Novel Therapies for Metastatic Melanoma: An Update on Their Use in Older Patients.
Cutaneous melanoma is the most aggressive form of skin cancer. With age as a risk factor, melanoma is projected to become a substantial healthcare burden. The clinical course of melanoma in older patients is different from that in middle-aged and younger patients: melanomas are thicker, have higher mitotic rates and are more likely to be ulcerated. Older patients also have a higher mortality rate, yet, paradoxically, have a lower rate of lymph node metastases. After decades of no significant progress in the treatment of this devastating disease, novel insights into the mechanisms underlying the pathophysiology of metastatic melanoma have led to new and remarkably efficient therapeutic opportunities. The discovery that about half of all melanomas carry BRAF mutations led to the introduction of targeted therapy with significant improvements in clinical outcomes. Although these drugs appear to be equally effective in older patients, specific considerations regarding adverse events are required. Besides targeted therapy, immunotherapy has emerged as an alternative therapeutic option. Antibodies that block cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) can induce responses with high durability. Despite an aging immune system, older patients seem to benefit to the same degree from these treatments, apparently without increased toxicity. In this review, we focus on the epidemiology, clinicopathological features, and recent developments of systemic treatment in cutaneous melanoma with regard to older patients.


A cross-sectional study on health differences between rural and non-rural U.S. counties using the County Health Rankings.
By examining 2013 County Health Rankings and Roadmaps data from the University of Wisconsin and the Robert Wood Johnson Foundation, this paper seeks to add to the available literature on health variances between United States residents living in rural and non-rural areas. We believe this is the first study to use the Rankings data to measure rural and urban health differences across the United States and therefore highlights the national need to address shortfalls in rural healthcare and overall health. The data indicates that U.S. residents living in rural counties are generally in poorer health than their urban counterparts. We used 2013 County Health Rankings data to evaluate differences across the six domains of interest (mortality, morbidity, health behaviors, clinical care, social and economic factors, and physical environment) for rural and non-rural U.S. counties. This is a cross-sectional study employing chi-square analysis and logit regression. We found that residents living in rural U.S. counties are more likely to have poorer health outcomes along a variety of measurements that comprise the County Health Rankings' indexed domains of health quality. These populations have statistically significantly (p ≤ 0.05) lower scores in such areas as health behavior, morbidity factors, clinical care, and the physical environment. We attribute the differences to a variety of factors including limitations in infrastructure, socioeconomic differences, insurance coverage deficiencies, and higher rates of traffic fatalities and accidents. The largest differences between rural and non-rural counties were in the indexed domains of mortality and clinical care. Our analysis revealed differences in health outcomes in the County Health Rankings' indexed domains between rural and non-rural U.S. counties. We also describe limitations and offer commentary on the need for more uniform measurements in the classification of the terms rural and non-rural. These results can influence practitioners and policy makers in guiding future research and when deciding on funding allocation.


Overexpression of heat shock protein Hsp27 protects against cerulein-induced pancreatitis.
Heat shock protein (Hsp) 27 regulates actin cytoskeletal dynamics, and overexpression of Hsp27 in fibroblasts protects against stress in a phosphorylation-dependent manner. Induction of Hsps occurs in acute pancreatitis, but Hsp27 has not been ascribed a specific role. To examine whether Hsp27 would ameliorate acute pancreatitis, we generated transgenic mice overexpressing human Hsp27 (huHsp27) or Hsp27 with the phosphorylatable residues Ser(15,78,82) mutated to aspartic acid (huHsp27-3D) to mimic phosphorylation or to alanine (huHsp27-3A), which is nonphosphorylatable. huHsp27 was expressed at high levels in the exocrine pancreas by use of a cytomegalovirus promoter. Protein expression was analyzed by Western blotting and immunofluorescence. Acute pancreatitis was induced with 6 or 12 hourly cerulein injections (50 microg/kg intraperitoneally) and its severity assessed by measuring serum amylase and lipase levels, pancreatic trypsin activity, edema, and morphologic changes by quantitative scoring of multiple histologic sections and visualization of filamentous actin. Systemic inflammatory effects were monitored by measuring lung myeloperoxidase activity (a marker of neutrophil infiltration). huHsp27 protein was overexpressed in the pancreas and localized to pancreatic acini. Acute pancreatitis was ameliorated by overexpression of huHsp27 and the huHsp27-3D mutant, which were associated with suppression of pancreatic trypsin activity and acinar cell injury and preservation of the actin cytoskeleton. In contrast, these changes were unaffected by overexpression of the nonphosphorylatable huHsp27-3A mutant. Pancreatic overexpression of huHsp27 protects against cerulein-induced acute pancreatitis in a specific phosphorylation-dependent manner and is associated with preservation of the actin cytoskeleton.


A novel method for endoluminal treatment of abdominal aortic aneurysms. With bare-metal Wallstent endoprostheses and endovascular coils.
The established therapy for symptomatic, expanding abdominal aortic aneurysms is open surgical replacement with an artificial graft. Over the last several years, there has been increasing enthusiasm for the use of endoluminal graft prostheses to exclude abdominal aortic aneurysms. However, even with rapid advances in stent graft technology, certain problems (i.e., large profile of the devices, risk of thromboembolism, poor flexibility, endoleak formation, and side-branch occlusion) have yet to be overcome. We present the case of an 85-year-old woman with multiple comorbid illnesses who underwent endoluminal repair of her expanding abdominal aortic aneurysms. We used bare-metal Wallstent endoprostheses (Schneider, Inc.; Minneapolis, Minn) in combination with endovascular coils (Cook, Inc.; Bloomington, Ind). The bare-metal Wallstent endoprostheses were used because the patient had severely narrowed iliac arteries and a large side branch originating from the aneurysm. The procedure was technically successful, and there was no significant morbidity. Follow-up angiographic evaluation at 6 months revealed no evidence of vascular enlargement; it also revealed preservation of important side branches, and spontaneous thrombosis of the aneurysms.


Long noncoding RNA NORAD promotes the progression of retinoblastoma by sponging miR 136-5p/PBX3 axis.
The article "Long noncoding RNA NORAD promotes the progression of retinoblastoma by sponging miR-136-5p/PBX3 axis, by X.-L. Yang, Y.-J. Hao, B. Wang, X.-L. Gu, X.-X. Wang, J.-F. Sun, published in Eur Rev Med Pharmacol Sci 2020; 24(3):1278-1287. DOI: 10.26355/eurrev_202001_20185. PMID: 32096159" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause.


Comparison of endobronchial needle aspiration with forceps and brush biopsies in the diagnosis of endobronchial lung cancer.
Endobronchial forceps biopsy (FB) specimens of lung carcinoma are not uncommonly interpreted as nondiagnostic owing to extensive crush artefact, necrosis, or insufficient tissue. FB cannot be performed in some endobronchial lung cancers (EBLCs) with massive bleeding tendency due to fragility and friability. Cytological studies from the brushings and washings may also be unproductive, increasing the bronchoscopist's frustration. The aim of this study was to compare the diagnostic yield and complications of endobronchial needle aspiration (EBNA) with those of FB and brush biopsy (BB) in EBLCs examined by fibreoptic bronchoscopy. A prospective sequential study was carried out on 151 in-patients with EBLC. Bronchial aspiration (BA), EBNA and BB were performed in the patients with respiratory distress and with accompanying tumours of high bleeding tendency, completely obstructing main bronchi (Group 1: 68 patients). BA, EBNA and FB were performed in those with either central or peripheral EBLCs but without respiratory distress and/or significant bleeding tendency (Group 2: 83 patients). In Group 1, the diagnostic yield of EBNA was found to be 90%, whereas that of BB was 66% (p < 0.05). In the same group, EBNA provided cell types in 95%, compared with 88% by BB (p > 0.05). EBNA was diagnostic in 92% of Group 2 patients, while FB established diagnosis in 78% of patients (p > 0.05). In determining cell type, no significant difference was found between EBNA (95%) and FB (97%) (p > 0.05). Regarding complications (only bleeding), there was no significant difference (p > 0.05) between EBNA (7%) and BB (13%), or between EBNA (4%) and FB (17%). We conclude that in endobronchial lung cancers: 1) the diagnostic yield of endobronchial needle aspiration is higher than brush biopsy; 2) endobronchial needle aspiration increases the yield of brush biopsy when forceps biopsy cannot be performed owing to significant bleeding; 3) endobronchial needle aspiration increases the diagnostic yield when a forceps biopsy specimen is inadequate because of crush artefact, necrosis, or tissue resistance; and 4) endobronchial needle aspiration is as safe as brush biopsy and forceps biopsy.


Alpha-fetoprotein and beta-human chorionic gonadotropin in amniotic fluid.
A series of data on amniotic fluid levels of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) are presented. Both hormones were observed to decrease with advancing gestational age. The diagnostic importance of AFP levels is confirmed, and the very high levels of beta-HCG in twin gestations are documented. A statistically significant correlation between the concentration of both hormones is demonstrated.


Chronic Hepatitis C Pathogenesis: Immune Response in the Liver Microenvironment and Peripheral Compartment.
Chronic hepatitis C (CHC) pathogenic mechanisms as well as the participation of the immune response in the generation of liver damage are still a topic of interest. Here, we evaluated immune cell populations and cytokines in the liver and peripheral blood (PB) to elucidate their role in CHC pathogenesis. B, CTL, Th, Treg, Th1, Th17, and NK cell localization and frequency were evaluated on liver biopsies by immunohistochemistry, while frequency, differentiation, and functional status on PB were evaluated by flow cytometry. TNF-α, IL-23, IFN-γ, IL-1β, IL-6, IL-8, IL-17A, IL-21, IL-10, and TGF-β expression levels were quantified in fresh liver biopsy by RT-qPCR and in plasma by CBA/ELISA. Liver CTL and Th1 at the lobular area inversely correlated with viral load (r = -0.469, p =0.003 and r = -0.384, p = 0.040). Treg correlated with CTL and Th1 at the lobular area (r = 0.784, p < 0.0001; r = 0.436, p = 0.013). Th17 correlated with hepatic IL-8 (r = 0.52, p < 0.05), and both were higher in advanced fibrosis cases (Th17 p = 0.0312, IL-8 p = 0.009). Hepatic cytokines were higher in severe hepatitis cases (IL-1β p = 0.026, IL-23 p = 0.031, IL-8 p = 0.002, TGF-β, p= 0.037). Peripheral NK (p = 0.008) and NK dim (p = 0.018) were diminished, while NK bright (p = 0.025) was elevated in patients vs. donors. Naïve Th (p = 0.011) and CTL (p = 0.0007) were decreased, while activated Th (p = 0.0007) and CTL (p = 0.0003) were increased. IFN-γ production and degranulation activity in NK and CTL were normal. Peripheral cytokines showed an altered profile vs. donors, particularly elevated IL-6 (p = 0.008) and TGF-β (p = 0.041). Total hepatic CTLs favored damage. Treg could not prevent fibrogenesis triggered by Th17 and IL-8. Peripheral T-lymphocyte differentiation stage shift, elevated cytokine levels and NK-cell count decrease would contribute to global disease.


Bilateral Lemierre's syndrome: a case report and literature review.
Lemierre's syndrome is characterized by thrombosis of the internal jugular vein that develops following an oropharyngeal infection. Sepsis and septic metastases frequently ensue and affect the lungs, the musculoskeletal system, and occasionally the liver. Most cases are caused by infection with Fusobacterium necrophorum. This infection responds to antibiotic therapy with beta-lactamase-resistant compounds that exert good anaerobic coverage. Anticoagulation and surgical intervention can be helpful in advanced cases. Fewer than 160 cases of classic Lemierre's syndrome have been described; approximately one-third of these reported cases have occurred since 1988. We describe a new case of Lemierre's syndrome that occurred in an otherwise healthy 27-year-old man. Thrombosis of both internal jugular veins extended through the subclavian system and into both upper extremities. The patient was treated with intravenous antibiotics and heparin during 14 days of hospitalization. He was discharged on oral clindamycin and warfarin sodium, and after 6 months he was able to return to full activity. To our knowledge, this is the first reported case of Lemierre's syndrome in which internal jugular vein thrombosis occurred bilaterally. By reporting this previously undescribed manifestation of Lemierre's syndrome, we hope to increase practitioner awareness of this disease entity.


P-wave indices and atrial fibrillation: cross-cohort assessments from the Framingham Heart Study (FHS) and Atherosclerosis Risk in Communities (ARIC) study.
Atrial fibrillation (AF) is associated with increased morbidity. P-wave indices (PWIs) measure atrial electrical function and are associated with AF. Study of PWI has been limited to single-cohort investigations, and their contributions to risk enhancement are unknown. We examined PWI from the FHS and ARIC study. We calculated 10-year AF risk using adjusted Cox models. We conducted cross-cohort meta-analyses for the PWI estimates and assessed their contributions to risk discrimination (c statistic), net reclassification index, and integrated discrimination improvement. After exclusions, the analysis included 3,110 FHS (62.6 ± 9.8 years, 56.9% women) and 8,254 ARIC participants (62.3 ± 5.6 years, 57.3% women, 20.3% black race). Over 10 years, 217 FHS and 458 ARIC participants developed AF. In meta-analysis, P-wave duration >120 milliseconds was significantly associated with AF (hazard ratio 1.55, 95% CI 1.29-1.85) compared with ≤120 milliseconds. P-wave area was marginally but not significantly related to AF (hazard ratio 1.31, 95% CI 0.95-1.80). P-wave terminal force was strongly associated with AF in ARIC but not FHS. P-wave indices had a limited contribution toward predictive risk beyond traditional risk factors and markers. P-wave indices are intermediate phenotypes for AF. They are associated with AF in cross-cohort meta-analyses but contribute minimally toward enhancing risk prediction.


Orthotopic liver transplantation in non-alcoholic fatty liver disease patients.
Non-alcoholic fatty liver disease (NAFLD) is a frequent etiology of liver disease in Western Countries and non-alcoholic steato-hepatitis (NASH) is becoming a leading indication for liver transplantation in US, with constant increase overtime. Specific co-morbidities correlated to the presence of obesity and associated with metabolic syndrome should always be ruled out in patients affected by NASH-related end-stage liver disease, who are potential candidates for liver transplantation. Patients transplanted for NAFLD present similar outcomes compared with patients transplanted for other indications. With regards to post-transplant outcomes in obese patients, available data are contradictory, with reported increased mortality only in patients with BMI >40. A new multidisciplinary protocol of liver transplantation and sleeve gastrectomy seems to be effective and safe in obese patients who were not able to lose weight before liver transplantation. However prospective studies are needed. The NASH recurrence rate after liver transplantation ranges between 20-40%, but its variability largely depends on the methodology used for the diagnosis (i.e. liver tests, liver histology or imaging technique).


Disease progression and outcomes in chronic kidney disease and renal transplantation.
It is unknown whether renal transplant recipients (RTR) have better outcomes and disease progression rates compared to patients with chronic kidney disease (CKD) when matched for the level of kidney function. We analyzed data on 1762 patients with CKD (N = 872) and RTR (N = 890) over 16 years, applying the new Kidney/Disease Outcomes Quality Initiative (K/DOQI) staging system for CKD in a single center retrospective study. Patients were further divided based their native kidney disease. We determined disease progression by the slope of creatinine clearance decline and patient and kidney survival rates adjusted for age, gender and stage of kidney function, using Cox proportional hazards models. The overall rate of creatinine clearance decline in patients with CKD was -6.6 +/- 8.7 mL/min/year compared to -1.9 +/- 4.7 mL/min/year in RTR (P < 0.0001). The rate of decline per stage of CKD was also significantly lower in RTR. Whereas overall kidney survival was higher in RTR compared to patients with CKD (49.6% vs. 17.2%, respectively, P < 0.001), patient survival was not statistically different between the two groups (74.7% vs. 80.3%, respectively, P = 0.25). RTR had similar mortality rates compared to patients with CKD despite enjoying slower rates of disease progression and better kidney survival rates. These data suggest that RTR are a unique subset of patients with CKD whose comorbid conditions likely offset the potential benefits of slower rates of progression.


Mechanism of activation of the Na+/H+ exchanger by arginine vasopressin in hepatocytes.
Arginine vasopressin has been shown to activate the Na+/H+ exchanger in hepatocytes by calcium/calmodulin-dependent processes. Whether this activation also involves protein kinase C and is associated with changes in the intracellular pH setpoint was investigated in this study. Changes in pHi and intracellular Ca++ concentration were measured with the fluorescent probes BCECF and quin-2, respectively. Intracellular pH recovery rate was calculated from time-dependent changes in intracellular pH in hepatocytes acid-loaded with sodium propionate. Arginine vasopressin, phorbol myristate acetate and thapsigargin stimulated intracellular pH recovery but did not increase basal intracellular pH. Arginine vasopressin and thapsigargin, but not phorbol myristol acetate, increased intracellular Ca++ concentration. The protein kinase C inhibitors staurosporine and calphostin C inhibited arginine vasopressin- and phorbol myristol acetate-induced, but not thapsigargin-induced, intracellular pH recovery. Neither staurosporine nor calphostin C affected arginine vasopressin- and thapsigargin-induced increases in intracellular Ca++ concentration, and no inhibitor affected basal intracellular pH recovery. Arginine vasopressin, phorbol myristol acetate and thapsigargin increased intracellular pH dependency of intracellular pH recovery without affecting intracellular pH setpoint. These results indicate that the activation of the Na+/H+ exchanger by arginine vasopressin is mediated both by Ca++/calmodulin and protein kinase C and may be due to enhanced interaction of H+ with the internal modifier site of the exchanger.


Synergistic neuroprotective effects of Geniposide and ursodeoxycholic acid in hypoxia-reoxygenation injury in SH-SY5Y cells.
Endoplasmic reticulum stress (ERS) and autophagy activation play important roles in the process of cerebral ischemia/reperfusion (I/R) injury. The synergistic protective effects of Geniposide and ursodeoxycholic acid against cellular apoptosis caused by oxygen-glucose deprivation-reoxygenation (OGD/R) were investigated using a Cell Counting Kit-8 assay, lactate dehydrogenase (LDH) assay, flow cytometry, quantitative polymerase chain reaction (qPCR), and western blotting to examine cellular viability, apoptosis, reactive oxygen species (ROS) levels, mRNA and protein levels, respectively, in relation to ERS and autophagy. We found that pretreatment with Geniposide improved cellular viability. Moreover, treatment with a combination of Geniposide and Tauroursodeoxycholic acid (TUDCA) (GT) protected injured cells better than Geniposide alone. Further studies showed that the increase in cellular ROS levels, and the overexpression of mRNA and proteins related to OGD/R-induced ERS and autophagy, were both counteracted by GT. Our study indicates that the protective effects of GT on OGD/R-induced apoptosis in SH-SY5Y cells are associated with the inhibition of ERS and autophagy.


Shigella.
Shigella strains capable of producing illness possess a 140 megadalton plasmid that determines its property of epithelial cell penetration. In the classic presentation, there is a descending intestinal tract infection beginning with the passage of small numbers of large-volume stools and progressing to the passage of many small-volume stools that contain blood and mucus. Shigellae are efficiently transmitted to contacts in person-to-person spread and only 200 viable cells are sufficient to produce illness in susceptible persons. Shigellosis should be suspected in persons with severe diarrhea, in those with fever, when bloody stools are passed, or when stool smears contain many leukocytes. The current treatment of choice is TMP-SMX or, in adults, a quinolone (norfloxacin or ciprofloxacin).


Olfactory function after functional endoscopic sinus surgery for chronic sinusitis.
One hundred and fifteen patients suffering from chronic sinusitis were observed to analyse the prevalence of olfactory dysfunction and the influence of FESS. Pre-operative questionnaires were supplemented by examination of olfactory thresholds and discrimination. Pre-operatively, 58% of the collective were aware or complained of any olfactory deficit. However, the olfactory tests demonstrated that of the collective 52% were hyposmic and 31% anosmic. Eight per cent of the hyposmic patients presented with an isolated reduction of their ability to discriminate odours. Post-operative improvements were found in 70%. Normosmia was post-operatively achieved in 25% of the hyposmic patients, but only in 5% of the anosmic patients. Olfaction changed to the worse in 8% after FESS. Therefore, the prevalence of olfactory dysfunction in chronic sinusitis is pre-operatively higher, and the rate of improvement is lower than generally assumed. The extent of sinus disease as measured by the degree of intranasal polyposis correlates with olfactory dysfunction. Resections of the middle turbinate may have a negative effect on olfaction, due to damage to the olfactory fila or alteration of the normal aerodynamic pattern within the olfactory cleft. However, this hypothesis is based on a few observations and needs to be verified by further investigations.


Long-term remission of schizophrenia in an adolescent treated with quetiapine.
The novel antipsychotic quetiapine has recently been reported to be a safe and effective treatment for adolescent psychosis in an open trial. However, there are currently no published data on its long-term tolerability and effectiveness. This report describes the successful long-term treatment of a 14-year-old girl diagnosed with schizophrenia. Continued improvement in positive symptoms was evident as long as 8 months into the treatment, and negative symptoms were still improving at 18 months. At 28 months of treatment, there were no apparent adverse effects. Long-term follow-up studies are needed to determine if the findings in this case can be generalized.


Full miscibility of disk- and rod-shaped mesogens in the nematic phase.
Mesogens containing rod-shaped moieties as well as one disk-shaped group exhibit nematic phase behavior and are entirely miscible with rod- and disk-shaped mesogens in the nematic phase. In the phase diagram, an extra nematic phase appears at nearly equimolar disk-rod ratios, where the nematic biaxial phase has been predicted.


Peptic ulcer bleeding today: risk factors and characteristics of the disease.
This study was undertaken to ascertain whether the modern effective anti-ulcer drugs have had any influence on the natural history of hemorrhagic peptic ulcer disease and other acid-related gastroduodenal bleeding disorders. In the prospective part of the study the anamnestic data of all 73 patients admitted to our hospital with a bleeding ulcer or related disease during the year 1989 were compared with the data of 73 patients subjected to elective upper GI tract endoscopy for abdominal symptoms other than bleeding, paying special attention to potential risk factors. There were no differences in previous ulcer history or operations for ulcer disease between these two groups. Cigarette smoking and coffee consumption were not different, but the bleeders consumed alcohol more often, and, in particular, they used ulcerogenic drugs or other hemorrhagic diathesis-provoking agents significantly more frequently than controls. In the retrospective part of the study these 73 patients were compared with the medical records of all 87 patients admitted to our hospital in 1976 for a bleeding peptic ulcer disease, to ascertain whether introduction of H2-blocking agents had had any influence on the nature of the patient population, characteristics of the disease, and severity of bleeding. The patients had become slightly older, and male preponderance was seen in both groups. The proportion of gastric ulcer had decreased, and duodenal ulcer had increased. In general, the bleeding seemed to become less severe but was more severe among women in both groups. In 1989 almost all patients were treated with H2 antagonists, and seven patients received additional medical therapy (vasopressin, somatostatin, or tranexamic acid).(ABSTRACT TRUNCATED AT 250 WORDS)


"The only thing I wonder is when I will have surgery again": everyday life for children with right ventricle outflow tract anomalies during assessment for heart surgery.
Children with right ventricle outflow tract anomalies require repeated heart surgeries, thereby needing regular preoperative assessments throughout their lifetime. This situation puts a heavy burden on these children. Thus, the aim of this study was to explore how children diagnosed with right ventricle outflow tract anomalies experience their heart disease and their everyday life during the preoperative assessment and after the decision on whether to perform a new cardiac surgery. Individual interviews were conducted with nine children between 9 to 17 years of age on three occasions from 2014 to 2016. In total there were 27 interviews which all were analyzed with thematic analysis. The analysis yielded three themes and eight subthemes. The theme Me and my heart disease concerns children's experiences of the heart disease. Almost all described symptoms and how they adapt in their everyday life. The theme Being me concerns the children's sense of self, where their heart disease was not prominent. The theme Being placed in someone else's hands describes how the assessment was more of a safety net at least until the decision of heart surgery. The children's symptoms, their experiences during the assessment, their future surgeries and how the heart disease affects their everyday life could be better understood as elements of their adaptation to the heart disease. In order to achieve individualized support based on the child's experiences and to ensure that these children are involved in their own care a child-centered approach is recommended.


Fever in children younger than three months of age. A pooled analysis.
Concern that febrile infants younger than 3 months of age are at high risk of serious infection has prompted a management policy of routine hospitalization with antibiotic administration. Ten published studies of febrile infants younger than 3 months of age were reviewed, and data were statistically combined to develop estimates of the risk of bacteremia and serious infection. Factors that predicted increased risk were similarly evaluated. Mean and median risk estimates included, respectively, 3.0 and 3.4 percent for bacteremia, 1.3 and 1.0 percent for septic meningitis, and 5.0 and 7.0 percent for pneumonia. These were no higher than comparable estimates for older infants. Clinical appearance was 92 percent sensitive in predicting bacteremia in 500 infants (23 of 25 cases). Younger age, higher fever, and elevated white blood cell count were associated with increased risk of serious infection. Data from these studies do not support the belief that febrile infants younger than 3 months are uniformly at greater risk of serious infection than older infants. Judicious evaluation of younger infants could lead to more selective, cost-efficient management.


[Immersion pulmonary edema].
Immersion pulmonary edema may occur during scuba diving, snorke-ling or swimming. It is a rare and often recurrent disease, mainly affecting individuals aged over 50 with high blood pressure. However it also occurs in young individuals with a healthy heart. The main symptoms are dyspnea, cough and hemoptysis. The outcome is often favorable under oxygen treatment but deaths are reported. A cardiac and pulmonary assessment is necessary to evaluate the risk of recurrence and possible contraindications to immersion.


Particle- and Gaseous Emissions from an LNG Powered Ship.
Measurements of particle number and mass concentrations and number size distribution of particles from a ship running on liquefied natural gas (LNG) were made on-board a ship with dual-fuel engines installed. Today there is a large interest in LNG as a marine fuel, as a means to comply with sulfur and NOX regulations. Particles were studied in a wide size range together with measurements of other exhaust gases under different engine loads and different mixtures of LNG and marine gas oil. Results from these measurements show that emissions of particles, NOX, and CO2 are considerably lower for LNG compared to present marine fuel oils. Emitted particles were mainly of volatile character and mainly had diameters below 50 nm. Number size distribution for LNG showed a distinct peak at 9-10 nm and a part of a peak at diameter 6 nm and below. Emissions of total hydrocarbons and carbon monoxide are higher for LNG compared to present marine fuel oils, which points to the importance of considering the methane slip from combustion of LNG.


[Progresses on Neandertal genomics].
Neandertal is our closest known relative and also an archaic hominid reserving the richest fossils. Whether the Neandertals exchanged their DNA with modern human or not is a matter of debate on the modern human origin. The progresses on the mitochondrial and nuclear genomes of Neandertals in recent years were reviewed in this paper. Recent study has revealed possible genetic contribution of Neandertals to the modern human to some extent, which arose the rethinking of modern human origin. The experiences gained in the research on Neandertals will benefit the study on archaic hominids, unravel the mystery of modern human origin, and enrich the relative theoretical systems in evolutionary biological field.


IRE1α promotes viral infection by conferring resistance to apoptosis.
The unfolded protein response (UPR) is an ancient cellular pathway that detects and alleviates protein-folding stresses. The UPR components X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1α (IRE1α) promote type I interferon (IFN) responses. We found that Xbp1-deficient mouse embryonic fibroblasts and macrophages had impaired antiviral resistance. However, this was not because of a defect in type I IFN responses but rather an inability of Xbp1-deficient cells to undergo viral-induced apoptosis. The ability to undergo apoptosis limited infection in wild-type cells. Xbp1-deficient cells were generally resistant to the intrinsic pathway of apoptosis through an indirect mechanism involving activation of the nuclease IRE1α. We observed an IRE1α-dependent reduction in the abundance of the proapoptotic microRNA miR-125a and a corresponding increase in the amounts of the members of the antiapoptotic Bcl-2 family. The activation of IRE1α by the hepatitis C virus (HCV) protein NS4B in XBP1-proficient cells also conferred apoptosis resistance and promoted viral replication. Furthermore, we found evidence of IRE1α activation and decreased miR-125a abundance in liver biopsies from patients infected with HCV compared to those in the livers of healthy controls. Our results reveal a prosurvival role for IRE1α in virally infected cells and suggest a possible target for IFN-independent antiviral therapy.


[Diagnosis and therapy of obstructive jaundice].
Obstructive jaundice is a sign of intra- or posthepatic blockage of bile flow. This diagnosis has to be differentiated from various other diagnoses such as disorders of bilirubin metabolism or hepatocellular causes of jaundice. An accurate evaluation of the past medical history and clinical examination of the patient can already establish obstruction as the cause of jaundice in most cases. For prevention of a cholangitis further imaging procedures should focus on rapidly establishing the cause and the location of obstruction. Further therapeutic procedures are dependent on the type of obstruction and the condition of the patient. Most importantly there should be a decompression of the biliary tree with ES or PTBD.


Antibacterial properties of the bicyclic pyrazolidinones.
LY173013 and LY186826 are bicyclic pyrazolidinones containing a novel aza-gamma-lactam ring structure. The antibacterial properties of these compounds appear to be related to those of beta-lactam antibiotics in that both classes of compounds share certain common binding molecules such as beta-lactamases and penicillin-binding proteins.


Properties of milk protein gels formed by phosphates.
We investigated the properties of gels that were formed by adding emulsifying salts, such as tetrasodium pyrophosphate (TSPP), to reconstituted milk protein concentrate solution. The pH of a 51 g/L milk protein concentrate solution was adjusted to 5.8 after adding TSPP. Milk protein concentrate solutions were placed in glass jars and allowed to stand at 25 degrees C for 24 h. Gels with the highest breaking force were formed when TSPP was added at a concentration of 6.7 mM, whereas no gel was formed when TSPP was added at concentrations of < or =2.9 or > or =10.5 mM. Several other phosphate-based emulsifying salts were tested but for these emulsifying salts, gelation only occurred after several days or at greater gelation temperatures. No gelation was observed for trisodium citrate. Gelation induced by TSPP was dependent on pH, and the breaking force of gel was greatest at pH 6.0. Furthermore, when the concentration of milk protein concentrate in solution was increased to 103 g/L, the breaking force of the gel increased, and a clearly defined network between caseins could be observed by using confocal scanning laser microscopy. These results suggest that TSPP-induced gelation occurs when the added TSPP acts with calcium as a cross-linking agent between dispersed caseins and when the balance between (a reduced) electrostatic repulsion and (enhanced) attractive (hydrophobic) interactions becomes suitable for aggregation and eventual gelation of casein molecules.


Problems in the optimal management of myasthenia gravis patients--a prospective clinical survey at Kalafong Hospital.
This study forms part of a clinical survey of problems in the optimal management of patients with inherited neuromuscular diseases seen at Kalafong Hospital in Pretoria. Our objectives were to determine the problems associated with providing patients with optimal management until true remission (cure), and to apply the findings to ongoing improvement of optimal management. This is the first report of the series. Twenty-six patients were studied prospectively from 1986 to 1998. Early sternal-splitting thymectomy on class II-V patients as well as anticholinesterases, corticosteroids, azathioprine, plasma exchange, intensive care and various combinations of these constituted part of the optimal management. An assessment of the total monthly income and distance from hospital was done for each patient. Five of the 15 thymectomised patients (33.3%) were lost to follow-up after reaching remission. Of the remaining 10 patients, 6 (40%) are in true remission and the remaining 4 (26.7%) are in pharmacological remission. Four of the 11 patients (36%) treated non-surgically were lost to follow-up. Of the remaining patients, 1 (9.1%) is in true remission and the remaining 6 (54.5%) are in pharmacological remission. The average monthly income of patients lost to follow-up in the thymectomised group was lower than that of patients who continued follow-up, and their homes were further away from hospital. In the non-surgical group the average monthly income of patients lost to follow-up was higher than that of patients who continued follow-up and their homes were nearer to the hospital. Early thymectomy (the aggressive approach) resulted in 40% cures, 26.7% pharmacological remissions, no mortality, minimal morbidity, and early discharge. Loss to follow-up was one of the biggest problems in providing optimal management for these patients. We modified optimal management in response to our patients' concerns without sacrificing excellence, and found that poverty and poor access to tertiary hospitals were possible contributory factors to loss to follow-up. Suggestions are made with regard to tackling the problems. Myasthenia gravis (MG) is a disorder of neuromuscular function resulting from an immunologically based premature destruction of acetylcholine receptors.


A nontoxic pain killer designed by modeling of pathological receptor conformations.
Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects. We hypothesized that exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral μ-opioid receptors at the source of pain generation. Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide-binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3',5'-monophosphate inhibition in vitro. It produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation, or addiction potential.


Synapse elimination and plasticity in developing human cerebral cortex.
Overproduction of structures including neurons, dendrites, and synapses occurs during development in many neural systems. In human beings cerebral cortex synaptogenesis takes place prenatally and during early infancy. Maximum synaptic density, absolute number of synapses, and number of synapses per neuron are reached by age 1 year. Subsequently, there is progressive synapse elimination that is most rapid during the preschool years. Overproduction of synapses may impart plasticity to the brain of young children. This property of developing brain may be exploited for retraining when function is impaired. An example is the reversal of amblyopia by forcing strabismic children to use their squinting eye.


Acid-induced chemoselective arylthiolations of electron-rich arenes in ionic liquids from sodium arylsulfinates: the reducibility of halide anions in [Hmim]Br.
An acid-induced protocol for the chemoselective arylthiolations of electron-rich arenes in ionic liquids from sodium arylsulfinates is introduced. The chemistry, in which [Hmim]Br (heaxylmethylimidazolium bromide) is used as both a solvent and a reducer, provides several advantages including odorless and simple operation, inexpensive reagents, recyclable solvents and gram-scale synthesis.


Aberrant expression of the sFRP and WIF1 genes in invasive non-functioning pituitary adenomas.
Non-functioning pituitary adenomas (NFPAs) are the most common pituitary tumors and mainly invade the sphenoid, cavernous sinus or dura mate. Aberrant regulation of the Wnt signaling pathway plays an important role in tumorigenesis. This study was designed to investigate the relationships between secreted frizzled-related proteins (sFRPs), WIF1 genes and the invasion of NFPAs by tissue microassays (TMAs) of samples from 163 patients. Significantly weaker staining of WIF1 and sFRP4 were detected in the invasive group compared with the non-invasive group by TMAs (p = 0.002, p < 0.001). Univariate analysis showed a significant correlation between tumor invasion and low expression of WIF1 and sFRP4 (p = 0.002, p < 0.001). A similar trend was observed when analyzing the mRNA and protein levels through RT-PCR and western blot experiments. Methylation of the WIF1 promoter was significantly increased in invasive NFPAs compared with the noninvasive group (p = 0.004). The average progression free survival time in the high WIF1 group was longer than that in the low WIF1 group (p = 0.025). Furthermore, RT-PCR measured the levels of 11 miRNAs targeting WIF1 according to the Targetscan database and PubMed. The levels of miRNA-137, miRNA-374a-5p and miRNA-374b-5p in the invasive group were 0.037-fold, 0.577-fold and 0.44-fold that of the noninvasive group (p = 0.003, p = 0.049 and p = 0.047). Overexpression of miRNA-137 could inhibit the proliferation and invasion of GH3 cells through cell viability and Transwell experiments (p < 0.05). Furthermore, the WIF1 level was upregulated after overexpression of miRNA-137 compared with miRNA-137-NC (control miRNA) in GH3 cells. Our data suggest that WIF1 may be potential biomarker for the aggressiveness of NFPAs. miRNA-137 plays an important role in the Wnt signaling pathway by affecting promoter methylation of WIF1.


A novel autosomal recessive limb-girdle muscular dystrophy with quadriceps atrophy maps to 11p13-p12.
Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of pathologies. We have identified a cohort of 14 French-Canadian patients from eight different families displaying a novel form of LGMD with an autosomal recessive inheritance. These patients share some features with previously described cases of 'quadriceps myopathy' that evolved into an LGMD. All demonstrate quadriceps femoris asymmetrical atrophy. Creatine kinase values were variable from normal to 6000 U/l. Clinical evaluations and MRI studies demonstrate a variable intrafamilial and interfamilial phenotype. Asymmetrical muscle involvement was clinically observed and confirmed by imaging. MRI studies suggest that the hamstrings and the adductor magnus are the first limb muscles to demonstrate fatty infiltration. Muscle pathology shows no sign of active inflammation but increased endomysial connective tissue associated with basal lamina duplication and collagen disorganization. A genome-wide scan using the two largest families uncovered linkage to marker D11S1360 on chromosome 11p12 [multipoint logarithm of the odds (LOD) score of 2.78]. Further genotyping for the eight families confirmed linkage to this new LGMD locus (multipoint LOD score of 4.56). Fine mapping subsequently defined a less than 3.3 cM candidate interval on 11p13-p12. Haplotype analysis of carrier chromosomes suggests that the most frequent mutation may account for up to 81.3% of French-Canadian mutations. In this study, we describe the chromosomal locus of a new form of recessive LGMD with prominent quadriceps femoris atrophy.


Primary eosinophilic granuloma of the oculomotor nerve. Case report.
The authors report the occurrence of primary eosinophilic granuloma of the oculomotor nerve without osseous involvement in a 68-year-old man. Histopathological and neuroradiological findings are discussed. This case demonstrates that eosinophilic granuloma should be included in the differential diagnosis of tumor in which cranial nerves are involved.


Options for taking time out of specialty training.
Trainees in higher specialty training programmes may have the option to take time out of their training programme to enhance or broaden their skills and perhaps develop a subspecialty interest. Traditionally, out of programme experience has been mostly taken by clinical academic trainees in order to undertake a higher research degree. However, there are a growing number of other ways to usefully spend time out of programme. This article is intended to highlight the range of opportunities and explain the modern processes for obtaining permissions to enable trainees to make good choices for themselves.


Stress-induced acidification may contribute to formation of unusual structures in C9orf72-repeats.
Expansion of the C9orf72 hexanucleotide repeat (GGGGCC)n·(GGCCCC)n is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both strands of the C9orf72 repeat have been shown to form unusual DNA and RNA structures that are thought to be involved in mutagenesis and/or pathogenesis. We previously showed that the C-rich DNA strands from the C9orf72 repeat can form four-stranded quadruplexes at neutral pH. The cytosine residues become protonated under slightly acidic pH (pH 4.5-6.2), facilitating the formation of intercalated i-motif structures. Using CD spectroscopy, UV melting, and gel electrophoresis, we demonstrate a pH-induced structural transition of the C-rich DNA strand of the C9orf72 repeat at pHs reported to exist in living cells under stress, including during neurodegeneration and cancer. We show that the repeats with lengths of 4, 6, and 8 units, form intercalated quadruplex i-motifs at low pH (pH < 5) and monomolecular hairpins and monomolecular quadruplexes under neutral-basic conditions (pH ≥ 8). Furthermore, we show that the human replication protein A (RPA) binds to the G-rich and C-rich DNA strands under acidic conditions, suggesting that it can bind to i-motif structures. In the proper sequence context, i-motif structures can form at pH values found in some cells in vivo. DNA conformational plasticity exists over broad range of solution conditions.


The relationships between mild cognitive impairment and phenotype in Parkinson's disease.
The concept of differing clinical phenotypes within Parkinson's disease (PD) is well represented in the literature. However, there is no consensus as to whether any particular disease phenotype is associated with an increased risk of mild cognitive impairment (MCI) using the newly proposed Movement Disorders Society diagnostic criteria for this feature. To explore the expression of PD-MCI in relation to the heterogeneity of idiopathic PD. A cluster analysis incorporating a range of specific demographic, clinical and cognitive variables was performed on 209 patients in the early stages of PD (between Hoehn and Yahr stages I-III). Post hoc analyses exploring variables not included in the clustering solution were performed to interrogate the veracity of the subgroups generated. This study identified four distinct PD cohorts: a younger disease-onset subgroup, a tremor dominant subgroup, a non-tremor dominant subgroup, and a subgroup with rapid disease progression. The present study identified a differential expression of PD-MCI across these subgroups, with the highest frequency observed in the non-tremor dominant cluster. The non-tremor dominant subgroup was also associated with a higher prevalence of freezing of gait, hallucinations, daytime somnolence, and rapid eye movement sleep behavior disorder compared with other subgroups. This study confirms the existence of heterogeneity within the early clinical stages of PD and for the first time highlights the differential expression of PD-MCI using the newly defined diagnostic criteria for this feature. An improved understanding of PD-MCI and its clinical relationships may lead to an improved understanding of the pathophysiology underlying heterogeneity in PD.


Nonvascularized iliac bone grafts for mandibular reconstruction--requirements and limitations.
Treatment of intraoral malignant tumors often leads to continuity defects of the mandible. Whereas the use of free vascularised flaps has shortcomings regarding donor site morbidity and a worse-fitting bone geometry, the nonvascularized iliac crest graft could be an alternative option. The purpose of this study was to describe the treatment outcome with nonvascularized iliac crest grafts over a 10-year period and to determine possible limitations of their use. Eighty-four patients with bicortical nonvascularized iliac crest grafts for mandibular reconstruction were examined at least one year after reconstruction. Patients' records and the radiological and/or surgical data were analyzed. Sixty-three patients (75%) showed complete healing, in 20 patients the treatment was not successful and in one patient the treatment result was unclear. Interestingly, comparing the successfully and the unsuccessfully treated patients, only the irradiation dose played a crucial role. Neither defect length nor defect localisation, nor time interval between resection and reconstruction were statistically significant parameters in graft success. Comparing only patients with malignancies, the non-irradiated patients had a higher success rate (77.3%). The nonvaslcularized iliac crest graft seems to be a reasonably reliable treatment option for reconstruction of mandibular defects up to about 5-6 cm in size. Radiotherapy is a strong confounder reducing the success rate. Necessary constraints are sufficient soft tissue conditions. However, primary reconstruction by free flaps (e.g. fibula flap) has a higher success rate in literature and should be preferred whenever possible.


An MnNCN-Derived Electrocatalyst for CuWO4 Photoanodes.
CuWO4 is a photoanode candidate in neutral pH, and manganese-based oxygen evolution reaction electrocatalysts are of high interest due to their low price and low toxicity. Considering the unexplored chemistry of transition-metal carbodiimides/cyanamides for the PEC water oxidation, we investigated MnNCN as an electrocatalyst for CuWO4 under AM 1.5G illumination in potassium phosphate electrolyte (pH 7). Surface functionalization of CuWO4 photoanodes with MnNCN increased the photocurrent from 22 to 30 μA cm-2 at 1.23 V vs RHE. Complementary structural analysis by means of XRD and XPS revealed that MnNCN forms a core-shell structure MnNCN@MnPO x in phosphate electrolyte and mimics a manganese phosphate electrocatalyst. As such, the surface chemistry of MnNCN significantly differs from previous studies on the cobalt analogue (CoNCN). A separately prepared MnNCN electrode developed a small but detectable photocurrent due to photogenerated holes inside the semiconducting carbodiimide core of the MnNCN@MnPO x structure.


DO BIOMARKERS VARY BY SOCIAL CLASS, EDUCATION AND REGION AND IS MIGRATION IMPORTANT? EVIDENCE FROM A COHORT OF BRITISH ADULTS.
The aim of this study was to test whether Body Mass Index (BMI), waist circumference, systolic and diastolic blood pressure, Forced Expiratory Volume (FEV1) and Peak Expiratory Flow (PEF) vary in relation to social class at birth and adulthood, educational level and region of residence, and also with inter-generational social, educational and regional mobility/migration. The study used 5702 adults (2894 males and 2718 females) from the longitudinal British National Child Development Study (all children born in England, Scotland and Wales during the first week in March 1958 with follow-up throughout childhood and adulthood, most recently at 55 years of age). In both sexes BMI and waist circumference tended to increase from social classes I+II to IV+V and higher social class was associated with higher mean FEV1 and PEF. Better-educated adults tended to have lower BMI and waist circumference, and higher mean FEV1 and PEF. Women from Wales had the highest mean BMI and waist circumference but the lowest mean PEF, while women in Scotland had the highest mean systolic blood pressure and the lowest mean FEV1. For men only, FEV1 and PEF showed regional variation and the lowest mean FEV1 was in Wales and the lowest PEF in Yorkshire & Humberside. Inter-generational social mobility was not found to be associated with any of the biomarkers, while educational mobility was related only to FEV1 and PEF. In both sexes, in unadjusted regression analysis regional migrant cohort members tended to have a lower mean BMI than sedentes. Regional male migrants also tended to have a lower waist circumference and a higher FEV1 and PEF than sedentes.


The effect of a platelet activating factor antagonist (BN 52021) on neurologic outcome and histopathology in a canine model of complete cerebral ischemia.
Research has demonstrated that platelet activating factor may modulate, in part, the severity of postischemic neurologic injury. The proposed mechanism involves a platelet activating factor-mediated release of cerebral cellular lipids and free fatty acids, resulting in increased cerebral edema and cell injury. The present study tested the hypothesis that a specific platelet activating factor antagonist, BN 52021, would improve neurologic outcome after 12 min of complete global cerebral ischemia in a canine model. Using an established canine model of complete cerebral ischemia, dogs were assigned randomly to receive, in a blinded fashion, either 20 mg/kg BN 52021 intravenously (N = 8) or placebo (N = 7) 5 min before cerebral ischemia. After cerebral ischemia and recovery, neurologic assessment was performed by a blinded observer for 72 h. Immediately thereafter, the brains were harvested and later were evaluated histologically by a neuropathologist blinded to the treatment groups. Dogs were well matched for systemic physiologic variables during all portions of the study. One placebo-treated dog and one BN 52021-treated dog were not included in the statistical analysis because of failure to meet preestablished protocol criteria. BN 52021, when compared to placebo, affected neither neurologic functional recovery nor overall histopathology scores. Regional histopathology was improved in BN 52021-treated dogs in only 1 of 18 brain regions studied (i.e., the parietal cortex). When both treatment groups were combined, there was a significant correlation between neurologic function rank and histopathology rank. The present data demonstrate that the platelet activating factor antagonist BN 52021, at a dose of 20 mg/kg intravenously given 5 min before cerebral ischemia, did not protect the brain from injury in this canine model of complete global ischemia.


Post Dural Puncture Subdural Hematoma: A Rare Iatrogenic Complication of Neuraxial Anesthesia.
Although post-dural puncture headache is a well-known complication of neuraxial anesthesia, subdural hematoma following epidural injection is a rare but potentially under-recognized complication. The following is the case of a young female patient with no significant past medical history who developed a persistent and severe headache following the introduction of epidural anesthesia for labor induction. Imaging demonstrated multiple small subdural hematomas with findings concerning intracranial hypotension. She eventually underwent a blood patch and reported immediate relief from her headache.


Allicin inhibits oxidative stress-induced mitochondrial dysfunction and apoptosis by promoting PI3K/AKT and CREB/ERK signaling in osteoblast cells.
Osteoporosis is a disease of the skeleton that is characterized by the loss of bone mass and degeneration of bone microstructure, resulting in an increased risk of fracture. Oxidative stress, which is known to promote oxidative damage to mitochondrial function and also cell apoptosis, has been recently indicated to be implicated in osteoporosis. However, there are few agents that counteract oxidative stress in osteoporosis. In the present study, the protective effects of allicin against the oxidative stress-induced mitochondrial dysfunction and apoptosis were investigated in murine osteoblast-like MC3T3-E1 cells. The results demonstrated that allicin counteracted the reduction of cell viability and induction of apoptosis caused by hydrogen peroxide (H2O2) exposure. The inhibition of apoptosis by allicin was confirmed by the inhibition of H2O2-induced cytochrome c release and caspase-3 activation. Moreover, the inhibition of apoptosis by allicin was identified to be associated with the counteraction of H2O2-induced mitochondrial dysfunction. In addition, allicin was demonstrated to be able to significantly ameliorate the repressed phosphoinositide 3-kinase (PI3K)/AKT and cyclic adenosine monophosphate response element-binding protein (CREB)/extracellular-signal-regulated kinase (ERK) signaling pathways by H2O2, which may also be associated with the anti-oxidative stress effects of allicin. In conclusion, allicin protects osteoblasts from H2O2-induced oxidative stress and apoptosis in MC3T3-E1 cells by improving mitochondrial function and the activation of PI3K/AKT and CREB/ERK signaling. The present study implies a promising role of allicin in oxidative stress-associated osteoporosis.


Predictors of Lymph Node Metastasis and Prognosis in pT1 Colorectal Cancer Patients with Signet-Ring Cell and Mucinous Adenocarcinomas.
The local excision of early colorectal cancer is limited by the presence of lymph node metastasis (LNM). Signet-ring cell carcinomas (SRC) and mucinous adenocarcinomas (MAC) are two relatively infrequent histological subtypes. However, little is known about the predictors of LNM and prognosis to support the feasibility of local excision in early-stage SRC and MAC. The Surveillance Epidemiology and End Results Database were used to identify all patients with pT1 adenocarcinomas, including conventional adenocarcinoma (AC), MAC, and SRC. The prevalence of LNM was assessed, and the long-term survival rate in the above three types of colorectal cancer was calculated. SRC accounted for 0.3% and MAC accounted for 4.4% of the entire cohort of colorectal adenocarcinomas. Compared to AC, MRC and SRC were more often located in the proximal colon, and exhibited a higher grade. The incidence of LNM in AC, MAC, and SRC was 10.6%, 17.2%, and 33.3% for colon cancers and 14.8%, 25.9%, and 46.2% for rectal cancers, respectively. In patients with lymph nodes resected no less than 12, incidence of LNM in AC, MRC, and SRC was 12%, 21%, and 44% for colon tumors and 17%, 30%, and 14% for rectal tumors, respectively. Although, colon patients MAC showed an entirely worse survival rate than AC, rectum patients MAC showed a similar prognosis to AC. We found that in patients with rectal tumors, SRC had a worse 3 and 5-year prognosis than AC. However, for colon cancers, the prognosis of SRC was similar to that of AC. Histology was not found to be an independent prognostic factor in multivariate survival analysis. MAC and SRC are two distinct subtypes of colorectal cancer that require special attention despite their relatively rare prevalence. pT1 patients with SRC of the rectum and patients with MAC of the colon have higher incidences of LNM, and with these adverse outcomes, local excision is not recommended. AlthoughMAC of the rectum and SRC of colon have a high rate of LNM, the prognosis of these types are similar to that of AC.


Occupational therapy for adults with problems in activities of daily living after stroke.
A stroke occurs when the blood supply to part of the brain is cut off. Activities of daily living (ADL) are daily home-based activities that people carry out to maintain health and well-being. ADLs include the ability to: eat and drink unassisted, move, go to the toilet, carry out personal hygiene tasks, dress unassisted, and groom. Stroke causes impairment-related functional limitations that may result in difficulties participating in ADLs independent of supervision, direction, or physical assistance.For adults with stroke, the goal of occupational therapy is to improve their ability to carry out activities of daily living. Strategies used by occupational therapists include assessment, treatment, adaptive techniques, assistive technology, and environmental adaptations. This is an update of the Cochrane review first published in 2006. To assess the effects of occupational therapy interventions on the functional ability of adults with stroke in the domain of activities of daily living, compared with no intervention or standard care/practice. For this update, we searched the Cochrane Stroke Group Trials Register (last searched 30 January 2017), the Cochrane Controlled Trials Register (The Cochrane Library, January 2017), MEDLINE (1946 to 5 January 2017), Embase (1974 to 5 January 2017), CINAHL (1937 to January 2017), PsycINFO (1806 to 2 November 2016), AMED (1985 to 1 November 2016), and Web of Science (1900 to 6 January 2017). We also searched grey literature and clinical trials registers. We identified randomised controlled trials of an occupational therapy intervention (compared with no intervention or standard care/practice) where people with stroke practiced activities of daily living, or where performance in activities of daily living was the focus of the occupational therapy intervention. Two review authors independently selected trials, assessed risk of bias, and extracted data for prespecified outcomes. The primary outcomes were the proportion of participants who had deteriorated or were dependent in personal activities of daily living and performance in activities of daily living at the end of follow-up. We included nine studies with 994 participants in this update. Occupational therapy targeted towards activities of daily living after stroke increased performance scores (standardised mean difference (SMD) 0.17, 95% confidence interval (CI) 0.03 to 0.31, P = 0.02; 7 studies; 749 participants; low-quality evidence) and reduced the risk of poor outcome (death, deterioration or dependency in personal activities of daily living) (odds ratio (OR) 0.71, 95% CI 0.52 to 0.96; P = 0.03; 5 studies; 771 participants; low-quality evidence). We also found that those who received occupational therapy were more independent in extended activities of daily living (OR 0.22 (95% CI 0.07 to 0.37); P = 0.005; 5 studies; 665 participants; low-quality evidence). Occupational therapy did not influence mortality (OR: 1.02 (95% CI 0.65 to 1.61); P = 0.93; 8 studies; 950 participants), or reduce the combined odds of death and institutionalisation (OR 0.89 (95% CI 0.60 to 1.32); P = 0.55; 4 studies; 671 participants), or death and dependency (OR 0.89 (95% CI 0.64 to 1.23); P = 0.47; 4 trials; 659 participants). Occupational therapy did not improve mood or distress scores (OR 0.08 (95% CI -0.09 to 0.26); P = 0.35; 4 studies; 519 participants; low-quality evidence). There were insufficient data to determine the effects of occupational therapy on health-related quality of life. We found no studies of consenting carers prior to study participation and therefore there were no carer-related outcomes in our review. There were insufficient data to determine participants' and carers' satisfaction with services.Using GRADE, the quality of evidence was low. The major limitation was the number of studies at unclear risk of selection bias and an inevitable high risk of performance and detection bias, as both participants and occupational therapists could not be blinded to the intervention. In addition, there was a sparseness of data for our outcomes of interest and we downgraded the quality of our evidence for these reasons. We found low-quality evidence that occupational therapy targeted towards activities of daily living after stroke can improve performance in activities of daily living and reduce the risk of deterioration in these abilities. Because the included studies had methodological flaws, this research does not provide a reliable indication of the likely effect of occupational therapy for adults with stroke.


Effects of atropine on atrial refractoriness and its dispersion in humans.
To evaluate the influence of atropine on atrial refractoriness and its dispersion, we studied ten subjects with sinus bradycardia who were otherwise healthy. Effective and functional refractory periods were measured at three sites of the right atrium (high, middle, and low in the lateral wall), in sinus rhythm and during atrial pacing (120/min), before and after i.v. administration of 0.04 mg/kg of atropine. Both before and after administration, dispersion of atrial refractoriness was determined from the range of refractory periods measured at the three atrial sites as the longest minus the shortest refractory period. Our data indicate that atropine was able to significantly reduce refractoriness and its dispersion. The study protocol allowed us to exclude the possibility that cycle length played a role. The antivagal effect of atropine seemed to explain our findings, even if the possibility that the drug had a direct effect could not be excluded.


ADHD patients fail to maintain task goals in face of subliminally and consciously induced cognitive conflicts.
Attention deficit hyperactivity disorder (ADHD) patients have been reported to display deficits in action control processes. While it is known that subliminally and consciously induced conflicts interact and conjointly modulate action control in healthy subjects, this has never been investigated for ADHD. We investigated the (potential) interaction of subliminally and consciously triggered response conflicts in children with ADHD and matched healthy controls using neuropsychological methods (event-related potentials; ERPs) to identify the involved cognitive sub-processes. Unlike healthy controls, ADHD patients showed no interaction of subliminally and consciously triggered response conflicts. Instead, they only showed additive effects as their behavioural performance (accuracy) was equally impaired by each conflict and they showed no signs of task-goal shielding even in cases of low conflict load. Of note, this difference between ADHD and controls was not rooted in early bottom-up attentional stimulus processing as reflected by the P1 and N1 ERPs. Instead, ADHD showed either no or reversed modulations of conflict-related processes and response selection as reflected by the N2 and P3 ERPs. There are fundamental differences in the architecture of cognitive control which might be of use for future diagnostic procedures. Unlike healthy controls, ADHD patients do not seem to be endowed with a threshold which allows them to maintain high behavioural performance in the face of low conflict load. ADHD patients seem to lack sufficient top-down attentional resources to maintain correct response selection in the face of conflicts by shielding the response selection process from response tendencies evoked by any kind of distractor.


Occupational Accidents with Agricultural Machinery in Austria.
The number of recognized accidents with fatalities during agricultural and forestry work, despite better technology and coordinated prevention and trainings, is still very high in Austria. The accident scenarios in which people are injured are very different on farms. The common causes of accidents in agriculture and forestry are the loss of control of machine, means of transport or handling equipment, hand-held tool, and object or animal, followed by slipping, stumbling and falling, breakage, bursting, splitting, slipping, fall, and collapse of material agent. In the literature, a number of studies of general (machine- and animal-related accidents) and specific (machine-related accidents) agricultural and forestry accident situations can be found that refer to different databases. From the database Data of the Austrian Workers Compensation Board (AUVA) about occupational accidents with different agricultural machinery over the period 2008-2010 in Austria, main characteristics of the accident, the victim, and the employer as well as variables on causes and circumstances by frequency and contexts of parameters were statistically analyzed by employing the chi-square test and odds ratio. The aim of the study was to determine the information content and quality of the European Statistics on Accidents at Work (ESAW) variables to evaluate safety gaps and risks as well as the accidental man-machine interaction.


Chemotaxis under agarose: a new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leukocytes and monocytes.
A variety of methods have been devised for the study of spontaneous and directed cell migration. Among these, the membrane filter method introduced by Boyden in 1962, with its more recent modifications, has become the technique of choice for studies of leukocyte migration in vitro. This method, however, cannot be applied without alteration to studies of chemotaxis and spontaneous migration of cells of different types. We describe in this report a new and simple method for studying human leukocyte chemotaxis, in vitro, which is based upon migration of cells under agarose gel. This method has application to both polymorphonuclear leukocytes and monocytes, permits measurement of both chemotaxis and spontaneous migration, requires fewer cells per test, and is rapid, simple, reproducible, and inexpensive to set up.


GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo.
JAK/STAT signaling is essential for a wide range of developmental processes in Drosophila melanogaster. The mechanism by which the JAK/STAT pathway contributes to these processes has been the subject of recent investigation. However, a reporter that reflects activity of the JAK/STAT pathway in all Drosophila tissues has not yet been developed. By placing a fragment of the Stat92E target gene Socs36E, which contains at least two putative Stat92E binding sites, upstream of GFP, we generated three constructs that can be used to monitor JAK/STAT pathway activity in vivo. These constructs differ by the number of Stat92E binding sites and the stability of GFP. The 2XSTAT92E-GFP and 10XSTAT92E-GFP constructs contain 2 and 10 Stat92E binding sites, respectively, driving expression of enhanced GFP, while 10XSTAT92E-DGFP drives expression of destabilized GFP. We show that these reporters are expressed in the embryo in an overlapping pattern with Stat92E protein and in tissues where JAK/STAT signaling is required. In addition, these reporters accurately reflect JAK/STAT pathway activity at larval stages, as their expression pattern overlaps that of the activating ligand unpaired in imaginal discs. Moreover, the STAT92E-GFP reporters are activated by ectopic JAK/STAT signaling. STAT92E-GFP fluorescence is increased in response to ectopic upd in the larval eye disc and mis-expression of the JAK kinase hopscotch in the adult fat body. Lastly, these reporters are specifically activated by Stat92E, as STAT92E-GFP reporter expression is lost cell-autonomously in stat92E homozygous mutant tissue. In sum, we have generated in vivo GFP reporters that accurately reflect JAK/STAT pathway activation in a variety of tissues. These reporters are valuable tools to further investigate and understand the role of JAK/STAT signaling in Drosophila.


Harmony as a convergence attractor that minimizes the energy expenditure and variability in physiological gait and the loss of harmony in cerebellar ataxia.
The harmony of the human gait was recently found to be related to the golden ratio value (ϕ). The ratio between the duration of the stance and that of the swing phases of a gait cycle was in fact found to be close to ϕ, which implies that, because of the fractal property of autosimilarity of that number, the gait ratios stride/stance, stance/swing, swing/double support, were not significantly different from one another. We studied a group of patients with cerebellar ataxia to investigate how the differences between their gait ratios and the golden ratio are related to efficiency and stability of their gait, assessed by energy expenditure and stride-to-stride variability, respectively. The gait of 28 patients who were affected by degenerative cerebellar ataxia and of 28 healthy controls was studied using a stereophotogrammetric system. The above mentioned gait ratios, the energy expenditure estimated using the pelvis reconstructed method and the gait variability in terms of the stride length were computed, and their relationships were analyzed. Matching procedures have also been used to avoid multicollinearity biases. The gait ratio values of the patients were farther from the controls (and hence from ϕ), even in speed matched conditions (P=0.011, Cohen's D=0.76), but not when the variability and energy expenditure were matched between the two groups (Cohen's D=0.49). In patients with cerebellar ataxia, the farther the stance-swing ratio was from ϕ, the larger the total mechanical work (R2adj=0.64). Further, a significant positive correlation was observed between the difference of the gait ratio from the golden ratio and the severity of the disease (R=0.421, P=0.026). Harmony of gait appears to be a benchmark of physiological gait leading to physiological energy recovery and gait reliability. Neurorehabilitation of patients with ataxia might benefit from the restoration of harmony of their locomotor patterns.


The Role of Extrinsic Rewards and Cue-Intention Association in Prospective Memory in Young Children.
The current study examined, for the first time, the effect of cue-intention association, as well as the effects of promised extrinsic rewards, on prospective memory in young children, aged 5-years-old (n = 39) and 7-years-old (n = 40). Children were asked to name pictures for a toy mole, whilst also having to remember to respond differently to certain target pictures (prospective memory task). The level to which the target picture was associated with the intention was manipulated across two conditions (low- or high-association) for all participants, whilst half of the participants were promised a reward for good prospective memory performance. Results showed a main effect of age, with the 7-year-olds outperforming the 5-year-olds. Furthermore, there was a main effect of reward, with those promised a reward performing better than those who were not. No effect was found for cue-association, with the participants of both age groups performing equally well in both association conditions. No significant interactions were found between any of the variables. The potentially important role of reward in young children's everyday prospective memory tasks, and possible reasons for the lack of a reflexive-associative effect, are discussed.


Synergistic effect of nicotinamide and choline administration on extracellular choline levels in the brain.
Experimental studies indicate that the availability of free choline is a rate-limiting step for acetylcholine synthesis in central cholinergic neurons, especially when the release of acetylcholine is increased. In the present study we applied the microdialysis technique to measure the concentration of extracellular choline in the rat hippocampus. The i.p. injection of 6, 20 and 60 mg/kg of choline chloride led to short-lasting elevations of the basal choline efflux (1.78 pmol/min) by 14, 26 and 131%. N-Methylnicotinamide, a metabolite of nicotinamide, has been reported to inhibit the outward transport of choline from the cerebrospinal fluid to the blood. The s.c. injection of 5 and 10 mmol/kg of nicotinamide caused increases of extracellular choline by 54 and 113%, respectively, and choline levels remained elevated for several hr. Moreover, the administration of 10 mmol/kg of nicotinamide dramatically potentiated the effects of exogenous choline administration on choline availability in the central nervous system. The effects of 6 and 20 mg/kg of choline chloride were increased by a factor of more than 10-fold when determined as area under the curve. Additional experiments demonstrated that neither nicotinamide nor N-methylnicotinamide (100 microM) have an influence on the uptake, metabolism or release of choline in the hippocampal slice preparation. It is likely, therefore, that nicotinamide, after metabolic conversion in the brain to N-methylnicotinamide, leads to a blockade of choline clearance from the brain. The combined administration of choline and of a choline transport blocker analogous to nicotinamide may be of potential use in central cholinergic dysfunction.


Synaptophysin expression as prognostic factor for survival in colorectal carcinomas.
The aim of this study is to assess the status of synapses in normal colorectal tissue compared to neoplastic colorectal tissue, and to correlate this status with survival in patients with colorectal neoplasia. Our study included 61 patients diagnosed with colorectal adenocarcinoma, representing the study group, and 53 patients diagnosed with benign conditions, that required a resection of a colorectal segment, representing the control group. We performed the immunohistochemical staining by using anti-synaptophysin antibody, which identifies synaptic vesicles and, so, we managed to analyze the expression of synapses in colorectal adenocarcinoma. Regarding both the signal area and integrated optical density (IOD) of the synaptophysin, the univariate analysis with a log-rank (Mantel-Cox) test indicated that patients with a low level of synaptophysin had a better overall survival rate than those with a high-level synaptophysin. Also, we noticed that tumor size, tumor invasion and lymph node metastasis were significantly associated with the overall survival rate, whereas the other clinicopathological features were not. In conclusion, the status of synaptic vesicles evaluated via synaptophysin expression in patients with colorectal cancer positively correlates with the survival rate and it can play a role in the neoplastic therapy process.


A randomized trial comparing laryngeal mask airway to endotracheal tube in children undergoing upper gastrointestinal endoscopy.
Although the efficacy of laryngeal mask airway (LMA) has been demonstrated for securing patency of the airway in children, it has not yet been compared to endotracheal tube (ET) in this population. This study aimed to compare the safety and efficacy of LMA vs. ET in children undergoing elective diagnostic upper gastrointestinal endoscopies. Sixty ASA I-III patients were randomly allocated to ET (Group I) or LMA (Group II). A set of cardiovascular and respiratory parameters were obtained before, during and after the endoscopic procedure. The recovery time and the time to discharge were also registered. The cardiovascular and respiratory parameters evaluated in the study varied across the different evaluation periods. However, they remained within physiological ranges and were not different between groups. The median (range) recovery time was 4 (2-10) min and the time to discharge was 58 (36-88) min in the ET group and 3 (1-7) min and 50 (35-67) min in the LMA group (P > 0.10), respectively. In a 16 month-old, 80 cm and 10 kg girl, we failed to secure the patency of the airway with LMA. In conclusion, the LMA was as effective and safe as ET for securing the airway of children undergoing diagnostic upper endoscopies. However, the 3% failure rate occurred with LMA.


The cancer burden in the oldest-old: Increasing numbers and disparities-A nationwide study in the Netherlands, 1990 to 2019.
Adults aged ≥80 years (the oldest-old) comprise the fastest growing age group in Western populations. Yet little is known about their cancer burden. In this nationwide study, we assessed their trends in incidence, treatment and survival over a 30-year period, and predicted their future cancer incidence. All 2 468 695 incident cancer cases during 1990 to 2019 were selected from the Netherlands Cancer Registry, of whom 386 611 were diagnosed in the oldest-old (16%). The incidence of the oldest-old was predicted until 2032. Net and overall survival (OS) were calculated. Patients were divided into four age groups (<80, 80-84, 85-89 and ≥90 years). The incidence of the oldest-old doubled between 1990 and 2019 and is expected to grow annually with 5% up to 2032. In virtually all cancers the share of oldest-old patients grew, but declined for prostate cancer (25% in 1990-1994 vs 13% in 2015-2019). The proportion of undetermined disease stage increased with age in most cancers. The application of systemic therapy increased, albeit less pronounced in the oldest-old than their younger counterparts (1990 vs 2019: 12%-34%, 3%-15%, 2%-7% and 1%-3% in <80, 80-84, 85-89 and ≥90 years old). Five-year OS of the oldest-old patients increased by 7 percentage points (to 26%) between 1990 to 1994 and 2015 to 2019 compared to 19 percentage points (to 63%) in <80 years old. The oldest-old cancer patients are a rapidly growing group who benefitted less from improvements in cancer treatment than younger patients, reflecting the multiple challenges faced in the care of the oldest-old.


Grasping and Pointing - Visual Conflict and Interference.
There have been many debates of the two-visual-systems (what vs. how or perception vs. action) hypothesis that was proposed by Goodale and his colleagues. Many researchers have provided a variety of evidence for or against the hypothesis. For instance, a study performed by Aglioti et al. offered good evidence for the two-visual-systems theory using the Ebbinghaus illusion, but some researchers who used other visual illusions failed to find consistent results. Therefore, we used a perceptual task of conflict or interference to test this hypothesis. If the conflict or interference in perception had an influence on the processing of perception alone and did not affect the processing of action, we could infer that the two visual systems are separated, and vice versa. In the current study, we carried out two experiments which employed the Stroop, Garner and SNARC paradigms and used graspable 3-D Arabic numerals. We aimed to find if the effects resulting from perceptual conflicts or interferences would affect participants' grasping and pointing. The results showed that the interaction between Stroop and numeral order (ascending or descending, or SNARC) was significant, and the SNARC effect significantly affected action, but the main effects of Stroop and Garner interference were not significant. The results indicated that, to some degree, perceptual conflict affects action processing. The results did not provide evidence for two separate visual systems.


Nodal Upstaging During Lung Cancer Resection Is Associated With Surgical Approach.
Recent reports indicate that thoracoscopic lobectomy for lung cancer may be associated with lower rates of surgical upstaging. We queried a statewide cancer registry for differences in upstaging rates and survival by surgical approach. The Kentucky Cancer Registry (KCR) collects data, including centralized pathology reporting, on cancer patients treated statewide. We performed a retrospective review from 2010 to 2012 to examine clinical and pathologic stage. We assessed rates of upstaging and whether the surgical approach, thoracotomy (THOR) versus minimally invasive techniques (video-assisted thoracic surgery; VATS), had an impact on final pathologic stage and survival. The KCR database from 2010 to 2012 contained information on 2830 lung cancer cases, 1964 having THOR procedure and 500 having VATS resections. Preoperatively, 36.4% of THOR were clinically stage 1a versus 47.4% VATS (p = 0.0002). Of these, final pathologic stage remained stage 1a in 30.5% of THOR procedures and 38.0% of VATS (p = 0.0002). The overall nodal upstaging rate for THOR was 9.9% and 4.8% for VATS (p = 0.002). Decreased nodal upstaging was found with VATS, independent of tumor size and extent of resection (odds ratio 0.6, 95% confidence interval [CI]: 0.387 to 0.985, p = 0.04). However, improved survival was found with VATS compared with THOR (hazard ratio 0.733, 95% CI: 0.592 to 0.907, p = 0.0042). Consistent with other reports, we report a lower upstaging rate with VATS. Nevertheless, there is a survival advantage in VATS patients. Although selection bias may play a role in these observed differences, the improved quality of life measures associated with VATS may explain survival improvement despite lower surgical upstaging.


[Findings on the functional planning of dentures].
Analysis of over 20,000 prosthetic treatments carried out in the area of one association of dentists working under the compulsory public health insurance plan shows that prior to the conclusion of the new financial agreements on prosthetics, a treatment plan based on the findings and aiming at appropriate functional rehabilitation had been prepared in half of all the cases only.


The airway response of horses with recurrent airway obstruction (heaves) to aerosol administration of ipratropium bromide.
The airway response to aerosol administration of the anticholinergic agent ipratropium bromide was determined in 8 horses with recurrent airway obstruction (heaves). The reversibility of airway obstruction was confirmed by measuring lung function before and during stabling; and by determining the response to atropine administration (0.02 mg/kg bwt intravenously). The dose-response to ipratropium bromide was determined using a Williams square design experiment in which 25, 50 or 75 micrograms ipratropium bromide/ml (4 ml/100 kg bwt) or the same volume of vehicle was administered to each horse by nebulisation. Lung function was measured before and 1 and 4 h after nebulisation. Vehicle had no effect on lung function. Ipratropium decreased the maximal change in pleural pressure during tidal breathing (delta Pplmax) and pulmonary resistance (RL) and increased dynamic compliance (Cdyn). At the 1 h measurement period, the effect on RL and Cdyn was dose-dependent. A separate experiment demonstrated that the duration of action of ipratropium was between 4 and 6 h.


Distress Tolerance and Symptom Severity as Mediators of Symptom Validity Failure in Veterans With PTSD.
Performance validity tests (PVTs) and symptom validity tests (SVTs) are necessary in clinical and research contexts. The extent to which psychiatric distress contributes to failure on these tests is unclear. The authors hypothesized that the relation between posttraumatic stress disorder (PTSD) and validity would be serially mediated by distress tolerance and symptom severity. Participants included 306 veterans, 110 of whom met full criteria for current PTSD. PVTs included the Medical Symptom Validity Test (MSVT) and b Test. The Structured Inventory of Malingered Symptomatology (SIMS) was used to measure symptom validity. MSVT failure was significantly and directly associated with PTSD severity (B=0.05, CI=0.01, 0.08) but not distress tolerance or PTSD diagnosis. b Test performance was not significantly related to any variable. SIMS failure was significantly associated with PTSD diagnosis (B=0.71, CI=0.05, 1.37), distress tolerance (B=-0.04, CI=-0.07, -0.01), and symptom severity (B=0.07, CI=0.04, 0.09). The serial mediation model significantly predicted all SIMS subscales. PTSD severity was associated with failing a memory-based PVT but not an attention-based PVT. Neither PVT was associated with distress tolerance or PTSD diagnosis. SVT failure was associated with PTSD diagnosis, poor distress tolerance, and high symptomatology. For veterans with PTSD, difficulty managing negative emotional states may contribute to symptom overreporting. This may reflect exaggeration or an inability to tolerate stronger negative affect, rather than a "cry for help."


Role of cysteinyl leukotrienes in airway inflammation and responsiveness following RSV infection in BALB/c mice.
Cysteinyl leukotrienes (CysLTs) contribute to the development of airway obstruction and inflammation in asthma; however little information is available on the role of these molecules in the pathophysiology of respiratory syncytial virus (RSV) bronchiolitis. This study was designed to evaluate the effects of RSV infection on CysLTs production in a well-established mouse infection model. Furthermore, we assessed the effect of anti-inflammatory agents (a leukotriene receptor antagonist, MK-571, and dexamethasone) on the functional and immune changes induced by RSV infection. Six to 8-wk-old BALB/c mice were infected with human RSV (strain A2). Measurements of airway function were performed using whole body plethysmography. Lung inflammation was assessed by cell counts, measurement of cytokines and CysLTs in bronchoalveolar lavage fluid (BALF) in the absence and presence of treatment with MK-571 or dexamethasone. RSV infection produced a marked increase in CysLTs in the BALF and lung tissue, recruitment of neutrophils and lymphocytes into the airways, increased IFN-gamma levels and airway hyperresponsiveness (AHR). Treatment with MK-571 decreased RSV-induced AHR without affecting the cellular and inflammatory responses to RSV. Dexamethasone decreased AHR and markedly reduced the recruitment of inflammatory cells and production of IFN-gamma. Our findings suggest CysLTs play an important role in the pathogenesis of RSV-induced airway dysfunction. Treatment with MK-571 decreases RSV-induced AHR but does not appear to alter the lung inflammatory responses to RSV. In contrast, dexamethasone decreases RSV-induced AHR but interferes with recruitment of inflammatory cells, resulting in decreased Th1 cytokines (a potentially Th2-prone environment) in this model. These studies support recent reports on the beneficial effects of CysLT receptor antagonist in human trials and provide a model for investigating the role of CysLTs in RSV bronchiolitis.


Nature of the complementation products formed by a complementing mutant of neurospora crassa.
The mutant am-14 produces no active nicotinamide adenine dinucleotide phosphate-linked glutamate dehydrogenase (GDH) and no protein showing immunological cross-reaction with the enzyme. Nevertheless, it shows complementation with several other am mutants in heterokaryons. Active GDH can be extracted from heterokaryons formed from am-14 and other mutants which, by themselves, produce more or less inactive varieties of the enzyme. The enzyme from am-14 + am-3 heterokaryons can be partially separated from am-3 mutant GDH on a diethylaminoethyl cellulose column. It is characterized by abnormally high thermolability and by a capacity for activation by glutamate. By the same procedure as brings about hybridization between mutant GDH proteins, it has been possible to recover enzyme with the properties of pure am-3 GDH from a partially purified am-14 + am-3 GDH preparation which was initially substantially free of unhybridized am-3 enzyme. This is interpreted as evidence that the active complementation product is a hybrid oligomer containing am-3 monomers and also am-14 monomers, the latter being unable to aggregate by themselves. Heterokaryons formed from am-14 and wild type produce GDH of abnormally high thermolability, presumably due to the formation of am-14 + am(+) hybrids.


Correlation between the Quality of Talent Training and Regional Economic Development Based on Multivariate Statistical Analysis Model.
Entering the era of knowledge economy, the economic value of talent education is more and more emphasized, and it contributes more and more to the local economy and injects new vitality into local economic development. However, there are still some difficulties in the synergistic development of talent education and local economy, such as the low degree of integration of "industry, profession, and employment" and the lack of synergy between schools and enterprises, which affects the high-quality development of talent education and restricts the long-term development of regional economy. This paper incorporates machine learning algorithms to construct a multivariate statistics analysis model based on the correlation analysis model between talent training quality and regional economic development. Based on the multi-variate statistical analysis theory and method, the qualitative analysis and quantitative analysis are closely combined to scientifically pick up the main indicators affecting the comprehensive quality of talent cultivation and overcome the drawbacks of artificial subjective assignment of values. Through the judicious selection of evaluation indexes, a scientific and fair evaluation model is established, and the targets of talent cultivation are combined with regional economic development, in a comprehensive analysis, which provides a new means for the development of the regional economy.


The effect of pulmonary rehabilitation on childhood asthma: a systematic review and meta-analysis.
Pulmonary rehabilitation (PR) is a comprehensive nursing intervention for lung function improvement in patients with respiratory diseases. This systematic review focused on further exploration of the unclear impacts of PR on childhood asthma. Web of Science, Cochrane Library, Embase, PubMed, and other databases were searched until May 2021. Randomized controlled trials (RCTs) comparing the effects of PR (including exercise training and education) and routine care on childhood asthma were included. Study selection, data extraction, and bias risk assessment were performed independently by two investigators. Fourteen RCTs involving 1401 patients were included. Relative to the control group, the total scores of the asthma quality of life questionnaire were evidently improved in the experimental group, including motor domain scores (MD=0.88, 95% CI: 0.67-1.09), symptom domain scores (MD=1.23, 95% CI: 0.61-1.85), and affective domain scores (MD=1.38, 95% CI: 0.63-2.14). Besides, 6-min walk distance (MD=2.01, 95% CI: 0.86-3.15) and asthma control test (MD=0.31, 95% CI: 0.02-0.60) were prominently improved. However, the maximum oxygen uptake (MD=0.81, 95% CI: -0.2 to 1.82) was not markedly improved. The forced expiratory volume in 1 s (MD=0.42, 95% CI: -0.29 to 1.13), and forced vital capacity (MD=0.07, 95% CI: -0.14 to 0.28) were not remarkably improved. There was an evident improvement in the peak expiratory flow (MD=1.22, 95% CI: 0.15-2.30). PR improves some lung functions, exercise tolerance and the quality of life of children with asthma, and it might work as a supplementary therapy for the treatment of childhood asthma. Moreover, more RCTs of high quality and in large sample size are needed for further confirmation.


High-resolution ultrasound in the preoperative and postoperative assessment of distal metatarsal osteotomy. Preliminary report.
High-resolution sonography was used to study eight patients with suspected plantarflexed metatarsals and associated painful pedal callousities to determine metatarsal head position as the etiology of the pressure keratosis. Ultrasonography demonstrated a plantarflexed metatarsal head in all eight patients. Using both 5 and 10 MHz transducers, the plantarflexed metatarsal position could be accurately assessed and thus could aid in determining the degree of surgical correction necessary to properly realign the depressed metatarsal. Ultrasonography also allowed a noninvasive and accurate assessment of the surgical correction postoperatively in five of the eight patients. This preliminary study suggests that high-resolution sonography has applicability in accurately assessing metatarsal position. In addition, this new technique is noninvasive and presents insights concerning the amount of surgical correction necessary for realignment without increased risk or pain to the patient.


[Application of exfoliated cells in early diagnosis of oral cancer].
Exfoliative cytology is a simple and non-invasive examination method that is easily accepted by the patient. A number of new techniques are used to further increase the accuracy of sample collecting. It is widely used in the detection of cervical, oral cavity and various coelom exfoliated cells. This article reviews the development of exfoliative cytology in oral cancer diagnosis. It is realized that the qualitative and quantitative analysis of cancer and precancerous lesions, through DNA quantitative analysis to calculate DNA index (DI value), multiple parameter analysis and statistical modeling calculation to evaluate oral cancer risk index (OCRI) of the patient has great significance in cancer screening, early diagnosis and prognosis review, especially in the field of oral cancer.


Coumarin content and physicochemical profile of Mikania laevigata extracts.
The 'guaco' lianous herb Mikania laevigata, which is widespread in Southern Brazil, is traditionally used to treat bronchitis, asthma and cough. This work investigates the influence of the extraction method, solvent:drug ratio, ethanol proportion, harvest season (summer or winter) and solvent heating on the physicochemical profile of the extracts (dry weight, density, pH) and the coumarin (1,2-benzopyrone) content determined by LC. Among the results obtained, it is observed that higher ethanol content increases the amount of coumarin in the extract. Leaves harvested in summer also produce an extract with a high coumarin yield. The most efficient method of extraction is percolation, independent of the solvent used.


[Variability in the flavinogenic activity of Pichia guilliermondi yeasts].
The natural and induced variability of the flavinogenic activity was studied in the strain of Pichia guilliermondii ATCC 9058. The flavinogenic activity of the collection strain showed normal distribution; the amount of riboflavin(RF) accumulated in the medium differed several times in the extreme variants. In the clones with the maximum and minimum accumulation of RF, the distribution of the variants was asymmetric, due to the appearance of the cells with an average flavinogenic activity. The clones have acquired almost the same flavinogenic activity after being transferred eight times on a fresh medium. The asymmetric distribution of the variants according to their flavinogenic activity was found also in the case of the clones obtained from the UV-irradiated cells. The mutants have been isolated, which synthesized 3-30 times more RF than the parent strain in the presence of iron doses optimal for the growth. Five mutants that were most active in producing RF differed in the sensitivity of their flavinogenesis to high concentrations of iron, yeast autolysate, and carbon sources.