Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift.
The recently emerged SARS-CoV-2 Omicron variant encodes 37 amino acid substitutions in the spike protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody-based therapeutics. Here we show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions in neutralizing activity were observed against Omicron compared to the ancestral pseudovirus in plasma from convalescent individuals and from individuals who had been vaccinated against SARS-CoV-2, but this loss was less pronounced after a third dose of vaccine. Most monoclonal antibodies that are directed against the receptor-binding motif lost in vitro neutralizing activity against Omicron, with only 3 out of 29 monoclonal antibodies retaining unaltered potency, including the ACE2-mimicking S2K146 antibody1. Furthermore, a fraction of broadly neutralizing sarbecovirus monoclonal antibodies neutralized Omicron through recognition of antigenic sites outside the receptor-binding motif, including sotrovimab2, S2X2593 and S2H974. The magnitude of Omicron-mediated immune evasion marks a major antigenic shift in SARS-CoV-2. Broadly neutralizing monoclonal antibodies that recognize RBD epitopes that are conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.


Representing HIV clinical terminology with SNOMED.
1. RESEARCH OBJECTIVES AND METHODS. Because of a need for a standard classification and coding system to encode data for HIV infected patients in the AIDS Program clinic at San Francisco General Hospital, we have begun a subset of clinical terms commonly used in the care of patients with HIV disease, and we have sought to represent these terms using terminology from the SNOMED International classification system. We selected a sample of key findings for AIDS primary care for the AIDS Registry database. The areas of chest x-ray findings, psychological problems, and patient symptoms were chosen because they were representative of a number of SNOMED International axes, including diagnoses, morphology, topography, and function. They also included modifiers representing the concepts of laterality, time, severity, and certainty. 2. RESULTS. As shown by the sample terms in the table below, the findings suggest that SNOMED is a good starting point for a standard classification and coding system to support the clinical care of patients with HIV disease. The next phase of the research will focus on the evaluation of the adequacy and acceptability of the SNOMED representation to clinicians in the AIDS clinic.


[ISRAELI GUIDELINES FOR THE TREATMENT OF HYPERLIPIDEMIA - 2014 UPDATE].
Atherosclerosis is one of the leading causes of morbidity and mortality in the world, including in Israel. This document updates the clinical recommendations of the Israeli medical societies (The Society for Research, Prevention and Treatment of Atherosclerosis, The Israel Heart Society, The Israel Association of Family Physicians, The Israel Society of Internal Medicine) from 2012. The need for an update stems from new studies and from the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. These recommendations take into account the guidelines of leading medical organizations in the world, as well as the specific circumstances and needs of the medical system in Israel.


Molecular and biochemical analysis of protective protein/cathepsin A mutations: correlation with clinical severity in galactosialidosis.
Mutations in the gene encoding lysosomal protective protein/cathepsin A (PPCA) are the cause of the lysosomal disorder galactosialidosis (GS). Depending on age of onset and severity of the symptoms, patients present with either an early infantile (EI), a late infantile (LI), or a juvenile/adult (J/A) form of the disease. To study genotype-phenotype correlation in this disorder, we have analyzed the mutations in the PPCA gene of eight clinically different patients. In two EI and one J/A patient, we have identified four novel point mutations (Val104Met, Leu208Pro, Gly411Ser and Ser23Tyr), that prevent phosphorylation and, hence, lysosomal localization and maturation of the mutant precursors. Two amino acid substitutions (Phe412Val and Tyr221Asn) are shared by five LI patients. These mutations appear to be pathognomonic for this phenotype, and determine the clinical outcome depending on whether they are present together or in combination with other mutations. The latter include a single base deletion and a novel amino acid change (Met378Thr), which generates an additional glycosylation site. Within the LI group, patients carrying the Phe412Val mutation are clinically more severe than those with the Tyr221Asn substitution. This is in agreement with the biochemical behavior of the Asn221-mutant protein, that is, like the Phe412Val protein, phosphorylated, routed to lysosomes and proteolytically processed, but its intralysosomal stability is intermediate between that of wild-type PPCA and Val412-PPCA. Overall, these results may explain the clinical heterogeneity observed in GS patients and may help to correlate mutant allelic combinations with specific clinical phenotypes.


Epigenetic pathways and glioblastoma treatment.
Glioblastoma multiforme (GBM) is the most common malignant adult brain tumor. Standard GBM treatment includes maximal safe surgical resection with combination radiotherapy and adjuvant temozolomide (TMZ) chemotherapy. Alarmingly, patient survival at five-years is below 10%. This is in part due to the invasive behavior of the tumor and the resulting inability to resect greater than 98% of some tumors. In fact, recurrence after such treatment may be inevitable, even in cases where gross total resection is achieved. The Cancer Genome Atlas (TCGA) research network performed whole genome sequencing of GBM tumors and found that GBM recurrence is linked to epigenetic mechanisms and pathways. Central to these pathways are epigenetic enzymes, which have recently emerged as possible new drug targets for multiple cancers, including GBM. Here we review GBM treatment, and provide a systems approach to identifying epigenetic drivers of GBM tumor progression based on temporal modeling of putative GBM cells of origin. We also discuss advances in defining epigenetic mechanisms controlling GBM initiation and recurrence and the drug discovery considerations associated with targeting epigenetic enzymes for GBM treatment.


[The effect of acute external gamma-irradiation and thyroid glands dysfunction on rat reproductive system and frequency of structural mutations in somatic cells of pregnant females and their offspring].
Experimental hypofunction of thyroid gland, caused by mercazolil administration, and acute external exposure to 0.5 and 1.0 Gy of gamma-irradiation were shown to result in disturbance of reproductive function in puberal females and of estrogenreceptor interaction, in reduction of pregnancy probability, increase in pre- and postimplantation lethality of fetuses as well as in rise in the frequency of structural mutations in somatic cells of pregnant rats and their offspring.


On the hydrogen activation by frustrated Lewis pairs in the solid state: benchmark studies and theoretical insights.
Recently, the concept of small molecule activation by frustrated Lewis pairs (FLPs) has been expanded to the solid state showing a variety of interesting reactivities. Therefore, there is a need to establish a computational protocol to investigate such systems theoretically. In the present study, we selected several FLPs and applied multiple levels of theory, ranging from a semi-empirical tight-binding Hamiltonian to dispersion corrected hybrid density functionals. Their performance is benchmarked for the computation of crystal geometries, thermostatistical contributions, and reaction energies. We show that the computationally efficient HF-3c method gives accurate crystal structures and is numerically stable and sufficiently fast for routine applications. This method also gives reliable values for the thermostatistical contributions to Gibbs free energies. The meta-generalized gradient approximated TPSS-D3 evaluated in a projector augmented plane wave basis set is able to produce sufficiently accurate reaction electronic energies. The established protocol is intended to support experimental studies and to predict new reactions in the emerging field of solid-state FLPs.This article is part of the themed issue 'Frustrated Lewis pair chemistry'.


Facial Expression of TIPI Personality and CHMP-Tri Psychopathy Traits in Chimpanzees (Pan troglodytes) : Evidence for Honest Signalling?
Honest signalling theory suggests that humans and chimpanzees can extract socially relevant information relating to personality from the faces of their conspecifics. Humans are also able to extract information from chimpanzees' faces. Here, we examine whether personality characteristics of chimpanzees, including measures of psychopathy, can be discerned based purely on facial morphology in photographs. Twenty-one chimpanzees were given naïve and expert personality ratings on the Ten Item Personality Inventory (TIPI) and the Chimpanzee Triarchic Model of Psychopathy (CHMP-Tri) before and following behavioural observations. Characteristics relating to openness, conscientiousness, extraversion, and disinhibition could be distinguished from the faces of chimpanzees. Individuals higher on disinhibition have lower scores on conscientiousness and emotional stability and higher scores on extraversion, while those higher on meanness have lower conscientiousness and agreeableness. Facial expressions are linked to personality traits present in the TIPI and CHMP-Tri models: the Relaxed Face and the Grooming Face were displayed more by chimpanzees higher on agreeableness, whereas the Compressed Lips Face was observed more in those individuals higher on boldness, and the Full Open Grin was displayed more by chimpanzees higher on extraversion but lower on emotional stability and conscientiousness. Facial expressions were also found to be associated with particular behavioural contexts, namely the Grooming Face in affiliative contexts and the Relaxed and Relaxed Open Mouth Faces in neutral contexts. Dominant chimpanzees display higher levels of boldness and more Compressed Lips Faces, Relaxed Open Mouth Faces, and Grooming Faces than subordinate individuals. These findings support and extend evidence for an honest signalling system and a personality structure shared between humans and chimpanzees. Future research could further explore how personality is conveyed through the face, perhaps through more than just singular aspects of character, and maybe reflecting what chimpanzees themselves are able to do.


Glucocorticoid receptor-mediated suppression of the interleukin 2 gene expression through impairment of the cooperativity between nuclear factor of activated T cells and AP-1 enhancer elements.
The immunosuppressant hormone dexamethasone (Dex) interferes with T cell-specific signals activating the enhancer sequences directing interleukin 2 (IL-2) transcription. We report that the Dex-dependent downregulation of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and calcium ionophore-induced activity of the IL-2 enhancer are mediated by glucocorticoid receptor (GR) via a process that requires intact NH2- and COOH-terminal and DNA-binding domains. Functional analysis of chloramphenicol acetyltransferase (CAT) vectors containing internal deletions of the -317 to +47 bp IL-2 enhancer showed that the GR-responsive elements mapped to regions containing nuclear factor of activated T cells protein (NFAT) (-279 to -263 bp) and AP-1 (-160 to -150 bp) motifs. The AP-1 motif binds TPA and calcium ionophore-induced nuclear factor(s) containing fos protein. TPA and calcium ionophore-induced transcriptional activation of homo-oligomers of the NFAT element were not inhibited by Dex, while AP-1 motif concatemers were not stimulated by TPA and calcium ionophore. When combined, NFAT and AP-1 motifs significantly synergized in directing CAT transcription. Such a synergism was impaired by specific mutations affecting the trans-acting factor binding to either NFAT or AP-1 motifs. In spite of the lack of hormone regulation of isolated cis elements, TPA/calcium ionophore-mediated activation of CAT vectors containing a combination of the NFAT and the AP-1 motifs became suppressible by Dex. Our results show that the IL-2-AP-1 motif confers GR sensitivity to a flanking region containing a NFAT element and suggest that synergistic cooperativity between the NFAT and AP-1 sites allows GR to mediate the Dex inhibition of IL-2 gene transcription. Therefore, a Dex-modulated second level of IL-2 enhancer regulation, based on a combinatorial modular interplay, appears to be present.


HOMOCYSTINURIA DUE TO CYSTATHIONINE SYNTHETASE DEFICIENCY: THE MODE OF INHERITANCE.
Deficiency of cystathioninie synthetase activity results in the clinical syndrome of homocystinuria. In both parents of a patient with homocystinuria, the hepatic cystathionine synthetase activity was 40 percent of that in unrelated control patients. These findings demonstrate that the metabolic error is inherited and suggest that the parents, although clinically normal, represent the heterozygous. state. A second case of homocystinuria also is shown to be associated with cystathionine synthetase deficiency.


Priming and stimulus-response learning in perceptual classification tasks.
Participants often respond more quickly and more accurately to a repeated stimulus compared to a non-repeated one, a phenomenon known as repetition priming. In semantic classification tasks priming appears to be largely attributable to the learning of stimulus-decision and stimulus-response associations, which allow participants to bypass many of the processes engaged during initial stimulus analysis. The current study tested whether stimulus-response learning plays a similarly dominant role in priming that occurs in perceptual classification tasks. Unfamiliar objects were used as stimuli to reduce the influence of semantic processes on priming and the task switched for all test trials to eliminate stimulus-decision learning. The results showed across-task priming as measured by reaction time facilitation and improved accuracy when the response remained the same during the encoding and test phases. When the response switched, similar levels of reaction time facilitation were observed, but priming as measured by accuracy was significantly reduced and no longer significant. These findings indicate that stimulus-response learning contributes to priming in perceptual classification tasks, but does not play a dominant role. Significant stimulus-level learning that is independent of the task and response also occurs and likely indexes facilitated perceptual processing of the objects.


Gut microbiome: pertinence in fibromyalgia.
The human gut microbiome constitutes a diverse and dynamic community of microorganisms that inhabit the digestive tract. In recent years, there is growing appreciation for the role of the gut microbiome in host health and disease. Gut bacteria are involved in the pathogenesis of numerous medical conditions in a variety of medical fields including gastroenterology, metabolic, rheumatologic, neurologic and psychiatric disorders. Recently, evidence is mounting that gut bacteria could also play a role in chronic pain and specifically fibromyalgia (FM). The composition of the gut bacterial community is altered in individuals with FM, with an altered abundance of a small subset of bacterial species. Some of these species, either with increased or decreased abundance in patients, have established metabolic activity which could have pertinence in the expression of FM symptoms. The putative mechanisms which could allow these bacterial species to affect pain, fatigue, mood and other symptoms include the entry of short-chain-fatty-acids, bile acids, neurotransmitters and bacterial antigens into the host circulation. While these are merely the first steps in understanding the role of the gut microbiome in chronic pain and specifically FM, one might envision exciting future perspectives for better mechanistic understanding of FM, for the development of objective diagnostic aids and potentially for new therapeutic modalities.


Aphagia and adipsia after kainic acid lesioning of the dorsomedial hypothalamic area.
Unlike rats which have electrolytic dorsomedial hypothalamic area lesions and are hypophagic and hypodipsic, the rats of the present study with dorsomedial hypothalamic area, kainic acid lesions (KAL) were postoperatively aphagic and adipsic. Subsequently, KAL rats rejected chow or a high-fat diet but ate a 30% sucrose-chow diet. Similarly the KAL rats were adipsic but drank a 30% sucrose solution. Slowly most of the KAL rats began to eat chow and drink tap water but remained hypophagic and hypodipsic. When tested for glucoprivic-induced feeding using 2-deoxy-D-glucose (200 or 400 mg/kg) the KAL rats, in contrast to the sham-operated controls, did not increase their food intake. During water deprivation the recovered KAL rats that would drink tap water ate, and following it they responded with an adequate increase in water consumption. During food deprivation the KAL rats, whether eating chow or sucrose-chow diet, drank, and subsequently the normally hypophagic rats actually ate more than the controls. Although the growth rate (linear and ponderal) of KAL rats was reduced compared with that of the controls, their body composition by indirect measurement was normal. The present data indicate that most of the dorsomedial hypothalamic syndrome results from damage to DMHA neurons and not to fibers of passage.


"I'm 100% for it! I'm a convert!": women's experiences of a yoga programme during treatment for gynaecological cancer; an interpretative phenomenological analysis.
To explore patients' experiences of taking part in a yoga intervention while undergoing treatment for gynaecological cancer. Sixteen women (age range 31-79 years; mean age 60) participated in focus groups based on a semi-structured question schedule. Resulting discussions were audio-recorded, transcribed verbatim and analysed using interpretative phenomenological analysis (IPA). Royal Derby Hospital, UK. Patients took part in a 10-week course of Hatha yoga, where they participated in a one hour long class per week. Three themes emerged from the data: applying breathing techniques, engaging in the physicality of yoga and finding a community. The first theme was particularly important to the patients as they noted the breadth and applicability of the techniques in their day-to-day lives. The latter two themes reflect physical and social perspectives, which are established topics in the cancer and yoga literature and are contextualised here within the women's experiences of cancer treatment. The women's perceptions of the programme were generally positive, providing a previously unseen view of the patient experience of participating in a yoga intervention. The difference between the women's prior expectations and lived experiences is discussed.


Flow and the inhibition of prothrombinase by antithrombin III and heparin.
Inhibition of prothrombinase by antithrombin III (ATIII) and heparin was investigated in a continuous-flow system. Phospholipid-coated capillaries, containing phospholipid-bound factor Xa and factor Va, were perfused with 1.0 mumol/L prothrombin and 0.5 nmol/L factor Va. At 25 degrees C and a flow rate of 32 microL/min (shear rate 28 seconds-1) the steady-state rates of prothrombin conversion depended linearly on the surface concentration of prothrombinase up to 2 fmol/cm2. The rate of thrombin generation was 952 +/- 43 (SE) mol/min/mol prothrombinase. When ATIII was included in the perfusate for 10 minutes, the free thrombin concentration at the outlet of the capillary was markedly reduced: a 50% neutralization was obtained at 0.7 mumol/L ATIII. However, the prothrombinase activity was not inhibited, as could be established after a subsequent perfusion with prothrombin and factor Va. At an ATIII concentration typical of normal plasma (2 mumol/L) a slight neutralization of prothrombinase was observed: 10% neutralization following a 10-minute perfusion. During a perfusion with ATIII in the absence of prothrombin, or in its presence with hirudin (2 mumol/L) also included in the perfusate, a more pronounced neutralization of prothrombinase was observed: 40% residual activity was obtained after a 10-minute perfusion. From this observation the suggestion comes forward that thrombin, continuously produced at the surface, consumes ATIII in the boundary layer. In this case the true ATIII concentration in the vicinity of surface-bound prothrombinase will be but a small fraction of the initial ATIII concentration in the bulk fluid. Unfractionated heparin and an ultra-low molecular weight heparin (pentasaccharide) did enhance the ATIII-dependent neutralization of prothrombinase, but to a much lesser extent than observed with small unilaminar phospholipid vesicles as the catalytic sites for prothrombinase assembly. The findings reported here support the notion that regulation of prothrombinase by heparin under in vivo conditions occurs at the stage of its formation, ie, through inhibition of free factor Xa and/or the generation of factor Va, rather than by direct inhibition of the prothrombinase activity.


S-glutathionylation of the Na,K-ATPase catalytic α subunit is a determinant of the enzyme redox sensitivity.
Na,K-ATPase is highly sensitive to changes in the redox state, and yet the mechanisms of its redox sensitivity remain unclear. We have explored the possible involvement of S-glutathionylation of the catalytic α subunit in redox-induced responses. For the first time, the presence of S-glutathionylated cysteine residues was shown in the α subunit in duck salt glands, rabbit kidneys, and rat myocardium. Exposure of the Na,K-ATPase to oxidized glutathione (GSSG) resulted in an increase in the number of S-glutathionylated cysteine residues. Increase in S-glutathionylation was associated with dose- and time-dependent suppression of the enzyme function up to its complete inhibition. The enzyme inhibition concurred with S-glutathionylation of the Cys-454, -458, -459, and -244. Upon binding of glutathione to these cysteines, the enzyme was unable to interact with adenine nucleotides. Inhibition of the Na,K-ATPase by GSSG did not occur in the presence of ATP at concentrations above 0.5 mm. Deglutathionylation of the α subunit catalyzed by glutaredoxin or dithiothreitol resulted in restoration of the Na,K-ATPase activity. Oxidation of regulatory cysteines made them inaccessible for glutathionylation but had no profound effect on the enzyme activity. Regulatory S-glutathionylation of the α subunit was induced in rat myocardium in response to hypoxia and was associated with oxidative stress and ATP depletion. S-Glutathionylation was followed by suppression of the Na,K-ATPase activity. The rat α2 isoform was more sensitive to GSSG than the α1 isoform. Our findings imply that regulatory S-glutathionylation of the catalytic subunit plays a key role in the redox-induced regulation of Na,K-ATPase activity.


Patient, client, consumer, or service user? An empirical investigation into the impact of labels on stigmatizing attitudes.
Currently there is no universally agreed upon language for those seeking psychiatric treatment, and labels commonly include patient, client, consumer, and service user. Although there is some research regarding preferences for label (Dickens & Picchioni, 2012), little is known about how people perceive an individual differently based on the label used. The current study examined whether specific labels were associated with more stigmatizing attitudes. Participants recruited through MTurk (N = 526) were randomized to read a vignette of a man named Harry, described as a patient, client, consumer, or service user with mental illness. After correctly recalling the label from the vignette, participants were assessed for stigmatizing attitudes toward Harry. ANOVAs indicated a no main effects of label on stigmatizing attitudes. A number of variables (e.g., overall stigma, dangerousness, segregation, and distance) revealed a significant interaction between label and prior mental health treatment: For those who have sought prior mental health treatment, the term client may be more stigmatizing than other labels. The current study did not find general differences in stigmatizing attitudes associated with mental health treatment label. Although preliminary, these findings suggest treatment labels may not significantly impact stigmatizing attitudes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Variation in the Early Host-Pathogen Interaction of Bovine Macrophages with Divergent Mycobacterium bovis Strains in the United Kingdom.
Bovine tuberculosis has been an escalating animal health issue in the United Kingdom since the 1980s, even though control policies have been in place for over 60 years. The importance of the genetics of the etiological agent, Mycobacterium bovis, in the reemergence of the disease has been largely overlooked. We compared the interaction between bovine monocyte-derived macrophages (bMDM) and two M. bovis strains, AF2122/97 and G18, representing distinct genotypes currently circulating in the United Kingdom. These M. bovis strains exhibited differences in survival and growth in bMDM. Although uptake was similar, the number of viable intracellular AF2122/97 organisms increased rapidly, while G18 growth was constrained for the first 24 h. AF2122/97 infection induced a greater transcriptional response by bMDM than G18 infection with respect to the number of differentially expressed genes and the fold changes measured. AF2122/97 infection induced more bMDM cell death, with characteristics of necrosis and apoptosis, more inflammasome activation, and a greater type I interferon response than G18. In conclusion, the two investigated M. bovis strains interact in significantly different ways with the host macrophage. In contrast to the relatively silent infection by G18, AF2122/97 induces greater signaling to attract other immune cells and induces host cell death, which may promote secondary infections of naive macrophages. These differences may affect early events in the host-pathogen interaction, including granuloma development, which could in turn alter the progression of the disease. Therefore, the potential involvement of M. bovis genotypes in the reemergence of bovine tuberculosis in the United Kingdom warrants further investigation.


Long-term AZT exposure alters the metabolic capacity of cultured human lymphoblastoid cells.
The antiretroviral efficacy of 3'-azido-3'-deoxythymidine (AZT) is dependent upon intracellular mono-, di-, and triphosphorylation and incorporation into DNA in place of thymidine. Thymidine kinase 1 (TK-1) catalyzes the first step of this pathway. MOLT-3, human lymphoblastoid cells, were exposed to AZT continuously for 14 passages (P(1)-P(14)) and cultured for an additional 14 passages (P(15)-P(28)) without AZT. Progressive and irreversible depletion of the enzymatically active form of the TK-1 24-kDa monomer with loss of active protein was demonstrated during P(1)-P(5) of AZT exposure. From P(15) to P(28), both the 24- and the 48-kDa forms of TK-1 were undetectable and a tetrameric 96-kDa form was present. AZT-DNA incorporation was observed with values of 150, 133, and 108 molecules of AZT/10(6) nucleotides at the 10 microM plasma-equivalent AZT dose at P(1), P(5), and P(14), respectively. An exposure-related increase in the frequency of micronuclei (MN) was observed in cells exposed to either 10 or 800 microM AZT during P(1)-P(14). Analysis of the cell cycle profile revealed an accumulation of S-phase cells and a decrease in G(1)-phase cells during exposure to 800 microM AZT for 14 passages. When MOLT-3 cells were grown in AZT-free media (P(15)-P(29)), there was a reduction in AZT-DNA incorporation and MN formation; however, TK-1 depletion and the persistence of S-phase delay were unchanged. These data suggest that in addition to known mutagenic mechanisms, cells may become resistant to AZT partially through inactivation of TK-1 and through modulation of cell cycle components.


High-Speed, Heavy-Load, and Direction-Controllable Photothermal Pneumatic Floating Robot.
Light-fueled actuators are promising in many fields due to their contactless, easily controllable, and eco-efficiency features. However, their application in liquid environments is complicated by the existing challenges of rapid deformation in liquids, light absorption of the liquid media, and environmental contamination. Here, we design a photothermal pneumatic floating robot (PPFR) using a boat-paddle structure. Light energy is converted into thermal energy of air by an isolated photothermal composite, which is then converted into mechanical energy of liquid to drive the movement of PPFRs. By understanding and controlling the photothermal actuation, the PPFR can achieve an average velocity of 13.1 mm s-1 in water and can be modified for remote on-demand differential steering and self-sustained oscillation. The PPFR may be modified to provide a lifting mechanism, capable of moving 4 times the PPFR mass. Various shapes and materials are suitable for the PPFR, providing a platform for liquid surface transporting, water sampling, pollutant collecting, underwater photography, and photocontrol robots in shallow water.


A hospital outbreak of gastroenteritis possibly related to the contamination of tap water by a small round structured virus.
Small round structured viruses (SRSVs) are a major cause of gastroenteritis in institutions and sensitive new molecular techniques allow rapid diagnosis and the establishment of control measures. In January 1999, a 10 day-long outbreak of gastroenteritis in a re-education ward, was reported by a hospital hygiene department. A potential common source of contamination was tap water. The stools of six patients with gastroenteritis and seven tap water samples from the hospital ward, were tested for SRSV by reverse transcription and polymerase chain reaction (RT-PCR): three stools and four water samples, all bacteriologically negative, were SRSV-positive. Nucleotide sequencing of a fragment of the SRSV polymerase gene showed that the sequences of the positive samples (two patients and four water samples) were identical (genogroup II). We cannot exclude interhuman transmission of SRSV together with viral soiling of some taps in the ward, but this hospital infection was more likely due to the transient contamination of the ward supply of drinking water with a SRSV strain.


A comparison of sib-pair linkage tests for disease susceptibility loci.
An analytical study is conducted of the properties of statistical tests to detect linkage between a disease locus and a very polymorphic marker locus when data on sib pairs are available. In most instances the most powerful test is the test based on the mean number of marker alleles shared identical by descent by the two members of a sib pair, and the most efficient sampling strategy is almost always to sample only pairs with both sibs affected. We show it is valid to use the information from all possible sib pairs as though they came from separate families when data on sibships of size three or larger are available, though more power may be obtained if different weights are given to the different sibship sizes.


[Identification of Melittin-Like Proteins with a Molecular Weight of 67 κDa that Interact with Na^(+)/K^(+)-ATPase].
Melittin, a peptide from bee venom, was found to be able to interact with many proteins, including calmodulin target proteins and ion-transporting P-type ATPases. It is assumed that melittin mimics a protein module involved in protein-protein interactions within cells. Previously, a Na^(+)/K^(+)-ATPase containing the α1 isoform of the catalytic subunit was found to co-precipitate with a protein with a molecular weight of about 70 κDa that interacts with antibodies against melittin by cross immunoprecipitation. In the presence of a specific Na^(+)/K^(+)-ATPase inhibitor (ouabain), the amount of protein with a molecular weight of 70 κDa interacting with Na^(+)/K^(+)-ATPase increases. In order to identify melittin-like protein from murine kidney homogenate, a fraction of melittin-like proteins with a molecular weight of approximately 70 κDa was obtained using affinity chromatography with immobilized antibodies specific to melittin. By mass spectrometry analysis, the obtained protein fraction was found to contain three molecular chaperones of Hsp70 superfamily: mitochondrial mtHsp70 (mortalin), Hsp73, Grp78 (BiP) of endoplasmic reticulum. These data suggest that chaperones from the HSP-70 superfamily contain a melittin-like module.


[Clinical and pathological features in IgA nephropathy with IgG deposition in the glomerular mesangial area].
To investigate the relationship between the clinical and pathological findings in IgA nephropathy with or without IgG deposition in the glomerular mesangial area. The data were collected from 122 patients with a diagnosis of IgA nephropathy by renal biopsy in the Third Affiliated Hospital of Southern Medical University between November, 2009 and February, 2016. All the samples were examined by light microscopy, immunofluorescence and electron microscopy. According to the results of immunofluorescence assay, the patients were divided into IgA group (n=63) and IgA-IgG group (n=59). The pathological classification of IgA nephropathy was analyzed according to Oxford classification and Lee's classification. The clinical and pathological findings were compared between the two groups. Compared with the patients with IgA nephropathy but without IgG deposition, patients with IgA nephropathy with IgG deposition had higher serum creatinine, higher 24-h urine protein, higher blood uric acid, higher triglyceride levels (P<0.05) and lower eGFR (P<0.05); more of these patients were in Lee's grade IV-V, had renal tubular atrophy and/or interstitial fibrosis, and had MEST scores more than 3 (P<0.05). Patients with IgA nephropathy with IgG deposition in the glomerular mesangial have severer clinical symptoms and more serious pathological changes. Measures should be taken to control IgG deposition in patients with IgA nephropathy to delay the progress of the disease.


Vitamin C: A Natural Inhibitor of Cell Wall Functions and Stress Response in Mycobacteria.
Tuberculosis, caused by Mycobacterium tuberculosis, has re-emerged as a threat to human race. Conventional antibiotic treatments are failing due to different stress response strategies adopted by bacterial pathogens. Since time immemorial, Vitamin C is known to protect against pathogens by boosting immunity in humans. Recently, Vitamin C has been shown to directly kill M. tuberculosis including multiple drug-resistant strains by generation of oxidative radicals through Fenton's reaction. Concurrently, it inhibits (p)ppGpp-mediated stringent response thus effectively shutting down long-term survival and persistence in mycobacteria. Here, we have discussed historical perspective and recent evidences on Vitamin C-mediated inhibition of several key pathways of M. tuberculosis such as (p)ppGpp synthesis and mycobacterial cell wall function. Several cell wall components including mycolic acids are critical for mycobacterial virulence. We observed downregulation of various mycolic acids in M. smegmatis upon treatment with Vitamin C, and data have been presented here. Vitamin C has been shown to inhibit the biofilm growth as well as disrupt the formed biofilm in mycobacteria. Additionally, Vitamin C role in cell-mediated and humoral immunity has been elucidated. Vitamin C is toxic at high concentration; therefore we have proposed the idea of derivatizing Vitamin C in order to lower the minimal inhibition concentration (MIC) necessary to target M. tuberculosis.


Exercise in patients with hip osteoarthritis - effects on muscle and functional performance: A randomized trial.
It is believed that clinical management of osteoarthritis should address muscle weakness to improve physical function and prevent disability and frailty. This sub-study investigated the effects of supervised progressive resistance training (RT), supervised Nordic Walking (NW), and unsupervised home-based exercise (HBE) on muscle and functional performance; and associations between these exercise-induced changes in persons with hip osteoarthritis. Forty-two patients with hip osteoarthritis were recruited from a larger RCT (NCT01387867). All the groups (RT, n = 15; NW, n = 12; HBE, n = 15) exercised 1 h 3 times/week for 4 months. Quadriceps cross-sectional area (QCSA, MRI-determined); quadriceps strength (QMVC); leg extensor power (LEP); functional performance (chair stands (30sCS); stair climbs (TSC); and 6-minute walk (6MWT)) were assessed at baseline and 4 months. Per protocol analyses (one-way ANOVA and Bonferroni test) showed significant between-group differences for improvements in QCSA in the most symptomatic leg favoring RT versus NW (2.3 cm2, 95% CI [0.6, 3.9]) and HBE (2.3 cm2 [0.8, 3.9]); and 30sCS (1.8 repetitions [0.2-3.3]), and 6MWT (35.1 m [3.5-66.7]) favoring NW versus HBE. Associations existed between exercise-induced changes in QCSA and QMVC (r = 0.366, p = .019) for the most symptomatic leg and between changes in 6MWT and QMVC (r = 0.320, p = .04) and LEP (r = 0.381, p = .01), respectively, for the least symptomatic leg. Resistance training appeared effective for improving muscle mass, but less effective for improving muscle strength, power, and functional performance. Only exercise-induced changes in muscle strength and power of the least symptomatic leg, not the most symptomatic leg, were related to changes in functional performance.


Cell-Free Hemoglobin-mediated Increases in Vascular Permeability. A Novel Mechanism of Primary Graft Dysfunction and a New Therapeutic Target.
Cell-free hemoglobin (CFH) is a potent oxidant associated with poor clinical outcomes in a variety of clinical settings. Recent studies suggest that acetaminophen (APAP), a specific hemoprotein reductant, can abrogate CFH-mediated oxidative injury and organ dysfunction. Preoperative plasma CFH levels are independently associated with primary graft dysfunction (PGD) after lung transplant ( 1 ). Our objectives were to determine whether CFH would increase lung vascular permeability in the isolated perfused human lung and whether APAP would limit these effects. Human lungs declined for transplant were inflated and perfused with Dulbecco's modified Eagle medium/5% albumin at a pulmonary artery pressure of 8-12 mm Hg. After steady state was achieved, CFH (100 mg/dl) was added to the perfusate ± APAP (15 μg/ml). Lung permeability was measured by continuous monitoring of lung weight gain and by extravasation of Evans blue dye-labeled albumin from the vasculature into bronchoalveolar lavage. To test the mechanism of increased permeability, human pulmonary microvascular endothelial cells were exposed to CFH (0.5 mg/ml) ± APAP (160 μM) for 24 hours and permeability was assessed by electrical cell-substrate impedance sensing. In the isolated perfused human lung, CFH increased lung permeability over 2 hours compared with control lungs (12% vs. 2% weight gain from baseline, P = 0.03). Increased vascular permeability was confirmed by a 4.8-fold increase in Evans blue dye-labeled albumin in the airspace compared with control lungs. Pretreatment with APAP prevented lung weight gain (P = 0.06 vs. CFH). In human pulmonary microvascular endothelial cells, CFH increased monolayer permeability (P = 0.03 vs. control), and this was attenuated by APAP (P = 0.045 vs. CFH). Circulating CFH increases vascular permeability in the isolated perfused human lung and paracellular permeability in lung microvascular endothelial cells. These effects may explain the association of plasma CFH levels with PGD. The hemoprotein reductant APAP attenuates the effects of CFH and merits further exploration as a potential therapy for PGD prevention.


Photoprotective Effect of Dietary Galacto-Oligosaccharide (GOS) in Hairless Mice via Regulation of the MAPK Signaling Pathway.
This study investigated the suppression of photoaging by galacto-oligosaccharide (GOS) ingestion following exposure to ultraviolet (UV) radiation. To investigate its photoprotective effects, GOS along with collagen tripeptide (CTP) as a positive control was orally administered to hairless mice under UVB exposure for 8 weeks. The water holding capacity, transepidermal water loss (TEWL), and wrinkle parameters were measured. Additionally, quantitative reverse-transcription polymerase chain reaction and Western blotting were used to determine mRNA expression and protein levels, respectively. The GOS or CTP orally-administered group showed a decreased water holding capacity and increased TEWL compared to those of the control group, which was exposed to UVB (CON) only. In addition, the wrinkle area and mean wrinkle length in the GOS and CTP groups significantly decreased. Skin aging-related genes, matrix metalloproteinase, had significantly different expression levels in the CTP and GOS groups. Additionally, the tissue inhibitor of metalloproteinases and collagen type I gene expression in the CTP and GOS groups significantly increased. Oral administration of GOS and CTP significantly lowered the tissue cytokine (interleukin-6 and -12, and tumor necrosis factor-α) levels. There was a significant difference in UVB-induced phosphorylation of JNK, p38, and ERK between the GOS group and the CON group. Our findings indicate that GOS intake can suppress skin damage caused by UV light and has a UV photoprotective effect.


The fracture liaison service: success of a program for the evaluation and management of patients with osteoporotic fracture.
Fracture care often represents the first opportunity for clinical management of osteoporosis; however, many patients do not receive any evaluation after a fracture. In Glasgow, Scotland, fewer than 10% of fracture patients underwent bone mineral density (BMD) testing. In an effort to better meet the needs of fracture patients by providing routine assessment and, where necessary, treatment for osteoporosis after their fracture, a novel service (The Fracture Liaison Service) was designed and implemented in two separate National Health Service trusts in Glasgow. An agreed-upon standard of care for men and women 50+ years of age with fractures was established in collaboration with orthopedic surgeons and primary care physicians. The Fracture Liaison Service assumes responsibility for fracture case-finding and for assessing and performing diagnostic evaluations (including axial DXA), and making specific treatment recommendations for the secondary prevention of osteoporotic fractures. During the first 18 months of operation, more than 4,600 patients with fractures of the hip, wrist, humerus, ankle, foot, hand, and other sites were seen by the Fracture Liaison Service's osteoporosis specialist nurses. Nearly three quarters of these patients were considered for BMD testing; treatment was recommended for approximately 20% of the patients without need for BMD testing. Overall, 82.3% of patients who had BMD testing were found to be osteopenic or osteoporotic at the hip or spine. The Fracture Liaison Service has successfully identified and evaluated most patients with fractures. Only those patients who declined were not evaluated. The ultimate success of the program will be measured by the subsequent fracture experience of these patients, but clear improvements in diagnosing and treating low bone mineral density in patients with fracture have already been demonstrated.


The dynamic TRPA1 channel: a suitable pharmacological pain target?
Acute pain detection is vital to navigate and survive in one's environment. Protection and preservation occur because primary afferent nociceptors transduce adverse environmental stimuli into electrical impulses that are transmitted to and interpreted within high levels of the central nervous system. Therefore, it is critical that the molecular mechanisms that convert noxious information into neural signals be identified, and their specific functional roles delineated in both acute and chronic pain settings. The Transient Receptor Potential (TRP) channel family member TRP ankyrin 1 (TRPA1) is an excellent candidate molecule to explore and intricately understand how single channel properties can tailor behavioral nociceptive responses. TRPA1 appears to dynamically respond to an amazingly wide range of diverse stimuli that include apparently unrelated modalities such as mechanical, chemical and thermal stimuli that activate somatosensory neurons. How such dissimilar stimuli activate TRPA1, yet result in modality-specific signals to the CNS is unclear. Furthermore, TRPA1 is also involved in persistent to chronic painful states such as inflammation, neuropathic pain, diabetes, fibromyalgia, bronchitis and emphysema. Yet how TRPA1's role changes from an acute sensor of physical stimuli to its contribution to these diseases that are concomitant with implacable, chronic pain is unknown. TRPA1's involvement in the nociceptive machinery that relays the adverse stimuli during painful disease states is of considerable interest for drug delivery and design by many pharmaceutical entities. In this review, we will assess the current knowledge base of TRPA1 in acute nociception and persistent inflammatory pain states, and explore its potential as a therapeutic pharmacological target in chronic pervasive conditions such neuropathic pain, persistent inflammation and diabetes.


Thermal deformations of solid mirrors.
The tensor equations of elasticity including temperature terms in nonorthogonal coordinates are presented in a form suitable for the method of dynamic relaxation. A nonorthogonal coordinate system that includes a wide class of circular solid mirrors or lenses is described. The equations may be solved for any prescribed temperature distribution. Computed results are given for several cases.


The Mad-Genius Paradox: Can Creative People Be More Mentally Healthy But Highly Creative People More Mentally Ill?
The persistent mad-genius controversy concerns whether creativity and psychopathology are positively or negatively correlated. Remarkably, the answer can be "both"! The debate has unfortunately overlooked the fact that the creativity-psychopathology correlation can be expressed as two independent propositions: (a) Among all creative individuals, the most creative are at higher risk for mental illness than are the less creative and (b) among all people, creative individuals exhibit better mental health than do noncreative individuals. In both propositions, creativity is defined by the production of one or more creative products that contribute to an established domain of achievement. Yet when the typical cross-sectional distribution of creative productivity is taken into account, these two statements can both be true. This potential compatibility is here christened the mad-genius paradox. This paradox can follow logically from the assumption that the distribution of creative productivity is approximated by an inverse power function called Lotka's law. Even if psychopathology is specified to correlate positively with creative productivity, creators as a whole can still display appreciably less psychopathology than do people in the general population because the creative geniuses who are most at risk represent an extremely tiny proportion of those contributing to the domain. The hypothesized paradox has important scientific ramifications.


Valuing and Sustaining (or Not) the Ability of Volunteer Community Health Workers to Deliver Integrated Community Case Management in Northern Ghana: A Qualitative Study.
Within the integrated community case management of childhood illnesses (iCCM) programme, the traditional health promotion and prevention role of community health workers (CHWs) has been expanded to treatment. Understanding both the impact and the implementation experience of this expanded role are important. In evaluating UNICEF's implementation of iCCM, this qualitative case study explores the implementation experience in Ghana. Data were collected through a rapid appraisal using focus groups and individual interviews during a field visit in May 2013 to Accra and the Northern Region of Ghana. We sought to understand the experience of iCCM from the perspective of locally based UNICEF staff, their partners, researchers, Ghana health services management staff, CHWs and their supervisors, nurses in health facilities and mothers receiving the service. Our analysis of the findings showed that there is an appreciation both by mothers and by facility level staff for the contribution of CHWs. Appreciation was expressed for the localisation of the treatment of childhood illness, thus saving mothers from the effort and expense of having to seek treatment outside of the village. Despite an overall expression of value for the expanded role of CHWs, we also found that there were problems in supporting and sustaining their efforts. The data showed concern around CHWs being unpaid, poorly supervised, regularly out of stock, lacking in essential equipment and remaining outside the formal health system. Expanding the roles of CHWs is important and can be valuable, but contextual and health system factors threaten the sustainability of iCCM in Ghana. In this and other implementation sites, policymakers and key donors need to take into account historical lessons from the CHW literature, while exploring innovative and sustainable mechanisms to secure the programme as part of a government owned and government led strategy.


[Effect of the opiate antagonist naloxone on the electrical activity of identified neurons in the edible snail].
The opiate antagonist naloxone modifies the electric activity of some identified neurons of the Helix lucorum which have not been preliminary exposed to the effect of exogenous opioids. Some neurons are excited while others are inhibited by naloxone, and in both cases the reaction may have both a short and long latent period. The reactions depend on naloxone dose and become less expressed or are blocked when naloxone is administered together with the agonists of opiate receptor (morphine, D-Ala2, D-Leu5-enkephalin, bremazocine and beta-endorphin). Opioids alone do not produce any effect on neurons. The effect of naloxone on neurons is assumed to be a result of the elimination by the opiate antagonist of the tonic effect of endogenous opioids by their replacing on opiate receptors which are constantly stimulated by endogenous ligands.


Contribution of liquid-phase and gas-phase ionization in extractive electrospray ionization mass spectrometry of primary amines.
In this study, we investigated how binary mixtures of compounds influence each other's signal intensity in electrospray ionization (ESI), extractive electrospray ionization (EESI) and secondary electrospray ionization (SESI) experiments. The experiments were conducted using a series of homologous primary amines (from 1-butyl to 1- decylamine). In every experiment, two of the amines were present, and all 21 possible combinations were measured with EESI, ESI and SESI as ionization sources. Except for the volatility, which decreases with increasing molecular weight, the physico-chemical properties of the amines are very similar, so that the intensity ratio obtained in each experiment provides information about discrimination effects occurring during the ionization process. The results show that for the relatively volatile compounds investigated, the EESI ionization mechanism resembles the SESI-like gas-phase charge transfer more than ESI-like analyte ionization in solution. In addition, almost no discrimination effects were observed in the spectra obtained in EESI experiments. Quantitative EESI experiments with nonylamine as internal standard showed that EESI is capable of providing both more accurate and more precise results than SESI and ESI.


Investigation on the Properties and on the Photo-Oxidation Behaviour of Polypropylene/Fumed Silica Nanocomposites.
This work investigates the effects of very small amounts of fumed silica on the morphology and on the rheological and mechanical behaviour of polypropylene nanocomposites and on their photo-oxidation behaviour. Polypropylene nanocomposites were prepared using a twin-screw corotating extruder with 0, 1 and 2 wt/wt% of SiO2. Morphological, mechanical, thermomechanical and rheological properties were examined. It was found that the viscosity of the matrix is reduced by the presence of the silica nanoparticles, suggesting a poor adhesion between the two phases and probably some lubricating effect. On the contrary, the mechanical and, in particular, the thermomechanical properties of the matrix are considerably improved by the presence of the silica. In particular, elastic modulus and tensile strength increases remarkably, and this effect becomes more and more remarkable with an increasing temperature. As for the photo-oxidation behaviour, the presence of silica improves the photostability of the polypropylene matrix. This effect has been attributed to both the barrier to the oxygen and to the absorbance of the UV radiation from the silica nanoparticles. Finally, no significant effect of the silica nanoparticles has been put in evidence on the crystallisation behaviour of the polypropylene. As for the effect of the silica content, the difference in the properties of the two nanocomposites is relatively small and all the measured properties depend much less than linearly with its amount. This has been correlated with the reaggregation of the nanoparticles that, having a larger size, decrease the contact area between the matrix and the filler.


Updated Meta-Analysis of Randomized Controlled Trials Comparing External Fixation to Intramedullary Nailing in the Treatment of Open Tibial Fractures.
Background: The purpose of this study was to collect all available randomized controlled trials (RCT) on the treatment of open tibial fractures with an external fixator (EF) and intramedullary nailing (IMN) for meta-analysis to provide reliable evidence-based data for clinical decision-making. Material and methods: The systematic review was undertaken in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and AMSTAR (Assessing the Methodological Quality of Systematic Review). An electronic search of PubMed, Cochrane Library, and Web of Science was performed until 1 March 2023 to identify RCTs which compared either IMN or EF to fix the open tibial fracture. Outcome measures were: postoperative superficial and deep infection, time to union, delayed union, malunion, nonunion and hardware failure. In addition, pain and health-related quality of life were evaluated after 3 and 12 months of follow-up. Results: Sixteen publications comprising 1011 patients were included in the meta-analysis. The pooled results suggested that the IMN technique had a lower postoperative superficial infection and malunion rate (RR = 3.56, 95%CI = 2.56-4.95 and RR = 1.96, 95%CI = 1.12-3.44, respectively), but higher hardware failure occurrence in contrast to EF (RR = 0.30; 95%CI = 0.13-0.69). No significant differences were found in the union time, delayed union or nonunion rate, and postoperative deep infection rate between the treatments. Lower levels of pain were found in the EF group (RR = 0.05, 95%CI = 0.02-0.17, p < 0.001). A difference in quality of life favoring IMN after 3 months was found (RR = -0.04, 95%CI = -0.05-0.03, p < 0.001), however, no statistical difference was found after 12 months (RR = 0.03, 95%CI = -0.05-0.11, p = 0.44). Conclusions: Meta-analysis presented reduced incidence rates of superficial infection, malunion, and health-related quality of life 3 months after treatment in IMN. However, EF led to a significant reduction in pain and incidence rate of hardware failure. Postoperative deep infection, delayed union, nonunion and health-related quality of life 12 months following therapy were similar between groups. More high-quality RCTs should be conducted to provide reliable evidence-based data for clinical decision-making.


Interleukin-3 in hematology and oncology: current state of knowledge and future directions.
Interleukin (IL)-3 is a multipotent hematopoietic growth factor produced by activated T cells, monocytes/macrophages and stroma cells. The human IL-3 gene is located on chromosome 5 near segment 5q31. The high-affinity receptor for human IL-3 is composed of alpha and beta subunits. IL-3 shares a common beta subunit with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-5; this subunit has been mapped to chromosome 22q13.1. The biological effects of IL-3 have been studied in human and murine hematopoietic cell lines and normal human marrow cells. Addition of IL-3 to the culture medium induces proliferation, maturation and probably self-renewal of pluripotent hematopoietic stem cells and cells of myeloid, erythroid and megakaryocytic lineages. Human IL-3 was cloned in 1986, and since then various clinical trials have assessed the in vivo potential of recombinant human (rhIL-3). Initial results of phase I/II studies of IL-3 at a dose of 5-10 microg/kg subcutaneously daily for 5-10 days in patients with relapsed lymphomas, small-cell lung cancer, breast cancer and ovarian cancer showed that post-chemotherapy application of IL-3 reduces chemotherapy delays and induces faster regeneration of granulocytes and platelets. However, these results were not confirmed in phase III studies. The role of IL-3 alone in the treatment of myelodysplastic syndromes (MDS), aplastic anemia (AA) and other bone marrow failure disorders have also been disappointing. However, preliminary studies of IL-3 in combination with chemotherapeutic agents and immunosuppression have demonstrated encouraging results in patients with MDS and AA respectively. The therapeutic potential of IL-3 in peripheral blood stem cell (PBSC) harvesting and priming of stem cells before harvest is beginning to be identified. Initial results of IL-3 combination with GM-CSF or later-acting growth factors such as granulocyte colony-stimulating factor (G-CSF) have yielded larger amounts of PBSC during harvesting. In recent years, the availability of synthetic IL-3 receptor (IL-3R) agonists and similar chimeric molecules with greater in vitro biological activity and fewer inflammatory side-effects has extended our options to employ and compare these molecules and rhIL-3 for the prevention of chemotherapy-induced myelosuppression. The role of IL-3 and IL-3R agonists in ex vivo expansion of stem cells, dendritic cell development and gene transfer requires further evaluation. It appears that future application of IL-3 in combination with other cytokines is an attractive way forward in the prevention of treatment-related mortality and morbidity in oncology patients. It also shows prospects for the development of new therapeutic strategies for dose escalation and immune modulation for cancer patients with relapsed and resistant disease.


Looking into the volcano with a Mid-IR DFB diode laser and Cavity Enhanced Absorption Spectroscopy.
We report on the first application of extended-wavelength DFB diode lasers to Cavity-Enhanced Absorption Spectroscopy in-situ trace measurements on geothermal gases. The emission from the most active fumarole at the Solfatara volcano near Naples (Italy) was probed for the presence of CO and CH(4). After passing through a gas dryer and cooler, the volcanic gas flow (98% CO(2)) was analysed in real time for the concentration of these species, whose relatively strong absorption lines could be monitored simultaneously by a single Distributed Feed-Back (DFB) GaSb-based diode laser emitting around 2.33 mum (4300 cm(-1)) at room temperature. The concentrations were found to be about 3 ppm and 75 ppm, respectively, while actual detection limits for these molecules are around 1 ppb. We discuss the possibility of detecting other species of interest for volcanic emission monitoring.


Excision of an atypical case of palatal bone exostosis: a case report.
Bone exostosis has long been described in the literature, appearing in most cases as a torus palatinus or mandibularis. These two variations are relatively common and affect approximately 30% of the world's population. Incidence is even higher when human skulls are examined post mortem, indicating that in some cases the exostosis is small and cannot be seen under the soft tissue. Removal of an exostosis is usually associated with the construction of a prothesis, but in rare cases such as the present, the lesion enlarges enough to affect speech and feeding. Few studies have reported the removal of such a large exostosis, and all were conducted in a hospital environment. In this case, complete removal was successfully conducted in an ambulatory clinic under local anesthesia.


Detection of type II endoleaks in abdominal aortic aneurysms after endovascular repair.
Abdominal aortic aneurysm (AAA) is a condition where the weakening of the aortic wall leads to its widening and the generation of a thrombus. To prevent a possible rupture of the aortic wall, AAA can be treated non-invasively by means of the endovascular aneurysm repair technique (EVAR), consisting of placing a stent-graft inside the aorta by a cateter to exclude the aneurysm sac from the blood circulation. A major complication is the presence of liquid blood turbulences, called endoleaks, in the thrombus formed in the space between the aortic wall and the stent-graft. In this paper we propose an automatic method for the detection of type II endoleaks in computer tomography angiography (CTA) images. The lumen and thrombus in the aneurysm area are first segmented using a radial model approach. Then, these regions are split into Thrombus Connected Components (TCCs) using a watershed-based segmentation and geometric and image content-based characteristics are obtained for each TCC. Finally, TCCs are classified into endoleaks and non-endoleaks using a multilayer Perceptron (MLP) trained on manual labeled sample TCCs provided by experts.


Fibrosing Mediastinits Causing Obstruction of Left Lower Lobar Bronchus: A Pediatric Case Report.
Fibrosing mediastinitis is a rare benign disorder characterized by the proliferation of dense fibrous tissue within the mediastinum. It typically manifests as localized or infiltrative soft-tissue masses in the middle mediastinum or hilar area, which cause compression and encasement of adjacent mediastinal structures, such as the vessels or airway. Here, we report a rare case of fibrosing mediastinitis in a 13-year-old girl that presented as a middle mediastinal mass lesion on CT scan with obliterating left lower lobar bronchus. The patient's symptoms and follow-up chest CT showed significant improvement following systemic corticosteroid treatment. As fibrosing mediastinitis can improve with systemic steroid therapy, radiologists must be aware of its radiologic findings when discriminating between infiltrating soft tissue lesions in the mediastinum.


[Familial aquagenic urticaria: report of two cases and literature review].
Aquagenic urticaria is a rare form of physical urticaria, characterized by pruritic wheals that appear following contact with water, independently of its temperature. There are few reports of cases of aquagenic urticaria, and only five include the familial form. We present the first case of familial aquagenic urticaria in Brazil (mother and daughter). Both patients presented wheals following contact with water, especially when showering, regardless of its temperature. The mother reported onset of urticaria four years before and the daughter presented wheals since birth. For diagnostic purposes, they were submitted to a challenge test with water, and both subjects presented wheals, as well as to tests using ice cubes in plastic bag with dermographometer and challenge tests for cholinergic urticaria, with no appearance of lesions, excluding other forms of physical urticaria.


Is sexual contact a major mode of hepatitis C virus transmission?
Medical opinion varies considerably regarding the transmission of hepatitis C virus (HCV) through sexual contact. Based on the study design, representativeness of the study population, and the methods used for case ascertainment, we analyzed 80 qualifying reports regarding the evidence for or against sexual transmission. Regarding heterosexual transmission, the weight of evidence is that there is no increased risk of sexual transmission of HCV among heterosexual couples in regular relationships. This risk increases among persons with multiple sexual partners (adjusted odds ratio [aOR] 2.2-2.9), but this association may be confounded by increased likelihood of injection drug use with increased number of partners. There appears to be a real increased risk for women coinfected with human immunodeficiency virus (HIV) or other sexually transmitted infections (aOR 3.3-3.9) and especially for HIV-infected gay men who are having sex with one another compared with HIV-uninfected men (aOR 4.1-5.7). HIV-infected gay men increase their risk of such transmission in association with practices that lead to mucosal trauma (multiple sexual partners, fisting, use of sex toys) and the presence of genital ulcerative disease. This review should inform, and not distract from, recommendations to reduce the risk of HCV transmission. Health care providers need to pay special attention to sexual transmission of HCV among HIV-infected individuals.


A new hypothesis on BV etiology: dichotomous and crisscrossing categorization of complex versus simple on healthy versus BV vaginal microbiomes.
BV may influence as many as one-third of women, but its etiology remains unclear. A traditional view is that dominance by Lactobacillus is the hallmark of a healthy vaginal microbiome and lack of dominance may make women BV-prone. Recent studies show that the human VMs can be classified into five major types, four of which possess type-specific dominant species of Lactobacillus. The remaining one (type IV) is not dominated by Lactobacillus and contains a handful of strictly anaerobic bacteria. Nevertheless, exceptions to the first hypothesis have been noticed from the very beginning, and there is not a definite relationship, suggested yet, between the five VM types and BV status. Here, we propose and test a novel hypothesis that assumes the existence of four VM types from dichotomous crisscrossing of "complex versus simple (high diversity or low dominance versus low diversity or high dominance)" on "healthy versus BV." Consequently, there are simple BV versus complex BV.


A quantitative measure for protein conformational heterogeneity.
Conformational heterogeneity is a defining characteristic of proteins. Intrinsically disordered proteins (IDPs) and denatured state ensembles are extreme manifestations of this heterogeneity. Inferences regarding globule versus coil formation can be drawn from analysis of polymeric properties such as average size, shape, and density fluctuations. Here we introduce a new parameter to quantify the degree of conformational heterogeneity within an ensemble to complement polymeric descriptors. The design of this parameter is guided by the need to distinguish between systems that couple their unfolding-folding transitions with coil-to-globule transitions and those systems that undergo coil-to-globule transitions with no evidence of acquiring a homogeneous ensemble of conformations upon collapse. The approach is as follows: Each conformation in an ensemble is converted into a conformational vector where the elements are inter-residue distances. Similarity between pairs of conformations is quantified using the projection between the corresponding conformational vectors. An ensemble of conformations yields a distribution of pairwise projections, which is converted into a distribution of pairwise conformational dissimilarities. The first moment of this dissimilarity distribution is normalized against the first moment of the distribution obtained by comparing conformations from the ensemble of interest to conformations drawn from a Flory random coil model. The latter sets an upper bound on conformational heterogeneity thus ensuring that the proposed measure for intra-ensemble heterogeneity is properly calibrated and can be used to compare ensembles for different sequences and across different temperatures. The new measure of conformational heterogeneity will be useful in quantitative studies of coupled folding and binding of IDPs and in de novo sequence design efforts that are geared toward controlling the degree of heterogeneity in unbound forms of IDPs.


A population-based survey of self-reported delays in breast, cervical, colorectal and lung cancer screening.
The early COVID-19 pandemic was associated with cessation of screening services, but the prevalence of ongoing delays in cancer screening into the third year of the pandemic are not well-characterized. In February/March 2022, a population-based survey assessed cancer needs in New Hampshire and Vermont. The associations between cancer screening delays (breast, cervical, colorectal or lung cancer) and social determinants of health, health care access, and cancer attitudes and beliefs were tested. Distributions and Rao-Scott chi-square tests were used for hypothesis testing and weighted to represent state populations. Of 1717 participants, 55% resided in rural areas, 96% identified as White race, 50% were women, 36% had high school or less education. Screening delays were reported for breast cancer (28%), cervical cancer (30%), colorectal cancer (24%), and lung cancer (30%). Delays were associated with having higher educational attainment (lung), urban living (colorectal), and having Medicaid insurance (breast, cervical). Low confidence in ability to obtain information about cancer was associated with screening delays across screening types. The most common reason for delay was the perception that the screening test was not urgent (31% breast, 30% cervical, 28% colorectal). Cost was the most common reason for delayed lung cancer screening (36%). COVID-19 was indicated as a delay reason in 15-29% of respondents; 12-20% reported health system capacity during the pandemic as a reason for delay, depending on screening type. Interventions that address sub-populations and reasons for screening delays are needed to mitigate the impact of the COVID-19 pandemic on cancer burden and mortality.


Linnemannia elongata (Mortierellaceae) stimulates Arabidopsis thaliana aerial growth and responses to auxin, ethylene, and reactive oxygen species.
Harnessing the plant microbiome has the potential to improve agricultural yields and protect plants against pathogens and/or abiotic stresses, while also relieving economic and environmental costs of crop production. While previous studies have gained valuable insights into the underlying genetics facilitating plant-fungal interactions, these have largely been skewed towards certain fungal clades (e.g. arbuscular mycorrhizal fungi). Several different phyla of fungi have been shown to positively impact plant growth rates, including Mortierellaceae fungi. However, the extent of the plant growth promotion (PGP) phenotype(s), their underlying mechanism(s), and the impact of bacterial endosymbionts on fungal-plant interactions remain poorly understood for Mortierellaceae. In this study, we focused on the symbiosis between soil fungus Linnemannia elongata (Mortierellaceae) and Arabidopsis thaliana (Brassicaceae), as both organisms have high-quality reference genomes and transcriptomes available, and their lifestyles and growth requirements are conducive to research conditions. Further, L. elongata can host bacterial endosymbionts related to Mollicutes and Burkholderia. The role of these endobacteria on facilitating fungal-plant associations, including potentially further promoting plant growth, remains completely unexplored. We measured Arabidopsis aerial growth at early and late life stages, seed production, and used mRNA sequencing to characterize differentially expressed plant genes in response to fungal inoculation with and without bacterial endosymbionts. We found that L. elongata improved aerial plant growth, seed mass and altered the plant transcriptome, including the upregulation of genes involved in plant hormones and "response to oxidative stress", "defense response to bacterium", and "defense response to fungus". Furthermore, the expression of genes in certain phytohormone biosynthetic pathways were found to be modified in plants treated with L. elongata. Notably, the presence of Mollicutes- or Burkholderia-related endosymbionts in Linnemannia did not impact the expression of genes in Arabidopsis or overall growth rates. Together, these results indicate that beneficial plant growth promotion and seed mass impacts of L. elongata on Arabidopsis are likely driven by plant hormone and defense transcription responses after plant-fungal contact, and that plant phenotypic and transcriptional responses are independent of whether the fungal symbiont is colonized by Mollicutes or Burkholderia-related endohyphal bacteria.


An international comparative analysis and roadmap to sustainable biosimilar markets.
Background: Although biosimilar uptake has increased (at a variable pace) in many countries, there have been recent concerns about the long-term sustainability of biosimilar markets. The aim of this manuscript is to assess the sustainability of policies across the biosimilar life cycle in selected countries with a view to propose recommendations for supporting biosimilar sustainability. Methods: The study conducted a comparative analysis across 17 countries from North America, South America, Asia-Pacific, Europe and the Gulf Cooperation Council. Biosimilar policies were identified and their sustainability was assessed based on country-specific reviews of the scientific and grey literature, validation by industry experts and 23 international and local non-industry experts, and two advisory board meetings with these non-industry experts. Results: Given that European countries tend to have more experience with biosimilars and more developed policy frameworks, they generally have higher sustainability scores than the other selected countries. Existing approaches to biosimilar manufacturing and R&D, policies guaranteeing safe and high-quality biosimilars, exemption from the requirement to apply health technology assessment to biosimilars, and initiatives counteracting biosimilar misconceptions are considered sustainable. However, biosimilar contracting approaches, biosimilar education and understanding can be ameliorated in all selected countries. Also, similar policies are sometimes perceived to be sustainable in some markets, but not in others. More generally, the sustainability of the biosimilar landscape depends on the nature of the healthcare system and existing pharmaceutical market access policies, the experience with biosimilar use and policies. This suggests that a general biosimilar policy toolkit that ensures sustainability does not exist, but varies from country to country. Conclusion: This study proposes a set of elements that should underpin sustainable biosimilar policy development over time in a country. At first, biosimilar policies should guarantee the safety and quality of biosimilars, healthy levels of supply and a level of cost savings. As a country gains experience with biosimilars, policies need to optimise uptake and combat any misconceptions about biosimilars. Finally, a country should implement biosimilar policies that foster competition, expand treatment options and ensure a sustainable market environment.


Selection of Salmonella typhimurium mutants with altered serine transhydroxymethylase regulation.
In Salmonella typhimurium the glyA gene product, serine transhydroxymethylase (E.C. 188.8.131.52.; L-serine:tetrahydrofolate-5,10-hydroxymethyltransferase) is responsible for the interconversion of serine and glycine. This reaction also provides the cell with one-carbon units from the 5,10-methylene-tetrahydrofolate formed during glycine synthesis. Despite the importance of this enzyme, however, no mutants in which its regulation has been specificially altered have been isolated. To isolate such mutants, we have devised a selection procedure using a strain (glyA951) in which the serine transhydroxymethylase activity is reduced. When this enzyme is completely repressed, the mutant requires gylcine for growth. Revertants which retain the glyA951 lesion, but no longer require glycine, have been isolated and the serine transhydroxymethylase regulation examined. One revertant has a 7-fold elevated serine transhydroxymethylase level, which can be repressed the normal amount (about 5-fold) when the cells are grown in supplemented media. Another revertant has only a 2-fold higher serine transhydroxymethylase level; however, the amount of repression is reduced. The new lesions in both mutants cotransduce with the glyA gene and are distinct from other mutations that alter the regulation of both serine transhydroxymethylase and the methionine biosyntheitc enzymes.


Reversible activation of succinate dehydrogenase.
1. Treatment of particulate respiratory chain preparations in ways expected to raise or lower the concentration of endogenous soluble low-molecular-weight compounds respectively increased and diminished the capacity of succinate dehydrogenase to become activated reversibly and ;spontaneously' when preparations were diluted in tris acetate buffer and incubated at 37 degrees . 2. Addition of critically low concentrations of recognized activators to preparations that failed to undergo reversible ;spontaneous' activation when incubated at 1mg. of protein/ml. conferred on them the capacity to do so. 3. Preparations with a diminished tendency to undergo reversible ;spontaneous' activation had an increased tendency to become irreversibly inactivated on prolonged incubation at 1mg. of protein/ml. in tris acetate. 4. Extraction procedures designed to demonstrate the presence of possible endogenous activators in enzyme preparations failed to reveal a single substance to which such a role could be conclusively attributed. A mixture of compounds was found, however, including certain amino acids that have been shown to act as activators. It is questionable whether these compounds would be present at sufficiently high concentrations to act as activators when enzyme preparations are diluted to 1mg. of protein/ml. 5. Despite the failure to demonstrate conclusively the presence of endogenous activators, the balance of evidence appears to favour the hypothesis that reversible ;spontaneous' activation of these preparations can best be explained by the presence of such substances, and a scheme describing the mechanism of activation and deactivation of succinate dehydrogenase is discussed in relation to these and other observations.


Efficacy of Infrared Vein Visualization versus Standard Technique for Peripheral Venous Cannulation in Infant and Toddler Populations: A Randomized Study.
Establishing intravenous (IV) access in younger patient populations via the traditional cannulation technique for procedures requiring anesthesia is often challenging. Infrared (IR) vein visualization is a modality that aids venous cannulation; however, few reports of this technique exist in the infant and toddler population. The primary aim of this study was to compare the efficacy of IR vein visualization to the standard cannulation technique for obtaining peripheral IV access in infant and toddler populations. Following Institutional Review Board (IRB) approval and written informed consent, children were randomly assigned to either a standard cannulation technique group or an IR vein visualization device group for venous cannulation. The primary outcome variable was the success rate of IV cannulation, and the secondary variables were the total number of attempts and the time to successful cannulation. No difference was noted between either group for first-attempt success rate (standard versus IR: 61.25% vs. 54.4%; p = 0.4) or time to establish IV cannulation (standard versus IR: median [interquartile range], 40 s [24-120] vs. 53 s [26-106]; p = 0.55). The anesthesiologist's grading of the anticipated difficulty of IV cannulation was a significant predictor of cannulation success (p = 0.0016). Our study demonstrated no significant benefit in utilizing the IR vein visualization device in terms of the overall success rate, number of attempts, and time to establish successful IV cannulation when compared to the standard technique. However, in difficult IV access situations, this device proved to be a valuable rescue adjunct.


Neurological toxicities associated with immune-checkpoint inhibitors.
Immune-checkpoint inhibitors (ICIs) constitute a novel class of agents recently approved to treat a number of human malignancies. Due to their immunomodulatory mechanism of action, ICIs can generate a wide range of immune-related adverse events (irAEs) of which neurological toxicities are of special interest because of their potential severity. The objective of this review is to examine the recent literature describing neurological irAEs and discuss their optimal management. As opposed to irAEs involving other organs, neurological complications of ICIs are uncommon. These complications encompass various toxicities of the central and peripheral nervous systems, including myositis, myasthenia gravis, demyelinating polyradiculoneuropathy, meningitis and encephalitis. Neurologic irAEs are often responsive to corticosteroids and other immune-modulating treatments (e.g. plasmapheresis, intravenous immunoglobulin), which have been used in patients presenting with severe neurologic irAEs or irAEs unresponsive to corticosteroids. Data from literature indicate that early treatment is critical for reducing the morbidity associated with neurologic irAEs. ICI-associated irAEs constitute a new group of neurologic complications of systemic anticancer therapies. Although potentially severe, these rare neurologic toxicities are often responsive to immune-modulating therapies. Early recognition and treatment is crucial for timely improvement of functional outcome and requires a multidisciplinary approach.


Plasminogen Activator Inhibitor-1 Controls Vascular Integrity by Regulating VE-Cadherin Trafficking.
Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, is expressed and secreted by endothelial cells. Patients with PAI-1 deficiency show a mild to moderate bleeding diathesis, which has been exclusively ascribed to the function of PAI-1 in down-regulating fibrinolysis. We tested the hypothesis that PAI-1 function plays a direct role in controlling vascular integrity and permeability by keeping endothelial cell-cell junctions intact. We utilized PAI-039, a specific small molecule inhibitor of PAI-1, to investigate the role of PAI-1 in protecting endothelial integrity. In vivo inhibition of PAI-1 resulted in vascular leakage from intersegmental vessels and in the hindbrain of zebrafish embryos. In addition PAI-1 inhibition in human umbilical vein endothelial cell (HUVEC) monolayers leads to a marked decrease of transendothelial resistance and disrupted endothelial junctions. The total level of the endothelial junction regulator VE-cadherin was reduced, whereas surface VE-cadherin expression was unaltered. Moreover, PAI-1 inhibition reduced the shedding of VE-cadherin. Finally, we detected an accumulation of VE-cadherin at the Golgi apparatus. Our findings indicate that PAI-1 function is important for the maintenance of endothelial monolayer and vascular integrity by controlling VE-cadherin trafficking to and from the plasma membrane. Our data further suggest that therapies using PAI-1 antagonists like PAI-039 ought to be used with caution to avoid disruption of the vessel wall.


Cobalt-55 positron emission tomography in traumatic brain injury: a pilot study.
Traumatic brain injury is usually assessed with the Glasgow coma scale (GCS), CT, or MRI. After such injury, the injured brain tissue is characterised by calcium mediated neuronal damage and inflammation. Positron emission tomography with the isotope cobalt-55 (Co-PET) as a calcium tracer enables imaging of affected tissue in traumatic brain injury. The aim was to determine whether additional information can be gained by Co-PET in the diagnosis of moderate traumatic brain injury and to assess any prognostic value of Co-PET. Five patients with recent moderately severe traumatic brain injury were studied. CT was performed on the day of admission, EEG within one week, and MRI and Co-PET within four weeks of injury. Clinical assessment included neurological examination, GCS, neuropsychological testing, and Glasgow outcome scale (GOS) after one year. Co-PET showed focal uptake that extended beyond the morphological abnormalities shown by MRI and CT, in brain regions that were actually diagnosed with EEG. Thus Co-PET is potentially useful for diagnostic localisation of both structural and functional abnormalities in moderate traumatic brain injury.


Acupuncture in sham device controlled trials may not be as effective as acupuncture in the real world: a preliminary network meta-analysis of studies of acupuncture for hot flashes in menopausal women.
Randomised controlled trials of acupuncture performed using sham interventions to control for the placebo effect have mostly used two types of sham techniques: techniques with minimal insertion of acupuncture needles with no additional stimulation (shallow needling control) and techniques with sham acupuncture devices that do not penetrate the skin (sham device control). To achieve successful blinding, sham device controlled acupuncture trials also use the acupuncture base unit in the verum acupuncture group, but in the shallow needling control trials this is not necessary for the verum acupuncture treatment. In this study, we analysed the estimated comparative effectiveness of these two verum acupuncture modalities in studies of acupuncture for menopausal hot flashes that used two types of sham control treatments. We conducted a network meta-analysis that included randomised controlled trials of acupuncture for hot flashes. Electronic databases, including Medline, Embase, Cochrane Library and AMED, were searched through March 2017. Data were extracted using a predefined data extraction tool by two independent reviewers. The risk of bias was assessed using the Cochrane risk of bias tool for randomised controlled trials. A five-node network meta-analysis was conducted based on the frequentist framework. Eight studies were included in this review. From the network meta-analysis, we found that verum acupuncture in the shallow needling controlled trials was more effective than verum acupuncture in the sham device controlled trials (SMD -7.27, 95% CI-9.11 to -5.43). Significant heterogeneity and inconsistency were not observed among the included studies or the comparisons. From this preliminary analysis, we found that different types of verum acupuncture may have different effect sizes with respect to the severity of menopausal hot flashes.


[A comparative study on open reduction and plating osteosynthesis and minimal invasive plating osteosynthesis in treating mid-distal humeral shaft fractures].
To compare the clinical results of two plating osteosynthesis techniques, open reduction and plating osteosynthesis (ORPO) and minimal invasive plating osteosynthesis (MIPO), in surgical treatment of mid-distal humeral shaft fractures. From March 2004 to October 2006, 40 cases of closed unilateral mid-distal humeral shaft fractures were surgically treated with MIPO or ORPO. In the MIPO treated group (n = 19), there were 14 males and 5 females, with a mean age of 39.05 years. Fractures involved in middle humeral shaft in 10 cases and distal fragment in 9 cases. According to OTA classification, there were 3 cases of type A, 13 cases of type B and 3 cases of type C. Four cases complicated by radial nerve palsies. In the ORPO treated group (n = 21), there were 13 males and 8 females with a mean age of 39.05 years, including 14 cases of type A and 7 cases of type B fractures according to OTA classification. The fractures involved in middle humeral shaft in 13 cases and distal fragment in 8 cases. Five cases complicated by radial nerve palsies. The time from injury to operation in both groups were 2 to 14 days. For patients in the MIPO group, fractures were closely reduced and fixated with an anterior placed plate inserted through two small incisions made at the anterior side of arm, away from fracture sites. The radial nerves were not exposed. For patients in the ORPO group, fractures were exposed, reduced, and fixated with an anterolateral or a posterior positioned plate after careful dissection and protection of radial nerve through an anterolateral or a posterior approach. The operation time, the occurrence of iatrogenic radial nerve palsy and the bone healing time were recorded. The functions of the affected shoulders and elbows were evaluated with UCLA end-result score and Mayo elbow perform index (MEPI), respectively. All the wounds in both groups healed primarily. There was no iatrogenic radial nerve palsies in the MIPO group after surgery; however, 5 cases of transient iatrogenic radial nerve palsies were identified in the ORPO group after surgery, and the function of radial nerve recovered in these cases at the last follow-up. Eighteen cases were followed up 14-44 months (mean 25.44 months) in MIPO group, and 19 cases were followed up 13-48 months (mean 32.11 months) in ORPO group. The mean bone healing time was 17.06 (12-32) weeks in MIPO group and 16.11 (8-58) weeks in ORPO group, showing no significant difference between two groups (P > 0.05). There was no nonunion and hardware failure in both groups. The mean forward flexion of the shoulder was 166.94 degrees (150-170 degrees) in MIPO group and 164.74 degrees (130-170 degrees) in ORPO group. The mean UCLA shoulder score was 34.78 (33-35) points in MIPO group and 34.42 (30-35) points in ORPO group. The mean range of motion of the elbow in MIPO and ORPO groups was 133.33 degrees (120-140 degrees) and 136.7 degrees (120-140 degrees), respectively. The MEPI in these two groups was 99.44 (90-100) and 99.74 (95-100) points, respectively. There was no statistically significant difference between two groups in all indexes mentioned above. The good results could be obtained when ORPO and MIPO technique are applied to treat mid-distal humeral shaft fractures. MIPO technique has advantages to not expose the radial nerve and to decrease the occurrence of iatrogenic radial nerve palsies.


Gastroprotective xanthones isolated from Garcinia achachairu: Study on mucosal defensive factors and H(+), K(+)-ATPase activity.
The present study was designed to investigate the gastroprotective effect of xanthones 7-preniljacareubin (PJB), 1,3,5,6-tetrahydroxy xanthone (THX), 3-demethyl-2-geranyl-4-prenylbellidypholine (DGP) and 1,5,8-trihydroxy-4', 5'-dimethyl-2H-pyrane (2,3:3,2)-4-(3-methylbut-2-enyl) xanthone (TDP) isolated of branches from G. achachairu. Their structures were identified through the spectroscopic analysis in comparison with previously reported data. The xanthones were tested at dose of 10 mg/kg against ethanol 60%/HCl 0.3 N-induced gastric ulcer in female swiss mice. The xanthones PJB, THX, DGP and TDP exhibit gastroprotective effect after intraperitoneal treatment, but only the first two displayed anti-ulcer activity after oral administration. Both PJB and THX augmented the antioxidative capacity of tissue by an increase in glutathione levels, as well as were able to prevent an increase in myeloperoxidase activity and tumor necrosis factor level. On the other hand, only THX showed an in vitro free radical scavenger activity, and only PJB avoided mucus depletion on gastric mucosa, which was not associated with an increase in mucin production at glandular level. In addition, PJB and THX inhibited the in vitro H(+)K(+)-ATPase activity at similar range as omeprazole. Together, these results demonstrate the anti-ulcer efficacy of xanthones isolated from G. achachairu, which can contribute for future directions in the development of effective strategies to improve gastric diseases.


Evaluation of the Catheter Clamp over Hydrophilic Guide Wire Central Venous Catheter Exchange Technique for Air Embolism Prophylaxis in an In Vitro Model.
To develop a reproducible in vitro model simulating central venous catheter (CVC) exchange with high potential for air embolization and test the hypothesis that a closed catheter clamp over hydrophilic guide wire exchange technique will significantly reduce the volume of air introduced during CVC exchange. The model consisted of a 16-F valved sheath, 240-mL container, and pressure transducer submerged in water in a 1,200-mL suction canister system. Continuous wall suction was applied to the canister to maintain negative pressure at -7 mm Hg or -11 mm Hg. Each trial consisted of 0.035-inch hydrophilic guide wire introduction, over-the-wire catheter exchange, and wire removal following clinical protocol. A total of 256 trials were performed, 128 trials at each pressure with the catheter clamp open (n = 64) or closed (n = 64) around the hydrophilic guide wire. There was a statistically significant lower volume of air introduced with closed clamp over-the-wire exchanges than with open clamp exchanges at both pressures (2-tailed t-test, P < .001). At -7 mm Hg, a mean of 48.0 mL (SD ± 9.3) of air was introduced with open clamp and 20.6 mL (SD ± 4.7) of air was introduced with closed clamp. At -11 mm Hg, 97.8 mL (SD ± 11.9) of air was introduced with open clamp and 37.8 mL (SD ± 6.3) of air was introduced with closed clamp. This study demonstrated the use of a reproducible in vitro model mimicking conditions causing air embolism during CVC exchange. Results showed that CVC exchange using closed catheter clamp over hydrophilic guide wire exchange technique significantly reduced the volume of air introduced per exchange.


Transport of Critically Ill Patients by the Anesthesia Versus the Intensive Care Unit Service: A Before-After Study of Operating Room Workflows.
We implemented a new policy at our institution where the responsibility for intensive care unit (ICU) patient transports to the operating room (OR) was changed from the anesthesia to the ICU service. We hypothesized that this approach would be associated with increased on-time starts and decreased turnover times. In the historical model, intubated patients or those on mechanical circulatory assistance (MCA) were transported by the anesthesia service to the OR ("pre-ICU Pickup"). In our new model, these patients are transported by the ICU service to the preoperative holding area (Pre-op) where care is transferred to the anesthesia service ("post-ICU Transfer"). If judged necessary by the ICU or anesthesia attending, the patient was transported by the anesthesia service ("post-ICU Pickup"). We retrospectively reviewed case tracking data for patients undergoing surgery before (January 2014 to May 2015) and after implementation (July 2016 to June 2017) of the new policy. The primary outcome was the proportion of elective, weekday first-case, on-time starts. To adjust for confounders including comorbidities and time trends, we performed a segmented logistic regression analysis assessing the effect of our intervention on the primary outcome. Secondary outcomes were turnover times and compliance with preoperative checklist documentation. We identified 95 first-start and 86 turnover cases in the pre-ICU Pickup, 70 first-start and 88 turnover cases in the post-ICU Transfer, and 6 turnover cases in the post-ICU Pickup group. Ignoring time trends, the crude proportion of on-time starts increased from 32.6% in the pre-ICU Pickup to 77.1% in the post-ICU Transfer group. After segmented logistic regression adjusting for age, sex, American Society of Anesthesiologists (ASA) physical status, Sequential Organ Failure Assessment (SOFA) score, respiratory failure, endotracheal intubation, MCA, congestive heart failure (CHF), valvular heart disease, and cardiogenic and hemorrhagic shock, the post-ICU Transfer group was more likely to have an on-time start at the start of the intervention than the pre-ICU Pickup group at the end of the preintervention period (odds ratio, 11.1; 95% confidence interval [CI], 1.3-125.7; P = .043). After segmented linear regression adjusting for the above confounders, the estimated difference in mean turnover times between the post-ICU Pickup and pre-ICU Transfer group was not significant (-6.9 minutes; 95% CI, -17.09 to 3.27; P = .17). In post-ICU Transfer patients, consent, history and physical examination (H&P), and site marking were verified before leaving the ICU in 92.9%, 93.2%, and 89.2% of the cases, respectively. No adverse events were reported during the study period. A transition from the anesthesia to the ICU service for transporting ICU patients to the OR did not change turnover times but resulted in more on-time starts and high compliance with preoperative checklist documentation.