An international collaborative study of the epidemiology of esophageal atresia or stenosis.
Epidemiologic data were analyzed for a total of 2,693 infants with esophageal atresia registered in nine congenital malformation registries around the world. The average recorded prevalence at birth was 2.6 per 10,000 births, with a significant variability among programs--and sometimes within a program--and a maximum prevalence of above 3 per 10,000 births. Clusters of infants with esophageal atresia were observed but may be random. An increasing rate was seen during the period 1965 to 1975 (Norway, South America, Sweden). The type of esophageal atresia was specified in only 439 cases, but no major differences were seen in the epidemiologic characteristics of infants with the most common type (distal fistula) and infants with other types. There was an excess of low birth weight and preterm birth, and infants with esophageal atresia had a birth weight 500 to 1,000 g less than normal infants in each gestational week. There was an excess of twins, apparently mainly or exclusively due to monozygotic twinning, but in only two pairs did both twins have esophageal atresia. There was no effect seen of maternal age, but low parity, irrespective of maternal age, was associated with an increased risk for esophageal atresia. Infant survival varied among programs and depended heavily on associated malformations. Among 1,107 sibs born before the proband and 385 born after the proband, only 25 (1.7%) had a serious malformation; three had esophageal atresia. In 57.3% of the infants with esophageal atresia, no other malformations were present, in 36.4% other major malformations were recorded, and in 6.3% there were chromosomal anomalies. The malformations present associated with esophageal atresia were analyzed: a large proportion entered the constellation sometimes called "caudal mesoderm spectrum of malformations": VATER, Potter, and caudal regression sequences.


Determinants of body weight changes during COVID-19 pandemic in older urban residents.
COVID‑19 pandemic is associated with unfavorable body weight changes. However, little is known about these changes in older individuals, a particularly vulnerable group with limited representation in both direct and online research. The aims of the study were to assess changes in body weight and determinants of thesechanges, and to evaluate the prevalence of COVID‑19 history and its impact on the changes in body weight in older individuals. The analysis included 2076 residents of Kraków, aged 60 to 84 years. Data on sociodemographic factors, lifestyle, history of COVID‑19, and changes in body weight were collected in 2021 and 2022 by a postal survey. Multinomial logistic regression analysis was used. COVID‑19 tests were performed in 29.3% of the participants, with one‑third of them being positive. A total of 14.3% of the participants had any history of COVID‑19. Almost two‑thirds of the study participants declared no change in their body weight during the pandemic, while 26.2% gained weight. The weight gain was associated with unfavorable sociodemographic and lifestyle conditions. Weight loss was reported by 11.3% of the participants, and it was associated with poor perceived health and a history of COVID‑19. After adjusting for covariates, the history of COVID‑19 was associated with about 4 times higher odds of weight loss in any case (odds ratio [OR], 2.69; 95% CI, 1.59-4.57 for nonhospitalized, and OR, 18.96; 95% CI, 5.64-63.73 for hospitalized individuals). Most people with a change in their body weight gained weight due to unfavorable lifestyle modifications, but the history of COVID‑19, especially hospitalization, was a strong determinant of body weight loss.


Atomoxetine for suppression of vasovagal syncope.
Vasovagal syncope (VVS) is a common clinical condition with few effective medical therapies. The study aimed to evaluate the effectiveness of atomoxetine in suppressing syncope in patients with recurrent VVS. This was a retrospective, open-label, observational case series of 12 patients taking atomoxetine for suppression of recurrent vasovagal syncope. We compared syncope frequency in the 1 year before atomoxetine and while subjects were taking atomoxetine. We used novel applications of the Poisson distribution to describe the results as a collection of n = 1 studies. There were 12 subjects, eight female, with a mean age 47 ± 22 years and a mean Calgary Syncope Symptom Score of 2 (diagnostic of vasovagal syncope). The patients received a mean dose of atomoxetine of 66 ± 16 mg (1.06 ± 0.21 mg/kg). The mean follow-up period was 1.21 ± 1.01 years. While taking atomoxetine, 11/12 patients appeared to improve and 7/12 had no syncope in follow-up (p = 0.0046). The annualized syncope frequency decreased from a median 5.5 (IQR 4, 6.75) syncope per year to 0 (IQR 0, 0.88) syncope per year (p = 0.002, Wilcoxon rank-sum test). According to the Poisson distribution, 7/12 subjects significantly improved with p values of < 0.0001 to 0.0235, 3/12 did not faint but had too brief follow-up times to detect significance, and 2/12 did not improve significantly. In this case series, atomoxetine was a promising oral agent for the prevention of vasovagal syncope. The Poisson distribution permits individual patient-level assessment of improvement and detects insufficient follow-up despite apparent improvement.


Measuring behavioral momentum.
The metaphor of behavioral momentum proposes that when ongoing operant behavior is disrupted, changes in response rate are directly related to a force-like aspect of the disruptor and inversely proportional to behavioral mass. Several data sets suggest that differential resistance to change between the components of a multiple schedule satisfies the requirements of a ratio scale and is additive when different disruptors and different dimensions of reinforcement are combined. Differential resistance also provides a basis for scaling force in relation to rate of food presentation between components as a disruptor, and for scaling mass in relation to food rate within a component as a reinforcer. Preference in concurrent chains with terminal links identical to multiple-schedule components also meets the requirements of ratio-scale measurement, is additive when different dimensions of reinforcement are combined, and provides convergent measurement of behavioral mass.


Pilot study of the DART tool - an objective healthcare simulation debriefing assessment instrument.
Various rating tools aim to assess simulation debriefing quality, but their use may be limited by complexity and subjectivity. The Debriefing Assessment in Real Time (DART) tool represents an alternative debriefing aid that uses quantitative measures to estimate quality and requires minimal training to use. The DART is uses a cumulative tally of instructor questions (IQ), instructor statements (IS) and trainee responses (TR). Ratios for IQ:IS and TR:[IQ + IS] may estimate the level of debriefer inclusivity and participant engagement. Experienced faculty from four geographically disparate university-affiliated simulation centers rated video-based debriefings and a transcript using the DART. The primary endpoint was an assessment of the estimated reliability of the tool. The small sample size confined analysis to descriptive statistics and coefficient of variations (CV%) as an estimate of reliability. Ratings for Video A (n = 7), Video B (n = 6), and Transcript A (n = 6) demonstrated mean CV% for IQ (27.8%), IS (39.5%), TR (34.8%), IQ:IS (40.8%), and TR:[IQ + IS] (28.0%). Higher CV% observed in IS and TR may be attributable to rater characterizations of longer contributions as either lumped or split. Lower variances in IQ and TR:[IQ + IS] suggest overall consistency regardless of scores being lumped or split. The DART tool appears to be reliable for the recording of data which may be useful for informing feedback to debriefers. Future studies should assess reliability in a wider pool of debriefings and examine potential uses in faculty development.


Characterization of ultraviolet light-induced relaxation of the isolated duodenum of the rat.
1 Isolated duodenum of the rat, exposed to ultraviolet (u.v.) light in the presence of NO2 ions, responded with reversible relaxation. 2 The photorelaxation response did not seem to involve any known receptor mechanisms and was independent of any ganglionic or neuronal influences. 3 Changes in the ionic environment of the tissue showed that NA+ and Ca2+ were essential for the photorelaxation. K+ depolarized-tissue did not show the photoresponse. 4 The presence of the metabolic inhibitors, iodoacetic acid, 2,4-dinitrophenol, sodium fluoride, sodium azide or potassium cyanide, abolished the photorelaxation response. 5 It is proposed that the photorelaxation of the tissue resulted from the liberation of metabolic energy following NO2 ion-dependent absorption of u.v. light energy, which in turn, interfered with the Na+ ion movement across the cell membrane.


Modeling the effects of elevation and precipitation on Rice (Oryza sativa L.) production considering multiple planting methods and cultivars in Central China.
In this study, we investigated the effects of elevation and precipitation on rice (Oryza sativa L.) production using the Crop Environment Resource Synthesis (CERES)-Rice model in Hubei province, China. We divided our study area into four zones based on elevation and precipitation. For each zone, our simulations were conducted using three planting methods: dry direct-seeded rice (DDSR), wet direct-seeded rice (WDSR), and transplanted-flooded rice (TFR), with three rice cultivars of different growth duration: Yangliangyou6 (long-duration), Huanghuazhan (mid-duration), and Lvhan1 (short-duration). Additionally, the optimal irrigation strategy for WDSR was determined with the CERES-Rice model. Our results indicated that the yields of WDSR with the optimal irrigation strategy were comparable with those of TFR in low-elevation regions but were less than the TFR yields in high-elevation areas. Furthermore, the rice yields increased at first and then decreased with increasing elevation, which was affected by growing period length and photosynthesis rate. Compared with the other two cultivars, the short-duration cultivar may be more suitable for growing in high-elevation regions. In addition, high precipitation could facilitate the cultivation of the long-duration cultivar in low-elevation regions, as it gives DDSR a yield potential comparable to that of WDSR for the short-duration cultivar in high-elevation regions. This study could help farmers choose optimal field management practices based on elevation and precipitation, ensuring sustainable and improved rice production.


Anaesthesiological airway management in Denmark: assessment, equipment and documentation.
Failed intubation remains one cause of anaesthesia-related morbidity and mortality. In a recent survey in Denmark, 20% of respondents reported preventable mishaps in airway management. Assessment of the airway, and its documentation, as well as the availability of various equipment to manage a difficult airway, and the existence of a failed intubation plan were surveyed by mailing a questionnaire to the clinical directors of all 69 anaesthesia departments in Denmark. Fifty-six departments (81%) returned the questionnaire. Pre-operative airway evaluation is performed in 90% of the departments. The tests included the mouth-opening test (77%), Mallampati score (48%), lower jaw protrusion (34%), neck mobility (63%), the measurement of the thyromental (11%) and sternomental distance (4%). The result of the tests are documented by 38% of the departments in the anaesthetic chart (96%), in the record (54%), on a card given to the patient (23%), in a letter sent to the patient's general practitioner (2%) or in a database (13%). The patients are personally informed in 82% of the departments. Only 54% of the departments have a failed intubation plan readily available. The preoperative assessment of the airways and its documentation is still unsatisfactory, as is communicating with the patient after a case of a difficult/impossible intubation. The adoption of internationally recognized recommendations might improve airway management and teaching to the best standard possible in the already well-equipped Danish anaesthetic departments.


Superficial warming and cooling of the leg affects walking speed and neuromuscular impairments in people with spastic paraparesis.
People with hereditary and spontaneous spastic paraparesis (HSSP) report that their legs are stiffer and walking is slower when their legs are cold. This study explored the effects of prolonged superficial cooling and warming of the lower leg on walking speed and local measures of neuromuscular impairments. This was a randomised pre- and post-intervention study of 22 HSSP participants and 19 matched healthy controls. On 2 separate occasions, one lower leg was cooled or warmed. Measurements included walking speed and measures of lower limb impairment: ankle movement, passive muscle stiffness, spasticity (stretch reflex size), amplitude and rate of force generation in dorsi- and plantarflexors and central and peripheral nerve conduction time/velocity. For both participants and controls, cooling decreased walking speed, especially for HSSP participants. For both groups, cooling decreased the dorsiflexor rate and amplitude of force generation and peripheral nerve conduction velocity and increased spasticity. Warming increased dorsiflexor rate of force generation and nerve conduction velocity and decreased spasticity. Superficial cooling significantly reduced walking speed for people with HSSP. Temperature changes were associated with changes in neuromuscular impairments for both people with spastic paraparesis and controls. This study does not support the use of localised cooling in rehabilitation for people with spastic paraparesis as reported in other neurological conditions. Rehabilitation interventions that help prevent heat loss (insulation) or improve limb temperature via passive or active means, particularly when the legs and/or environment are cool, may benefit people with spastic paraparesis.


Beneficiaries of Rehabilitation.
Recent research and the actions of the World Health Organization (WHO) have clarified the nature and value of rehabilitation as a key health strategy of the 21st century. However, strengthening rehabilitation in national health systems around the world is a challenge, partly because there is not an evidence-based argument that rehabilitation is a good economic and social investment. This argument, in turn, depends on characterizing the current and potential beneficiaries of rehabilitation, namely the individuals who could benefit from rehabilitation services whether or not they currently receive these services. Although identifying current beneficiaries is essential for evaluating the current demand for rehabilitation in existing health systems, as well as for making the economic investment case for rehabilitation within national health systems, it is only by characterizing potential beneficiaries that we can identify unmet needs and the potential social effect of rehabilitation. The objective of this study is to take a preliminary step toward both tasks by offering an overview of intuitively plausible approaches to characterizing beneficiaries of rehabilitation and to highlight limitations and challenges with each approach. We rely on the WHO's definition of rehabilitation, particularly the aim of rehabilitation to "optimize functioning and reduce disability," as our starting point.


Elevated pH-mediated mitigation of aluminum-toxicity in sweet orange (Citrus sinensis) roots involved the regulation of energy-rich compounds and phytohormones.
For the first time, we used targeted metabolome to investigate the effects of pH-aluminum (Al) interactions on energy-rich compounds and their metabolites (ECMs) and phytohormones in sweet orange (Citrus sinensis) roots. The concentration of total ECMs (TECMs) was reduced by Al-toxicity in 4.0-treated roots, but unaffected significantly in pH 3.0-treated roots. However, the concentrations of most ECMs and TECMs were not lower in pH 4.0 + 1.0 mM Al-treated roots (P4AR) than in pH 3.0 + 1.0 mM Al-treated roots (P3AR). Increased pH improved the adaptability of ECMs to Al-toxicity in roots. For example, increased pH improved the utilization efficiency of ECMs and the conversion of organic phosphorus (P) from P-containing ECMs into available phosphate in Al-treated roots. We identified upregulated cytokinins (CKs), downregulated jasmonic acid (JA), methyl jasmonate (MEJA) and jasmonates (JAs), and unaltered indole-3-acetic acid (IAA) and salicylic acid (SA) in P3AR vs pH 3.0 + 0 mM Al-treated roots (P3R); upregulated JA, JAs and IAA, downregulated total CKs, and unaltered MEJA and SA in P4AR vs pH 4.0 + 0 mM Al-treated roots (P4R); and upregulated CKs, downregulated JA, MEJA, JAs and SA, and unaltered IAA in P3AR vs P4AR. Generally viewed, raised pH-mediated increments of JA, MEJA, total JAs, SA and IAA concentrations and reduction of CKs concentration in Al-treated roots might help to maintain nutrient homeostasis, increase Al-toxicity-induced exudation of organic acid anions and the compartmentation of Al in vacuole, and reduce oxidative stress and Al uptake, thereby conferring root Al-tolerance. In short, elevated pH-mediated mitigation of root Al-stress involved the regulation of ECMs and phytohormones.


Flaccid quadriparesis associated with Yersinia enterocolitis-induced hypokalemia.
A 23-year-old woman presented with diarrhea, flaccid quadriparesis, a low serum potassium level, and an elevated creatine kinase level. A stool culture yielded Yersinia enterocolitica, and a muscle biopsy was compatible with a hypokalemic myopathy. The patient's diarrhea responded to sulfamethoxazole and trimethoprim therapy. We suggest that Y enterocolitica be added to the group of intestinal pathogens capable of producing hypokalemia and rhabdomyolysis.


Cerebral iodized lipid embolization via a pulmonary arteriovenous shunt: rare complication of transcatheter arterial embolization for hepatocellular carcinoma.
We report the first European case of cerebral iodized lipid embolism post transcatheter arterial embolization for hepatocellular carcinoma. Lipiodol emboli and corresponding multifocal brain ischemia were documented with computed tomography (CT) and magnetic resonance (MR) in the acutely symptomatic patient. Transcranial Doppler sonography with contrast indicated a right-to-left shunt, while on a follow-up CT scan lipiodol embolization was detected in both lungs. Dilated pulmonary vessels and thick vascular channels were seen in the vicinity of the right diaphragm suggestive of pulmonary arteriovenous shunt. The patient symptoms regressed with supportive care alone, but he died 5 months later due to hepatic failure unrelated to the procedure.


[An unusual form of cogwheel macula degeneration: central and paramacular alveolar pigment epitheliopathy (author's transl)].
A peculiar and rare form of spoke-like macular lesion is described as found bilaterally in a 53 year old woman. The unmistakable ophthalmoscopic and angiographic findings are also discussed. Although the clinical picture can be explained by a pigment epitheliopathy with secondary involvement of the neuroepithelium, the precise etiology of this fundus disease still remains problematic.


Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantitative determination of gamithromycin in animal plasma, lung tissue and pulmonary epithelial lining fluid.
A sensitive and specific method for the quantitative determination of gamithromycin in animal plasma, lung tissue and pulmonary epithelial lining fluid (PELF) using liquid chromatography combined with heated electrospray ionization tandem mass spectrometry (LC-MS/MS) was developed. The sample preparation was rapid, straightforward and consisted of a deproteinization and phospholipid removal step using an Oasis(®) Ostro™ 96-well plate (chicken, turkey and calf plasma) or HybridSPE(®)-Phospholipid SPE cartridges (pig plasma and turkey lung tissue), while a liquid-liquid extraction with diethyl ether in alkaline medium was used for PELF of turkey poults. Chromatography was performed on a C18 Hypersil GOLD column using 0.01M ammonium acetate in water with a pH of 9, and acetonitrile as mobile phases. The MS/MS instrument was operated in the positive electrospray ionization mode and the following selected reaction monitoring transitions were monitored for gamithromycin (protonated molecule>product ion): m/z 777.45>619.35 and m/z 777.45>157.80 for quantification and identification, respectively. The method was validated in-house: matrix-matched calibration graphs were prepared and good linearity (r≥0.99) was achieved over the concentration ranges tested (2.5-10,000ngmL(-1) for chicken, pig and calf plasma; 5.0-2500ngmL(-1) for turkey plasma; 50-10,000ngg(-1) for turkey lung tissue and 20-1000ngmL(-1) for turkey PELF). Limits of quantification (LOQ) were 2.5ngmL(-1) for chicken, pig and calf plasma and 5.0ngmL(-1) for turkey plasma, while the limits of detection (LOD) ranged between 0.007 and 0.07ngmL(-1). For lung tissue and PELF, respective LOQ and LOD values of 50ngg(-1) and 0.76ngg(-1) (lung tissue) and 20ngmL(-1) and 0.1ngmL(-1) (PELF) were obtained. The results for the within-day and between-day precision, expressed as relative standard deviation (RSD), fell within the maximal RSD values. The accuracy fell within -30% to +10% (concentrations 1-10ngmL(-1)) or -20% to +10% (concentrations>10ngmL(-1) or ngg(-1)) of the theoretical concentration. The method was successfully applied for the quantitative determination of gamithromycin in plasma samples of chickens, turkeys, pigs and calves; and in lung tissues and PELF of turkeys, all derived from pharmacokinetic studies in these animal species.


Spontaneous CSF fistula as a manifestation of idiopathic intracranial hypertension.
Spontaneous cerebrospinal fluid (CSF) fistula, of unknown origin, is a rare condition whose aetiology is increasingly related to idiopathic intracranial hypertension (IIH). This study tries to raise awareness that they should not be considered as two different processes, but that fistulas can be a form of debut, requiring a study and subsequent treatment. Repair techniques are described, as well as the study of HII. We treated 8 patients, 5 women and three men, aged between 46 and 72 years, with a diagnosis of spontaneous CSF fistula, four nasal and four otics who underwent surgical treatment. After repair, a diagnostic study was performed for IIH by MRI and Angio-MRI, presenting in all cases a transverse venous sinus stenosis. The intracranial pressure values obtained by lumbar puncture showed values of 20mm Hg or higher. All patients were diagnosed with HII. The one-year follow-up did not reveal any recurrence of the fistulas, maintaining a control of the HII. Despite their low frequency of both cranial CSF fistula and IIH, an association of both conditions should be considered by continuing the study and surveillance of these patients after fistula closure.


Mesenteric ischemia.
Mesenteric ischemia secondary to vascular disease remains a significant problem in patients presenting with acute abdominal conditions, especially if they are elderly. Although rare, it is nevertheless an important and perhaps increasing cause of death or significant morbidity. Occasionally, it may be a mode of dying, but more often, it is the reason for death. Individual cases can manifest an almost overwhelming spectrum from chronic to acute, mild to catastrophic, arterial to venous, occlusive to hemodynamic, extensive to limited, or precisely diagnosed to accidentally found. Treatment principles are well defined, but continued refinement of supportive therapies of several types is occurring. In contrast, improved screening tests that can lead to early specific etiologic diagnosis remain at the experimental stage. Thus, good "clinical suspicion" is foremost and essential.


Presence and chromosomal subtyping of Legionella species in potable water systems in 20 hospitals of Catalonia, Spain.
To investigate the presence and clonal distribution of Legionella species in the water supply of 20 hospitals in Catalonia, Spain. 20 hospitals in Catalonia, an area of 32,000 km2, located in northeast Spain. Environmental cultures of 186 points of potable water supply and 10 cooling towers were performed for the presence of Legionella species. Following filtration and acid treatment, the samples were seeded in selective MWY (modified Wadowsky Yee)-buffered charcoal yeast extract-alpha agar. All isolates obtained were characterized microbiologically and genotyped by SfiI pulsed-field gel electrophoresis (PFGE). 73 of 196 water samples, representing 17 of the 20 hospitals included in the study, were positive for Legionella pneumophila (serogroups 1, 2-14, or both). The degree of contamination ranged from 200 to 74,250 colony-forming units/L. Twenty-five chromosomal DNA subtypes were detected by PFGE. A single DNA subtype was identified in 10 hospitals, 2 DNA subtypes were observed in 6 hospitals, and 1 hospital exhibited 3 different DNA subtypes. Each hospital had its own Legionella DNA subtype, which was not shared with any other hospitals. Legionella was present in the water of most of the hospitals studied; each such hospital had a unique, dominant chromosomal DNA subtype. The verification of several genomic DNA restriction profiles in such a small geographic area demonstrates the great genetic diversity of Legionella in the aquatic environment.


Study roadmap for high-throughput development of easy to use and affordable biomarkers as diagnostics for tropical diseases: a focus on malaria and schistosomiasis.
Interventions are currently being used against 'infectious diseases of poverty', which remain highly debilitating and deadly in most endemic countries, especially malaria, schistosomiasis, echinococcosis and African sleeping sickness. However, major limitations of current 'traditional' methods for diagnosis are neither simple nor convenient for population surveillance, and showed low sensitivity and specificity. Access to novel technologies for the development of adequate and reliable tools are expressly needed. A collaborative project between African Network for Drugs and Diagnostics Innovation and partner institutions in Africa and China aims to screen suitable serological biomarkers for diagnostic pipelines against these 'diseases of the poor'. Parasite-specific exposed versus unexposed individuals were screened and sera or urine/stools were collected through case-control studies in China and African countries. Target genes/open reading frames were selected, then will be cloned and cell-free expressed, quantified and immuno-detected. Target antigens/epitopes will be probed and screened with sera from exposed or unexposed individuals using a high-throughput antigen screening platform as the study progresses. The specificity and sensitivity of highly immunoreactive biomarkers will be evaluated as well, using enzyme-linked immunosorbent assays or dipsticks. This roadmap explicitly unfolds the integrated operating procedures with focus on malaria and schistosomiasis, for the identification of suitable biomarkers that will aid the prioritization of diagnostics for population use. However, there is need to further validate any new diagnostic through comparison with standard methods in field deployable tests for each region. Our expectations for the future are to seek regulatory approval and promote the use of diagnostics in endemic areas.


Comparison of zinc reduction with platinum reduction for analysis of deuterium-enriched water samples for the doubly labeled water technique.
Isotope ratio mass spectrometry of hydrogen and oxygen is frequently used to determine total energy expenditure (TEE) using doubly labeled water. Conventionally, hydrogen isotope ratio is determined in hydrogen gas generated from water samples using zinc reduction. We compare this with a new automated platinum method to determine the ratios of hydrogen isotopes in deuterium-enriched water samples. The platinum method of sample preparation was compared with the zinc method in three ways: analytical variation in deuterium enrichment (within sample; n = 51), analytical variation in TEE estimates (within sample set; n = 10), and level of agreement of TEE estimates between both methods (n = 14). For the zinc method, the standard deviation for multiple sets of triplicate 2H2O sample analysis was +/-4.36 per thousand and +/-2.07 per thousand for platinum. The correlation between TEE estimates when sample sets were analyzed in duplicate was r = 0.89 for zinc and r = 0.83 for platinum. The intercept and slope of the regression line were significantly different from the line of identity for duplicate TEE estimates by zinc but were not different from the line of identity for platinum. After correction for the intra-assay variation of each method, the correlation between zinc and platinum for TEE was 0.77, and the intercept, but not the slope, of the regression was significantly different from the line of identity. The mean difference between the zinc method and the platinum method was 56 kcal/day, and the 95% confidence interval was -438 to 550 kcal/day. These data suggest that the platinum method is at least as reliable as the zinc method as a sample preparation technique for isotope ratio mass spectrometry of deuterium-enriched water samples. The platinum method is also less costly and less labor-intensive than the zinc method.


The effect of acute aromatase inhibition on breast parenchymal enhancement in magnetic resonance imaging: a prospective pilot clinical trial.
The breast is highly hormonally sensitive especially to the sex steroid hormone estrogen. Both physiological and iatrogenic steroid hormone modifications could affect how the breast tissue may appear in breast imaging techniques. We hypothesized that estrogen deprivation therapy could reduce breast nonspecific enhancement on magnetic resonance imaging (MRI). This study was a prospective pilot phase II clinical trial. The study was approved by Health Canada and the institutional research ethics board, and participants signed informed consent forms. Sixteen healthy postmenopausal women were enrolled, and 14 completed the study. Baseline breast MRI was done followed 1 month later by administration of a high-dose aromatase inhibitor (letrozole 12.5 mg/day) for 3 successive days before a second breast MRI. Background breast parenchymal enhancement was compared between the pretreatment and posttreatment studies. There was a statistically significant reduction of the average background breast enhancement after treatment with aromatase inhibitors compared with baseline MRI. Of particular interest, specific areas of benign breast enhancement were reduced after aromatase inhibitor treatment. No significant adverse effects were recorded using this relatively high dose of the aromatase inhibitors. This preliminary study provided evidence that aromatase inhibitors could reduce the parenchymal background enhancement of benign breast tissue during MRI and may improve the specificity of the technique.


Antigen-specific T contrasuppressor factor in cell-mediated immunity: interactions leading to eradication of the tolerant state.
Interactions between a T cell-derived, antigen-specific, contrasuppressor factor (TcsF) and immune T cells that block the action of T suppressor factors and allow the transfer of cellular immunity into tolerant recipients are described. Immune T cells from contact-sensitized donors are capable of transferring specific immunity into normal recipients but not into animals rendered tolerant to the specific antigen. Brief exposure of the immune cells to the TcsF enables the effective transfer of immunity into such tolerant recipients. In addition, treated immune cells become resistant to subsequent exposure to T suppressor factor (capable of inhibiting transfer of immunity to normal recipients). A cyclophosphamide-sensitive, I-J+, Ly-2 T transducer cell is required in the immune donor cell population for contrasuppression to be induced by the TcsF plus specific antigen. These cells release an antigen-non-specific contrasuppressive factor capable of rendering immune targets, depleted of transducer cells, resistant to suppression (either by suppressor factor or in the tolerant recipient). The results indicate that contrasuppression in contact sensitivity is antigen specific and that the balance of suppression and contrasuppression determines tolerance vs responsiveness in this system. The symmetrical resemblance of the contrasuppressive interactions to those of suppression in contact sensitivity are discussed.


AAV-P125A-endostatin and paclitaxel treatment increases endoreduplication in endothelial cells and inhibits metastasis of breast cancer.
Endostatin potentiates the antimitotic effects of paclitaxel (taxol) on endothelial cells (ECs). P125A-endostatin and taxol-treated ECs showed multipolar spindles and nuclear lobulation, leading to mitotic catastrophe and cell death. Induction of nuclear abnormalities was found to be dependent on β-catenin levels as wnt-mediated overexpression of β-catenin reversed the changes in nuclear morphology. These results prompted us to investigate whether antiangiogenic gene therapy and paclitaxel chemotherapy can synergistically inhibit angiogenesis and tumor growth. We first determined the effect of combination treatment in a transgenic mouse model of breast cancer. Intramuscular injection of recombinant adeno-associated virus type-2 virus induced sustained expression of P125A-endostatin. In vivo studies showed that combination therapy inhibited mammary cancer growth, delayed the onset of multifocal mammary adenocarcinomas, decreased tumor angiogenesis and increased survival in treated mice. In a second model, female athymic mice were orthotopically transplanted with a metastatic human breast cancer cell line. Antiangiogenic gene therapy in combination with paclitaxel inhibited tumor angiogenesis and lung/lymph-node metastasis in this model. These studies demonstrate cooperation between endostatin gene therapy and chemotherapy to inhibit tumor initiation, growth and metastasis.


Enhancing antifungal properties of chitosan by attaching isatin-piperazine-sulfonyl-acetamide pendant groups via novel imidamide linkage.
World health organization listed fungi as priority pathogens in 2022 to counter their adverse effects on human well-being. The use of antimicrobial biopolymers is a sustainable alternative to toxic antifungal agents. In this study, we explore chitosan as an antifungal agent by grafting a novel compound N-(4-((4-((isatinyl)methyl)piperazin-1-yl)sulfonyl)phenyl) acetamide (IS). The acetimidamide linkage of IS to chitosan herein was confirmed by 13C NMR and is a new branch in chitosan pendant group chemistry. The modified chitosan films (ISCH) were studied using thermal, tensile, and spectroscopic methods. The ISCH derivatives strongly inhibit fungal pathogens of agricultural and human importance, namely Fusarium solani, Colletotrichum gloeosporioides, Myrothecium verrucaria, Penicillium oxalicum, and Candida albicans. ISCH80 showed an IC50 value of 0.85 μg/ml against M. verrucaria and ISCH100 with IC50 of 1.55 μg/ml is comparable to the commercial antifungal IC50 values of Triadiamenol (3.6 μg/ml) and Trifloxystrobin (3 μg/ml). Interestingly, the ISCH series remained non-toxic up to 2000 μg/ml against L929 mouse fibroblast cells. The ISCH series showed long-standing antifungal action, superior to our lowest observed antifungal IC50 values of plain chitosan and IS at 12.09 μg/ml and 3.14 μg/ml, respectively. ISCH films are thus suitable for fungal inhibition in an agricultural setting or food preservation.


Machine learning-based models for predicting mortality and acute kidney injury in critical pulmonary embolism.
We aimed to use machine learning (ML) algorithms to risk stratify the prognosis of critical pulmonary embolism (PE). In total, 1229 patients were obtained from MIMIC-IV database. Main outcomes were set as all-cause mortality within 30 days. Logistic regression (LR) and simplified eXtreme gradient boosting (XGBoost) were applied for model constructions. We chose the final models based on their matching degree with data. To simplify the model and increase its usefulness, finally simplified models were built based on the most important 8 variables. Discrimination and calibration were exploited to evaluate the prediction ability. We stratified the risk groups based on risk estimate deciles. The simplified XGB model performed better in model discrimination, which AUC were 0.82 (95% CI: 0.78-0.87) in the validation cohort, compared with the AUC of simplified LR model (0.75 [95% CI: 0.69-0.80]). And XGB performed better than sPESI in the validation cohort. A new risk-classification based on XGB could accurately predict low-risk of mortality, and had high consistency with acknowledged risk scores. ML models can accurately predict the 30-day mortality of critical PE patients, which could further be used to reduce the burden of ICU stay, decrease the mortality and improve the quality of life for critical PE patients.


Preparation of a partially carboxymethylated cotton gauze and study of its hemostatic properties.
In this study, we attempted to modify cotton gauze by partial carboxymethylation by varying the reaction time and concentration of monochloroacetic acid and sodium hydroxide. For each experiment, the relative value of the degree of substitution (DS) of the modified cotton gauze was evaluated and the whole blood clotting time (WBCT) and water absorption property were compared with cotton gauze and Surgicel. This revealed that, following an initial decrease, WBCT gradually increased. Using rabbit ear artery and liver haemorrhage models, the performance of the optimal modified gauze was compared to that of Surgicel and unmodified cotton gauze. The average bleeding times in the presence of modified cotton gauze in the rabbit ear arteries and the liver were 51.7s and 60.6s, while those with Surgicel and the unmodified cotton gauze were 76.8s and 95.5s, and 93.2s and 129.2s, respectively. The hemostatic and biocompatibility properties were evaluated using in vivo degradation experiments. This revealed that the modified gauze and Surgicel were totally degraded within 6 weeks.


Allogenic umbilical cord blood-mesenchymal stem cells are more effective than antibiotics in alleviating subclinical mastitis in dairy cows.
Subclinical mastitis is an inflammatory disease that affects the milk production, fertility, and lifespan of animals, leading to significant losses to dairy industry. Antibiotics therapies are resulting in suboptimal benefits in treating subclinical mastitis due to prevalent antibiotic resistance in dairy herds. In a quest to develop alternative therapy, umbilical cord-derived mesenchymal stem cells (UCB-MSCs) and its extracellular vesicles (UCB-MSC-EVs) are used, in the present study, to validate its safety and efficacy as potential therapy for treatment of subclinical mastitis in dairy cows with respect to conventional antibiotic therapy (ABT). We isolated, in vitro cultured, and characterized the UCB-MSCs as well as UCB-MSC-EVs. The repeated infusions of low dose MSCs and EVs were delivered in healthy animals for safety analysis, followed by the same administrations in infected animals for therapeutic efficacy analysis. UCB-MSCs and UCB-MSC-EVs were found to be safe at 2 doses with 7-day gap of 5 × 107 cells/injection and EV equivalent to 500 μg protein in DPBS, respectively. Efficacy trials demonstrated significantly decreased somatic cell count to safe levels in milk samples of UCB-MSCs and UCB-MSC-EVs treated groups compared to antibiotic group. The leucocytes expression of anti-inflammatory cytokines, anti-microbial peptides, and angiogenic genes were significantly upregulated in UCB-MSCs and UCB-MSC-EVs treated groups as compared to antibiotic therapy group. Antibiotic therapy and UCB-MSC-EV groups failed to significantly decrease the gene expression of pro-inflammatory cytokine. In conclusion, the administration of UCB-MSCs and UCB-MSC-EVs through intravenous and local routes was found to be safe and efficacious for alleviating subclinical mastitis in dairy cows.


The role of newer antiglutamatergic agents as mood-stabilizers in bipolar disorder.
In bipolar patients, maintenance treatment with anticonvulsive agents is a valid alternative to lithium. These agents have widely varying mechanisms of action. Some of these medications focus on the current understanding of antiglutamatergic mechanisms of action and their treatment implications for bipolar disorders.


Volumetric brain magnetic resonance imaging analysis in children with obstructive sleep apnea.
Pediatric Obstructive Sleep Apnea (OSA) is associated with neurocognitive deficits. Cerebral structural alterations in the frontal cortex, cerebellum, and hippocampus have been reported in adult OSA patients. These brain areas are important for executive functioning, motor regulation of breathing, and memory function, respectively. Corresponding evidence comparing cerebral structures in pediatric OSA patients is limited. The objective of this study is to investigate MRI differences in cortical thickness and cortical volume in children with and without OSA. Prospective, single institutional case-control study. Forty-five children were recruited at a pediatric tertiary care center (27 with OSA; mean age 9.9 ± 1.9 years, and 18 controls; mean age 10.5 ± 1.0 years). The OSA group underwent magnetic resonance imaging (MRI), polysomnography (PSG) and completed the Pediatric Daytime Sleepiness Scale (PDSS) and the Child's Sleep Habits Questionnaire (CSHQ). High-resolution T1-weighted MRI was utilized to examine cortical thickness and gray and white matter volume in children with OSA compared to a healthy group of demographically-comparable children without OSA selected from a pre-existing MRI dataset. Children with OSA showed multiple regions of cortical thinning primarily in the left hemisphere. Reduced gray matter (GM) volume was noted in the OSA group in multiple frontal regions of the left hemisphere (superior frontal, rostral medial frontal, and caudal medial frontal regions). Reduced white matter (WM) volume in both the left and right hemisphere was observed in regions of the frontal, parietal, and occipital lobes in children with OSA. This study noted differences in cortical thickness and GM and WM regional brain volumes in children with OSA. These findings are consistent with other pediatric studies, which also report differences between healthy children and those with OSA. We found that the severity of OSA does not correlate with the extent of MRI alterations.


Phthalates and their effects on human health: Focus on erythrocytes and the reproductive system.
Plastics, long-chain artificial polymers, are used worldwide with a global production of 350 million tonnes per year. Various degradation processes transform plastics into smaller fragments divided into micro, meso and macroplastics. In various industries, such as construction, certain plastic additives are used to improve flexibility and enhance performance. Plastic additives include phthalates (PAE), dibutyl phthalate (DPB) and diethyl phthalate (DEP). Due to the use of plastics and plastic additives, these small fragments of different shapes and colours are present in all environmental compartments. For their characteristics, PAEs can be introduced particularly by ingestion, inhalation and dermal absorption. They can accumulate in the human body, where they have already been identified in blood, amniotic fluid and urine. The purpose of this review is to gather the effects that these plastic additives have on various systems in the human body. Being endocrine disruptors, the effects they have on erythrocytes and how they can be considered targets for xenobiotics have been analysed. The influence on the reproductive system was also examined. Phthalates are therefore often overused. Due to their properties, they can reach human tissues and have a negative impact on health. The aim of this review is to give an overview of the presence of phthalates and their hazards. Therefore, the use of these plastic additives should be reduced, replaced and their disposal improved.


MicroResearch--Finding sustainable solutions to local health challenges in East Africa.
The urgent need in Africa for research capacity building has been recognized by African leaders and governments for many years. However, lack of large research funding opportunities has been seen as a major obstacle to improving research capacity in precisely those countries that need it the most. Microfinance has shown that a small infusion of capital can "prime the pump" to creative local economic productivity. In a similar way, MicroResearch has proven effective in promoting a similar bottom-up strategy to find sustainable solutions to local health challenges through local community focused research. Specifically, MicroResearch through hands-on didactic courses, mentoring and small-scale research funding promotes small research projects that improve research skills across the entire health-care provider spectrum to unleash a culture of inquiry. This in turn stimulates health care providers to identify the locally most relevant obstacles that need to be overcome and implement locally feasible and sustainable solutions. MicroResearch is a bottom-up strategy proven effective at finding sustainable solutions to local health challenges.


Mate preference and avoidance in female rats following treatment with scopolamine.
The effects of the muscarinic antagonist, scopolamine, on the behavior of female rats in a mate preference test were determined. Ovariectomized rats were primed with sufficient doses of estradiol benzoate (0.25 micrograms for 3 days) and progesterone (500 micrograms) to activate full sexual receptivity. Beginning 15 min after intraperitoneal injection of saline (0.4 ml/kg) or scopolamine hydrochloride (1 mg/kg), females were tested in an arena divided into three compartments. Females treated with scopolamine clearly avoided a compartment occupied by a gonadally intact stimulus male, instead preferring a compartment occupied by a castrated male or an empty neutral compartment. Direct contact with an intact male was a critical feature of this avoidance because females treated with scopolamine did not avoid intact males that were confined within a chamber that prevented physical contact between the male and female. Results indicate that female rats treated with scopolamine avoid direct physical contact with sexually active males, possibly due to an alteration in sexual motivation and/or the aversive nature of this interaction.


TRIM5alpha association with cytoplasmic bodies is not required for antiretroviral activity.
The tripartite motif (TRIM) protein, TRIM5alpha, restricts infection by particular retroviruses. Many TRIM proteins form cytoplasmic bodies of unknown function. We investigated the relationship between cytoplasmic body formation and the structure and antiretroviral activity of TRIM5alpha. In addition to diffuse cytoplasmic staining, the TRIM5alpha proteins from several primate species were located in cytoplasmic bodies of different sizes; by contrast, TRIM5alpha from spider monkeys did not form cytoplasmic bodies. Despite these differences, all of the TRIM5alpha proteins exhibited the ability to restrict infection by particular retroviruses. Treatment of cells with geldanamycin, an Hsp90 inhibitor, resulted in disappearance or reduction of the TRIM5alpha-associated cytoplasmic bodies, yet exerted little effect on the restriction of retroviral infection. Studies of green fluorescent protein-TRIM5alpha fusion proteins indicated that no TRIM5alpha domain is specifically required for association with cytoplasmic bodies. Apparently, the formation of cytoplasmic bodies is not required for the antiretroviral activity of TRIM5alpha.


Plant cannabinoids: a neglected pharmacological treasure trove.
Most of the cannabinoids in Cannabis sativa L. have not been fully evaluated for their pharmacological activity. A publication in this issue presents evidence that a plant cannabinoid, Delta(9)-tetrahydrocannabivarin is a potent antagonist of anandamide, a major endogenous cannabinoid. It seems possible that many of the non-psychoactive constituents of this plant will be of biological interest.


ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3 in a complex to promote PIKfyve activity and functionality.
PtdIns(3,5)P(2) (with PtdIns indicating phosphatidylinositol) is vital in the differentiation and development of multicellular organisms because knockout of the PtdIns(3,5)P(2)-synthesizing enzyme PIKfyve (phosphoinositide kinase for position 5 containing a FYVE finger domain) or its associated regulator ArPIKfyve is lethal. In previous work with endogenous proteins, we identified that Sac3, a phosphatase that turns over PtdIns(3,5)P(2), associates with the PIKfyve-ArPIKfyve biosynthetic complex. However, whether the three proteins suffice for the organization/maintenance of this complex [referred to as the PAS (PIKfyve-ArPIKfyve-Sac3) complex], how they interact with one another, and what the functional relevance of this ternary association would be remained unresolved. Using co-immunoprecipitation analyses in transfected mammalian cells with increased or decreased levels of the three proteins, singly or in double versus triple combinations, herein we report that the triad is sufficient to form and maintain the PAS complex. ArPIKfyve is the principal organizer interacting with both Sac3 and PIKfyve, whereas Sac3 is permissive for maximal PIKfyve-ArPIKfyve association in the PAS complex. We further identified that ArPIKfyve scaffolds the PAS complex through homomeric interactions, mediated via its conserved C-terminal domain. Introduction of the C-terminal peptide fragment of the ArPIKfyve-ArPIKfyve contact sites effectively disassembled the PAS complex and reduced the in vitro PIKfyve lipid kinase activity. Exploring insulin-regulated GLUT4 translocation in 3T3L1 adipocytes as a functional readout, a process that is positively regulated by PIKfyve activity and ArPIKfyve levels, we determined that ectopic expression of the ArPIKfyve C-terminal peptide inhibits GLUT4 surface accumulation. Our data indicate that the PAS complex is organized to provide optimal PIKfyve functionality and is maintained via ArPIKfyve homomeric and heteromeric interactions.


Molecular phylogenetics of the species-rich genus Habenaria (Orchidaceae) in the New World based on nuclear and plastid DNA sequences.
Habenaria is a large genus of terrestrial orchids distributed throughout the tropical and subtropical regions of the world. The integrity and monophyly of this genus have been under discussion for many years, and at one time or another, several genera have been either included in a broadly defined Habenaria or segregated from it. In this study, the phylogenetic relationships of the Neotropical members of the genus and selected groups of African Habenaria were investigated using DNA sequences from the nuclear internal transcribed spacer (ITS) region and the plastid matK gene sampled from 151 taxa of Habenaria from the Neotropics (ca. 51% of the total) as well as 20 species of Habenaria and Bonatea from the Old World. Bayesian and parsimony trees were congruent with each other, and in all analyses, the Neotropical species formed a highly supported group. African species of Habenaria in sections Dolichostachyae, Podandria, Diphyllae, Ceratopetalae and Bilabrellae, and the Neotropical clade formed a highly supported "core Habenaria clade", which includes the type species of the genus from the New World. The topology of the trees indicates an African origin for the Neotropical clade and the low sequence divergence among the Neotropical species suggests a recent radiation of the genus in the New World. Species of Bonatea and Habenaria sections Chlorinae and Multipartitae formed a well-supported clade that was sister to the "core Habenaria clade". The Neotropical clade consists of at least 21 well-supported subgroups, but all Neotropical sections of the current sectional classification are paraphyletic or polyphyletic and will need extensive revision and recircumscription. Most of the Neotropical subgroups formed morphologically uniform assemblage of species, but some cases of morphological divergence within subgroups and convergence between subgroups indicated that morphology alone can be misleading for inferring relationships within the genus. The genera Bertauxia, Kusibabella and Habenella, segregated from New World Habenaria, are not monophyletic and a revision of the sectional classification rather than a generic division seems most appropriate. Our results do not support an extensive generic fragmentation of Habenaria as previously suggested and will provide a framework for revising the infrageneric classification and investigating the patterns of morphological evolution and geographical distribution of the genus in the New World.


Review: Porous Metal Filters and Membranes for Oil-Water Separation.
In recent years, oil-water separation has been widely researched to reduce the influences of industrial wastewater and offshore oil spills. A filter membrane with special wettability can achieve the separation because of its opposite wettability for water phase and oil phase. In the field of filter membrane with special wettability, porous metal filter membranes have been much investigated because of the associated high efficiency, portability, high plasticity, high thermal stability, and low cost. This article provides an overview of the research progress of the porous metal filter membrane fabrication and discusses the future developments in this field.


No evidence for a relationship between farm or transformation process locations and antibiotic resistance patterns of Pseudomonas population associated with rainbow trout (Oncorhynchus mykiss).
Study the relationship between antibiotic resistance patterns of Pseudomonas isolated from farmed rainbow trout fillets and farm or transformation process locations. Pseudomonas strains were isolated from rainbow trout sampled in two differently located farms and filleted in laboratory or in a processing factory. One hundred and twenty-five isolates were confirmed as belonging to Pseudomonas using CFC selective media, Gram staining, oxidase test and quantitative polymerase chain reaction methods. Fifty-one isolates from separate fish fillets were further identified using MALDI-TOF mass spectrometry, and the minimal inhibitory concentrations (MIC) of 11 antibiotics were also determined by microdilution method. Most of the isolates belonged to the Pseudomonas fluorescens group (94.1%), and no relationship was established between antibiotic resistance patterns and sampling locations (farms or filleting areas). Multiple resistance isolates with high MIC values (from 64 µg ml-1 to more than 1024 µg ml-1 ) were identified. Antibiotic resistance patterns found in Pseudomonas isolates were not influenced by farms or transformation process locations. Seven isolates were found highly resistant to four different antibiotic classes. This study does not provide evidence of a relationship between farm or transformation process locations on antibiotic resistance patterns of Pseudomonas population.


Investigation of Crystal Structures in Structure-Based Virtual Screening for Protein Kinase Inhibitors.
Protein kinases are important drug targets in several therapeutic areas ,and structure-based virtual screening (SBVS) is an important strategy in discovering lead compounds for kinase targets. However, there are multiple crystal structures available for each target, and determining which one is the most favorable is a key step in molecular docking for SBVS due to the ligand induce-fit effect. This work aimed to find the most desirable crystal structures for molecular docking by a comprehensive analysis of the protein kinase database which covers 190 different kinases from all eight main kinase families. Through an integrated self-docking and cross-docking evaluation, 86 targets were eventually evaluated on a total of 2608 crystal structures. Results showed that molecular docking has great capability in reproducing conformation of crystallized ligands and for each target, the most favorable crystal structure was selected, and the AGC family outperformed the other family targets based on RMSD comparison. In addition, RMSD values, GlideScore, and corresponding bioactivity data were compared and demonstrated certain relationships. This work provides great convenience for researchers to directly select the optimal crystal structure in SBVS-based kinase drug design and further validates the effectiveness of molecular docking in drug discovery.


Intravoxel Incoherent Motion Diffusion Weighted Magnetic Resonance Imaging for Differentiation Between Nasopharyngeal Carcinoma and Lymphoma at the Primary Site.
The aim of the study was to investigate the utility of intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (DWI) for differentiating nasopharyngeal carcinoma (NPC) from lymphoma. Intravoxel incoherent motion-based parameters including the apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), and fD* (the product of D* and f) were retrospectively compared between 102 patients (82 with NPC, 20 with lymphoma) who received pretreatment IVIM DWI. Compared with lymphoma, NPC exhibited higher ADC, D, D*, fD* values (P < 0.001) and f value (P = 0.047). The optimal cutoff values (area under the curve, sensitivity, and specificity, respectively) for distinguishing the 2 tumors were as follows: ADC value of 0.761 × 10 mm/s (0.781, 93.90%, 55.00%); D, 0.66 × 10 mm/s (0.802, 54.88%, 100.00%); D*, 7.89 × 10 mm/s (0.898, 82.93%, 85.00%); f, 0.29 (0.644, 41.46%, 95.00%); and fD*, 1.99 × 10 mm/s (0.960, 85.37%, 100.00%). Nasopharyngeal carcinoma exhibits different IVIM-based imaging features from lymphoma. Intravoxel incoherent motion DWI is useful for differentiating lymphoma from NPC.


Improving performance of deep learning models using 3.5D U-Net via majority voting for tooth segmentation on cone beam computed tomography.
Deep learning allows automatic segmentation of teeth on cone beam computed tomography (CBCT). However, the segmentation performance of deep learning varies among different training strategies. Our aim was to propose a 3.5D U-Net to improve the performance of the U-Net in segmenting teeth on CBCT. This study retrospectively enrolled 24 patients who received CBCT. Five U-Nets, including 2Da U-Net, 2Dc U-Net, 2Ds U-Net, 2.5Da U-Net, 3D U-Net, were trained to segment the teeth. Four additional U-Nets, including 2.5Dv U-Net, 3.5Dv5 U-Net, 3.5Dv4 U-Net, and 3.5Dv3 U-Net, were obtained using majority voting. Mathematical morphology operations including erosion and dilation (E&D) were applied to remove diminutive noise speckles. Segmentation performance was evaluated by fourfold cross validation using Dice similarity coefficient (DSC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV). Kruskal-Wallis test with post hoc analysis using Bonferroni correction was used for group comparison. P < 0.05 was considered statistically significant. Performance of U-Nets significantly varies among different training strategies for teeth segmentation on CBCT (P < 0.05). The 3.5Dv5 U-Net and 2.5Dv U-Net showed DSC and PPV significantly higher than any of five originally trained U-Nets (all P < 0.05). E&D significantly improved the DSC, accuracy, specificity, and PPV (all P < 0.005). The 3.5Dv5 U-Net achieved highest DSC and accuracy among all U-Nets. The segmentation performance of the U-Net can be improved by majority voting and E&D. Overall speaking, the 3.5Dv5 U-Net achieved the best segmentation performance among all U-Nets.


Performance evaluation of in vitro diagnostic kits for hepatitis B virus infection using the regional reference panel of Japan.
Hepatitis B virus (HBV) infection is a global public health concern. Precise and sensitive detection of viral markers, including HBV DNA and HBs antigen (Ag), is essential to determine HBV infection. The sensitivities and specificities of 5 HBV DNA and 14 HBsAg kits were evaluated using World Health Organization International Standards (WHO IS) and the Regional Reference Panel (RRP) consisting of 64 HBsAg-negative and 80 HBsAg-positive specimens. All 5 HBV DNA kits detected HBV DNA in the WHO IS at a concentration of 10 IU/mL. The sensitivity and specificity to the RRP were 98.8-100% and 96.9-100%, respectively. HBV DNA titers were well correlated among the 5 kits regardless of HBV genotype. However, discordance of the HBV DNA titer was found in 5 specimens measured by CAP/CTM HBV v2.0. Among 12 automated HBsAg kits, the minimum detectable concentrations in the WHO IS varied from 0.01 to 0.1 IU/mL. Two lateral flow assays were positive for WHO IS concentrations greater than or equal to 1.0 and 0.1 IU/mL, respectively. When analyzed by the RRP, 12 automated kits exhibited a sensitivity of 98.8-100%, and 2 lateral flow assays showed sensitivities of 93.8% and 100%. The specificities of HBsAg kits were 100%. In the quantification of HBsAg, some kits showed a poor correlation of measurements with each other and showed up to a 1.7-fold difference in the regression coefficient of HBsAg titers. There were variations in the correlations of measurements among HBsAg kits when analyzed by genotype. Five HBV DNA kits showed sufficient sensitivity and specificity to determine HBV infection. HBV DNA titers were compatible with each other irrespective of HBV genotypes. HBsAg kits had enough sensitivity and specificity to screen for HBV infection. One of the lateral flow assays had a nearly equivalent sensitivity to that of the automated HBsAg kit. HBsAg titers quantified by the evaluated kits were not compatible across the kits. Genotype-dependent amino acid variations might affect the quantification of HBsAg titers.


Probiotic prophylaxis after pullthrough for Hirschsprung disease to reduce incidence of enterocolitis: a prospective, randomized, double-blind, placebo-controlled, multicenter trial.
Hirschsprung-associated enterocolitis (HAEC) is one of the most troublesome problems encountered after a pullthrough. We hypothesized that prophylactic administration of probiotics after a pullthrough procedure would decrease the incidence of HAEC. A prospective, double-blind, placebo-controlled, randomized trial was conducted at 2 children's hospitals. Infants undergoing pullthrough were randomized to probiotic or placebo for a period of 3 months post-pullthrough. Primary outcome was incidence of post-operative HAEC. Other outcomes included severity of HAEC by clinical grade, number of HAEC episodes and extent of aganglionosis. Pearson Chi Square analysis, as well as logistic regression, was used for statistical analysis. Sixty-two patients were recruited (Sites: A=40; B=22). One was lost to follow up and one immediate post-op death was not included in final analysis. Probiotics were administered to 32 patients. Distribution of placebo/probiotics was equal between sites (P=0.858). Mean age at pullthrough was 6.5 ± 8.1(± SD) months. The incidence of HAEC was 28.3%. The incidence of HAEC was not statistically different between probiotic and placebo study groups. Incidence of HAEC was not reduced with prophylactic probiotics. Future studies are needed to better determine the etiology and possible ways of preventing this complex condition.


Normal-tissue toxicities of thoracic radiation therapy: esophagus, lung, and spinal cord as organs at risk.
The evolution of therapeutic approaches for lung cancer illustrates the trend for treatment intensification, with hopes that dose-intense chemotherapy regimens, higher radiation therapy (RT) doses, or novel fractionation schemes will result in prolongation of survival. Current chemotherapy- and RT-intense regimens may not be intensified further without addressing dose-limiting toxicities such as esophagitis. It is important to understand factors pre-disposing to esophagitis so that strategies to minimize its severity can be investigated. Pulmonary complications such as pneumonitis and fibrosis from RT (with or without chemotherapy) are dose and volume dependent. Methods to better identify the target tissues and improved RT-delivery systems may facilitate increasing target doses or reducing doses to adjacent normal tissues. Biologic predictors may allow clinicians in the future to individualize RT treatment based on a patient's toxicity risk profile. Radiation myelopathy is still the most feared radiation complication of lung cancer treatment. The authors address the known parameters that influence the incidence of thoracic radiation myelopathy and the putative factors that could be considered when a clinician may be required to push the spinal cord dose in favor of tumor control.


Evaluation and Management of Hip and Pelvis Injuries.
Injuries to the hip and pelvis among runners can be among the most challenging to treat. Advances in the understanding of running biomechanics as it pertains to the lumbopelvic and hip regions have improved the management of these conditions. Conservative management with an emphasis on activity modification and neuromuscular exercises should comprise the initial plan of care, with injection therapies used in a supportive manner.


Treatment of chronic bacterial prostatitis with ciprofloxacin.
Thirty two patients with proven chronic bacterial prostatitis were treated with ciprofloxacin 500 mg twice daily orally for four weeks. The causative organisms, cultured from prostatic fluid were Enterobacteriaceae (19 patients), enterococci (9), staphylococci (4), streptococci (3), non-fermentative Gram-negative rods (2) and anaerobic bacteria (9). Nineteen patients had pure cultures, 13 mixed cultures. The susceptibility of all organisms to ciprofloxacin, sulfamethoxazole, trimethoprim and doxycyclin was determined by agar dilution. The effect of therapy was measured by clinical parameters and by repeated cultures of prostatic fluid during and after therapy up to six months. Clinical cure (at one month after therapy) was obtained in 22 patients, improvement in seven; two patients did not respond, one patient had to stop during therapy because of severe nausea. No other side effects were noted. Ciprofloxacin may be a useful alternative drug in the treatment of prostatitis.


Modeling Bitcoin Prices using Signal Processing Methods, Bayesian Optimization, and Deep Neural Networks.
Bitcoin is a volatile financial asset that runs on a decentralized peer-to-peer Blockchain network. Investors need accurate price forecasts to minimize losses and maximize profits. Extreme volatility, speculative nature, and dependence on intrinsic and external factors make Bitcoin price forecast challenging. This research proposes a reliable forecasting framework by reducing the inherent noise in Bitcoin time series and by examining the predictive power of three distinct types of predictors, namely fundamental indicators, technical indicators, and univariate lagged prices. We begin with a three-step hybrid feature selection procedure to identify the variables with the highest predictive ability, then use Hampel and Savitzky-Golay filters to impute outliers and remove signal noise from the Bitcoin time series. Next, we use several deep neural networks tuned by Bayesian Optimization to forecast short-term prices for the next day, three days, five days, and seven days ahead intervals. We found that the Deep Artificial Neural Network model created using technical indicators as input data outperformed other benchmark models like Long Short Term Memory, Bi-directional LSTM (BiLSTM), and Convolutional Neural Network (CNN)-BiLSTM. The presented results record a high accuracy and outperform all existing models available in the past literature with an absolute percentage error as low as 0.28% for the next day forecast and 2.25% for the seventh day for the latest out of sample period ranging from Jan 1, 2021, to Nov 1, 2021. With contributions in feature selection, data-preprocessing, and hybridizing deep learning models, this work contributes to researchers and traders in fundamental and technical domains.


The prevalence of dementia with Lewy bodies in a rural area of China.
Data on the prevalence of dementia with Lewy bodies (DLB) in China are limited. The aim of this study was to estimate the prevalence of DLB in individuals aged 60 years and older and to analyze the associated risk factors and clinical features of DLB. We conducted a cross-sectional, two-phase, door-to-door, population-based study that included 5542 participants aged at least 60 years who resided in Ji County. In phase I of the study, we used the Mini-Mental State Examination, the Clinical Dementia Rating scale, and the Activities of Daily Living scale to screen for dementia. Any person who was suspected of having dementia underwent a clinical examination, blood tests, and a neuroimaging examination to confirm the diagnosis of dementia. In phase II of the study, we further screened eligible participants for DLB using consensus guidelines for the clinical and pathologic diagnosis of DLB. The overall prevalence of DLB in the total population of 5542 study participants was 1.05%; the prevalence of DLB was 10.10% in the population with dementia. Compared to individuals without cognitive impairment, patients with DLB were less engaged in social activities. Having fewer than 5 years of formal education might be a risk factor for DLB. The three core symptoms of DLB - fluctuating cognition, visual hallucinations, and Parkinsonism - were observed in 60.34%, 68.97%, and 63.79% of patients with DLB, respectively. Our study provides the first information of the prevalence of DLB in a rural area of China.


Community physicians' cooperation with a program of in-home comprehensive geriatric assessment.
To study the cooperation of primary care physicians with a community-based prevention and health promotion program for older persons, to study physician factors related to cooperation, and to determine any relationship between physician cooperation and patient adherence to program recommendations and patient satisfaction with health care. A survey administered in subjects' homes and physicians' offices in Santa Monica, California. Patients (n = 81) were intervention group subjects in a 3-year, randomized, controlled trial of in-home comprehensive geriatric assessment paired with prevention and health promotion. Physicians (n = 50) were selected if they had been contacted at least once by a study nurse practitioner about one of these patients. Physician cooperation was rated by study nurse practitioners. Physicians were interviewed to identify factors associated with cooperation. Patients' satisfaction with health care and adherence were measured prospectively throughout the 3-year program. Physicians exhibiting better cooperation had fewer years in practice (P = .03) and were more likely to discuss the program with their patients (P = .005), see benefit for their patients from the program (P = .02), and rate program information as useful (P = .002). Higher physician cooperation did not predict higher patient satisfaction (P = .23) but did predict higher patient adherence to program recommendations (P = .02). Physicians rated as cooperative were more likely to have a positive appraisal of the program, and their patients had higher adherence to program recommendations. These findings suggest that strategies for increasing primary care physician cooperation might improve effectiveness of similar community-based prevention and health promotion programs.


Modeling antitumor activity in xenograft tumor treatment.
To analyze responses of solid tumors to treatment with antitumor therapy, we applied nonparametric mixed-effects models to investigate tumor volumes measured over a fixed. The population and individual response functions were approximated by penalized splines. Linear mixed-effects modeling was applied in the implementation of the estimation. We applied the approach to an analysis of a real xenograft study of a new antitumor agent, temozolomide, combined with irinotecan. The model fitted the data very well. We conducted a sensitivity analysis to determine the effect of informative dropout. We also propose an intuitive approach to a comparison of the antitumor effects of two different treatments. Biological interpretations and clinical implications are discussed.


Xenopus transcription factor IIIA. Evidence for heterogeneity of Zn2+ binding affinities and specific labeling of cysteine 287.
The release of Zn2+ from transcription factor IIIA (TFIIIA) was examined with the metallochromic indicator 4-(2-pyridylazo)resorcinol (PAR) in the absence and presence of p-hydroxymercuriphenylsulfonate (PMPS). With 0.5 mM PAR, approximately 5 eq of Zn2+ were released from TFIIIA, but no Zn2+ release was detected from the 7 S ribonucleoprotein. The PMPS-promoted Zn2+ release from TFIIIA was 8.7 +/- 0.4 eq of Zn2+ of which approximately 4 eq of Zn2+ rebound to TFIIIA upon displacement of the mercurial with excess 2-mercaptoethanol. These results suggest that at least two affinity classes of Zn2+ binding sites exist in TFIIIA, one of which is released to 0.5 mM PAR in the absence of PMPS. Also, 18 of the 23 cysteine residues of TFIIIA reacted with 5,5'-dithiobis-(2-nitrobenzoic acid). The kinetic data of PAR and 5,5'-dithiobis-(2-nitrobenzoic acid) reactions with TFIIIA were similar, and the spectral changes were characterized by at least three exponential terms. Both TFIIIA and the 7 S particle were reacted with the thiol-specific fluorescent probe N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine (1,5-I-AEDANS). Complete trypsin hydrolysis followed by reverse-phase high pressure liquid chromatography analysis of peptide mixtures showed only one fluorescent peak from the AEDANS-labeled 7 S particle whereas numerous fluorescent peaks were observed with AEDANS-labeled TFIIIA. This further indicates exposure of cysteine residues from Zn2+ binding domains in TFIIIA. Cys287 was identified as the site of modification by amino acid sequencing of the isolated fluorescent peptide from the derivatized 7 S particle. Limited papain cleavage of the AEDANS-labeled 7 S particle indicated that the modified cysteine is located within a 34-kDa TFIIIA fragment. Gel retardation and transcription assays showed that TFIIIA, which had been purified from the AEDANS-labeled 7 S particle, was capable of binding to the internal control region of 5 S RNA gene and retained transcription activity. Thus, Zn2+ binding domains and all but 1 cysteine residue are buried in the 7 S particle, thereby facilitating site-specific labeling of TFIIIA.


Malignant proliferating trichilemmal tumours: an histopathological and immunohistochemical study of three cases with DNA ploidy and morphometric evaluation.
Malignant proliferating trichilemmal tumours (MPTT) are rare neoplasms capable of tissue invasion and metastasis, the diagnosis of which is based essentially on histological features. In difficult cases, however, evaluation of additional parameters may be needed to diagnose malignancy. We report three cases of MPTT in which, in addition to the histological features, we have determined the DNA ploidy, nuclear area and proliferative fraction. CD34 immunoreactivity has also been tested. Two cases were aneuploid, and one diploid with increased proliferating index. PCNA immunostaining labelled 40% and 80% of tumour cells in aneuploid tumours and 30% of the diploid neoplasm. In all cases, nuclear area was consistent with large pleomorphic tumour cells. No CD34 immunostaining was detected. Aneuploidy is common in MPTT, particularly in tumours with a high proliferative fraction. Loss of CD34 immunoreactivity is an additional feature of potential, though limited, value. Therefore, evaluation of the DNA content, proliferation markers and CD34 immunostaining may be helpful in the diagnosis of MPTT.


Recent advances in urologic laparoscopic surgeries: laparoendoscopic single-site surgery, natural orifice transluminal endoscopic surgery, robotics and navigation.
Laparoscopic surgery was developed at the end of the 1980s and has been utilized in almost all urologic surgical procedures. It offers the benefits of less invasiveness and earlier recovery than open surgery. The introduction of laparoendoscopic single-site surgery has offered reduced pain and improved cosmetic satisfaction to patients. Scarless nephrectomy has been realized with transvaginal natural orifice transluminal endoscopic surgery in women. The development of surgical robots has decreased the technical difficulty of complicated procedures, shortened the learning curve, and improved perioperative outcomes relative to laparoscopic surgery. Surgical navigation using real-time sonography, augmented reality, fluorescence, or radioisotope images will improve the quality of these surgeries.


Alteration in Ca2+ availability involved in antigen-induced airway hyperresponsiveness in rats.
The origin of Ca2+ contributing to the enhancement of acetylcholine-induced bronchial smooth muscle constriction in airway hyperresponsiveness induced by antigen challenge was investigated. Under Ca(2+)-free (concomitant with 10(-6) M nicardipine) conditions, the contractile responses of bronchial rings to 1 mM acetylcholine were significantly greater in rings from rats with hyperresponsive airways (0.15 +/- 0.04 g) than those of rings from normal rats (0.02 +/- 0.004 g; P < 0.05). The cumulatively administered Ca2+ induced a markedly greater bronchoconstriction in rings from rats with hyperresponsive airways in Ca(2+)-free solution when muscles were pretreated with 1 mM acetylcholine (in the presence of 10(-6) M nicardipine) than in rings from normal rats, whereas no significant difference in Ca(2+)-induced bronchoconstriction was observed between the two groups when muscles were pretreated with 60 mM K+ (in the presence of 10(-6) M atropine). These findings suggest that enhancement of the availability of Ca2+ released from intracellular stores and/or influxed through receptor-operated Ca2+ channels in airway smooth muscles might be involved in the airway hyperresponsiveness to acetylcholine in rats.


Birth asphyxia. I. Measurement of visual evoked potential (VEP) in the healthy fetus and newborn lamb.
The visual evoked potential (VEP) of five healthy, near-term exteriorized fetal lambs was compared with the VEP obtained from the same animals during the first hour after ventilation. Characteristics of the individual wave components and their relationship to blood pressure, heart rate, and arterial blood gas measurements concomitantly obtained were examined. Results show that the VEP of the healthy fetus is a stable, reproducible signal consisting of four basic components, and that the latencies (msec) and the amplitude (mu V) of the individual components of the VEP are similar to those of the newborn. In two related experiments, fetal asphyxia of unknown duration was encountered during fetal exteriorization an instrumentation. In the first case, neonatal, acidosis persisted despite aggressive resuscitation efforts and was accompanied by an atypical VEP. In the second case, the neonatal VEP obtained after 15 min of resuscitation was markedly depressed despite restoration of acid-base balance but gradually recovered during the remainder of the 1-hr newborn period. In conclusion, the VEP is a reproducible measure of cortical function in the healthy fetus and neonate and may reflect the acute status of cerebral function during fetal asphyxia and neonatal resuscitation.


Two-Year Functional Outcomes of Operative vs Nonoperative Treatment of Completely Displaced Midshaft Clavicle Fractures in Adolescents: Results From the Prospective Multicenter FACTS Study Group.
The optimal treatment of midshaft clavicle fractures is controversial. Few previous comparative functional outcome studies have investigated these fractures in adolescents, the most commonly affected epidemiologic subpopulation. The purpose was to prospectively compare the outcomes of operative versus nonoperative treatment in adolescents with completely displaced midshaft clavicle fractures. The study hypothesis was that surgery would yield superior outcomes. Cohort study; Level of evidence, 2. Patients aged 10 to 18 years treated for a midshaft clavicle fracture over a 5-year period at 1 of 8 pediatric centers were prospectively screened, with independent treatment decisions determined by individual musculoskeletal professionals. Demographics, radiographic clinical features, complications, and patient-reported outcomes (PROs) were prospectively recorded for 2 years. Regression and matching techniques were utilized to adjust for potential age- and fracture severity-based confounders for creation of comparable subgroups for analysis. Of 416 adolescents with completely displaced midshaft clavicle fractures, 282 (68) provided 2-year PRO data. Operative patients (n = 88; 31%) demonstrated no difference in sex (78% male) or athletic participation but were older (mean age, 15.2 vs 13.5 years; P < .001), had more comminuted fractures (49.4% vs 26.3%; P < .001), and had greater fracture shortening (25.5 vs 20.7 mm; P < .001) than nonoperative patients (n = 194; 69%). There was no difference in mean PRO scores or rates of "suboptimal" scores (based on threshold values established a priori) between the operative and nonoperative treatment groups (American Shoulder and Elbow Surgeons, 96.8 vs 98.4; shortened version of the Disabilities of the Arm, Shoulder and Hand, 3.0 vs 1.6; EuroQol [EQ] visual analog scale, 93.0 vs 93.9; EQ-5 Dimensions index, 0.96 vs 0.98), even after regression and matching techniques adjusted for confounders. Operative patients had more unexpected subsequent surgery (10.4% vs 1.4%; P = .004) and clinically significant complications (20.8% vs 5.2%; P = .001). Overall, nonunion (0.4%), delayed union (1.9%), symptomatic malunion (0.4%), and refracture (2.6%) were exceedingly rare, with no difference between treatment groups. Surgery demonstrated no benefit in patient-reported quality of life, satisfaction, shoulder-specific function, or prevention of complications after completely displaced clavicle shaft fractures in adolescents at 2 years after injury. NCT04250415 (ClinicalTrials.gov identifier).


Genetic and molecular analyses reveal G6PC as a key element connecting glucose metabolism and cell cycle control in ovarian cancer.
We aimed to evaluate the role of glucose-6-phosphatase, catalytic subunit (G6PC) in ovarian cancer and to exploit its therapeutic potential. With reproduction of The Cancer Genome Atlas (TCGA) database, we studied expressions of genes in the glucose metabolism pathways in silico. The cBioPortal For Cancer Genomics was used to study the clinical, pathological and molecular profiles of G6PC. In vitro studies were performed to validate the function of G6PC and the effect of genetic and pharmaceutical G6PC inhibition. In 158 ovarian cancer (OvCa) patients with complete RNA-seq data, G6PC expression was increased in 27 patients (17 %). Both overall survival (OS) and disease-free period were significantly shorter in cases with increased G6PC level. Significantly decreased total and phosphorylated CDKN1B level was noted in OvCa with increased G6PC expression. Silenced G6PC in OvCa cells induced decreased cell proliferation, viability, invasiveness and anchorage-independent cell growth. G6PC silencing also induced enhanced cell cycle control proteins and restoration of CDKN1B level. Pharmaceutical inhibition of G6PC with specific compound showed similar effects to genetic silencing. G6PC played dual roles both in glucose metabolism and cell cycle control in OvCa, which potentiated it a promising therapeutic target.


Ethanol fumigation combined with modified atmosphere packaging delays potato greening under light.
Potato greening under light causes post-harvest loss and compromises progress being made in the potato industry. In this study, we investigated the inhibiting effects of ethanol fumigation treatment on potato greening and water loss under light. This paper also examined the different treatments on the relationship between starch granule size and potato greening. Our results suggested that ethanol fumigation combined with modified atmosphere packaging have an effective in improving the overall visual quality and maintained a higher a* value and lower chlorophyll concentration. Ethanol fumigation combined with modified atmosphere packaging treatment deterred greening and water loss compared to the alone treatment. This was due to the larger starch granule size and fewer grana lamellae around the amyloplasts. Our results provide an effectively strategy that treating potatoes with 600 μL L-1 ethanol combined with modified atmosphere packaging to delay potato greening and explain the underlying mechanism of ethanol inhibition of potato greening.


Forensic evidence in atrocity trials: A risky sampling strategy?
In the light of the recent judgments issued by the International Criminal Court (ICC), including two acquittals and one very recent condemnation of the accused on all charges, analysing and assessing evidentiary practice before the Court is all the more pressing. This article focuses on one particular type of evidence used by the Prosecution, namely, forensic evidence, to critically review how it has been used so far at the ICC and consider whether the prosecutorial strategy of focusing on a certain sample of crimes is finally paying off.


Body composition and energy metabolism in normotensive and hypertensive pregnancy.
To determine whether the insulin resistance syndrome and altered body composition are features of hypertensive pregnancy. Women were recruited in the third trimester of pregnancy from the antenatal clinic, day assessment unit, and maternity ward of St George Hospital, Sydney. Women with pre-eclampsia (n = 12), gestational hypertension (n = 12), essential hypertension in pregnancy (n = 11), and normotensive pregnancy (n = 10). Energy metabolism was assessed by indirect calorimetry to measure basal metabolic rate and diet-induced thermogenesis. Body composition was measured as lean body mass, total body water and fat mass by bio-electrical impedance. Blood was collected for measurement of glucose, insulin and lipid profiles. Insulin resistance was indirectly assessed by the insulin and glucose concentrations and diet-induced thermogenesis. Women with essential hypertension and gestational hypertension were heavier than women with normotensive pregnancies both pre-pregnancy and in the third trimester, whereas women with pre-eclampsia were similar to those with normotensive pregnancy. Women with essential hypertension were otherwise similar to normotensive pregnancy but women with gestational hypertension had a reduced diet-induced thermogenesis and almost double insulin levels. Women with pre-eclampsia had a similar body composition and insulin levels but reduced basal metabolic rate, diet-induced thermogenesis and glucose levels compared with normotensive pregnancy. Women who develop gestational hypertension, but not pre-eclampsia, are more likely to be overweight. Women with essential hypertension are similar to women with normotensive pregnancy throughout pregnancy. Both gestational hypertension and pre-eclampsia appear to be associated with some degree of insulin resistance, greater than that occurring in normal pregnancy.


Empathic responding in children of battered mothers.
The present study assessed the empathic abilities of children whose mothers had been the targets of conjugal violence. Thirty-two mothers and their preschool children served as subjects. There were equal numbers of boys and girls. Half of the mothers had a history of having been abused by their husbands while the other half came from non-violent relationships. The instability of the abused mothers' familial relationships was further established by means of a Home Climate Questionnaire. Analysis of this instrument revealed that although abusive husbands were not reported to be physically violent with their children, they were more verbally aggressive than their non-abusive counterparts. Four measures assessed the empathic abilities of the children: role-enactment, social inference, role-taking, and social behavior. A 2-way MANOVA (multivariate analysis of variance) run on these measures indicated a significant main effects of groups on all but the social behavior measure. There was also a significant groups by sex of child interaction on the role-taking measure. The results suggest the early and pervasive influence which marital discord may have on the empathic abilities of young children. Both direct and vicariously mediated forces may influence this facet of the child's social development.


Nitric oxide metabolites in gnotobiotic piglets orally infected with Salmonella enterica serovar typhimurium.
Reactive NO metabolites play a distinct role in the control of Salmonella enterica serovar Typhimurium (ST; a facultative intracellular pathogen) in susceptible host. A significant increase of nitrite and/or nitrate plasma levels, 3-nitro-tyrosine expression and pathological changes in mesenteric lymph nodes have been observed in gnotobiotic piglets orally infected for 1 d with a virulent strain of ST but not in piglets infected with a rough mutant of ST.


IAEA Nuclear Data Section: provision of atomic and nuclear databases for user applications.
The Nuclear Data Section (NDS) of the International Atomic Energy Agency (IAEA) provides a wide range of atomic and nuclear data services to scientists worldwide, with particular emphasis placed on the needs of developing countries. Highly focused Co-ordinated Research Projects and multinational data networks are sponsored under the auspices of the IAEA for the development and assembly of databases through the organised participation of specialists from Member States. More than 100 data libraries are readily available cost-free through the Internet, CD-ROM and other media. These databases are used in a wide range of applications, including fission- and fusion-energy, non-energy applications and basic research studies. Further information concerning the various services can be found through the web address of the IAEA Nuclear Data Section: and a mirror site at IPEN, Brazil that is maintained by NDS staff:.


Middle segment pancreatectomy: a useful tool in the management of pancreatic neoplasms.
Small, benign or low grade malignant tumours located in the neck of the pancreas are usually treated with enucleation. However if enucleation is too risky because of possible damage to the main pancreatic duct, standard pancreatic resections are performed. Such operations can lead to impaired long term exocrine-endocrine function. Middle segment pancreatectomy consists of a limited resection of the midportion of the pancreas and can be performed in selected patients affected by tumours of the pancreatic neck. Middle segment pancreatectomy is a safe and feasible procedure for treating tumours of the pancreatic neck; in experienced hands it is associated with no mortality but with high morbidity; the rate of "clinical" pancreatic fistula is about 20%. Moreover, it allows the surgeon to preserve pancreatic parenchyma and consequently long term endocrine and exocrine pancreatic function.


[Prostate hypertrophy. Surgical experience in Belgium. Multi-center study of 1,140 patients of 80 years and older].
An inquiry organized by the Belgian Society of Surgery brought data on the mortality and morbidity of surgery on patients of 80 years and older for benign prostatic hypertrophy in a total number of 1,140 operations. Consensus exist to see this surgery as planned surgery. The mortality was 73 (6.3%) without statistical difference between endoscopic and open surgery. The morbidity of 824 patients was 165. This last figure relates to the big series in the literature. The mortality is in direct relation to the age of the patients. Evaluation of cardio-pulmonary risk (70.8% of the mortality), operation on indication at earlier diagnosis and prospective studies on the risk of operation in this population group are indicated.


Utilization of palliative care and its associated factors among adult cancer patients in Hawassa University comprehensive specialized hospital oncology center, Hawassa, Ethiopia, 2021: a cross-sectional study.
To assess the utilization of palliative care (PC) and its associated factors among adult cancer patients in Hawassa University Comprehensive Specialized Hospital (HUCSH) oncology center, Hawassa, Ethiopia, 2021. An institution-based cross-sectional study was conducted among adult cancer patients. Randomly selected adult cancer patients (≥ 18 years of age) attending their treatment at HUCSH oncology center PC unit were included. Data was collected from June to August, 2021. The aim was to interview 185 patients. A structured questionnaire was used to collect the data. Data entry was done using Epi-Data version 4.6 and bivariate and multivariate logistic regression models were used in SPSS for analysis. Out of 180 study respondents, 66% were aged 50 years or older. Sixty-three percent were characterized to have a better utilization of PC services. Patients aged below 50 years (adjusted odds radio (AOR) = 2.7; 95% CI = 1.13-6.63), with a higher educational status (grade 9 to 12 or college/university graduation (AOR = 1.46; 95% CI = 0.41-5.21, and AOR = 3.23; 95% CI = 0.98-10.61, respectively), with a higher income >5,500 Birr (AOR = 2.7; 95% CI = 0.51-5.76), with and good accessibility of PC services (AOR = 2.99; 95% CI = 1.21-3.28) were significantly associated with better utilization of PC services. The current study revealed two thirds of patients had better utilization of PC services. Older patients with low educational status and income and those living in rural areas had worse access to PC services. It is recommended to improve information provision about PC especially for older patients and patients with low education and to improve accessibility for patients in suburban and rural areas.


Multiple rearrangements and activated expression of c-myc induced by woodchuck hepatitis virus integration in a primary liver tumour.
Woodchuck hepatitis virus (WHV) is a small, partially double-stranded DNA virus. Like the related human hepatitis B virus (HBV), WHV induces acute and chronic hepatitis and hepatocellular carcinoma (HCC) in its natural host. WHV DNA integration into c-myc and N-myc, resulting in deregulated expression of these genes, has been described previously in woodchuck HCC. We have analysed a woodchuck liver tumour in which WHV DNA was integrated in the c-myc gene. The virus insertion provoked multiple alterations in one c-myc allele, probably involving secondary deletions and mutations. Integrated viral DNA, including promotor and enhancer sequences, acted as an insertional mutagen, leading to enhanced expression of heterogenous c-myc transcripts ranging from 7.2 to 14 kb in size, strikingly longer than normal 2.3-kb c-myc RNA. These results provide an additional example in which the oncogenic activation of a myc gene by cis-acting effect of WHV insertion may play a critical role in virus-induced woodchuck HCC.


UL84-independent replication of human cytomegalovirus strain TB40/E.
The UL84 gene of human cytomegalovirus is implicated in the initiation of viral DNA replication during lytic infection. UL84 is essential for replication of a cloned viral origin of lytic replication (oriLyt) in vitro and mutants of strains AD169 or Towne with deletions or insertions in UL84 fail to grow in cells permissive for wild type virus. Here we show that UL84 is dispensable for replication of a strain TB40/E clone derived from a bacterial artificial chromosome. The genomes of the fibroblast-adapted strains AD169 and Towne are altered substantially from the consensus for strains that have not been propagated extensively in cell culture. The parental TB40/E genome conforms to the consensus genomic organization. Accordingly, natural HCMV strains may possess replication capability that extends beyond the known oriLyt-dependent replication system of laboratory strains.


Right ventricular responses to massive and submassive pulmonary embolism.
It is critically important to quickly recognize and treat acute pulmonary embolism (PE). Submassive and massive PEs are associated with right ventricular (RV) dysfunction and may culminate in RV failure, cardiac arrest, and death. A rapid and coordinated diagnostic and management approach can maximize success and save lives.


Linking APOE-ε4, blood-brain barrier dysfunction, and inflammation to Alzheimer's pathology.
The APOE-ε4 genotype is a risk factor for late-onset Alzheimer's disease (AD) as well as vascular pathology. Given the increased risk of blood-brain barrier (BBB) dysfunction and inflammation among APOE-ε4 carriers, we aimed to examine whether BBB dysfunction and inflammation contribute to the relationship between APOE and AD key pathologies, as measured in the cerebrospinal fluid (CSF). We applied bootstrapped regression and path analyses involving Q-albumin CSF/plasma ratio (a BBB/blood-CSF barrier function marker), interleukins (IL-1β, IL-6, and IL-12p70; inflammation markers), and CSF p-Tau181 and amyloid-β1-42 (AD pathology markers) of 97 participants (aged 38-83 years) from a university memory clinic. Our results showed that relationship between BBB dysfunction and AD pathology is modulated by IL-6 and these associations appear to be driven by the APOE-ε4 genotype. This suggests that APOE-ε4-related vascular factors are also part of the pathway to AD pathology, in synergy with an elevated immune response, and could become targets for trials focused on delaying AD.