Introduction of hospital quality measures may lead to a temporary decrease in patient outcomes.
To analyse the impact of hospital quality indicators on hip fracture mortality in Israel. A retrospective observational study. Data were collected on all patients aged ≥65 years with an isolated hip fracture in the years 2010-2016 from the Israel's National Trauma Registry. These data were then cross checked with information on co-morbidities and medication intake from the Clalit medical fund. All successfully matched patients constituted the study population. The main outcome measures were in-hospital and 1-year mortality. Trend analysis of surgery on hip fractures within 48 h of hospitalisation (referred to as early hip fracture surgeries) and mortality was performed. The introduction of the proportion of early hip fracture surgeries as an official quality parameter in 2013 was considered an intervention. The proportion of early hip fracture surgeries continuously increased during the study period and, after the introduction of the quality measure, a significant increase in the uniformity of practice among hospitals was observed. The mortality trend was not related to the early surgeries trend, with a sharp upward spike detected in 2014, followed by a gradual return to previous levels in the subsequent years. The analysis has shown that when adjusting for demographic factors and co-morbidity, both in 2010-2013 and in 2015-2016, a clear benefit in survival existed for patients who were operated on within the first 48 h. In 2014, which was the first year of open publication of achieved quality measures reported in the media, no such benefit was found. Even when an improvement in a promoted practice is achieved, its positive impact on clinical outcomes may be delayed, possibly indicating the need for a learning period.


Dual-specificity MAP kinase phosphatases (MKPs) and cancer.
There are ten mitogen-activated protein kinase (MAPK) phosphatases (MKPs) that act as negative regulators of MAPK activity in mammalian cells and these can be subdivided into three groups. The first comprises DUSP1/MKP-1, DUSP2/PAC1, DUSP4/MKP-2 and DUSP5/hVH-3, which are inducible nuclear phosphatases. With the exception of DUSP5, these MKPs display a rather broad specificity for inactivation of the ERK, p38 and JNK MAP kinases. The second group contains three closely related ERK-specific and cytoplasmic MKPs encoded by DUSP6/MKP-3, DUSP7/MKP-X and DUSP9/MKP-4. The final group consists of three MKPs DUSP8/hVH-5, DUSP10/MKP-5 and DUSP16/MKP-7 all of which preferentially inactivate the stress-activated p38 and JNK MAP kinases. Abnormal MAPK signalling will have important consequences for processes critical to the development and progression of human cancer. In addition, MAPK signalling also plays a key role in determining the response of tumour cells to conventional cancer therapies. The emerging roles of the dual-specificity MKPs in the regulation of MAPK activities in normal tissues has highlighted the possible pathophysiological consequences of either loss (or gain) of function of these enzymes as part of the oncogenic process. This review summarises the current evidence implicating the dual-specificity MKPs in the initiation and development of cancer and also on the outcome of treatment.


Follicular unit transplantation: 2005.
The recognition that the follicular unit is a discrete, anatomic and physiologic entity, and that preserving it through stereomicroscopic dissection is the best way to ensure the naturalness of the restoration, has brought hair transplantation into the twenty-first century. Issues yet to be resolved include determining the maximum density and number of grafts that can be used safely in a single session, deciding whether it is preferable to premake recipient sites or immediately place grafts into sites as they are made, and defining the precise role of follicular unit extraction. The essence of providing the best care for patients rests on proper patient selection, establishing realistic expectations, and using nonsurgical management for young persons who are just starting to thin.


Predictive model for the growth kinetics of Staphylococcus aureus in raw pork developed using Integrated Pathogen Modeling Program (IPMP) 2013.
A predictive model was performed to describe the growth of Staphylococcus aureus in raw pork by using Integrated Pathogen Modeling Program 2013 and a polynomial model as a secondary predictive model. S. aureus requires approximately 180 h to reach 5-6 log CFU/g at 10 °C. At 15 °C and 25 °C, approximately 48 and 20 h, respectively, are required to cause food poisoning. Predicted data using the Gompertz model was the most accurate in this study. For lag time (LT) model, bias factor (Bf) and accuracy factor (Af) values were both 1.014, showing that the predictions were within a reliable range. For specific growth rate (SGR) model, Bf and Af were 1.188 and 1.190, respectively. Additionally, both Bf and Af values of the LT and SGR models were close to 1, indicating that IPMP Gompertz model is more adequate for predicting the growth of S. aureus on raw pork than other models.


The removal from plasma of chylomicrons and remnants is reduced in heterozygous familial hypercholesterolemia subjects with identified LDL receptor mutations: study with artificial emulsions.
Chylomicron remnants bind to both their specific receptors (LRP) and to the LDL receptor (LDLR) in the liver. There is controversy whether disturbances of chylomicron metabolism occur in subjects with familial hypercholesterolemia (FH). The aim of this study was to evaluate whether there are defects on the removal from plasma of chylomicrons and their remnants in heterozygous FH patients with determined LDLR mutations. We studied 20 heterozygous FH patients (43.2±12 years old, 60% males) and 50 normolipidemic subjects matched for age and gender. FH subjects were not in use of LDL-lowering drugs for at least 6 weeks. The removal from plasma of chylomicrons and their remnants was measured by isotopic decay after venous injection of a chylomicron-like emulsion radiolabeled with (14)C-cholesteryl ester ((14)C-CE) and (3)H-triolein ((3)H-TO). These track respectively removal from plasma of chylomicrons and remnants and lipolysis. There was a significant reduction in the fractional catabolic rates (FCR in h(-1)) of (14)C-CE in FH in comparison with normolipidemics: 0.048 (1.46.10(-7); 0.57) vs. 0.71(0.049; 1.62), [median (25th-75th percentile)], p=0.003. No differences were found in FCR of (3)H-TO between FH and controls, respectively 1.62 (1.02; 2.331) and 1.914 (1.34; 2.878), p=0.405. In conclusion heterozygous FH subjects had a significant decrease on the removal from plasma of chylomicrons and their remnants compared with normolipidemics.


The influence of selected water quality parameters on the decay rate and exoenzymatic activity of detritus of Nymphaea alba L. floating leaf blades in laboratory experiments.
A chemostat study was conducted to investigate the influence of water quality parameters related to acidification processes on the decomposition of floating leaves of Nymphaea alba L. HCO inf3sup- and total Al concentration and pH influenced the decay rate. The activity of four cell-wall decaying exoenzymes was measured in the detritus. The activity of two types of pectic enzyme and xylanase was low under acid conditions. Cellulase activity was little affected. The exoenzyme activity seemed to be influenced by the pH of the water within the detritus. Inhibition of pectic enzymes under acid conditions may be an important factor causing the slow decay of macrophyte remains in acid waters.


Changes in vertebral artery blood flow following normal rotation of the cervical spine.
Extreme rotation of the cervical spine may cause compromised vertebral artery (VA) blood flow. This is of particular interest to manual therapists because of the potential risks associated with these movements. The question is whether the decreased blood flow is significant and therefore likely to cause vertebrobasilar insufficiency/ischemia (VBI) and whether contralateral and ipsilateral rotations are equally affected. Several studies measuring VA blood flow have been reported. However, different parts of the VA were studied, in small samples of normal subjects and patients over a wide range of ages. Hence, the results are controversial. To investigate intracranial VA blood flow in normal male subjects and female subjects, aged 20 to 30 years, in neutral and maximally rotated cervical spinal positions. Transcranial Doppler sonography was used to measure intracranial VA blood flow, with the cervical spine in neutral and then rotated maximally to the left and later to the right. The sample consisted of 60 male subjects and 60 female subjects (240 VAs). Comparisons between the neutral and rotated head positions were made within and between the groups. There was a significant decrease (P =.001) in intracranial VA blood flow following cervical spine rotation, irrespective of side but greater on the contralateral side, in the total sample and in male subjects. Female subjects had a significantly higher blood flow than male subjects, and although they showed a significant decrease with contralateral rotation, there was no significant difference in blood flow on the ipsilateral side. Maximal rotation of the cervical spine may significantly affect vertebral artery blood flow, particularly when used in the treatment of patients with underlying vascular pathology.


Initial human myeloid/dendritic cell progenitors identified by absence of myeloperoxidase protein expression.
Myeloperoxidase (MPO) represents an early-appearing and highly reliable intracellular myeloid lineage marker molecule. MPO protein can be detected in a subset of human hematopoietic bone marrow progenitor cells and in granulomonopoietic (GM) cells. However, other myeloid-related cell types such as epidermal Langerhans-type dendritic cells (LC) lack MPO. Therefore, human myeloid progenitors might be subdivided based on MPO protein expression into functional subsets. Here we identified two consecutive myelopoietic cell stages, i.e., early myeloid progenitors that lack MPO, as well as their immediate MPO+ progeny. MPO- myeloid progenitors possess previously described granulomonocyte (GM) progenitor-associated cell-surface characteristics (CD34+CD45RA+CD13+lin-). They are specifically recruited and can be expanded in cultures of CD34+ cord blood cells in response to early-acting hematopoietic cytokines. Furthermore, cell fractions enriched in MPO- myeloid progenitors efficiently developed along Langerhans-type dendritic cell (LC) and granulomonocytic (GM) lineages, whereas progeny enriched in MPO+ cells showed diminished LC potential. In line with this, peripheral blood progenitors, known to possess LC differentiation potential, lacked MPO expression. We conclude that differential expression of MPO therefore further characterizes cells with myeloid or LC potential.


Number of genomic imbalances correlates with the overall survival for adrenocortical cancer in childhood.
Adrenocortical tumours (ACT) in children are rare and, if malignant, often associated with poor prognosis. Relevant cytogenetic factors for prognosis are hardly available. We analysed 14 adrenocortical cancers (ACC) of children by comparative genomic hybridisation (CGH). The total number of genomic imbalances ranged from 1 to 17 in individual tumour samples. The most common imbalances were +1q (57%), +12p (50%), +12q (50%), +1p (43%), +7q (42%), +9q (42%), +15q (42%), and -4q (57%), -11q (57%), -4p (42%), and -16q (42%). The median number of genomic changes was 5.5 (n = 8) in pT1-pT2 and 15.5 (n = 6) in pT3-pT4 tumours. The median number was 4 in the eight patients, who remain in remission more than 51 months and 15.5 in the six patients, who have died from the disease within 44 months. Moreover, all seven patients with less than 10 individual imbalances were in remission (median follow-up 72 months), while all but one patient with 10 and more individual imbalances (n = 7) have died from the disease (median survival time 30 months). Comparison of the data from children and adults revealed characteristic differences. Gain of 1p and loss of 4p, 4q and 16q are frequent in childhood and rare in adults. Inversely, loss of 1p is rare in childhood but frequent in adult ACT. The number of CGH imbalances appeared to have a predictive value for overall survival in paediatric ACC.


Conversion of sustained into nonsustained ventricular tachycardia during therapy assessment by programmed ventricular stimulation: criterion for a positive drug effect?
Serial electropharmacologic testing using up to 11 different antiarrhythmic drugs was performed in 130 consecutive patients (107 men, 23 women, ages 56 +/- 12) with inducible sustained ventricular tachycardia (VT). After 4 +/- 2.3 drug tests, complete suppression of VT inducibility (defined as less than 6 consecutive beats, mean 1.4 +/- 1.6) was achieved in 86 patients (66%), whereas in 44 patients (34%) nonsustained VTs (greater than or equal to 6 consecutive beats, less than 30 seconds in duration) were still inducible. There was no statistical difference between both groups regarding age, sex, underlying heart disease, ejection fraction or entry arrhythmia. After a mean follow-up period of 19 +/- 17 months, 24 patients (18%) had died, 8 (6%) suddenly. Eight patients (6%) experienced recurrent sustained VT. Symptomatic recurrences (sudden death or VT) occurred in 10 (11%) and 6 patients (13%, difference not significant), respectively. Probability of arrhythmia-free survival was comparable for patients with 0 to 5, 6 to 10, 11 to 15 and 16 to 32 inducible ventricular complexes with discharge medication. The negative predictive value of electropharmacologic drug testing was about 89%, irrespective of the maximal number of inducible complexes used for the definition of a negative test result. It is therefore concluded that conversion of sustained into nonsustained VT during therapy assessment by programmed ventricular stimulation indicates a positive drug effect.


Diurnal mice (Mus musculus) and other examples of temporal niche switching.
Examples are presented of nocturnal animals becoming diurnal or vice versa as a result of mutations, genetic manipulations, or brain lesions. Understanding these cases could give insight into mechanisms employed when switches of temporal niche occur as part of the life cycle, or in response to circumstances such as availability of food. A two-process account of niche switching is advocated, involving both a change in clock-controlled outputs and a change in the direct response to light (i.e. masking). An emerging theme from this review is the suggestion that retinal inputs have a greater role in switching than suspected previously.


Individual and Collective Positive Health Behaviors and Academic Achievement Among U.S. High School Students, Youth Risk Behavior Survey 2017.
We examined associations between academic grades and positive health behaviors, individually and collectively, among U.S. high school students. Cross-sectional study design. Data were from the 2017 national Youth Risk Behavior Survey. Response rates were 75% for schools, 81% for students, and 60% overall (n = 14,765 students). Youth in grades 9th-12th. We focused on youth behaviors that can prevent or delay the onset of chronic health conditions. Seven dietary, 3 physical activity, 2 sedentary screen time, and 4 tobacco product use behaviors were assessed. Variables were dichotomized (0/1) to indicate that a score was given to the positive health behavior response (e.g.,, did not smoke cigarettes = 1). A composite score was created by summing each positive health behavior response among 16 total health behaviors. Multivariable logistic regression analyses for each individual health behavior, and a multivariable negative binomial regression for the composite score, were conducted with self-reported academic grades, controlling for sex, grade in school, race/ethnicity, and body mass index (BMI) categories. Controlling for covariates, students who reported mostly A's had 2.0 (P < .001) more positive health behaviors; students who reported mostly B's had 1.3 (P < .001) more positive health behaviors; and students who reported mostly C's had .78 (P < .001) more positive health behaviors, compared to students who reported mostly D's/F's. Higher academic grades are associated with more positive individual and cumulative health behaviors among high school students. Understanding these relationships can help inform efforts to create a healthy and supportive school environment and strive for health equity.


Densitometric measurements of C bands of chromosomes 1, 9, 16, and Y in leukemic and preleukemic disorders.
Fifty-six patients with blood disorders (23 with chronic myeloid leukemia, 14 with acute myeloblastic leukemia, seven with acute lymphoblastic leukemia, one with chronic lymphocytic leukemia, and 11 with preleukemia states) were studied. A quantitative and objective method of C band length analysis with well-matched controls was used. The C bands of chromosome pairs 1, 9, and 16 presented a normal distribution that was similar in patients and controls, whereas the Y chromosome presented an abnormal distribution. Smaller C bands in 1qh and higher indexes of intrapair heteromorphism in pairs 1 and 9 were detected in the CML group; the group of acute leukemias (myeloblastic and lymphoblastic) presented a smaller index only in pair 1qh. No other differences in length, heteromorphism, inversion frequency, or sex were detected.


Importance of subtyping in psychopharmacogenetic studies.
Research on the importance of genetic and environmental risk factors (multifactorial) in the etiology of mental disorders and substance use disorders (alcoholism) is now growing rapidly. Biological and psychological studies in this field should include basic concepts of medical genetics and take heterogeneity (multidimensionality) of mental disorders into account. One of the best means to cope with heterogeneity is to redefine the diagnostic phenotype at different levels: biochemical, behavioral, familial. Data are presented where the introduction of different quantitative definitions of the phenotype and their analysis by multivariate technics are used for better understanding of alcoholic disorders.


Comparison of the inhibition of deoxynivalenol and T-2 toxin on bovine and porcine platelet function.
A platelet model system has been used to investigate the inhibitory effects of deoxynivalenol (DON, vomitoxin) and T-2 toxin, alone and in combination. In both bovine and porcine systems, the most dramatic effect observed was the instability in the platelet aggregates formed in the presence of the mycotoxins. Bovine platelets were more sensitive to the inhibitory effects of both of the mycotoxins than porcine platelets and in both species T-2 toxin was a more effective platelet inhibitor than DON. The mycotoxins may inhibit platelet function by a similar mechanism since an additive inhibitory response was observed when DON and T-2 toxin were added together to platelet suspensions.


The smooth endoplasmic reticulum in neurohypophysial axons of the rat: possible involvement in transport, storage and release of neurosecretory material.
The intra-axonal organization of the smooth endoplasmic reticulum was studied in the neurohypophysis of rats during and after water deprivation. Parallel to conventional electron microscopy, the material was treated with a double impregnation staining technique specifically designed to contrast the intracellular membranous system. In conventionally stained ultrathin sections from severely dehydrated rats most axons appeared to be free of membranous organelles, whereas corresponding axons treated with the double-impregnation technique generally exhibited a highly developed system of smooth endoplasmic reticulum. In axonal endings, both techniques revealed a profusion of microvesicles in intimate relationship with tubular elements of the smooth endoplasmic reticulum. In short-term (12h) rehydrated rats, a similarly developed system of smooth endoplasmic reticulum was stilll observed at all axonal levels with both procedures. After 24 to 48 h or rehydration the tubules of the smooth endoplasmic reticulum exhibited, in double impregnated material, numerous dilatations which resembled the adjacent neurosecretory granules. In conventionally stained ultrathin sections, an accumulation of electron dense material occurred within tubules of the smooth endoplasmic reticulum in the more proximal axonal segments, while in the more terminal segments, which contained numerous elongated granules, membrane continuity was frequently observed between newly formed granules and the smooth endoplasmic reticulum. After 7 days of rehydration the general pattern of the axonal smooth endoplasmic reticulum was comparable to that in untreated rats. These results are discussed in the light of a suggested involvement of the axonal smooth endoplasmic reticulum in the non-granlular transport of neurosecretory material in connection with (1) storage in distally formed granules, and (2) release via microvesicles.


Auricle Schwannoma: Presentation of a Rare Case and Review of Existing Literature.
Schwannomas are extremely rare over auricle. Despite the extensive somatogenic neural innervations of the pinna, schwannomas are never amongst the differentials for a benign auricular mass. Previously published articles have all agreed on the rarity of this lesion occurring over the auricle. However, none of the articles have tackled and extensively reviewed the auricle schwannomas (AS) as an individual entity. The article aim to review previously published cases of AS along with an illustrative case, and provide a better insight regarding demographic, clinicopathological and immunohistochemical features of this neural tumor in a rare site. A systemic review of English literature was performed after using a sensitive search strategy involving three different databases (PubMed, Google Scholar and Embase). A total of nine cases were included. They mostly presented in young adults as a slow growing tumor (mean duration: 3.17 years) and showed a slightly higher male predominance (male/female ratio 1.25:1). They were mostly located over lateral surface (66.67%) with a predilection for left ear (77.78%). Conventional histological variant has only been reported. Complete surgical excision was performed for all the cases without any reports of recurrence or malignant transformation. AS present as a solitary, painless, firm and well-encapsulated lesion, mostly over the lateral auricle surface. Preoperative clinical diagnosis is difficult and radiological investigations do not hold much importance. FNAC is inconclusive and diagnosis mandates histopathologic examination. The nerve of tumor origin is difficult to precisely identify. Complete surgical excision is the treatment of choice. Post-operative prognosis is excellent.


Plant derivatives in the treatment of alcohol dependency.
The present review summarizes the findings of the effects of extracts of purified compounds from several plants on alcohol intake in alcohol-preferring rats. These include St. John's wort (Hypericum perforatum, HPE), kudzu (Pueraria lobata) and ibogaine (Tabernanthe iboga). Alcohol-preferring (P), Marchigian Sardinian (msP), high-alcohol-drinking (HAD), Fawn-Hooded (FH) rats were allowed to drink alcohol or water voluntarily to establish baseline levels. Pure compounds (puerarin, daidzin, daidzein or analogs) isolated from kudzu, extracts from HPE or ibogaine and its analog were given by either intraperitoneal or oral administration. After acute administration, all agents dose-dependently reduced alcohol intake with minimal effects on food intake. Puerarin and HPE were also effective following chronic treatment. Overall, it is clear that pure compounds (daidzin, puerarin), extracts from St. John's wort, ibogaine and an ibogaine analog suppress alcohol intake in animal models of excessive drinking with minimal effects on other appetitive behaviors. Although the true mechanisms of action of these compounds on alcohol intake are not fully understood, with the current information, it appears that these compounds exert their effects by modulating several neuronal systems implicated in drinking behavior. However, their role in the future of pharmacotherapy for alcoholism will depend upon the outcome of carefully conducted clinical trials.


Left ventricular diastolic abnormalities other than valvular heart disease in antiphospholipid syndrome: An echocardiographic study.
Antiphospholipid syndrome (APS) can be primary or secondary to other autoimmune disorders. Besides valvular heart disease (VHD) and coronary artery disease (CAD), little is known about the impact of APS on left ventricular (LV) function. After excluding CAD, relevant VHD and heart failure, 69 patients (mean age = 43.9 years, 40 with primary and 29 with secondary APS) were assessed by echo-Doppler. Sixty-nine heathy controls, matched for age and sex, formed the control group. APS was diagnosed in presence of at least one clinical criteria and one confirmed laboratory criteria, including lupus anticoagulant (LA) titre. The adjusted global APS score (aGAPSS), derived from the combination of risk factors for thrombosis and autoimmune-antibody profile was calculated. Patients had similar blood pressure and heart rate, but higher body mass index (BMI) than controls. LV mass index (p = 0.007) and left atrial volume index (p < 0.01) were greater, while early diastolic velocity (e') was lower (p = 0.003) and E/e' higher (p = 0.007) in APS. Primary APS patients had lower E/A and e' compared to both controls and secondary APS, while E/e' was higher in secondary APS than in controls. APS patients with diastolic dysfunction were older but did not differ for risk factors prevalence from those with normal/indeterminate diastolic function. In the pooled APS, LA positivity was independently associated with e' and E/e' after adjusting for age, BMI and aGAPSS in separate multivariate models. In APS, LV diastolic abnormalities are detectable. They are more pronounced in primary APS and independently associated with LA positivity.


Evaluation of vt2-subtyping methods for identifying vt2g in verotoxigenic Escherichia coli.
Verotoxin-producing Escherichia coli (VTEC) are important pathogens that can cause severe human disease, including haemorrhagic colitis and haemolytic-uraemic syndrome. A new variant of verotoxin, vt2g, has recently been described. It was possible to find this variant for the first time in Argentina among VTEC isolated from cattle. The present study evaluated the identification of this gene with three conventional methods used for subtyping the vt2 gene. The results show that it is possible to screen VTEC strains for the presence of vt2g without the implementation of new protocols.


Cell division and trichome breakage inBeggiatoa.
The process ofBeggiatoa trichome division was elucidated through phase-contrast microscopy and transmission and scanning electron microscopy. Trichome breakage and dispersion is accomplished by the formation of sacrificial cells (necridia) at various points within the trichome. Upon dying, the sacrificial cells lyse, dividing the trichome into two daughter trichomes. This process is identical with that found in many oscillatorian blue-green bacteria, but differs from the mechanism of trichome division in most of the other flexuous gliding bacteria. Cellular division within the trichome occurs by septation, involving the cytoplasmic membrane and the electron-dense L2 (peptidoglycan) layer. The outer envelope layers do not take part in division.


Chronic Microcystin-LR-Induced α-Synuclein Promotes Neuroinflammation Through Activation of the NLRP3 Inflammasome in Microglia.
Microcystin-LR (MC-LR) has been confirmed to cause blood-brain barrier disruption and enter the brain tissue, resulting in non-negligible toxic effects. However, the neurotoxicity of MC-LR is mainly unknown. This study revealed that MC-LR disrupted the function of the ubiquitin-proteasome system in neurons, which inhibited the degradation of α-synuclein (α-syn), leading to its release from neurons for transport into microglia. α-Syn is the main component of Lewy bodies, which has been identified as one of the main pathological features of Parkinson's disease (PD). In vitro, we observed that α-syn mediated by MC-LR activated HMC3 cells and polarized them towards M1 type. In addition, we confirmed that α-syn was transported into HMC3 cells through TLR4 receptors and activated the NLRP3 inflammasome, which in turn enhanced the maturation and release of IL-18 and IL-1β. In the mouse models of chronic MC-LR exposure, a large number of inflammatory factors (IL-6, IL-1β, and TNF-α) were deposited in brain tissue, and activation of NLRP3 in microglia was also observed in the midbrain. Collectively, MC-LR exposure promoted the pathological spread of α-syn from cell to cell, activated NLRP3 inflammasome in microglia, and generated neuroinflammation, in which the TLR4 receptor played a substantial effect.


Arresting progressive atherosclerosis by immunization with an anti-glycosaminoglycan monoclonal antibody in apolipoprotein E-deficient mice.
Atherogenesis is associated with the early retention of low-density lipoproteins (LDL) in the arterial intima by interaction with glycosaminoglycan (GAG)-side chains of proteoglycans. Retained LDL undergo reactive oxygen species-mediated oxidation. Oxidized LDL trigger oxidative stress (OS) and inflammation, contributing to atherosclerosis development. Recently, we reported the preventive anti-atherogenic properties of the chimeric mouse/human monoclonal antibody (mAb) chP3R99-LALA, which were related to the induction of anti-chondroitin sulfate antibody response able to inhibit chondroitin sulfate dependent LDL-enhanced oxidation. In the present work, we aimed at further investigating the impact of chP3R99-LALA mAb vaccination on progressive atherosclerosis in apolipoprotein E-deficient mice (apoE(-/-)) fed with a high-fat high-cholesterol diet receiving 5 doses (50 µg) of the antibody subcutaneously, when ~5% of the aortic area was covered by lesions. Therapeutic immunization with chP3R99-LALA mAb halted atherosclerotic lesions progression. In addition, aortic OS was modulated, as shown by a significant (p<0.05) reduction of lipid and protein oxidation, preservation of antioxidant enzymes activity and reduced glutathione, together with a decrease of nitric oxide levels. chP3R99-LALA mAb immunization also regulated aortic NF-κB activation, diminishing the proinflammatory IL1-β and TNF-α gene expression as well as the infiltration of macrophages into the arterial wall. The therapeutic immunization of apoE(-/-) with progressive atheromas and persistent hypercholesterolemia using chP3R99-LALA mAb arrested further development of lesions, accompanied by a decrease of aortic OS and NF-κB-regulated pro-inflammatory cytokine gene expression. These results contribute to broaden the potential use of this anti-GAG antibody-based immunotherapy as a novel approach to target atherosclerosis at different phases of progression.


LG186: An inhibitor of GBF1 function that causes Golgi disassembly in human and canine cells.
Brefeldin A-mediated inhibition of ADP ribosylation factor (Arf) GTPases and their guanine nucleotide exchange factors, Arf-GEFs, has been a cornerstone of membrane trafficking research for many years. Brefeldin A (BFA) is relatively non-selective inhibiting at least three targets in human cells, Golgi brefeldin A resistance factor 1 (GBF1), brefeldin A inhibited guanine nucleotide exchange factor 1 (BIG1) and brefeldin A inhibited guanine nucleotide exchange factor 2 (BIG2). Here, we show that the previously described compound Exo2 acts through inhibition of Arf-GEF function, but causes other phenotypic changes that are not GBF1 related. We describe the engineering of Exo2 to produce LG186, a more selective, reversible inhibitor of Arf-GEF function. Using multiple-cell-based assays and GBF1 mutants, our data are most consistent with LG186 acting by selective inhibition of GBF1. Unlike other Arf-GEF and reported GBF1 inhibitors including BFA, Exo2 and Golgicide A, LG186 induces disassembly of the Golgi stack in both human and canine cells.


Loss of Xenopus cadherin-11 leads to increased Wnt/β-catenin signaling and up-regulation of target genes c-myc and cyclin D1 in neural crest.
Xenopus cadherin-11 (Xcadherin-11) is an exceptional cadherin family member, which is predominantly expressed in cranial neural crest cells (NCCs). Apart from mediating cell-cell adhesion it promotes cranial NCC migration by initiating filopodia and lamellipodia formation. Here, we demonstrate an unexpected function of Xcadherin-11 in NCC specification by interfering with canonical Wnt/β-catenin signaling. Loss-of-function experiments, using a specific antisense morpholino oligonucleotide against Xcadherin-11, display a nuclear β-catenin localization in cranial NCCs and a broader expression domain of the proto-oncogene cyclin D1 which proceeds c-myc up-regulation. Additionally, we observe an enhanced NCC proliferation and an expansion of specific NCC genes like AP2 and Sox10. Thereby, we could allocate NCC proliferation and specification to different gene functions. To clarify which domain in Xcadherin-11 is required for early NCC development we tested different deletion mutants for their rescue ability in Xcadherin-11 morphants. We identified the cytoplasmic tail, specifically the β-catenin binding domain, to be necessary for proper NCC development. We propose that Xcadherin-11 is necessary for controlled NCC proliferation and early NCC specification in tuning the expression of the canonical Wnt/β-catenin target genes cyclin D1 and c-myc by regulating the concentration of the nuclear pool of β-catenin.


Effects of reciprocal crosses on agronomic performance of tritordeum.
Tritordeums (Tritordeum Ascherson et Graebner) are the amphiploids derived from the crosses between Hordeum chilense and durum or bread wheats. Primary tritordeums are obtained using H. chilense as female parent and therefore they exhibit H. chilense cytoplasm. The effect of wheat cytoplasm on agronomic performance of tritordeums was investigated. We developed four pairs of reciprocal F1 lines only differing in their cytoplasm, donated from wheat or H. chilense alternatively. The agronomic performance of reciprocal F1 lines contrasting for their cytoplasm was evaluated. The following traits were assessed: leave and tillers number one month after sowing, plant height, anthesis date, total number of ears, number of spikelets per spike, fertility of the main spike, length and wide of the flag leaf in the main stem and thousand kernel weight. Reciprocal F1 lines did not differ for any of the agronomic traits evaluated with the exception of anthesis date in the pair THC1726/HTC1727. Therefore, both wheat and H. chilense cytoplasms can be used in tritordeum breeding.


L-fucose metabolism in mammals. Kinetic studies on pork liver 2-keto-3-deoxy-L-fuconate:NAD+ oxidoreductase.
Pork liver 2-keto-3-deoxy-L-fuconate:NAD+ oxidoreductase has been shown to convert 2-keto-3-deoxy-L-fuconate to a 6-carbon acid tentatively identified as 2,4(or 5)-diketo-5(or 4)-monohydroxyhexanoate. The enzyme has a pH optimum of 10. 5 or higher. It is stabilized by dithiothereitol and inhibited by p-hydroxymercuribenzoate and heavy metals (Ag+, Hg2+, Co2+, Cd2+, Pb2+, Zn2+, and Cu2+), suggesting the presence of a functionally essential sulfhydryl group; pre-treatment of enzyme with NAD+ prevents inhibition by p-hydrocymercuribenzoate and heavy metals indicating that this sulfhydryl group may be near the NAD+ binding site. The enzyme has an absolute requirement for NAD+; NADP+ is an ineffective coenzyme. Several lines of evidence indicate that the same enzyme acts on both 2-keto-3-deocy-L-fuconate and 2-keto-3-deoxy-D-arabonate; thus, the pure enzyme acts on both substrates, the two substrates have very similar kinetic parameters (Km values are: 2-keto-3-deocy-L-fuconate, 0.20 mM; 2-keto-3-deoxy-D-arabonate, 0.25 mM; NAD+ for either substrate, 0.22 to 0.25 mM), the two substrates show identical pH and temperature profiles and the two substrates compete for common enzyme active sites. A large number of other sugars and sugar acids, including several 2-keto-3-deoxyaldonates, were ineffective as substrates. The dehydrogenase was also found in calf, beef, lamb, mouse, and rat liver. These studies when considered together with previous studies on the metabolism of L-fucose in pork liver indicate the presence of a soluble enzyme pathway capable of converting L-fucose to 2,4(or 5)-diketo-5(or 4)-monohydroxyhexanoate; this pathway can also convert D-arabinose, and probably L-galactose, to the analogous derivatives (diketomonohydroxypentanoate and diketodihydroxyhexanoate, respectively.


Intra-articular metacarpal head fractures.
One hundred and three intra-articular metacarpal head fractures in 100 patients are presented and classified by anatomical involvement on roentgenographic examination. The fractures were epiphyseal (Salter-Harris type III, n = 4), ligament avulsions from metacarpal head (n = 17), osteochondral (n = 8), oblique (sagittal, n = 22), vertical (coronal, n = 4), horizontal (transverse, n = 4), comminuted (n = 31), boxer's fractures with extension into the joint (n = 3), loss of substance (n = 6), and occult compression with avascular necrosis (n = 4). Experience with fractures involving large intra-articular defects suggests that they should be reconstructed to give a congruous metacarpal head; the digit should then be mobilized as early as technically feasible.


Corilagin protects the acute lung injury by ameliorating the apoptosis pathway.
This study elucidates the protective effect of corilagin in acute lung injury rat model. Lung injury induced by ischemia/reperfusion (I/R) model was established by isolating the lungs from the rats. Ischemia was produced for the duration of 1h and thereafter reperfusion was done for 90min in isolated lung in presence and absence of corilagin (20 and 40mg/ml). Effect of corilagin was evaluated by estimating the pulmonary vein oxygen partial pressure (PaO2), airway compliance and tidal volume. Moreover the level of oxidative stress parameter, pro inflammatory parameters, phosphorylation of JNK and apoptosis rate was estimated in lung tissues. There was significant increase in the PaO2, airway compliance and tidal volume in corilagin treated group than I/R group. Treatment with corilagin significantly increases the activity of superoxide dismutase (SOD) and level of adenosine triphosphate (ATP) and decreases the level of MDA in the tissue homogenate of I/R induced lung injury model. Whereas expressions of proinflammatory gene such as tumor necrosis factor α, interlukin-6, IL-1β and cycloxygenase -2 (COX-2) was found to be reduced in corilagin treated group than I/R group. Posphorylation of JNK and apoptotic rate was also found to be decreased in corilagin treated group than I/R group. Present report concludes that treatment with corilagin attenuates the lung injury in ex vivo I/R induced lung injury rat model by decreasing oxidative stress, pro-inflammatory mediators and its anti apoptotic activity.


Long-term results of definitive treatment in elderly patients with localized prostate cancer.
The indication and effectiveness of definitive local treatment for prostate cancer in patients with a limited life expectancy remains to be established. This study is a retrospective analysis of the long-term clinical outcome of elderly patients with localized prostate cancer treated by radiotherapy or a radical prostatectomy. From 1982 to 1992, 37 patients with localized prostate cancer, aged 70 years or older, were treated initially by a pelvic lymphadenectomy and then with either external radiotherapy (n = 1 7) or a radical retropubic prostatectomy (n = 20). Lymph node metastasis was negative in all the cases, and no patients received hormonal treatment after the lymphadenectomy. The outcome of all patients was evaluated in June 1997. The 10-year overall and relative survival rates for the radiotherapy group were 27% and 85%, which were not significantly different from the rates of patients in the prostatectomy group (38% and 74%, respectively). The 5-year progression free rates for the radiotherapy group and the prostatectomy group were 63% and 95%, respectively (P= 0.06). In elderly patients with localized prostate cancer, the superiority of a radical prostatectomy over radiotherapy was not demonstrated in terms of either overall or relative survival rates, although the progression rate tended to be higher in patients in the radiotherapy group. The indication of definitive treatment in elderly patients should be further studied incorporating a quality of life assessment.


Evaluating a skills centre: learning psychomotor skills--a review of the theory.
The formal teaching of skills based on the theoretical principles of skill acquisition has, so far, been practised by teachers responsible for preparing students for their first adult clinical placement on the diploma programme. Whether teachers on other programmes are using similar models of skill acquisition has been surveyed, and the results are presently being analysed. This approach to teaching skills within the context of the Skills Centre is also being evaluated. However, as indicated in the introduction to this paper, it is important to develop and implement the theoretical foundations for skills teaching before any evaluative research on it can take place (Chen 1986). Now these foundations are in place, the evaluative strategy can proceed.


Can understanding the neurobiology of body dysmorphic disorder (BDD) inform treatment?
We aim to provide a clinically focused review of the neurobiological literature in body dysmorphic disorder (BDD), with a focus on structural and functional neuroimaging. There has been a recent influx of studies examining the underlying neurobiology of BDD using structural and functional neuroimaging methods. Despite obvious symptom similarities with obsessive-compulsive disorder (OCD), no study to date has directly compared the two groups using neuroimaging techniques. Studies have established that there are limbic and visual cortex abnormalities in BDD, in contrast to fronto-striatal differences in OCD. Such data suggests affect or visual training maybe useful in BDD.


Inhibition of protein crystallization by evolutionary negative design.
Why are proteins so hard to crystallize? We propose an 'evolutionary negative design' principle to explain this difficulty. Proteins have evolved to avoid crystallization because crystallization compromises the viability of the cell. Evolutionary negative design is supported by much evidence in the literature, including the effect of mutations on the crystallizability of a protein, the correlations found in the properties of crystal contacts in bioinformatics databases, and the positive use of protein crystallization by bacteria and viruses.


The impact of diet, body composition, and physical activity on child bone mineral density at five years of age-findings from the ROLO Kids Study.
Bone health is extremely important in early childhood because children with low bone mineral density (BMD) are at a greater risk of bone fractures. While physical activity and intake of both calcium and vitamin D benefit BMD in older children, there is limited research on the determinants of good bone health in early childhood. The aim of this cross-sectional study was to investigate the impact of diet, physical activity, and body composition on BMD at five years of age. Dietary intakes and physical activity levels were measured through questionnaires. Whole body BMD was measured by dual-energy X-ray absorptiometry in 102 children. Child weight, height, circumferences, skinfolds and serum 25-hydroxyvitamin D (25OHD) concentrations were assessed. There was no association between BMD and dietary calcium, dietary vitamin D, 25OHD, physical activity, or sedentary behaviour. Several measures of body composition were significantly positively associated with BMD; however, neither fat mass nor lean body mass was associated with BMD.Conclusion: Although we found no association between self-reported dietary and lifestyle factors and bone health in early years, increased body size was linked with higher BMD. These findings are important as identifying modifiable factors that can improve bone health at a young age is of utmost importance.What is Known:• Bone health is extremely important in early childhood, as children with low bone mineral density (BMD) are at greater risk of bone fractures.• Physical activity has been found to be beneficial for bone health in adolescents, and body composition has also been associated with BMD in teenage years.• Limited research on the determinants of good bone health in early childhood.What is New:• No association between self-reported lifestyle and dietary factors with bone health in early childhood.• Increased body size was associated with higher BMD at five years of age.


Recovery in bipolar depression: Post-hoc analysis of a placebo-controlled lurasidone trial followed by a long-term continuation study.
In this post-hoc analysis, rates of remission and recovery were evaluated in patients with bipolar depression treated with lurasidone. Outpatients meeting DSM-IV-TR criteria for bipolar I depression, were randomized to 6 weeks of once-daily, double-blind treatment with lurasidone 20-60mg, lurasidone 80-120mg or placebo, followed by a 6-month, open-label, flexible-dose, lurasidone continuation study. Recovery was defined as meeting criteria for combined symptomatic remission (Montgomery-Asberg Depression Rating Scale total score ≤12) and functional remission (all Sheehan Disability Scale domain scores ≤3) sustained for at least 3 months in the 6-month continuation study. A significantly higher proportion of lurasidone-treated patients met criteria for combined symptomatic remission and functional remission (33.3%, 91/273) compared to the placebo group (21.0%, 30/143, p<0.05, NNT=9) at the 6-week study endpoint. In the 6-month continuation study, the proportion of lurasidone-treated patients achieving sustained recovery was 60.7% (85/140) and 44.9% (31/69), for patients who continued lurasidone treatment and who switched from placebo to lurasidone, respectively. The definition of recovery used has not been previously validated and the analysis was post hoc. Lack of a control group in the continuation study limits data interpretation. Recovery in patients with bipolar depression was assessed based on rates of combined symptomatic and functional remission sustained over time. A majority of patients initially treated with lurasidone in the acute phase achieved recovery status in the continuation study. Treatment with lurasidone (vs. placebo) earlier in the course of the bipolar depressive episode increased the likelihood of subsequent recovery.


Effects of the dietary incorporation of olive leaves on growth performance, digestibility, blood parameters and meat quality of growing pigs.
In a preliminary study the oxidative stability and tocopherol content of pork meat were shown to be improved by olive leaf (OL) feed supplementation at 50 and 100 g kg(-1) . However, growth performance was affected negatively. Therefore the objective of the present study was to assess the influence of OL supplementation at a lower level on feed digestibility, growth performance and meat quality. Pigs were fed a basal diet (control), a basal diet with 25 g OL kg(-1) (OL2.5) or a basal diet with 50 g OL kg(-1) (OL5). The incorporation of OL significantly decreased growth rates (P = 0.010) and backfat thickness (P = 0.035) and increased feed/gain ratio (P = 0.032) in the OL5 group. Feed/gain ratio increased more for females (P = 0.001). The incorporation of OL decreased the crude fat (P = 0.006) and protein (P = 0.037) digestibility of both OL diets. Nevertheless, OL was effective in increasing the tocopherol content of meat (P = 0.009). However, meat from pigs fed the OL diets showed similar conjugated diene content, pH and colour parameters to that from pigs fed the control diet, even after 6 days of storage at 4 °C. The data indicate that olive leaves may be included in pig diets at 25 g kg(-1) in order to improve the tocopherol content of meat without excessively compromising growth performance.


Transcutaneous Electrical Nerve Stimulation (TENS) in the Emergency Department for Pain Relief: A Preliminary Study of Feasibility and Efficacy.
Given the high rates of opioid addiction and overdose in the United States, non-opioid means of treating pain are increasingly needed. Transcutaneous electrical nerve stimulation (TENS) therapy is an effective non-opioid modality for treating pain, but has not yet been routinely used in emergency department (ED) settings. In this study we asked the following questions: Are TENS units a feasible treatment for pain in the ED? How effective are TENS units for the management of pain in a general ED population? At our institution, we performed a pilot study using TENS units for pain. Patients in the ED were given, at the discretion of the ED provider, TENS units for the treatment of pain. Patients could be included for acute or chronic pain on whatever part of the body that was safe to use with TENS. A chart review of patients receiving TENS units in the ED (n=110) revealed that TENS was useful in relieving pain, along with other treatments, in 99% of cases. When surveyed, 83% of patients reported a functional improvement while using the TENS, and 100% of patients would recommend a TENS unit to a family or friend. When surveyed, 100% of ED staff observed that TENS units were effective in treating pain for patients, and 97% would want to use them if they themselves were patients. Overall, in this small pilot study, TENS units appeared to be effective in our ED for reducing pain, when added to standard treatment. Additional studies are needed to determine which conditions are most responsive to TENS therapy, and the magnitude of pain reduction when used alone.


Differential distribution of sperm subpopulations and incidence of pleiomorphisms in ejaculates of captive howling monkeys (Alouatta caraya).
The aim of this study was to develop an objective method to determine the incidence of pleiomorphisms and its influence on the distribution of sperm morphometric subpopulations in ejaculates of howling monkeys (Alouatta caraya) by using a combination of computerized analysis system (ASMA) and principal component analysis (PCA) methods. Ejaculates were collected by electroejaculation methods on a regular basis from five individuals maintained under identical captive environmental, nutritional, and management conditions. Each sperm head was measured for dimensional parameters (Area [A, (square micrometers)], Perimeter [P, (micrometers)], Length [L, (micrometers)], and Width [W, (micrometers)]) and shape-derived parameters (Ellipticity [(L/W)], Elongation [(L - W)/(L + W)], and Rugosity [(4лA/P (2))]). PCA revealed two principal components explaining more than the 96 % of the variance. Clustering methods and discriminant analyzes were performed and seven separate subpopulations were identified. There were differences (P < 0.001) in the distribution of the seven subpopulations as well as in the incidence of abnormal pleiomorphisms (58.6 %, 49.8 %, 35.1 %, 66.4 %, and 55.1 %, P < 0.05) among the five donors tested. Our results indicated that differences among individuals related to the incidence of pleiomorphisms, and sperm subpopulational structure was not related to the captivity conditions or the sperm collection method, since all individuals were studied under identical conditions. In conclusion, the combination of ASMA and PCA is a useful clinical diagnostic resource for detecting deficiencies in sperm morphology and sperm subpopulations in A. caraya ejaculates that could be used in ex situ conservation programs of threatened species in Alouatta genus or even other endangered neotropical primate species.


Ribavirin disposition in high-risk patients for acquired immunodeficiency syndrome.
Ribavirin is a broad-spectrum antiviral drug that has in vitro activity against human immunodeficiency virus. To determine the kinetics of ribavirin, 17 symptom-free homosexual men with lymphadenopathy were studied. Single doses of ribavirin, 600, 1200, or 2400 mg, were given orally or intravenously. The plasma ribavirin concentration-time profiles were well fitted by a three-compartment open model. Ribavirin followed linear kinetics over the dose range studied. The mean 1-hour postinfusion concentrations after intravenous ribavirin, 600, 1200, and 2400 mg, were 8.0, 19.7, and 37.1 mumol/L, respectively. The mean +/- SD plasma beta-phase half-life, terminal-phase (gamma) half-life, and volume of distribution at steady state were 2.0 +/- 1.1 hours, 35.5 +/- 14.0 hours, and 647 +/- 258 L, respectively. The mean ribavirin renal clearance and total body clearance were 99 +/- 30 and 283 +/- 37 ml/min, respectively. After an oral dose of 600, 1200, and 2400 mg, the mean peak plasma ribavirin concentrations (which occurred 1.5 hours after administration) were 5.1, 9.9, and 12.6 mumol/L, respectively. The mean absorption half-life and bioavailability of ribavirin were 0.5 hour and 45%. Ribavirin had no plasma protein binding and the drug accumulated within red blood cells. In conclusion, ribavirin is incompletely absorbed from the gastrointestinal tract, its renal excretion accounts for approximately one third of the drug's elimination, and drug accumulation (greater than threefold) will result with repetitive dosing at the 6- to 8-hour dosing interval currently used.


Alfalfa mosaic virus temperature-sensitive mutants. V. The nucleotide sequence of TBTS 7 RNA 3 shows limited nucleotide changes and evidence for heterologous recombination.
Nucleotide sequence determination of the coat protein cistron of the alfalfa mosaic virus (AIMV) temperature-sensitive mutant, Tbts 7 (uv) revealed a small number of point mutations of which only one results in the replacement of an amino acid: the asparagine residue at position 126 is replaced by an aspartate residue. RNA transcribed in vitro from a Tbts 7 cDNA 4 clone directed the production in vitro of a polypeptide which shows the same altered electrophoretic mobility in SDS-polyacrylamide gels as the Tbts 7 coat protein. Nucleotide sequence analysis of the 32-kDa open reading frame revealed some base changes, but none of these lead to changes in the primary structure of the protein. The 5'-terminal sequence of Tbts 7 RNA 3 was analyzed by cDNA cloning. At least three different types of nontranslated leader sequences were found, indicating considerable heterogeneity at the 5' end of the mutant RNA 3. The results indicated that the low abundance of RNA 3-containing particles in Tbts 7 virus preparations might be due to malfunctioning of the 5' terminus of Tbts 7 RNA 3 during replication.


A research agenda for adolescent-centered primary care in the United States.
Little attention has been given to how primary care can be transformed to better meet the needs of adolescents. To help generate the evidence needed, The National Alliance to Advance Adolescent Health convened an invitational conference in 2012 in Washington, DC. Participants from various disciplines identified a set of prioritized recommendations pertaining to 3 topics: increasing adolescent and parent engagement and self-care management; improving preventive care and identifying conditions early; and integrating physical, behavioral, and reproductive health services. This commentary includes the top three recommendations for each topic area and concludes with a brief examination of federal and private funding prospects.


The distribution of CR1, and Alu-like family of interspersed repeats, in the chicken genome.
We have studied the distribution of CR1, a family of short interspersed repeats, in the chicken genome; this family is homologous to the AluI family of man and to the B1-B2 families of mouse. Hybridization with a suitable probe showed that the vase majority of CR1 are located on the heaviest major component (1.708) of the genome which only represents 9% of chicken DNA. Some repeats were also found on the 1.702 and 1.704 components, but none on the 1.699 component (components are denoted by their buoyant densities in CsCl). The GC content of the repeats, 48%, matches that, 47%, of the major component mainly harboring it.


Improving cell and gene therapy safety and performance using next-generation Nanoplasmid vectors.
The cell and gene therapy industry has employed the same plasmid technology for decades in vaccination, cell and gene therapy, and as a raw material in viral vector and RNA production. While canonical plasmids contain antibiotic resistance markers in bacterial backbones greater than 2,000 base pairs, smaller backbones increase expression level and durability and reduce the cell-transfection-associated toxicity and transgene silencing that can occur with canonical plasmids. Therefore, the small backbone and antibiotic-free selection method of Nanoplasmid vectors have proven to be a transformative replacement in a wide variety of applications, offering a greater safety profile and efficiency than traditional plasmids. This review provides an overview of the Nanoplasmid technology and highlights its specific benefits for various applications with examples from recent publications.


Primary cutaneous lymphomas: exploration of 10-year data from supraregional mutlidisciplinary team meetings in Glasgow, UK.
Primary cutaneous lymphomas (PCLs) are non-Hodgkin lymphomas, presenting in the skin. They are classified into cutaneous B-cell lymphomas (CBCLs) or cutaneous T-cell lymphomas (CTCLs). The most common CTCL subtypes are mycosis fungoides (MF) and Sézary syndrome (SS). All patient's cases should be discussed at a specialist multidisciplinary team (MDT) meeting. This is the first published review, to our knowledge, of PCL MDT case discussion in the UK. Patient cases between 2008 and 2019 were reviewed to assess: frequency of PCL subtype, documentation of CTCL staging and management of MF/SS. Of 356, 103 (29%) were CBCLs and the majority (n = 200, 56%) were CTCLs. MF/SS was the diagnosis in 120 (34%). Staging was documented in 44% (n = 53) of patients with MF/SS. Management largely followed guidelines for MF/SS, topical corticosteroids were the most common treatment (n = 93, 78%). Frequency of PCL subtype is largely comparable with previously published data. Documentation of CTCL staging is low, but higher than other reports. Our work begins to address the gap in real-world data on CTCLs. A standardized approach to data collection would inform clinical practice.


Endoplasmic Reticulum Stress Induced by Toxic Elements-a Review of Recent Developments.
Endoplasmic reticulum of all eukaryotic cells is a membrane-bound organelle. Under electron microscope it appears as parallel arrays of "rough membranes" and a maze of "smooth vesicles" respectively. It performs various functions in cell, i.e., synthesis of proteins to degradation of xenobiotics. Bioaccumulation of drugs/chemicals/xenobiotics in the cytosol can trigger ER stress. It is recognized by the accumulation of unfolded or misfolded proteins in the lumen of ER. Present review summarizes the present status of knowledge on ER stress caused by toxic elements, viz arsenic, cadmium, lead, mercury, copper, chromium, and nickel. While inorganic arsenic may induce various glucose-related proteins, i.e., GRP78, GRP94 and CHOP, XBP1, and calpains, cadmium upregulates GRP78. Antioxidants like ascorbic acid, NAC, and Se inhibit the expression of UPR. Exposure to lead also changes ER stress related genes, i.e., GRP 78, GRP 94, ATF4, and ATF6. Mercury too upregulates these genes. Nickel, a carcinogenic element upregulates the expression of Bak, cytochrome C, caspase-3, caspase-9, caspase-12, and GADD 153. Much is not known on ER stress caused by nanoparticles. The review describes inter-organelle association between mitochondria and ER. It also discusses the interdependence between oxidative stress and ER stress. A cross talk amongst different cellular components appears essential to disturb pathways leading to cell death. However, these molecular switches within the signaling network used by toxic elements need to be identified. Nevertheless, ER stress especially caused by toxic elements still remains to be an engaging issue.


A sensitivity analysis using alternative toxic equivalency factors to estimate U.S. dietary exposures to dioxin-like compounds.
EPA recommends sensitivity analyses when applying the toxic equivalency factor (TEF) method to evaluate exposures to dioxin-like compounds (DLCs). Applying the World Health Organization's (WHO) 2005 TEF values and estimating average U.S. daily dietary intakes of 25 DLCs from eight food categories, we estimate a toxic equivalency (TEQ) intake of 23 pg/day. Among DLCs, PCB 126 (26%) and 1,2,3,7,8-PeCDD (23%) dominate TEQ intakes. Among food categories, milk (14%), other dairy (28%), beef (25%), and seafood (18%) most influenced TEQ intakes. We develop two approaches to estimate alternative TEF values. Based on WHO's assumption regarding TEF uncertainty, Approach1 estimates upper and lower TEFs for each DLC by multiplying and dividing, respectively, its individual TEF by ± half a log. Based on compiled empirical ranges of relative potency estimates, Approach2 uses percentile values for individual TEFs. Total TEQ intake estimates using the lower and upper TEFs based on Approach1 were 8 and 68 pg TEQ/day, respectively. The 25th and 75th percentile TEFs from Approach2 yielded 12 and 28 pg TEQ/day, respectively. The influential DLCs and food categories remained consistent across alternative TEFs, except at the 90th percentile using Approach2. We highlight the need for developing underlying TEF probability distributions.


Exploring the Core Prescription and Underlying Mechanism of Traditional Chinese Medicine in Treating Allergic Rhinitis in Children: A Real- World Study Based on an Illustrious Senior Traditional Chinese Medicine Practitioner.
Traditional Chinese medicine (TCM) is widely used to treat allergic rhinitis (AR) in China, especially in children. However, due to the complicated composition rules and unclear underlying mechanisms, effective herbal prescriptions' popularization and application are limited. This study tried to detect the core prescription of herbs in treating AR in children, reveal its mechanism based on the ingredients' network, and explore the main signaling pathways. We screened medical records of children patients with AR who were treated by TCM in DongZhiMen Hospital from Aug 2009 to Jan 2020 and adopted a descriptive analysis method on herbal characteristics. We used association rules to mine core prescriptions and used network pharmacology to establish the ingredient-target-pathway network through online databases and TCMSP, Genecards, KEGG pathway, Excel, R-Studio, and Cytoscape software. The analysis of 1,092 clinical visits highlighted that the principle of formulating prescription was as follows: 'pungent and warm herbs were used more frequently while cold-natured herbs were paid equal attention as warm-natured herbs.' The core prescription was formed by FangFeng, BaiZhi, CangErzi, and ChanTui. These herbs covered 130 underlying targets and 141 signaling pathways of AR, which mainly had an effect on signal transduction and immunoregulation. The core prescription based on these real-world clinical records includes FangFeng, BaiZhi, CangErzi, and ChanTui. It principally acts on targets of signal transduction pathways and immune pathways.


A human ImmunoChip cDNA microarray provides a comprehensive tool to study immune responses.
DNA microarray technology has developed rapidly in recent years and has become an essential tool, providing novel approaches to biomedical research. In this paper, we describe a self-designed ImmunoChip cDNA array for immunological research. With a comprehensive selection of genes of interest, we can focus on key signalling pathways and molecular mechanisms at relatively low cost compared to commercial platforms which are usually targeted at global screening of gene expression. To validate the efficiency of the ImmunoChip, we studied T helper cell polarization to functionally distinct subsets (Th1 and Th2). We also developed a tool for quality control of cDNA microarrays that assesses the technical quality of an ImmunoChip. The information produced with the quality control tool is shown to be valuable for extracting correct information from cDNA microarrays. Gene expression measurements with ImmunoChip are in agreement with the results obtained using oligonucleotide microarrays and with published quantitative RT-PCR data. The ImmunoChip provides reliable measurements and gives new insights into various aspects of human immune responses.


Drug and alcohol use in Tanzanian road traffic collision drivers.
Road traffic collisions (RTCs) are an important public health problem in low and middle-income countries (LMIC), where 90% of RTC deaths occur. The World Health Organization has suggested strategies to address excess mortality from RTCs including efforts to combat driving after using alcohol or drugs. Data on the impact of drug and alcohol use on RTCs is limited in many low-resource settings including Tanzania. We sought to examine the prevalence of drug and alcohol use in Tanzanian RTC drivers. This prospective, observational study was conducted in the emergency centre (EC) of Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania. We enrolled adult drivers presenting within 24 h of an RTC. We collected a saliva test of blood alcohol content (BAC) and a urine drug screen (UDS) and administered a validated substance use disorder screening tool, the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Patients were excluded from individual analyses if they could not produce saliva or urine or answer questions. Primary outcomes were rates of positive BAC, UDS and self-reported risky alcohol and drug use patterns. We screened 5264 trauma patients and enrolled 418, in whom 190 had a BAC, 364 had a UDS, and 410 had a complete ASSIST. 15 of 190 patients (7.9%) had a positive BAC, and 67/361 (18.7%) had a positive UDS for at least one drug. ASSIST scores showed 75/410 (18.3%) patients were at moderate or high risk for alcohol use disorder. Few were at risk for disordered use of other non-tobacco substances. In our population of RTC drivers, positive BAC and UDS tests were rare but many patients were at risk for an alcohol use disorder. Ideal screening for substance use in Tanzanian trauma populations may involve a combination of objective testing and a verbal screening tool.


Evoked potentials in children with oxidative metabolic defects leading to Leigh syndrome.
We studied evoked potentials in 15 children (age range: 2 wks to 4 yrs; mean: 10 mos) with metabolic disturbances that led to Leigh syndrome. These disturbances included deficiencies of pyruvate dehydrogenase (N = 5), complex 1 (N = 7), complex 4 or cytochrome oxidase (N = 2), and complex 5 (N = 1) deficiencies. Subsequent studies were performed in 11 children. All of the children with pyruvate dehydrogenase deficiency had abnormal brainstem auditory evoked potentials (BAEPs) due to poor morphology and reproducibility of the waveforms; central conduction time was normal in 4 of 5 initial studies. The patients with complex 4 or cytochrome oxidase deficiency had abnormal BAEPs, due to increased interpeak latencies and low amplitude or absent waves IV/V. Six of 7 of the children with complex 1 deficiency had normal BAEPs. The remaining patient (the youngest, age 6 wks) had only waves I and II bilaterally and suffered from the rapidly progressive form of complex 1 deficiency; the other 6 with complex 1 deficiency had the slowly progressive form. The one patient with complex 5 deficiency had normal BAEPs when first tested at 4 mos; abnormal BAEPs with loss of later waves were observed 10 weeks later. The visual evoked potentials and somatosensory evoked potentials usually were abnormal in these patients, but the findings were not specific to the patient subgroups. In all but one patient, subsequent studies disclosed a lack of normal maturational changes and/or deterioration across all 3 modalities. The BAEPs appeared to covary with the specific metabolic findings in these patients and with the patient's clinical course, but no BAEP could be considered characteristic of Leigh syndrome.


Textrema hopkinsi gen. et sp. n. (Digenea: Cryptogonimidae) from the largemouth bass of central Texas.
Textrema hopkinsi gen. et sp. n. is described from Micropterus salmoides from central Texas. Textrema is most similar to the genus Multigonotylus but differs in having a single gomotyl. The new genus is placed in the family Cryptogonimidae.


Nutritional support of the critically ill and injured patient.
The understanding of the importance of nutrition, particularly in the critically ill patient, is based on the known physiologic consequences of malnutrition. It includes respiratory muscle function, cardiac function, the coagulation cascade balance, electrolyte and hormonal balance, and renal function. Nutrition affects emotional and behavioral responses, functional recovery, and the overall cost of health care. The need to identify and treat the malnourished or potentially malnourished patient is a critical aspect of patient management. Much is known of catabolic and hypermetabolic state caused by trauma and burns. The response to injury needs to be mediated. There is much to learn about the intervention of that response through adjuvant nutritional therapy.


Glomerulosclerosis develops in Thy-1 nephritis under persistent accumulation of macrophages.
To clarify the relationship between macrophages and development of glomerulosclerosis, the authors developed a new experimental nephritis model with macrophages persisting in Thy-1 nephritis. Methyl-cellulose was administered intraperitoneally in addition to the intravenous injection of the anti-Thy-1 antibody to Wistar rats. Foamy macrophages influxed into the lytic mesangium and stayed to form nodular aggregates. Mesangial cells proliferated with the formation of extracellular matrices around these nodular aggregates of macrophages. Immunohistochemical analyses revealed that alpha-smooth muscle actin (alpha-SMA) was expressed in the proliferative area around these nodules of foamy macrophages from day 7. Type I collagen and type IV collagen were also expressed around the foamy macrophages in correspondence with alpha-SMA expression from day 7. The electron microscopic study revealed that collagen fibrils were formed around the transformed mesangial cells. The expression of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31), a marker of glomerular vasculature endothelial cells, was not found in the area occupied by the foamy macrophages, suggesting the impairment of glomerular reconstruction. Macrophages may participate in the progression of glomerulosclerosis in Thy-1 nephritis by enhancing the production of the extracellular matrix through transformed mesangial cells and preventing reconstruction of the capillary network.


MULTIMODAL IMAGING FEATURES AND TREATMENT RESPONSES OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO CENTRAL SEROUS CHORIORETINOPATHY.
To investigate features of central serous chorioretinopathy with choroidal neovascularization (CNV) on multimodal imaging and analyze their association with treatment response. A total of 37 patients with chronic central serous chorioretinopathy complicated by CNV were divided into bevacizumab and photodynamic therapy groups, and each group was subdivided into responders and nonresponders according to subretinal fluid status at 3 months. We assessed multimodal imaging parameters (subfoveal choroidal thickness; vortex vein engorgement; choroidal vascular hyperpermeability; and CNV morphologic pattern, area, and vessel density) and analyzed their association with treatment responses. Responders in the bevacizumab group showed thinner subfoveal choroidal thickness (384.0 ± 103.2 vs. 398.3 ± 87.1 µm, P = 0.042), smaller CNV area (0.512 ± 0.267 vs. 1.323 ± 0.481 mm2, P = 0.007), open-circuit pattern (84.6% vs. 12.5%, P < 0.001), and capillary fringe (69.2% vs. 37.5%, P = 0.001) than nonresponders. Responders in the photodynamic therapy group had thicker subfoveal choroidal thickness (420.1 ± 93.5 vs. 395.7 ± 6.5 µm, P = 0.021), more quadrants with engorged vortex veins extending to the macula (P = 0.012), and intense choroidal vascular hyperpermeability (57.1% vs. 50.0%, P = 0.026) than nonresponders. Choroidal neovascularization showing closed-circuit pattern (85.7% vs. 0%, P = 0.001) and peripheral loop (64.3% vs. 0%, P = 0.001) demonstrated a good response to photodynamic therapy. Heterogeneous features of choroidal hyperpermeability, thickness, and CNV morphology in CNV accompanying central serous chorioretinopathy are associated with different therapeutic responses to bevacizumab and photodynamic therapy treatments.


Triple-layer (au@perylene)@polyaniline nanocomposite: unconventional growth of faceted organic nanocrystals on polycrystalline Au.
Unconventional crystal growth: core/shell nanocrystals were obtained by growth of a dominant single-crystalline phase of perylene over polycrystalline Au nanoparticle seeds and isolated by coating with polyaniline (PANI) shells. Perylene is released in the presence of sodium dodecyl sulfate (SDS) micelles. The TEM images show (Au@perylene)@PANI nanocomposites before and after complete release of perylene leaving Au@PANI (inset).


Effect of ventilation rate on recovery after cardiac arrest in a pediatric animal model.
To assess the impact of two different respiratory rates in hemodynamic, perfusion and ventilation parameters in a pediatric animal model of cardiac arrest (CA). An experimental randomized controlled trial was carried out in 50 piglets under asphyxial CA. After ROSC, they were randomized into two groups: 20 and 30 respirations per minute (rpm). Hemodynamic, perfusion and ventilation parameters were measured 10 minutes after asphyxia, just before ROSC and at 5, 15, 30 and 60 minutes after ROSC. Independent medians test, Kruskal-Wallis test and χ2 test, were used to compare continuous and categorical variables, respectively. Spearman's Rho was used to assess correlation between continuous variables. A p-value <0.05 was considered significant. Arterial partial pressure of carbon dioxide (PaCO2) was significantly lower in the 30 rpm group after 15 minutes (41 vs. 54.5 mmHg, p <0.01), 30 minutes (39.5 vs. 51 mmHg, p < 0.01) and 60 minutes (36.5 vs. 48 mmHg, p = 0.02) of ROSC. The percentage of normoventilated subjects (PaCO2 30-50 mmHg) was significantly higher in the 30 rpm group throughout the experiment. pH normalization occurred faster in the 30 rpm group with significant differences at 60 minutes (7.40 vs. 7.34, p = 0.02). Lactic acid levels were high immediately after ROSC in both groups, but were significantly lower in the 20 rpm group at 30 (3.7 vs. 4.7 p = 0.04) and 60 minutes (2.6 vs. 3.6 p = 0.03). This animal model of asphyxial CA shows that a respiratory rate of 30 rpm is more effective to reach normoventilation than 20 rpm in piglets after ROSC. This ventilation strategy seems to be safe, as it does not cause hyperventilation and does not affect hemodynamics or cerebral tissue perfusion.


Inhibition of iodothyronine 5'-deiodinase by iopanoic acid does not block nuclear T3 accumulation during rat fetal development.
We studied the effect of iopanoic acid (IOP), an iodinated contrast medium, on iodothyronine 5'-deiodinase (5'D) and nuclear T3 content (nT3) in fetal tissues. In 18- and 20 day-old fetuses from control dams, nT3 was higher in interscapular brown adipose tissue (IBAT, 69 +/- 5 and 281 +/- 8 fmol/mg of DNA) than in brain (16 +/- 2 and 42 +/- 3 fmol/mg of DNA) or liver (5.6 +/- 1 and 27 +/- 2 fmol/mg of DNA). IOP administration (10 mg, twice daily) to pregnant rats on days 18 and 19 postconception significantly blocked 5'D activity in fetal IBAT and brain at day 20. Liver 5'D was not affected. The rise in nT3 was not modified by IOP treatment in IBAT, but it was enhanced in brain and liver of IOP-treated fetuses on day 20. In contrast, in adult rats, IOP treatment reduced IBAT nT3. Prolongation of IOP treatment until day 21 decreased fetal body weight on day 22 and inhibited IBAT 5'D. No change was produced in mitochondrial oxidative capacity, the subunit II of cytochrome oxidase, or uncoupling protein mRNA expression in IBAT from IOP-treated fetuses. Thus, the finding that IOP does not decrease the nT3 of fetal IBAT explains the lack of effect of IOP on uncoupling protein expression in fetuses, in contrast with the known decrease in adults. Present results also show that IOP increases nT3 in brain and liver, indicating a general incapacity of IOP to decrease nT3 in fetal tissues. It is concluded that the effects of IOP during fetal life differ from those in adults.


Evidence for an endothelial cell-derived factor which stimulates the growth of human peripheral blood mononuclear cells.
Evidence is provided which demonstrates that conditioned media of cultured endothelial cells derived from human umbilical veins contained a factor which stimulated peripheral blood mononuclear cell [3H]thymidine uptake. A dose-dependent response in peripheral blood mononuclear cell [3H]thymidine uptake was obtained when cells were incubated with increasing concentrations of supernatant of endothelial cell cultures. Studies on temporal kinetics demonstrated that stimulatory activity was evident when mononuclear cells had been incubated with endothelial cell supernatant for 120 hr or more. Preliminary characterization showed the growth immunoregulatory factor to have a molecular weight greater than 100,000 Da.


Electric field-induced fusion of yeast protoplasts. The role of different physical and chemical factors.
Electrofusion between cells of yeast strains with different genetic markers are investigated. The yield of fusion products depends strongly on the field conditions and the different compounds in the fusion media.


Incisional hernia repair: tensiometry for the selection of the appropriate procedure.
To audit the early and late results of repairs of incisional hernias before and after the introduction of peroperative tensiometry. Retrospective study. University hospital, Germany. 675 operations on 553 patients in 18 years. Before we introduced tensiometry we closed 560 incisional hernias by direct suture and 63 by the inlay-onlay technique. Since we took up tensiometry the numbers were 9 and 43, respectively. Postoperative complications including recurrences. Recurrences developed in 246/560 (44%) after direct suture in the early series, compared with 2/9 (22%) after adoption of tensiometry. After inlay-onlay operations there were 4/63 (6%) recurrences before, and 1/43 (2%) after adoption of tensiometry. Tensiometry allows the surgeon to tailor his operation to the conditions that he finds during the operation.


Enhanced coagulation with polyaluminum chlorides: role of pH/alkalinity and speciation.
Enhanced coagulation is considered to be among the best available techniques (BAT) for disinfection by-product (DBP) precursor removal in water treatment. Improving existing understanding requires further consideration of nuances of chemical speciation relative to source water chemistry. In this paper, the effect of alkalinity/pH and speciation on inorganic polymer flocculants, polyaluminum chlorides (PACls) for enhanced particle and natural organic matter (NOM) removal was investigated. Three kinds of well-characterized typical source waters in China with low, moderate, and high alkalinity were selected. Performance of coagulants is controlled not only by preformed species but also by those formed in situ. At neutral and basic pH values, PACls with higher basicity (ratio of OH(-)/Al), which have more stable preformed Alb (the rapid reacted species as in ferron assay), are more efficient for turbidity and NOM removal. At slightly acidic pH, PACls with lower basicity are more efficient since more Alb can be formed in situ. Optimal NOM removal was achieved at pH 5.5-6.5 for all PACls. Basicity, speciation, and dosage of coagulant should be optimized based on raw water alkalinity to enhance the removal efficiency of NOM.


Mice genetically selected for differences in open-field activity after ethanol.
Starting from a population of genetically heterogeneous mice, selective breeding is being used to develop lines differing in sensitivity to ethanol-induced open-field activity. Mice are tested twice for 4 min in an open field. The first test is between min 2-6 after injection of saline. Twenty-four hr later, a similar test is performed after injection of ethanol (1.5 g/kg). Two independent FAST lines are being selected for ethanol-induced increases in activity, and two independent SLOW lines are being selected for ethanol-induced decreases. After four generations of selection, the lines have diverged significantly. These lines should be useful for exploring the neuropharmacological basis for the activating and rewarding properties of ethanol.


Influence of glycosylation on IL-12 family cytokine biogenesis and function.
The interleukin 12 (IL-12) family of cytokines regulates T cell functions and is key for the orchestration of immune responses. Each heterodimeric IL-12 family member is a glycoprotein. However, the impact of glycosylation on biogenesis and function of the different family members has remained incompletely defined. Here, we identify glycosylation sites within human IL-12 family subunits that become modified upon secretion. Building on these insights, we show that glycosylation is dispensable for secretion of human IL-12 family cytokines except for IL-35. Furthermore, our data show that glycosylation differentially influences IL-12 family cytokine functionality, with IL-27 being most strongly affected. Taken together, our study provides a comprehensive analysis of how glycosylation affects biogenesis and function of a key human cytokine family and provides the basis for selectively modulating their secretion via targeting glycosylation.


CTLM as an adjunct to mammography in the diagnosis of patients with dense breast.
The purpose was to evaluate the utility of computed tomographic laser mammography (CTLM) as an adjunct examination to mammography in women with dense breast tissue. We retrospectively compared the findings of mammography, CTLM, and adjunct CTLM to mammography with pathology of 155 women scheduled for biopsy or surgery. Positive lesions were observed more significantly in malignant than benign lesions. The sensitivity of mammography vs. mammography+CTLM was 34.4% vs. 81.57% among extremely dense breasts and 68.29% vs. 95.34% among heterogeneously dense breasts. CTLM could distinguish benign lesions from malignant lesions and is not affected by breast density.


Minimal clinically important difference of the Functional Living Index-Emesis in patients with gynecological malignant tumor: A post hoc analysis of a single-arm study.
This study aimed to explore the impact of minimum clinically important difference (MCID) of the Functional Living Index-Emesis (FLIE) in patients with gynecologic malignancies. This post hoc analysis included patients with gynecological malignant tumors in the Department of Oncology of our hospital between October 2020 and October 2021. A total of 149 patients (aged 50.05 ± 12.24 years) were included. Most of the patients were married (75.8%), lived in the city (60.4%), and had a history of motion sickness (75.8%). The degree of nausea (9.00 [0.00, 16.00] vs. 30.00 [16.00, 48.00], P < 0.001) and vomiting (9.00 [0.00, 16.00] vs. 30.00 [16.00, 48.00], P < 0.001) were significantly improved after treatment. Taking the options in the scale as the subjective anchor, the MCID of FLIE for nausea and vomiting were 28.5 and 29 in anchor-based analysis, respectively. In the distribution-based analysis, the MCID of FLIE for nausea and vomiting were 2.41, 6.04, and 9.66; and 2.31, 5.78, and 9.24 in effect size of 0.2, 0.5, and 0.8, respectively. The MCID of FLIE for nausea and vomiting in patients with gynecological malignant tumors was 28.5 and 29 in the anchor-based analysis, with higher specificity, and 6.04 and 5.78 in the distribution-based analysis, with higher sensitivity. The development of the MCID scale might be used to interpret the clinical significance of chemotherapy-induced nausea and vomiting in patients with gynecological malignancies and help to calculate the sample size for future clinical trials.


Arachidonate-induced thrombosis in mice: effects of gender or testosterone and estradiol administration.
Sodium arachidonate (i.v.) has previously been shown to induce pulmonary emboli formation and a dose dependent cyanosis and respiratory depression in mice. Subsequently, we found that male mice are significantly more sensitive to arachidonate than females. Aspirin given orally 2 hours prior to arachidonate administration inhibits the responses of both males and females. Pretreatment with depo-testosterone markedly increases the effect of arachidonate in both males and females and depo-estradiol pretreatment reduces the responses in all mice. This exacerbation by testosterone of the arachidonate response and the attenuating effects of estradiol is consistent with data reported using other thrombogenic techniques.


Population differentiation and germination ecology in Stellaria media (L.) Vill.
Population differentiation in Stellaria media was studied with regard to life-cycle strategy and germination ecology. Two populations were identified in the study area, growing side by side, W1 and W2. The life-span of population W1 is much shorter than that of population W2, especially under summer conditions: 1-2 months versus 4-6 months; the time to flowering differs accordingly. Germination properties of seed produced under summer, winter, and field conditions were studied. Fresh seeds produced at 20° C showed good germination (ca. 75%) over a broad range of temperatures in the case of population W1, but seeds of population W2 showed appreciable germination only at high temperatures (ca. 30%). Seeds produced at 7° C showed very little (population W2) or no germination at all (population W1). To simulate seasonal changes in temperature, a "comprehensive" germination scheme was developed which enabled the response of hydrated seeds to two temperature cycles (cold-warm-cold and warm-cold-warm) to be tested. The two populations reacted differently. At the end of the cycles, only a few seeds of population W1, but about half of the seeds of population W2, remained dormant. The data obtained were used to study the effects of differential germination ecology on the dynamics of the two populations. In a reconstruction of the courses of development, the populations were shown to possess different strategies. Population W1 builds up a uniform seed stock, and population W2 a phenotypically diverse seed reserve. The implications for population dynamics are discussed.


Google Trends application for the study of information search behaviour on oropharyngeal cancer in Spain.
Oropharyngeal cancer is estimated to continue to increase in the next decades. Prevention strategies and knowing the current situation of knowledge and concern of the population about this disease is necessary. Infodemiology is valuable to monitor health information-seeking behaviour trends and epidemiology. The objective of this study is to analyze the use and evolution, through Google trends as a source of information, of internet-based information-seeking behaviour related to the oropharyngeal cancer in Spain and related to mass media stories. Using Google Trends, the terms "throat cancer', "HPV", "laryngeal cancer", "tonsil cancer" and "oral cancer". The searches volume and trend were analyzed using a Jointpoint regression method from January 2009 to July 2019. The most searched term was "HPV", with a search volume index of 61, followed by "throat cancer" (SVI = 25). The trend of the term "HPV" increased 6.1% annually (p < 0.000), with a linear correlation of both terms of 0.52 (p < 0.000). The greatest number of searches was carried out in the north of Spain, the most repeated query being "oral sex AND cancer". A correlation between the news in the media and the increase in the volume of searches for the terms was found. Any news stories, new interventions or aetiology related to oropharyngeal cancer can manifest as an increase in information-seeking behaviours for "throat cancer" on Google. Understanding healthcare information-seeking behaviour is essential in order to control and plan the quality of knowledge provided by health organisations, advocacy groups and health professionals regarding head and neck cancers.


The stability of yeast invertase is not significantly influenced by glycosylation.
Yeast invertase exists in two different forms. The cytoplasmic enzyme is nonglycosylated, whereas the external invertase contains about 50% carbohydrate of the high mannose type. The protein moieties of both enzymes are identical. The two invertases have been used previously as a model system to investigate the influence of covalently linked carbohydrate chains on the stability of large glycoproteins, and controversial results were obtained. Here, we measured thermal and denaturant-induced unfolding by various probes, such as the loss of enzymatic activity, and by the changes in absorbance and fluorescence. The ranges of stability of the two invertases were found to be essentially identical, indicating that the presence of a high amount of carbohydrate does not significantly contribute to the stability of external invertase. Earlier findings that invertase is stabilized by glycosylation could not be confirmed. The stability of this glycoprotein is apparently determined by the specific interactions of the folded polypeptide chain. Unlike the glycosylated form, the carbohydrate-free invertase is prone to aggregation in the denatured state at high temperature and in a partially unfolded form in the presence of intermediate concentrations of guanidinium chloride.


Investigating potential disparities in clinical trial eligibility and enrollment at an NCI-designated comprehensive cancer center.
Although barriers to trial accrual are well-reported, few studies have explored trial eligibility and trial offers as potential drivers of disparities in cancer clinical trial enrollment. We identified patients with gastrointestinal (GI) or head/neck (HN) malignancies who were seen as new patients at the University of Michigan Health Rogel Cancer Center in 2016. By exhaustive review of the electronic medical record, we assessed the primary outcomes: (1) eligibility for, (2) documented offer of, and (3) enrollment in a clinical trial. All 41 of the clinical trials available to these patients were considered. Independent variables included clinical and non-clinical patient-related factors. We assessed associations between these variables and the primary outcomes using multivariable regression. Of 1446 patients, 43% were female, 15% were over age 75, 6% were Black. 305 (21%) patients were eligible for a clinical trial. Among eligible patients, 154 (50%) had documentation of a trial offer and 90 (30%) enrolled. Among the GI cohort, bivariate analyses demonstrated that older age was associated with decreased trial eligibility. Bivariate analyses also demonstrated that Black race was associated with increased trial offer. After adjustment, patients 75 or older were less likely to be eligible for a clinical trial in the GI cohort; however, we found no significant associations between race and any of the outcomes after adjustment. Among eligible GI patients, we found no significant associations between non-clinical factors and enrollment. Among the HN cohort, bivariate analyses demonstrated that female sex, older age, Black race, and unpartnered marital status were associated with decreased likelihood of trial offer; however, we found no significant associations between race, age, and marital status and any of the outcomes after adjustment. We found no significant associations between non-clinical factors and eligibility after adjustment; however, women were less likely to be offered and to enroll in a clinical trial in the HN cohort. Factors associated with eligibility, documented offer, and enrollment differed between disease site cohorts at our institution. Future work is needed to ensure the equitable inclusion of women and elderly patients in clinical trials.


[Immune deficiences during pyoderma gangrenosum associated with a polycythemia vera].
A deficiency in cellular immunity was demonstrated in a patient suffering from polycythaemia rubra vera in the myelofibrosis stage. Intradermal reactions to classical antigens (candidine, trichophytine, streptokinase, streptodornase, tuberculine) were negative, as was the di-nitrofluorobenzene test. However, the T lymphocyte count was normal. There was no disturbance in humoral immunity. Phagocytosis was normal but leucocyte migration, studied in vitro, was nil. The possibility of an intrinsic abnormality in the polynuclear neutrophil is evoked.


[Rhinopneumonia and equine viral arteritis: seroepidemiological study in the northeast of Tunisia].
A seroepidemiological survey was realized in the Nord-Est Tunisia to study the prevalence of complement fixing and neutralizing antibodies to equine rhinopneumonitis and viral arteritis of horse, respectively. Four hundred sera were tested, using complement fixation reaction and seroneutralization test. The results show that 8.75% of sera have antibodies to viral arteritis and only 1.25% are positive for equine rhinopneumonitis.


[Not Available].
To evaluate the minimum effective dose of pure DON leading to measurable losses in weight gain and feed consumption a special feeding experiment was created to compare the effect of DON in natural contaminated wheat and - for the first time - a non-cereal diet (potato) spiked with pure DON. Examined parameters were weight gain, feed consumption and blood parameters.Three trials were conducted. In the first trial a concentration of 4000 µg DON/kg feed was used. In the second and third trial we used concentrations of 4000 and 6000 µg DON/kg feed. Severe effects on feed consumption and weight gain were found only in the second trial (naturally contaminated wheat ad lib.). By contrast, no differences in any parameter were found in the first (restricted feeding) and third trial (non-cereal diet spiked with pure DON ad lib.).


Oxygen-oxygen distances in protein-bound crystallographic water suggest the presence of protonated clusters.
The availability of high-resolution X-ray structures has shown that proteins contain numerous water molecules, but their role is still not fully understood. Protonated and deprotonated water species are often involved in biochemical reactions. However protons are exceedingly difficult to detect directly because they are electron-poor species. The oxygen‑oxygen distance of the crystallographic water molecules was analyzed in a large high-resolution data set. Moreover, a detailed analysis was carried out on the protein-bound water in the available structures of carbonic anhydrase II and cytochrome c oxidase, chosen as protein models in which protonated and deprotonated water species play a significant role. The analysis shows an excess of water-water distances below the expected value for hydrogen bond. In the cavities and on the surface of the considered model proteins, clusters of water molecules are found, whose structure suggests the presence of chemical species deriving from self-ionization of water. The presence of a small maximum below the hydrogen bond threshold in the oxygen‑oxygen distance distribution of crystallographic water molecules, along with the location of many of these water clusters, suggest the presence of Zundel-like structures in, or near, the proteins. Particularly significant is the presence of such structures in protein regions which have been identified as proton antennae or channels. This work shows the possibilities, still unexplored, offered by this type of analysis in detecting in structures obtained by X-ray diffraction the presence of aqueous protons or hydroxide ions, which are chemical species as important as elusive.


Ethnic discordance in serum anti-Müllerian hormone in European and Indian healthy women and Indian infertile women.
Does anti-Müllerian hormone (AMH) differ between healthy European and Indian women, and are potential ethnic differences modified by infertility diagnosis? Cross-sectional analysis of three prospectively recruited cohorts (n = 2758); healthy European women (n = 758), healthy community cohort from Kolhapur, India (n = 400) and infertility cohort from Kolhapur, India (n = 1600). AMH was determined by assay. Ethnicity, age and cause of infertility were modelled using additive quantile regression models. Healthy Indian women had lower AMH than their healthy European counterparts (population estimates 20.0% lower [95% CI 7.2-36.5]), with increasing discordance with increasing age; at 25 years AMH was 11.9% lower (95% CI 9.4-14.1), increasing to 40.0% lower (95% CI 0-64.6) by age 45. Comparison of healthy and infertile Indian women revealed differences that were related to cause of infertility. Women whose male partner had severe oligoasthenoteratozoospermia (n = 95) had similar AMH to controls; women with polycystic ovary syndrome (n = 220) had higher AMH, especially in those <30 years, and in women with a principal diagnosis of unexplained infertility (n = 757) AMH was lower (median difference 22.6% lower; 95% CI 9.1-37.7) than controls. AMH is substantially lower in healthy Indian women at all ages than their European counterparts. Infertile Indian women have variable differences in AMH from healthy Indian controls, with the extent and direction of differences primarily reflecting the underlying cause of infertility. Recognition of ethnic and cause-specific differences are critical to ensure accurate contextualizing of results and clinical outcomes for patients.