Contribution of PKC to beta-hexosaminidase-induced airway smooth muscle proliferation.
beta-Hexosaminidases (Hex) A and B promote mitogenesis via airway smooth muscle (ASM) mannose receptor. The objective of this study was to elucidate the contribution of protein kinase C (PKC) in Hex-induced mitogenesis in ASM cells (ASMC). Exposure of ASMC to Hex caused increases in both the calcium-dependent and the calcium-independent PKC activities. Both downregulation of PKC and PKC inhibitors staurosporine and calphostin C diminished Hex-induced DNA synthesis and cell number. Hex-induced DNA synthesis was enhanced by a diacylglycerol kinase inhibitor, R-59022, which was blocked by calphostin C. These data suggest that activation of PKC in part mediates Hex-induced mitogenesis in ASMC.


Pediatric Invasive Aspergillosis.
Invasive aspergillosis (IA) is a disease of increasing importance in pediatrics due to growth of the immunocompromised populations at risk and improvements in long-term survival for many of these groups. While general principles of diagnosis and therapy apply similarly across the age spectrum, there are unique considerations for clinicians who care for children and adolescents with IA. This review will highlight important differences in the epidemiology, clinical manifestations, diagnosis, and therapy of pediatric IA.


Sialoadhesin, a macrophage sialic acid binding receptor for haemopoietic cells with 17 immunoglobulin-like domains.
Sialoadhesin is a macrophage-restricted adhesion molecule of 185 kDa that mediates sialic acid-dependent binding to cells. It is expressed strongly by macrophages in lymphoid and haemopoietic tissues where it is likely to mediate cell-cell interactions. Here we report the molecular cloning of murine sialoadhesin and show that it is a new member of the immunoglobulin (Ig) superfamily with 17 Ig-like domains. COS cells transfected with a cDNA encoding full-length sialoadhesin bound mouse bone marrow cells in a sialic acid-dependent manner. Alternatively spliced cDNAs, predicting soluble forms of sialoadhesin containing the first three or 16 Ig-like domains of sialoadhesin, were expressed in COS cells and the respective proteins purified. When immobilized on plastic, the 16-domain form bound cells in a sialic acid-dependent manner, suggesting that sialoadhesin can function in both secreted and membrane-bound forms. The most similar proteins in the database were CD22, myelin-associated glycoprotein, Schwann cell myelin protein and CD33. Like sialoadhesin, CD22 mediates sialic acid-dependent cell adhesion. The sequence similarity of sialoadhesin to CD22 and related members of the Ig superfamily indicates the existence of a novel family of sialic acid binding proteins involved in cell-cell interactions.


'Our Families are Killing Us': HIV/AIDS, Witchcraft and Social Tensions in the Caprivi Region, Namibia.
The importance of exploring 'indigenous' constructions of illness is vital when explanatory models of ill health differ markedly from dominant biomedical paradigms. In the Caprivi region of Namibia, an upsurge of witchcraft accusations can be seen as a direct reaction to increasing AIDS-related illness and deaths, and to changes in socio-economic attitudes and expectations. The mobilization of witchcraft narratives provides a socially acceptable explanation for illness, and can positively influence decisions regarding the care and identity of the ill person. However, drawing upon data collected at kin and village level, this paper demonstrates that while witchcraft accusations can avert stigma and blame away from the ill person, they can also result in significant disruption to livelihoods, and place considerable tension upon key social capital networks at a time when the household is particularly vulnerable. Such findings have significant implications for the effectiveness of HIV prevention and AIDS mitigation initiatives, and for livelihood security.


Non-invasive assessment of ventricular force-frequency relations in the univentricular circulation by tissue Doppler echocardiography: a novel method of assessing myocardial performance in congenital heart disease.
To describe the first clinical application of a novel tissue Doppler derived index of contractility, isovolumic acceleration (IVA), in the assessment of the ventricular myocardial force-frequency relation (FFR) in the univentricular heart (UVH). Prospective study. Tertiary referral centre. Non-invasive assessment of the myocardial FFR by tissue Doppler echocardiography during atrial pacing. IVA was used to measure the FFR of the systemic ventricle in patients with structurally normal hearts and in patients with UVHs. Basal IVA of the normal hearts (mean (SD) 1.9 (0.3) m/s2) was significantly greater than that of UVHs in patients with a dominant right ventricle (RV) (1.0 (0.3) m/s2) or left ventricle (LV) (0.8 (0.7) m/s2; p < 0.05 for both). Neither the absolute nor percentage change from basal to peak values of IVA with pacing differed between the three groups. Peak force developed by the normal LV was significantly greater than that of the UVH, dominant LV group but not different from that of the UVH, dominant RV group. Contractility at basal heart rate is depressed in patients with UVH compared with the normal LV. Analysis of ventricular FFRs exposes further differences in myocardial contractility. There is no evidence that contractile function of the dominant RV is inferior to that of the dominant LV over a physiological range of heart rates.


[The closed method of intramedullary fixation of forearm fractures].
The authors demonstrate a group of 27 patients subjected to intramedullary osteosynthesis of the forearm by means of Kirschner wires, using closed surgery. They prefer the described method in patients suffering from multiple injuries who have devastated soft parts of the forearm and in unstable fractures in children. The authors draw attention to the fact that they have achieved very good results by the simple surgical method they described.


Maternal hypoglycaemia on the 50 g oral glucose challenge test - evaluation of obstetric and neonatal outcomes.
To discuss obstetric and neonatal outcomes of maternal hypoglycaemia observed after the 50 g oral glucose challenge test. A retrospective evaluation was made of the results of patients at 24-28 weeks gestation of a live singleton pregnancy who underwent a 50 g OGCT at the Health Sciences University Gazi Yaşargil Training and Research Hos-pital, between September 2016 and August 2017. In the 50 g OGCT, 1-hour blood glucose results were divided into Low OGCT (< 90 mg/dL) and Normal OGCT (90-139 mg/dL). The groups were compared in respect of obstetrics and neonatal outcomes. Of 2623 pregnant patients applied with the 50 g OGCT, blood glucose was < 140 mg/dL in 77.16% (n = 2024), with 11.9% (n = 312) in the Low OGCT group, and the remaining 65.26% (n = 1712) in the Normal OGCT group. Based on the comparison of the groups, the SGA rate was 7% in the Low OGCT group and 4% in the Normal OGCT group; the 5th minute APGAR score was < 7 in 2% of the Low OGCT group and in 1% of the Normal OGCT group, while caesarean section rates were 25% and 32% respectively (p < 0.05). The results of the study showed a significant association between maternal hypoglycaemia and increased SGA rate, decreased 5-minute APGAR scores and reduced caesarean section rates, and this relationship should be confirmed with further comprehensive studies.


[Sequelae of dental trauma: forensic medical aspects].
Dental trauma is a frequent condition which may occur alone or in combination with craniofacial trauma and/or other injuries. Many factors influence the gravity of the trauma and subsequent prognosis including age, anterior state, trauma etiology, treatment and follow up. In order to establish a prudent provisional or definitive expertise, the medical expert must have a panoramic view of the trauma. Time should be taken to consolidate facts and estimate prejudices on sound evidence. In certain cases outcome can be predicted. The medical expert should provide advice and counselling both for the patient and the mandating authority. In this article, iatrogenic dental accidents occurring during anesthesia or extraction will not be discussed.


Hemodialysis patients perceived exercise benefits and barriers: the association with health-related quality of life.
Patients on hemodialysis have less exercise capacity and lower health-related quality of life than healthy individuals without chronic kidney disease (CKD). One of the factors that may influence exercise behavior among these patients is their perception of exercise benefits and barriers. The present study aimed to assess the perception of hemodialysis patients about exercise benefits and barriers and its association with patients' health-related quality of life. In this cross-sectional study, 227 patients undergoing hemodialysis were randomly selected from two dialysis centers. Data collection was carried out using dialysis patient-perceived exercise benefits and barriers scale (DPEBBS) and kidney disease quality of life short form (KDQOL-SF). Data were analyzed using SPSS software ver. 21. The mean score of DPEBBS was 68.2 ± 7.4 (range: 24 to 96) and the mean KDQOL score was 48.9 ± 23.3 (range: 0 to 100). Data analysis by Pearson correlation coefficient showed a positive and significant relationship between the mean scores of DPEBBS and the total score of KDQOL (r = 0.55, p < 0.001). Moreover, there was a positive relationship between the mean scores of DPEBBS and the mean score of all domains of KDQOL. Although most of the patients undergoing hemodialysis had a positive perception of the exercise, the majority of them do not engage in exercise; it could be contributed to the barriers of exercise such as tiredness, muscle fatigue, and fear of arteriovenous fistula injury. Providing exercise facilities, encouraging the patients by the health care provider to engage in exercise programs, and incorporation of exercise professionals into hemodialysis centers could help the patients to engage in regular exercise.


Lysinibacillus massiliensis Panniculitis Masquerading as Erythema Nodosum: A Case Report.
Lysinibacillus massiliensis, formerly Bacillus massiliensis, is an environmental Gram-positive bacillus that is generally non-pathogenic. Rare case reports in immunosuppressed patients have described sepsis with this organism. In this study, we report a case of L massiliensis as a cause of infectious panniculitis mimicking erythema nodosum after infusion of autologous adipose-derived stem cells in an immunosuppressed patient with refractory Crohn's disease. This case highlights the importance of care providers to consider exposures and host factors when interpreting culture results with otherwise benign organisms.


The conservative management of self-inflicted chemical burns: Case report and literature review.
Chemical burns, particularly injuries related to psychiatric illnesses, are underreported in the literature. We present two cases of self-inflicted alkali chemical burns managed conservatively. Frequent clinical review of the burn was aimed to ensure appropriate healing and compliance with the treatment plan based on regular dressing changes. A 24-year-old woman presented during the first day of the initial injury with a minor self-inflicted chemical burn to the right forearm. The causative agent was an oven cleaner containing sodium hydroxide triggering an alkali-based burn. The surface area of the injury was 0.5% total body surface area (TBSA) full-thickness burn. The patient had a complex psychiatric history diagnosed with personality disorder, anxiety and depression. A 55-year-old woman presented with a self-inflicted left forearm full-thickness burn (0.5% TBSA). This was five days after the initial injury from an oven cleaner containing sodium hydroxide. The patient had a psychiatric history of anxiety and depressive disorder.The mainstay of burn management was conservative with regular dressing changes and a topical agent. Telemedicine via a designated email address was given to the patient for virtual clinical burn review and any urgent issues. Photograph of the initial burn was taken, and clinic visits were scheduled to determine healing progress. Self-inflicted chemical burns are to be managed within a multidisciplinary setting including early psychiatric involvement. We advocate a holistic approach to determine conservative or operative management, taking into account patient factors, burn complexity and clinician's judgement to streamline the treatment plan. Chemical burns due to self-harm are rare to see in clinical practice. A review of two cases secondary to intentional burns sustained using an oven cleaning material. Patients had psychiatric issues and were on medications to control symptoms. Close observation with regular dressings and topical cream would allow burns to heal without the need for an operation. Our recommendation would be to treat these burns with dressings and regular follow up in the clinic or virtually till healed.


Effects of anesthetic agents and fasting duration on 18F-FDG biodistribution and insulin levels in tumor-bearing mice.
Small-animal PET has opened the way for imaging (18)F-FDG uptake in murine tumor models, but the need for anesthesia raises concern over its potential influence on (18)F-FDG kinetics. We thus investigated such effects on cultured cells and on tumor-bearing mice after short- and long-term fasting. Lewis lung carcinoma (LLC) cells and cardiomyoblasts were treated for 2 h with a 100 micromol/L concentration of xylazine, ketamine, xylazine plus ketamine (Xy/Ke), or pentobarbital and were measured for (18)F-FDG uptake. LLC tumor-bearing C57BL6 mice that had been kept fasting for either 4 or 20 h were injected with Xy/Ke, pentobarbital, or saline and were administered 1.8 MBq of (18)F-FDG 15 min later. Biodistribution studies and plasma glucose and insulin assays were performed 45 min after injection. Separate anesthetized and control mice underwent (18)F-FDG PET. (18)F-FDG uptake in LLC cells was unaffected by anesthetic agents, whereas xylazine and ketamine caused a small increase of uptake in cardiomyoblasts. In mice kept fasting 4 h, Xy/Ke induced a marked elevation of (18)F-FDG activity (percentage injected dose [%ID]) in blood (6.8 +/- 0.9%ID/g vs. 1.1 +/- 0.6%ID/g) and kidneys while decreasing myocardial uptake (2.3 +/- 1.3%ID/g vs. 4.7 +/- 1.8%ID/g). Target-to-blood ratios were significantly reduced. Pentobarbital caused a moderate increase in blood activity (2.5 +/- 0.8%ID/g), decreased myocardial uptake (2.8 +/- 0.5%ID/g), and reduced target-to-blood ratios. PET images of mice kept fasting 4 h were consistent with the biodistribution data. Insulin levels were lower with Xy/Ke and higher with pentobarbital. In mice kept fasting 20 h, Xy/Ke and pentobarbital increased blood (18)F-FDG activity (5.5 +/- 2.2 and 4.9 +/- 0.9%ID/g vs. 2.4 +/- 0.3%ID/g) and reduced target-to-blood ratios, but these changes were substantially attenuated, compared with those in mice kept fasting 4 h. In addition, insulin levels were low and unaffected by anesthesia. Xy/Ke anesthesia markedly elevates blood (18)F-FDG activity and reduces tumor uptake ratios through inhibition of insulin release in mice kept fasting 4 h, whereas pentobarbital induces a similar but less severe response through insulin resistance. These metabolic effects, however, are substantially attenuated after 20 h of fasting. Hence both the choice of anesthetic and the duration of fasting have important effects on (18)F-FDG kinetics and PET images of tumor-bearing mice and should be considered when such studies are performed.


A Designed Approach to Enantiodivergent Enamine Catalysis.
The rational design and implementation of enantiodivergent enamine catalysis is reported. A simple secondary amine catalyst, 2-methyl-l-proline, and its tetrabutylammonium salt function as an enantiodivergent catalyst pair delivering the enantiomers of α-functionalized aldehyde products in excellent enantioselectivities. This novel concept of designed enantiodivergence is applied to the enantioselective α-amination, aldol, and α-aminoxylation/α-hydroxyamination reactions of aldehydes.


Predicting Pharmacodynamic Drug-Drug Interactions through Signaling Propagation Interference on Protein-Protein Interaction Networks.
As pharmacodynamic drug-drug interactions (PD DDIs) could lead to severe adverse effects in patients, it is important to identify potential PD DDIs in drug development. The signaling starting from drug targets is propagated through protein-protein interaction (PPI) networks. PD DDIs could occur by close interference on the same targets or within the same pathways as well as distant interference through cross-talking pathways. However, most of the previous approaches have considered only close interference by measuring distances between drug targets or comparing target neighbors. We have applied a random walk with restart algorithm to simulate signaling propagation from drug targets in order to capture the possibility of their distant interference. Cross validation with DrugBank and Kyoto Encyclopedia of Genes and Genomes DRUG shows that the proposed method outperforms the previous methods significantly. We also provide a web service with which PD DDIs for drug pairs can be analyzed at http://biosoft.kaist.ac.kr/targetrw.


C-terminal-truncated hepatitis B virus X protein enhances the development of diethylnitrosamine-induced hepatocellular carcinogenesis.
Hepatitis B virus X protein (HBx) is involved in the development of hepatocellular carcinoma (HCC). The HBx sequence is a preferential site of integration into the human genome, leading to the formation of C-terminal-truncated HBx proteins (Ct-HBx). We previously reported that Ct-HBx proteins were able to potentiate cell transformation in vitro. Our present goal was to compare the ability of Ct-HBx and full-length HBx (FL-HBx) proteins to develop or enhance HCC in transgenic mice. In the absence of treatment, neither Ct-HBx- nor FL-HBx-transgenic mice developed HCC. In young mice treated with diethylnitrosamine (DEN) at 8 months of age, a significantly higher incidence and number of liver lesions were observed in Ct-HBx mice than in FL-HBx and control mice. The earlier development of tumours in Ct-HBx-transgenic mice was associated with increased liver inflammation. At 10 months, macroscopic and microscopic analyses showed that, statistically, FL-HBx mice developed more liver lesions with a larger surface area than control mice. Furthermore, during DEN-induced initiation of HCC, Ct-HBx- and FL-HBx-transgenic mice showed higher expression of IL-6, TNF-α and IL-1β transcripts, activation of STAT3, ERK and JNK proteins and an increase in cell apoptosis. In conclusion, in DEN-treated transgenic mice, the expression of Ct-HBx protein causes a more rapid onset of HCC than does FL-HBx protein. HBV genome integration leading to the expression of a truncated form of HBx protein may therefore facilitate HCC development in chronically infected patients.


[Application of support vector machines to classification of blood cells].
The support vector machine (SVM) is a new learning technique based on the statistical learning theory. It was originally developed for two-class classification. In this paper, the SVM approach is extended to multi-class classification problems, a hierarchical SVM is applied to classify blood cells in different maturation stages from bone marrow. Based on stepwise decomposition, a hierarchical clustering method is presented to construct the architecture of the hierarchical (tree-like) SVM, then the optimal control parameters of SVM are determined by some criterion for each discriminant step. To verify the performances of classifiers, the SVM method is compared with three classical classifiers using 3-fold cross validation. The preliminary results indicate that the proposed method avoids the curse of dimensionality and has greater generalization. Thus, the method can improve the classification correctness for blood cells from bone marrow.


Orthopaedic perspective on bone metastasis.
The incidence of cancer is increasing worldwide, with the advent of a myriad of new treatment options, so is the overall survival of these patients. However, from an orthopaedic perspective, there comes the challenge of treating more patients with a variety of metastatic bone lesions. The consequences of such lesions can be significant to the patient, from pain and abnormal blood results, including hypercalcemia, to pathological fracture. Given the multiple options available, the treatment of bone metastasis should be based on a patient-by patient manner, as is the case with primary bone lesions. It is imperative, given the various lesion types and locations, treatment of bone metastasis should be performed in an individualised manner. We should consider the nature of the lesion, the effect of treatment on the patient and the overall outcome of our decisions. The dissemination of primary lesions to distant sites is a complex pathway involving numerous cytokines within the tumour itself and the surrounding microenvironment. To date, it is not fully understood and we still base a large section of our knowledge on Pagets historic "seed and soil" theory. As we gain further understanding of this pathway it will allow us develop more medical based treatments. The treatment of primary cancers has long been provided in a multi-disciplinary setting to achieve the best patient outcomes. This should also be true for the treatment of bone metastases. Orthopaedic surgeons should be involved in the multidisciplinary treatment of such patients given that there are a variety of both surgical fixation methods and non-operative methods at our disposal.


Recovery from neurological deficits following biotin treatment in a biotinidase Km variant.
A 15-year-old boy suffered from progressive bilateral optic neuropathy of acute onset at the age of 10 years. Subsequently he developed spastic paraparesis and a predominantly motor type neuro-axonal neuropathy in all limbs. The basic error has been elucidated to be due to an unusual biotinidase Km variant with biphasic enzyme kinetics causing systemic biotin depletion and consequent multiple biotin-dependent carboxylase deficiency. After daily oral substitution with 10 mg biotin metabolic derangements subsided rapidly. Follow-up studies over one year after substitution with biotin demonstrated remarkable recovery from part of the previously present neuro-ophthalmological, motor and cognitive deficits. The previously extinguished flash-evoked visual potentials now showed clear responses after six months of substitution with biotin. In contrast with reports in literature, these findings indicated that neurological damage associated with biotinidase deficiency, rather than being permanent, is to some extent reversible.


Comparative organization of nitrogen fixation-specific genes from Azotobacter vinelandii and Klebsiella pneumoniae: DNA sequence of the nifUSV genes.
In the facultative anaerobe Klebsiella pneumoniae 17 nitrogen fixation-specific genes (nif genes) have been identified. Homologs to 12 of these genes have now been isolated from the aerobic diazotroph Azotobacter vinelandii. Comparative studies have indicated that these diverse microorganisms share striking similarities in the genetic organization of their nif genes and in the primary structure of their individual nif gene products. In this study the complete nucleotide sequence of the nifUSV gene clusters from both K. pneumoniae and A. vinelandii were determined. These genes are identically organized on their respective genomes, and the individual genes and their products exhibit a high degree of interspecies sequence homology.


[Risk factors for citrate accumulation in patients with liver failure undergoing continuous renal replacement therapy with regional citrate anticoagulation].
To investigate the risk factors of citrate accumulation in patients with liver failure treated with regional citrate anticoagulated continuous renal replacement therapy (RCA-CRRT). The clinical data of liver failure patients with RCA-CRRT admitted to department of intensive care unit (ICU) of Nantong Third People's Hospital from January 2017 to June 2020 were retrospectively analyzed. The selected patients were divided into citrate accumulation group and control group according to whether there was citrate accumulation (serum total calcium/free calcium ratio ≥ 2.4) during CRRT. The age, acute physiology and chronic health evaluation II (APACHE II), mean arterial pressure (MAP), norepinephrine (NE) dose, blood lactic acid (Lac) concentration, liver function status, citrate dose, filter time and prognosis of the patients were compared between the two groups. Unconditional Logistic regression was used to analyze the risk factors for citrate accumulation. Among 48 patients with RCA-CRRT and liver failure, 20 patients had citrate accumulation (accumulation group), and a total of 96 CRRTs were performed; the remaining 28 patients did not have citrate accumulation (control group), a total of 106 CRRTs were performed. There were no significant differences in age and APACHE II score between the two groups. Compared with the control group, the MAP in the accumulation group was lower [mmHg (1 mmHg = 0.133 kPa): 66.9±13.6 vs. 86.4±8.3, P = 0.032], and the dosage of NE (μg/min: 16.3±8.4 vs. 5.9±2.8, P = 0.015) and lactic acid level (mmol/L: 4.89±1.45 vs. 2.98±0.87, P = 0.004) were higher, the damage of liver function was more serious [total bilirubin (TBil, μmol/L): 220.4±45.2 vs. 163.4±43.8, P = 0.012; Child-Pugh score: 12.0±2.5 vs. 8.8±1.4, P = 0.029; model for end-stage liver disease (MELD) score: 31.30±8.22 vs. 21.78±6.40, P = 0.041], hourly citric acid dosage (mmol/h: 27.4±6.9 vs. 19.3±4.9, P = 0.032) and total citric acid dosage (mmol: 3 393±809 vs. 1 819±502, P = 0.039) were higher. Although there were no significant differences in the length of ICU stay, total length of hospitalization stay and cost of hospitalization between the two groups, the 28-day mortality of the accumulation group was higher than that of the control group (60.0% vs. 28.6%, P = 0.039). Unconditional Logistic regression analysis showed that MAP [odds ratio (OR) = 2.901, 95% confidence interval (95%CI) was 0.921-19.493, P = 0.019], NE dosage (OR = 2.098, 95%CI was 1.923-12.342, P = 0.002), Lac level (OR = 5.201, 95%CI was 3.211-9.433, P = 0.012), Child-Pugh score (OR = 1.843, 95%CI was 0.437-7.420, P = 0.018), MELD score (OR = 3.012, 95%CI was 0.384-12.843, P = 0.031), hourly citric acid dosage (OR = 4.254, 95%CI was 1.734-11.839, P = 0.011) and total citric acid dosage (OR = 4.109, 95%CI was 1.283-18.343, P = 0.001) were risk factors for citrate accumulation. In patients with tissue hypoperfusion and severe liver function damage, citrate anticoagulation should be avoided or the dosage of citric acid should be reduced, in order to avoid citrate accumulation.


Advances and applications of genetically modified pig models in biomedical and agricultural field.
Compared with rodents, pigs are closer to humans in terms of anatomy, metabolism and physiology, so they are ideal animal models of human diseases and xenotransplantation donors. In addition, as one of the most important livestock in China, pigs are closely related to our lives in terms of breeding improvement, disease prevention and animal welfare. In this review, we mainly summarize the research progress and future application of genetically modified pig models in the fields of xenotransplantation, molecular breeding and human disease models. We wish to take this opportunity to raise the awareness of researchers in related fields on cutting-edge technologies such as gene editing and understand the significance of genetically modified pig models in life science research.


Consolidation of human somatosensory memory during motor learning.
Sensorimotor learning is a bidirectional process associated with concurrent neuroplastic changes in the motor and somatosensory system. While motor memory consolidation and retention have been extensively studied during skill acquisition, little is known about the formation and consolidation of somatosensory memory associated with motor learning. Using a robotic exoskeleton, we tracked markers of somatosensory and motor learning while healthy participants trained to make goal-directed wrist reaching movements over five days and evaluated retention for up to 10 days after practice. Markers of somatosensory learning were changes in wrist position sense bias (systematic error) and precision (random error). The main results are as follows: First, somatosensory (proprioceptive) memory consolidation shows signs of cost savings with repeated sensorimotor training - the same feature is known for motor memory formation. Moreover, somatosensory learning generalized to untrained workspace. Second, somatosensory learning over days can be characterized as an early improvement in sensory precision and a later improvement in sensory bias. Third, the time course of learning gains in position sense acuity coincided with improvements in spatial movement accuracy. Finally, the gains of somatosensory learning were retained for several days. Improvements in position sense bias were still visible up to 3 days after the end of practice for the trained workspace positions, but decayed faster in the untrained workspace. Improvements in position sense precision were retained for up to 10 days and were workspace independent. The findings are consistent with the view that an internal model of somatosensory joint space is formed during motor learning.


Impact of temperature-dependent phage expression on Pseudomonas aeruginosa biofilm formation.
Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that forms robust biofilms in the different niches it occupies. Numerous physiological adaptations are required as this organism shifts from soil or aquatic environments to a host-associated lifestyle. While many conditions differ between these niches, temperature shifts are a factor that can contribute to physiological stress during this transition. To understand how temperature impacts biofilm formation in this pathogen, we used proteomic and transcriptomic tools to elucidate physiological responses in environment-relevant vs. host-relevant temperatures. These studies uncovered differential expression of various proteins including a phage protein that is associated with the EPS matrix in P. aeruginosa. This filamentous phage was induced at host temperatures and was required for full biofilm-forming capacity specifically at human body temperature. These data highlight the importance of temperature shift in biofilm formation and suggest bacteriophage proteins could be a possible therapeutic target in biofilm-associated infections.


Burn Resuscitation Practices in North America: Results of the Acute Burn ResUscitation Multicenter Prospective Trial (ABRUPT).
ABRUPT was a prospective, noninterventional, observational study of resuscitation practices at 21 burn centers. The primary goal was to examine burn resuscitation with albumin or crystalloids alone, to design a future prospective randomized trial. No modern prospective study has determined whether to use colloids or crystalloids for acute burn resuscitation. Patients ≥18 years with burns ≥ 20% total body surface area (TBSA) had hourly documentation of resuscitation parameters for 48 hours. Patients received either crystalloids alone or had albumin supplemented to crystalloid based on center protocols. Of 379 enrollees, two-thirds (253) were resuscitated with albumin and one-third (126) were resuscitated with crystalloid alone. Albumin patients received more total fluid than Crystalloid patients (5.2 ± 2.3 vs 3.7 ± 1.7 mL/kg/% TBSA burn/24 hours), but patients in the Albumin Group were older, had larger burns, higher admission Sequential Organ Failure Assessment (SOFA) scores, and more inhalation injury. Albumin lowered the in-to-out (I/O) ratio and was started ≤12 hours in patients with the highest initial fluid requirements, given >12 hours with intermediate requirements, and avoided in patients who responded to crystalloid alone. Albumin use is associated with older age, larger and deeper burns, and more severe organ dysfunction at presentation. Albumin supplementation is started when initial crystalloid rates are above expected targets and improves the I/O ratio. The fluid received in the first 24 hours was at or above the Parkland Formula estimate.


Do the Transmissible Liability Index (TLI) and Adolescent Cannabis Use Predict Paranoid and Schizotypal Symptoms at Young Adulthood?
Background: Adolescent cannabis use is an established risk factor for the development of psychosis, but the premorbid vulnerability factors and specificity versus generality of the psychotic symptom domains affected in cannabis-psychosis relationships remain incompletely understood. To improve our understanding of these relationships, we used longitudinal data to examine the individual and interactive effects of preadolescent transmissible liability to substance use disorders (SUD), measured via the transmissible liability index (TLI), and adolescent cannabis use on the development of two distinct psychotic symptom domains, paranoid and schizotypal personality traits in young adulthood. Methods: We performed secondary analysis of data from the Center for Education and Drug Abuse (CEDAR) study, which longitudinally assessed offspring of men with (N = 211) and without (N = 237) lifetime history of SUD at ages 10-12, and across adolescence as they transitioned to young adulthood. TLI scores were calculated at age 10-12, self-reported cannabis use was assessed at age 16, and paranoid and schizotypal symptoms were assessed at age 19. Results: Cannabis use at age 16 and family history of SUD were significantly associated with paranoid and schizotypal symptoms at age 19, but TLI scores were not. The interactive effect of TLI x cannabis use was also not significant. Paranoid and schizotypal symptoms showed different dose-dependent sensitivities to cannabis exposure at age 16. Conclusions: These findings indicate that adolescent cannabis use and family history of SUD differentially contribute to the development of paranoid and schizotypal personality traits through mechanisms that do not include behavioral disinhibition.


Impact of ambient humidity on child health: a systematic review.
Changes in relative humidity, along with other meteorological factors, accompany ongoing climate change and play a significant role in weather-related health outcomes, particularly among children. The purpose of this review is to improve our understanding of the relationship between ambient humidity and child health, and to propose directions for future research. A comprehensive search of electronic databases (PubMed, Medline, Web of Science, ScienceDirect, OvidSP and EBSCO host) and review of reference lists, to supplement relevant studies, were conducted in March 2013. All identified records were selected based on explicit inclusion criteria. We extracted data from the included studies using a pre-designed data extraction form, and then performed a quality assessment. Various heterogeneities precluded a formal quantitative meta-analysis, therefore, evidence was compiled using descriptive summaries. Out of a total of 3797 identified records, 37 papers were selected for inclusion in this review. Among the 37 studies, 35% were focused on allergic diseases and 32% on respiratory system diseases. Quality assessment revealed 78% of the studies had reporting quality scores above 70%, and all findings demonstrated that ambient humidity generally plays an important role in the incidence and prevalence of climate-sensitive diseases among children. With climate change, there is a significant impact of ambient humidity on child health, especially for climate-sensitive infectious diseases, diarrhoeal diseases, respiratory system diseases, and pediatric allergic diseases. However, some inconsistencies in the direction and magnitude of the effects are observed.


Constitutive activation of Jak/STAT proteins in Epstein-Barr virus-infected B-cell lines from patients with posttransplant lymphoproliferative disorder.
Posttransplant lymphoproliferative disease (PTLD) is a major complication after bone marrow and solid organ transplantation. The disease encompasses a spectrum of abnormal, Epstein-Barr virus (EBV)-associated B-cell proliferations. We have previously shown that EBV-infected, spontaneous lymphoblastoid cell lines (SLCL) derived from PTLD patients require autocrine interleukin (IL)-10 to proliferate. To determine if cytokine signal transduction is involved in the autonomous growth of the SLCL, the activation states of the Jak/STAT signaling pathway proteins were analyzed in three different SLCL, termed JB7, MF4, and VB4. The tyrosine phosphorylation (P-tyr) states of the Janus kinases (Jaks) and signal transducers and activators of transcription (STAT) proteins were examined by immunoprecipitation and immunoblot. Activated STAT dimer formation was determined by electromobility shift assays. All three SLCL, but not the Daudi Burkitt's lymphoma B-cell line, expressed the four known Jak kinases constitutively tyrosine phosphorylated, with particularly high levels of P-tyr Jak1 in the JB7 line. STAT1 and STAT3, but not STAT2 or STAT5, are also constitutively activated in all SLCL. The ability of the activated STAT proteins to form DNA-binding dimers was confirmed by electromobility shift assay. The SLCL, but not the Daudi line, express activated STAT complexes composed of STAT1 and STAT3. Another EBV-infected B-cell line, isolated from a lymph node biopsy after kidney transplantation, is phenotypically similar to the other SLCL in both surface antigen and activated STAT1 and STAT3 expression. These data support the presence of a constitutively active autocrine signaling pathway consistent with IL-10 in the SLCL.


Presentation of Wegener's granulomatosis in young patients.
We have reviewed 50 cases of Wegener's granulomatosis, seen at the New England Medical Center Hospital between 1970 and 1984, and were impressed that 10 (20%) of these patients were under 25 years of age, with ages ranging from 13 to 23 years. Closer examination of this younger group revealed striking differences in their presenting symptoms and organ involvement when compared to the older group of patients. The presentation of these young patients was varied, with no single predominant symptom. Patients presented with otalgia and otitis media or hearing loss, fulminant sinusitis, arthralgias, and even corneal ulcers. Only one patient had "typical" rhinitis and nasal congestion. This group also had a disproportionate number of patients with involvement of the oral cavity, skin, and trachea. Biopsy of these sites frequently demonstrated necrotizing vasculitis. Three of our 50 patients had intracranial involvement, leading to transient hemiplegia in the first, permanent hemiplegia in the second, and a seizure disorder in the third. Two of these patients were in the younger age group. The proportion of patients with limited and generalized Wegener's granulomatosis was the same in both the younger and older age groups. All the younger patients, however, had manifestations of the disease in the head and neck, while four of the older patients had no symptoms in the upper respiratory tract. The number of young patients in our study emphasizes the fact that Wegener's granulomatosis, indeed, occurs in the younger patient and with a greater frequency than previously supposed. This study suggests that in the teenager and young adult, with an unusual constellation of symptoms of the head and neck and accompanying systemic problems, a diagnosis of Wegener's granulomatosis should be seriously considered.


Superior mesenteric vein thrombosis presented transient false positivity for lupus anticoagulant under heparin treatment.
A 24-year-old Japanese man was admitted because of massive haematemesis and melaena with persistent abdominal pain. Markedly bloody ascites and severely oedematous small intestine were recognized, and angiography then revealed superior mesenteric vein thrombosis. After resection of the necrotic small intestine, continuous intravenous infusion of heparin and urokinase was performed. This patient had no familial or personal history of thrombosis. On the 15th day after operation, an initial search for lupus anticoagulant revealed that the prothrombin time (PT) ratio and dilute activated partial thromboplastin time (aPTT) were positive under heparin treatment, without evidence of rheumatic or connective tissue disease. Thrombocytopenia was observed with a nearly normocellular bone marrow. A follow-up examination 1 year later still revealed an increased aPTT. However, all tests for antiphospholipid antibodies had been negative including dilute aPTT for about 2 years since the 15th day after operation. These findings suggest that, in this patient, superior mesenteric vein thrombosis has not been associated with primary antiphospholipid syndrome but is probably idiopathic. Positive tests for lupus anticoagulant in the initial period may be unreliable due to heparin treatment.


Glutamine dipeptide-supplemented parenteral nutrition improves the clinical outcomes of critically ill patients: A systematic evaluation of randomised controlled trials.
Early randomised controlled trials (RCTs) testing whether parenteral nutrition regimens that include glutamine dipeptides improves the outcomes of critically ill patients demonstrated convincingly that this regimen associates with reduced mortality, infections, and hospital stays. However, several new RCTs on the same question challenged this. To resolve this controversy, the present meta-analysis was performed. Stringent eligibility criteria were used to select only those RCTs that tested the outcomes of critically ill adult patients without hepatic and/or renal failure who were haemodynamically and metabolically stabilised and who were administered glutamine dipeptide strictly according to current clinical guidelines (via the parenteral route at 0.3-0.5 g/kg/day; max. 30% of the prescribed nitrogen supply) in combination with adequate nutrition. The literature research (PubMed, Embase, Cochrane Central Register of Controlled Trials) searched for English and German articles that had been published in peer-review journals (last entry March 31, 2015) and reported the results of RCTs in critically ill adult patients (major surgery, trauma, infection, or organ failure) who received parenteral glutamine dipeptide as part of an isoenergetic and isonitrogenous nutrition therapy. The following data were extracted: infectious complications, lengths of stay (LOS) in the hospital and intensive care unit (ICU), duration of mechanical ventilation, days on inotropic support, and ICU and hospital mortality rates. The selection of and data extraction from studies were performed by two independent reviewers. Fifteen RCTs (16 publications) fulfilled all selection criteria. They involved 842 critically ill patients. None had renal and/or hepatic failure. The average study quality (Jadad score: 3.8 points) was well above the predefined cut-off of 3.0. Common effect estimates indicated that parenteral glutamine dipeptide supplementation significantly reduced infectious complications (relative risk [RR] = 0.70, 95% CI 0.60, 0.83, p < 0.0001), ICU LOS (common mean difference [MD] -1.61 days, 95% CI -3.17, -0.05, p = 0.04), hospital LOS (MD -2.30 days, 95% CI -4.14, -0.45, p = 0.01), and mechanical ventilation duration (MD -1.56 days, 95% CI -2.88, -0.24, p = 0.02). It also lowered the hospital mortality rate by 45% (RR = 0.55, 95% CI 0.32, 0.94, p = 0.03) but had no effect on ICU mortality. Visual inspection of funnel plots did not reveal any potential selective reporting of studies. This meta-analysis clearly confirms that when critically ill patients are supplemented with parenteral glutamine dipeptide according to clinical guidelines as part of a balanced nutrition regimen, it significantly reduces hospital mortality, infectious complication rates, and hospital LOS. The latter two effects indicate that glutamine dipeptide supplementation also confers economic benefits in this setting. The present analysis indicates the importance of delivering glutamine dipeptides together with adequate parenteral energy and nitrogen so that the administered glutamine serves as precursor in various biosynthetic pathways rather than simply as a fuel.


Generation of vectorial optical fields with slot-antenna-based metasurface.
A transmission-type metasurface composed of carefully designed rectangular slot antennas for the generation of vectorial optical fields is proposed and demonstrated. Acting as local linear polarizers, these slot antennas enable the spatial modulation of optical fields in amplitude, phase, and polarization for the cross-polarized component of the scattered field. As an illustration, a metasurface capable of forming a radially polarized scattered field with specific vectorial beam patterns with appropriate excitation at normal incidence is designed, fabricated, and tested. The radially polarized scattered field is designed to be further tightly focused by a high numerical aperture objective lens in order to obtain a uniform longitudinally polarized optical needle field along the propagation direction. Characterization experiments demonstrate that its overall extinction ratio satisfies the amplitude modulation requirement, and a corresponding π phase modulation is realized as proposed.


Barotrauma in critically ill COVID-19 patients: a retrospective case-control study.
There is increased incidence of barotrauma in COVID-19 patients, probably due to disease pathology, oxygen therapy and coughing. We aimed to retrospectively compare the characteristics, associations and outcomes of COVID-19 patients with and without barotrauma in the intensive care unit (ICU). All adults admitted between October 1st and December 31st 2020 in the ICUs of a COVID-19 hospital were retrospectively analysed for presence of a 'barotrauma event' (presence of at least one of pneumothorax, pneumomediastinum, subcutaneous emphysema or bronchopleural fistula). A control group was formed by matching each case to a patient belonging to the same gender and age range from the remaining patients in the cohort, i.e., those without barotrauma. Demographic details, ICU stay details, details of oxygen therapy and ventilation, and outcomes were noted and compared. Of 827 patients, 30 patients (3.6%) developed barotrauma events. The typical patient was middle aged (median age 55.5 years) and male (73.3%). The mortality rate was significantly higher in the barotrauma group (83.3% vs. 43.3%, P < 0.001), and odds of survival decreased by 85% if barotrauma occurred (OR 0.15; 95% CI: 0.46-0.51). Patients who developed barotrauma spent a longer time on a high-flow nasal cannula (median 6.7 vs. 1.73 days, P = 0.04), and mechanical ventilation (median 9.54 vs. 0.867 days, P < 0.001), and had a longer ICU stay (median 15.5 vs. 9 days, P = 0.014). The most common event was pneumothorax (26/30). Barotrauma in the COVID-19 ICU is associated with prolonged ICU stay, higher odds of mortality and longer duration spent on mechanical ventilation and a high-flow nasal cannula. Key words: barotrauma, ICU, COVID-19, mortality, pneumothorax.


Distinct spatiotemporal distributions of the N-methyl-D-aspartate receptor channel subunit mRNAs in the mouse cervical cord.
The distribution of five N-methyl-D-aspartate (NMDA) receptor channel subunit mRNAs in the mouse spinal cord from embryonic day 13 (E13) through postnatal day 56 (P56) was semiquantitatively examined at the cervical level via in situ hybridization with subunit-specific oligonucleotide probes. Signals for the epsilon 1 subunit mRNA were restricted to the most ventral portion of the spinal cord during embryonic stages. They extended to all laminae of the spinal cord except for the lamina 2 (substantia gelatinosa) during postnatal development. A wide expression of the epsilon 2 subunit mRNA was found in the spinal gray matter from E13 through neonatal stages, but the signals became restricted to the lamina 2 by P21. No significant signals for the epsilon 3 subunit mRNA were detected in the spinal cord at any developmental stages. The epsilon 4 subunit mRNA was distributed widely in the spinal cord during embryonic and early postnatal periods but decreased nearly to background levels by P21. In contrast to the differential distribution of the epsilon subunit mRNAs, the zeta 1 subunit mRNA was found ubiquitously at each developmental stage examined. These findings suggest that the molecular organization of the epsilon subunits may be different between the dorsal horn and the remaining regions in the mature spinal cord, which provides a molecular basis for functional heterogeneity of the NMDA receptor channel. Moreover, this spatial heterogeneity might be generated through drastic alterations in the subunit composition of the channel complex during spinal cord development.


[Some characteristic features of RI-cisternography in infancy and childhood (author's transl)].
There are few reports which discussed normal RI-cisternography in infancy and childhood. The cisternograms of the children between 2 months and 13 year-old were classified under a criteria into three groups; 17 normal cases, 135 borderline cases and 77 abnormal cases. The former two groups were compared with each other and characteristic findings of RI-cisternography in infants and children were appreciated clinically. And we attempted to establish normal RI-cisternography. The characteristic findings are: 1) When the images of cisterna magna is dilated, it can not be concluded directly that the abnormality of posterior fossa are suspected. 2) The bulk flow of CSF in infancy and childhood flows faster in intracranial subarachnoid space as well as intraspinal than the flow of adults. 3) Early ventricular reflux seems to be not valuable clinically. But we would like to emphasize that the incidence of these findings are variable as children grow older. The mechanism of this phenomenon needs further investigation.


Role of PKA in the anti-Thy-1 antibody-induced neurite outgrowth of dorsal root ganglionic neurons.
Thy-1 is highly expressed in the mammalian nervous system. Our previous study showed that addition of anti-Thy-1 antibody to cultured dorsal root ganglionic (DRG) neurons promotes neurite outgrowth. In this study, we identified a novel signaling pathway mediating this event. Treatment with function-blocking anti-Thy-1 antibodies enhanced neurite outgrowth of DRG neurons in terms of total neurite length, longest neurite length, and total neurite branching points. To elucidate the possible signal transduction pathway involved, activation of kinases was evaluated by Western blotting. Transient phosphorylation of protein kinase A (PKA) and mitogen-activated kinase kinase (MEK) was induced after 15 min of anti-Thy-1 antibody treatment. Pretreatment with a PKA inhibitor (PKI) or an MEK inhibitor, PD98059, significantly decreased the neurite outgrowth response triggered by anti-Thy-1 antibody, indicating the involvement of both kinases. In addition, anti-Thy-1 antibody treatment also induced transient phosphorylation of cyclic AMP-response element-binding protein (CREB) and this effect was also blocked by a PKI or PD98059. Furthermore, the fact that PKI abolished anti-Thy-1 antibody-induced MEK phosphorylation showed that PKA acts upstream of the MEK-CREB cascade. In summary, the PKA-MEK-CREB pathway is a new pathway involved in the neurite outgrowth-promoting effect of anti-Thy-1 antibody.


Super-Resolution in Digital Breast Tomosynthesis: Limitations of the Conventional System Design and Strategies for Optimization.
Our previous work explored the use of super-resolution as a way to improve the visibility of calcifications in digital breast tomosynthesis. This paper demonstrates that there are anisotropies in super-resolution throughout the reconstruction, and investigates new motion paths for the x-ray tube to suppress these anisotropies. We used a theoretical model of a sinusoidal test object to demonstrate the existence of the anisotropies. In addition, high-frequency test objects were simulated with virtual clinical trial (VCT) software developed for breast imaging. The simulated objects include a lead bar pattern phantom as well as punctate calcifications in a breast-like background. In a conventional acquisition geometry in which the source motion is directed laterally, we found that super-resolution is not achievable if the frequency is oriented in the perpendicular direction (posteroanteriorly). Also, there are positions, corresponding to various slices above the breast support, at which super-resolution is inherently not achievable. The existence of these anisotropies was validated with VCT simulations. At locations predicted by theoretical modeling, the bar pattern phantom showed aliasing, and the spacing between individual calcifications was not properly resolved. To show that super-resolution can be optimized by re-designing the acquisition geometry, we applied our theoretical model to the analysis of new motion paths for the x-ray tube; specifically, motions with more degrees of freedom and with more rapid pulsing (submillimeter spacing) between source positions. These two strategies can be used in combination to suppress the anisotropies in super-resolution.


The Resurgence of Hallucinogen Drugs in Clinical Research.
Since the dawn of civilization, ancient cultures have utilized hallucinogens from plants and fungi in the context of religious and healing practices. Recently, their use has expanded to other cultures. Hallucinogens are natural or synthetic substances that alter the perception of reality at nontoxic doses, producing intense psychological and physiological effects. The initial research on hallucinogens began in the 1950s. However, their non-medical use, studies without proper controls, and negative social opinion resulted in legal restrictions that limited their use for clinical and preclinical research for more than two decades. A renewed interest in studying hallucinogens as potential therapeutic agents for treating different psychiatric conditions has recently re-emerged. This review summarizes the effects of main hallucinogen drugs and their therapeutic potential. Classic hallucinogens such as LSD, dimethyltryptamine, psilocin, and mescaline have chemical structures similar to serotonin and directly activate 5-hydroxy-tryptamine (5-HT2A) receptors. Ketamine is a dissociative anesthetic with antagonist effects at the glutamatergic N-methyl-D-aspartate receptor, indirectly activating 5-HT2A receptors. Ketamine has rapid antidepressant effects and reduces suicidal ideation, but its effects are short-lasting. Other hallucinogens are under study. It is necessary to continue this research with a more rigorous methodology and include studying the long-term effects of psychedelics use.


Comparative electrophysiological, functional, and histological studies of nerve lesions in rats.
The aim of this study was to establish a nerve lesion model to compare serial electrophysiological and functional outcome measures with histological findings. The relative significance of the parameters in lesions of diverse severity, the time course of recovery, and the tools for serial longitudinal studies after nerve lesions were studied in rats. We compared weekly electrophysiological and functional studies for 100 or 150 days in rats after crush or section/suture of the sciatic nerve at midthigh level. Finally, tibial nerves were taken for histology. We confirmed that recovery was faster and more complete in nerves regenerating after crush than after section, irrespective of method of evaluation. Furthermore, continuous maturational changes occurred in control nerves, and such continuous growth-related changes should be taken into account when evaluating maturational changes during nerve regeneration. A lack of correlation between evaluation methods supports that functional, morphological, and physiological parameters show different aspects of the recovery process after nerve lesions, and that these outcome measures should be included separately in therapeutic studies.


[A Report from the Front Line of New Coronavirus Treatment].
Our hospital has been at the forefront of the treatment of novel coronavirus infections in Japan, starting with patients who contracted the disease on the cruise ship"Diamond Princess", and now accepting more than 470 patients with moderate disease. Today our hospital continues to expand its dedicated beds for infected patients, and has been confronted with a variety of problems in terms of treatment system, treatment strategy, and local medical structure. In this article, we review the events that occurred on the frontline from the early days of patient admission to the hospital over a year later, through 3 phases of increased infection, and summarize as objectively as possible the impact of these events on general practice, including cancer care.


Social network and social support influence mortality in elderly men. The prospective population study of "Men born in 1914," Malmö, Sweden.
The objective of this study was to determine whether there is an association of all-cause mortality with different aspects of social network, social support, and social influence. The study sample (n = 621) was a random half of all male residents of Malmö, Sweden, born in 1914, of whom 500 (80.5%) were interviewed and examined in 1982-1983. On the basis of a model with carefully defined and well-differentiated concepts integrated in a theoretic framework of social resources, an instrument was developed to measure different aspects of social network, social support, and social influence. During the follow-up period from September 1982 to November 1987, 67 (13.4%) of the 500 participants died. In univariate analysis, a higher mortality risk was found among men with low availability of emotional support and low adequacy of social participation and among men living alone (crude relative risk = 2.3, 2.3, and 1.7, respectively). These relative mortality risks changed little after adjustments for social class, health status at baseline, cardiovascular risk factors, alcohol intake, physical activity, and body mass index in the multivariate analysis (adjusted relative mortality risk = 2.5, 2.2, and 2.0 for men with low availability of social support and low adequacy of social participation and for men living alone, respectively). These findings are consistent with the existence of a general effect of social network and social support on mortality among elderly men.


Long-lasting pigmentation more than its intensity is a reliable indicator of skin sun resistance.
The currently adopted method for predicting sun sensitivity is Fitzpatrick's classification which however is based on self-reported burning tendency and tanning ability. Determination of the individual UV susceptibility based on non-subjective parameters. Minimal erythema dose (MED), intensity and duration of pigmentation on days 5, 9 and 16 following 1 MED and the levels of the melanin marker pyrrole-2,3,5-tricarboxylic acid (PTCA) were analysed in non-red-haired subjects (50, aged 20-46 years). Phenotype groups or phototypes showed a good correlation with PTCA yields and the persistence of pigmentation on day 16, but not with MED values. MED values did not show a significant correlation with PTCA yields. On the other hand, high values on day 16 were exhibited only by subjects having PTCA values higher than 200 ng/mg. Measurement persistence of pigmentation on day 16 represents a non-invasive and easy-to-perform method to evaluate photoprotection in those individuals escaping straightforward classification based on phenotype or anamnesis.


Human bone marrow lymphocytes. Cytotoxic effector cells in the bone marrow of normal individuals.
This study was undertaken to determine the capability of lymphocytes in the bone marrow of normal individuals to mediate nonspecific killer cell functions in assays of phytohemagglutinin (PHA)-induced cellular cytotoxicity, and antibody-dependent cellular cytotoxicity (ADCC) against 51Cr-labeled chicken erythrocyte target cells. Relatively pure mononuclear cell suspensions were obtained from bone marrow aspirates in 30 normal volunteers by sucrose gradient centrifugations and from the peripheral blood of the same individuals by Hypaque-Ficoll density centrifugations. At an effector: target ratio of 10:1, the PHA-induced cellular cytotoxicity of peripheral blood was 78.8 +/- 1.3%, while that of bone marrow was not significantly less at 66 +/- 9% (P greater than 0.1). At low effector:target ratios, the ADCC of bone marrow was negligible, while at higher effector:target ratios (20:1) bone marrow ADCC was 69 +/- 3.7%, which was comparable to that of peripheral blood. The lymphocytes themselves in the mononuclear cell suspensions of both peripheral blood and bone marrow were capable of cytotoxicity activity since depletion of monocytes from the suspensions by adherence to rayon wool and G-10 Sephadex columns did not remove the cytotoxic activity. Blocking of the Fc receptor on the effector cells by the addition of aggregated gamma globulin to the cultures suppressed the ADCC but not the PHA-induced cellular cytotoxicity of both peripheral blood and bone marrow, indicating that ADCC is dependent on an Fc receptor on the effector cell in both compartments. These studies demonstrate that the bone marrow of normal humans contains populations of lymphoid cells which have highly efficient killer cell capacities. It is uncertain what portion of these cells arise in the bone marrow and what portion enter the bone marrow parenchyma as part of the recirculating lymphocyte pool. These findings have relevance in the clearer understanding of the killer cell potential of grafted human marrow, as well as the bone marrow sequestration of functionally capable lymphocyte subpopulations in disease states and during chemotherapy.


Pontibacter liquoris sp. nov. and Pontibacter vulgaris sp. nov., two novel bacteria isolated from the pit mud of Chinese liquor.
Two pink-pigmented bacterial strains, designated NBU2971T and NBU2972T, were isolated from the pit mud of a Chinese liquor. Phylogenetic analyses based on 16S rRNA gene sequences suggested that strains NBU2971T and NBU2972T formed a distinct lineage within the family Hymenobacteraceae and were closely related to members of the genus Pontibacter. 16S rRNA gene sequences revealed that strain NBU2971T showed highest similarity of 97.9 % to Pontibacter arcticus 2b14T, and strain NBU2972T showed the highest similarity of 96.9 % to Pontibacter deserti JC215T. The 16S rRNA gene sequence similarity, average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the two novel strains were 95.2, 73.8 and 19.6 %, respectively, suggesting that they represent different species. The ANI and dDDH values between two novel strains and related species of genus Pontibacter were well below the threshold limit for prokaryotic species delineation. The genomic DNA G+C contents of strains NBU2971T and NBU2972T were 51.3 and 44.5 mol%, respectively. The major cellular fatty acids of the two novel strains were iso-C15 : 0 and summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B). The major polar lipid of both novel strains was phosphatidylethanolamine. The only respiratory quinone was MK-7. Combining results of phenotypic, chemotaxonomic and genotypic data, strains NBU2971T and NBU2972T are considered to be two representatives in the genus Pontibacter, which the name Pontibacter liquoris sp. nov. and Pontibacter vulgaris sp. nov. are proposed. The type strains of the new species are NBU2971T (=KCTC 82916T=MCCC 1K06395T) and NBU2972T (=KCTC 82917T=MCCC 1K06396T), respectively.


[Pernicious anemia in a thalassemic patient - difficulties of the diagnosis].
The bone marrow aspiration, which was done in a leukopenic, hypochromic, microcytic, progressive anemic, thalassemic patient, revealed megaloblastic morphology. The low level of vitamin B12 and the reticulocytosis following the B12 supportation strenghtened the diagnosis of pernicious anemia. The set of the right diagnosis has been delayed by the fact that even in severe anemia one could not obtain the typical signs of B12 deficiency, having a hypochromic, microcytic erythrocyte morphology, due to the thalassemia minor disorder. Orv Hetil. 2018; 159(33): 1368-1371.


Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease.
This study compared the molecular lipidomic profile of LDL in patients with nondiabetic advanced renal disease and no evidence of CVD to that of age-matched controls, with the hypothesis that it would reveal proatherogenic lipid alterations. LDL was isolated from 10 normocholesterolemic patients with stage 4/5 renal disease and 10 controls, and lipids were analyzed by accurate mass LC/MS. Top-down lipidomics analysis and manual examination of the data identified 352 lipid species, and automated comparative analysis demonstrated alterations in lipid profile in disease. The total lipid and cholesterol content was unchanged, but levels of triacylglycerides and N-acyltaurines were significantly increased, while phosphatidylcholines, plasmenyl ethanolamines, sulfatides, ceramides, and cholesterol sulfate were significantly decreased in chronic kidney disease (CKD) patients. Chemometric analysis of individual lipid species showed very good discrimination of control and disease sample despite the small cohorts and identified individual unsaturated phospholipids and triglycerides mainly responsible for the discrimination. These findings illustrate the point that although the clinical biochemistry parameters may not appear abnormal, there may be important underlying lipidomic changes that contribute to disease pathology. The lipidomic profile of CKD LDL offers potential for new biomarkers and novel insights into lipid metabolism and cardiovascular risk in this disease.


Primary liver cancers in Japan.
Statistical analyses have been made by the Liver Cancer Study Group of Japan of 4031 cases of primary liver cancers diagnosed at 155 institutes during the period of Jan. 1, 1968-Dec. 31, 1977, based on the questionnaire in the form of individual file. They comprised 2411 cases of hepatocellular carcinoma, 268 of cholangiocellular carcinoma, 58 of the mixed type, 69 of hepatoblastoma, 23 of others, and 1202 cases with only clinical diagnosis. The survey and analyses mostly based on the histology-proven cases included gross anatomical and histological features of tumors, grades of anaplasia and growth patterns of tumor cells, pathology of noncancerous liver portion, frequency of accompanying cirrhosis or fibrosis, distant metastases, past history, frequency of hepatitis in the past history, frequency of positive HBsAg and anti-HBs, familial clustering of positive HBsAg tests, age distribution, subjective symptoms, objective signs, serum alpha-fetoprotein, celiac angiography findings, number of operations performed, kinds of surgical approaches made, extents of hepatic resection, prognosis in terms of survival in relation to various surgical treatments, chemotherapeutic agents used and routes of administration, prognosis as related to the accompanying parenchymal liver disease, and overall survival.


Impact of endotoxin on the expression of drug transporters in the placenta of HIV-1 transgenic (HIV-Tg) rats.
Inflammatory responses in HIV (+) patients may be exacerbated due to reports of subclinical endotoxemia and existing immune dysregulation. As inflammation has been reported to mediate changes in the expression of transporters, this could be potentiated in pregnant HIV (+) women. Similar to humans, the HIV-Tg rat model develops immune dysregulation and chronic AIDS-like conditions. Our objective was to examine the expression of placental drug transporters in HIV-Tg rats in response to low-dose endotoxin. Pregnant HIV-Tg rats or wild-type littermates (WT) were treated with low dose bacterial endotoxin 0.1mg/kg (n=8) or 0.25mg/kg (n=4-6) on GD18 and placentas were harvested 18h later. Placental and hepatic expression of transporters and cytokines were examined using qRT-PCR and Western blotting. As compared to WT, endotoxin administration increased the hepatic and placental expression of IL-6 and TNF-α to a greater extent in HIV-Tg rats (p<0.05). The placental mRNA and protein expression of Abcb1a and Slco2b1 was significantly decreased in endotoxin-treated HIV-Tg but not WT rats and downregulation of Slco4a1 mRNA was more pronounced in the HIV-Tg group (p<0.05). These changes significantly correlated with the placental expression of pro-inflammatory cytokines. Abcc3 mRNA expression was increased in the placenta of endotoxin treated WT rats only, while placental expression of Abcc1, Abcc2 and Abcc4 was not significantly affected in both WT and HIV rats. Endotoxin imposed a pronounced downregulation in the hepatic expression of Abcb1a, Abcc2, Abcc4, Abcg2, Slco1a1, Slco1b2 and Slc29a1 in both HIV-Tg and WT rats; however, Abcb1b expression was increased in HIV but not WT rats. Our results indicate that low-dose endotoxin resulted in an augmented inflammatory response in HIV-Tg rats accompanied with significant changes in the placental expression of several drug transporters. Our data suggests that subclinical endotoxemia and other co-existing infections may alter the placental transfer of drugs in the HIV population.


Genome-wide identification of Tribolium dorsoventral patterning genes.
The gene regulatory network controlling dorsoventral axis formation in insects has undergone drastic evolutionary changes. In Drosophila, a stable long-range gradient of Toll signalling specifies ventral cell fates and restricts BMP signalling to the dorsal half of the embryo. In Tribolium, however, Toll signalling is transient and only indirectly controls BMP signalling. In order to gain unbiased insights into the Tribolium network, we performed comparative transcriptome analyses of embryos with various dorsoventral pattering defects produced by parental RNAi for Toll and BMP signalling components. We also included embryos lacking the mesoderm (produced by Tc-twist RNAi) and characterized similarities and differences between Drosophila and Tribolium twist loss-of-function phenotypes. Using stringent conditions, we identified over 750 differentially expressed genes and analysed a subset with altered expression in more than one knockdown condition. We found new genes with localized expression and showed that conserved genes frequently possess earlier and stronger phenotypes than their Drosophila orthologues. For example, the leucine-rich repeat (LRR) protein Tartan, which has only a minor influence on nervous system development in Drosophila, is essential for early neurogenesis in Tribolium and the Tc-zinc-finger homeodomain protein 1 (Tc-zfh1), the orthologue of which plays a minor role in Drosophila muscle development, is essential for maintaining early Tc-twist expression, indicating an important function for mesoderm specification.


Near- to far-field characteristics of acoustic radiation through plug flow jets.
This paper reports a theoretical study of the radiation of sound through jet exhausts. It focuses on the transition from near field to far field by considering the features of the near-field solution and how these features translate to the far field. The main focus of this work is the importance in some cases of lateral waves radiating from the jet. While the presence of lateral waves has long been recognized, there has been no systematic investigation of the practical consequences of these waves in the prediction of sound propagation through round jets. The physical mechanisms involved in the generation of these waves are presented as well as the conditions under which they become significant. Another issue is the possibility of "channeled waves" inside the jet associated with strong sound radiation in the forward arc. This paper also discusses the validity of the far-field approximation when lateral waves are present. It is shown that the standard far-field approximation can be improved by adding correction terms that account for the presence of the lateral waves and channeled waves. The challenge posed to computational aeroacoustics by these near-field effects is also discussed.


Analysis of magnetic resonance signal intensity changes in the sacrococcygeal region of patients with uterine fibroids treated with high intensity focused ultrasound ablation.
Objective: To evaluate the magnetic resonance (MR) signal intensity changes in the sacrococcygeal region of patients with uterine fibroids treated with high intensity focused ultrasound (HIFU).Materials and Methods: Two hundred and sixty-seven patients with uterine fibroids treated with HIFU between January and December 2016 were retrospectively reviewed. All patients underwent enhanced pre- and post-HIFU MRI. Multivariate analysis was used to assess the relationship between the factors and the signal intensity changes in the sacrum and the soft tissue adjacent to the sacrum.Results: Among the 267 patients, 122 (46%) had MR signal intensity changes in the sacrum and/or the soft tissue adjacent to the sacrum after HIFU. Multivariate analysis showed that the position of the uterus, the distance from the dorsal side of the fibroid to the sacrum, and the ablation efficiency were significantly correlated with MR signal intensity changes in the sacrum and the soft tissue adjacent to the sacrum. Further analysis showed a significant relationship between the location of the MR signal intensity changes and uterine size, the enhancement degree of the uterus. Leg pain was only seen in patients with MR signal intensity changes both in the sacrum and the soft tissue adjacent to the sacrum.Conclusions: The location of the uterus, the distance between the dorsal side of the fibroids to the sacrum, and ablation efficiency have a significant relationship with the MR signal intensity changes. The size of the uterus and the degree of enhancement are related to the locations of MR signal changes.


Time pressure and the application of decision rules: choices and judgments among multiattribute alternatives.
The effects of time pressure on decisions and judgments were studied and related to the use of different decision rules in a multiattribute decision task. The decision alternatives were students described by their high school grades in Swedish, Psychology and Natural Science. The subjects were asked to choose the student they thought would be most able to follow a university program and graduate as a school psychologist. On the basis of earlier findings using the same kind of decision task (Svenson et al., 1990) it was hypothesised that subjects under time pressure would prefer candidates having the maximum grade across all attributes to a greater extent than subjects under no time pressure. Furthermore, it was hypothesised that subjects under time pressure would also focus more on the most important attribute and choose the alternatives being best on that attribute. The results supported these hypotheses.


Islet Amyloid Polypeptide Promotes Amyloid-Beta Aggregation by Binding-Induced Helix-Unfolding of the Amyloidogenic Core.
Amyloid aggregation of amyloid-beta (Aβ) and islet amyloid polypeptide (IAPP) is associated with Alzheimer's disease (AD) and type-2 diabetes (T2D), respectively. With T2D being the risk factor for AD and the ability of IAPP to cross the blood-brain barrier, the coaggregation of Aβ and IAPP has been explored to understand the cross-talk between the two diseases. Recent studies demonstrated that soluble IAPP could significantly accelerate the aggregation of Aβ while preformed amyloids of IAPP were poor "seeds" for Aβ aggregation. Here, we apply all-atom discrete molecular dynamics simulations to investigate possible molecular mechanisms for the accelerated coaggregation of IAPP and Aβ42 comparing to Aβ42 aggregation alone, which was confirmed by the complementary thioflavin-T fluorescence assay. Our simulation results suggest that peptides in the mixture tend to form heterodimers as the first step toward their coaggregation. Strong interpeptide interactions with IAPP in the heterodimer shift the helical conformation of Aβ42 in its amyloidogenic central hydrophobic core, residues 16-22 (Aβ16-22), to the extended conformation ready to form β-sheets. Our study suggests that the unfolding of Aβ16-22 helix contributes to the aggregation free-energy barrier and corresponds to the rate-limiting conformational change for Aβ42 aggregation. Therefore, we propose that soluble IAPP promotes the aggregation of Aβ42 by binding-induced conformational change of Aβ42 in its amyloidogenic core and thus reduced aggregation free-energy barrier.


Weight change, obesity and risk of prostate cancer progression among men with clinically localized prostate cancer.
Obesity is associated with an increased risk of fatal prostate cancer. We aimed to elucidate the importance and relevant timing of obesity and weight change for prostate cancer progression. We identified 5,158 men diagnosed with localized prostate cancer (clinical stage T1/T2) from 1986 to 2012 in the Health Professionals Follow-up Study. Men were followed for biochemical recurrence and lethal prostate cancer (development of distant metastasis or prostate cancer-specific mortality) until 2012. Cox regression estimated hazard ratios (HRs) for body mass index (BMI) at age 21, BMI at diagnosis, "long-term" weight change from age 21 to diagnosis and "short-term" weight change over spans of 4 and 8 years preceding diagnosis. Because weight, weight change and mortality are strongly associated with smoking, we repeated analyses among never smokers only (N = 2,559). Among all patients, neither weight change nor BMI (at age 21 or at diagnosis) was associated with lethal prostate cancer. Among never smokers, long-term weight gain was associated with an increased risk of lethal disease (HR for gaining >30 pounds vs. stable weight [±10 pounds] 1.59, 95% CI, 1.01-2.50, p-trend = 0.06). Associations between weight change, BMI and lethal prostate cancer were stronger for men with BMI ≥ 25 at age 21 compared to those with BMI < 25. Weight change and obesity were not associated with an increased risk of biochemical recurrence. Our findings among never smoker men diagnosed with localized prostate cancer suggest a positive association between long-term weight gain and risk of lethal prostate cancer. Metabolic changes associated with weight gain may promote prostate cancer progression.


Increased hospitalizations for asthma among children in the Washington, D.C. area during 1961-1981.
Hospital admissions for childhood asthma to three university affiliated hospitals in the Washington D.C. area (Children's Hospital National Medical Center, CHNMC, Prince George's General Hospital, PGGH, and Holy Cross Hospital, HCH) for the period 1961-1981 increased at least three to 18 fold. The over-all population of children less than or equal to 14 years of age increased, at most, only 1.5 fold by 1970, and thereafter decreased gradually until the end of the study. This increase in pediatric asthma hospitalizations has occurred despite significant improvements in the ambulatory management of the asthmatic child. In particular, the amount of specific anti-asthmatic medication prescribed for these patients has grown markedly. The increased hospitalization is most likely due to an increase in the occurrence of severe asthma in children, particularly black children.


Another Round of "Clue" to Uncover the Mystery of Complex Traits.
A plethora of genetic association analyses have identified several genetic risk loci. Technological and statistical advancements have now led to the identification of not only common genetic variants, but also low-frequency variants, structural variants, and environmental factors, as well as multi-omics variations that affect the phenotypic variance of complex traits in a population, thus referred to as complex trait architecture. The concept of heritability, or the proportion of phenotypic variance due to genetic inheritance, has been studied for several decades, but its application is mainly in addressing the narrow sense heritability (or additive genetic component) from Genome-Wide Association Studies (GWAS). In this commentary, we reflect on our perspective on the complexity of understanding heritability for human traits in comparison to model organisms, highlighting another round of clues beyond GWAS and an alternative approach, investigating these clues comprehensively to help in elucidating the genetic architecture of complex traits.


A helpline for patients with chronic dermatological conditions.
A telephone line was set up for patients with chronic dermatological diseases in response to patients' concerns about having a point of contact for advice and for more appropriate and timely access to care when they needed to be seen. The aims were firstly to improve the quality of care and empower patients by providing advice and support with a safety net for those discharged from the authors' service. The second aim was to increase efficiency by reducing unnecessary return appointments. An audit was undertaken to evaluate the telephone service. This showed that patients were reassured that they could access the service according to their needs. There was a high level of satisfaction with the initiative and the advice received. The data also showed that there was a significant improvement in the ratio of new outpatient slots to return appointment slots and waiting times for a first appointment.


Cholecystokinin synthesizes and secretes leptin in isolated canine gastric chief cells.
It is well recognized that a product of obese (ob) locus and body weight control hormone, leptin, acts on both short-term satiety for meal-induced termination of food intake (gastric phase) and long-term satiety for energy expenditure via the hypothalamus. The considerable sources of leptin are chief cells for gastric phase and adipocytes for the long-term satiety. The objective of this study was to demonstrate if CCK enhances leptin synthesis and secretion in isolated canine gastric chief cells. Confocal immunofluorescence studies showed that the CCK-A receptor and leptin were colocalized in the endoplasm. Western blotting demonstrated that canine chief cells expressed the leptin peptide and its protein level was enhanced by CCK treatment. An ELISA further showed that CCK dose-dependently secreted leptin from isolated canine chief cells. This was reproduced by the high-affinity CCK-A receptor agonist, CCK-OPE. These results indicate that canine chief cells synthesize and secrete leptin in response to CCK via the high-affinity state of the CCK-A receptor.


[A new therapeutic scene in the treatment of the chronic hepatitis for virus C].
The need of new alternatives for the treatment of the chronic hepa - titis C, the appearance of the new antiviral ones that act directly on the cycle of replicación of the virus C, so called antiviral agents, they have never supposed a spectacular advance in the increase of the rates of treatment, so much for the patients before treated or naive. This new stage of the treatment is going to be, undoubtedly, more complex and, for this reason, a still major specialization will need if it is necessary to obtain an ideal managing of the patients. In addition, that these new medicaments will carry a significant increase of the expense associated with this pathology, key circumstance in the frame of economic context and of difficulty in the sustainability that Spanish public suffers the sanitary system, the individualization and the establishment of the factors that can predict the maximum benefit of every type of therapy turns out to be priority. The predictive factors of response that can affect the capture of decisions clinical practice are the stadium of fibrosis, the favorable genotype of the IL28B and the attainment of viral rapid response. The undoubted impact, so much welfare as pharmacoeconomic that the arrival of boceprevir and telaprevir will have in the hospitable centers forces us to the optimization and consensus in the use of these medicaments and to the exigency of obtaining the maximum of answers of the same ones. The latter aspect is very tied to the accomplishment of a followup pharmaceutical individualized and of quality, based on a model of Pharmaceutical Care centred on basic props as the involution of the adherence, given the additional complexity that add the new medicaments, the identification, prevention and managing of the adverse effects inherent in the triple therapy. Besides it, they were turning out to be key the establishment of new strategies of management farmacoeconomic of this type of based therapies in clinical results and with a multidisciplinary participation of all the professionals of the health involved in the managing of this therapy.


A model for the prediction of digoxin-drug interactions at the renal tubular cell level.
Digoxin-drug interactions are relatively common causes of digitalis toxicity. Recently, the clinical importance of the renal tubular secretion of digoxin has been proven by documenting drug interactions at this level. The authors describe a model using cultured renal tubular cell monolayers that can be used to predict drug interactions with the cardiac glycoside. This model accurately documents known clinical digoxin interactions such as those with verapamil and propafenone. The common feature of these interactions is that they involve P-glycoprotein substrates (e.g., digoxin, vincristine, vinblastine) or inhibitors (e.g., quinidine, cyclosporine). In the case of the newly described interaction of digoxin with itraconazole, the model preceded the emergence of clinical cases.


Analysis of hallux valgus angles automatically extracted from 3D foot scans taken in North America, Europe, and Asia.
The forefoot is the foot part most affected by ill-fitting shoes. Footwear fitting considers the measurements of length, width, and arch length. Toe shape has not yet been used in sizing feet and fitting shoes. This study aims to investigate the variation in toe shape, as measured by the hallux valgus angle. An automatic and reproducible hallux valgus angle measuring method using 3D foot scans with no palpation markers is proposed and applied to about half a million samples collected across North America, Europe, and Asia. The measuring method is robust and can detect the medial contour along the proximal phalanx even in extreme cases. The hallux valgus angle has a normal distribution with long tails on both sides in the general population. Large dispersions of HVA values were observed for both genders and in all three geographical regions. Practitioner summary: The hallux valgus angle has a broad distribution in the general population. Females have larger hallux valgus angles than males, and people from Asia have larger hallux valgus angles than people from North America and Europe. Shoe toe boxes should be designed to fit the actual shapes of shoppers' toes. The proposed method for measuring HVA opens a new opportunity to study the causal relationship between shoe wearing habits and HVA on a large scale.


Mortality Rate of House Flies (Diptera: Muscidae) Exposed to Insecticidal Granular Fly Baits Containing Indoxacarb, Dinotefuran, or Cyantraniliprole.
The mortality rate of a field population of house fly (Musca domestica L.) was determined for a granular fly bait containing the active ingredient indoxacarb, which was compared to two commercially available granular fly baits containing either dinotefuran or cyantraniliprole. Indoxacarb was applied at three different application rates 0.498, 0.986, and 1.972 g/m2 (low, medium, and high). Time to 50% mortality was fastest for dinotefuran (5.7 h) and slowest for the low application rate of indoxacarb (10.3 h). Time to 90% mortality was fastest for the high application rate of indoxacarb (27.7 h) and slowest for dinotefuran (51.0 h) and cyantraniliprole (45.9 h). Among the three indoxacarb application rates, the high rate reached both 50 and 90% fly mortality significantly faster than the low rate. The medium rate did not significantly differ from either the high or low application rates. Dinotefuran bait produced greater fly mortality than all other treatments at 30-min post-exposure, with mortality for remaining baits exceeding controls by 3- to 6-h post-exposure. All insecticidal baits produced similar fly mortality by 6-h post-exposure and >94% fly mortality by 96-h post-exposure, indicating that each may be effective in a fly management program. Flies consumed a similar amount of the indoxacarb (regardless of application rate) and dinotefuran baits, but consumed less of the cyantraniliprole bait, suggesting a feeding irritancy or toxicity effect manifested during consumption. Nevertheless, flies consumed enough cyantraniliprole bait to cause mortality similar to other baits by 6-h post-exposure.


Altered neurotrophic factors' expression profiles in the nucleus of the solitary tract of spontaneously hypertensive rats.
Our previous findings suggest that the nucleus of the solitary tract (NTS), a pivotal region for regulating the set point of arterial pressure, exhibits abnormal inflammation in pre-hypertensive and spontaneously hypertensive rats (SHRs), with elevated anti-apoptotic and low apoptotic factor levels compared with that of normotensive Wistar-Kyoto (WKY) rats. Whether this chronic condition affects neuronal growth and plasticity in the NTS remains unknown. To unveil the characteristics of the neurodevelopmental environment in the NTS of SHRs, we investigated the expression of neurotrophic factors transcripts in SHRs. RT(2) Profiler PCR Array targeting rat neurotrophins and their receptors was used to screen for differentially expressed transcripts in the NTS of SHRs compared to that of WKY rats. Protein expression and physiological functions of some of the differentially expressed transcripts were also studied. Gene and protein expressions of glial cell line-derived neurotrophic factor family receptor alpha-3 (Gfrα-3) factor were both upregulated in the NTS of adult SHRs. Gene expressions of corticotropin-releasing hormone-binding protein (Crhbp), interleukin-10 receptor alpha (Il-10ra) and hypocretin (Hcrt) were downregulated in the NTS of adult SHRs. The Gfrα-3 transcript was increased and the Hcrt transcript was decreased in the NTS of young pre-hypertensive SHRs, suggesting that these profiles are not secondary to hypertension. Moreover, microinjection in the NTS of hypocretin-1 decreased blood pressure in adult SHRs. These results suggest that altered neurotrophic factors transcript profiles may affect the normal development and function of neuronal circuitry that regulates cardiovascular autonomic activity, thereby resulting in manifestations of neurogenic hypertension in SHRs.


Xenogeneic collagen matrix with coronally advanced flap compared to connective tissue with coronally advanced flap for the treatment of dehiscence-type recession defects.
For root coverage therapy, the connective tissue graft (CTG) plus coronally advanced flap (CAF) is considered the gold standard therapy against which alternative therapies are generally compared. When evaluating these therapies, in addition to traditional measures of root coverage, subject-reported, qualitative measures of esthetics, pain, and overall preferences for alternative procedures should also be considered. This study determines if a xenogeneic collagen matrix (CM) with CAF might be as effective as CTG+CAF in the treatment of recession defects. This study was a single-masked, randomized, controlled, split-mouth study of dehiscence-type recession defects in contralateral sites; one defect received CTG+CAF and the other defect received CM+CAF. A total of 25 subjects (8 male, 17 female; mean age: 43.7 +/- 12.2 years) were evaluated at 6 months and 1 year. The primary efficacy endpoint was recession depth at 6 months. Secondary endpoints included traditional periodontal measures, such as width of keratinized tissue and percentage of root coverage. Subject-reported values of pain, discomfort, and esthetic satisfaction were also recorded. At 6 months, recession depth was on average 0.52 mm for test sites and 0.10 mm for control sites. Recession depth change from baseline was statistically significant between test and control, with an average of 2.62 mm gained at test sites and 3.10 mm gained at control sites for a difference of 0.4 mm (P = 0.0062). At 1 year, test percentage of root coverage averaged 88.5%, and controls averaged 99.3% (P = 0.0313). Keratinized tissue width gains were equivalent for both therapies and averaged 1.34 mm for test sites and 1.26 mm for control sites (P = 0.9061). There were no statistically significant differences between subject-reported values for esthetic satisfaction, and subjects' assessments of pain and discomfort were also equivalent. When balanced with subject-reported esthetic values and compared to historical root coverage outcomes reported by other investigators, CM+CAF presents a viable alternative to CTG+CAF, without the morbidity of soft tissue graft harvest.


[Granule-accumulation in VERO cells used for determination of antitoxin titration by micro cell culture method: II. Nature of granules and influence on the potency testing of diphtheria toxoid].
Accumulation of granules occurs in VERO cells when mouse serum was added in high concentration. The nature of the granule and influence of the granule-accumulation on the potency testing of diphtheria antitoxin were studied. The concentration of triglyceride in VERO cells increased 15 folds after 24 hours of incubation by the addition of undiluted mouse serum. Kinetical study of the increase of triglyceride and electron microscope observation suggested that the accumulated granules might be oil droplets with an average diameter of 0.27 micron. The end point reaction of neutralization of diphtheria toxin by the standard antitoxin was analyzed by the addition of mouse serum to the micro cell culture using VERO cells. The mean values of the end point reactions in the cell cultures added with high concentrations of mouse serum were -2.324, -2.338 and -2.346, while that of the control group was -2.343. The variance of these mean values in the experiment and control groups were 0.0017, 0.0024, 0.0017 and 0.0021, respectively. A test of homogeneity of variance for these data showed no significant difference between them. Furthermore, antitoxin titer of the serum specimens of mouse immunized with diphtheria toxoids determined by the micro cell culture method were compared with that obtained by rabbit skin test; a high correlation between the antitoxin titers by the two techniques was recognized. The results were comparable with those of guinea-pig sera. From these results it is evident that little influence, if any, was observed in the potency testing of diphtheria antitoxin using VERO cells, in spite of the remarkable accumulation of granules.


Stormorken Syndrome Caused by a Novel STIM1 Mutation: A Case Report.
Objective: To identify the gene mutation of Stormorken syndrome and review the published Stromal Interaction Molecule 1 (STIM1) mutation phenotype. Methods: We described the clinical and molecular aspects of a Chinese female with Stormorken syndrome by laboratory tests, muscle biopsies, and genetic analysis. We used this information to summarize all the mutation sites reported in the literature. We also reviewed the clinical features of published cases with a gain of function mutations of STIM1. Results: A 12-year-old Chinese female presented with skin purpura in the lower limbs and stroke-like episodes. Muscle biopsy and microscopic examination revealed atrophy in her skeletal muscle. Genetic analysis identified a novel heterozygous missense mutation, a c.1095G>C transition (NM_003156.3), which caused a p.K365N amino acid substitution in the protein and affected a STIM1-orai1-activation region (SOAR). Conclusions: The novel variant c.1095G>C transition (NM_003156.3) was located in the SOAR, which expands the phenotypic spectrum of STIM1 variants in human disorders and may define the molecular basis of Stormorken syndrome.


Rapidly deteriorating course in Dutch hereditary spastic paraplegia type 11 patients.
Although SPG11 is the most common complicated hereditary spastic paraplegia, our knowledge of the long-term prognosis and life expectancy is limited. We therefore studied the disease course of all patients with a proven SPG11 mutation as tested in our laboratory, the single Dutch laboratory providing SPG11 mutation analysis, between 1 January 2009 and 1 January 2011. We identified nine different SPG11 mutations, four of which are novel, in nine index patients. Eighteen SPG11 patients from these nine families were studied by means of a retrospective chart analysis and additional interview/examination. Ages at onset were between 4 months and 14 years; 39% started with learning difficulties rather than gait impairment. Brain magnetic resonance imaging showed a thin corpus callosum and typical periventricular white matter changes in the frontal horn region (known as the 'ears-of the lynx'-sign) in all. Most patients became wheelchair bound after a disease duration of 1 to 2 decades. End-stage disease consisted of loss of spontaneous speech, severe dysphagia, spastic tetraplegia with peripheral nerve involvement and contractures. Several patients died of complications between ages 30 and 48 years, 3-4 decades after onset of gait impairment. Other relevant features during the disease were urinary and fecal incontinence, obesity and psychosis. Our study of 18 Dutch SPG11-patients shows the potential serious long-term consequences of SPG11 including a possibly restricted life span.