Incertitude diagnostique et action politique : une association de parents face aux politiques de l'autisme, 1982-2017.
The definition of diagnostic categories, such as autism, is not always consensual. It can be the cause of political struggles between various actors, including professionals, public administrations or patient associations. However, little is known about the situation of patient or parent associations in these "diagnostic politics." We assert here that these associations are more sensitive to the politics of definition than is suggested by the current historiography. Through an analysis of discourses and strategies of the Quebec Autism Society from 1982 to 2017, we document the role that this association intended to play in the politics of autism and we show how the adoption by the state of diagnostic-based policies intensify definitional debates in civil society, including among parents.


HISTORICAL VERSUS SELECTIONIST EXPLANATIONS IN EVOLUTIONARY BIOLOGY.
Abstract- Evolutionary changes require historical explanations, yet these are limited by the evolutionary processes we entertain and investigate. Using phylogenetic analysis, adaptation and natural selection can be tested as historical claims, but this is appropriate only in those special cases where change follows the scheme of one character-one function, singled out in new environmental circumstances. Systematic treatment of the evolutionary origin of characters (in particular, origin through ecological and developmental flexibility) lies outside the scope of selectionist explanations. Structural hypotheses about regularities in the directions of change, also analyzed phylogenetically, expand the scope of historical explanation to include the origin of characters, yet retain the view of organisms as passive and constrained objects of evolutionary change. Historical biology needs to encompass both the active responses of organisms and the construction by organisms of their own environments. For this to be realized will require changes in the concepts and practices of evolutionary biology, including a re-examination of the Lamarckian theme that the active responses of organisms have evolutionary significance-the rarity of individual-to-individual transmission of "acquired" characters does not disprove the possibility of their frequency increasing in a population.


Short-term efficacy and safety of personalized antiplatelet therapy for patients with acute ischaemic stroke or transient ischaemic attack: A randomized clinical trial.
The aim of this study was to determine whether the testing strategy for clopidogrel and/or aspirin resistance using CYP2C19 genotyping or urinary 11-dhTxB2 testing has an impact on clinical outcomes. A multicentre, randomized, controlled trial was conducted at 14 centres in China from 2019 to 2021. For the intervention group, a specific antiplatelet strategy was assigned based on the CYP2C19 genotype and 11-dhTxB2, a urinary metabolite of aspirin, and the control group received nonguided (ie, standard of care) treatment. 11-dhTXB2 is a thromboxane A2 metabolite that can help quantify the effects of resistance to aspirin in individuals after ingestion. The primary efficacy outcome was new stroke, the secondary efficacy outcome was a poor functional prognosis (a modified Rankin scale score ≥3), and the primary safety outcome was bleeding, all within the 90-day follow-up period. A total of 2815 patients were screened and 2663 patients were enrolled in the trial, with 1344 subjects assigned to the intervention group and 1319 subjects assigned to the control group. A total of 60.1% were carriers of the CYP2C19 loss-of-function allele (*2, *3) and 8.71% tested positive for urinary 11-dhTxB2- indicating aspirin resistance in the intervention group. The primary outcome was not different between the intervention and control groups (P = .842). A total of 200 patients (14.88%) in the intervention group and 240 patients (18.20%) in the control group had a poor functional prognosis (hazard ratio 0.77, 95% confidence interval [CI] 0.63 to 0.95, P = .012). Bleeding events occurred in 49 patients (3.65%) in the intervention group and 72 patients (5.46%) in the control group (hazard ratio 0.66, 95% CI 0.45 to 0.95, P = .025). Personalized antiplatelet therapy based on the CYP2C19 genotype and 11-dhTxB2 levels was associated with favourable neurological function and reduced bleeding risk in acute ischaemic stroke and transient ischaemic attack patients. The results may help support the role of CYP2C19 genotyping and urinary 11-dhTxB2 testing in the provision of precise clinical treatment.


Multisystem Toxicity in Cancer: Lessons from NASA's Countermeasures Program.
Astronauts and cancer patients are subject to similar multisystem physiological toxicities. Over the past sixty years, NASA developed a state-of-the-art countermeasures program (CMP) to characterize and mitigate the physiological consequences of spaceflight. Here, we propose a NASA-modeled CMP to elucidate and abrogate physiological toxicities in patients with cancer.


Mechanisms in rabbit aorta for hyperglycaemia-induced alterations in angiotensin II and norepinephrine effects.
The (Na+,K+)-ATPase activity operative in rabbit aortic intima-media incubated with normal plasma levels of glucose and myo-inositol (70 mumol/l) is decreased when the glucose content of the medium is raised from 5 to 10 mmol/l or higher; this effect is prevented by aldose reductase inhibitors and by raising the myo-inositol content of the medium to 500 mumol/l. The decrease in (Na+,K+)-ATPase activity results from the loss of a component normally regulated (stimulated) by endogenously released adenosine through a receptor that stimulates phosphatidylinositol turnover in a discrete pool. The replenishment of this phosphatidylinositol pool selectively requires myo-inositol transport and is inhibited when increased polyol pathway activity impairs myo-inositol transport at a normal plasma level. Adenosine is a vasodilator, some endothelium-released vasodilators modulate the responses to vasoconstrictors by stimulating an increase in (Na+,K+)-ATPase activity in vascular smooth muscle. Whether adenosine mediates this effect in angiotensin II or norepinephrine-stimulated aorta was examined. Angiotensin II (100 nmol/l) and norepinephrine (1 mumol/l) evoked marked increases in (Na+,K+)-ATPase activity in aortic intima-media incubated with 5 mmol/l glucose and 70 mumol/l myo-inositol, which were inhibited when adenosine deaminase was added or the medium myo-inositol omitted to inhibit myo-inositol transport. Raising the medium glucose to 30 mmol/l inhibited the angiotensin II and norepinephrine-evoked increases in (Na+,K+)-ATPase activity, and this was prevented when tolrestat (10 mumol/l) was added or the myo-inositol content of the medium was raised from 70 to 500 mumol/l.(ABSTRACT TRUNCATED AT 250 WORDS)


The prevalence of analgesics containing dextropropoxyphene or codeine in individuals suspected of driving under the influence of drugs.
To investigate the prevalence of analgesics containing dextropropoxyphene (DXP) or codeine in individuals suspected of driving under the influence of drugs, we analysed all blood samples in which drugs were screened for in cases of suspected drunken driving in Sweden during the years 1992-1997. DXP was found in 130 (2.7%) and codeine in 388 (7.9%) of the 4896 drug-screened cases. The ratio between the number of DXP and of codeine cases and prescription of defined daily dose/1000 inhabitants during a 12-month period (DDD) was determined. The quotient for DXP was trebled from 1992 (0.99) to 1997 (2.89), while the codeine quotient decreased by 9% (from 6 to 5.5). The blood samples showed polydrug use in all but 28 cases of the 486 cases where DXP and/or codeine was found. In 71% of the 486 cases benzodiazepines were also present and in 38% of the cases amphetamine and/or cannabis were present. It was concluded that analgesics containing DXP or codeine are not drugs of primary interest in this specific population. Nevertheless, because of the high toxicity of DXP, especially when combined with alcohol or other drugs, the increase in the DXP prevalence gives reason for concern, since the studied population represents a group of individuals who use large doses of therapeutic or illegal drugs.


Early association of electrocardiogram alteration with infarct size and cardiac function after myocardial infarction.
Myocardial infarction (MI) is the main cause of heart failure, but the relationship between the extent of MI and cardiac function has not been clearly determined. The present study was undertaken to investigate early changes in the electrocardiogram associated with infarct size and cardiac function after MI. MI was induced by ligating the left anterior descending coronary artery in rats. Electrocardiograms, echocardiographs and hemodynamic parameters were assessed and myocardial infarct size was measured from mid-transverse sections stained with Masson's trichrome. The sum of pathological Q wave amplitudes was strongly correlated with myocardial infarct size (r = 0.920, P < 0.0001), left ventricular ejection fraction (r = -0.868, P < 0.0001) and left ventricular end diastolic pressure (r = 0.835, P < 0.0004). Furthermore, there was close relationship between MI size and cardiac function as assessed by left ventricular ejection fraction (r = -0.913, P < 0.0001) and left ventricular end diastolic pressure (r = 0.893, P < 0.0001). The sum of pathological Q wave amplitudes after MI can be used to estimate the extent of MI as well as cardiac function.


Co-occurrence of nonsense mutations in MSH6 and MSH2 in Lynch syndrome families evidencing that not all truncating mutations are equal.
The majority of pathogenic mismatch repair (MMR) gene mutations detected in Lynch syndrome patients are truncating (frameshift or nonsense). However, the classification of terminal truncating mutations is sometimes difficult and predictive testing based on non-deleterious variants can have very serious consequences. Here, we report eight probands that have two germline nonsense mutations, namely MSH6 c.1030C>T, p.(Gln344Ter) and MSH2 c.2785C>T, p.(Arg929Ter), and one additional patient who presented only the MSH2 mutation previously reported as deleterious. The novel MSH6 truncating mutation was classified as deleterious, as it is predicted to encode a protein with loss of 1017 amino acid residues. The MSH2 mutation, which is expected to encode a protein lacking six amino acid residues, was considered a variant of unknown significance. Five tumors of the eight double-mutant individuals had normal MSH2 expression, whereas MSH6 immunoexpression was lost in all evaluable cases. None of the variants were detected in normal controls or associated with other MMR germline mutations in our series. This study emphasizes that not all truncating mutations are equal and that one must be cautious in the interpretation of the presumed deleterious effect of terminal frameshift or nonsense mutations.


Proteomic analysis of egg white proteins during the early phase of embryonic development.
Avian egg albumen participates in embryonic development by providing essential nutrients as well as antimicrobial protection. Although various biological functions of egg white proteins were suggested during embryogenesis, global changes of these proteins under incubation conditions remained uninvestigated. This study presents a proteomic analysis on the change of egg white proteins during the first week of embryonic development. By using 2-DE, together with MALDI-TOF MS/MS, thirty protein spots representing eight proteins were identified showing significant changes in abundance during incubation. An accelerating degradation of ovalbumin was observed in a wide range of molecular weight. In addition, four protein complexes were predicted according to the detected molecular weight increase. Among these speculated protein complexes, an ovalbumin spot coupled with RNA-binding protein was detected. The absence of these protein complexes before incubation, followed by the constant increase in abundance during incubation indicates conceivable pivotal roles in embryonic development. To better understand the function of the proteins identified in this study, discrepancies of egg white protein changes between fertilized and unfertilized chicken eggs were additionally demonstrated. These findings will provide insight into the embryogenesis process to improve our knowledge of egg white proteins in regulating and supporting early embryonic development.


Prophylactic total thyroidectomy using the minimally invasive video-assisted approach in children with multiple endocrine neoplasia type 2.
There have been few reports of prophylactic thyroidectomy using the minimally invasive video-assisted thyroidectomy (MIVAT) approach in children with multiple endocrine neoplasia 2 (MEN2). We conducted a retrospective review of a prospectively maintained database of patients who underwent MIVAT for total thyroidectomy. Six children underwent MIVAT; RET codon mutations identified were 634, 620, 611, and 918. Mean operative time was 93 minutes (range, 68-105 minutes). Five patients were discharged on the first postoperative day; however, 1 patient had a postoperative hematoma and was discharged 2 days postoperatively. There were no cases of laryngeal nerve palsy or postoperative hypoparathyroidism. High levels of satisfaction with postoperative cosmesis were reported. Calcitonin levels have been undetectable at follow-up thus far (mean follow-up, 42.8 months). Although our outcomes are similar to those reported using the traditional approach, it is important to note that MIVAT is essentially the same operation, just performed through a smaller incision, with resulting benefits in terms of pain, cosmesis and, perhaps, morbidity.


Wide-track polycentric total knee arthroplasty: one year follow-up study.
The use of a peritoneal catheter enhances diagnosis using arthroscopy by affording a clear visibility of the knee joint. The accuracy in diagnosis is significantly enhanced using this method of irrigation. No better method of irrigation is available for cases of acute knee joint injuries.


Memory retrieval as a self-propagating process.
Retrieval of a subset of studied items and the presentation of those items as retrieval cues typically impair retrieval of the other items. Previous research on this self-limiting property of memory retrieval has relied heavily on short retention intervals and similar context between encoding and test. Here, we examined retrieval dynamics also after a prolonged retention interval with different spatial and social context between encoding and test, conditions that mimic people's remembering in many situations of daily life. For both unrelated word lists and more integrated prose material, we found retrieval and cuing to impair recall of other studied items after a short retention interval, but to improve recall in the prolonged retention interval condition. The results demonstrate that retrieval dynamics depend critically on situation, indicating that quite often in daily life, retrieval may be a self-propagating, rather than a self-limiting process.


[A case of Hodgkin's disease with thrombocytopenic purpura, polyneuritis, and cytomegalovirus pneumopathy (author's transl)].
A patient with Hodgkins disease developed successively, a thrombocytopenic purpura, a polyneuristis and a pneumopathy, during a period of remission, and over a period of time lasting 3 months. The authors discuss the possibility of cytomegalovirus being the causative agent.


Angiogenin is expressed in human dermal papilla cells and stimulates hair growth.
The perifollicular vasculature undergoes hair-cycle dependent expansion and degeneration. Multiple soluble factors derived from dermal papilla cells (DPCs) may act on surrounding blood vessels to influence angiogenesis, growth and differentiation, and thereby regulate cyclic hair growth. The goal of this study was to examine the expression of angiogenin, a potent angiogenic factor, in human DPCs, and to determine its role in hair growth. Reverse transcription polymerase chain reaction (RT-PCR), western blotting, immunofluorescence and ELISA analyzes were used to investigate the expression of angiogenin in human DPCs, while semi-quantitative RT-PCR was used to assess angiogenin mRNA expression in murine skin phased at different stages of the hair cycle. We detected angiogenin expression in DPCs, where it was found to be localized to the cytoplasm. Angiogenin mRNA was expressed in murine skin in a hair-cycle dependent manner, with maximum levels observed at the late anagen. Local injection of angiogenin promoted skin angiogenesis and induced anagen VI. In vitro studies showed that angiogenin significantly enhanced the elongation of hair follicles, and stimulated DPCs and ORS keratinocytes to proliferate. Taken together, these findings show that angiogenin is expressed in human DPCs, where it might contribute to hair growth directly, by stimulating DPCs and ORS keratinocytes to proliferate, or indirectly, by inducing local vascularization.


Distally Based Medial Hemisoleus Muscle Flap for Wound Coverage in the Distal Third of the Leg.
Wound healing and coverage of soft tissue defects of distal tibia are challenging. Free tissue transfer is treatment of choice for distal tibial defects. However, resources for free tissue transfer are not readily available and they increase morbidity to host. Local and regional flaps play a key role in management of these defects with less demanding or specialized requirements. The soleus muscle flap is the workhorse flap for midtibia soft tissue defects and is used in reverse fashion to reach the distal third of the tibia. Despite minor complications, distally based medial hemisoleus flap is reliable in limb salvage cases.


Recent progress in histochemistry and cell biology.
Studies published in Histochemistry and Cell Biology in the year 2011 represent once more a manifest of established and newly sophisticated techniques being exploited to put tissue- and cell type-specific molecules into a functional context. The review is therefore the Histochemistry and Cell Biology's yearly intention to provide interested readers appropriate summaries of investigations touching the areas of tissue biology, developmental biology, the biology of the immune system, stem cell research, the biology of subcellular compartments, in order to put the message of such studies into natural scientific-/human- and also pathological-relevant correlations.


Directors of continuing nursing education: a national survey of educational needs.
Advancing technology and healthcare reform necessitate continuing nursing education to maintain competence. This study assesses the knowledge and skills needed to function as a director of continuing nursing education in a variety of settings, estimates the supply of qualified applicants for vacant director positions, and identifies essential academic needs of someone preparing for the director's position.


Food and Drug Administration perspective: Advancing product development for non-healing chronic wounds.
The US Food and Drug Administration (FDA) understands that innovative product development is essential to addressing the unmet medical need of non-healing chronic wounds. Barriers to product development for non-healing chronic wounds may involve but are not limited to a dearth of biological models, challenges in drug delivery, challenges in clinical trial execution, and limited commercial viability. This perspective article discusses FDA's renewed focus on non-healing chronic wounds and outlines efforts to address identified barriers to product development for non-healing chronic wounds. In collaboration with key wound healing stakeholders including academia, professional associations, patient groups, reimbursement organizations and industry, FDA intends to help advance product development for non-healing chronic wounds for the ultimate betterment of patients.


Characterization and possible opioid modulation of N-methyl-D-aspartic acid induced increases in serum luteinizing hormone levels in the developing male rat.
It has been previously reported that the excitatory amino acid, N-methyl-D-aspartic acid (NMDA), elicits prompt increases in serum luteinizing hormone (LH) levels in young male rats. The present studies were carried out to determine whether the effects of NMDA on LH were mediated by the release of LHRH from the hypothalamus. We also examined whether NMDA-sensitive neuronal pathways interacted with the endogenous opioid system regulating LHRH release and the ontogeny of NMDA-evoked increases in serum LH. We found that the age-response curve for NMDA-induced increases in LH was an inverted U; at early ages (10 and 15 days) the amino acid was marginally effective in increasing LH levels, it became maximally effective from post-natal days 20-40 and thereafter rapidly lost its efficacy such that it was virtually inactive in adult animals. Dose-response curves revealed that adult animals were more than 10-fold less sensitive to NMDA than their younger counterparts. Our studies also demonstrated that NMDA increased LH via a direct effect on the hypothalamic release of LHRH since a potent LHRH antagonist competitively inhibited the effects of NMDA. Finally, we observed that morphine competitively inhibited the effects of NMDA on LH release, suggesting a relationship between NMDA-sensitive neuronal pathways and those endogenous opioid-containing systems which are known to regulate LH release.


Deletion of sphingosine kinase 1 ameliorates hepatic steatosis in diet-induced obese mice: Role of PPARγ.
Sphingolipid metabolites have emerged playing important roles in the pathogenesis of nonalcoholic fatty liver disease, whereas the underlying mechanism remains largely unknown. In the present study, we provide both in vitro and in vivo evidence showing a pathogenic role of sphingosine kinase 1 (SphK1) in hepatocellular steatosis. We found that levels of SphK1 expression were significantly increased in steatotic hepatocytes. Enforced overexpression of SphK1 or treatment with sphingosine 1-phosphate (S1P) markedly enhanced hepatic lipid accumulation. In contrast, the siRNA-mediated knockdown of SphK1 or S1P receptors, S1P2 and S1P3, profoundly inhibited lipid accumulation in hepatocytes. Moreover, Sphk1(-/-) mice exhibited a significant amelioration of hepatosteatosis under diet-induced obese (DIO) conditions, compared to wild-type littermates. In addition, DIO-induced up-regulation of PPARγ and its target genes were significantly reduced by SphK1 deficiency. Furthermore, treatment of hepatocytes with S1P induces a dose-dependent increase in PPARγ expression at the transcriptional level. Blockage of S1P receptors and the Akt-mTOR signaling profoundly inhibited S1P-induced PPARγ expression. Notably, down-regulation of PPARγ by using its siRNA significantly diminished the pro-steatotic effect of SphK1/S1P. Thus, the study demonstrates a new pathway connecting SphK1 and PPARγ involved in the pathogenesis of hepatocellular steatosis.


The immune response of young turkeys to haemorrhagic enteritis virus infection at different levels and sources of methionine in the diet.
Haemorrhagic enteritis (HE) of turkeys was first described in 1937 in the USA, while in Poland it was first diagnosed in 1987. Polish haemorrhagic enteritis virus (HEV) isolates are usually low pathogenic and trigger a subclinical disease. Unfortunately, even the low- pathogenic HEV strains cause severe immunosuppression leading to secondary bacterial infections and huge economic losses. The objective of this study was to evaluate if the influence of Met on HEV infected turkeys immune response can be differentiated by both its level and source. Met is one of the amino acids that not only play a nutritional role but also participate in and regulate key metabolic pathways and immune response. In our study, the birds were assigned to 4 dietary treatments which differed in Met levels (0.55 and 0.78% in weeks 1-4 of age and 0.45 and 0.65% in weeks 5-8 of age, respectively) and sources (DL-methionine (DLM) or DL-methionine hydroxy analogue (MHA)). The HEV added the percentage of CD4+ cells and decreased the percentage of IgM+ cells in the blood, spleen and caecal tonsils (CTs) of turkeys. In addition, it increased the percentage of CD4+CD25+ cells in blood, and interleukin-6 (IL-6) level in plasma. The higher dose of Met led to a significant decrease in the percentages of CD4+, CD8+ and CD4+IL-6+ cell subpopulations in the blood of HEV-infected and uninfected turkeys and to an increase in the percentage of IgM+ B cells in CTs. Turkeys administered feeds with an increased Met content displayed a decrease in plasma IL-6 levels and an increase in plasma IgA levels. The results of this study indicate that HEV infection impairs the immune function in turkeys. Met content in the feed has a moderate effect on the immune response in HEV-infected turkeys. The source of this amino acid appears not be as important as its dose, because value of the analysed parameters did not differ significantly between turkeys receiving feeds with DLM or MHA. In the uninfected turkeys, the higher by 40% (than recommended by NRC) level of Met in the feeds had a positive effect on humoral immunity parameters.


Design, synthesis and biological evaluation of WZ4002 analogues as EGFR inhibitors.
A series of thirty two anilinopyrimidines derived from WZ4002 has been synthesized and evaluated for percentage inhibition of six different EGFR kinases using LanthaScreen binding assay method (EGFR d746 - 750) or Z'LYTE assay method (EGFR-WT, EGFR d746 - 750, EGFR T790M, EGFR T790M L858R, EGFR C797S and EGFR T790M L858R C797S). Ortho-hydroxyacetamide 10 exhibited complete inhibition of all the six kinases at 10µM. Against the triple mutant, EGFR T790M C797S L858R, compounds 9-12 exhibited complete inhibition at 10µM and nearly complete inhibition at 1µM. The target compounds were also evaluated using the MTT assay to determine their cytotoxic activity against human non-small cell lung cancer cells (PC9, PC9GR and H460) and mouse leukemic cells (Ba/F3 WT and Ba/F3T 3151). Overall, 7, 9-12, 30 and 31 were found to be the most potent compounds across all five cell lines.


Assessment and management of atherosclerosis in the athletic patient.
Many patients and physicians correctly associate physical activity with reduced cardiovascular morbidity and mortality. Vigorous physical exertion is paradoxically associated with a transient increase in the risk of cardiovascular events and sudden cardiac death. This review extrapolates data from the general population to the management of athletes with symptoms suspicious for coronary artery disease or with prior cardiac events. A history to elicit an athlete's concerns and symptoms combined with a physical examination should guide the decision for preparticipation exercise testing for athletes without prior cardiac events. Athletes with established coronary artery disease should receive aggressive secondary prevention regimens, with special attention to adverse effects that may be unique to this group. There may be benefit in taking time away from competitive athletics to allow for stabilization of coronary artery disease with cholesterol-lowering therapy and, therefore, reduction of future risk. Exercise testing is important for defining risk before the return to participation for athletes who have sustained a cardiac event. Many athletes will ultimately be able to return to full participation provided they have received aggressive therapy and understand the residual risk associated with vigorous physical exertion in the setting of coronary artery disease.


Muscle water and electrolytes in relation to nutritional status in gastric carcinoma.
Muscle water and electrolytes were studied preoperatively in 22 patients with gastric carcinoma. Compared to controls, extracellular water and hence total muscle water was increased, but intracellular water was normal. Muscle sodium and chloride levels were increased in these patients while potassium and magnesium levels were normal. Based on nutritional assessment the patients were divided into wellnourished (group I, n = 7) with no or minor signs of malnutrition and malnourished (group II, n = 15) with signs of pronounced malnutrition. The wellnourished patients had normal content of muscle water and electrolytes, while in the malnourished an increase in total water, sodium and chloride in muscle tissue was found. The difference between the two groups, could be explained by malnutrition alone, since tumour size, histology, metastatic spread and operability did not differ between the two groups. A negative correlation was found between total water and both albumin and creatinine-height index which further indicates a close relationship between nutritional status and muscle water and electrolytes. In addition these findings revive the interest in nutritional assessment as a simple way of identifying metabolically deranged patients.


Bi2S3 quantum dots in situ grown on MoS2 nanoflowers: An efficient electron-rich interface for photoelectrochemical N2 reduction.
Photoelectrocatalysis is considered a green, environmentally friendly, sustainable technology for NH3 synthesis. However, the low efficiency of ammonia synthesis is currently the primary problem in photoelectrochemical nitrogen reduction reactions (PEC NRR). Herein, a nanocomposite BQD/MS developed through the in-situ growth of Bi2S3 quantum dots (BQD) on MoS2 (MS) nanoflowers was demonstrated as an efficient PEC NRR catalyst. Experimental results showed that the strong interaction between BQD and MS modulated the interfacial charge distribution and increased the electron density on the MS side. Meanwhile, the excellent structure of BQD/MS promoted the effective migration of photogenerated electrons from excited BQD to the MS surface. The electron-rich MS reaction interface was conducive to cleaving the stable NN bond and improving the N2 reduction performance. As a result, the prepared BQD/15MS photocathode obtained an excellent Faradaic efficiency of 33.2% and an NH3 yield of 18.5 μg h-1 mg-1, which was about three times that of bare MS.


Human T-cell leukaemia virus is not lysed by human serum.
Retroviruses isolated from avian, feline, murine and simian sources have been found to be inactivated and lysed by normal human serum. There is much evidence that complement is activated directly by retroviruses in the absence of antibody. Thus, human complement is thought to function as a natural defence mechanism against horizontal infection by retroviruses. Recently, a novel retrovirus, human T-cell leukaemia virus (HTLV), has been shown to be associated with adult T-cell leukaemia/lymphoma (ATL). A large number of healthy adults in south-west Japan, the West Indies and Africa carry antibodies against HTLV and these seropositive individuals are considered to be carriers of HTLV. Thus, horizontal spread of HTLV occurs frequently among humans. We set out to determine whether HTLV reacts with human complement, and report here that, unlike other animal retroviruses, HTLV is not lysed by normal human serum--this might explain the infectivity and persistence of HTLV in humans.


Allozyme variation in stable flies (Diptera: Muscidae).
Polyacrylamide gel electrophoresis was used to resolve allozymes in the cosmopolitan blood-feeding stable fly, Stomoxys calcitrans (L.). Nineteen of 38 loci were polymorphic (53%). Mean heterozygosities among all loci and among only polymorphic loci were 0.096 and 0.182, respectively. These gene diversity measures are about half those among other muscid Diptera. Variation in gene frequencies was examined in 10 natural stable fly populations from Iowa and Minnesota. Gene frequencies were homogeneous at five of eight loci among six populations in 1990 and eight of eight loci among four populations in 1992. Wright's F statistics showed no significant departure from random mating among stable flies. It was concluded that gene flow compensates for any local differentiation in stable fly populations.


Simultaneous upgrading of biomass-derived sugars to HMF/furfural via enzymatically isomerized ketose intermediates.
Recently, exploring fermentative or chemical pathways that convert biomass-derived sugars to fuels/chemicals has attracted a lot of interest from many researchers. We are investigating a hydrocarbon pathway from mixed sugars via 5-hydroxymethyl furfural (HMF) and furfural intermediates. To achieve this goal, we must first convert glucose and xylose to HMF and furfural in favorable yields. Current processes to produce HMF/furfural generally involve the use of acid catalysts in biphasic systems or solvents such as ionic liquids. However, the yield from transforming glucose to HMF is lower than the yield of furfural from xylose. In this study, we present an efficient chemical pathway simultaneously transforming glucose and xylose to HMF and furfural via ketose intermediates, i.e., fructose and xylulose, which were generated from glucose and xylose via enzymatic isomerization. In the enzymatic isomerization, by adding sodium borate to complex with the ketoses, xylose conversion reached equilibrium after 2 h with a conversion of 91% and glucose conversion reached 84% after 4 h. By enzymatically isomerizing the aldoses to ketoses, the following dehydration reactions to HMF and furfural could be performed at low process temperatures (i.e., 110-120 °C) minimizing the side reactions of the sugars and limiting the degradation of furfurals to humins and carboxylic acids. At 120 °C, pH 0.5, and 15 min reaction time, mixed ketose sugars were converted to HMF and furfural in yields of 77% and 96%, respectively (based on starting aldose concentrations). Taken together, our results demonstrate that this combined biological and chemical process could be an effective pathway to simultaneously convert biomass-derived glucose and xylose to HMF and furfural, for use as intermediates in the production of hydrocarbons.


Relationships between maximum temperature and heat-related illness across North Carolina, USA.
Heat kills more people than any other weather-related event in the USA, resulting in hundreds of fatalities each year. In North Carolina, heat-related illness accounts for over 2,000 yearly emergency department admissions. In this study, data on emergency department (ED) visits for heat-related illness (HRI) were obtained from the North Carolina Disease Event Tracking and Epidemiologic Collection Tool to identify spatiotemporal relationships between temperature and morbidity across six warm seasons (May-September) from 2007 to 2012. Spatiotemporal relationships are explored across different regions (e.g., coastal plain, rural) and demographics (e.g., gender, age) to determine the differential impact of heat stress on populations. This research reveals that most cases of HRI occur on days with climatologically normal temperatures (e.g., 31 to 35 °C); however, HRI rates increase substantially on days with abnormally high daily maximum temperatures (e.g., 31 to 38 °C). HRI ED visits decreased on days with extreme heat (e.g., greater than 38 °C), suggesting that populations are taking preventative measures during extreme heat and therefore mitigating heat-related illness.


A calcium-permeable non-selective cation channel in the thick ascending limb apical membrane of the mouse kidney.
Non-selective cation channels have been described in the basolateral membrane of the renal tubule, but little is known about functional channels on the apical side. Apical membranes of microdissected fragments of mouse cortical thick ascending limbs were searched for ion channels using the cell-free configuration of the patch-clamp technique. A cation channel with a linear current-voltage relationship (19pS) that was permeable both to monovalent cations [P(NH4)(1.7)>P(Na) (1.0)=P(K) (1.0)] and to Ca(2+) (P(Ca)/P(Na)≈0.3) was detected. Unlike the basolateral TRPM4 Ca(2+)-impermeable non-selective cation channel, this non-selective cation channel was insensitive to internal Ca(2+), pH and ATP. The channel was already active after patch excision, and its activity increased after reduced pressure was applied via the pipette. External gadolinium (10(-5)M) decreased the channel-open probability by 70% in outside-out patches, whereas external amiloride (10(-4)M) had no effect. Internal flufenamic acid (10(-4)M) inhibited the channel in inside-out patches. Its properties suggest that the current might be supported by the TRPM7 protein that is expressed in the loop of Henle. The conduction properties of the channel suggest that it could be involved in Ca(2+) signaling.


Effect of ingestion of glucose on fibrinolytic activity and prothrombin time in diabetic and non-diabetic persons.
Effect of ingestion of 50 g of glucose on euglobulin clot lysis time and prothrombin time was studied in 14 diabetic and 12 non-diabetic persons. There was no significant change in euglobulin clot lysis time and prothrombin time after ingestion of glucose in the non-diabetic group. In the diabetic group, ingestion of glucose resulted in significant increase in euglobulin clot lysis time at the end of one hr which returned to initial level at the end of two hours even though blood glucose level at two hrs was still higher than fasting level. Increase in clot lysis time has no correlation to the blood glucose level. There was no significant change in prothrombin time after glucose ingestion.


Significance of a soft-coagulation system with monopolar electrode for hepatectomy: A retrospective two-institution study by propensity analysis.
The VIO soft-coagulation system (VIO) with a monopolar electrode is a novel hemostatic device that provides hemostasis by superficial contact at the bleeding site without carbonization. Because heat injury remains a concern, surgical records and postoperative liver dysfunction were retrospectively evaluated in a cohort study. Between September 2010 and March 2016, 322 patients underwent hepatectomy in which hemostatic devices were used at two institutions. Surgical results with use of VIO at one institute (VIO group) were compared with those without use of VIO at a second institute (control group), and propensity analysis was performed. In limited resection and segmentectomy or sectionectomy performed in the VIO group, the prevalence of liver cirrhosis was significantly higher and the operation time was significantly longer in comparison with the control group (p < 0.05). In all hepatectomies, postoperative levels of total bilirubin and aspartate or alanine transaminase tended to be increased and prothrombin activity tended to be lower in the VIO group in comparison with the control group (p < 0.05). The prevalence of hepatic failure in the VIO group was significantly higher in comparison with that in the control group (p < 0.05). In cases of segmentectomy or sectionectomy, blood loss was significantly increased in the VIO group in comparison with that in the control group (p < 0.05) Propensity score matching showed that although the surgical records and outcomes were not significantly different between the groups, postoperative liver dysfunction was significant in the VIO group in comparison with the control group (p < 0.05). Mild postoperative hepatic thermal injury with VIO was confirmed, and therefore, surgeons should take care when using the VIO system to make frequent wide resected cuts on the surface of the liver.


Different profiles of buprenorphine-induced analgesia and antihyperalgesia in a human pain model.
Different mechanisms were proposed for opioid-induced analgesia and antihyperalgesia, which might result in different pharmacodynamics. To address this issue, the time course of analgesic and antihyperalgesic effects of intravenous (i.v.) and sublingual (s.l.) buprenorphine was assessed in an experimental human pain model. Fifteen volunteers were enrolled in this randomized, double-blind, and placebo controlled cross-over study. The magnitude of pain and the area of secondary hyperalgesia following transcutaneous stimulation were repetitively assessed before and up to 150 min after administration of (1) 0.15 mg buprenorphine i.v. and placebo pill s.l., (2) 0.2 mg buprenorphine s.l. and saline 0.9% i.v. or (3) saline 0.9% i.v. and placebo pill s.l. as a control. The sessions were separated by 2 week wash-out periods. For both applications of buprenorphine the antihyperalgesic effects were more pronounced as compared to the analgesic effects (66+/-9 vs. 26+/-5% and 43+/-10 vs. 10+/-6%, for i.v. and s.l. application, respectively). This contrasts the pattern for the intravenous administration of pure mu-receptor agonists in the same model in which the antihyperalgesic effects are weaker. The apparent bioavailability of buprenorphine s.l. as compared to buprenorphine i.v. was 58% with a 15.8 min later onset of antinociceptive effects. The half-life of buprenorphine-induced analgesic and antihyperalgesic effects were 171 and 288 min, respectively. In contrast to pure mu-receptor agonists, buprenorphine exerts a lasting antihyperalgesic effect in our model. It will be of major clinical interest whether this difference will translate into improved treatment of pain states dominated by central sensitization.


Homotransplantation of the liver in a patient with hepatoma and hereditary tyrosinemia.
A girl with hereditary tyrosinemia, diagnosed at 6 months of age, was treated with a diet restricted in phenylalanine and tyrosine. At 9 1/2 years of age she developed an acutely enlarged liver and spleen, and the diagnosis of hepatocarcinoma was made. The patient received a liver transplant and tyrosine metabolites became normal while she was receiving a regular diet. Three months later, an infected thrombosis of the portal vein caused her death. Liver transplant appears to be an effective method of enzyme replacement in tyrosinemia and should be considered for prevention of hepatoma.


A protocol for the treatment of hypertrophic scars and keloids.
Hypertrophic scars and keloids still present problems in both white and pigmented skin. A treatment protocol is proposed: Hypertrophic scars are primarily treated with intralesional injections of corticosteroids or with compression therapy. Surgical scar revision is only secondarily indicated. Recurrent and resistant hypertrophic scars are surgically excised and postoperatively irradiated (twice with 400-cGy 7-MeV electron irradiation).


Unexpected remarkable stability of primary ozonides derived from alkenyl stannanes. One-pot synthesis of 1,2-diols from alkynes.
Primary ozonides derived from alkenyl stannanes display an unusual stability and can be transformed into 1,2-diols by treatment with dimethyl sulfide and borane-methyl sulfide complex. This observation has been incorporated into the development of a novel one-pot strategy for the conversion of alkynes into 1,2-diols.


Unsaturated C3,5,7,9-Monocarboxylic Acids by Aqueous, One-Pot Carbon Fixation: Possible Relevance for the Origin of Life.
All scientific approaches to the origin of life share a common problem: a chemical path to lipids as main constituents of extant cellular enclosures. Here we show by isotope-controlled experiments that unsaturated C3,5,7,9-monocarboxylic acids form by one-pot reaction of acetylene (C2H2) and carbon monoxide (CO) in contact with nickel sulfide (NiS) in hot aqueous medium. The primary products are toto-olefinic monocarboxylic acids with CO-derived COOH groups undergoing subsequent stepwise hydrogenation with CO as reductant. In the resulting unsaturated monocarboxylic acids the double bonds are mainly centrally located with mainly trans-configuration. The reaction conditions are compatible with an origin of life in volcanic-hydrothermal sub-seafloor flow ducts.


Use of testicular versus ejaculated sperm for intracytoplasmic sperm injection among men with cryptozoospermia: a meta-analysis.
To examine outcomes of intracytoplasmic sperm injection (ICSI) using testicular versus ejaculated sperm among men with cryptozoospermia. Meta-analysis. Not applicable. Men with cryptozoospermia undergoing consecutive ICSI cycles using ejaculated or testicular sperm. A systematic search was performed using PubMed (inception to August 2015). Inclusion criteria were studies comparing ICSI outcomes among men with cryptozoospermia using ejaculated and testicular sperm. Primary outcomes included ICSI fertilization or pregnancy rates (PRs). Secondary analysis included number of retrieved oocytes, maternal and paternal ages. Meta-analysis of weighted data using a random effects model was performed. Results are reported as relative risk or weighted mean differences (WMD) with 95% confidence intervals (CI). Five cohort studies were included, encompassing 272 ICSI cycles and 4,596 injected oocytes. There were no differences in ICSI PRs (relative risk [RR] 0.53, 95% CI 0.19-1.42, I(2) = 67%) or fertilization rates (RR 0.91, 95% CI 0.78-1.06, I(2) = 73%) between testicular and ejaculated sperm groups. There was a significant trend toward increasing maternal age (WMD 1.69 years, 95% CI -2.71 to -0.66) and paternal age (WMD 2.61 years, 95% CI -4.73 to -0.48) with testicular sperm. There was no difference between numbers of oocytes retrieved (WMD 0.95, 95% CI -0.15 to 2.05). Post-hoc power analysis revealed pβ <20% for PR analysis and pβ <10% for fertilization rate analysis. The existing literature does not support a recommendation for men with cryptozoospermia to use testicular sperm in preference over ejaculated sperm for ICSI.


An atypical case of delayed radiation necrosis of the brain.
A patient had radiation necrosis of the brain after treatment for a chromophobe adenoma of the pituitary. Atypically, and in contrast to most previously reported cases, clinical symptoms and signs were few. The computerized tomographic findings are discussed with a review of the relevant literature.


Predictive performance of different NTCP techniques for radiation-induced esophagitis in NSCLC patients receiving proton radiotherapy.
This study aimed to compare the predictive performance of different modeling methods in developing normal tissue complication probability (NTCP) models for predicting radiation-induced esophagitis (RE) in non-small cell lung cancer (NSCLC) patients receiving proton radiotherapy. The dataset was composed of 328 NSCLC patients receiving passive-scattering proton therapy and 41.6% of the patients experienced ≥ grade 2 RE. Five modeling methods were used to build NTCP models: standard Lyman-Kutcher-Burman (sLKB), generalized LKB (gLKB), multivariable logistic regression using two variable selection procedures-stepwise forward selection (Stepwise-MLR), and least absolute shrinkage and selection operator (LASSO-MLR), and support vector machines (SVM). Predictive performance was internally validated by a bootstrap approach for each modeling method. The overall performance, discriminative ability, and calibration were assessed using the Negelkerke R2, area under the receiver operator curve (AUC), and Hosmer-Lemeshow test, respectively. The LASSO-MLR model showed the best discriminative ability with an AUC value of 0.799 (95% confidence interval (CI): 0.763-0.854), and the best overall performance with a Negelkerke R2 value of 0.332 (95% CI: 0.266-0.486). Both of the optimism-corrected Negelkerke R2 values of the SVM and sLKB models were 0.301. The optimism-corrected AUC of the gLKB model (0.796) was higher than that of the SVM model (0.784). The sLKB model had the smallest optimism in the model variation and discriminative ability. In the context of classification and probability estimation for predicting the NTCP for radiation-induced esophagitis, the MLR model developed with LASSO provided the best predictive results. The simplest LKB modeling had similar or even better predictive performance than the most complex SVM modeling, and it was least likely to overfit the training data. The advanced machine learning approach might have limited applicability in clinical settings with a relatively small amount of data.


Matrix-assisted laser desorption ionization-time of flight mass spectrometry identification of peptide citrullination site using Br signature.
Enzymatic conversion of arginine to citrulline by peptidyl arginine deiminase is associated with peptide presentation and development of autoimmunity in rheumatoid arthritis. In order to facilitate identification of the citrullination site, citrulline residue was modified using 4-bromophenyl glyoxal, and 194Da mass increase and incorporation of the Br signature were confirmed by MALDI-TOF MS. Using this approach, we identified four and five citrullination sites of bovine serum albumin and bovine fibrinogen, respectively. MALDI-TOF/TOF MS was used to unambiguously identify two citrullination sites from bovine fibrinogen.


Isothermal chemical denaturation of large proteins: Path-dependence and irreversibility.
State functions (e.g., ΔG) are path independent and quantitatively describe the equilibrium states of a thermodynamic system. Isothermal chemical denaturation (ICD) is often used to extrapolate state function parameters for protein unfolding in native buffer conditions. The approach is prudent when the unfolding/refolding processes are path independent and reversible, but may lead to erroneous results if the processes are not reversible. The reversibility was demonstrated in several early studies for smaller proteins, but was assumed in some reports for large proteins with complex structures. In this work, the unfolding/refolding of several proteins were systematically studied using an automated ICD instrument. It is shown that: (i) the apparent unfolding mechanism and conformational stability of large proteins can be denaturant-dependent, (ii) equilibration times for large proteins are non-trivial and may introduce significant error into calculations of ΔG, (iii) fluorescence emission spectroscopy may not correspond to other methods, such as circular dichroism, when used to measure protein unfolding, and (iv) irreversible unfolding and hysteresis can occur in the absence of aggregation. These results suggest that thorough confirmation of the state functions by, for example, performing refolding experiments or using additional denaturants, is needed when quantitatively studying the thermodynamics of protein unfolding using ICD.


Co-localization of SCPB-like and FMRFamide-like immunoreactivities in crustacean nervous systems.
A monoclonal antibody to the molluscan small cardioactive peptide SCPB and a polyclonal antibody to FMRFamide were used to localize antigens in the stomatogastric nervous system and brain of two species of Cancer. Both antibodies labeled cell bodies, axons, and neuropilar processes in the brain and in the stomatogastric nervous system. All of the SCPB immunoreactive neurons were co-labeled with antibody to FMRFamide. However, antibody to FMRFamide labeled additional neurons of the commissural ganglion and the brain that were not immunoreactive to the monoclonal SCPB antibody.


Arteriovenous malformation of the orbit and palate.
A patient was reported in which orbital and retinal arteriovenous malformations were noted. The value of oral examination in discovery of another palatal arteriovenous malformation is discussed.


Clinic for Multimorbidity: An Innovative Approach to Integrate General Practice and Specialized Health Care Services.
Caring for patients with multimorbidity in general practice is increasing in amount and complexity. To integrate care for patients with multimorbidity and to support general practitioners (GPs), the Clinic for Multimorbidity (CM) was established in 2012 at Silkeborg Regional Hospital, Denmark. This case study aims to describe the CM and the patients seen in it. CM is an outpatient clinic that offers a comprehensive one-day assessment of the patient's complete health status and medication. GPs can refer patients with complex multimorbidity (≥2 chronic conditions). It involves collaboration across medical specialties and healthcare professions. The assessment is completed with a multidisciplinary conference and recommendation.In all, 141 patients were referred to the CM between May 2012 and November 2017. The median age was 70 years, 80% had more than five diagnoses, and in median patients had a usage of 11 drugs (IQI, 7-15). Physical and mental health was reported low (SF-12 score: 26 and 42). In median four specialties were involved and 4 examinations (IQI, 3-5) conducted. The CM offers innovative care by bridging and exceeding conventional boundaries of disciplines, professions, organizations, and primary and specialized care. The patients represented a very complex group, requiring many examinations and involvement of several specialists.


The effect of coexisting autoimmune thyroiditis in children with Type 1 diabetes on optical coherence tomography results.
To assess the influence of thyroid hormones status and coexistence of autoimmune thyroiditis on optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) results in children with Type 1 diabetes (T1D). In the prospective, observational study (n = 175) we analyzed the impact of thyroid hormones on OCT results and the differences between the matched groups of children with T1D (n = 84; age = 13.14 ± 3.6; diabetes duration = 5.99 ± 3.3 years) and the children with T1D and autoimmune thyroiditis (AT) (n = 20; age = 13.94 ± 3.6; diabetes duration = 6.7 ± 4 years). We analyzed the following parameters: fovea avascular zone (FAZ), foveal thickness (FT), parafoveal thickness (PFT), ganglion cell complex (GCC), loss volume (global-GLV, focal-FLV), capillary vessel density: superficial (whole-wsVD, foveal-fsVD, parafoveal-psVD), and deep (whole-wdVD, foveal-fdVD, parafoveal-pdVD. The differences between the groups were tested by the unpaired t-Student test, Mann-Whitney U test as appropriate, whereas p level .05 was recognized as significant. We detected the significant correlations between thyroid-stimulating hormone (TSH) level and PFT (r = -0.14; p < .05), psVD (r = -0.18; p < .005). The level of free triiodothyronine (FT3) was correlated with psVD (r = -0.14; p < .05). We found significant correlation between free thyroxine (FT4) and fsVD (r = -0.17; p < .01). In the studied T1D and AT groups there were statistical differences in FT (p < .005), PFT (p < .03), GCC (p < .01), and GLV (p < .003). We did not observe any significant differences in the FAZ area between the groups. In our patients the co-occurrence of T1D and AT worsens the status of retinal parameters. Further studies are necessary to observe these relations and their potential influence on the occurrence of diabetic retinopathy (DR).


Patch Materials for Pulmonary Artery Arterioplasty and Right Ventricular Outflow Tract Augmentation: A Review.
Patch augmentation of the right ventricular outflow tract (RVOT) and pulmonary artery (PA) arterioplasty are relatively common procedures in the surgical treatment of patients with congenital heart disease. To date, several patch materials have been applied with no agreed upon clinical standard. Each patch type has unique performance characteristics, cost, and availability. There are limited data describing the various advantages and disadvantages of different patch materials. We performed a review of studies describing the clinical performance of various RVOT and PA patch materials and found a limited but growing body of literature. Short-term clinical performance has been reported for a multitude of patch types, but comparisons are limited by inconsistent study design and scarce histologic data. Standard clinical criteria for assessment of patch efficacy and criteria for intervention need to be applied across patch types. The field is progressing with improvements in outcomes due to newer patch technologies focused on reducing antigenicity and promoting neotissue formation which may have the ability to grow, remodel, and repair.


Inspection of thermal jump conditions on nanofluids with nanoparticles and multiple slip effects.
The significance of slip boundary conditions with thermal radiation implications on a steady flow of nano suspension over a rotating disk with a constant magnetic field is discussed in this research investigation. Here Iron oxide [Formula: see text], Zirconium dioxide [Formula: see text], and Titanium [Formula: see text] are recruited as nanoparticles and water [Formula: see text] as a host fluid. The appropriate similarities transformations are used to transfer main PDEs into a system of nonlinear ODEs. The set of ODEs is then solved via shooting approach (bvp4c solver) a built-in function in MATLAB. The depictical outcomes of the physical flow parameters like thermal radiation and velocity slip parameters are revealed and clarified with the assist of figures. The slip parameter significantly reduces the velocity profiles, according to this investigation. The pressure is declined for the higher estimates of the magnetic parameter. The thermal profile was uplifted for the rising values of the thermal radiation parameter. Meteorology, meteorological, atmospheric research, biochemical engineering, power engineering, transportation production, solar energy transformations, sensing micro fabrication, tumblers in polymer manufacturing, and other fields will benefit from this suggested model. The suggested study has been developed in response to these kinds of practical consequences. This work is unique in that it investigates the consequences of a magnetic field, slip boundary conditions, and thermal radiation on nanoparticles flow across a disk. The recent study is innovative, and it could be used by other researchers to learn more about the heat exchange behavior and reliability of working fluids.


Hybrid immunity in older adults is associated with reduced SARS-CoV-2 infections following BNT162b2 COVID-19 immunisation.
Older adults, particularly in long-term care facilities (LTCF), remain at considerable risk from SARS-CoV-2. Data on the protective effect and mechanisms of hybrid immunity are skewed towards young adults precluding targeted vaccination strategies. A single-centre longitudinal seroprevalence vaccine response study was conducted with 280 LCTF participants (median 82 yrs, IQR 76-88 yrs; 95.4% male). Screening by SARS-CoV-2 polymerase chain reaction with weekly asymptomatic/symptomatic testing (March 2020-October 2021) and serology pre-/post-two-dose Pfizer-BioNTech BNT162b2 vaccination for (i) anti-nucleocapsid, (ii) quantified anti-receptor binding domain (RBD) antibodies at three time-intervals, (iii) pseudovirus neutralisation, and (iv) inhibition by anti-RBD competitive ELISA were conducted. Neutralisation activity: antibody titre relationship was assessed via beta linear-log regression and RBD antibody-binding inhibition: post-vaccine infection relationship by Wilcoxon rank sum test. Here we show neutralising antibody titres are 9.2-fold (95% CI 5.8-14.5) higher associated with hybrid immunity (p < 0.00001); +7.5-fold (95% CI 4.6-12.1) with asymptomatic infection; +20.3-fold, 95% (CI 9.7-42.5) with symptomatic infection. A strong association is observed between antibody titre: neutralising activity (p < 0.00001) and rising anti-RBD antibody titre: RBD antibody-binding inhibition (p < 0.001), although 18/169 (10.7%) participants with high anti-RBD titre (>100BAU/ml), show inhibition <75%. Higher RBD antibody-binding inhibition values are associated with hybrid immunity and reduced likelihood of infection (p = 0.003). Hybrid immunity in older adults was associated with considerably higher antibody titres, neutralisation and inhibition capacity. Instances of high anti-RBD titre with lower inhibition suggests antibody quantity and quality as independent potential correlates of protection, highlighting added value of measuring inhibition over antibody titre alone to inform vaccine strategy.


Design and comparative characterization of RecA variants.
RecA plays a central role in DNA repair and is a main actor involved in recombination and activation of the SOS response. It is also used in the context of biotechnological applications in recombinase polymerase isothermal amplification (RPA). In this work, we studied the biological properties of seven RecA variants, in particular their recombinogenic activity and their ability to induce the SOS response, to better understand the structure-function relationship of RecA and the effect of combined mutations. We also investigated the biochemical properties of RecA variants that may be useful for the development of biotechnological applications. We showed that Dickeya dadantii RecA (DdRecA) had an optimum strand exchange activity at 30 °C and in the presence of a dNTP mixture that inhibited Escherichia coli RecA (EcRecA). The differences between the CTD and C-tail of the EcRecA and DdRecA domains could explain the altered behaviour of DdRecA. D. radiodurans RecA (DrRecA) was unable to perform recombination and activation of the SOS response in an E. coli context, probably due to its inability to interact with E. coli recombination accessory proteins and SOS LexA repressor. DrRecA strand exchange activity was totally inhibited in the presence of chloride ions but worked well in acetate buffer. The overproduction of Pseudomonas aeruginosa RecA (PaRecA) in an E. coli context was responsible for a higher SOS response and defects in cellular growth. PaRecA was less inhibited by the dNTP mixture than EcRecA. Finally, the study of three variants, namely, EcPa, EcRecAV1 and EcRecAV2, that contained a combination of mutations that, taken independently, are described as improving recombination, led us to raise new hypotheses on the structure-function relationship and on the monomer-monomer interactions that perturb the activity of the protein as a whole.


Take a look at the bright side: effects of contrast polarity on gaze direction judgments.
Observers are inaccurate when judging the gaze direction of eyes shown in negative rather than positive polarity. On the basis of this polarity effect, it has been proposed that gaze is perceived as directed from the dark part of the eye. Our experiment investigated whether direction judgments simply follow this heuristic, as has been suggested. Participants judged the gaze direction of eyes shown at different eccentricities in positive or negative polarity. The error pattern revealed that most errors were incorrect "straight" judgments, suggesting that judgments do not merely follow the heuristic "the dark part does the looking." We suggest that gaze judgments are based on the outcome of a competition between gaze direction signals: Whereas luminance cues may indicate that gaze is directed from the dark part of the eye, geometric cues may indicate the opposite. This interpretation is supported by reduced overall error rates, and fewer incorrect "straight" responses, for more extreme gaze directions.


Retracted: Application of the Deep Learning Algorithm and Similarity Calculation Model in Optimization of Personalized Online Teaching System of English Course.
[This retracts the article DOI: 10.1155/2021/8249625.].


A simplified approach to the external lateral nasal osteotomy: a technical note.
Lateral osteotomy is usually performed to narrow a wide nasal base, widen a narrow nasal base, straighten deviated nasal bones, or close an (iatrogenic) open roof deformity. Based on the approach used, nasal osteotomy can be classified as external or internal. Although nasal osteotomy is an essential part of cosmetic rhinoplasty, it can be very difficult for young surgeons to perform external osteotomy. This article focuses on external osteotomy and its essential concepts. In addition, a new splint-guide method is introduced, which can help young surgeons perform external osteotomy in a very safe and predictable manner.


Reinforcement of tonic vibration reflex and exteroceptive vibration-induced flexion reflex in finger flexion muscles by forced respiration.
The effects of forced respiration on tonic vibration reflex (TVR) and exteroceptive vibration-induced flexion reflex (VFR) were studied in healthy man. vibration (100 Hz) applied to finger flexion muscles or the volar side of the middle finger induced a slowly augmenting facilitation of the TVR, which has mono-and polysynaptic components, and VFR, which is polysynaptic. Forced inspiration and forced expiration facilitated these slowly augmenting processes in both reflexes. Respiration reinforces both proprioceptive and exteroceptive reflexes elicited by vibration.


Excitotoxicity as a stochastic process.
1. Neuronal death following excitotoxic insult appears to be a stochastic process involving transition through an intermediate biochemical state. 2. Hydrogen ion accumulation in the hours after toxic glutamate exposure may indicate that this transition has occurred.


Fibres and films made from DNA and CTMA-modified DNA embedded with gold nanorods and organic light-emitting materials.
The scaffolding of deoxyribonucleic acid (DNA) makes DNA molecules effective templates for hosting various types of nanomaterials. Recently, electrospun fibres formed by a variety of polymers have begun to see use in a number of applications, such as filtration in energy applications, insulation in thermodynamics and protein scaffolding in biomedicine. In this study, we constructed electrospun fibres and thin films made of DNA and cetyltrimethylammonium chloride (CTMA)-modified DNA (CDNA) embedded with dyes, organic light-emitting materials (OLEMs), and gold nanorods (GNRs). These materials provide significant advantages, including selectivity of dimensionality, solubility in organic and inorganic solvents, and functionality enhancement. In addition, coaxial fibres made of CDNA were constructed to demonstrate the feasibility of constructing relatively complex fibres with an electrospinner. To determine the basic physical characteristics of the fibres and thin films containing GNRs and OLEMs, we conducted current measurements, photoluminescence (PL) measurements, X-ray photoelectron spectroscopy (XPS), and ultraviolet-visible (UV-Vis) spectroscopy. The currents in DNA and CDNA were found to exhibit Ohmic behaviour, while the PL emission could be controlled by OLEMs. In addition, the XPS provided the chemical configuration of samples, and the UV-Vis spectra revealed the plasmon resonance of GNR. Due to their simple fabrication and enhanced functionality, these DNA and CDNA fibres and thin films could be used in various devices (e.g., filters or blocking layers) and sensors (e.g., gas detectors and bio sensors) in a number of industries.


Salvage gamma knife surgery for recurrent glossopharyngeal neuralgia following microvascular decompression: a retrospective case series.
Although microvascular decompression (MVD) is recognized as the preferred therapy for drug-resistant idiopathic glossopharyngeal neuralgia (GPN), the management of recurrent GPN following MVD is seldom mentioned in the current literature. This study aims to demonstrate the efficacy and safety of salvage Gamma Knife surgery (GKS) in the treatment of recurrent GPN after MVD. From October 2012 to January 2018, seven patients (three males and four females) underwent salvage GKS for recurrent GPN following MVD, including two patients who received repeat GKS due to pain recurrence after their initial GKS salvage. The median age was 69 years (range 49-81 years) at first GKS and 72 years (67 years; 77 years) at second GKS. The delivered dose was 80 or 90 Gy at first GKS and 90 Gy at second GKS. Pain outcome was assessed according to the Barrow Neurological Institute (BNI) score. The median duration of follow-up after first GKS was 68 months (range 29-89 months) and 45 months (56 months; 33 months) after second GKS. The median time to pain response was 24 days (range, 6-80 days). One patient experienced palatoglossal hyperesthesia after first GKS, and no complications were noted after second GKS. At the last follow-up, 4 patients were BNI I, 1 was BNI II, and 2 was BNI IIIa. Salvage GKS is safe and effective for treating recurrent GPN after MVD, even for patients who experienced pain recurrence following their initial GKS salvage.


Methylcholanthrene-induced tumors in resistant and sensitive Jensen sarcoma rats. i. effect of fresh prepared MC emulsion.
By two subcutaneous or intramuscular injections of 20-methylcholanthrene (MC), 5 mg/animal in vegetal oil, followed after 74 days by 10 mg of MC emulsion, sarcomata were obtained in 63.6% of Jensen sarcoma-resistant rats (R) and in 36.8% of Jensen sarcoma-sensitive rats (S). One of the induces sarcomas, transplanted from R to R and then to S rats, presented a very high antigenicity: it strongly immunised receptive rats against the induced sarcoma and also, in a lower degree, against the Jensen sarcoma. Antigenicity was maintained up to the tenth passage.


The Implications of Policies on the Welfare of Free-Roaming Cats in New Zealand.
A lack of national legislation for cat management in New Zealand poses challenges for ensuring that practices are consistently humane and effective. In this paper, we review the current cat management policies in New Zealand and the implications they have on the welfare of free-roaming cats (from here on, referred to as 'cats'). Our review demonstrates that there are multiple policy mechanisms used to manage cats in New Zealand for a variety of reasons, including animal welfare, pest management, and nuisance, and that these different policies have both positive and negative implications for cat welfare. We provide context pertaining to New Zealanders' acceptance of current or future laws and regulations and compare the New Zealand policy landscape with other countries, with a particular emphasis on Australia, to identify potential directions and outcomes of increased regulation. We discuss the future of the regulatory environment in New Zealand, including the need to better understand the impact of policies on cats, people, and other animals in urban, rural, and wild spaces. We further discuss the need to better understand the cat-human relationship for future policy decisions and offer a solution based on national cat legislation.


Suzuki-Miyaura Cross-Coupling of Benzylic Bromides Under Microwave Conditions.
A procedure for benzylic Suzuki-Miyaura cross-coupling under microwave conditions has been developed. These conditions allowed for heterocyclic compounds to be coupled. Optimum conditions found were Pd(OAc)(2), JohnPhos as the catalyst and ligand, potassium carbonate as base, and DMF as the solvent. Using these conditions, a library of structurally diverse compounds was synthesized.


Genetic analysis of Borrelia.
DNA homology studies were performed on Borrelia hermsii, B. duttoni, B. crocidurae and the O. coriaceus spirochete. These organisms had a genus level relationship with each other. B. hermsii was 17 to 53% homologous with B. duttoni, B. crocidurae, and the O. coriaceus spirochetes; B. crocidurae was 17-32% related to B. hermsii, B. anserina and the O. coriaceus spirochete, and the O. coriaceus spirochete was 28-50% related to B. hermsii, B. crocidurae and B. anserina. The O. coriaceus spirochete was 10% homologous with B. burgdorferi, the etiologic agent of Lyme disease. Plasmid DNA was detected in these strains of Borrelia. Southern blot analysis of plasmid DNA from these strains suggested little or no homology with plasmid DNA from B. hermsii used as a probe. A plasmid of 9.2 kilobases was seen in B. burgdorferi strain CT1. This plasmid was shown to be a tandem repeat with unit length of 4.6 kilobases. Sequences corresponding to this plasmid were detected in several fresh tick isolates from North America, and were not seen in any animal, human or European isolates surveyed. The role in the biology of the spirochete played by this plasmid is unknown.


A novel mathematical model identifies potential factors regulating bone apposition.
The development of pharmaceutical treatments for bone disease can be enhanced by mathematical models that predict their effects on matrix apposition during cancellous bone remodelling. Therefore, a mathematical model was constructed to simulate the rate of focal bone formation from the number of osteoid-forming osteoblasts at one microsite and their rate of activity. The number of mature osteoid-forming cells was simulated from a relationship describing the proliferation of preosteoblasts. Osteoblast activity was described by Michaelis-Menten enzyme kinetic equations adapted to describe cellular activity. The model incorporates the negative feedback effects on the rates of bone apposition due to the reduction in size of mature osteoblasts with continuing differentiation and the reduction in number of osteoid-forming cells with apoptosis and osteocyte formation. In addition, the rate of mineralisation is limited according to osteoid substrate availability. Results of sensitivity analysis revealed the amount of bone formed at one microsite to be more sensitive to changes in factors that controlled cell growth during proliferation and the number of mature osteoid-forming osteoblasts than to those that determined cellular activity. Matrix and osteocyte signalling were shown to have potentially important roles in controlling rates of osteoid apposition in normal, healthy bone. This simple model supports the critical role of controlled mitotic growth in normal bone apposition. It can also help to explain how the homeostatic processes of bone resorption and apposition during remodelling can be disrupted by growth factors that affect the mitotic fraction and division time of proliferative preosteoblast cells.


Immunohistochemical analysis of inflammatory infiltrates around the injection site of a streptococcal preparation, OK-432, in rat tongue.
On the assumption that neutrophils around the injection site of OK-432, a heat- and penicillin-treated lyophilized preparation of the Su strain of Streptococcus pyogenes, enhance immunologic response through the production of Interleukin-1 (IL-1), OK-432 was injected into rat tongue, and specimens from the tongue were immunohistochemically investigated at various intervals after the injection, to clarify the process of inflammatory and immune responses at the injection site. Neutrophils and mononuclear cells appeared around the OK-432 injection site after 1 hour, increased to their maximum level at 24 hours, and then decreased from the 3rd to the 7th day. IL-1 was detected on neutrophils 3 hours after the injection, and OX-08-positive cells (suppressor/cytotoxic T cells and the majority of natural killer cells) remarkably increased. OX-39-positive cells (IL-2 receptor) appeared after 12 hours. These results suggest that neutrophils around the injection site of OK-432 at early phases of inflammation play a role in the expression of BRM function through IL-1.


Glutathione depletion prevents diet-induced obesity and enhances insulin sensitivity.
Excessive accumulation of reactive oxygen species (ROS) in adipose tissue has been implicated in the development of insulin resistance and type 2 diabetes. However, emerging evidence suggests a physiologic role of ROS in cellular signaling and insulin sensitivity. In this study, we demonstrate that pharmacologic depletion of the antioxidant glutathione in mice prevents diet-induced obesity, increases energy expenditure and locomotor activity, and enhances insulin sensitivity. These observations support a beneficial role of ROS in glucose homeostasis and warrant further research to define the regulation of metabolism and energy balance by ROS.


[Surgery].
2007 was marked by a growing trend towards minimal invasive surgery and enhanced recovery, especially in visceral surgery. In comparison to the laparoscopic revolution in the eighties, Natural orifice transluminal endoscopic surgery (NOTES) must be watched on closely, and will probably have to be taken into account in a near future. Minimal invasive procedures in oesophageal cancer surgery have proved both efficient and oncologically safe. Implementation of Fast track protocols now permits a much faster patient's return to normal daily activity. In hepatobiliary and pancreatic surgery, multidisciplinary efforts have been done to better select patients, widen the indications and increase efficiency.


Corticosteroids influence the mortality and morbidity of acute critical illness.
Use of corticosteroids for adrenal supplementation and attenuation of the inflammatory and immune response is widespread in acute critical illness. The study hypothesis was that exposure to corticosteroids influences the mortality and morbidity in acute critical illness. This case-control retrospective study was performed in a single multidisciplinary intensive care unit at a tertiary care institution and consisted of 10,285 critically ill patients admitted between 1 January 1999 and 31 December 2004. Demographics, comorbidities, acute illness characteristics including severity measured by Sequential Organ Failure Assessment, concurrent medications, therapeutic interventions and incidence of infections were obtained from electronic medical records, were examined with multiple regression analysis and were adjusted for propensity of corticosteroid exposure. The primary outcome was hospital death, and the secondary outcome was transfer to a care facility at hospital discharge. Corticosteroid exposure in 2,632 (26%) patients was characterized by younger age, more females, higher Charlson comorbidity and maximal daily Sequential Organ Failure Assessment scores compared with control patients. Corticosteroids potentiated metabolic and neuromuscular sequels of critical illness with increased requirements for diuretics, insulin, protracted weaning from mechanical ventilation, need for tracheostomy and discharge to a care facility. Early exposure to corticosteroids predisposed to recurrent and late onset of polymicrobial and fungal hospital-acquired infections. Corticosteroids increased the risk for death or disability after adjustments for comorbidities and acute illness characteristics. Corticosteroids increased the risk for death or disability in critical illness. Hospital-acquired infections and metabolic and neuromuscular sequels of critical illness were exacerbated by corticosteroids. Careful appraisal of the indications for use of corticosteroids is necessary to balance the benefits and risks from exposure in acute critical illness.


A sterile insect technique pilot trial on Captiva Island: defining mosquito population parameters for sterile male releases using mark-release-recapture.
The sterile insect technique (SIT), which involves area-wide inundative releases of sterile insects to suppress the reproduction of a target species, has proven to be an effective pest control method. The technique demands the continuous release of sterilized insects in quantities that ensure a high sterile male:wild male ratio for the suppression of the wild population over succeeding generations. For these releases, it is important to determine several ecological and biological population parameters, including the longevity of the released males in the field, the dispersal of the released males and the wild pest population size. The Lee County Mosquito Control District initiated a study in a 47-ha portion of Captiva Island (Florida, USA), an island with a total area of 230 ha, to define biological SIT parameters for Aedes aegypti (L.), an invasive disease-vectoring mosquito known to be difficult to control due to a combination of daytime biting activity, use of cryptic breeding habitats that are difficult to target with conventional night-time ultra-low volume methods, and emerging resistance to commonly used insecticides. Another goal was to assess patterns of dispersal and survival for laboratory-reared sterile Ae. aegypti males released over time in the pilot site. These parameters will be used to evaluate the efficacy of a SIT suppression program for Ae. aegypti on Captiva Island. Over the course of seven mark-release-recapture studies using single- and multiple-point releases, 190,504 sterile marked males were released, for which the recapture rate was 1.5% over a mean period of 12 days. The mean distance traveled by sterile males of the local strain of Ae. aegypti that has colonized Captiva Island was 201.7 m from the release point, with an observed maximum traveled distance of 404.5 m. The released sterile mosquitoes had a probability of daily survival of 0.67 and an average life expectancy of ~ 2.46 days. These data together with the population size estimate and sterile:wild ratio provide a solid basis for planning the SIT operational phase which is aimed at mosquito population suppression.


Nephrotic syndrome associated with chronic persistent hepatitis B in an HIV antibody positive patient.
Several renal diseases have been reported to complicate both hepatitis B and human immunodeficiency virus infection. Establishing the exact renal diagnosis in patients with multiple viral infections requires renal biopsy. Exposure to human immunodeficiency virus may not determine renal histopathology. Although exact prognosis depends on a definitive diagnosis, treatment options may be limited in the face of several viral infections and concurrent exposure to human immunodeficiency virus.


Detection of Rickettsia spp. in ticks of wildlife fauna from Costa Rica: First report of Rickettsia rhipicephali in Central America.
In the past two decades, new species of Rickettsia have been detected and described worldwide, some of them considered pathogenic for humans. Although Costa Rica is considered a biodiversity hotspot, the knowledge about rickettsiae in sylvatic ecosystems and wild animals is scarce. The aim of this preliminary study was to detect and identify species of Rickettsia in ticks collected from wild animals in Costa Rica. A total 119 ticks were collected from 16 animal host species belonging to diverse vertebrate families (Didelphidae, Procyonidae, Felidae, Choloepodidae, Bradypodidae, Myrmecophagidae, Tayassuidae, Tapiridae, Phyllostomidae, Bufonidae, Geoemydidae, Boidae, Colubridae), and they were grouped into 43 pools to detect the presence of Rickettsia spp. DNA by PCR targeting the gltA gene. In positive pools, amplicons of the ompA, sca5 (ompB), and/or htrA genes were also amplified to identify the species present. The identification of some ticks was also confirmed by molecular methods. Four species of Rickettsia were detected in eight (19%) tick pools: Rickettsia amblyommatis in four pools of Amblyomma geayi (host: Caluromys derbianus) and one pool of Amblyomma cf. parvum (host: Nasua narica), Rickettsia rhipicephali in one pool of Dermacentor latus (host: Tayassu pecari), 'Candidatus Rickettsia colombianensi' in one pool of Amblyomma sp. nymphs (host: Boa constrictor), and Rickettsia sp. genotype IbR/CRC in one pool of Ixodes cf. boliviensis (host: Puma concolor). This is the first molecular detection of R. rhipicephali in Central America, and of 'Candidatus R. colombianensi' in Costa Rica. Results show that diverse wild animals and their ticks are associated with several species of rickettsiae in Costa Rica, which may come in contact with humans and other domestic animals in sylvatic environments.


Qualitative and quantitative determination of R-phycoerythrin from Halymenia floresia (Clemente) C. Agardh by polyacrylamide gel using electrophoretic elution technique.
R-Phycoerythrin is one of the phycobiliproteins widely found in seaweeds. In this study, we have shown to extract and purify R-Phycoerythrin from the south east cost Indian red seaweed Halymenia floresia. R-Phycoerythrin was extracted in 50mM phosphate buffer (pH 7.0). The preparative native PAGE purification was employed alternative to the chromatography and therefore can be scaled up efficiently. Both the yield and the purity of R-Phycoerythrin are very effective. The purified R-Phycoerythrin showed a single band on the examination by native PAGE electrophrosis. SDS-PAGE analysis showed five bands at 16kDa, 21kDa, 30kDa, 39kDa and 47kDa which corresponds to the α, β and γ', γ and αβ subunits. This preparative method for R-Phycoerythrin purification can offer a reference for R-Phycoerythrin purification from other marine red macro algae.


[Critical analysis on the use of the homeostasis model assessment (HOMA) indexes in the evaluation of the insulin resistance and the pancreatic beta cells functional capacity].
Beta-cell dysfunction and insulin resistance are interrelated metabolic abnormalities in the aetiology of Type 2 Diabetes. In several countries, increases in the prevalence of obesity and diabetes have been observed in association with the presence of insulin resistance. In this context, measurement of insulin resistance and beta-cell function is useful. The HOMA indexes (Homeostasis Model Assessment) have been widely used, representing an alternative for the evaluation of these parameters, particularly as a fast, easy and cheap method. This review discusses the origin and evolution of the HOMA index, as well as details of the method, analyzing features related to its validation and the cutoff limits for its interpretation.


Cavernous hemangioma. Why is peripheral filling at scintigraphy so rare?
Peripheral filling at dynamic CT occurs frequently with cavernous hemangiomas, yet this phenomenon is a rare finding on Tc-99m RBC imaging. A case of peripheral filling of a cavernous hemangioma with scintigraphy is reported and the rationale for its infrequent occurrence is discussed.


Implementation of a prehospital triage system for patients with chest pain and logistics for primary percutaneous coronary intervention in the region of Amsterdam, the Netherlands.
We aimed to describe the logistics of a prehospital triage system for patients with acute chest pain in the region of Amsterdam, The Netherlands. Ambulance electrocardiograms (ECGs) were evaluated immediately in 1 of the percutaneous coronary intervention (PCI)-capable centers. Patients accepted for primary PCI (PPCI) were directly transferred to the catheterization laboratory. Two thousand three hundred fifty ECGs of 2,192 patients were transmitted to the region's intervention centers. Median duration of chest complaints before ambulance dispatch was 67 minutes; ambulance crews recorded the first ECG within 7 minutes after arrival. Actual transmission of the ECG took an additional (median) 10 minutes. Seven hundred eleven patients (32.4%) were transported to the catheter laboratory and were treated with PPCI. Time between first prehospital ECG and start of PPCI procedure was 66 minutes. The PPCI procedure started 36 minutes after ambulance arrival at the hospital. In conclusion, the results of this study compare favorably to other reported performances of prehospital triage systems of PPCI for ST-segment elevated myocardial infarction and demonstrate that the European Society of Cardiology and American Heart Association guidelines for treatment of patients with ST-segment elevated myocardial infarction can be met.


Correlation of EUS measurement with pathologic assessment of neoadjuvant therapy response in esophageal carcinoma.
EUS-measured reduction in tumor size after neoadjuvant therapy has previously been correlated with downstaging and improved survival in patients with esophageal cancer. The aim of this study was to determine whether tumor changes measured by EUS correspond to pathologically assessed chemoradiotherapy-induced tumor regression. Forty-one patients with esophageal cancer treated with combined modality treatment were studied. After initial EUS, patients completed a cisplatin/carboplatinum, 5-fluorouracil, and radiotherapy regimen and underwent repeat EUS before resection. A positive response on EUS was defined as a 50% reduction in maximal tumor cross-sectional area. Chemoradiotherapy-induced tumor regression was assessed in resection specimens by using a previously defined pathologic scoring system based on the extent of tumor proliferation into adjacent fibrosis. Pathologic tumor regression was present in 23, indeterminate in 5, and minimal or absent in 13 patients. EUS measured a positive response in 20 of 23 (87%) patients with CRT-induced tumor regression and a negative response in 10 of 13 (77%) patients with absent tumor regression (p < 0.001). EUS had a positive predictive value of 80% for pathologic tumor regression. Measurement of tumor size by EUS is a reliable clinical method for assessing pathologic tumor regression before surgery.


The outcome of tactile touch on stress parameters in intensive care: a randomized controlled trial.
The study aimed to investigate the effects of a five-day tactile touch intervention in order to find new and unconventional measures to moderate the detrimental influence of patients' stressors during intensive care. The hypothesis was that tactile touch would decrease stress indicators such as anxiety, glucose metabolism, blood pressure, heart rate and requirements of sedative drugs and noradrenalin. A randomized controlled trial was undertaken with 44 patients, which were assigned either to tactile touch or standard treatment (a rest hour). Observations of the stress indicators were made before, during and after the intervention or standard treatment. The study showed that tactile touch led to significantly lower levels of anxiety. The circulatory parameters suggested increased circulatory stability indicated by a reduction in noradrenalin requirement. The results need to be further validated through studies with larger sample sizes.


Neurofeedback as a nonpharmacological treatment for adults with attention-deficit/hyperactivity disorder (ADHD): study protocol for a randomized controlled trial.
Neurofeedback has been applied effectively in various areas, especially in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). This study protocol is designed to investigate the effect of slow cortical potential (SCP) feedback and a new form of neurofeedback using near-infrared spectroscopy (NIRS) on symptomatology and neurophysiological parameters in an adult ADHD population. A comparison of SCP and NIRS feedback therapy methods has not been previously conducted and may yield valuable findings about alternative treatments for adult ADHD. The outcome of both neurofeedback techniques will be assessed over 30 treatment sessions and after a 6-month follow-up period, and then will be compared to a nonspecific biofeedback treatment. Furthermore, to investigate if treatment effects in this proof-of-principle study can be predicted by specific neurophysiological baseline parameters, regression models will be applied. Finally, a comparison with healthy controls will be conducted to evaluate deviant pretraining neurophysiological parameters, stability of assessment measures, and treatment outcome. To date, an investigation and comparison of SCP and NIRS feedback training to an active control has not been conducted; therefore, we hope to gain valuable insights in effects and differences of these types of treatment for ADHD in adults. This study is registered with the German Registry of Clinical Trials: DRKS00006767 , date of registration: 8 October 2014.


Laryngocele: A Rare Case Report and Review of Literature.
Laryngocele is an abnormal cystic dilatation of the saccule of the larynx. It communicates with the laryngeal lumen and contains air. Laryngocele can be classified as internal (within the larynx), external (outside the larynx) and mixed (both). It is a rare entity. Hereby, we are reporting a case of laryngocele, which presented to us with a diagnostic quandary. After confirming the diagnosis by radiology, patient was operated upon by external approach. In the following article, we also discuss the establishment of the diagnosis and review different surgical modalities for the management of various types of laryngocele.


Phenotypic variation in electromorphs previously considered to be genetic markers in Microtus ochrogaster.
The allelic frequencies of the plasma enzymes transferrin (Tf) and leucine aminopeptidase (LAP) have been shown previously to correlate with population density, population growth rate and mortality in Microtus ochrogaster. Such changes in allozymic frequencies of Tf and LAP have been used by others as evidence supporting the Chitty/Krebs genetic-behavioral hypothesis of population growth. In this study, prairie voles were captured in midwinter and in midsummer, and brought to the lab where their allozymes of Tf and LAP were determined. The voles were then placed in controlled environments approximating some of the conditions of other seasons of the year, and their allozymes were redetermined in subsequent weeks. Changes in allozymes occurred in all experiments. Animals subected to opposite seasons (i.e. captured in winter and subjected to summer conditions, and captured in summer and subjected to winter environments) had the highest percentage of changes in electromorphs. A review of the literature revealed a plethora of evidence that Tf and LAP proteins could change electromorphs on starch gels in response to differences in blood chemistry and presumably to physiological state influenced by diet, reproductive state, and disease. Thus, since it appears that electromorphs of Tf and LAP proteins can change in voles subjected to different environments, and that these proteins may change in electronegativity in response to the physiological state of the animals, observed changes in allelic frequencies in populations of voles may be of limited value as evidence for the proposed genetic-behavioral hypothesis explaining population cycles.


Mas-related gene (Mrg) C receptors inhibit mechanical allodynia and spinal microglia activation in the early phase of neuropathic pain in rats.
Mas-related gene (Mrg) C receptors are exclusively expressed in the trigeminal and dorsal root ganglia (DRG). However, their functional roles are poorly understood. This study was aimed to determine the effect of MrgC receptors on pain hypersensitivity in the early phase of neuropathic pain and its underlying mechanisms. Intrathecal (i.t.) administration of the selective MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) at 1 or 10nmol attenuated mechanical allodynia one day after L5 spinal nerve ligation (SNL) surgery. I.t. BAM8-22 (10 nmol) inhibited SNL-induced microglia activation in the spinal dorsal horn on day 2 post-SNL. The BAM8-22 treatment also abolished SNL-induced upregulation of neuronal nitric oxide synthesis (nNOS) in the dorsal root ganglia (DRG). On the other hand, SNL, but not sham, surgery reduced the expression of MrgC receptor mRNA in the injured L5 DRG without changing thier levels in the adjacent uninjured L4 or L6 DRG on day 2 following the surgery. These results suggest that the activation of MrgC receptors can relieve pain hypersensitivity by the inhibition of nNOS increase in DRG neurons and microglia activation in the spinal dorsal horn in the early time following peripheral nerve injury. This study provides evidence that MrgC receptors could be targeted as a novel therapy for neuropathic pain with limited unwanted effects.


Signaling in rat brainstem via Gpr160 is required for the anorexigenic and antidipsogenic actions of cocaine- and amphetamine-regulated transcript peptide.
Recent work identified Gpr160 as a candidate receptor for cocaine- and amphetamine-regulated transcript peptide (CARTp) and described its role in pain modulation. The aims of the present study were to determine if Gpr160 is required for the CARTp's ability to reduce food intake and water intake and to initially identify the distribution of Gpr160-like immunoreactivity (Gpr160ir) in the rat brain. A passive immunoneutralization approach targeting Gpr160 was used to block the behavioral effects of a pharmacological dose of CARTp in the fourth cerebroventricle (4V) of rats and to determine the importance of endogenously produced CARTp in the control of ingestive behaviors. Passive immunoneutralization of Gpr160 in the 4V blocked the actions of CARTp to inhibit food intake and water intake. Blockade of Gpr160 in the 4V, independent of pharmacological CART treatment, caused an increase in both overnight food intake and water intake. The decrease in food intake, but not water intake, caused by central injection of CARTp was demonstrated to be interrupted by prior administration of a glucagon-like peptide 1 (GLP-1) receptor antagonist. Gpr160ir was observed in several, distinct sites throughout the rat brain, where CARTp staining has been described. Importantly, Gpr160ir was observed to be present in both neuronal and nonneuronal cell types. These data support the hypothesis that Gpr160 is required for the anorexigenic actions of central CARTp injection and extend these findings to water drinking. Gpr160ir was observed in both neuronal and nonneuronal cell types in regions known to be important in the multiple pharmacological effects of CARTp, identifying those areas as targets for future compromise of function studies.


Adjuvant chemotherapy is associated with an overall survival benefit regardless of age in ER+/HER2- breast cancer pts with 1-3 positive nodes and oncotype DX recurrence score 20 to 25: an NCDB analysis.
The RxPONDER trial found that among breast cancer patients with estrogen receptor positive (ER+) breast cancer, 1-3 positive axillary nodes, and a recurrence score of ≤25, only pre-menopausal women benefitted from adjuvant chemoendocrine therapy; postmenopausal women with similar characteristic did not benefit from adjuvant chemotherapy. We aimed to replicate the RxPonder trial using a larger patient cohort with real world data to determine whether a RS threshold existed where adjuvant chemotherapy was beneficial regardless of age. The National Cancer Database (NCDB) was queried for women with ER+, human epidermal growth factor receptor 2 (HER2) negative breast cancer, 1-3 positive axillary nodes, and RS ≤25 who received endocrine (ET) only or chemo-endocrine therapy (CET). Cox regression interaction was explored between CET and age as a surrogate for menopausal status. The final analytic cohort included 28,427 eligible women: 7,487 (26.3%) received adjuvant CET and 20,940 (73.7%) ET. In the entire cohort, RS had a normal distribution, with a median score of 14. After correcting for demographic and clinical variables, a threshold effect was observed with RS >20 being associated with a significantly inferior overall survival (OS) (P value range: < 0.001-0.019). In women with RS of 20-25, CET was associated with a significant improvement in OS compared to ET alone, regardless of age (age <=50: HR = 0.334, P=0.002; age>50: HR=0.521, P=0.019). Among women with ER+/HER2- breast cancer with 1-3 positive nodes, and a RS of 20-25-in contrast to the RxPONDER trial-we observed that CET was associated with an OS benefit in women regardless of age.