Thoracoscopic Lobectomy Produces Long-Term Survival Similar to That with Open Lobectomy in Cases of Non-Small Cell Lung Carcinoma: A Propensity-Matched Analysis Using a Population-Based Cancer Registry.
There is a lack of large, prospective, randomized studies comparing thoracoscopic and open lobectomy in terms of long-term survival in the setting of NSCLC. Additionally, large case series evaluating the issue are limited. Until now, whether thoracoscopic lobectomy entails a long-term survival benefit compared with open lobectomy not been determined. Data were obtained from the National Health Insurance Research Database published in Taiwan. We included patients treated with open lobectomy or thoracoscopic lobectomy. In this retrospective review, the clinicopathologic characteristics of 5222 patients with lung cancer during the period 2004-2010 were analyzed. Patients were stratified according to clinical stage. Overall survival (OS) was compared between patients treated with open and those treated with thoracoscopic lobectomy and was also compared between patients in the three different clinical stages. Propensity-matching analysis and multivariate analysis were performed. Open lobectomy was performed on 3058 patients (58.6%) and thoracoscopic lobectomy on 2164 (41.4%). Propensity matching produced 1848 patients in each group. The 1-year, 3-year, and 5-year OS rates for propensity-matched patients treated with open lobectomy were 93.4%, 79.3%, and 65.5%, respectively. The 1-year, 3-year, and 5-year OS rates for propensity-matched patients treated with thoracoscopic lobectomy were 94.1%, 80.9%, and 68.7%, respectively. The difference was not statistically significant. In multivariate analysis, surgical resection (open versus thoracoscopic) was not an independent prognostic factor. This propensity-matched study suggests that open and thoracoscopic lobectomy are associated with similar long-term survival in the setting of lung cancer. Thoracoscopic lobectomy is an acceptable surgical treatment of lung cancer.


Morphometric analysis of arteriolar diameters in experimental nephropathies: application of microvascular casts.
Renal arteriolar diameters were measured, using microvascular resin casts, in two hyperfiltration models of rats: the remnants kidney of subtotal nephrectomy (NX) and streptozotocin-induced diabetic kidney (DM). In the NX, the blood pressure was elevated, urinary protein excretion was markedly increased and glomeruli were severely damaged. In the DM, although the blood pressure remained normal, urinary protein excretion was significantly increased and glomeruli were damaged but to a lesser extent than in the NX group. In the NX group, the afferent arteriole was dilated and the efferent arteriole was constricted. In the DM group, the afferent arteriole was dilated, while the efferent arteriole remained unchanged. The results showed that afferent arteriolar dilatation was seen in both the NX and DM groups, possibly leading to the glomerular damage. In the NX group, the systemic high blood pressure and efferent arteriolar constriction augmented glomerular damage significantly.


Effects of blackberry (Morus nigra L.) consumption on serum concentration of lipoproteins, apo A-I, apo B, and high-sensitivity-C-reactive protein and blood pressure in dyslipidemic patients.
This study investigated blackberry (Persian mulberry) effects on apo A-I, apo B, high-sensitivity-C-reactive protein (hs-CRP), and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in dyslipidemic patients. In this 8-week randomized clinical trial, 72 dyslipidemic patients were randomly divided into two groups: Intervention (300 mL/day blackberry juice with pulp) and control group (usual diets). Before and after the intervention, fasting blood samples were taken from both groups and serum concentration of lipoprotein, apo A-I and apo B, serum lipids (total cholesterol, low-density lipoprotein, high-density lipoprotein [HDL], and triglyceride), hs-CRP were measured. Blood pressure before and after the study was measured with a mercury manometer. At week 8 in the intervention group, apo A-I and HDL increased significantly (P = 0.015, P = 0.001, respectively), apo B and hs-CRP decreased significantly (P = 0.044, P = 0.04, respectively). Mean changes in apo A-I and HDL and apo B/apo A-I ratio were significant between the groups (P = 0.005, P = 0.014, and P = 0.009, respectively). After 8 weeks, there was a significant difference between hs-CRP mean values (P = 0.01) of the groups. At week 8, SBP decreased significantly (P = 0.005) in the intervention group with no significant differences for SBP mean values between the groups. No significant changes were observed in other lipid parameters and DBP in the intervention group and between the groups. Blackberry consumption may exert beneficial effects on apolipoproteins, blood pressure, and inflammatory markers in individuals with lipid disorders.


[The study of the sensitive and specificity on HBV DNA replication by HBV-lP detecting].
To detect HBV-LP and HBV DNA of the patients with hepatitis B, and to study the sensitive and specificity of HBV-LP detecting and its evaluate on for clinical application. The ELISA was used for HBV-LP detecting and RT-PCR for HBV DNA detecting. The sensitive and specificity of HBV-LP and HBV DNA were 64.89%, 99.68%, 60.63% and 100% respectively (P > 0.05); +LR, -LR were 202.78, 60.63, 0.3522 and 0.3937, and there were significance between +LR of the detecting (P < 0.005). The sensitive and specificity of HBV-LP and HBV DNA detecting are considerable, +LR of HBV-LP are higher comparing HBV DNA. The HBV-LP is better serology index for detecting replication of HBV DNA.


Pituitary abscess.
Three cases of pituitary abscess are presented. The history of recurrent attacks of aseptic meningitis, together with radiological and clinical features suggestive of pituitary tumor, appear to form a fairly typical picture of the condition. Long follow-up was possible in two of the cases. There are no radiological features which distinguish the lesion from pituitary tumor, hence the importance of recognizing the significance of such a clinical presentation with radiological evidence of sellar enlargement. Pituitary abscesses seem to occur in preexisting pituitary tumors. The possible relationship with pituitary infarction is discussed.


A solution for isomerization of pyrethroid insecticides in gas chromatography.
Isomerization of pyrethroid insecticides was observed during extraction and gas chromatography (GC) analysis. An improvement in sensitivity was noted for pyrethroids in sediment extracts in comparison to pure solvent. Stability of pyrethroids using different solvents and analyte additives were investigated, and GC injection conditions were optimized. Polar solvents enhanced pyrethroid isomerization, while hexane was the best choice as an analytical solvent. Acetic acid was used successfully as an isomer-stabilizing agent for GC analysis of pyrethroids. Acidified (0.1% acetic acid) hexane prevented pyrethroid isomerization, increased peak intensity up to 1.9 times, and calibration curve linearity (relative standard deviation for response factors) 0.8-12.5 times compared to hexane alone.


1,25-Dihydroxyvitamin D3 increases bone alkaline phosphatase isoenzyme levels in human osteogenic sarcoma cells.
The specific activity of alkaline phosphatase was increased in two human osteogenic sarcoma cell lines, SAOS and TE85, after treatment with 1,25 dihydroxy-vitamin D3 (1,25(OH)2D3). Enzyme activity increased when the cells were incubated with concentrations of 1,25(OH)2D3 between 10(-9) and 10(-7) M and cell growth was not inhibited at these concentrations. The specific activity of alkaline phosphatase was 4- to 7-fold higher than that in the control cells after 5 to 7 days of continuous exposure to 1,25(OH)2D3. Immunochemical studies demonstrated that the enzyme from both control and 1,25(OH)2D3-treated cultures cross-reacted with antisera specific for the phosphatase isoenzyme produced by normal human bone, and did not cross-react with antisera specific for the placental alkaline phosphatase isoenzyme. The increased enzyme activity in cultures induced with 1,25(OH)2D3 correlated with an absolute increase in the number of bone-specific phosphatase molecules, as determined by radioimmunoassay. No effect on alkaline phosphatase activity was observed when the cells were treated with other vitamin D metabolites or with 5-bromo-2'-deoxyuridine. Comparative studies demonstrated that hydrocortisone, another steroid hormone, increased the phosphatase activity with a different time course than did 1,25(OH)2D3. High affinity cytoplasmic receptors for 1,25(OH)2D3 and hydrocortisone were found in the SAOS and TE85 cells.


Association between osteoarthritis and urinary tract infection in older adults: A nationwide population-based cohort study.
Osteoarthritis (OA) may increase urinary tract infection (UTI) in older adults. However, this issue remains unclear. We identified 8599 older patients (≥65 years) with OA, and an equal number of older patients without OA, matched by age, sex, and index date from the Taiwan National Health Insurance Research Database between 2001 and 2005. Past histories, including UTI and underlying comorbidities, were included in the analyses. Comparisons for any UTI, ≥1 hospitalization for UTI, and ≥3 hospitalizations for UTI between the 2 cohorts by following up until 2015 were performed. In both cohorts, the percentages of age subgroups were 65-74 years (65.7%), 75-84 years (30.1%), and ≥85 years (4.2%). The male sex was 42.4%. Patients with OA had an increased risk of any UTI compared with those without OA after adjusting for all past histories (adjusted hazard ratio [AHR]: 1.72; 95% confidence interval [CI]: 1.64-1.80). Compared with patients without OA, patients with OA also had an increased risk of ≥1 hospitalization for UTI and ≥3 hospitalizations for UTI (AHR: 1.13; 95% CI: 1.06-1.19 and AHR: 1.25; 95% CI: 1.13-1.38, respectively). In addition to OA, age 75-84 years, female sex, history of UTI, benign prostatic hyperplasia, indwelling urinary catheter, cerebrovascular disease, dementia, and urolithiasis were independent predictors for any UTI. This study showed that OA was associated with UTI in older adults. We suggest appropriately managing OA and controlling underlying comorbidities to prevent subsequent UTI.


Rh(III)-Catalyzed C-C/C-N Coupling of Imidates with α-Diazo Imidamide: Synthesis of Isoquinoline-Fused Indoles.
Imidate esters and diazo compounds have been established as bifunctional substrates for the construction of biologically active fused heterocycles via rhodium-catalyzed C-H activation and C-C/C-N coupling. This reaction occurs under mild conditions with high efficiency, step economy, and low catalyst loading.


Association between Household Exposure to Secondhand Smoke and Dental Caries among Japanese Young Adults: A Cross-Sectional Study.
The long-term effects of secondhand smoke (SHS) on dental caries among Japanese young adults remain unclear. The purpose of this cross-sectional study was to evaluate whether household exposure to SHS is associated with dental caries in permanent dentition among Japanese young adults. The study sample included 1905 first-year university students (age range: 18-19 years) who answered a questionnaire and participated in oral examinations. The degree of household exposure to SHS was categorized into four levels according to the SHS duration: no experience (-), past, current SHS < 10 years, and current SHS ≥ 10 years. Dental caries are expressed as the total number of decayed, missing, and filled teeth (DMFT) score. The relationships between SHS and dental caries were determined by logistic regression analysis. DMFT scores (median (25th percentile, 75th percentile)) were significantly higher in the current SHS ≥ 10 years (median: 1.0 (0.0, 3.0)) than in the SHS-(median: 0.0 (0.0, 2.0)); p = 0.001). DMFT ≥ 1 was significantly associated with SHS ≥ 10 years (adjusted odds ratio: 1.50, 95% confidence interval: 1.20-1.87, p < 0.001). Long-term exposure to SHS (≥10 years) was associated with dental caries in permanent dentition among Japanese young adults.


Expressive/suppressive anger-coping responses, gender, and types of mortality: a 17-year follow-up (Tecumseh, Michigan, 1971-1988).
This study examined prospectively (1971-1988) the relationship between anger-coping responses, gender, and mortality (N = 91) in a representative sample of men (N = 324) and women (N = 372), aged 30 to 69, from the Tecumseh Community Health Study. Anger-coping was measured by responses to hypothetical unfair anger-provoking situations. Cox proportional hazard regressions were used adjusted for seven health risk factors (age, smoking, relative weight, systolic blood pressure (SBP), bronchial problems, FEV1, and cardiovascular (CV) risk). Men's suppressed anger interacted significantly with SBP and also with bronchial problems to predict both all-cause and CV mortality. Women showed direct relationships between suppressed anger and early mortality (all-cause, CV, and cancer). Women also showed an interaction of spouse-suppressed anger and SBP for all-cause and CV mortality. Data suggest men who expressed their anger died earlier of cancer (N = 16) deaths. Suppressed anger at the time of an unjust attack may become chronic resentment (intermittent rage or hatred) about which little is known and requires research. The design for future research should experimentally measure both suppressed anger-coping responses (after an unfair attack) and morbidity (eg, blood pressure, bronchitis, immune disorder, etc.) to predict prospectively to earlier mortality.


Anaerobic biodegradation of weathered polychlorinated biphenyls (PCBs) in contaminated sediments of Porto Marghera (Venice Lagoon, Italy).
The biodegradation of weathered polychlorinated biphenyls (PCBs) (mono and di-chlorinated biphenyls along with PCBs partially ascribed to Aroclor 1242 and 1254) occurring at 1.5-2.5 mg/kg in three different sediments collected from the Porto Marghera contaminated area of Venice Lagoon (Italy) was reported in this study. Strictly anaerobic, slurry microcosms consisting of sediments suspended (at 25% v/v) in a marine salt medium, lagoon water or lagoon water supplemented with NaHCO3 and Na2S were developed and monitored for PCB transformation, sulfate consumption and methane (CH4) production for 6 months. A marked depletion of highly chlorinated biphenyls along with the accumulation of low-chlorinated, often ortho-substituted biphenyls was observed in the biologically active microcosms, where a remarkable consumption of sulfate and/or a significant production of CH4 were also detected. Notably, a more extensive PCB transformation was observed in the microcosms developed with site water (both without or with NaHCO3 plus Na2S), where both the initial concentration of sulfate and sulfate consumption were five fold-higher than in the corresponding microcosms with salt medium. These data indicate that weathered PCBs of the three contaminated sediments of Porto Marghera utilized in this study can undergo reductive dechlorination, probably mediated by indigenous sulfate-reducing and/or methanogenic bacteria.


Interaction between tyrosineZ and substrate water in active photosystem II.
In the field of photosynthetic water oxidation it has been under debate whether Tyrosine(Z) (Tyr(Z)) acts as a hydrogen or an electron acceptor from water. In the former concept, direct contact of Tyr(Z) with substrate water has been assumed. However, there is no direct evidence for the interaction between Tyr(Z) and substrate water in active Photosystem II (PSII), instead most experiments have been performed on inhibited PSII. Here, this problem is tackled in active PSII by combining low temperature EPR measurements and quantum chemistry calculations. EPR measurements observed that the maximum yield of Tyr(Z) oxidation at cryogenic temperature in the S(0) and S(1) states was around neutral pH and was essentially pH-independent. The yield of Tyr(Z) oxidation decreased at acidic and alkaline pH, with pKs at 4.7-4.9 and 7.7, respectively. The observed pH-dependent parts at low and high values of pH can be explained as due to sample inactivation, rather than active PSII. The reduction kinetics of Tyr(Z)(.) in the S(0) and S(1) states were pH independent at pH range from 4.5 to 8. Therefore, the change of the pH in bulk solution probably has no effect on the Tyr(Z) oxidation and Tyr(Z)(.) reduction at cryogenic temperature in the S(0) and S(1) states of the active PSII. Theoretical calculations indicate that Tyr(Z) becomes more difficult to oxidize when a H(2)O molecule interacts directly with it. It is suggested that Tyr(Z) is probably located in a hydrophobic environment with no direct interaction with the substrate H(2)O in active PSII. These results provide new insights on the function and mechanism of water oxidation in PSII.


Preventive Effect of High-Dose Digestive Enzyme Management on Development of Nonalcoholic Fatty Liver Disease after Pancreaticoduodenectomy: A Randomized Controlled Clinical Trial.
Nonalcoholic fatty liver disease (NAFLD) is a complication of pancreaticoduodenectomy (PD). We conducted a randomized clinical trial to determine if high-dose digestive enzymes prevented the development of NAFLD after PD. This parallel-group, nonblinded, multicenter study enrolled patients undergoing elective PD at Shinshu University School of Medicine, from June 2011 to April 2017. Patients were randomly assigned to receive normal-dose (Excelase: 3.0 g/day [Meiji Seika Pharma Holdings Co, Ltd]) or high-dose digestive enzyme treatment (Excelase: 3.0 g/day; Pancreatin [Tokyo Chemical Industry Co Ltd]: 3.0 g/day; Berizym [Kyowa Pharmaceutical Industry Co Ltd]: 3.0 g/day; and Toughmac-E [Ono Pharmaceutical Co, Ltd]: 3.0 g/day) within 1 week after surgery. Because patients in the control group switched interventions upon receiving a diagnosis of NAFLD, intention-to-treat analysis was used. The primary endpoint was incidence of NAFLD within 1 year, and the secondary endpoints were the incidences of NAFLD at 1, 3, 6, and 12 months and the rate of improvement in NAFLD with high-dose transfer in the control group. The secondary analysis comprised assessment of risk factors for the development of NAFLD. Eighty-four patients were randomly assigned (42 per group), 80 of whom were finally analyzed (39 normal-dose, 41 high-dose). The incidence of NAFLD was significantly lower in the high-dose (8 of 41) compared with the normal-dose (25 of 39) patients (p < 0.001). Multivariate analysis identified normal-dose (odds ratio [OR] 14.65, p < 0.001), total protein ≤ 6.5g/dL (OR 9.01, p = 0.018), pre-albumin ≤ 22.0 mg/dL (OR 7.71, p = 0.018), and pancreatic function diagnostic test ≤ 70% (OR 6.66, p = 0.009) as independent risk factors. There were no adverse effects. The model was accurate (c-index = 0.92) and reliable (Hosmer-Lemeshow test p = 0.32). High-dose administration of digestive enzymes significantly reduced the onset of NAFLD after PD compared with normal-dose administration. Registration number: UMIN000005595 (http://www.umin.ac.jp/ctr/).


Primary localized amyloidosis of the ureter with osseous metaplasia presenting as a suspicious ureteral mass.
Primary amyloidosis of the ureter is a rare disease that is difficult to distinguish from urothelial carcinoma. Only 50 cases of primary ureter amyloidosis have been reported since it was first described in 1937. Of these, only five cases of ureter amyloidosis with osseous metaplasia were reported. In this study, we report the clinical presentation of ureter primary amyloidosis that presented as a mass with osseous metaplasia. The aim of this study is to provide clinicians with knowledge about the clinical/radiologic manifestation that raise the suspicion of amyloidosis, bearing in mind the importance of differentiating it from other "malignant" processes.


Endovascular treatment of carotid cavernous aneurysms: complications, outcomes and comparison of interventional strategies.
The best treatment modality for cavernous carotid aneurysms (CCA) remains unclear. We treated 82 CCA in 79 patients with endovascular coiling (n=14), stent assistance (n=53), and carotid vessel deconstruction (CVD) (n=15). Favorable outcomes were defined as a Glasgow Outcome Scale of 4 to 5 without worsening signs or symptoms. Mean CCA size was 13.3±9.2 mm, and CCA treated with CVD were larger (p=0.010). Fourteen patients had incidental CCA, 40 (50.6%) had cranial nerve palsies (CNP), and 25 (31.7%) had pain leading to diagnosis. Immediate occlusion (>95%) occurred in 91.5% of aneurysms. Ischemic or hemorrhagic complications developed following eight treatments (9.8%) and three were permanent (3.7%). There were no deaths, and favorable discharge outcome occurred following 87.8% of procedures. Although there was no difference in immediate occlusion or complications amongst treatment cohorts, fewer permanent complications (0% versus 10.3%, p=0.041) and favorable discharge outcomes (p=0.039) were associated with stent assisted treatment. Follow-up was available following 75 procedures (mean 21.4±17.4 months). Recanalization occurred in 36% of patients and retreatment in 25%. Patients presenting with CNP improved over time (p<0.001); 54% of patients presenting with CNP remained unchanged while 46% improved; there was no difference in improvement rates stratified by treatment. Favorable follow-up outcome occurred after 96% of treatments and those receiving stents were more likely to have favorable outcome in multivariate analysis (p=0.039). Endovascular therapy is a safe and effective therapy for CCA. When possible, stent assisted therapy may be the best option with fewer complications and low recanalization rates.


Surveillance and epidemiological characterization of human adenovirus infections among outpatient children with acute gastroenteritis during the COVID-19 epidemic in Shanghai, China.
Human adenovirus (HAdV) has been recognized as one of the common enteric viruses associated with acute gastroenteritis (AGE) in children. The aim of this study was carried out to illustrate the epidemiological characterization of HAdV Infections among children younger than 15 years in Shanghai during COVID-19. During May 2020 and April 2022, 1048 fecal samples were collected from children ≤ 15 years diagnosed with AGE in the Children's Hospital of Fudan University. HAdV was identified by PCR and sequenced with specific primers. All the obtained sequences were analyzed by MEGA (version 6.0). Demographic information and clinical features data were also collected and analyzed. In total, 97 (9.3%, 97/1048) samples were detected to be HAdV during May 2020 and April 2022. We found an atypical upsurge in HAdV infection in the year 2021 after a major suppression in the year 2020. Approximately 84.5% (82/97) of HAdV-infected children were aged 0-60 months. Among the 97 HAdV-positive samples, only two species and five genotypes were detected. HAdV-F (88.7%, 86/97) was the most prevalent species and HAdV-F41 (87.6%, 85/97) was the most common genotype. Diarrhea, vomiting, and fever were the main clinical manifestations in children infected with HAdV. The children aged from 0 to 12 months showed simpler patterns of clinical presentation than those of children older than 13 months. Our findings described the epidemiological changes of HAdV infection in children with AGE during the COVID-19, which further underscored the importance of continuous surveillance of HAdV at both local and global scales.


Alterations in cerebral ventricle size in children with congenital heart disease.
Children with tetralogy of Fallot (TOF) and superior cavopulmonary anastomoses (SCPA) can have chronically elevated central venous pressure (CVP), which has been postulated to put patients at risk for cerebral ventriculomegaly. We aimed to examine cerebral ventricle size in children with these congenital heart lesions before and after surgery to determine how changes in CVP affect ventricle size. We reviewed the records of patients who underwent SCPA or TOF repair between 2006 and 2015. Patients with pre- or post-operative cranial imaging were included. Frontal-occipital (FO) horn ratios were calculated as measures of cerebral ventricle volume. Reported normal mean FO ratio is 0.37 ± 0.03. Patient characteristics including occipito-fronto circumference (OFC) and available CVP measurements were recorded. CVP, FO ratios, and OFC percentiles were compared using paired and unpaired t tests and Wilcoxon matched pairs signed-rank test as appropriate. We reviewed 44 patients who underwent SCPA and 31 patients who underwent TOF repair who had cranial imaging studies available. In the 22 patients who underwent SCPA and had pre- and post-operative imaging, mean FO ratios significantly increased from 0.37 ± 0.03 to 0.40 ± 0.04 (P < 0.001). In contrast, in the seven patients with TOF with pre- and post-operative imaging, FO ratio was elevated at baseline and remains so after surgical repair, 0.43 ± 0.08 to 0.42 ± 0.08 (P = 0.65). Similar patterns were noted with OFC percentiles, which were significantly increased as compared to baseline after SCPA (P < 0.001) but were not significantly changed after TOF repair (P = 0.58). Finally, when available, preoperative and postoperative CVP measurements of all patients were examined, CVP increased in patients who underwent SCPA, from 6.5 ± 2 mmHg preoperatively to 9.1 ± 2.3 mmHg postoperatively (P < 0.001), while CVP remained statistically unchanged in patients who underwent TOF repair, 12.9 ± 3.3 mmHg preoperatively to 14.4 ± 3.1 mmHg postoperatively (P = 0.2). Cerebral ventriculomegaly was observed in patients with SCPA and TOF, and the observed changes in FO ratio and OFC may be related, at least in part, to CVP.


Lung function at 16-19 years in males and females born very prematurely.
To determine if there were differences in lung function at 16-19 years of age between males and females born very prematurely. Females compared with males would have superior lung function and exercise capacity. Cohort study. Those born at less than 29 weeks of gestational age. Lung function testing (spirometry, oscillometry, diffusion capacity, lung clearance index, and plethysmography), a shuttle sprint test for exercise capacity, and a respiratory symptoms questionnaire. Amongst 150 participants, males had poorer lung function compared with females with mean z score differences (95% CI [confidence interval]) after adjustment: forced expiratory flow at 75% (FEF75 ) (-0.60 [-0.97,-0.24]), forced expiratory flow at 50% (FEF50 ) (-0.39 [-0.72,-0.07]), forced expiratory flow at 25%-75% (FEF25-75 ) (-0.62 [-0.98,-0.26]), the ratio of the forced expiratory volume in the first one second to the forced vital capacity of the lungs (FEV1 :FVC ratio) (-0.71 [-1.09,-0.34]), diffusing capacity of the lungs for carbon monoxide (DLCO) (-0.41 [-0.78,-0.03]), diffusing capacity of the lung for carbon monoxide divided by alveolar volume (DLCO/VA) (-0.57 [-0.86,-0.28]). Exercise capacity and self-reported exercise were both significantly better in males than females (46% males achieving between 1250 and 1500 m shuttle sprint distance vs. 4.8% females) and 74% males versus 67% females undertaking some exercise. There were no significant differences by sex in the prevalence of either wheeze or current asthma. Males had poorer lung function than females at age 16-19 years, but their exercise capacity was superior to females.


Nephroblastoma occurring in a multilocular cystic kidney.
A case of a nephroblastoma in a multilocular cystic kidney in a 5-year-old child is reported and the related literature is reviewed. Because of the unreliability of preoperative and intraoperative diagnostic modalities in identifying a coincidental nephroblastoma nephrectomy is recommended for multilocular cystic disease of the kidney in children.


Activation and modulation of recombinantly expressed serotonin receptor type 3A by terpenes and pungent substances.
Serotonin receptor type 3 (5-HT3 receptor) is a ligand-gated ion channel that is expressed in the central nervous system (CNS) as well as in the peripheral nervous system (PNS). The receptor plays an important role in regulating peristalsis of the gastrointestinal tract and in functions such as emesis, cognition and anxiety. Therefore, a variety of pharmacologically active substances target the 5-HT3 receptor to treat chemotherapy-induced nausea and vomiting. The 5-HT3 receptors are activated, antagonized, or modulated by a wide range of chemically different substances, such as 2-methyl-serotonin, phenylbiguanide, setrones, or cannabinoids. Whereas the action of all of these substances is well described, less is known about the effect of terpenoids or fragrances on 5-HT3A receptors. In this study, we screened a large number of natural odorous and pungent substances for their pharmacological action on recombinantly expressed human 5-HT3A receptors. The receptors were functionally expressed in Xenopus oocytes and characterized by electrophysiological recordings using the two-electrode voltage-clamp technique. A screening of two odorous mixes containing a total of 200 substances revealed that the monoterpenes, thymol and carvacrol, act as both weak partial agonists and positive modulators on the 5-HT3A receptor. In contrast, the most effective blockers were the terpenes, citronellol and geraniol, as well as the pungent substances gingerol, capsaicin and polygodial. In our study, we identified new modulators of 5-HT3A receptors out of the classes of monoterpenes and vanilloid substances that frequently occur in various plants.


Menadione and ethacrynic acid inhibit the hypoxia-inducible factor (HIF) pathway by disrupting HIF-1α interaction with p300.
Hypoxia is a general characteristic of most solid malignancies and intimately related to neoplastic diseases and cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor (HIF)-1α that elicits transcriptional activity through recruitment of the CREB binding protein (CBP)/p300 coactivator. Targeted blockade of HIF-1α binding to CBP/p300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, we identified inhibitors against the interaction between HIF-1α and p300 by a fluorescence polarization-based assay employing a fluorescently-labeled peptide containing the C-terminal activation domain of HIF-1α. Two small molecule inhibitors, menadione (MD) and ethacrynic acid (EA), were found to decrease expression of luciferase under the control of hypoxia-responsive elements in hypoxic cells as well as to efficiently block the interaction between the full-length HIF-1α and p300. While these compounds did not alter the expression level of HIF-1α, they down-regulated expression of a HIF-1α target vascular endothelial growth factor (VEGF) gene. Considering hypoxia-induced VEGF expression leading to highly aggressive tumor growth, MD and EA may provide new scaffolds for development of tumor therapeutic reagents as well as tools for a better understanding of HIF-1α-mediated hypoxic regulation.


Identifying the important outcomes to measure for pharmacy-led, clinical services within primary care: A nominal group technique approach.
The introduction of clinical pharmacy services is part of a multi-disciplinary approach to reduce pressure on primary care. Ascertaining the impact of clinical pharmacists in general practice is vital to ensure intended benefits are achieved. However, this is complicated by poor quality evidence, multiple interventions, and a lack of agreement regarding outcome measures. To develop an outcomes framework for clinical pharmacy services delivered in Scottish general practice using a consensus methodology. A modified nominal group technique (NGT) was conducted using Microsoft Teams and Qualtrics. This involved a pre-NGT questionnaire, silent generation of ideas, round robin, discussions, ranking, and a final consensus exercise. A selective sampling strategy recruited experienced pharmacists from Scottish health regions. NGT ranking results were used to signify relative importance of the outcome areas. NGT discussions underwent inductive thematic analysis to explore key areas considered. Overall, 13 (median: 24 years of experience) pharmacists participated, representing 11 of 14 Scottish regions. In total, 21 outcome areas, derived from the literature and a pre-NGT questionnaire, were considered during the NGT ranking exercise. Consensus identified five important outcome areas: Patient Experience, Medication Related Adverse Events, Cost-Effectiveness, Medication Optimisation, and Health Related Quality of Life. Thematic analysis highlighted the importance of the outcome framework's target audience, factors influencing the interpretation of outcomes, and the feasibility of the associated outcome measures. The five key outcome areas will facilitate evidence-based decisions regarding service delivery. Future work should develop a measurement plan, involving routinely collected sources of outcomes data. The feasibility of collecting outcomes in the real-world context should be considered, identifying measures which are easy to collect within existing data infrastructures. This paper describes a replicable method to gain consensus for a national approach to data collection from a strong theoretical basis using an online methodology.


Vaccines against human parasitic diseases: an overview.
There are no vaccines currently available to control the major human parasitic diseases, although there is evidence of acquired immunity and resistance to reinfection in most of the parasitic infections. The present manuscript concentrates on the vaccines for parasitic diseases that are in the most advanced stages of development: malaria, leishmaniasis and schistosomiasis. Vaccines for malaria and leishmaniasis have been taken to clinical trials while vaccines for schistosomiasis are being considered for Phase I (assessment of safety and immune responsiveness in volunteers). We have attempted to give a factual account of the present status of knowledge of vaccines against human parasitic diseases, emphasizing both the successes and setbacks. We do not intend to cover the enormous literature in the field but have concentrated on the most promising antigenic preparations. Finally, some new approaches for the development of vaccines are discussed including nucleic acid vaccines and the use of cytokines as adjuvants.


Successful endoscopic closure with an over-the-scope clip for sigmoid colon perforation due to bile duct stent migration.
An 86-year-old woman presented with a history of endoscopic papillary sphincterotomy for bile duct stones and diverticulitis. The patient was admitted as an emergency case of acute cholangitis due to choledocholithiasis, underwent endoscopic bile duct stenting, and was discharged with a plan for endoscopic lithotripsy. One month later, the patient was readmitted owing to abdominal pain. Abdominal computed tomography at admission showed that the bile duct stent had migrated to the sigmoid colon and the presence of a small amount of extraintestinal gas, suggesting a colonic perforation. Lower gastrointestinal endoscopy showed adhesions and intestinal stenosis in the sigmoid colon, probably after diverticulitis, and the bile duct stent that had perforated the same site. The stent was removed and endoscopic closure of the perforation was performed using an over-the-scope clip. Abdominal computed tomography 8 days after the closure showed no extraintestinal gas. The patient resumed eating and was discharged on the 14th day of admission. There was no recurrence of abdominal pain. Endoscopic closure of sigmoid colon perforation due to bile duct stent migration using an over-the-scope clip has not been reported thus far, and it may be a new treatment option in the future.


Iatrogenic ureteral injury: can adult repair techniques be used on children?
Iatrogenic ureteral injury in children is a rare occurrence, with sparse literature available regarding optimal repair techniques. We reviewed our experience in the management of iatrogenic pediatric ureteral injuries, particularly with respect to initial versus delayed diagnoses. All pediatric iatrogenic ureteral injuries repaired by a single surgeon during 1986-2007 were reviewed. Ten injuries were repaired over 20 years. Median patient age was 12 years. Injuries occurred during five open tumor resections, three laparoscopic procedures and two ureteroscopies. Diagnosis was immediate in four patients. Median ureteral defect length was 4 cm (range 2-5). All underwent ureteral reimplantation and psoas hitch Boari flap. Median follow up was 1 year, with no obstruction noted. Diagnosis was delayed in six patients by a median of 21 days. Five children (83%) were managed by temporary percutaneous nephrostomy tube and one (17%) by ureteral stent. Delayed repair was performed 1-3 months later. In the patients with laparoscopic or ureteroscopic injuries the median ureteral defect length was 4 cm (range 3-6). All underwent ureteral reimplantation and psoas hitch Boari flap. Median follow up was 1 year, with no obstruction noted. One child had a proximal ureteral defect 8 cm long; delayed ileal ureter was performed with good results 4 years postoperatively. Pediatric iatrogenic ureteral injuries are rare and may be repaired by both immediate and delayed techniques as circumstances demand. Standard techniques used in the adult population may be employed in children with the expectation of good long-term results.


The isolation of DNA from agarose gels by electrophoretic elution onto malachite green-polyacrylamide columns.
Electrophoretic elution of DNA coupled with direct adsorption onto malachite green-polyacrylamide columns was used to isolate double- and single-stranded DNA from agarose gels. Subsequently, DNA was eluted with a high salt buffer and filtered through Sephadex which permitted recovery of the DNA in a low salt buffer at concentrations suitable for heteroduplex analysis by electron microscopy. This method was tested by examining heteroduplexes formed from the isolated complementary single strands of T7 wild type DNA and a T7 deletion mutant. More than 80% of the reannealed molecules were intact heteroduplexes showing the deletion loop. Irradiation of single-stranded DNA with 254 nm light resulted in distorted, convoluted heteroduplexes while 366 nm light did not show this effect.


Percentage of biopsy cores positive for malignancy and biochemical failure following prostate cancer radiotherapy in 3,264 men: statistical significance without predictive performance.
To define and incorporate the impact of the percentage of positive biopsy cores (PPC) into a predictive model of prostate cancer radiotherapy biochemical outcome. The data of 3264 men with clinically localized prostate cancer treated with external beam radiotherapy at four institutions were retrospectively analyzed. Standard prognostic and treatment factors plus the number of biopsy cores collected and the number positive for malignancy by transrectal ultrasound-guided biopsy were available. The primary endpoint was biochemical failure (bF, Phoenix definition). Multivariate proportional hazards analyses were performed and expressed as a nomogram and the model's predictive ability assessed using the concordance index (c-index). The cohort consisted of 21% low-, 51% intermediate-, and 28% high-risk cancer patients, and 30% had androgen deprivation with radiotherapy. The median PPC was 50% (interquartile range [IQR] 29-67%), and median follow-up was 51 months (IQR 29-71 months). Percentage of positive biopsy cores displayed an independent association with the risk of bF (p=0.01), as did age, prostate-specific antigen value, Gleason score, clinical stage, androgen deprivation duration, and radiotherapy dose (p<0.001 for all). Including PPC increased the c-index from 0.72 to 0.73 in the overall model. The influence of PPC varied significantly with radiotherapy dose and clinical stage (p=0.02 for both interactions), with doses<66 Gy and palpable tumors showing the strongest relationship between PPC and bF. Intermediate-risk patients were poorly discriminated regardless of PPC inclusion (c-index 0.65 for both models). Outcome models incorporating PPC show only minor additional ability to predict biochemical failure beyond those containing standard prognostic factors.


Pacemaker diagnostics in atrial fibrillation: limited usefulness for therapy initiation in a pacemaker practice.
We aimed to determine the practical value of pacemaker diagnostics for atrial fibrillation (AF) in an unselected general pacemaker practice, specifically workflow and initiation of anticoagulation or antiarrhythmic drug (AAD) therapy. We prospectively followed consecutive pacemaker interrogations over a period of 1 year to identify patients with AF (burden from 1% to 99%). We contacted referring physicians with AF details, and then determined whether the information resulted in therapeutic changes. Of the 1,100 pacemakers interrogated, 728 were dual chamber (DDDs) with AF diagnostic capability. AF was recorded in 73 (10%) but seven had limited information, leaving 66 patients; of these, 42 (63%) patients were already anticoagulated and in five (7%) patients, anticoagulation had been stopped because of complications. Initial diagnosis of AF was made by the pacemaker in 17 patients (26% of 66; 2% of 728); four (6% of 66) patients were newly initiated on anticoagulation. Of the 66 patients, 17 patients were already on AADs; 49 (74%) had satisfactory rate control or had other issues; only two (3% of 66; 0.3% of 728) received new AADs. Of 728 patients with DDD pacemakers, only 17 were newly discovered to have AF, and six (0.8%) had changes in medications based on the pacemaker data. Adding pacemaker-derived data to existing clinical information had little therapeutic impact, due to a combination of cumbersome workflow, and because AF was usually known to practitioners. Developments in automated monitoring systems may provide more accessible and therapeutically useful information.


Differential modulation of transforming growth factor-betas and cyclooxygenases in the platelet lysates of male F344 rats by dietary lipids and piroxicam.
Platelets are implicated in the pathogenesis of various chronic diseases including cancer. The main objective of the present study was to determine if dietary fish oil and piroxicam, known modulators of colon tumorigenesis, effect transforming growth factor (TGF)-betas and cyclooxygenase (COX) isozymes in the platelets of colon tumor-bearing male F344 rats. TGF-betas and COXs are important in the development of chronic illnesses including colon cancer. Animals harboring preneoplastic colonic lesions were randomly allocated to a low fat diet (5% by weight--low corn oil, LFC) and three high fat diets (23% by weight--high corn oil, HFC; high corn oil containing 150-ppm piroxicam, HFC+P; and high fish oil, HFF) for 16 weeks. TGF-beta1, TGF-beta2, COX-1 and COX-2 protein levels were assessed in the platelets by Western blot analysis. Active TGF-beta1 (12.5 kDa) level was significantly lower in the platelets of the HFC+P group (p < 0.001), whereas precursor TGF-beta1 (39 kDa) level was significantly lower in the platelets of the HFF group (p < 0.001). The anti-rabbit TGF-beta2 polyclonal antibody did not detect the 13-kDa active TGF-beta2 protein in the platelets. However a 29-kDa protein, potentially a precursor of TGF-beta2, was detected in the platelets of all the groups and was significantly lower in the HFC+P and HFF groups than in LFC and HFC (p < 0.001). COX-1 level was significantly lower in the HFF group than the other three groups (p < 0.001). COX-2 protein was detected in the platelets of all diet groups. Piroxicam in the presence of high corn oil (HFC+P) significantly lowered the level of COX-2 (p < 0.001), without having any effect on COX-1 level. These findings conclusively show that LFC and HFC differ from HFF and HFC+P, and piroxicam differs from fish oil, in regulating the levels of TGF-betas and COX in the platelets. This supports the conjecture that the levels of bioactive constituents of the platelets are profoundly modulated by dietary lipids, which in turn could influence the pathogenesis of chronic illnesses.


Benign lymphocytic angiitis and granulomatosis: experience with three cases.
Of three patients with lung-biopsy-proven benign lymphocytic angiitis and granulomatosis, two experienced complete resolution of their disease from therapy with chlorambucil and one underwent spontaneous remission with no drug therapy after lung biopsy and removal of a benign spindle cell thymoma. Clinically, it is difficult to determine whether benign lymphocytic angiitis is a low-grade (prelymphomatous) lymphoma or a vasculitis. Its position in this spectrum of diseases is uncertain. Nonetheless, benign lymphocytic angiitis and granulomatosis corresponding to a low-grade angiocentric immunoproliferative lesion is a clinicopathologically useful concept.


Facet-Dependent Catalytic Performance of Au Nanocrystals for Electrochemical Nitrogen Reduction.
Nanostructured metal catalysts have attracted great interest due to their extraordinary performance for electrocatalysis including electrochemical nitrogen reduction (ENRR). However, their working mechanisms for ENRR are still not fully understood. Herein, seven monofaceted polyhedral Au nanocrystals were synthesized and systemically compared to elucidate the relation between Au crystal facets and NRR performance. It is found that polyhedra with high-index facets catalytically outperform those with low-index facets. Specifically, Au nanostars enclosed with (321) facets show a high NH3 production rate of 2.6 μg h-1 cm-2 (20 μg h-1 mg-2) and faradaic efficiency of 10.2% at -0.2 V, which are 3.1- and 5.1-folds larger than those of nanocubes enclosed with (100) facets. As revealed by theoretical investigation, a larger energy barrier for reduction of H+ to H* (ΔGH*) hinders occurrence of HER on the Au(321) surface, thus ensuring better NRR selectivity. Meanwhile, a lower energy barrier for formation of N2H2* on the catalyst surface and a larger energy barrier for decomposing the formed N2H2* back into N2 and 2H* jointly favor a higher NH3 production rate. This study provides mechanistic insights into ENRR and rational design of metal nanocrystals for electrocatalysis.


Optimal myocardial preservation with an acalcemic crystalloid cardioplegic solution.
The effect of the calcium and oxygen contents of a hyperkalemic glucose-containing cardioplegic solution on myocardial preservation was examined in the isolated working rat heart. The cardioplegic solution was delivered at 4 degrees C every 15 minutes during 2 hours of arrest, maintaining a myocardial temperature of 8 degrees +/- 2 degrees C. Hearts were reperfused in the Langendorff mode for 15 minutes and then resumed the working mode for a further 30 minutes. Groups of hearts were given the oxygenated cardioplegic solution containing an ionized calcium concentration of 0, 0.25, 0.75, or 1.25 mmol/L or the same solution nitrogenated to reduce the oxygen content and containing 0 or 0.75 mmol ionized calcium per liter. The myocardial adenosine triphosphate concentrations at the end of arrest in these six groups of hearts were 15.6 +/- 1.2, 9.5 +/- 0.5, 8.2 +/- 1.1, 4.9 +/- 1.8, 10.1 +/- 2.0, and 1.6 +/- 0.4 nmol/mg dry weight, respectively. At 5 minutes of working reperfusion, the percentages of prearrest aortic flow were 80 +/- 2, 62 +/- 4, 33 +/- 6, 37 +/- 5, 48 +/- 7 and 46 +/- 8, respectively. The differences among the groups in adenosine triphosphate concentrations and in functional recovery diminished during reperfusion. In hearts given the hypoxic calcium-containing solution, there was a marked increase in coronary vascular resistance during the administration of successive doses of cardioplegic solution, which was rapidly reversible upon reperfusion. These data indicate that hearts given the acalcemic oxygenated solution had better adenosine triphosphate preservation during arrest and better functional recovery than hearts in any other group. Addition of calcium to the oxygenated cardioplegic solution decreased adenosine triphosphate preservation and functional recovery. Oxygenation of the acalcemic solution increased adenosine triphosphate preservation and functional recovery. The lowest adenosine triphosphate levels at end arrest were observed in hearts given the hypoxic calcium-containing solution. In the setting of hypothermia and multidose administration, the addition of calcium to a cardioplegic solution resulted in increased energy depletion during arrest and depressed recovery.


Synthesis of different chiral amino gamma-butyrolactones and amino gamma-butenolides.
Different transformations of chiral epoxy esters 1 afford two different amino gamma-butyrolactones 2 and 6, and amino gamma-butenolides 8, by different nucleophilic opening-closing processes. [reaction: see text]


Synthesis and carbonic anhydrase inhibitory properties of sulfamides structurally related to dopamine.
A series of novel sulfamides incorporating the dopamine scaffold were synthesized. Reaction of amines and tert-butyl-alcohol/benzyl alcohol in the presence of chlorosulfonyl isocyanate (CSI) afforded sulfamoyl carbamates, which were converted to the title compounds by treatment with trifluoroacetic acid or by palladium-catalyzed hydrogenolysis. Inhibition of six α-carbonic anhydrases (CAs, EC 188.8.131.52), that is, CA I, CA II, CA VA, CA IX, CA XII and CA XIV, and two β-CAs from Candida glabrata (CgCA) and Mycobacterium tuberculosis (Rv3588) with these sulfamides was investigated. All CA isozymes were inhibited in the low micromolar to nanomolar range by the dopamine sulfamide analogues. K(i)s were in the range of 0.061-1.822 μM for CA I, 1.47-2.94 nM for CA II, 2.25-3.34 μM for CA VA, 0.041-0.37 μM for CA IX, 0.021-1.52 μM for CA XII, 0.007-0.219 μM for CA XIV, 0.35-5.31 μM for CgCA and 0.465-4.29 μM for Rv3588. The synthesized sulfamides may lead to inhibitors targeting medicinally relevant CA isoforms with potential applications as antiepileptic, antiobesity antitumor agents or anti-infective.


Abstinence and Use of Community-Based Cessation Treatment After a Motivational Intervention Among smokers with Severe Mental Illness.
Motivational interventions help people with mental illness try to quit smoking, but few studies have evaluated factors associated with this groups' cessation with community treatment. We examined predictors of abstinence after a brief motivational intervention among smokers with severe mental illness. Education, stage of change post intervention, and use of cessation treatment predicted any 1-week period of self-reported abstinence over 6 months (29%). Cessation treatment mediated the relationship between stage of change and abstinence. Because treatment was the key modifiable predictor of abstinence, future research should establish strategies that improve motivation for, access to, and retention in cessation treatment. Clinical Trials Identifier NCT01412866.


[The immune system in aging].
The immune system changes during life time. In this article we review which kinds of alterations take place. To exclude changes based on illnesses or chronical diseases, the SENIEUR protocol was performed, which defines "healthy elderly people". We focus on alterations in lymphocyte subsets, immunoglobulins and the cytokine network. Monocytes, eosinophils and basophils are without change during life, whereas the number of neutrophils and natural killer (NK) cells increase with aging. T- and B-lymphocytes are diminished in number as well as in function. The serum levels of immunoglobulins are mostly increased. The balance between TH1- and TH2-cells is disturbed and also TH1- and TH2-specific cytokines. Theses changes and their effects on the health status of the elderly are discussed in detail.


Acid phosphatase activity in normal and denervated chick skeletal muscle.
Histochemical and biochemical changes in acid phosphatase activity were studied in the normal and denervated gastrocnemii of chick for a maximum period of 8 weeks. In the normal muscle, fibre heterogeneity with respect muscles exhibit greater susceptibility to degenerative changes on account of denervation. Quantitatively higher enzyme levels in the denervated muscles confirm the lytic role of acid phosphatase.


Longitudinal extension of oedema in experimental spinal cord injury--evidence for two types of post-traumatic oedema.
As in brain, another, obviously hydrostatic, type of oedema develops in the acutely injured spinal cord of the rabbit in addition to vasogenic oedema. The authors arrived at this finding by means of fluorescent tracer studies histological examinations, and measurements of tissue water, sodium and potassium. Longitudinal spread of vasogenic oedema remained limited to the zone of the epicentre and its surroundings. Hyperhydration, which appears gradually in the remote segments and is associated with increased sodium content, has the characteristics of plasma-ultrafiltrate.


Preservation of second formant transitions during simultaneous communication: a locus equation perspective.
This study investigated the preservation of second formant transition acoustic cues to intelligibility in speech produced during simultaneous communication (SC) from a locus equation perspective. Twelve normal hearing, experienced sign language users were recorded under SC and speech alone (SA) conditions speaking a set of sentences containing monosyllabic words designed for measurement of second formant frequencies in consonant-vowel-consonant (CVC) syllables. Linear regression fits made to coordinates representing second formant transition onset and offset frequencies following stop consonant release of CVC syllables (locus equations) were used to examine place of articulation cues in both SA and SC conditions. Although results indicated longer sentence durations for SC than SA, locus equation slopes and intercepts obtained from speech produced during SC were virtually identical to those obtained during SA, indicating no degradation of stop consonant acoustic cues during SC. This conclusion is consistent with previous research indicating that temporal alterations produced by SC do not involve violations of other rules of spoken English. As a result of this activity, the participant will be able to (1) describe SC; (2) explain the role of SC in communication with children who are deaf; (3) describe second formant transitions in English speech; and (4) identify second formant transition patterns in speech produced during SC.


Profiling of polyphenols for in-depth understanding of Tartary buckwheat sprouts: Correlation between cultivars and active components, dynamic changes and the effects of ultraviolet B stress.
Tartary buckwheat sprouts have a high nutritional value and are gluten-free, and polyphenols are their main active constituents. However, information regarding the active constituents' difference of Tartary buckwheat sprouts grown from seeds with different morphology, at different developmental stages and environments is limited. Here, we developed a LC-MS-based targeted metabolomics approach to analyze polyphenols (46 flavonoids and 6 anthraquinones) in 40 Tartary buckwheat sprouts varieties. Both flavonoids and anthraquinones contributed to significant differences in sprouts grown from seed with different color or shape. Twenty-seven differential compounds were all at a higher level in 3-day-old sprouts, and the fold change from 3-day-old to 8-day-old sprouts was 1.42-6.64. A total of 25 differential compounds were all significantly upregulated upon UV-B radiation, especially for epicatechin. This study is valuable not only for better breeding cultivars of Tartary buckwheat sprouts, but also assessing their metabolic quality.


Effectiveness of structured teaching program on parents' knowledge about child physical abuse.
The issue of child physical abuse (CPA) is complex and challenging to study. According to World Health Organization fact sheets for 2020, about 3 in 4 children between 2 and 4 years of age regularly face physical maltreatment by parents or caregivers. It may cause a lifelong impact on physical and mental health. To assess the parents' knowledge and to evaluate the effectiveness of the structured teaching program (STP) regarding child physical abuse (CPA) among parents. The pre-experimental, "One-group Pre-test Post-test design" was adopted for this study. Parents of children who were admitted for treatment in the child psychiatry centre (CPC) of a tertiary care referral center between January 2019 and January 2020 were recruited for this study. Thirty parents were recruited with a convenience sampling technique. The study was conducted through an online platform (Zoom). Pre-test and post-tests were conducted through Google survey form. Data were collected with a self-developed knowledge questionnaire on CAP. An online structured teaching program (STP) was administered for three alternative days after the pre-test assessment. The post-test assessment was conducted at a two-point time, that is immediately after the STP and after the one-week gap. Descriptive and inferential statistics were used to analyze the data. "One-group Pre-test Post-test design" was adopted for this study. Parents of children who were admitted for treatment in the child psychiatry centre (CPC) of a tertiary care referral center between January 2019 and January 2020 were recruited for this study. Thirty parents were recruited with a convenience sampling technique. The study was conducted through an online platform (Zoom). Pre-test and post-tests were conducted through Google survey form. Data were collected with a self-developed knowledge questionnaire on CAP. An online structured teaching program (STP) was administered for three alternative days after the pre-test assessment. The post-test assessment was conducted at a two-point time, that is immediately after the STP and after the one-week gap. Descriptive and inferential statistics were used to analyze the data. The pre-test knowledge assessment means score regarding child physical abuse was found to be 12, with a standard deviation of 1.73. In the post-test one, 17.30 ± 1.39 and in the post-test two, 16 ± 1.55 with P < 0.001. Analysis revealed statistically significant improvement was found in the post-test knowledge regarding child physical abuse among the parents. There was no significant (p < 0.05) relationship found between the socio-demographic variables of the participants and their pre-intervention knowledge scores on child physical abuse. The study findings reveal that parents have a fair knowledge of CPA and the STP was effective and feasible to administer in improving the subjects' knowledge regarding child physical abuse.


Hypertensive encephalopathy presenting as status epilepticus in a three year old.
Hypertensive encephalopathy is one of the few neurologic emergencies in which prompt diagnosis and treatment can prevent permanent neurological damage. This syndrome is rarely seen in children. To discuss the recognition of hypertensive encephalopathy as a cause of acute neurological changes in children. We present the case of a 3-year-old boy who presented to the Emergency Department with seizures due to hypertensive encephalopathy. A review of the literature on the subject follows the case report. Hypertensive encephalopathy is a rare cause of acute neurological changes in children that can cause permanent damage if not recognized early. This case illustrates the importance of considering this syndrome as a potential cause of neurological symptoms, especially as neuroimaging can initially be misleading.


Signaling cascades involved in neuroprotection by subpicomolar pituitary adenylate cyclase-activating polypeptide 38.
In neuronal/glial cocultures, pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) prevented neuronal death induced by gp120, lipopolysaccharide (LPS), or other toxic agents, but the dose response of the neuroprotective effect is bimodal, with a peak at a subpicomolar concentration and another peak at a subnanomolar to nanomolar concentration. Although the signaling cascade involved in neuroprotection by nanomolar concentration of the peptide has been shown to be mediated by activation of cAMP-dependent protein kinase and subsequent activation of mitogen-activated protein kinase (MAPK), the mechanism for neuroprotection by a subpicomolar level of PACAP38 remains elusive. In the present study, the signaling involved in neuroprotection by subpicomolar PACAP38 was studied in rat neuronal/glial cocultures. Addition of PACAP38 stimulated expression and activation of extracellular signal-related kinase-type MAPK with a peak response at 10-13 M; greater concentrations of the peptide induced lesser response. cAMP production also increased at subpicomolar levels of PACAP38, but the level remained unchanged at a level four to five times higher than the base level at concentrations below 10-11 M. cAMP then started increasing again dose-dependently in a range >10-11 M PACAP38. Lipopolysaccharide (LPS)-induced neuronal death, indicated by increased release of neuron-specific enolase, was suppressed by PACAP38 in a bimodal fashion. Neuroprotection by 10-12 M PACAP38 was completely abolished by a MAPK kinase-1 inhibitor, PD98059, and also partially suppressed by Rp-cAMP, a cAMP-dependent protein kinase inhibitor. Moreover, neuroprotection by a nanomolar level of PACAP38 was completely suppressed by Rp-cAMP but not affected by PD98059. We conclude that neuroprotection by subpicomolar PACAP38 is mainly mediated by the signaling pathway involving MAPK activation and partially regulated by cAMP-dependent protein kinase activation. Furthermore, PACAP38 stimulated expression of activity- dependent neuroprotective protein (ADNP), with a peak at 10-13 M. Greater doses of the peptide induced lesser response. However, 10-13 M PACAP38-stimulated expression of ADNP was not affected by PD98059. This suggests that neuroprotection by subpicomolar PACAP38 might be mediated partially by expression of ADNP, but the major events for neuroprotection by subpicomolar PACAP38 remain to be identified.


Gradations of emulation learning in infants' imitation of actions on objects.
This study explored different gradations of emulation in the imitation of actions on objects by 17-month-olds. Experiment 1 established levels of behavioral reproduction following prerecorded video demonstrations similar to those levels following live demonstrations. In Experiment 2, two digitally modified videos, where object movements or body movements critical to producing the target action were highlighted in isolation, were developed. Infants produced the target action equally frequently by observing the object movement video and observing the unmodified video. In contrast, their performance was much less successful based on the body movement video. In Experiment 3, the performance obtained following the object movement video was similar to that following a further video that emphasized the object movements produced in unsuccessful attempts to produce the target action. These findings suggest that emulation in the form of object movement reenactment or affordance learning plays a role in the social learning of actions on objects during infancy.


Characterization of photoproducts and global ecotoxicity of chlorphenesin: A preservative used in skin care products.
Photolysis experiments of chlorphenesin, used as a preservative in cosmetic products, were performed in aqueous solution and on a cream used in cosmetics. Three by-products resulting from the direct UV-visible photodegradation of chlorphenesin were characterized by chromatography (gas and liquid) coupled with tandem mass spectrometry (GC-MS/MS and LC-HR MS/MS) and found in both solutions. In vitro tests on Vibrio fischeri bacteria showed that the overall ecotoxicity of chlorphenesin increased with increasing irradiation time in both samples. In silico QSAR (Quantitative Structure Activity Relationship) tests were performed using T.E.S.T. (Toxicity Estimation Software Tool). Among the degradation compounds identified, 4-chlorophenol must contribute to the increased ecotoxicity of the photolyzed solution since the in silico LC50 estimated for all tests performed are always lower than those obtained for chlorphenesin.


Treatment of advanced gastric cancer with oral etoposide, leucovorin and tegafur: experience with an oral modification of the etoposide, leucovorin and 5-fluorouracil (ELF) regimen.
Recent data have suggested enhanced therapeutic activity with prolonged administration of both etoposide as well as fluoropyrimidines in the treatment of gastrointestinal malignancies. Based on this rationale, we investigated the clinical effectiveness and tolerance of an oral modification of the widely applied etoposide, leucovorin and 5-fluorouracil (ELF) regimen in patients with advanced gastric cancer. 32 patients with advanced gastric cancer were treated with oral etoposide (100 mg), leucovorin (3 x 100 mg), and tegafur (3 x 200 mg) over 14-21 days for a maximum of six cycles. Objective response was seen in only 5 patients (16%), stable disease was documented in 7 (22%), while the remaining patients progressed during therapy. The median time to progression was 2.8 months (range 0.7-12 months) and median overall survival was 6 months (range 1-18+ months). Due to grade 3 nausea/emesis, 8 patients discontinued treatment prematurely, while 12 patients experienced anorexia and progressive weight loss. Haematological toxicity was modest, with 4 patients developing asymptomatic grade 3-4 granulocytopenia. We conclude that this oral combination regimen cannot be recommended for the treatment of advanced gastric cancer.


Alcohol, cannabis and other drugs and subsequent suicide ideation and attempt among young Mexicans.
To report results from a follow-up study of alcohol, cannabis and other drugs on suicidal behavior. We estimated prospective associations of substance use as a risk factor for incident suicide ideation and attempt, from a follow-up conducted in 2013 (n = 1071) of the original Mexican Adolescent Mental Health Survey conducted in 2005. Cannabis use before age 15 (ideation risk ratio (RR) = 3.97; 95% confidence interval (CI) = 1.43-11.03; attempt RR = 5.23; 95% CI = 1.17-23.32), early onset of DSM-IV drug use disorder (DUD) among cannabis users (ideation RR = 3.30; 95% CI = 1.11-9.84; attempt RR = 4.14; 95% CI = 1.28-13.36), high frequency of cannabis use (RR for attempts = 4.60; 1.03-20.60) and recent DSM-IV-DUD among cannabis users (RR for attempts = 4.74; 1.09-20.57) increased the RR. For "other drug use", significant results were found among those with high frequency use of other drugs such that they had a higher RR of suicide attempt (5.04; 1.03-24.64). For alcohol, only those who initiated alcohol before age 15 had higher RRs of suicide attempt (1.79; 1.00-3.20). Those who used cannabis at an early age, early onset of DSM-IV-DUD, and those with heavy cannabis use and recent DSM-IV-DUD among cannabis users in the last 12-months had increased risk of suicide ideation and attempt. Drugs other than cannabis showed some of these associations, but to a lesser degree. Prevention of substance use and treatment of those already engaged in drug use, by decreasing suicide ideation and attempt, may help to prevent suicide in Mexico.


Simultaneous Imaging and Photodynamic-Enhanced Photothermal Inhibition of Cancer Cells Using a Multifunctional System Combining Indocyanine Green and Polydopamine-Preloaded Upconversion Luminescent Nanoparticles.
This work introduces a novel multifunctional system called UPIPF (upconversion-polydopamine-indocyanine-polyethylene-folic) for upconversion luminescent (UCL) imaging of cancer cells using near-infrared (NIR) illumination. The system demonstrates efficient inhibition of human hepatoma (HepG2) cancer cells through a combination of NIR-triggered photodynamic therapy (PDT) and enhanced photothermal therapy (PTT). Initially, upconversion nanoparticles (UCNP) are synthesized using a simple thermal decomposition method. To improve their biocompatibility and aqueous dispersibility, polydopamine (PDA) is introduced to the UCNP via a ligand exchange technique. Indocyanine green (ICG) molecules are electrostatically attached to the surface of the UCNP-polydopamine (UCNP@PDAs) complex to enhance the PDT and PTT effects. Moreover, polyethylene glycol (PEG)-modified folic acid (FA) is incorporated into the UCNP-polydopamine-indocyanine-green (UCNP@PDA-ICGs) nanoparticles to enhance their targeting capability against cancer cells. The excellent UCL properties of these UCNP enable the final UCNP@PDA-ICG-PEG-FA nanoparticles (referred to as UPIPF) to serve as a potential candidate for efficient anticancer drug delivery, real-time imaging, and early diagnosis of cancer cells. Furthermore, the UPIPF system exhibits PDT-assisted PTT effects, providing a convenient approach for efficient cancer cell inhibition (more than 99% of cells are killed). The prepared UPIPF system shows promise for early diagnosis and simultaneous treatment of malignant cancers.


Prognostic and immunological role of Asporin across cancers and exploration in bladder cancer.
Asporin (ASPN) has been identified as a player in tumorigenesis, but its precise roles and modulatory function are largely unknown. In the present study, ASPN expression was first explored, followed by a prognostic evaluation of ASPN and a comprehensive investigation of the connections between ASPN and immunomodulation, immune cell infiltration and potential compounds on a pancancer level. Finally, ASPN expression was validated in bladder urothelial carcinoma (BLCA) tissues, and the potential function of ASPN, including its effects on migration and invasion capabilities, was investigated in tumor cells. The expression of ASPN exhibited significant variation across cancers and was found to be associated with patient prognosis. In addition, the expression level of APSN was markedly correlated with the abundances of infiltrating immune cells and cancer-associated fibroblasts and the expression levels of immunomodulatory genes based on the results of pancancer analysis. Metastasis and immune-associated signaling pathways were identified in enrichment analysis based on ASPN expression. Finally, we confirmed that ASPN expression increased with the degree of malignancy in BLCA tissues and cell lines and that low expression of ASPN hindered the migration and invasion of cells. ASPN has the potential to be a biomarker of cancer prognosis and a therapeutic target, and it also has predictive capability for the progression of BLCA.


Edaphovirga cremea gen. nov., sp. nov., isolated from the rhizospheric soil of Codonopsis clematidea.
A Gram-negative, facultatively anaerobic, non-motile, nonspore- forming, coccoid or rod-shaped and creamy-pigmented bacterium, designated SYP-B2100T, was isolated from the rhizospheric soil of Codonopsis clematidea in the Xinjiang Uygur Autonomous Region, China. The optimal growth occurred at 28°C, pH 5.0, in the absence of NaCl. The cells tested positive in catalase and methyl red tests but negative in oxidase, urease, gelatinase, milk coagulation, and peptonisation, H2S production, nitrate reduction, and Voges-Proskauer tests. The major isoprenoid quinone was ubiquinone-8 (Q-8). The major cellular fatty acids were C16:0 and summed feature 8. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylglycerol. The 16S rRNA gene sequence of strain SYP-B2100T was the most similar to that of Rahnella inusitata DSM 30078T (96.9%) within the family Enterobacteriaceae. The genomic DNA G + C content of strain SYP-B2100T was 50.3 mol%. The combined data from the phylogenetic, morphological, physiological, biochemical, and chemotaxonomic analyses presented in this study support the conclusion that strain SYP-B2100T represents a novel species of a new genus, for which the name Edaphovirga cremea gen. nov., sp. nov. is proposed; the type strain is SYPB2100T (= CGMCC 1.5857T = DSM 105170T = KCTC 62024T).


A minimal fate-selection switch.
To preserve fitness in unpredictable, fluctuating environments, a range of biological systems probabilistically generate variant phenotypes--a process often referred to as 'bet-hedging', after the financial practice of diversifying assets to minimize risk in volatile markets. The molecular mechanisms enabling bet-hedging have remained elusive. Here, we review how HIV makes a bet-hedging decision between active replication and proviral latency, a long-lived dormant state that is the chief barrier to an HIV cure. The discovery of a virus-encoded bet-hedging circuit in HIV revealed an ancient evolutionary role for latency and identified core regulatory principles, such as feedback and stochastic 'noise', that enable cell-fate decisions. These core principles were later extended to fate selection in stem cells and cancer, exposed new therapeutic targets for HIV, and led to a potentially broad strategy of using 'noise modulation' to redirect cell fate.


Splenic red cell pooling: a diagnostic feature in polycythaemia.
Total red cell volumes and splenic red cell pools were measured in 31 patients with polycythaemia. 22 had polycythaemia vera (PV), 12 of whom had clinically detectable splenomegaly, and nine patients had secondary polycythaemia (PS). The mean red cell pool was 192.8 ml (SD 126.6) in PV (all cases), and 130.9 ml (SD 28.4 ml) in PV without splenomegaly; it was 61.1 ml (SD 8.3 ml) in PS. When expressed relative to spleen size (in cm), differences were even more striking: PV (all cases)--mean 13.7 ml/cm (SD 4.3); PV without splenomegaly--mean 12.7 ml/cm (SD 2.2); PS--mean 6.6 ml/cm (SD 1.2). Measurement of splenic red cell pool thus appears to be a valuable diagnostic tool for distinguishing between PV and PS. The findings point to the presence in PV of a splenic structural abnormality which is not simply an effect of the increased circulating red cell mass.


Communication and Competencies Across Undergraduate BSN Programs and Curricula.
An investigation was conducted to assess for and describe health communication instruction in entry-level baccalaureate (BSN) programs. This cross-sectional descriptive study examined entry-level baccalaureate degree nursing programs in the United States. A three-step process was used: (1) online survey of directors of BSN programs, (2) online survey of simulation directors, and (3) analysis of course titles and descriptions. Communication instruction remains primarily knowledge-based rather than skills-based. The findings of this study confirm there is ambiguity in defining the scope of communication instruction across curricula, as well as radical differences in the inclusion of communication in course descriptions and content. There is a need for clear definition of the scope of health communication skill development across BSN programs for communication behaviors to be measured and competency to be determined. A knowledge-building approach to communication instruction does not align with new plans for competency-based nursing education. [J Nurs Educ. 2021;60(11):618-624.].


Possible harm from glucocorticoid drugs misuse in the early phase of SARS-CoV-2 infection: a narrative review of the evidence.
Since the publication of the RECOVERY trial, the use of glucocorticoid drugs (GC) has spread for the treatment of severe COVID-19 worldwide. However, the benefit of dexamethasone was largest in patients who received mechanical ventilation or supplemental oxygen therapy, while no benefit was found among patients without hypoxemia. In addition, a positive outcome was found in patients who received dexamethasone after several days of symptoms, while possible harm could exist if administered early. The right time interval for GC administration is still a matter of debate. Previous studies showed that an early GC use during the first phase of the disease, when viral replication peaks, may negatively affect the innate immune response through several mechanisms, such as the inhibition of pro-inflammatory and antiviral cytokine production and signaling pathway, including type I interferon, that is fundamental to counteract the virus and that was found to be impaired in several patients with life-threatening COVID-19. The GC misuse can lead to a more severe disease even in patients who do not have the established risk factors, such as obesity and cardiovascular diseases. In our focused review, we describe the role of immune response in viral infections, especially SARS-CoV-2, and discuss the potential harms of GC misuse in COVID-19.


Phytophthora, Nothophytophthora and Halophytophthora diversity in rivers, streams and riparian alder ecosystems of Central Europe.
Waterways are ideal pathways for Phytophthora dispersal and potential introduction to terrestrial ecosystems. While many Phytophthora species from phylogenetic clades 6, 9 and 10 are predominant oomycetes in watercourses due to their adaptation to a lifestyle as saprotrophs and opportunistic pathogens of riparian plants, species from clades 2, 7 and 8 are predominantly soil- or airborne using aquatic habitats as temporal niches for spreading and invading terrestrial sites along the watercourses. In contrast to forest ecosystems, knowledge of Phytophthora diversity in watercourses in Central Europe is limited. Between 2014 and 2019 extensive surveys of streams and rivers were undertaken across Austria, in South Moravia, Czech Republic and Žilina province, Slovakia to unveil the diversity and distribution of Phytophthora and related oomycetes. In addition, in Austria riparian forests of black alder (Alnus glutinosa) and grey alder (A. incana) in lowlands and in the Alps were examined. A variety of Phytophthora species from clades 2, 6, 7, 8, 9 and 10 were isolated, with clade 6 species showing the widest distribution and abundance. Furthermore, interspecific clade 6 hybrids and other oomycetes such as Halophytophthora fluviatilis and undescribed Nothophytophthora spp. were also obtained. In riparian alders, symptoms of Phytophthora infections were associated with species from the P. × alni complex and P. plurivora. Phytophthora plurivora was most common in alder stands whereas P. uniformis was the oomycete species occurring at the highest altitude in alpine riparian areas. The online version contains supplementary material available at 10.1007/s11557-023-01898-1.


A protocol improves GP recording of long-term sickness absence risk factors.
If general practitioners (GPs) were better informed about patients' risks of long-term sickness absence (LTSA), they could incorporate these risk assessments into their patient management plans and cooperate more with occupational physicians to prevent LTSA. To evaluate the effectiveness of a protocol helping GPs in recording risks of LTSA and in co-operating with occupational physicians (OPs). Twenty-six GPs (co-operating in four groups) in Amsterdam, The Netherlands, participated in a controlled intervention study. Fourteen GPs were the protocol-supported intervention group and twelve GPs were the reference group. Outcome measures were consultations containing work-related information, information about two risk factors for LTSA, referrals to OPs and contacts of OPs with GPs and patients. Outcomes were identified through an electronic search in the GPs' information systems. Entries containing information were independently scored by two investigators. The proportions of patients with consultations documenting LTSA-pertinent items were compared between the groups, accounting for differences at baseline. There was no increase in consultations containing work-related information. Recording of risk factor information increased in the intervention group; the difference was 4.5% [95% CI 1.5-7.6] and 1.8% (95% CI -0.8 to 4.4) for the two risk factors. The referral rate to the OP increased by 2.9% (95% CI 1.2-4.5). There was no effect on contacts of OPs with GPs or with patients. Protocol-supported consultations may lead to a modest increase in information regarding two risk factors for LTSA in GPs' electronic records and to more referrals to OPs.


Data on induction of brown/beige adipocytes in mouse retro-orbital adipose tissues.
The data presented here are related to the research article entitled "Inducible brown/beige adipocytes in retro-orbital adipose tissues" [1]. Brown and beige adipocytes dissipate stored energy through the generation of heat by using mitochondrial uncoupling protein 1 (Ucp1), which is a mammalian brown/beige adipocyte-specific protein that promotes proton leakage across the inner mitochondrial membrane. Both cells up-regulate Ucp1 expression in response to β-adrenergic receptor activation such as cold exposure. Here, we provide data on induction of Ucp1 positive cells in retro-orbital white adipose tissues (WAT) from cold exposed both male and female mice. The fluctuation of eye surface temperature was monitored during the cold exposure. In addition, distribution of tyrosine hydroxylase positive bundles was observed in the retro-orbital WAT from the mice.


Evaluation of upper extremity vasculature with high-resolution ultrasound.
Twenty-eight vascular and perivascular lesions of the upper extremity in 21 patients were studied from August 1982 to December 1982 by means of a 10 MHz real-time B-mode ultrasound unit. They included eight perivascular masses, 16 arterial repairs, and five thrombosed or occluded arteries. Imaging of arteries that ranged in size from a brachial to a digital artery was reliable. Vessels were tracked proximally and distally while changes in wall compliance, luminal diameter, wall diameter, intimal integrity, and luminal compression were observed dynamically. Size, location, acoustic characteristics, and extent of vascular involvement could be determined in cases of perivascular masses. Sonographic findings were confirmed by arteriography, dynamic radionuclide imaging, computerized tomography, or surgical exploration. Ultrasonography eliminated the need for preoperative arteriography in some cases. In no instances were our ultrasonographic impressions in error when correlated with results of more invasive techniques. No adverse effects were encountered. We concluded that real-time 10 MHz ultrasonography is a safe, noninvasive, reproducible, and accurate technique that can be used quantitatively and qualitatively on the upper extremity after surgery to assess patency, pulse dynamics, and anastomotic characteristics of arterial repairs and before surgery to evaluate perivascular masses for acoustic characteristics, location, and influence on adjacent vascular structures.


Biomedical document relation extraction with prompt learning and KNN.
Document-level relation extraction is designed to recognize connections between entities a cross sentences or between sentences. The current mainstream document relation extraction model is mainly based on the graph method or combined with the pre-trained language model, which leads to the relatively complex process of the whole workflow. In this work, we propose biomedical relation extraction based on prompt learning to avoid complex relation extraction processes and obtain decent performance. Particularity, we present a model that combines prompt learning with T5 for document relation extraction, by integrating a mask template mechanism into the model. In addition, this work also proposes a few-shot relation extraction method based on the K-nearest neighbor (KNN) algorithm with prompt learning. We select similar semantic labels through KNN, and subsequently conduct the relation extraction. The results acquired from two biomedical document benchmarks indicate that our model can improve the learning of document semantic information, achieving improvements in the relation F1 score of 3.1% on CDR.


Improved outcomes, fewer cesarean deliveries, and reduced litigation: results of a new paradigm in patient safety.
In a health care delivery system with an annual delivery rate of approximately 220,000, a comprehensive redesign of patient safety process was undertaken based on the following principles: (1) uniform processes and procedure result in an improved quality; (2) every member of the obstetric team should be required to halt any process that is deemed to be dangerous; (3) cesarean delivery is best viewed as a process alternative, not an outcome or quality endpoint; (4) malpractice loss is best avoided by reduction in adverse outcomes and the development of unambiguous practice guidelines; and (5) effective peer review is essential to quality medical practice yet may be impossible to achieve at a local level in some departments. Since the inception of this program, we have seen improvements in patient outcomes, a dramatic decline in litigation claims, and a reduction in the primary cesarean delivery rate.


Immune lysis of Trypanosoma congolense: generation of a soluble covalent complex of variant surface glycoprotein and bovine complement component C3b.
Organisms of Trypanosoma congolense variant antigenic type TC13 (VAT TC13) were incubated, at 37 degrees C for 60 min, with fresh bovine serum in the presence of antibody specific for the variant surface glycoprotein (VSG). Upon immune lysis, soluble VSG (54 kDa) and a larger complex (about 225 kDa), containing VSG, was detected in the supernatant fluid of the mixture. Neither soluble VSG nor the VSG complex were detected when fresh bovine serum was incubated with organisms of T. congolense in the absence of specific antibody. Within a narrow range of low antibody concentration, the release of soluble VSG and the formation of the VSG complex were correlated with the amount of specific antibody added to the mixture. The VSG complex could be precipitated with rabbit antibodies specific for VSG of VAT TC13 or antibodies specific for bovine complement C3. The VSG complex was detected by Western blot with rabbit anti-VSG of VAT TC13 as well as rabbit antibovine C3. The complex was found to consist of VSG covalently bound to bovine complement component C3b. Potential pathophysiological implications are discussed.


Effects of galactosemia in utero.
There is direct evidence that in galactosemia, due to galactose-1-phosphate uridyltransferase deficiency, galactose, galactose-1-phosphate and galactitol accumulate in the fetus by week 20 of gestation. The metabolic abnormality may develop earlier than this, however, since the key enzymes in galactose metabolism have been shown to be present in normal fetal liver from the 10th week of gestation. There has been a single report of increased galactitol in amniotic fluid obtained at 10 weeks gestation, the outcome being a baby affected with galactosemia. Cataract formation in the fetus is rare and the only direct evidence that galactosemia may have harmful effects in utero. However, it has been concluded that the liver pathology seen in some patients who died in the neonatal period originated prenatally, and some studies have found that galactosemia is associated with reduced birth weight. Reports of two patients with histologically normal ovaries very soon after birth have been cited as evidence against gonadal dysfunction arising during fetal life, but it should be noted that this is not a constant feature in female galactosemics. Other observations, particularly those made from animal models, would suggest that ovarian dysfunction is most likely to have been caused in utero.


Lymphocyte sparing normal tissue effects in the clinic (LymphoTEC): A systematic review of dose constraint considerations to mitigate radiation-related lymphopenia in the era of immunotherapy.
Radiation-related lymphopenia has been associated with suboptimal tumor control rates leading to inferior survival outcomes. To date, no standardized dose constraints are available to limit radiation dose to resident and circulating lymphocyte populations. We undertook this systemic review of the literature to provide a synopsis of the dosimetric predictors of radiation-related lymphopenia in solid malignancies. A systematic literature review of PubMed (National Institutes of Health), Cochrane Central (Cochrane collaboration), and Google Scholar was conducted with the following keywords: "radiation", "lymphopenia", "cancer", "dosimetric predictors" with an inclusion deadline of May 31, 2022. Studies that met prespecified inclusion criteria were designated either Good, Fair, or Poor Quality based on the Newcastle-Ottawa quality assessment. The dosimetric parameters derived from Good Quality studies were tabulated as LymphoTEC dose constraints. Dosimetric parameters derived from Fair and Poor-quality studies were grouped as optional. An initial systematic search of the literature yielded 1,632 articles. After screening, a total of 48 studies met inclusion criteria and were divided into the following categories: central nervous system (CNS, 6), thoracic (11), gastrointestinal (26), gynecologic (2), head and neck, breast, and genitourinary (one each) cancers. Lung mean dose, heart mean dose, brain V25, spleen mean dose, estimated dose to immune cells, and bone marrow V10 were among the strongest predictors for severe lymphopenia related to radiotherapy. Optimizing the delivery of radiation therapy to limit dose to lymphocyte-rich structures may curb the negative oncologic impact of lymphocyte depletion. The dose constraints described herein may be considered for prospective validation and future use in clinical trials to limit risk of radiation-related lymphopenia and possibly improve cancer-associated outcomes.


Familial t(X;2) (p223;q323) with partial trisomy 2q and male and female balanced carriers.
A familial t(X;2) (p223;q323) is responsible for partial trisomy 2q in the proposita, a 3-year-old girl with severe mental retardation and hypotrophia. It is present in the balanced state in the mother, two daughters, and one son. X-replication was studied after BUDR incroporation and acridine orange staining. The reproductive impairment of balanced X/autosome translocations is discussed.


Cell-based arrays for the identification of interacting polypeptide domains or epitopes.
The specific regions on proteins which are responsible for protein-protein interaction are called interacting domains, or epitopes in case of antigen-antibody binding. These domains are one feature to characterize proteins and are important in clinical diagnostics and research. For the mapping of such domains the use of protein/peptide arrays has become popular. Regardless of which kind of array, the major requirements are a high number of candidates arranged in the array, high quality, ease of use, and cost-effectiveness. Here, the authors describe a general protocol for mapping the interacting domains of proteins demonstrated by a high affinity protein interaction, the interaction of an antibody to an antigen. The chapter describes a stepwise protocol from library production to the verification of the domain by the use of an automated cell-based polypeptide array, which comprises the named requirements of a good array.


Far-field P-wave sensing by the right ventricular lead of conventional dual chamber pacemakers.
This report describes two cases of far-field sensing of the P wave by the ventricular channel of conventional DDD pacemakers programmed to a relatively high sensitivity to promote sensing of ventricular extrasystoles. Ventricular pacing was maintained in both cases when the ventricular channel was not inhibited. One case was caused by displacement of a bipolar ventricular lead towards the right ventricular inflow tract. The other case occurred only in relation to an atrial extrasystole in the absence of ventricular lead displacement.


Non-stationary spatial filtering and accelerated curve fitting for parametric imaging with dynamic PET.
A non-stationary spatial low pass filter was developed and implemented in combination with an accelerated non-linear curve fitting routine to create low noise-high contrast images of physiological parameters with dynamic positron emission tomography. The method was applied to 18F-2-fluoro-2-deoxyglucose (FDG) studies, and images of local blood volume, kinetic rate constants, precursor pool volume and glucose metabolism were generated. Noise reduction and contrast preservation was demonstrated in a simulated pie phantom and a study of a patient with a recent brain infarct. Considerably improvement in quantitative accuracy of pixel parameter values was observed in the phantom study in comparison with unprocessed or conventionally smoothed images.


Are granisetron and ondansetron equivalent in the clinic?
There are no published direct trials of granisetron vs. ondansetron. Difficulties exist in comparing reported trials because of differences in methodology, especially in response criteria. In this review, a comparison is made between ondansetron and granisetron by recalculating the complete response criterion for granisetron, standardising it against that in the ondansetron programme (i.e. no vomiting). Weighted means have been calculated for three areas of study. Against cisplatin-induced emesis the (weighted) mean percentage of complete responders were calculated at 64% (range 49-77%) for granisetron and 49% (range 40-55%) for ondansetron. Against moderately emetogenic stimuli, the response rates were 76% (range 68-80%) and 73% (range 60-87%) respectively. For fractionated chemotherapy the response rates were 57% and 27% for granisetron and ondansetron respectively. Although not shown by formal statistical analysis, these results suggest that a clinical advantage for granisetron may exist.


Ability of the Analgesia Nociception Index variations to identify a response to a volume expansion of 250 mL of crystalloids in the operating room (REVANI): a prospective observational study.
Analgesia Nociception Index (ANI) is a device based on analysis of the R-R interval and respiratory sinus arrhythmia to assess the balance between sympathetic and parasympathetic activity. The autonomic system is directly affected by load changes. Therefore, monitoring sympathetic tone and its change could theoretically allow tracking of load changes during volume expansion. The aim of the present study was to determine whether changes in ANI are able to track the increase in stroke volume caused by volume expansion (SV). This prospective observational study included mechanically ventilated patients undergoing neurosurgery and benefiting from SV monitoring. Exclusion criteria were cardiac dysfunction, arrhythmias, beta-blockade therapy, and dysautonomia. SV was optimized by fluid administration of 250 ml of crystalloid fluid. A positive fluid increase was defined as a SV increase of 10% or more from baseline. Changes in SV and medium ANI (ANIm) were recorded before and 4 to 5 min after volume expansion. Sixty-nine patients had 104 fluid challenges (36 positive and 68 negative). Volume expansion resulted in a greater ANI increase in responders than in nonresponders. The change in ANIm > 5 predicted fluid responsiveness with a sensitivity of 68.4% (95% CI: 67.4% to 69.5%) and a specificity of 51.2% (95% CI: 50.1% to 52.3%). The area under the receiver operating characteristic curve was 0.546 (95% CI: 0.544 to 0.549) and appeared to be affected by remifentanil dose and baseline ANI. Changes in ANIm induced by fluid challenge is not able to predict fluid responsiveness in mechanically ventilated patients undergoing neurosurgery. Clinical trial registration: NCT04223414.


Corticospinal tract location in internal capsule of human brain: diffusion tensor tractography and functional MRI study.
We attempted to elucidate the corticospinal tract location at the posterior limb of the internal capsule in the human brain. Ten healthy volunteers were recruited. Probabilistic mapping was performed using the functional MRI activation resulting from a hand motor task as region of interest 1 and the corticospinal tract area of the anterior pons as region of interest 2. The average location of the highest density point of the corticospinal tract was mid-posterior portion with the standard from the most medial point to the most posterior point of the lenticular nucleus. In conclusion, we demonstrated that the corticospinal tract for the hand descended through the posterior portion of the posterior limb at the mid-thalamic level.


Downregulation of protein phosphatase 2A activity in HeLa cells at the G2-mitosis transition and unscheduled reactivation induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA).
In the cell cycle the transition from G2 phase to cell division (M) is strictly controlled by protein phosphorylation-dephosphorylation reactions effected by several protein kinases and phosphatases. Although much indirect and direct evidence point to a key role of protein phosphatase 2A (PP2A) at the G2/M transition, the control of the enzyme activity prior to and after the transition are not fully clarified. Using synchronized HeLa cells we determined the PP2A activity (i.e. the increment sensitive to inhibition by 2nM okadaic acid) in immunoprecipitates obtained with antibodies raised against a conserved peptide sequence (residues 169-182, Ab(169/182)) of the PP2A catalytic subunit (PP2A C). Two different substrates were offered: the phospho-peptide KR(p)TIRR and histone H1 phosphorylated by means of the cyclin-dependent protein kinase p34(cdc2). The results indicate that in HeLa cells the specific activity of PP2A towards both substrates goes through a minimum in late G2 phase and stays low until metaphase. Treatment of G2 cells with TPA (10(-7) M) caused a reactivation of the downregulated PP2A activity within 20 min, i.e. the same time frame within which TPA was shown earlier to block HeLa cells at the transition from G2 to mitosis [Kinzel et al., 1988. Cancer Res. 48, 1759-1762]. Activation of PP2A was also induced by TPA in mitotic cells. The low activity of PP2A in mitotic cells was accompanied by a strong reaction of mitotic PP2A C with anti-P-Tyr antibodies in Western blots, which was reversed by treatment of mitotic cells with TPA. The results suggest that the activity of cellular PP2A requires downregulation for the transition from G2 phase to mitosis. Unscheduled reactivation of PP2A induced by TPA in late G2 phase appears to inhibit the progress into mitosis.