Limb accelerations during sleep are related to measures of strength, sensation, and spasticity among individuals with spinal cord injury.
To evaluate the relationship between measures of neuromuscular impairment and limb accelerations (LA) collected during sleep among individuals with chronic spinal cord injury (SCI) to provide evidence of construct and concurrent validity for LA as a clinically meaningful measure. The strength (lower extremity motor score), sensation (summed lower limb light touch scores), and spasticity (categorized lower limb Modified Ashworth Scale) were measured from 40 adults with chronic (≥ 1 year) SCI. Demographics, pain, sleep quality, and other covariate or confounding factors were measured using self-report questionnaires. Each participant then wore ActiGraph GT9X Link accelerometers on their ankles and wrist continuously for 1-5 days to measure LA from movements during sleep. Regression models with built-in feature selection were used to determine the most relevant LA features and the association to each measure of impairment. LA features were related to measures of impairment with models explaining 69% and 73% of the variance (R²) in strength and sensation, respectively, and correctly classifying 81.6% (F1-score = 0.814) of the participants into spasticity categories. The most commonly selected LA features included measures of power and frequency (frequency domain), movement direction (correlation between axes), consistency between movements (relation to recent movements), and wavelet energy (signal characteristics). Rolling speed (change in angle of inclination) and movement smoothness (median crossings) were uniquely associated with strength. When LA features were included, an increase of 72% and 222% of the variance was explained for strength and sensation scores, respectively, and there was a 34% increase in spasticity classification accuracy compared to models containing only covariate features such as demographics, sleep quality, and pain. LA features have shown evidence of having construct and concurrent validity, thus demonstrating that LA are a clinically-relevant measure related to lower limb strength, sensation, and spasticity after SCI. LA may be useful as a more detailed measure of impairment for applications such as clinical prediction models for ambulation.


Infection control operations of a large hospital in Taiwan to prevent nosocomial outbreaks during COVID-19 pandemic.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) is highly contagious, with a potential to cause large nosocomial outbreaks in the hospital setting. We report the advance deployment of comprehensive, multi-level infection control measures in a 3,700-bed large hospital to prevent nosocomial outbreaks of COVID-19 during the pandemic. We implemented a series of dynamic infection control policies during the pandemic. A confirmed COVID-19 case was defined by positive real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. All healthcare worker (HCW) having symptoms or close contact with the confirmed case received the RT-PCR test. A total of 5,722 patients were tested in our hospital from January to May 2020. Twenty-five patients were confirmed COVID-19, including two inpatients. A cluster of 4 HCWs with COVID-19 associated with the 2nd inpatient was identified in the early stage of epidemic. Our enhanced traffic control bundling, mask wearing, hand hygiene and environmental cleaning were reinforced after the outbreak. All other confirmed cases were identified at our outdoor quarantine station or epidemic clinic afterwards, and the results of testing for 146 symptomatic HCWs were all negative. Integrated teamwork, advance deployment of infection control measures and efficient diagnostic testing and response protected HCW and facilities from large SARS-CoV-2 outbreaks and preserved the capacity and function of the health care system during the pandemic.


Birth order and parental age in microphthalmos and other ocular diseases.
We compared the distribution of birth order and maternal and paternal ages of blind school children throughout Japan with that of the total Japanese population of the corresponding age groups and with that of a subgroup of children with acquired blindness. The number of first-born children with microphthalmos was smaller, and the number of second-, third-, or fourth-born children was larger, as compared with the control groups. The differences were highly statistically significant by chi-square test. There was a less pronounced indication of birth order effect in amblyopia, congenital cataract, and optic nerve atrophy, which involved more first-borns than in the controls. The distribution of maternal age was also different from the control group in microphthalmos, congenital cataract, corneal opacity, and optic nerve atrophy. Less mothers in their 20s and more in their 30s produced children with these conditions. We believe this finding may be partly related to the rapid decline in infant mortality and in the incidence of congenital blindness in Japan.


Partial beneficial effects of the so called "silent iodine prophylaxis" on iodine deficiency disorders (IDD) in northeastern Sicily endemia.
The prevalence of goiter among schoolchildren and the daily urinary iodine excretion in the general population were evaluated in 4 municipalities in the endemic goiter area in Northeastern Sicily in two different surveys. The first, carried out in 1977-1978, covered 2,493 (91%) schoolchildren; the second, in 1987-1988, covered 2,167 (92%) schoolchildren. A dramatic decrease in goiter prevalence was apparent in each community as follows: in Castell'Umberto (3,904 inhabitants, altitude 641/750 m above sea level) goiter prevalence (G) decreased from 79.7% to 44.2% with a percent reduction (%r) of 44.5 and an increase in 24-h urinary iodine excretion (UIE) from 22.3 +/- 16.4 micrograms/24 h (n = 30) to 48.7 +/- 43.4 (n = 50). A similar trend was apparent in Tortorici (10,194 inhabitants, 475/700 m) where G decreased from 62.2 to 26.5% (% r 57.4) with a UIE increase from 28.4 +/- 29.6 (n = 35) to 47.6 +/- 59.3 (n = 40); in Sinagra (3,387 inhabitants, 300 m) where G decreased from 61.6 to 32.7% (% r 46.9) and UIE increased from 26.0 +/- 21.1 (n = 25) to 66.6 +/- 69.6 (n = 102) and in Sant'Angelo di Brolo (5,732 inhabitants, 380 m) where G decreased from 48.7 to 27.5% (% r 43.5) and UIE increased from 26.3 +/- 16.7 (n = 30) to 47.7 +/- 73.8 (n = 34). These events are clearly related and certainly dependent on the changed alimentary habits in the area due to the improved distribution of frozen food and industrially prepared dairy products, eventually enriched by iodine.(ABSTRACT TRUNCATED AT 250 WORDS)


miR-141-3p enhanced radiosensitivity of CRC cells.
Colorectal cancer (CRC) is recognized as one of the frequently diagnosed malignancies and numerous microRNAs (miRs) are identified to be active in CRC. The purpose of this work was to clarify the effect of miR-141-3p on radiosensitivity of CRC cells. Firstly, CRC cell lines were cultured and applied to construct radiation-resistant CRC cells via X-ray treatment. The expression levels of miR-141-3p and long non-coding RNA DLX6 antisense RNA 1 (lncRNA DLX6-AS1) in CRC cells were measured using real-time quantitative polymerase chain reaction. After transfection with miR-141-3p mimics and 24 h treatment with 6-MV X-ray (0, 2, 4, 6 Gy), the survival fraction (SF) and the colony formation ability of CRC cells were determined using the cell counting kit-8 and colony formation methods. The interactions between miR-141-3p and DLX6-AS1 were analyzed using the dual-luciferase assay. The impact of miR-141-3p on DLX6-AS1 stability was detected after the addition of actinomycin-D. The role of DLX6-AS1 in radiosensitivity of CRC cells was explored by transfecting oe-DLX6-AS1 into radiation-resistant CRC cells overexpressing miR-141-3p. The relative expression levels of miR-141-3p were downregulated in CRC cells and further declined in radiation-resistant cells. Upregulation of miR-141-3p relative expression reduced SF and the colony formation ability while amplified radiosensitivity of radiation-resistant CRC cells. miR-141-3p directly bound to DLX6-AS1 to reduce DLX6-AS1 stability, and therefore downregulated DLX6-AS1 expression. DLX6-AS1 overexpression counteracted the role of miR-141-3p overexpression in amplifying radiosensitivity of radiation-resistant CRC cells. miR-141-3p binding to DLX6-AS1 significantly decreased DLX6-AS1 stability and expression, promoting radiosensitivity of CRC cells.


The low energy X-ray spectrometry technique as applied to semiconductors.
We describe the recent introduction of low energy X-ray emission spectrometry as a metrology technique to control the fabrication process in the integrated circuit industry. The benefits of this particular analytical method and the wide field of potential applications are addressed.


The role of glial fibrillary acidic protein in the diagnosis of central nervous system tumors.
Eighty glial and non-glial brain tumors have been studied to date using an immunologically specific and highly sensitive method of staining GFA protein which is applicable to formalin fixed and paraffin embedded tissue. Eight of these cases have been described and illustrated in some detail. GFA protein was present in all astrocytes and astrocytomas studied and in a proportion of ependymal cells and ependymomas. Some tumor cells have been demonstrated by this method to be glial despite the complete lack of blue fibrillar staining with PTAH and the absence of all morphological similarity to glial cells. In such cases the demonstration of GFA protein by this method has been valuable in establishing a diagnosis. In addition to its diagnostic value in specific cases, the method promises to shed light on unsolved problems of tumor cytogenesis.


Comparison of subjective lameness evaluation, force platforms and an inertial-sensor system to identify mild lameness in an equine osteoarthritis model.
When mild lameness exists, agreement between clinicians is often controversial due to its subjective nature. The goal of the study was to compare subjective and objective methods to identify the presence of mild lameness using an established model of osteoarthritis (OA) in which OA was induced by creating a unilateral carpal osteochondral fragment (OCF) in the middle carpal joint of 16 horses. Subjective lameness evaluations (blinded and unblinded), force platforms (FP), and an inertial-sensor system (ISS) were used to detect forelimb lameness at four time points. Limbs identified as lame by each method were compared as well as compared with the OCF limb at each time point. Spearman correlations were calculated between all outcome parameters. Independent of time, blinded subjective evaluation (54%) and the ISS (60%) identified a higher percentage of horses as lame in the OCF limb compared to FP (40%). Blinded subjective evaluation and the ISS agreed which forelimb was lame more often (50%) compared with blinded subjective evaluation and the FP (38%). Induction of mild lameness within the OCF limb was supported by an increase in the frequency of horses considered lame by both subjective evaluations the ISS and a decrease (3.6%) in mean (among all horses) peak vertical force from baseline to post OCF induction. The percentage of horses identified as lame in the OCF limb, independent of time, was highest with the ISS (60%) followed by blinded subjective evaluation (51%) and the FP (42%). It was concluded that the best agreement was between subjective evaluation and the inertial-sensor system.


Region-specific expression of brain-derived neurotrophic factor splice variants in morphine conditioned place preference in mice.
It is well established that brain-derived neurotrophic factor (BDNF) plays a pivotal role in brain plasticity-related processes, such as learning, memory and drug addiction. However, changes in expression of BDNF splice variants after acquisition, extinction and reinstatement of cue-elicited morphine seeking behavior have not yet been investigated. Real-time PCR was used to assess BDNF splice variants (I, II, IV and VI) in various brain regions during acquisition, extinction and reinstatement of morphine-conditioned place preference (CPP) in mice. Repeated morphine injections (10mg/kg, i.p.) increased expression of BDNF splice variants II, IV and VI in the hippocampus, caudate putamen (CPu) and nucleus accumbens (NAcc). Levels of BDNF splice variants decreased after extinction training and continued to decrease during reinstatement induced by a morphine priming injection (10mg/kg, i.p.). However, after reinstatement induced by exposure to 6 min of forced swimming (FS), expression of BDNF splice variants II, IV and VI was increased in the hippocampus, CPu, NAcc and prefrontal cortex (PFC). After reinstatement induced by 40 min of restraint, expression of BDNF splice variants was increased in PFC. These results show that exposure to either morphine or acute stress can induce reinstatement of drug-seeking, but expression of BDNF splice variants is differentially affected by chronic morphine and acute stress. Furthermore, BDNF splice variants II, IV and VI may play a role in learning and memory for morphine addiction in the hippocampus, CPu and NAcc.


Camel milk ameliorates diabetes in pigs by preventing oxidative stress, inflammation and enhancing beta cell function.
The purpose of the study was to determine how camel milk affects hyperglycemia, beta-cell function, oxidative stress, and inflammatory markers in type 2 diabetic pigs. Twenty-five (25) pigs were separated into five (5) groups of five pigs each, with five (5) non-diabetic and twenty (20) diabetic pigs in each group. Groups 1 and 2 received distilled water as the standard control and diabetic control groups, respectively, while Groups 3 and 4 received camel milk at 250 mL/day and 500 mL/day, respectively, and Group 5 received metformin at 500 mg/day. The experiment lasted ten weeks. At the end of the ten weeks, all the pigs were euthanized. Treatments with camel milk substantially enhance glucose fasting levels by reducing hyperglycemia in diabetic pigs, significant level at (p < 0.05). When pigs given camel milk were compared with untreated diabetic pigs, there was a substantial rise (p < 0.05) in superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) levels. Also, camel milk substantially lowered the levels of interleukin (IL-1β) and tumour necrosis factor-alpha (TNF-α) in diabetic pig serum. Similarly, immunohistochemical analysis of islet cells revealed an increase in insulin production, implying improved glycemic control and the eventual commitment of glucose to glycolysis. The bioactive-mediated anti-hyperglycemic and insulin release potential of camel milk treatments contributed to improving type 2 diabetes mellitus. Camel milk improved beta-cell function while reducing oxidative stress and inflammation in type 2 diabetic pigs.


The prediction of hearing thresholds with auditory steady-state responses for cochlear implanted children.
The objectives of this study were to investigate the efficacy of auditory steady-state response (ASSR) in predicting cochlear implanted children's actual behavioural thresholds at various frequencies. Twenty-two children with cochlear implants (Nucleus 24 devices) participated in this study. Behavioural thresholds and/or ASSR in cochlear implanted children were obtained to determine the predictive accuracy rates and errors by comparing the estimated range of thresholds with the actual behavioural thresholds. Stable ASSR threshold results were obtained in 22 cochlear implanted children. The predictive accuracy rates were the highest and prediction errors were the smallest at 4000 Hz, among the four tested frequencies, using either the Rance 1995 or the Rance 2002 linear regression formulae. The Rance 2002 regression formulae had a higher predictive accuracy and fewer errors than the Rance 1995 regression formulae in predicting the hearing threshold of cochlear implanted patients at all tested frequencies. Both behavioural thresholds and ASSR thresholds revealed significant improvements after cochlear implantation. ASSR may be used as a tool in predicting hearing thresholds after cochlear implantation in children. The predictive accuracy is best at 4000 Hz with the Rance 2002 linear regression formulae.


Predictive value of cytokine/chemokine responses for the disease severity and management in children and adult cases with COVID-19.
The disease course of children with coronavirus disease 2019 (COVID-19) seems milder as compared with adults, however, actual reason of the pathogenesis still remains unclear. There is a growing interest on possible relationship between pathogenicity or disease severity and biomarkers including cytokines or chemokines. We wondered whether these biomarkers could be used for the prediction of the prognosis of COVID-19 and improving our understanding on the variations between pediatric and adult cases with COVID-19. The acute phase serum levels of 25 cytokines and chemokines in the serum samples from 60 COVID-19 pediatric (n = 30) and adult cases (n = 30) including 20 severe or critically ill, 25 moderate and 15 mild patients and 30 healthy pediatric (n = 15) and adult (n = 15) volunteers were measured using commercially available fluorescent bead immunoassay and analyzed in combination with clinical data. Interferon gamma-induced protein 10 (IP-10) and macrophage inflammatory protein (MIP)-3β levels were significantly higher in patient cohort including pediatric and adult cases with COVID-19 when compared with all healthy volunteers (p ≤ .001 in each) and whereas IP-10 levels were significantly higher in both pediatric and adult cases with severe disease course, MIP-3β were significantly lower in healthy controls. Additionally, IP-10 is an independent predictor for disease severity, particularly in children and interleukin-6 seems a relatively good predictor for disease severity in adults. IP-10 and MIP-3β seem good research candidates to understand severity of COVID-19 in both pediatric and adult population and to investigate possible pathophysiological mechanism of COVID-19.


Determinants of outcome after surgical treatment of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries.
Identification of variables influencing surgical outcome in patients treated for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. A total of 90 consecutive patients (median age, 12 months; range, 20 days to 35 years), who had primarily undergone either 1-stage unifocalization (n = 69) or palliation to promote native pulmonary arterial development (n = 21), were studied. Chromosome 22q11 deletion had occurred in 37% of the cases. Ventricular septal defect closure was accomplished in 70 patients (78%), with a mean postoperative right/left ventricular pressure ratio of 0.48 ± 0.14. The rate of 14-year survival, freedom from conduit reintervention, and freedom from percutaneous intervention on the pulmonary arteries was 75%, 46%, and 52%, respectively. At a median interval of 95 months (range, 1.5-164 months), the right/left ventricular pressure ratio did not differ significantly from early postoperatively. Univariate analysis showed that an absence of confluent intrapericardial pulmonary arteries favorably affected the postoperative right/left ventricular pressure ratio after ventricular septal defect closure (P = .04). Kaplan-Meier estimates showed age of 30 days or younger (P = .0004) and weight of 3 kg or less (P = .0004) at unifocalization and chromosome 22q11 deletion (P = .001) significantly affected survival. Chromosome 22q11 deletion was significantly associated with mortality, even in the Cox regression model (hazard ratio, 8.26; P = .003). Finally, ventricular septal defect closure during single-stage and single/multiple-stage procedures significantly correlated with both early (P = .0013 and P < .00001, respectively) and overall (P = .013 and P = .0007, respectively) survival. The results of surgery were satisfactory and durable, despite the need for repeated percutaneous or surgical reinterventions. The outcomes were negatively affected by neonatal age and low body weight and positively affected by simultaneous or staged ventricular septal defect closure. Finally, chromosome 22q11 deletion remained an independent variable affecting survival.


Nutrient removal efficiency in a rice-straw denitrifying bioreactor.
Rice straw was used as a carbon source in a denitrifying bioreactor, for the removal of nutrients from agricultural drainage. Nutrient removal efficiency was evaluated by: (a) nutrient loading rates (low, medium, and high); (b) hydraulic retention time, and (c) comparison with another carbon source (woodchip). The results show that concentrations of nitrate nitrogen (NO3(-)-N), ammonia nitrogen (NH4(+)-N), total nitrogen (TN), and orthophosphate phosphorus (PO4(3-)-P) in the rice-straw bioreactor effluents were reduced by 53%, 25%, 40%, and 35%, respectively, compared with influents at the medium nutrient loading rate (NO3(-)-N: 10-15 mg N L(-1), NH4(+)-N: 10-15 mg N L(-1), PO4(3-)-P: 1.0-1.5 mg P L(-1)) and long hydraulic retention time (HRT, 24h), with a corresponding denitrification rate (DR) of 0.40 mg N L(-1)h(-1). Moreover, the rice-straw bioreactor showed significantly higher (p<0.05) nutrient removal efficiency than the woodchip bioreactor at the medium nutrient loading rate and 24h HRT.


Risk factors for postoperative adverse outcomes and secondary surgery in pediatric patients with unilateral ectopic ureterocele associated with the duplex system.
Ectopic ureterocele management in children remains a controversial subject without a clear consensus. The purpose of this study was to explore the risk factors for adverse outcomes and secondary surgery in pediatric patients with unilateral ectopic duplex system ureterocele, a complex urinary system deformity with controversial treatment. We retrospectively reviewed 75 patients with unilateral ectopic duplex system ureterocele who underwent surgery at the Shengjing Hospital of China Medical University between January 1, 2008, and September 31, 2020. Demographic characteristics, preoperative data, surgical procedures, postoperative adverse outcomes, and secondary surgery were recorded. Adverse outcomes were defined as new-onset VUR and BOO after surgery. The risks of adverse outcomes and secondary surgery were evaluated using multivariate binary logistic regression and expressed as adjusted odds ratios with 95% confidence intervals. Adverse outcomes occurred in 25 (33.3%) patients, including 24 (32.0%) with new-onset vesicoureteral reflux and 1 (1.3%) with bladder outlet obstruction. Seven (9.3%) patients required secondary surgery. The independent risk factors for adverse outcomes were transurethral endoscopic incision and transurethral endoscopic puncture (transurethral endoscopic incision vs. upper pole partial nephrectomy: OR = 11.049, P = 0.004; transurethral endoscopic puncture vs. upper pole partial nephrectomy: OR = 33.222, P = 0.002). The definitive treatment for duplex system ureterocele remains controversial. We found that transurethral endoscopic incision or puncture was an independent risk factor for adverse outcomes. The main limitation of this study would be its retrospective nature and relatively short follow-up period. Furthermore, 30 children were younger than 5 years at last follow up, and thus, we could not efficiently evaluate their voiding function. Transurethral endoscopic incision or puncture is effective for decompressing the obstruction of the upper urinary tract in acute urosepsis in ectopic duplex system ureterocele. Although more than half of patients with unilateral ectopic duplex system ureterocele suffered from new-onset vesicoureteral reflux after transurethral endoscopic incision or puncture, few of them required secondary surgery.


Cytokines from the tumor microenvironment modulate sirtinol cytotoxicity in A549 lung carcinoma cells.
Cytokines in tumor microenvironment play an important role in the success or failure of molecular targeted therapies. We have chosen tumor necrosis factor α (TNF-α), TNF related apoptosis inducing ligand (TRAIL), insulin-like growth factor 1 (IGF-1) and transforming growth factor β (TGF-β) as representative pro-inflammatory, pro-apoptotic, anti-apoptotic and anti-inflammatory tumor derived cytokines. Analysis of Oncomine database revealed the differential expression of these cytokines in a subset of cancer patients. The effects of these cytokines on cytotoxicity of FDA approved drugs - cisplatin and taxol and inhibitors of epidermal growth factor receptor - AG658, Janus kinase - AG490 and SIRT1 - sirtinol were assessed in A549 lung cancer cells. TRAIL augmented cytotoxicity of sirtinol and IGF-1 had a sparing effect. Since TRAIL and IGF-1 differentially modulated sirtinol cytotoxicity, further studies were carried out to identify the mechanisms. Sirtinol or knockdown of SIRT1 increased the expression of death receptors DR4 and DR5 and sensitized A549 cells to TRAIL. Increased cell death in presence of TRAIL and sirtinol was caspase independent and demonstrated classical features of necroptosis. Inhibition of iNOS increased caspase activity and switched the mode of cell death to caspase mediated apoptosis. Interestingly, sirtinol or SIRT1 knockdown did not increase IGF-1R expression. Instead, it abrogated ligand induced downregulation of IGF-1R and increased cell survival through PI3K-AKT pathway. In conclusion, these findings reveal that the tumor microenvironment contributes to modulation of cytotoxicity of drugs and that combination therapy, with agents that increase TRAIL signaling and suppress IGF-1 pathway may potentiate anticancer effect.


Identification of ampullary and isthmic oviductal fluid proteins that associate with the bovine sperm membrane.
The objective of this study was to define the complement of ampullary and isthmic oviductal fluid proteins that associate with the sperm membrane during the non-luteal and luteal stages of the oestrous cycle. Oviductal fluid was obtained from three dairy cows via indwelling cannulae in the ampulla and isthmus of the same oviduct. Daily samples of oviductal fluid were combined by region and stage of the cycle to create pools consisting of non-luteal isthmic, luteal isthmic, non-luteal ampullary, and luteal ampullary oviductal fluid. An aliquot from each oviductal fluid pool was biotinylated by incubation in biotin reagent. Spermatozoa from three fertile bulls were pooled, washed and incubated for 4 h in each of the four pools of biotinylated oviductal fluid. After incubation, sperm membrane proteins were solubilized, and proteins subjected to one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blotting. The biotinylated oviductal fluid proteins that associated with the sperm membranes were detected by avidin-horseradish peroxidase and diaminobenzidine substrate. Eight oviductal fluid proteins with apparent molecular weights of 97, 75, 66, 55, 48, 34, 28 and 24 kDa were consistently detected to associate with the sperm membrane. Differences in ampullar and isthmic fluid proteins that associated with sperm during the luteal and non-luteal stage of the oestrous cycle were not detected.


[Determination of deoxyribonucleic acid with pararosaniline by a resonance light-scattering method].
The method is based on the enhancement effect of the resonance light-scattering (RLS) of pararosaniline by DNA. In the pH rang of 0.5-1.5, the enhanced intensity of pararosaniline RLS at 355 nm is proportional to the concentration of DNA in the rang of 0.20-15 micrograms.mL-1. The detection limit is 36 ng.mL-1. This method is simple, rapid and has been applied satisfactorily to the determination of DNA in mixed samples.


Effect of laparoscopic liver resection on postoperative delirium in elderly patients with hepatocellular carcinoma.
Delirium is a multifactorial and heterogeneous syndrome that is defined as acutely altered consciousness. This retrospective multicenter study evaluated the impact of postoperative delirium after liver resection for hepatocellular carcinoma (HCC) in elderly patients. Patients aged ≥75 years, who underwent curative liver resection for HCC at nine university hospitals from April 2010 to December 2017, were evaluated to compare short- and long-term outcomes between patients with and without delirium. Risk factors for delirium were determined using multivariate regression analysis. The rate of postoperative delirium was 14.2% (n = 80) in the study cohort of 562 patients. Multivariate analysis revealed smoking history, hypertension, sleeping pill consumption, and open liver resection as risk factors for postoperative delirium. The rate of other causes of death was significantly higher in the delirium group than in the no-delirium group although the rate of death at 1 year due to HCC or liver failure was similar between the two groups (p = .015). The 1-year mortality rates due to vascular diseases were 71.4% and 15.4% in the delirium and no-delirium groups, respectively (p = .022). The 1-, 3-, and 5-year survival rates after liver resection were 86.6%, 64.1%, and 36.5% in the delirium group and 91.3%, 71.2%, and 56.9% in the no-delirium group, respectively (p = .046). The multivariate analysis revealed the possible benefits of laparoscopic liver resection in reducing the rate of postoperative delirium after liver resection for HCC in elderly patients.


Effects of hypoxia and HIFs on cancer metabolism.
Cancer cells are characterized by rapid proliferation and require adaptive metabolic responses to allow continued biosynthesis and cell growth in the setting of decreased oxygen (O(2)) and nutrient availability. The hypoxia-inducible factors (HIFs) are a common link between adaptation to low O(2), changes in cancer metabolism, and malignant progression. The HIF-α subunits differentially regulate metabolic enzymes and other key factors involved in glycolysis, changes in redox status, and oxidative phosphorylation. Importantly, metabolic changes can, in turn, regulate HIF activity. Finally, changes in metabolism under hypoxia lead to important crosstalk between cancer cells and the stromal compartment of the microenvironment.


Growing skull fractures: progressive evolution of brain damage and effectiveness of surgical treatment.
The growing skull fracture of childhood is a well-known but variously interpreted syndrome. Attempts have been made to find different pathogeneses for clinical and pathological patterns that are really successive phases of a single process, arising from the interaction of three basic conditions: (1) head injury with a large gaping fracture; (2) corresponding dural tear; (3) occurrence nearly always in infancy (the first year of life or period of maximum brain growth). This combination of factors alters the normal distribution of the intracranial pressure vectors and the fracture behaves like a "neosuture" with abnormal growth of the skull on the injured side. Simultaneously, the ventricular system tends to deform, dilating and shifting towards the side of the fracture. Three cases, successfully treated at a very late stage, are described. The good surgical results confirm the validity of the surgical method and its underlying theoretical basis.


Fetal jejunoileal atresia with persistent omphalomesenteric duct.
A case of fetal jejunoileal atresia in association with persistent omphalomesenteric duct is presented. The dilated stomach and proximal and distal duodenum produced a multiple bubble sign on the prenatal sonogram. The neonate underwent exploratory laparotomy, excision of the persistent omphalomesenteric duct, gastrotomy, and colostomy. Possible causes of jejunoileal atresia are presented.


Cross-modality image translation: CT image synthesis of MR brain images using multi generative network with perceptual supervision.
Computed tomography (CT) and magnetic resonance imaging (MRI) are the mainstream imaging technologies for clinical practice. CT imaging can reveal high-quality anatomical and physiopathological structures, especially bone tissue, for clinical diagnosis. MRI provides high resolution in soft tissue and is sensitive to lesions. CT combined with MRI diagnosis has become a regular image-guided radiation treatment plan. In this paper, to reduce the dose of radiation exposure in CT examinations and ameliorate the limitations of traditional virtual imaging technologies, we propose a Generative MRI-to-CT transformation method with structural perceptual supervision. Even though structural reconstruction is structurally misaligned in the MRI-CT dataset registration, our proposed method can better align structural information of synthetic CT (sCT) images to input MRI images while simulating the modality of CT in the MRI-to-CT cross-modality transformation. We retrieved a total of 3416 brain MRI-CT paired images as the train/test dataset, including 1366 train images of 10 patients and 2050 test images of 15 patients. Several methods (the baseline methods and the proposed method) were evaluated by the HU difference map, HU distribution, and various similarity metrics, including the mean absolute error (MAE), structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), and normalized cross-correlation (NCC). In our quantitative experimental results, the proposed method achieves the lowest MAE mean of 0.147, highest PSNR mean of 19.27, and NCC mean of 0.431 in the overall CT test dataset. In conclusion, both qualitative and quantitative results of synthetic CT validate that the proposed method can preserve higher similarity of structural information of the bone tissue of target CT than the baseline methods. Furthermore, the proposed method provides better HU intensity reconstruction for simulating the distribution of the CT modality. The experimental estimation indicates that the proposed method is worth further investigation.


Benzo[e]pyrene metabolism in rat liver microsomes: dependence of the metabolite profile on the pretreatment of rats with various monooxygenase inducers.
Benzo[r]pyrene (B[e]P) is metabolized by liver microsomes of untreated rats to trans-4,5-dihydroxy-4,5-dihydrobenzo(e)pyrene and 1- as well as 3-hydroxybenzo[e]pyrene as shown by g.l.c. and mass spectrometry of their trimethylsilyl ethers. After pretreatment of the rats with various monooxygenase inducers oxidation at the 9/10-position was also observed. In addition, secondary oxidation to dihydrodiolepoxides and the formation of a tetrol, tentatively identified as 4,5,9,10-tetrahydroxy-4,5,9,10-tetrahydrobenzo[e]pyrene was detected after incubation of B[e]P with liver microsomes of rats treated with polycyclic aromatic hydrocarbons. However, no formation of the supposed ultimate carcinogen, the 9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydrobenzo[e]pyrene could be observed after any of the pretreatments.


Breast Cancer in India: Screening, Detection, and Management.
Breast cancer is the most common cancer in urban Indian women and the second most common cancer in all Indian women. The epidemiology as well as biology of this cancer seems to be different in the Indian subcontinent when compared with the West. The lack of population-based breast cancer screening programs and delay in seeking a medical consult due to financial and social reasons, including lack of awareness and fear related to a cancer diagnosis, results in delayed diagnosis.


Low-level mosaic trisomy 13 at amniocentesis associated with a favorable outcome in a pregnancy.
We present low-level mosaic trisomy 13 at amniocentesis associated with a favorable outcome in a pregnancy. A 39-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+13[8]/46,XY[20]. The woman underwent cord blood sampling at 22 weeks of gestation. Cytogenetic analysis of cord blood revealed a karyotype of 47,XY,+13[2]/46,XY[98]. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cord blood revealed 10% gene dosage increase in chromosome 13. Prenatal ultrasound findings were unremarkable. After genetic counseling, the parents decided to continue the pregnancy, and a 2,280-g healthy male baby was delivered at 38 weeks of gestation. The parental karyotypes were normal. The cord blood at birth had a karyotype of 47,XY,+13[1]/46,XY[49]. At age one month, interphase fluorescence in situ hybridization (FISH) analysis revealed no trisomy 13 signals in 100/100 buccal mucosal cells, and trisomy 13 signals in 2/54 (3.7%) urinary cells compared with 0/60 cells in the normal control. The neonate was doing well and presented neither phenotypic abnormalities nor psychomotor disorders at age two months. Low-level true mosaic trisomy 13 at amniocentesis without ultrasound abnormalities can be associated with a favorable outcome.


Lobachevsky crystallography made real through carbon pseudospheres.
We realize Lobachevsky geometry in a simulation lab, by producing a carbon-based energetically stable molecular structure, arranged in the shape of a Beltrami pseudosphere. We find that this structure: (i) corresponds to a non-Euclidean crystallographic group, namely a loxodromic subgroup of SL(2, Z); (ii) has an unavoidable singular boundary, that we fully take into account. Our approach, substantiated by extensive numerical simulations of Beltrami pseudospheres of different size, might be applied to other surfaces of constant negative Gaussian curvature, and points to a general procedure to generate them. Our results also pave the way to test certain scenarios of the physics of curved spacetimes owing to graphene's unique properties.


Heterogeneity of weight gain after initiation of Elexacaftor/Tezacaftor/Ivacaftor in people with cystic fibrosis.
The introduction of the novel therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been effective in improving weight gain in both clinical trials and real-world studies. However, the magnitude of this effect appears to be heterogeneous across patient subgroups. This study aims to identify potential determinants of heterogeneity in weight gain following 6-month ETI therapy. We conducted a multicenter, prospective cohort study enrolling 92 adults with CF at two major CF centers in Italy with follow-up visit at one month and six months from ETI initiation. The treatment's effect on weight changes was evaluated using mixed effect regression models that included subject-specific random intercepts and fixed effects for potential predictors of treatment response, time and a predictor-by-time interaction term. The mean weight gain at six months from the start of treatment was 4.6 kg (95% CI: 2.3-6.9) for the 10 patients with underweight, 3.2 kg (95% CI: 2.3-4.0) for the 72 patients with normal weight, and 0.7 kg (95% CI: -1.6-3.0) for the 10 patients with overweight. After six months of ETI treatment, 8 (80%) of the patients with underweight transitioned to the normal weight category, while 11 (15.3%) of the normal-weight patients became overweight. The major determinants of heterogeneity in weight gain were the baseline BMI and the presence of at least one CFTR residual function mutation, explaining 13% and 8% of the variability, respectively. Our results indicate that ETI is highly effective in improving weight gain in underweight subjects with CF. However, our data also suggests the need for close monitoring of excess weight gain to prevent potential cardiometabolic complications.


Intracellular study of oculomotor neurons in the rat.
The electrical and morphological properties of oculomotor neurons were investigated in the rat with intracellular recordings and intracellular horseradish peroxidase staining. Motoneurons were identified by their antidromic response to electrical stimulation of the ipsilateral medial rectus muscle. The antidromic action potential was followed by a delayed depolarization and an afterhyperpolarization of 20-50 ms in duration. The whole neuron input resistance calculated from intensity/voltage curves, was found between 4 and 15 M omega. Passive membrane properties showed the existence of anomalous rectifications. Motoneurons were studied on the basis of their responses to long-lasting depolarizing current pulses. The intensity/frequency curves suggest the existence of two ranges of discharges. The average intensity frequency slope during the steady state was 33 imp/s/nA. Ten oculomotor neurons were intracellularly labelled with horseradish peroxidase and fully reconstructed. The soma (23-33 microns in diameter) gave off five-eight primary dendrites which could extend over 600-800 microns from the soma. The oculomotor neurons were principally oriented in the sagittal plane. The soma size of oculomotor neurons was not related to the size of proximal tree. According to our observations, the morphological features of motoneurons did not allow us to predict the whole neuron input resistance. The comparison between in vivo and in vitro studies of oculomotor neurons revealed one major difference in the input resistance of the whole neuron which was three times higher in slices.


Revisiting the dynamic and thermodynamic processes driving the record-breaking January 2014 precipitation in the southern UK.
Many attribution studies of precipitation extreme events have attempted to estimate the thermodynamic contribution (linked to temperature changes) and the dynamic contribution (linked to the atmospheric circulation). Those studies are based on statistical decompositions of atmospheric fields, and essentially focus on the horizontal motion of the atmosphere. This paper proposes a framework that decomposes those terms from first physical principles, which include the vertical atmospheric motion that has often been overlooked. The goal is to take into account the driving processes of the extreme event. We revisit a recent example of extreme precipitation that was extensively investigated through its relation with the atmospheric circulation. We find that although the horizontal motion plays a minor (but important) role, the vertical motion yields a dominating contribution to the event that is larger than the thermodynamic contribution. This analysis quantifies the processes leading to high winter precipitation rates, and can be extended for further attribution studies.


A new procedure for the synthesis of polyethylene glycol-protein adducts; effects on function, receptor recognition, and clearance of superoxide dismutase, lactoferrin, and alpha 2-macroglobulin.
A new, simplified technique for the synthesis of polyethylene glycol (PEG) derivatives of proteins utilizing 1,1'-carbonyldiimidazole for PEG activation, is described. PEG derivatives of superoxide dismutase, alpha 2-macroglobulin, alpha 2-macroglobulin-trypsin, and lactoferrin were prepared and studied. Superoxide dismutase coupled to PEG preserved 95% of its original activity while its plasma half-life increased from 3.5 min to 9 or more hours depending on the PEG derivative studied. PEG-derivatized alpha 2-macroglobulin showed decreased protease binding activity but PEG derivatives of performed alpha 2-macroglobulin-trypsin demonstrated no loss of activity. The plasma clearance of PEG-alpha 2-macroglobulin-trypsin was prolonged significantly compared to native alpha 2-macroglobulin-trypsin, particularly when a high-molecular-weight PEG was coupled to the protease inhibitor complex. The plasma clearance half-life of lactoferrin was increased 5- to 20-fold by this modification. Trinitrobenzenesulfonic acid titration studies demonstrated that epsilon-amino groups of lysine residues are modified by the coupling of carbonyldiimidazole-activated PEG to proteins.


Midwives' experiences of routine antenatal questioning relating to men's violence against women.
to describe and use the experience gained by antenatal-care midwives who routinely questioned pregnant women about personally experienced violence. qualitative, using focus-group discussions. antenatal care in a city in south-central Sweden. 21 midwives. the midwives participated in any one of five focus-group discussions held by the same moderator and observer. The discussions were audiotaped, transcribed verbatim and analysed using qualitative content analysis. the importance of routine questioning about violence was emphasised in all groups. Midwives felt they had failed in their duty when women were not questioned. The two main obstacles to such questioning were the delicacy of the subject and the routine of inviting the partner to all visits. The perceived delicacy underlined the need to devise a natural setting for the questioning. The midwives wanted to connect questions about abuse with related subjects routinely established in early pregnancy. As the partner was invited to every visit, it was not practicable to establish a procedure whereby the assessment was connected with a particular visit. Other obstacles included the following: time constraints, oversight, a preconceived notion of who might be a victim of abuse and language difficulties. The midwives emphasised the importance of training, easy access to support for abused women, and personal counselling for midwives. They described their role as raising awareness of the problem of male violence, reducing the shame of being abused, informing, giving emotional support and mediating help. in order to ensure that the establishment of experience of violence is a routine enquiry in antenatal care, midwives must have a reasonable opportunity of carrying out such questioning. A routine that offers each woman a private consultation will ease the questioning and save time and distress.


Translational standby sites: how ribosomes may deal with the rapid folding kinetics of mRNA.
We have previously shown that stable base-pairing at a translational initiation site in Escherichia coli can inhibit translation by competing with the binding of ribosomes. When the base-pairing is not too strong, this competition is won by the ribosomes, resulting in efficient translation from a structured ribosome binding site (RBS). We now re-examine these results in the light of RNA folding kinetics and find that the window during which a folded RBS is open is generally much too short to recruit a 30S ribosomal subunit from the cytoplasm. We argue that to achieve efficient expression, a 30S subunit must already be in contact with the mRNA while this is still folded, to shift into place as soon as the structure opens. Single-stranded regions flanking the structure may constitute a standby site, to which the 30S subunit can attach non-specifically. We propose a steady-state kinetic model for the early steps of translational initiation and use this to examine various quantitative aspects of standby binding. The kinetic model provides an explanation of why the earlier equilibrium competition model predicted implausibly high 30S-mRNA affinities. Because all RNA is structured to some degree, standby binding is probably a general feature of translational initiation.


Information-seeking coping behaviors during painful procedures in African-American children with sickle cell disease.
This study examined the frequency of information-seeking coping behaviors in 37 African-American children (ages 5-17 years) with sickle cell disease during venipuncture. The relationships between coping behaviors and child- and parent-reported pain and observational distress were also assessed. The majority of children attended to the procedure, but did not seek information via questions. This pattern of coping was only partially effective at reducing distress and had no relation to pain. This pattern of coping is discussed within the context of cultural factors that may be important in understanding responses to procedural pain in pediatric sickle cell disease.


Hindlimb extensor reflex of spinal rats given tranylcypromine stereoisomers.
The hindlimb extensor reflex of reserpinized, spinal rats was used to determine whether tranylcypromine (dl-TCP) and its stereoisomers (d-TCP and l-TCP) after tryptaminergic neurotransmission. dl-TCP and d-TCP caused an extensor reflex while l-TCP failed to cause a reliable extensor reflex. Neither H 22/54 nor nialamide affected the extensor reflex in rats given dl-TCP, while H 22/54 reduced the reflex in rats given d-TCP. The results suggest that dl-TCP and d-TCP have direct as well as indirect actions on tryptaminergic neurotransmission.


The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea-pig ileum.
Morphine depresses the twitch and tetanus of stimulated guinea-pig ileum by reducing acetylcholine released from cholinergic nerve endings. Acetylcholine output per shock falls to roughly the same residual amount at varying stimulation rates. Since normal output per shock declines with increasing stimulus frequency, the proportionate effect of morphine diminishes as stimulus frequency rises. Acute "tolerance" to morphine and a state of "morphinedependence" can be produced. Phenadoxone, dihydromorphinone, metopon, methadone, and heroin are more active, codeine and pethidine less active, than morphine. Nalorphine also depresses the twitch and can desensitize the gut both to itself and to morphine.


Patient safety: a multifaceted issue.
John Tingle, Lecturer in Law, Birmingham Law School, University of Birmingham, discusses the need for an integrated approach to patient safety, and the argument that error is inevitable and risk can only be managed.


Metallothioneins and cytosolic metals in Neomysis integer exposed to cadmium at different salinities.
In the present study the induction of metallothioneins (MTs) and its relation to cytosolic metal concentrations (Zn, Cu and Cd) in the euryhaline crustacean Neomysis integer exposed to Cd at different salinities was studied. N. integer was exposed to the same free cadmium ion activity of 5.74 x 10(-9) mol l(-1) (i.e. 1/5 of the 96 h LC(50) value expressed as cadmium activity) in hypo-osmotic (5 psu), isosmotic (16 psu) and hyper-osmotic media (25 psu) for 7 days. In this way, the effect of salinity on cadmium speciation was eliminated and therefore the physiological effect of salinity on Cd accumulation and MT induction could be studied. The accumulation of cytosolic Cd in N. integer changed with salinity from 1.11+/-0.05 micromol l(-1) at 5 psu up to 1.43+/-0.17 micromol l(-1) at 25 psu. This could indicate that the physiological response of euryhaline estuarine invertebrates like N. integer to salinity changes can influence the rate of trace metal uptake from solution. While the salinity changes did not cause significant differences in cytosolic Zn concentrations (mean value of all tested salinities: 34.4+/-2.8 micromol l(-1)), an inverse relationship between salinity and cytosolic Cu concentration was observed. The highest concentration of 15.7+/-2.3 micromol Cul(-1) was determined at 5 psu and the lowest 10.9+/-1.4 micromol Cul(-1) at 25 psu. This could point to a possible relationship between the copper concentration and the hemocyanin metabolism in N. integer. This is the first time that differential pulse voltammetry method was applied to MT assays with N. integer. Although the exposure to Cd resulted in a higher Cd cytosolic concentration, no subsequent MT increase was detected. The significant positive correlation between MT levels and cytosolic Cu concentrations (Spearman correlation coefficient r(s)=0.356, p=0.009) implies a strong relationship between MT and Cu in N. integer.


Magnetic resonance imaging-based volumetry differentiates progressive supranuclear palsy from corticobasal degeneration.
Because there are no biological markers for the clinical diagnosis of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), we established a mathematical model based on three-dimensional magnetic resonance (MR) imaging to differentiate between these parkinsonian disorders. Using MR imaging-based volumetry we studied the pattern of atrophic changes in patients with probable, possible or definite PSP (n = 33) or CBD (n = 18). Patients were compared with 22 controls with similar age. To establish a mathematical model that would allow for differentiation of PSP, CBD and controls we performed a discriminant analysis. We found a significant reduction in average brain, brainstem, midbrain and frontal gray matter volumes in patients with PSP, whereas patients with CBD showed atrophy of parietal cortex and corpus callosum. With the exception of reduced midbrain volumes in PSP, the measured volumes of anatomical structures showed an extensive overlap with the normal range on an individual basis. Using only post mortem confirmed cases of PSP (n = 8) and CBD (n = 7) as well as all controls, the volumes of midbrain, parietal white matter, temporal gray matter, brainstem, frontal white matter and pons were identified to separate best between groups and were used to construct a model with two canonical variables. This model allowed to correctly predict the diagnosis in 95% of controls as well as in 76% of all PSP and 83% of all CBD patients. Similar results were obtained only when patients with a possible and probable diagnosis of PSP and CBD, who were not involved in the development of the discriminant analysis, were classified. 3D-MR imaging-based volumetry may help to differentiate PSP from CBD ante mortem.


Increased serum IL-36γ levels are associated with disease severity in myasthenia gravis patients.
Interleukin 36 (IL-36), as a gradually recognized cytokine, is involved in the occurrence and evolution of autoimmune diseases. Nevertheless, the relationship between myasthenia gravis (MG) and IL-36 is rarely reported. We evaluated the serum levels of IL-36 (IL-36α, IL-36β and IL-36γ) by enzyme-linked immunosorbent assay (ELISA). Further, clinical parameters in 97 MG patients and 49 healthy controls (HCs) were carefully measured. Serum IL-36γ levels were significantly elevated in the MG patients compared with the HCs (p < 0.0001). Compared to those in remission, patients in the acute phase exhibited higher levels of IL-36α and IL-36γ (p = 0.038 and p = 0.011, respectively). Furthermore, patients with generalized MG (GMG) exhibited markedly higher serum IL-36γ levels than those with ocular MG (OMG) (p = 0.003). The serum levels of IL-36γ in patients with MG were increased and positively correlated with disease severity and may thus have potential as a serological MG marker.


Thyroid disruption in male goldfish (Carassius auratus) exposed to leachate from a municipal waste treatment plant: Assessment combining chemical analysis and in vivo bioassay.
Several classes of thyroid-disrupting chemicals (TDCs) have been found in refuse leachate, but the potential impacts of leachate on the thyroid cascade of aquatic organisms are yet not known. In this study, we chemically analyzed frequently reported TDCs, as well as conducted a bioassay, to evaluate the potential thyroid-disrupting effects of leachate. We used radioimmunoassay to determine the effects of leachate exposure on plasma 3,3',5-triiodo-l-thyronine (T3), 3,3',5,5'-l-thyroxine (T4), and thyroid-stimulating hormone (TSH) levels in adult male goldfish (Carassius auratus). We also investigated the impacts of leachate treatment on hepatic and gonadal deiodinases [types I (D1), II (D2), and III (D3)] and gonadal thyroid receptor (TRα-1 and TRβ) mRNA expressions by using real-time polymerase chain reaction. The results indicated the presence of five TDCs (bisphenol A, 4-t-octylphenol, di-n-butyl phthalate, di-n-octyl phthalate, and diethylhexyl phthalate); their mean concentrations in the leachate were 18.11, 2.76, 4.86, 0.21, and 9.16 μg/L, respectively. Leachate exposure induced plasma T3 and TSH levels in male fish, without influencing the plasma T4 levels. The highly elevated D2 mRNA levels in the liver were speculated to be the primary reason for the induction of plasma T3 levels. Disruption of thyroid functions by leachate was also suggested by the up-regulation of D1 and D2 as well as TRα-1 mRNA levels in the gonads. Prominent thyroid disruptions despite the very low TDC concentrations in the exposure media used in the bioassay strongly indicated the existence of unidentified TDCs in the leachate. Our study indicated the necessity of conducting in vivo bioassays to detect thyroid dysfunctions caused by leachate.


Rheumatoid arthritis in the developing world.
The general impression is that rheumatoid arthritis (RA) has a lower prevalence and a milder course in developing countries. Epidemiological studies from different regions show that varying prevalence is possibly related to urbanization. The data suggest that where severe disability does occur, it presents a significant health challenge because of scarce medical and social resources. Disease-modifying anti-rheumatic drugs (DMARDs) remain the mainstay of therapy to alter the natural history of the disease. New therapies are unlikely to be of general benefit in the developing world because of financial constraints and increased risk of infections, particularly tuberculosis, associated with the use of tumour necrosis factor-alpha blockers. Instead, future research in poorer communities should be directed at assessing the burden of disease, the role of early aggressive therapy with DMARDs in combination with glucocorticoids for the majority of patients with RA, and finally, sourcing targeted biological therapies through clinical trials and grants for compassionate use in patients with refractory disease.


A phase I pharmacodynamic trial of bortezomib in combination with doxorubicin in patients with advanced cancer.
This phase I trial sought to define the toxicity, maximally tolerated dose (MTD) and pharmacodynamics of a combination of bortezomib and doxorubicin in patients with advanced malignancies. Twenty-six patients were treated with bortezomib intravenously on days 1, 4, 8 and 11, with doxorubicin also administered intravenously on days 1 and 8, both in a 21-day cycle. Dosing ranged from 1.0 mg/m(2) of bortezomib with 15 mg/m(2) of doxorubicin to 1.5 mg/m(2) of bortezomib with 20 mg/m(2) of doxorubicin. Pharmacodynamic studies performed included assessment of levels of 20S proteasome activity and ubiquitin-protein conjugates. The combination of bortezomib and doxorubicin was generally well tolerated. There were two dose limiting toxicities (DLT) at dose cohort 3 (1.3 mg/m(2) bortezomib, 20 mg/m(2) doxorubicin) and 2 DLT at dose cohort 3a (1.5 mg/m(2) bortezomib, 15 mg/m(2) doxorubicin). DLT seen included neutropenia, thrombocytopenia, and neuropathy. In addition, one patient developed grade 3 central nervous system toxicity in cycle 2 (not a DLT). One patient with hormone refractory prostate cancer had a partial response. Proteasome inhibition in whole blood was demonstrated and an increase in ubiquitin-protein conjugates was observed in peripheral blood mononuclear cells of most patients. Bortezomib and doxorubicin can be administered safely. The recommended phase II dose for this 21-day cycle is bortezomib 1.3 mg/m(2 )intravenously on days 1, 4, 8 and 11, and doxorubicin 20 mg/m(2) intravenously on days 1 and 8. This combination may be of special interest in multiple myeloma, given the activity of both drugs in that disease.


Structure-function analysis of an evolutionary conserved protein, DAP3, which mediates TNF-alpha- and Fas-induced cell death.
A novel approach to the isolation of positive mediators of programmed cell death, based on random inactivation of genes by expression of anti sense RNAs, was employed to identify mediators of interferon-gamma-induced apoptosis. One of the several genes identified is DAP3, which codes for a 46 kDa protein with a potential nucleotide-binding motif. Structure-function studies of the protein indicate that the intact full-length protein is required for its ability to induce apoptosis when overexpressed. The N-terminal 230 amino acids, on the other hand, act in a dominant-negative fashion. Both of these functions are dependent on the integrity of the nucleotide binding motif. Expression of anti-sense DAP3 RNA and of the dominant interfering form of DAP3 both protected cells from apoptosis induced by activation of Fas and tumor necrosis factor alpha (TNF-alpha) receptors. Thus, DAP3 is implicated as a positive mediator of these death-inducing stimuli. It functions downstream of the receptor signaling complex and its death promoting effects depend on caspase activity. In the nematode Caenorhabditis elegans, a potential homolog of DAP3 showing 35% identity and 64% similarity to the human protein was isolated. Overexpression of the nematode DAP3 cDNA in mammalian cells induced cell death, indicating that the protein is conserved at the functional level as well as the structural level.


Anatomical gift donation.
To effectively address the issue of anatomical gift donation, nurses need to be knowledgeable about the laws governing it, the donation process, and dealing with people in crisis. Supporting bereaved families in a sensitive and caring manner becomes a major facet of nursing care.


Electro-mechanical failures and lactate production during fatigue.
The electrical and mechanical failures observed during sustained and intermittent electrically triggered (30 Hz) contractions of human flexor carpi ulnaris were compared with the blood lactate concentration. The changes recorded during contractions sustained for 60 s were compared with those observed during a series of sixty 1 s contractions separated by 1 s intervals, and also with the changes during the first 30 min of recovery. No significant (P less than 0.05) difference in force reduction or maximal venous lactate concentration was observed in either fatigue test, although electrical failure differed significantly (P less than 0.05). The recovery of electrical failure was poorly correlated with the reduction in lactate concentration following both sustained (r = -0.70) and intermittent contractions (r = 0.72). In contrast, the recovery in tetanic tension, rate of tension development and time to half relaxation correlated closely with the reduction in venous lactate concentration (r = -0.95, -0.93 and 0.96 respectively). It is suggested that, of the peripheral processes which appear to play a dominant role in peripheral fatigue, lactate production controls mechanical failure directly.


The effects of exercise on lipogenic enzyme activity and glyceride synthesis by liver homogenates of diabetic rats.
The purpose of this study was to determine if exercise ameliorates the elevated levels of triglycerides in diabetic rats and also to determine if the capacity of liver to synthesize glycerides correlates with changes in plasma triglyceride levels. Forty female rats were divided into four groups: sedentary control, sedentary diabetic, exercised control, and exercised diabetic. Diabetes was induced by intravenous injection of alloxan (40 mg/kg), and control rats were sham-dosed with physiologic saline. All rats remained sedentary in their cages for the first week after the injections. The exercised groups were exercised for seven consecutive days for 2 h/d at 20 m/min (0 grade). All rats were killed 24 hours after the last exercise bout. Blood glucose levels were significantly higher in the diabetic group than the nondiabetic counterparts, but exercise did not affect glucose levels in either the diabetic or nondiabetic groups. Exercise, however, significantly lowered plasma triglyceride and free fatty acid levels in both diabetic and nondiabetic rats. The activities of the five enzymes involved in fatty acid synthesis were all depressed in the diabetic rats compared to controls, and exercise had no effect on the activities of the enzymes. The capacity of liver to synthesize total lipids, diglycerides, or triglycerides was not different in the diabetic rats from that of nondiabetic rats, and exercise did not change that. Only phospholipid synthesis from glycerol-3-phosphate was affected by diabetes. It is concluded that exercise ameliorates the elevations in plasma triglyceride levels that result from diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)


Infants' interoception is associated with eye contact in dyadic social interactions.
Interoception, that is, the perception of visceral stimuli, is the basis of socio-emotional development. However, no studies have demonstrated the relationship between the two in infants. This study aimed to elucidate the relationship between interoception and social behavior in infants and mothers. Visual preference for cardio-visual synchronous and asynchronous stimuli was assessed using a preferential-looking paradigm in 6-month infants and their mothers. The infant-mother interaction was also measured to assess social behavior, such as eye contact and positive facial expressions. The results showed that infants looked at asynchronous cardio-visual stimuli longer than synchronous cardio-visual stimuli, whereas mothers looked at synchronous cardio-visual stimuli longer than asynchronous cardio-visual stimuli. The proportion of looking time toward asynchronous cardio-visual stimuli in infants was positively correlated with infant-mother gaze and affect (positive facial expression) synchrony. Furthermore, mediation analyses showed that the relationship between infants' interoception and eye contact behavior is attributable to mother's positive facial expression. Our findings suggest that in infant-mother interactions, infants' interoception may play a role in eye contact behavior through the mother's positive facial expression, highlighting the importance of infants' interoception on social cognitive development.


Fast carbonization using fluidized bed for biochar production from reed black liquor: optimization for H2S removal.
The biochar was produced from fast pyrolysis of reed black liquor using fluidized bed. Response surface methodology and the central composite design (CCD) were employed for determining optimal adsorbents with maximum H2S removal capacity. The operational parameters such as carbonization temperature (°C), duration (min) and space velocity (SV, L min(-1) kg(-1)) were chosen as independent variables in CCD. The statistical analysis indicates that the effects of carbonization temperature, duration, SV and combined effect of carbonization temperature and duration are all significant to the H2S removal capacity. The optimal condition for achieving the maximum H2S adsorption capacity for biochar is obtained as the follows: carbonization temperature (500°C), duration (5.7 min), SV (7300 L min(-1) kg(-1)) with H2S removal reaching 60 mg g(-1). The dynamic experimental results indicate a good performance in H2S removal by the produced biochar.


Quantitation of the Regional Lymph Node Metastatic Burden and Prognosis in Malignant Mammary Tumors of Dogs.
As in women, regional lymph node status impacts survival in dogs with malignant mammary tumors. However, few studies have evaluated regional lymph node metastases in dogs with malignant mammary gland tumors. To estimate overall survival based on the assessments of the lymph node status and the morphologic and morphometric features in female dogs with malignant mammary gland tumors. In total, 178 lymph nodes from 97 female dogs were assessed and reviewed, and after confirmation by immunohistochemistry (IHC), 161 lymph nodes were selected for analysis of metastases. Animals were considered metastasis-free (negative lymph nodes) only after IHC analysis for cytokeratin AE1/AE3. The number of positive lymph nodes, the number of metastatic foci, the maximum diameter and the area of metastasis were analyzed, and estimates of overall survival were made. Dogs with metastasis had lower mean survival than those with metastasis-free regional lymph nodes, showing a direct relationship between the number of affected lymph nodes and shorter survival. However, histologic analysis of the lymph nodes identified lower survival rates in animals with macrometastases and isolated tumor cells, areas of metastasis >20.11 mm², and metastatic diameters >7.32 mm. The identification of ≥1 lymph nodes positive for metastasis and morphometric characterization of lymphatic metastases indicate the prognostic relevance of lymph nodes status in dogs with mammary tumors.


Augmented Reality (AR) Supporting Citizen Engagement in Circular Economy.
Improving the public's awareness of and engagement with sustainable practices is essential for transitioning from a linear to a circular economy (CE). This task is not trivial; however, research into new ways of effectively supporting awareness and engagement, especially in view of digitalization trends, is still missing. In this study, we investigate the ability of augmented reality (AR) technology to improve awareness of CE practices and to engage citizens, inclusively, in the CE approach. Specifically, we report on the development of a novel AR engagement tool and present the results of two studies undertaken using this tool to assess the reliability and validity of this engagement practice. The first study focuses on the citizens of a municipality in Greece, and the second focuses on the general public outside the municipality boundaries. Attributes related to user engagement, such as novelty, aesthetics, perceived usability, endurability, focused attention, self-efficacy, perceived learning, and interest in the topic, were assessed, as were factors affecting these attributes related to the participants' knowledge of CE principles and exposure to similar technologies. The two studies indicate that the AR engagement tool increased social inclusion and community cohesion and was able to successfully bring CE principles and benefits to the public's attention. Higher engagement levels were observed in participants who had limited exposure to the concept of CE prior to using the AR tool, and its use was found to improve their confidence and interest in CE. This study aspires to contribute to the ongoing discourse on the use of mobile AR and to support further evidence-based development of digital tools for public awareness and engagement. The online version contains supplementary material available at 10.1007/s43615-021-00137-7.


Comparison of three methods for generating group statistical inferences from independent component analysis of functional magnetic resonance imaging data.
To evaluate the relative effectiveness of three previously proposed methods of performing group independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) data. Data were generated via computer simulation. Components were added to a varying number of subjects between 1 and 20, and intersubject variability was simulated for both the added sources and their associated time courses. Three methods of group ICA analyses were performed: across-subject averaging, subject-wise concatenation, and row-wise concatenation (e.g., across time courses). Concatenating across subjects provided the best overall performance in terms of accurate estimation of the sources and associated time courses. Averaging across subjects provided accurate estimation (R > 0.9) of the time courses when the sources were present in a sufficient fraction (about 15%) of 100 subjects. Concatenating across time courses was shown not to be a feasible method when unique sources were added to the data from each subject, simulating the effects of motion and susceptibility artifacts. Subject-wise concatenation should be used when computationally feasible. For studies involving a large number of subjects, across-subject averaging provides an acceptable alternative and reduces the computational load.


Electro-catalytic oxidation of phenacetin with a three-dimensional reactor: Degradation pathway and removal mechanism.
Phenacetin is a common analgesic, anti-arthritic and anti-rheumatic drug. This study dealt with the degradation of phenacetin in alkaline media using a three-dimensional reactor with particle electrodes. Particular attention was paid to the degradation pathway and the reaction mechanism in the system. Liquid chromatography coupled with time-of-flight mass spectrometry was used to identify the intermediates. The phenacetin was observed to be firstly cut off the branch chains main by direct oxidation, and then the intermediates further degraded to ring opening products by hydroxyl radical resulting from indirect oxidation and finally mineralized to CO2, H2O. A possible removal mechanism was proposed that direct and indirect oxidation together did effect on the pollutants with oxygen.


Spousal Concordance for Objectively Measured Sedentary Behavior and Physical Activity Among Middle-Aged and Older Couples.
Although it has been proposed that 1 spouse's health behaviors might correlate with the other spouse's health behavior among married couples, few studies have focused on sedentary behavior. This study examined whether objectively measured sedentary behavior and physical activity are correlated with each other and whether attachment to one's spouse moderates such correlations among middle-aged and older married couples. Seventy-two couples participated in the survey. This study measured time engaged in sedentary behavior and moderate-to-vigorous physical activity (MVPA), step counts by an accelerometer for 7 days, and attachment to one's spouse, age, education, and frailty by questionnaires. Multiple regression analyses showed that the sedentary behaviors of 1 spouse statistically significantly regressed on those of the other spouse (β = .30-.47). The regressions of husbands' MVPA and step counts on those of their wives were statistically marginally significant (β = .22-.25), while the regressions of wives' MVPA and step counts on those of their husbands were not statistically significant (β = .15-.18). The interaction terms of the attachment with one's spousal accelerometer variables on those of the other spouse were not statistically significant (β = -.02 to .16). This study revealed that sedentary behaviors were correlated with each other among couples and attachment to one's spouse did not moderate these correlations. Sedentary behaviors of 1 spouse might influence the other, regardless of attachment to one's spouse. The concordance for physical activity was weaker than that for sedentary behavior.


Comparison of Visual Performance and Patient Satisfaction After Multifocal Intraocular Lens Implantation and During Multifocal Contact Lens Wear After Monofocal Intraocular Lens Implantation: A Pilot Study.
To compare the visual performance and patient satisfaction in multifocal intraocular lens (IOL)-implanted eyes and multifocal contact lens (CL)-wearing eyes undergoing monofocal IOL implantation. We retrospectively assessed visual acuity at all distances (0.3, 0.5, 0.7, 1, and 5 m), contrast sensitivity function, patient satisfaction score, and the rate of spectacle independence in the multifocal IOL and multifocal CL groups. Binocular visual acuity at 0.3, 0.5, 0.7, 1, and 5 m was 0.05 ± 0.11, - 0.02 ± 0.09, - 0.02 ± 0.09, - 0.02 ± 0.09, and - 0.04 ± 0.07, respectively, in the multifocal IOL group and 0.25 ± 0.13, 0.04 ± 0.10, 0.01 ± 0.09, - 0.01 ± 0.07, and 0.00 ± 0.08, respectively, in the multifocal CL group. We found significant differences in visual acuity at all distances. The area under the log contrast sensitivity function was 1.32 ± 0.14 and 1.33 ± 0.16 in the multifocal IOL and CL groups, respectively (p = 0.444). The patient satisfaction score for overall vision was 80.2 ± 20.6 and 82.9 ± 10.5 (p = 0.889), and the rate of spectacle independence was 23.4% and 41.7% in the multifocal IOL and CL groups, respectively (p = 0.277). According to our experience, both multifocal IOLs and CLs provided good near-to-distance binocular vision and subsequent high patient satisfaction in daily activities with acceptable contrast sensitivity, suggesting their viability for presbyopic correction in elderly subjects.


Ca2+ oscillations and Ca2+ influx in Xenopus oocytes expressing a novel 5-hydroxytryptamine receptor.
1. We expressed a novel 5-hydroxytryptamine receptor (SRL) in Xenopus oocytes and monitored cytosolic Ca2+ through the endogenous Ca(2+)-dependent Cl- channel activity using the double electrode voltage-clamp technique. 2. 5-Hydroxytryptamine (5-HT; 200 nM) led to an initial rapid oscillatory current followed by a pronounced secondary one, which lasted long after 5-HT wash-out (20-40 min) and was not affected by the receptor antagonist yohimbine. 3. Both phases of the current were abolished by heparin demonstrating a key role for IP3-induced Ca2+ release. 4. Caffeine (10 mM) alone did not evoke a current but reduced both phases of the current evoked by 5-HT. Ryanodine had no effect. No evidence for Ca(2+)-induced Ca2+ release was found. 5. The secondary current activated by 5-HT was sensitive to changes in extracellular Ca2+, suggesting it was evoked by Ca2+ influx. Reducing external Na+ did not affect this current, demonstrating that it was rather specific for Ca2+. 6. The Ca2+ influx pathway was much more sensitive to Cd2+ than other divalent ions (Co2+, Mn2+, Sr2+, Ba2+). It was insensitive to verapamil. 7. Injection of D-myo-inositol 1,4,5-trisphosphate, 3-deoxy-3-fluoro (IP3-F; an analogue not metabolized to D-myo-inositol 1,3,4,5-tetrakisphosphate (IP4)), evoked either an oscillatory current or a rapid current followed by a sustained secondary one. The latter was sensitive to external Ca2+ and was blocked by Cd2+. Heparin dramatically reduced the IP3-F-evoked current. 8. Perfusion in Ca(2+)-free solution, once a secondary current had been generated, significantly decreased the amount of intracellular Ca2+ mobilized by 5-HT, indicating that the Ca2+ influx pathway plays an important role in pool refilling. 9. Block of Ca2+ influx by Cd2+ in cells that were oscillating transiently increased the amplitude and then either abolished the oscillations or made them irregular. This effect was also elicited by increasing external Ca2+. 10. These results demonstrate that 5-HT, acting via IP3, both releases Ca2+ from internal stores and evokes a pronounced Ca2+ influx. This last step is activated by pool depletion and is important for both refilling of the agonist-sensitive stores and modifying the oscillatory pattern.


Male Experience and Sociodemographic Characteristics of Premarital Pregnancy: Based on a Nationwide Population-Based Survey Among Urban and Rural Chinese Youths.
Little is known about the male experience of premarital pregnancy (MEPP) and the sociodemographic characteristics of unmarried male youths involved in pregnancy. This study estimates the prevalence of MEPP and identifies the sociodemographic factors associated with it among Chinese unmarried youths aged 15-24 years, using data from the Survey of Youth Access to Reproductive Health in China. Descriptive analyses and χ2 tests were applied to explore the number and prevalence of MEPP, and logistic regressions were used to identify the associated factors. As a result, among 2,853 sexually experienced male youths, 597 individuals reported 852 partner pregnancies caused by them during their lifetime, with a weighted prevalence rate of 20.87% (95% CI [18.85%, 22.88%]). Among these pregnancies, 78.05% ended in induced abortion. Factors like living with only the father (OR: 4.16, 95% CI [2.22, 7.8]) and the low level of education of the father (junior high school or below, OR: 1.60, 95% CI [1.04, 2.46]) were associated with MEPP among unmarried male youth. Furthermore, there is a marked difference between the rural and urban youth in factors associated with MEPP. The findings in this study highlight the importance of and need for strategies and interventions targeting male youths, in order to improve sexual education and reproductive services.


Longitudinal clinicoelectrophysiologic study of a case of Lafora disease proven by skin biopsy.
A longitudinal clinicoelectrophysiologic study was undertaken of a 15-year 2-month-old girl with Lafora disease who was diagnosed by skin biopsy and an immunohistochemical method with antisera against Lafora bodies. From age 10 years 5 months, 4 months after onset, EEG disclosed progressive deterioration of background activity and incremental increase in epileptic discharges. Photosensitivity was unique: Occipital spikes and diffuse spike-wave discharges were provoked by low-frequency repetitive photic stimuli but without elicitation of myoclonic seizures. Photosensitivity completely disappeared after age 13 years 10 months. High-voltage somatosensory evoked potentials (SEPs) and high-voltage flash visual evoked potentials (F-VEPs) were seen before age 13. After age 13, progressive prolongation of I-III and I-V interpeak latencies of auditory brainstem responses (ABRs), progressive prolongation of latencies of photoevoked eyelid microvibrations, delayed latencies of pattern-reversal visual evoked potentials, and a decrease in the V/I amplitude ratio of ABRs and the previously high F-VEP amplitudes were observed.


Size dependent nanomechanics of coil spring shaped polymer nanowires.
Direct laser writing (DLW) via two-photon polymerization (TPP) has been established as a powerful technique for fabrication and integration of nanoscale components, as it enables the production of three dimensional (3D) micro/nano objects. This technique has indeed led to numerous applications, including micro- and nanoelectromechanical systems (MEMS/NEMS), metamaterials, mechanical metamaterials, and photonic crystals. However, as the feature sizes decrease, an urgent demand has emerged to uncover the mechanics of nanosized polymer materials. Here, we fabricate coil spring shaped polymer nanowires using DLW via two-photon polymerization. We find that even the nanocoil springs follow a linear-response against applied forces, following Hooke's law, as revealed by compression tests using an atomic force microscope. Further, the elasticity of the polymer material is found to become significantly greater as the wire radius is decreased from 550 to 350 nm. Polarized Raman spectroscopy measurements show that polymer chains are aligned in nanowires along the axis, which may be responsible for the size dependence. Our findings provide insight into the nanomechanics of polymer materials fabricated by DLW, which leads to further applications based on nanosized polymer materials.


DNA extraction from formalin-fixed material.
The principal challenges facing PCR-based analyses of DNA extracted from formalin-fixed materials are fragmentation of the DNA and cross-linked protein-DNA complexes. Here, we present an efficient protocol to extract DNA from formalin-fixed or paraffin-embedded tissues (FFPE). In this protocol, protein-DNA cross-links are reversed using heat and alkali treatment, yielding significantly longer fragments and larger amounts of PCR-amplifiable DNA than standard DNA extraction protocols.


Three-Way Junction-Assisted Rolling Circle Amplification Integrated with trans-Cleavage of Cas12a for Sensitive and Reliable Detection of miRNA.
MicroRNAs (miRNAs) serve a crucial role in numerous biological processes, such as acute pancreatitis development. Due to its low abundance and high similarity among homogeneous family members, sensitive and reliable detection of microRNA remains a formidable challenge. By combining the three-way junction-assisted rolling circle amplification (RCA) with the trans-cleavage of Cas12a, we propose a novel fluorescent technique for sensitive miRNA detection. In order to increase the amplification efficiency of RCA-based methods, catalytic hairpin amplification (CHA) is incorporated into the RCA process, playing the roles of specific target recognition and three-way junction formation. Consequently, the method demonstrated a six-orders-of-magnitude detection range and a LOD as low as 27 aM, making it a promising method for the early diagnosis of various diseases.


Coenzyme Q10: a novel gastroprotective effect via modulation of vascular permeability, prostaglandin E₂, nitric oxide and redox status in indomethacin-induced gastric ulcer model.
Coenzyme Q10 is an essential cofactor in the mitochondrial electron transport pathway, and is endowed for its potent antioxidant capacity; characters that endorse its implication in several clinical practices and as a food supplement. Nevertheless, its potential gastro-protective effect, in acute models, has never been assessed, which is the objective of this study. Since indomethacin mediated gastropathy is multifaceted, including mitochondrial dysfunction and generation of reactive oxygen species, thus, the indomethacin-induced gastric injury serves as a convenient animal model for this work. Rats treated with indomethacin revealed mucosal hemorrhagic lesions, increased microvascular permeability and inhibited prostaglandin E₂ and mucus content. Redox imbalance was reflected by decreased mucosal glutathione (GSH), nitric oxide and glutathione peroxidase contents/activity, along with elevated lipid peroxides. Pretreatment with CoQ10 caused discernible decrease in indomethacin-induced gastric lesions, vascular permeability and lipid peroxide content. In addition, prostaglandin E₂ and GSH levels were restored, while those of nitric oxide and glutathione peroxidase were elevated significantly above normal; however, mucus formation was not altered significantly. The positive effects were comparable to those of sucralfate, the standard drug used herein, except for the mucus and prostaglandin E₂ levels that were increased above normal by sucralfate. CoQ10-mediated gastroprotective effect involves preservation of microvascular permeability, elevation of prostaglandin E₂, improvement of redox status, as well as boosting of nitric oxide. Nevertheless, maintaining gastric mucus content is ruled out.


Transcriptome analysis of human brain tissue identifies reduced expression of complement complex C1Q Genes in Rett syndrome.
MECP2, the gene mutated in the majority of Rett syndrome cases, is a transcriptional regulator that can activate or repress transcription. Although the transcription regulatory function of MECP2 has been known for over a decade, it remains unclear how transcriptional dysregulation leads to the neurodevelopmental disorder. Notably, little convergence was previously observed between the genes abnormally expressed in the brain of Rett syndrome mouse models and those identified in human studies. Here we carried out a comprehensive transcriptome analysis of human brain tissue from Rett syndrome brain using both RNA-seq and microarrays. We identified over two hundred differentially expressed genes, and identified the complement C1Q complex genes (C1QA, C1QB and C1QC) as a point of convergence between gene expression changes in human and mouse Rett syndrome brain. The results of our study support a role for alterations in the expression level of C1Q complex genes in RTT pathogenesis.


Sclerotherapy for lymphatic malformations of head and neck: Systematic review and meta-analysis.
Percutaneous sclerotherapy is a commonly used modality for treatment of lymphatic malformations (LMs) of the head, face, and neck. The safety and efficacy of sclerotherapy with various agents for diverse pathologic types of LMs have not been fully established. We present the results of a systematic review and meta-analysis examining the safety and efficacy of percutaneous sclerotherapy for treatment of LMs of the head, face, and neck. We searched PubMed, MEDLINE, and Embase from 2000 to 2018 for studies evaluating the safety and efficacy of percutaneous sclerotherapy of head, face, and neck LMs. Two independent reviewers selected studies and abstracted data. The primary outcomes were complete and partial resolution of the LM. Data were analyzed using random-effects meta-analysis. There were 25 studies reporting on 726 patients included. The overall rate of complete cure of any pathologic type of LM after percutaneous sclerotherapy with any agent was 50.5% (95% confidence interval, 36.6%-64.3%). Macrocystic lesions had a cure rate of 53.1% compared with cure rates of 35.1% for microcystic lesions and 31.1% for mixed lesions. Regarding agents, doxycycline had the highest cure rate (62.4%) compared with all other agents. Overall permanent morbidity or mortality was 1.2% (95% confidence interval, 0.4%-2.0%) with no deaths. I2 values were >50% for most outcomes, indicating substantial heterogeneity. Our systematic review and meta-analysis of 25 studies and >700 patients found that percutaneous sclerotherapy is a safe and effective modality for treatment of LMs of the head, neck, and face.


Relationship of Having Hobbies and a Purpose in Life With Mortality, Activities of Daily Living, and Instrumental Activities of Daily Living Among Community-Dwelling Elderly Adults.
This study's aim was to clarify the relationship of having hobbies and a purpose in life (PIL; in Japanese, ikigai) with mortality and a decline in the activities of daily living (ADL) and instrumental ADL (IADL) among the community-dwelling elderly. Prospective observational data from residents aged ≥65 years who were at increased risk for death (n = 1853) and developing a decline in ADL (n = 1254) and IADL (n = 1162) were analyzed. Cox proportional hazard models were used for mortality analysis of data from February 2011 to November 2014. ADL and IADL were evaluated using the Barthel Index and the Tokyo Metropolitan Institute of Gerontology Index of Competence, respectively. ADL and IADL were assessed at baseline and follow-up and were evaluated using logistic regression models. Fully adjusted models included terms for age, gender, BMI, income, alcohol intake, smoking history, number of chronic diseases, cognitive function, and depression. During the follow-up of eligible participants, 248 had died, 119 saw a decline in ADL, and 178 saw a decline in IADL. In fully adjusted models, having neither hobbies nor PIL was significantly associated with an increased risk of mortality (hazard ratio 2.08; 95% confidence interval [CI], 1.47-2.94), decline in ADL (odds ratio 2.74; 95% CI, 1.44-5.21), and decline in IADL (odds ratio 1.89; 95% CI, 1.01-3.55) compared to having both hobbies and PIL. Although effect modifications by cognitive functioning and depression cannot be ruled out, our findings suggest that having hobbies and PIL may extend not only longevity, but also healthy life expectancy among community-dwelling older adults.


Tauroursodeoxycholic acid and secondary damage after spinal cord injury in rats.
Greater clinical understanding of the pivotal role of apoptosis in spinal cord injury (SCI) has led to new and innovative apoptosis-based therapies for patients with an SCI. Tauroursodeoxycholic acid (TUDCA) is a biliary acid with antiapoptotic properties. To our knowledge, this is the first study in the English language to evaluate the therapeutic efficacy of TUDCA in an experimental model of SCI. Thirty rats were randomized into three groups (sham-operated, trauma only, and trauma plus TUDCA treatment) of 10 each. In groups 2 and 3, spinal cord trauma was produced at the T8-T10 level via the Allen weight drop technique. Rats in group 3 were treated with TUDCA (200 mg/kg intraperitoneal) 1 min after trauma. The rats were killed either 24 h or 5 days after injury. The neuroprotective effect of TUDCA on injured spinal cord tissue and the effects of that agent on the recovery of hind-limb function were assessed. The efficacy of treatment was evaluated with histopathologic examination and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) analysis. Histopathologic characteristics were analyzed by comparison of hematoxylin-and-eosin stained specimens. Neurologic evaluations were performed 24 h, 3 days, and 5 days after trauma. Hind-limb function was assessed with the inclined plane technique of Rivlin and Tator and the modified version of Tarlov's grading scale. Twenty-four hours after injury, there was a significantly higher number of apoptotic cells in the lesioned spinal cord group than in the sham-operated control group. Treatment of the rats with TUDCA significantly reduced the number of apoptotic cells (4.52+/-0.30 vs. 2.31+/-0.24 in group 2) and the degree of tissue injury. Histopathologic examination showed that group 3 rats had better spinal cord architecture compared with group 2 rats. Five days after injury, the mean inclined plane angles in groups 1, 2, and 3 were 65.50 degrees +/- 2.09, 42.00 degrees +/- 2.74, and 53.50 degrees +/- 1.36. Motor grading of the rats revealed a similar trend. These differences were statistically significant (p<0.05). The mechanism of neuroprotection in the treated rats, although not yet elucidated, may be related to the marked antiapoptotic properties of TUDCA. A therapeutic strategy using TUDCA may eventually lead to effective treatment of SCI without toxic effects in humans.


Retinal topography of the neonatal crossed aberrant exuberant projection to the inferior colliculus in the pigmented rat.
The retinal topography of the neonatal transient projection to the inferior colliculus was investigated in pigmented rats by injecting the retrograde fluorescent tracer Fast Blue into the colliculi. The results show that the projection arises from a small population of ganglion cells scattered across the entire contralateral retina, and that the transient projection is therefore not merely an overshoot of axons from the peripheral nasal retina whose appropriate target is the caudal pole of the superior colliculus.


Carpal growth and function after pediatric transcarpal hand replant: case report.
This case discusses the technique, postoperative course, and functional outcomes 5 years after an amputation between the cartilaginous anlages of the growing carpus in a 7-year-old boy. The lunate remained attached to the arm, whereas the scaphoid and the remainder of the carpus were contained within the amputated part. After 5 years, the patient had 94% growth compared to the other side, a Minnesota dexterity test in the 75th percentile, 0/10 pain, near-normal sensation, grip strength 17% of the other side, and lateral pinch 79% of the other side.


Three distinct regions in a rat TFIID subunit containing histone H4 homology.
A cDNA encoding a rat transcription factor IID (TFIID) subunit (p80), with histone H4 homology, was isolated and sequenced. The deduced amino acid (aa) sequence predicts a 678-aa protein with 97% identity to the human and 42% to the Drosophila melanogaster (Dm) homologues. Homologies between three species indicate the presence of three distinct regions.


The interplay between unexpected events and behavior in the development of explicit knowledge in implicit sequence learning.
Some studies in implicit learning investigate the mechanisms by which implicitly acquired knowledge (e.g., learning a sequence of responses) becomes consciously aware. It has been suggested that unexpected changes in the own behavior can trigger search processes, of which the outcome then becomes aware. A consistent empirical finding is that participants who develop explicit knowledge show a sudden decrease in reaction times, when responding to sequential events. This so called RT-drop might indicate the point of time when explicit knowledge occurs. We investigated whether an RT-drop is a precursor for the development of explicit knowledge or the consequence of explicit knowledge. To answer this question, we manipulated in a serial reaction time task the timing of long and short stimulus-onset asynchronies (SOA). For some participants, the different SOAs were presented in blocks of either long or short SOAs, while for others, the SOAs changed randomly. We expected the participants who were given a blocked presentation to express an RT-drop because of the predictable timing. In contrast, randomly changing SOAs should hamper the expression of an RT-drop. We found that more participants in the blocked-SOA condition than in the random-SOA condition showed an RT-drop. Furthermore, the amount of explicit knowledge did not differ between the two conditions. The findings suggest that the RT-drop does not seem to be a presupposition to develop explicit knowledge. Rather, it seems that the RT-drop indicates a behavioral strategy shift as a consequence of explicit knowledge.


The viability of Mycoplasma iowae at 40 C in turkey semen.
Mycoplasma iowae was mixed with turkey semen, incubated at 40 C in a water bath, and sampled at different intervals. The M. iowae remained viable throughout a 48-hr incubation period.


A comparative evaluation of retromandibular versus Modified Risdon approach in surgical treatment of condylar fracture.
The purpose of this study was aimed to compare the efficiency and safety of retromandibular versus modified Risdon approach using periangular incision for open reduction and internal fixation of low subcondylar mandibular fracture. Open reduction and internal fixation with different plating systems were utilized via retromandibular approach (group I) and via modified Risdon approach with periangular incision (group II). Twenty four (n= 24) condylar fractures in 21 adult patients were divided randomly into two equal groups (12 each) according to the cutaneous incision (approach) utilized. The evaluation score for scarring in group I it was excellent in 9 patients, good in 2 patients and acceptable in only one patient (Mean 2.4 ± SD 3.38). While in group II was excellent in 10 patients and good in 2 patients (Mean 2.4 ± SD 3.87) and the p value was 0.591. Symptoms of transient facial nerve weakness were noted in only 3 patients in group I with slight to moderate dysfunction (Mean 2 ± SD 3.21), while only one patient had facial nerve weakness in group II with House - Brackman score of 2 immediate postoperatively and this got resolved in 6 weeks (Mean 2 ± SD 4.04) and the p value was 0.00022. Within the limitations of the study it seems that a modified Risdon approach using periangular incision for reduction and fixation of low subcondylar fracture should be preferred whenever possible because it yields better outcomes.