cuniculus) and European brown hare (Lepus europaeus) that emerged in the 1970-1980s, namely, rabbit haemorrhagic disease virus (RHDV) and European brown hare syndrome virus (EBHSV), according to the host species from which they had been first detected. However, the diversity of lagoviruses has recently expanded to include new related viruses with varying pathogenicity, geographic distribution and host ranges. Together with the frequent recombination observed amongst circulating viruses, there is a clear need to establish precise guidelines for classifying and naming lagovirus strains. Therefore, here we propose a new nomenclature based on phylogenetic relationships. In this new nomenclature, a single species of lagovirus would be recognized and called Lagovirus europaeus. The species would be divided into two genogroups that correspond to RHDV- and EBHSV-related viruses, respectively. Genogroups could be subdivided into genotypes, which could themselves be subdivided into phylogenetically well-supported variants. Based on available sequences, pairwise distance cutoffs have been defined, but with the accumulation of new sequences these cutoffs may need to be revised. We propose that an international working group could coordinate the nomenclature of lagoviruses and any proposals for revision.


Antitumor effects by Wilfoside C3N treatment in ECA109 cells.
C21 steroidal glycoside (C21) is one of the most bioactive compounds of Cynanchum auriculatum Royle, known as Baishouwu, and possesses potent antitumor activity. Wilfoside C3N is one of the two most abundant and active C21 in it. The aim of this study was to further investigate the antitumor activity of C3N and to clarify its signaling pathway. The growth inhibition ofECA109 cells induced by C3N was assessed. Western blot analysis, reverse-transcription PCR, caspase-2 and Fas activity assay, and knockdown of caspase-2 with siRNA were used to study the apoptotic mechanisms. We showed that C3N inhibited the proliferation of ECA109 cells moderately in a dose and time-dependent manner and induced apoptosis in the ECA109 cell line through a mitochondrial pathway by triggered cytochrome c release from the mitochondria, with caspase-2 functioning upstream of caspase-9 rather than association with Fas and caspase-8. Furthermore, C3N-driven apoptotic events were associated with downregulation of Bcl-2. These results suggest that C3N-induced apoptosis of ECA109 cells in vitro was dependent on caspase-2 or mitochondria or caspase-9 and independent of the Fas-FasL or caspase-8 pathway.


Tracking the prevention of folic acid-preventable spina bifida and anencephaly.
The fortification of wheat flour with folic acid prevents most cases of spina bifida and anencephaly by raising serum folate levels among women capable of bearing children, as does encouraging women to consume folic acid supplements prior to pregnancy. Unfortunately, surveillance is conducted in few countries where the need is greatest. A method for assessing the prevention of these birth defects is presented that combines fortification program information with country case prevalence estimates. This approach suggests that about 70% of all cases could be prevented within a year of implementation of fortification programs, were it not for the inertia of regulatory agencies. Professional researchers and clinicians can help combat this situation by becoming advocates for child health in their respective countries.


AutoRoot: open-source software employing a novel image analysis approach to support fully-automated plant phenotyping.
Computer-based phenotyping of plants has risen in importance in recent years. Whilst much software has been written to aid phenotyping using image analysis, to date the vast majority has been only semi-automatic. However, such interaction is not desirable in high throughput approaches. Here, we present a system designed to analyse plant images in a completely automated manner, allowing genuine high throughput measurement of root traits. To do this we introduce a new set of proxy traits. We test the system on a new, automated image capture system, the Microphenotron, which is able to image many 1000s of roots/h. A simple experiment is presented, treating the plants with differing chemical conditions to produce different phenotypes. The automated imaging setup and the new software tool was used to measure proxy traits in each well. A correlation matrix was calculated across automated and manual measures, as a validation. Some particular proxy measures are very highly correlated with the manual measures (e.g. proxy length to manual length, r2 > 0.9). This suggests that while the automated measures are not directly equivalent to classic manual measures, they can be used to indicate phenotypic differences (hence the term, proxy). In addition, the raw discriminative power of the new proxy traits was examined. Principal component analysis was calculated across all proxy measures over two phenotypically-different groups of plants. Many of the proxy traits can be used to separate the data in the two conditions. The new proxy traits proposed tend to correlate well with equivalent manual measures, where these exist. Additionally, the new measures display strong discriminative power. It is suggested that for particular phenotypic differences, different traits will be relevant, and not all will have meaningful manual equivalent measures. However, approaches such as PCA can be used to interrogate the resulting data to identify differences between datasets. Select images can then be carefully manually inspected if the nature of the precise differences is required. We suggest such flexible measurement approaches are necessary for fully automated, high throughput systems such as the Microphenotron.


[Evaluation of outpatient rehabilitation: goals, conceptual framework and study design of a health and pension insurance joint research project].
In Germany the statutory health and pension insurance schemes are the main providers of medical rehabilitation, the majority of rehabilitation measures being given in an inpatient setting. Over the last few years, the health and pension insurance schemes have strengthened the extension of outpatient rehabilitation, and have funded a comprehensive evaluation study in this context. In this evaluation study outpatient rehabilitation in centres with different conceptual backgrounds is compared with inpatient rehabilitation in rehab clinics, indications considered being cardiology and orthopaedics. Overall, 14 rehab centres and more than 2000 patients were included in the project. The patients were interviewed and medically examined before and after the measure. A follow-up was done after six and twelve months. In addition to the rehabilitants themselves, the rehab centre physicians as well as the office-practice physicians were interviewed about the outcome of the rehab measure. One year after rehabilitation, data were collected from the relevant health and pension insurance funds concerning the benefits the patients had received. Due to the study's non-experimental design, validity of the results is confined to rehabilitants participating on an outpatient basis and who had been found medically suited for this type of rehabilitation, were capable of travelling to the rehab centre on their own within less than 45 minutes and had voluntarily opted for the outpatient setting. The findings of the study show that outpatient rehabilitants' motivation and expectations differ from those found in inpatient rehabilitation. The health economics analysis performed is restricted to the costs involved in the rehabilitation measure as such as well as the health-related benefits provided to the rehabilitants in the twelve-month study period. The issue of whether increasing outpatient rehab measures will lead to decreasing costs in the rehab system as a whole had not been considered in the framework of this project.


Cloning and sequencing of an exoglucanase gene from Streptomyces sp. M 23, and its expression in Streptomyces lividans TK-24.
A gene encoding exoglucanase (CBHII) of Streptomyces sp. M 23 was cloned and sequenced. The cbhII gene consisted of 1359 bp capable of encoding a polypeptide of 453 amino acids with a calculated molecular mass of 45,175 Da. The deduced amino acid sequence showed homology with those of cellulases belonging to family 6 of the glycosyl hydrolases. The cbhII gene was subcloned into the plasmid pSEV1 and expressed in Streptomyces lividans TK-24. The transformed cells were able to secrete the enzyme efficiently in an active form. The CBHII expressed by S. lividans TK-24 was purified to homogeneity by SDS-polyacrylamide gel and characterized. The recombinant CBHII was stable up to 50 degrees C and more than 30% of the original activity remained after heating at 100 degrees C for 10 min. The amino-terminal amino acid sequence of the recombinant CBHII was identified as GPAAPTARVD. These results agreed well with the properties of the authentic CBHII.


Upregulation of interferon-alpha receptor expression in hydroxyurea-treated leukemia cell lines.
Interferon-alpha (IFN-alpha) shows its antitumor effect through binding to specific cell surface receptors. A DNA synthesis inhibitor, hydroxyurea (HU), has been successfully combined with IFN-alpha to improve the efficiency of IFN therapy for chronic myelogenous leukemia (CML). To understand the mechanism of this combination effect, expression of IFN-alpha receptors on the CML cell line, K562, was studied before and after treatment with HU. Cells were treated with HU at a dose of 0, 0.1, 0.2, or 0.4 mmol/L for 48 hours. Binding assays were performed using 125I-labeled IFN-alpha at 4 degrees C. Cell cycle analysis was carried out using flow cytometer following staining cellular DNA with propidium iodide. Northern blot analysis was performed to evaluate the inducibility of interferon regulatory factor-1 (IRF-1) gene expression by IFN-alpha. Hydroxyurea-treated cells showed a dose- and time-dependent increase in binding of 125I-labeled IFN-alpha (maximal 2.5-fold). The increase of binding was caused by an increase in the number of binding sites with a constant receptor affinity. Similar results were obtained in the Burkitt's lymphoma cell line, Daudi. Cell cycle analyses suggested that upregulation of the IFN receptor may have occurred as a result of the alteration in the cell cycle distribution. Furthermore, IFN-alpha induction of the IFN-inducible gene IRF-1 mRNA in HU-treated K562 cells was 2-fold higher than that in untreated cells. Thus, HU may have an ability to enhance the response to IFN-alpha probably because of its ability to upregulate the IFN-alpha receptors, suggesting that this may be involved in the mechanism of effective combination therapy of IFN-alpha with HU.


Impact of preoperative atrial fibrillation in patients with left ventricular assist device: A systematic review and meta-analysis.
Atrial fibrillation (AF) is a common finding in patients evaluated for left ventricular assist device (LVAD). There is conflicting data regarding the mortality risk as well as the thromboembolic risk in patients with preoperative AF who undergo LVAD implantation. We examined these risks by performing a meta-analysis. We performed a literature search of Pubmed, EMBASE, SCOPUS, and Cochrane from inception to February 2018. The eligible studies were used to compare mortality rate and thromboembolic risk between AF and Non-AF (NAF) groups after LVAD implantation. We obtained 391 articles from our search strategy. Seven retrospective studies were included and accounted for 5823 LVAD patients (AF 1589; NAF 4234). The median follow-up duration ranged from 7-24 months. The pooled analysis revealed a significantly increased risk of mortality in preoperative AF patients who underwent LVAD operation compared to those with NAF (Risk Ratio [RR] 1.16, 95% CI 1.05-1.28, I2 = 0%). Five studies reported thromboembolism events involving 1359 preoperative AF and 3893 NAF patients. The pooled analysis did not show a statistically significant association between risk of thromboembolic event and preoperative AF (Risk Ratio [RR] 1.08, 95% CI 0.86-1.36, I2 = 76.2%). Our study shows that preoperative AF may be associated with a higher mortality rate. This study is limited by the fact that the data are pooled from retrospective studies. Further prospective studies are warranted in order to validate these results.


The impact of partner's behaviour on pregnancy related outcomes and safe child-birth in Pakistan.
Pakistan is one of the nations with the worst statistics for pregnancy-related outcomes. Health programmes in underdeveloped nations frequently ignore the role of partners in maternal health, which is a crucial contributing factor in these worst situations. This research study aims to explore the role of husbands in maternity care and safe childbirth in Pakistan. The data for this study comes from the Pakistan Maternal Mortality Survey 2019. The k-Modes clustering algorithm was implemented to generate clusters from the dataset. Cluster profiling was used to identify the problems in pregnancy-related outcomes in cases where women live away from their partners. The chi-square test and logistic regression model were fitted to identify the significant factors associated with women's health and safe childbirth. The finding of the study reveals that the partner's support during and after pregnancy plays a vital role in maternal health and safe child-birth. It was revealed that the women living away from their partners have certain health problems during pregnancy. These problems include Vaginal bleeding, Excessive vomiting, Chest pain, Cough, High B.P, Excessive weight gain, Body aches, Swelling of feet, and Swelling of the face. This also leads to complications and health problems in the postpartum period. Due to a lack of antenatal care from the spouse during pregnancy, the women who lived away from their partners lost their pregnancies. The study concludes that the husband's emotional and financial support substantially impacts the overall health of expecting mothers and the safety of delivery in Pakistan. Given its potential advantages for mother and child health outcomes, male engagement in health education must be acknowledged and addressed. The finding of the study is of immense importance, as it guides the policymakers to arrange various awareness programs for the male partners to support their pregnant spouse and provide proper antenatal care.


Introduction to the Symposium.
In June 1995, the National Institute on Alcohol Abuse and Alcoholism sponsored a symposium on "Alcohol and Osteoporosis" at the Research Society on Alcoholism in Steamboat Springs, Colorado. The goals of the symposium were to: (a) disseminate current information on the effects of alcohol on osteoporosis, both deleterious and beneficial; (b) discuss the mechanisms, direct and indirect, by which alcohol affects bone remodeling; and (c) encourage research in the area of alcohol and osteoporosis. This report provides an introduction to the problem, as well as to the three scientific presentations. Key Words: Alcohol, Osteoporosis, Bone.


A Sensitive and Biodegradable Pressure Sensor Array for Cardiovascular Monitoring.
An array of highly sensitive pressure sensors entirely made of biodegradable materials is presented, designed as a single-use flexible patch for application in cardiovascular monitoring. The high sensitivity in combination with fast response time is unprecedented when compared to recent reports on biodegradable pressure sensors (sensitivity three orders of magnitude higher), as illustrated by pulse wave velocity measurements, toward hypertension detection.


Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the 'effector' region.
We have characterized two new ras-related genes rap1 and rap2 from a human cDNA library, by hybridization with the Drosophila Dras3 gene at low stringency conditions. The rap1 and rap2 genes encode proteins of 184 and 183 amino acid respectively with molecular weights of 20.9 kd and 20.7 kd. These proteins are 53% and 46% identical to the human K-ras protein and share several properties with the classical ras proteins. The C-terminal cysteine involved in the membrane anchoring as well as the GTP binding regions of the p21 ras proteins are present in the rap proteins suggesting that these proteins could bind GTP/GDP and have a membrane localization. The most striking difference between the rap and ras proteins resides in their 61st amino acid. As in the Drosophila Dras3 protein, both rap proteins have a threonine instead of the glutamine found at position 61 of the classical ras proteins. Furthermore the putative effector domain of the ras proteins is strictly conserved in the rap1 protein whereas only one amino acid difference is found in the rap2 protein. This suggests that the rap proteins might interact with the same effector as the ras proteins.


Theoretical study of the structure and optical properties of carbon-doped rutile and anatase titanium oxides.
The structure and optical properties of carbon-doped titanium oxides, TiO2, in the rutile and anatase forms have been investigated theoretically from first principles. Two possible doping sites were studied, carbon at an oxygen site (anion doping) and carbon at a titanium site (cation doping). The calculated structures suggest that cation-doped carbon atoms form a carbonate-type structure, whereas anion-doped carbon atoms do not invoke any significant structural change. A density-of-states analysis revealed three in-gap impurity states for anion doping. The optical properties of anion-doped cells qualitatively agree with the experimentally reported visible-light absorbance values. We ascribe part of the absorption to transitions from the valence band to one of the impurity states. These transitions should be able to promote photocatalytic reactions, because electron holes in the valence band are considered to be crucial for this process. Neither in-gap impurity states nor visible-light absorbance were observed in the case of cation doping. The effect of oxygen vacancies was also investigated. Introduction of oxygen vacancies into anion-doped TiO2 populates the impurity states and thus suppresses photocatalysis. The interaction of a doped carbon atom with an oxygen vacancy at a finite spatial separation was also carried out. The possibility of either a carbon-oxygen vacancy pair or higher carbon-oxygen vacancy complex existing is discussed.


The fetus, not the mother, elicits maternal immunologic rejection: lessons from discordant dizygotic twin placentas.
Our objective was to elucidate the pathogenesis of twin discordance in four dizygotic pregnancies where only one of the twins had IUGR due to chronic villitis. We identified four cases of dizygotic twin placentas over a period of four years with evidence of chronic villitis. There was no clinical or pathologic evidence of TORCH, bacterial infection, preeclampsia or autoimmune disorders. Placentas were weighed, processed for histologic examination and stained with CD45RO (clone UCHL1) mouse monoclonal antibody, which identifies T-cells. All placentas were dichorionic, with two being fused. Birth weight differences were 29%, 41%, 17% and 10%. Villitis was more marked in the placenta of the twin that weighed less and correlated with the degree of weight discordance. On examining the junction between the fused dichorionic placentas, the chorionic villi from the smaller twin contained numerous T-cells, whereas the villi associated with the less affected twin, showed little to no T-cells. We describe a series of dizygotic twin placentas where the more severe the chronic villitis, the more affected the placenta and fetus. Since the maternal environment was constant for each of these twins, differences in villitis severity appears to be attributable to differences in the ability of each placenta to induce a maternal immune response.


Strontium Fixation by Lime Contained in Soils.
The suitability of soils for the disposal of radioactive strontium waste products is determined in part by the amount and properties of calcium carbonate in the soil. Analyses of the strontium ion concentrations in the effluent solution of soil columns and x-ray diffraction patterns suggest that a fraction of the strontium ions is precipitated as strontium carbonate.


Human myocardial ATP content and in vivo contractile function.
The study was designed to characterize the relationship between the metabolite content of human cardiac muscle and in vivo cardiac function. ATP, total adenine nucleotides, and NAD were quantified in human myocardial biopsies using high performance liquid chromatography. Right ventricular endomyocardial biopsies were obtained from 43 patients with dilated cardiomyopathy, 6 with restrictive cardiomyopathy, 10 with normal systolic and diastolic function, and from 24 cold preserved human donor hearts. Transmural samples of failing right and left ventricular free walls were obtained during cardiac transplantation surgery in 8 patients. ATP, total adenine nucleotides, and NAD were similar in the cold-preserved donor hearts and in right ventricular endomyocardial biopsies from the 10 individuals with normal systolic and diastolic function. In contrast, these values were significantly depressed in tissue samples from patients with dilated or restrictive cardiomyopathy. There was a significant correlation between ATP and pulmonary capillary wedge pressures but not ejection fractions. Declines in the sizes of myocardial ATP, adenine nucleotide, and pyridine nucleotide pools in the human myocardium are associated primarily with diastolic but not systolic dysfunction.