The influence of level of care on admission to neonatal care for babies of low-risk nullipara.
To analyze the risk of admission to neonatal care for newborns of low-risk nullipara and its variation with level of care of the maternity unit. The sample included infants born to low-risk nulliparas from the PREMODA study of 138 French maternity units (n=3652). Medical records of children admitted to neonatal care were reviewed to determine the reasons for admission and the severity of morbidity. The risk factors associated with admission to neonatal care, including maternal, infant and delivery unit characteristics, were studied by univariable analysis, followed by a multivariable analysis using a multilevel logistic model. The newborns of 3.5% (n=129) of the nulliparous mothers at low risk were admitted to neonatal care at birth. The two principal reasons were infections (57%) and respiratory diseases (19%). Babies born in level 2 maternity units were twice as likely to be admitted to neonatal care as those born in level 1 units (ORa=2.0 [1.1-3.7]) and those born in level 3 units, 1.5 times more often, although this was not statistically significant (ORa=1.5 [0.8-2.8]). Babies admitted to neonatal care after delivery in level 1 had more severe morbidity (n=4, 26.7%) than those admitted from level 2 (n=4, 5.7%) or level 3 (n=3, 6.8%) facilities (p=0.046). In low-risk populations, the level of care could have an influence on the decision to admit babies to neonatal care at birth. These findings add to the on-going debate about the optimal organization of care for women at low obstetrical risk.


Plasmodium vivax-associated acute respiratory distress syndrome after extended travel in Afghanistan.
A 21-year-old soldier developed anorexia, vomiting, diarrhea and fever 10 days after returning to the United States from an 8-month deployment in Afghanistan. His symptoms persisted over the next 5 days until he presented in respiratory failure with a partial pressure oxygen: concentration of inspired oxygen (PaO(2):FiO(2)) ratio of 63, requiring urgent intubation and ventilator support. Chest roentgenogram revealed diffuse bilateral alveolar opacities consistent with acute respiratory distress syndrome. Although sputum and blood cultures did not reveal a causative agent, Giemsa-stained blood smears were positive for Plasmodium vivax alone, which was later confirmed by small subunit ribosomal RNA polymerase chain reaction amplification. After a tenuous course marked by splenic rupture and prolonged requirement for ventilator support, the patient ultimately recovered. Although generally considered benign, this and other recent reports of vivax malaria-associated lung injury emphasize the need for persistent pursuit of the diagnosis in febrile travelers returning from vivax endemic locations as well as aggressive monitoring for and management of life-threatening complications.


The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation.
The mechanism of Tat transactivation was studied by treating cell lines containing Tat-defective viruses with purified Tat protein. These cell lines constitutively produce very low levels of virus in the absence of Tat, as measured by p24 antigen levels. Virus production can be increased greater than 30,000-fold by adding exogenous Tat. Tat addition increases mRNA levels early in the viral life cycle, and Tat is required for Rev function to become evident. There is no evidence for a translational effect of Tat. Nuclear run-on experiments show that the increase in mRNA levels is due to an increased efficiency of elongation of nascent transcripts. These results suggest that Tat may be a gene-specific elongation factor.


Isolation and properties of the transcription complex of Escherichia coli RNA polymerase.
A procedure is described which permits complete separation of a transcription complex formed with template DNA, growing RNA chain and functioning RNA polymerase, from RNA polymerase molecules which have bound to DNA but not initiated RNA synthesis. The method is based on the marked stability of the transcription complex to dissociation by high concentrations of CsCl or CS2SO4 which enable banding the complex after equilibrium centrifugation. With use of the newly developed procedure, affinity of Escherichia coli RNA polymerase to T7 phage DNA was found to increase during initiation of RNA synthesis but then decrease concomitant with elongation of RNA chain presumably due to migration of the enzyme to DNA sites of weak affinity. Under the conditions of maximum affinity, the transcription complex contained one core polymerase for each T7 DNA if it was isolated by centrifugation in CsCl; in contrast, 2-6 enzyme molecules remained attached on the complex when the centrifugation was carried out in Cs2SO4. Thus, RNA polymerases bound to different sites of transcription initiation appear to be distinguished based on the affinity of interaction. Attempts are also described to isolate the transcription complex in vivo by Cs2SO4 centrifugation by Brij 58-deoxycholate lysate of lysozyme-treated Escherichia coli cells. The isolated complex contained approx. 50 polymerase molecules per Escherichia coli genome as well as other unidentified proteins.


Promyelocytic leukemia protein PML inhibits Nur77-mediated transcription through specific functional interactions.
The promyelocytic leukemia protein PML is a tumor and growth suppressor and plays an important role in a multiple pathways of apoptosis and regulation of cell cycle progression. Our previous studies and others also documented a role of PML in transcriptional regulation through its association with transcription coactivator CBP and transcription corepressor HDAC. Here, we showed that PML is a potent transcriptional repressor of Nur77, an orphan receptor and a member of the steroid receptor superfamily of proteins. We found that PML represses Nur77-mediated transactivation through a physical and functional interaction between the two proteins. PML interacts with Nur-77 in vitro in a GST-pull down assay and in vivo by coimmunoprecipitation assay. PML/Nur77 colocalized in vivo in a double immunofluorescent staining and confocal microscopic analysis. Our study further showed that the coiled-coil domain of PML interacts with the DNA-binding domain of Nur77 (amino acids 267-332). Electrophoretic mobility shift assay demonstrated that PML interferes with Nur77 DNA binding in a dose-dependent manner. This study indicates that PML interacts with the DNA-binding domain of Nur77 and represses transcription by preventing it from binding to the target promoter. This study supports a role of PML/Nur77 interaction in regulating cell growth and apoptosis.


Transient global amnesia after cerebral angiography. A case report.
We report on a case of transient global amnesia after cerebral angiography in which a nonionic contrast medium was used. The complication observed showed no evidence of any definite cause.


Oligomeric protein complexes of apolipoproteins stabilize the internal fluid environment of organism in redfins of the Tribolodon genus [Pisces; Cypriniformes, Cyprinidae].
One of the most important functions of plasma proteins in vertebrates is their participation in osmotic homeostasis in the organism. Modern concepts about plasma proteins and their capillary filtration are based on a model of large monomeric proteins that are able to penetrate the interstitial space. At the same time, it was revealed that a considerable amount of oligomeric complexes are present in the low-molecular-weight (LM) protein fraction in the extracellular fluids of fishes. The functions of these complexes are unknown. In the present study, we investigated the LM-fraction proteins in the plasma and interstitial fluid (IF) of redfins of the genus Tribolodon. This fish alternatively spends parts of its life cycle in saline and fresh waters. We identified the protein Wap65, serpins and apolipoproteins in this fraction. By combining the methods of 2D-E under native and denaturing conditions with MALDI, we demonstrated that only apolipoproteins formed complexes. We showed that serum apolipoproteins (АроА-I, Аро-14) were present in the form of homooligomeric complexes that were dissociated with the release of monomeric forms of proteins in the course of capillary filtration to IF. Dissociation of homooligomers is not directly correlated with the change in salinity but is correlated with seasonal dynamics. We found that there was a significant decrease in the total protein concentration in IF relative to plasma. Therefore, we suggested that dissociation of homooligomeric complexes from various apolipoproteins supports the isoosmoticity of extracellular fluids relative to capillary wall stabilization through a fluid medium in fish.


Evidence of Diagnostic and Treatment Delay in Seronegative Rheumatoid Arthritis: Missing the Window of Opportunity.
To compare the time from first joint swelling to fulfillment of the American College of Rheumatology/European League Against Rheumatism classification criteria between patients with seropositive and seronegative rheumatoid arthritis (RA) and to assess the impact of seronegative status on the time from first joint swelling to initiation of disease-modifying antirheumatic drug (DMARD) therapy and achievement of remission. Times from first provider-documented joint swelling to fulfillment of the 1987 and 2010 American College of Rheumatology/European League Against Rheumatism criteria and to the clinical diagnosis of RA were measured in a population-based cohort of adults with incident RA between January 1, 2009, and December 31, 2014. Disease characteristics and achievement of remission were compared between seropositive (rheumatoid factor positive and/or anti-citrullinated peptide antibody positive) and seronegative (rheumatoid factor negative/anti-citrullinated peptide antibody negative) patients. The median time from first joint swelling to fulfillment of the 1987 (48 [interquartile range (IQR), 0-300] days vs 2 [IQR, 0-45] days; P=.001) and 2010 (14 [IQR, 0-196] days vs 0 [IQR, 0-29] days; P=.004) classification criteria and the median time from first joint swelling to the clinical diagnosis of RA (187 [IQR, 13-503] days vs 11 [IQR, 0-76] days; P<.001) were significantly longer in seronegative patients than in seropositive patients. The median time from first joint swelling to first prescribed DMARD therapy was significantly longer in seronegative patients (40 [IQR, 5-199] days vs 14 [IQR, 0-73] days; P=.01). Patients with seronegative RA were less likely to achieve remission (28% vs 50% at 5 years after fulfillment of the 2010 criteria; P=.007), but there was no difference when the patient global score was removed from the remission definition. Patients with seronegative RA experienced a delay in diagnosis, according to both the 1987 and 2010 classification criteria, as well as a delay in the initiation of DMARD therapy. Patients with seronegative RA were also less likely to attain remission, suggesting that the window of opportunity for intervention may be more frequently missed in this group.


Benefits and adverse effects associated with yoga practice: A cross-sectional survey from India.
Benefits and adverse effects of yoga were reported in surveys from different countries. The present study aimed to (i) determine the benefits and adverse effects of yoga in yoga experienced persons in India and (ii) correlate these effects of yoga with factors related to the individual and their yoga practice. This convenience sampling in-person survey reports benefits and adverse effects of yoga in 3135 yoga experienced persons. The benefits of yoga were reported by 94.5 percent of the respondents. The three most common benefits were improvement in: (i) physical fitness, (ii) mental state and (iii) cognitive functions. An adverse effect of yoga was reported by 1.9 percent of the respondents. The three most common adverse effects reported were: (i) soreness and pain, (ii) muscle injuries and (iii) fatigue. The following factors showed a significant association (in all cases p < 0.05 Chi square test; Cramer's V > 0.10) with reported benefits of yoga: (i) experience of yoga in months, (ii) time spent practicing yoga in a week, (iii) number of yoga techniques practiced, and (iv) whether awareness was maintained during the yoga practice or not. Benefits of yoga practice to physical health were the most common, with soreness and pain the most common adverse effect of yoga. Yoga practice related factors influence the benefits of yoga.


Bidirectional regulation of stress responses by galanin in mice: involvement of galanin receptor subtype 1.
The neuropeptide galanin has been shown to play a role in psychiatric disorders as well as in other biological processes including regulation of pain threshold through interactions with three G-protein coupled receptors, galanin receptor subtypes 1-3 (GalR1-3). While most of the pharmacological studies on galanin in stress-related disorders have been done with rats, the continuous development of genetically engineered mice involving galanin or its receptor subtype(s) validates the importance of mouse pharmacological studies. The present study on mice examined the homeostatic, endocrinological and neuroanatomical effects of the galanin, injected intracerebroventricularly (i.c.v.), in regulation of stress responses after restraint stress. Furthermore, the roles of GalR1 on these effects were studied using GalR1 knockout (KO) mice. The core body temperature and the locomotor activity were monitored with radio telemetry devices. Galanin (i.c.v.) decreased locomotor activity and exerted a bidirectional effect on the restraint stress-induced hyperthermia; a high dose of galanin significantly attenuated the stress-induced hyperthermic response, while a low dose of galanin moderately enhanced this response. The bidirectional effect of galanin was correlated with changes in stress hormone levels (adrenocorticotropic hormone and corticosterone). To neuroanatomically localize the effects of galanin on stress response, cFos immunoreactivity was assessed in galanin receptor rich areas; paraventricular nucleus (PVN) of the hypothalamus and the locus coeruleus (LC), respectively. A high dose of galanin significantly induced cFos activity in the LC but not in the PVN. In GalR1KO mice, a high dose of galanin failed to induce any of the above effects, suggesting the pivotal role of GalR1 in decreased locomotor activity and stress-resistant effects caused by galanin i.c.v. injection studied here.


Year-long weight-loss classes could prevent more illnesses.
Offering year-long programmes of weight loss classes could prevent hundreds of additional cases of hypertension, diabetes and heart disease.


Determination of Magnetic Parameters of Maghemite (γ-Fe2O3) Core-Shell Nanoparticles from Nonlinear Magnetic Susceptibility Measurements.
Method of determining of magnetic moment and size from measurements of dependence of the nonlinear magnetic susceptibility upon magnetic field is proposed, substantiated and tested for superparamagnetic nanoparticles (SPNP) of the "magnetic core-polymer shell" type which are widely used in biomedical technologies. The model of the induction response of the SPNP ensemble on the combined action of the magnetic harmonic excitation field and permanent bias field is built, and the analysis of possible ways to determine the magnetic moment and size of the nanoparticles as well as the parameters of the distribution of these variables is performed. Experimental verification of the proposed method was implemented on samples of SPNP with maghemite core in dry form as well as in colloidal systems. The results have been compared with the data obtained by other methods. Advantages of the proposed method are analyzed and discussed, particularly in terms of its suitability for routine express testing of SPNP for biomedical technology.


Loteprednol etabonate gel 0.5% vs prednisolone acetate suspension 1% for the treatment of inflammation after cataract surgery in children.
To compare loteprednol etabonate (LE) gel 0.5% with prednisolone acetate suspension (PA) 1% for the treatment of inflammation after cataract surgery in children. Eleven sites in the United States. Randomized, double-masked, parallel-group, noninferiority study. Eligible patients were aged 11 years or younger and candidates for routine, uncomplicated cataract surgery. Patients were randomized to a 4-week postsurgical regimen with LE gel 0.5% or PA 1%, twice on the day of surgery, 4 times daily for 2 weeks, twice daily for 1 week, and once daily for 1 week. Assessments included anterior chamber (AC) cells/flare, anterior chamber inflammation (ACI), synechiae, precipitates on the intraocular lens/cornea, visual acuity, and intraocular pressure. The intent-to-treat population comprised 105 patients (LE gel, n = 53; PA 1%, n = 52) including 52 patients aged 3 years or younger. Patients achieved a similar mean ACI grade on postoperative day 14 (primary efficacy endpoint) whether treated with LE gel 0.5% or PA 1% (difference = 0.006, 2-sided 95% CI, -0.281 to 0.292). Similar ACI outcomes additionally were observed in patients aged 3 years or younger. LE gel 0.5% and PA 1% also appeared equally effective in resolving inflammation at all visits (days 7, 14, and 28 postsurgery), based on categorical distributions of ACI, AC cells, and AC flare scores/grades (P ≥ .06). Synechiae and corneal/IOL precipitates occurred infrequently with no significant differences between groups. No safety or tolerability concerns were identified, including no treatment-related IOP increases. LE gel 0.5% was safe and effective in treating pediatric postcataract surgical inflammation, with similar outcomes as PA 1%.


Chylothorax: a complication of subclavian vein catheterization and parenteral hyperalimentation.
A case is presented in which a unique combination of events occurred as a complication of subclavian vein catheterization. Extravasation of intravenous hyperalimentation solution occurred, resulting in mediastinitis and venous obstruction of the jugulosubclavian confluence bilaterally. Bilateral chylothorax resulted which was successfully managed by conservative means. The methods used and the rationale for their employment are discussed.


Skin injuries in forensic histopathology: a descriptive study.
Histopathology is commonly used in forensic medicine. Only few studies are available in the literature about the correlation between skin wounds histopathology and survival time or other medicolegal data. The aim of this study was to illustrate the usefulness of histopathological analysis of skin wounds in forensic daily practice and to evaluate its correlation with the clinical and police investigation data. In this single-center, retrospective, and descriptive study, we included 198 forensic pathology cases, from the files of the Legal Medicine and Biopathology Departments of the University Hospital of Nancy, with a total of 554 skin samples. Basing on the police investigations (n = 43), the median survival time between the main related trauma and death was 83 min. The histopathological analysis concluded to 2% of post-mortem lesions (absence of hemorrhage) and 55% of perimortem or undetermined lesions (hemorrhage without inflammation); 8% of the lesions had an estimated time interval between more than 10 min and several hours, 22% between several hours and several days, and 14% between several days and several weeks. Histopathological dating was statistically associated with wound location (p < 0.01), the type of injury, hypothermia, positive toxicology, histopathological hepatic lesions, and survival time (p < 0.001). In conclusion, the histopathological analysis of skin wounds allowed to propose a survival time in almost half of cases, with a significant correlation with the police investigation-based estimation of survival time, but also other parameters such as wound location or toxicology. It however lacks of accuracy, and further studies are needed to develop new markers, notably based on immunohistochemistry.


Insights into the mechanism of carbonate formation through reductive cleavage of carbon dioxide with low-valent uranium centers.
The low-valent U(III) complexes [((t-BuArO)3mes)U] and [((AdArO)3N)U] react with CO2 to form the bridging carbonate complexes [{((t-BuArO)3mes)U}2(mu-kappa2:kappa2-CO3)] and [{((AdArO)3N)U}2(mu-eta1:kappa2-CO3)]. Uranium(IV) bridging oxo complexes have been determined to be the intermediate in these transformations.


A comparative study on the use of bovine and murine monoclonal antibodies for passive immunization in cattle.
In the present experiments the efficacy of murine and bovine monoclonal antibodies for passive immunization in cattle was compared. The in vivo immunoneutralization of pregnant mare serum gonadotrophin (PMSG) by murine and bovine antibodies after repeated administration was chosen as a model for this study. Results indicate that repeated injections of murine monoclonal antibodies against PMSG (mMCA) alone did not, or only to a small extent, elicit an anti-mouse immune response. The simultaneous administration of mMCA and PMSG resulted in relatively high levels of anti-mouse antibodies after the second injection, leading to a decrease in neutralizing activity of mMCA. The results suggest that the neutralizing activity of mMCA is inhibited more by anti-idiotypic than by anti-isotypic antibodies against mMCA. In vivo, the bovine monoclonal antibody against PMSG (bMCA) only partially neutralizes PMSG. After repeated administration of bMCA, either alone or in combination with PMSG, no anti-bMCA antibodies could be detected in our assay system. In addition, no change in plasma levels of bMCA and PMSG compared with levels after the first injection was observed. Although it has to be confirmed by further experiments whether our findings can be generalized, the present results suggest that for repeated passive immunization in cattle homologous antibodies are to be preferred above heterologous antibodies.


Socio-ecological and pharmacy-level factors associated with buprenorphine stocking at pharmacies in New York City.
Research is lacking on community and pharmacy-level factors that are associated with stocking buprenorphine. To address these gaps, this study applied a socio-ecological framework to estimate the association between community- and pharmacy-level factors and buprenorphine stocking among a sample of pharmacies in New York City. A telephone survey recruitment strategy was used to administer surveys to 662 pharmacies on the New York City Naloxone Standing Order Pharmacy list in 2018. The survey assessed pharmacy-level factors of private spaces to consult with pharmacists, type of pharmacy (chain/independent), size of pharmacy, having buprenorphine in stock and being open on nights and weekends. Socio-ecological variables drawn from census tract and public health data consisted of racial and ethnic composition, rates of poverty, rates of people without insurance, and rates of overdose. Mixed effects logistic regression estimated odds ratios (OR) of carrying buprenorphine in stock after adjusting for socio-ecological and pharmacy-level factors. Fewer than half of the pharmacies reported having buprenorphine in stock (43.81% n = 290). Logistic regression analyses indicate that several pharmacy-level factors - the number of private spaces (aOR=1.67 95% CI=1.20, 2.32 p=.002), large size of the pharmacy (aOR=1.52 95% CI=1.04, 2.22, p=.032), having naloxone in stock (aOR=1.54, 95%CI=1.03, 2.32 p=.037), as well as neighborhood-level factors of higher rates of poverty (aOR=2.07 95%CI=1.07, 4.02 p<.001) and higher rates of uninsured residents were associated with carrying buprenorphine (aOR=0.23 95%CI=0.14,.38). Using a socio-ecological framework, this study identified inequities in pharmacy stocking of buprenorphine by neighborhood rates of health insurance. At the pharmacy level, increasing private spaces for consultation and encouraging co-stocking of naloxone with buprenorphine stocking may reduce inequalities in buprenorphine availability.


Sex, Bugs and Rock 'n' Roll: Insects in Music Videos.
The appearance of insects in music videos was examined. The most common taxa observed were Lepidoptera, then Hymenoptera, with Coleoptera, Araneae, Diptera, and Orthoptera essentially tied for third most represented. Insect music videos have increased in frequency over time, probably as an artifact of industry growth. Swarms and infestations were common in insect videos (appearing in 26%), as were chimeric insectoid humans (19%), and, to a lesser extent, giant insects (5%), but not all of these representations were used to induce horror. Some insect music videos have garnered awards, and many of the songs associated with them have been very successful. There were many animated insect sequences, but also images of specimens that were sufficiently detailed to allow identification of the species. The insect groups observed reflect both positive and negative values. There is some indication that insects are not viewed in such a negative light as they once were, providing hope for improving attitudes of humans toward insects.


Therapist-rated outcomes in a randomized clinical trial comparing cognitive behavioral therapy and psychodynamic therapy for major depression.
The efficacy of psychodynamic therapy (PDT) for depression is debated due to a paucity of high-quality studies. We compared short psychodynamic supportive psychotherapy (SPSP) to cognitive behavioral therapy (CBT) in a randomized clinical trial. We used therapist-rated outcomes to examine how the course of change during treatment could be best represented and to compare treatment efficacy, hypothesizing non-significant differences. Three hundred and forty-one adults meeting DSM-IV criteria for a depressive episode and with Hamilton Depression Rating Scale (HAM-D) scores ≥14 were randomized to 16 sessions of individual manualized CBT or SPSP. Severely depressed patients (HAM-D>24) received additional antidepressant medication. After each session, therapists rated the Clinical Global Impression Scale subscales 'Severity of Illness' (CGI-S) and 'Global Improvement' (CGI-I), and the DSM-IV Axis V Global Assessment of Functioning Scale (GAF). We fitted growth curves using mixed model analyses with intention-to-treat samples. CGI-S and GAF scores during treatment were best represented by a linear symptom decrease. CGI-I scores were best represented by an S-shaped curve with relative more improvement in the first and last phases than in the middle phase of treatment. No significant post-treatment treatment differences were found. A non-significant trend for a treatment effect on CGI-S scores vanished when controlling for therapist gender and profession. Therapists were not specifically trained for CGI and GAF assessments. These findings add to the evidence-base of PDT for depression. Therapist characteristics and differences between severity and improvement measures might influence ratings and need to be taken into account when using therapist-rated outcome measures.


Relationship between the chemical structure and anti-tumour activity of glucans prepared from Grifora umbellata.
Glucans from Grifora umbellata and their enzyme-treated fractions have been tested for antitumour activity against subcutaneously implanted Sarcoma 180 (solid type). The results indicate that the basic common unit of the glucans is of primary importance for the antitumour activity, which is also influenced by the type of sugar linkage, length of branch, branching frequency, molecular size, and molecular conformation.


Gap Junction Modulation of Low-Frequency Oscillations in the Cerebellar Granule Cell Layer.
Local field potential (LFP) oscillations in the granule cell layer (GCL) of the cerebellar cortex have been identified previously in the awake rat and monkey during immobility. These low-frequency oscillations are thought to be generated through local circuit interactions between Golgi cells and granule cells within the GCL. Golgi cells display rhythmic firing and pacemaking properties, and also are electrically coupled through gap junctions within the GCL. Here, we tested if gap junctions in the rat cerebellar cortex contribute to the generation of LFP oscillations in the GCL. We recorded LFP oscillations under urethane anesthesia, and examined the effects of local infusion of gap junction blockers on 5-15 Hz oscillations. Local infusion of the gap junction blockers carbenoxolone and mefloquine resulted in significant decreases in the power of oscillations over a 30-min period, but the power of oscillations was unchanged in control experiments following vehicle injections. In addition, infusion of gap junction blockers had no significant effect on multi-unit activity, suggesting that the attenuation of low-frequency oscillations was likely due to reductions in electrical coupling rather than a decreased excitability within the granule cell layer. Our results indicate that electrical coupling among the Golgi cell networks in the cerebellar cortex contributes to the local circuit mechanisms that promote the occurrence of GCL LFP slow oscillations in the anesthetized rat.


Promoting physical activity in Out-of-School-Time programs: we built the bridge--can we walk over it?
This commentary describes physical activity standards for Out-of-School Time programs and argues that their widespread adoption presents important opportunities for research on their implementation and impact.


Supplementation of polyphenol-rich grapes attenuates colitis, colitis-associated colon cancer, and disease-associated dysbiosis in mice, but fails to mitigate colitis in antibiotic-treated mice.
Polyphenols are known to interact with gut microbes that play key roles in maintaining gut health, but the role of gut microbiota modulation by polyphenols in mitigating colonic diseases is not fully established. We hypothesize that the interaction of polyphenols with the gut microbiota contributes to the attenuation of colitis and colitis-associated colon cancer (CAC). To test this hypothesis, we examined the effects of dietary supplementation of polyphenol-rich grape powder (GP) on azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced colitis, CAC, and the gut microbiota in mice (study 1), and further compared anti-colitis effects of GP in regular and antibiotic-treated mice (study 2). Compared to the control diet that has matched non-polyphenol contents, 10% GP, but not 3% GP, attenuated AOM-DSS-induced colitis and tumor multiplicity by 29% (P<.05). Ten percent GP increased gut bacterial evenness and counteracted CAC-induced decrease of bacterial evenness and changes in microbial composition. Remarkably, the estimated gut bacterial functional profiles of healthy mice and diseased mice fed 10% GP were similar, and both were significantly different from those of diseased mice fed the control diet. Furthermore, 10% GP increased the relative abundance of butyrate-producing bacteria in the Lachnospiraceae family and enhanced the concentrations of fecal butyrate. Additionally, 10% GP mitigated DSS-induced colitis in conventional mice, but not the antibiotic-treated, gut microbe-depleted mice. Collectively, our studies demonstrate that grape polyphenols alleviate colonic diseases and prevent disease-associated dysbiosis, and their interaction with the gut microbiota may play a causative role in the protection of gut health.


Extended-spectrum beta-lactamases: structure and kinetic mechanism.
Recent years have seen an explosion in the numbers of extented spectrum class A beta-lactamases (ESBLs). The steady-state kinetic parameters for hydrolysis of beta-lactams by ESBLs is discussed in the light of what is known about the structure of these mutant enzymes.


Cortical connectivity in fronto-temporal focal epilepsy from EEG analysis: A study via graph theory.
It is believed that effective connectivity and optimal network structure are essential for proper information processing in the brain. Indeed, functional abnormalities of the brain are found to be associated with pathological changes in connectivity and network structures. The aim of the present study was to explore the interictal network properties of EEG signals from temporal lobe structures in the context of fronto-temporal lobe epilepsy. To complete this aim, the graph characteristics of the EEG data of 17 patients suffering from focal epilepsy of the fronto-temporal type, recorded during interictal periods, were examined and compared in terms of the affected versus the unaffected hemispheres. EEG connectivity analysis was performed using eLORETA software in 15 fronto-temporal regions (Brodmann Areas BAs 8, 9, 10, 11, 20, 21, 22, 37, 38, 41, 42, 44, 45, 46, 47) on both affected and unaffected hemispheres. The evaluation of the graph analysis parameters, such as 'global' (characteristic path length) and 'local' connectivity (clustering coefficient) showed a statistically significant interaction among side (affected and unaffected hemisphere) and Band (delta, theta, alpha, beta, gamma). Duncan post hoc testing showed an increase of the path length in the alpha band in the affected hemisphere with respect to the unaffected one, as evaluated by an inter-hemispheric marker. The affected hemisphere also showed higher values of local connectivity in the alpha band. In general, an increase of local and global graph theory parameters in the alpha band was found in the affected hemisphere. It was also demonstrated that these effects were more evident in drug-free patients than in those undergoing pharmacological therapy. The increased measures in the affected hemisphere of both functional local segregation and global integration could result from the combination of overlapping mechanisms, including reactive neuroplastic changes seeking to maintain constant integration and segregation properties. This reactive neuroplastic mechanism seeking to maintain constant integration and segregation properties seems to be more evident in the absence of antiepileptic treatment.


Quantitative X-ray phase contrast computed tomography with grating interferometry : Biomedical applications of quantitative X-ray grating-based phase contrast computed tomography.
The ability of biomedical imaging data to be of quantitative nature is getting increasingly important with the ongoing developments in data science. In contrast to conventional attenuation-based X-ray imaging, grating-based phase contrast computed tomography (GBPC-CT) is a phase contrast micro-CT imaging technique that can provide high soft tissue contrast at high spatial resolution. While there is a variety of different phase contrast imaging techniques, GBPC-CT can be applied with laboratory X-ray sources and enables quantitative determination of electron density and effective atomic number. In this review article, we present quantitative GBPC-CT with the focus on biomedical applications.


Aging-Related Microstructural Alterations Along the Length of the Cingulum Bundle.
The aim of this study was to investigate the aging-related structural changes of the cingulum, one of the major components of the limbic network, which has a critical role in emotion, attention, and memory. Thirty-five healthy young adults (22.3 ± 2.7 years) and 33 healthy older adults (69.5 ± 3.5 years) were recruited. Diffusion weighted imaging data were acquired with a b-value = 2000 sec/mm2 and 61 diffusion directions and 4 non-weighted images. The fiber directions in each voxel were based on the constrained spherical deconvolution model. The cingulum was segmented into three branches using deterministic tractography (subgenual, retrosplenial, and parahippocampal), using a region-of-interest-based approach. Atlas-based tractography was the method used to obtain the output tracts of each branch of the cingulum. Along-tract analysis was performed on each branch. We found a statistically significant change with aging in the left subgenual branch of the cingulum with a decrease in fractional anisotropy and axial diffusivity, as well as an increase in radial diffusivity. No statistically significant differences were found between young and older groups in the other two branches. This study adds to knowledge about how the cingulum changes structurally along its entire length during aging in a more detailed way, thanks to an advanced methodological approach.


High-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice.
Body mass has a positive effect on bone health. Whether mass derived from an obesity condition or excessive fat accumulation is beneficial to bone has not been established; neither have the mechanisms by which obesity affects bone metabolism. The aim of this study was to examine the effects of obesity on bone structure and osteoblastic expression of key markers involved in bone formation and resorption in a diet-induced obesity mouse model. Six-wk-old male C57BL/6 mice (n=21) were assigned to two groups and fed either a control (10 kcal% energy as fat) or high-fat diet (HFD, 45 kcal% energy as fat) for 14 weeks. Bone marrow stromal/osteoblastic cells (BMSC) were cultured. Osteoprogenitor activity [alkaline phosphatase (ALP) positive colonies] and mineralization (calcium nodule formation) were determined. Gene expression was measured using quantitative real-time PCR. Bone structure of proximal and midshaft tibia was evaluated by micro-computed tomography. Mice fed the HFD were 31% heavier (P<0.01) than those fed the control diet. There were more ALP positive colony forming units at d 14 and calcium nodules at d 28 of culture by BMSC from HFD mice than from control mice (P<0.01). Receptor activator of NF-kappaB ligand (RANKL) mRNA levels and the ratio of RANKL to osteoprotegerin expression in HFD animals was higher (P<0.01) than in control diet animals. Serum tartrate-resistant acid phosphatase levels were higher in HFD fed mice when compared to control diet fed mice (P<0.05). There were no significant differences in tibial fat-free weight, length, and cortical parameters of midshaft between the two groups. Compared with control mice, tibial trabecular bone volume was reduced, and trabecular separation was increased in HFD mice. Trabecular number was lower (P<0.05) and connectivity density tended to be less (P=0.07) in HFD mice than in control mice. In conclusion, our data indicate that obesity induced by a high-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice.


Expression of phosphatase of regenerating liver-3 in squamous cell carcinoma of the cervix.
To investigate the significance of PRL-3 expression in progression and metastasis of squamous cell carcinoma of the cervix (SCC). PRL-3 expression was detected by immunohistochemistry in 22 normal cervical epithelia, 30 moderate-severe dysplasia (CIN II-III) and 90 SCC cases. A total of 28 patients with SCC had lymph node metastasis, and PRL-3 expression of metastatic lymph node was detected. The association between PRL-3 expression and various clinical pathological variables in 90 patients with SCC was analyzed. Expression of PRL-3 in SCC was higher than that in normal and CINII-III, as well as higher in CINII-III than in normal (P<0.05 in all instances). PRL-3 expression was significantly different between different tumor sizes, lymph-vascular space invasion status and lymph node metastasis status (P<0.05 in all instances). PRL-3 expression in lymph node metastasis was significantly higher than that in primary SCC (P=0.049). In lymph node metastasis, the frequency of staining in cytoplasm predominantly was higher than that in matched primary cancers (P=0.001). PRL-3 may be involved in carcinogenesis of cervix and lymph node metastases of SCC and serves as an unfavorable prognostic factor in patients with SCC. PRL-3 localization in plasma may be related with cancer progress and metastasis.


Paraneoplastic pemphigus associated with post-transplant lymphoproliferative disorder after small bowel transplantation.
PNP is a malignancy-associated autoimmune mucocutaneous syndrome due to autoantibodies against plakins, desmogleins, and other components of the epidermis and basement membrane of epithelial tissues. PNP-causing malignancies comprise mainly lymphoproliferative and hematologic neoplasms. PNP is extremely rare, especially in children. Here, we present the first case of a child who developed PNP on a PTLD after small bowel transplantation because of a severe genetic protein-losing enteropathy. The patient in this case report had a severe stomatitis, striate palmoplantar keratoderma, and lichenoid skin lesions. In addition, she had marked esophageal involvement. She had lung pathology due to recurrent pulmonary infections and ventilator injury. Although we found no evidence of BO, she died from severe pneumonia and respiratory failure at the age of 12 years. It is exceptional that, despite effective treatment of the PTLD, the girl survived 5 years after her diagnosis of PNP. We hypothesize that the girl survived relatively long after the PNP diagnosis due to strong T-cell suppressive treatments for her small bowel transplantation.


TAM-derived extracellular vesicles containing microRNA-29a-3p explain the deterioration of ovarian cancer.
Extracellular vesicles (EVs) secreted from tumor-associated macrophages (TAMs) are known to generate an immune-suppressive environment conducive to the development of ovarian cancer (OC). We tried to elucidate the role of TAM-derived exosomal microRNA (miR)-29a-3p in OC. miR-29a-3p, forkhead box protein O3 (FOXO3), and programmed death ligand-1 (PD-L1) expression was determined and their interactions evaluated. EVs were isolated, followed by determination of the uptake of EVs by OC cells, after which the proliferation and immune escape facilities of the OC cells were determined. OC xenograft models were constructed with EVs in correspondence with in vivo experiments. Overexpressed miR-29a-3p was detected in OC, and miR-29a-3p promoted OC cell proliferation and immune escape. EVs derived from TAMs enhanced the proliferation of OC cells. miR-29a-3p was enriched in TAM-EVs, and TAM-EVs delivered miR-29a-3p into OC cells. Downregulated FOXO3 was identified in OC, whereas miR-29a-3p targeted FOXO3 to suppress glycogen synthase kinase 3β (GSK3β) activity via the serine/threonine protein kinase (AKT)/GSK3β pathway. Inhibition of TAM-derived exosomal miR-29a-3p decreased PD-L1 to inhibit OC progression through the FOXO3-AKT/GSK3β pathway in vitro and in vivo. Taken together, the current studies highlight the FOXO3-AKT/GSK3β pathway and the mechanism by which TAM-derived exosomal miR-29a-3p enhances the expression of PD-L1 to facilitate OC cell proliferation and immune escape.


The effect of epidermal growth factor on epithelial healing after penetrating keratoplasty in human eyes.
Two groups of patients were assigned randomly to treatment with epidermal growth factor or placebo after penetrating keratoplasty. In all cases, the epithelium was removed completely from the graft by scrubbing at the close of surgery. One group of patients received topically applied growth factor or placebo in a solution with preservative solution four times a day on the day of surgery and twice a day for two days thereafter. The second group of patients received one-half the concentration of growth factor or placebo in a solution without preservative eight times a day for four days beginning the day before surgery. Healing was assessed twice a day by color photography after instillation of 2% fluorescein; the percent area of the remaining epithelial defect was determined with a planimeter. No therapeutic benefit was demonstrated in the eyes treated with growth factor in either group of patients.


The impact of a three-tiered model of nursing redeployment during the COVID-19 pandemic: A cross-sectional study.
The COVID-19 pandemic resulted in extreme system pressures, requiring redeployment of nurses to intensive care units. We aimed to assess the impacts of a 3-tiered pandemic surge model on nurses working in intensive care units during the COVID-19 pandemic. In this cross-sectional study, 931 nurses (464 intensive care and 467 redeployed nurses) who worked within four adult units in Western Canada during pandemic surge(s) were invited via email to participate in a survey. The survey explored the impact of redeployment, rapid unit orientations, just-in-time training, and the 3-tiered model of nursing during pandemic surge. Burnout was measured utilizing the Copenhagen Burnout Inventory questionnaire. A total of 191 survey responses were retained (59 intensive care nurses and 132 redeployed). Survey results are reported by tier, with outcomes varying based on team leadership, intensive care unit, and redeployment nursing roles. Burnout in personal and workplace domains was present amongst all nursing tiers, while only team leadership roles experienced burnout in the patient domain. Overall, team leadership roles and permanent intensive care nurses experienced the highest rates of burnout. Redeployed nurses reported numerous aids to success including support from colleagues, prior experience, and educational supports. Skill-based orientation, ongoing education, optimized scheduling, role clarity, and mitigators of psychological impacts were identified by respondents as potential facilitators of redeployment and surge models. Nurses working within this tiered model experienced high degrees of burnout, with highest prevalence amongst team leads and intensive care nurses. Optimization of support for and interventions aimed at improving well-being are important considerations going forward. Targeted strategies are required to support education, role transition, and optimize competency and role clarity during nursing redeployment for overcapacity surge. Essential strategies to support redeployed nurses include individualized competency assessments pre-redeployment and prior to role transitions, pairing redeployed nurses with the same intensive care nurse consistently, and availability of a nurse educator or resource for additional just-in-time training supports. Contingency disaster strategies should also include interventions targeting staff wellness and prevention of burnout, as well as identify scenarios in which redeployment may increase risks of psychological harm. Debriefing and peer-to-peer support models may increase the efficiency of psychological support for nurses, though additional research is required. Lastly, given enaction of tiered models of nursing care is largely a novel occurrence in the intensive care unit, leadership training is required to support frontline nurses taking on supervisory roles within these team models.


Influence of Familial Risk for Depression on Cortico-Limbic Connectivity During Implicit Emotional Processing.
Imbalances in cortico-limbic activity and functional connectivity (FC) supposedly underlie biased emotional processing and present putative intermediate phenotypes (IPs) for major depressive disorder (MDD). To prove the validity of these IPs, we assessed them in familial risk. In 70 healthy first-degree relatives of MDD patients and 70 controls, brain activity and seed-based amygdala FC were assessed during an implicit emotional processing task for fMRI containing angry and fearful faces. Using the generalized psychophysiological interaction approach, amygdala FC was assessed (a) across conditions to provide comparable data to previous studies and (b) compared between conditions to elucidate its implications for emotional processing. Associations of amygdala FC with self-reported negative affect were explored post hoc. Groups did not differ in brain activation. In relatives, amygdala FC across conditions was decreased with superior and medial frontal gyrus (SFG, MFG) and increased with subgenual and perigenual anterior cingulate cortex (sgACC, pgACC). NA was inversely correlated with amygdala FC with MFG, pgACC and their interaction in relatives. Relatives showed aberrant condition-dependent modulations of amygdala FC with visual cortex, thalamus and orbitofrontal cortex. Our results do not support imbalanced cortico-limbic activity as IP for MDD. Diminished amygdala-dorsomedial prefrontal FC in relatives might indicate insufficient regulatory capacity, which appears to be compensated by ventromedial prefrontal regions. Differential task-dependent modulations of amygdala FC are discussed as a stronger involvement of automatic instead of voluntary emotional processing pathways. Reliability and etiological implications of these results should be investigated in future studies including longitudinal designs and patient-risk-control comparisons.


CLINICAL AND LABORATORY JUSTIFICATION FOR USE OF POLYVALENT BACTERIOPHAGE IN TECHNIQUE OF DELAYED PRESCRIBING OF ANTIBIOTICS IN PATIENTS WITH ARS.
The aim: Of research was to evaluate the effectiveness of bacteriophage in patients with acute rhinosinusitis in respect of technique of delayed prescribing of antibiotics. Materials and methods: There were examined 155 patients who were given irrigation therapy with isotonic solution of sea water 4 times a day and mometasone furoate of 100 mg twice a day for 10 days. The patients of intervention group (n - 80) were additionally prescribed the polyvalent bacteriophage endonasally, in drops of 2-10 ml 3 times a day. Results: The patients in the control group were observed the decrease in intensity of rhinorrhea, nasal congestion and post-nasal drip on the third day of supervision (p < 0.05), the reduction in bacterial load with Staphylococcus aureus, S. pneumoniae, Haemophilus influenza and M. Catarrhalis (р <0,005), the increase of IgА and sIgA levels (p<0,005) and the reduction in prescription of antibacterial medications by 20%. Conclusions: Adding of polyvalent bacteriophage contributes to reducing the use of antibiotics and is recommended in the framework of the strategy of delayed prescribing of antibiotics.


Cryo-EM structures of two human B cell receptor isotypes.
The B cell receptor (BCR) complex plays a critical role in B cell development and immune responses. The assembly mechanisms underlying the BCR complex remain unknown. We determined the cryo-electron microscopy (cryo-EM) structures of human IgG-BCR and IgM-BCR, which consist of membrane-bound immunoglobulin molecules (mIg) and Igα/β subunits at a 1:1 stoichiometry. Assembly of both BCR complexes involves their extracellular domains, membrane-proximal connection peptides, and transmembrane (TM) helices. The TM helices of mIgG and mIgM share a conserved set of hydrophobic and polar interactions with Igα/β TM helices. By contrast, the IgG-Cγ3 and IgM-Cμ4 domains interact with extracellular Ig-like domains of Igα/β through head-to-tail and side-by-side modes, respectively. This work reveals the structural basis for BCR assembly and provides insights into BCR triggering.


Sensitized Photooxidation of Ortho-Prenyl Phenol: Biomimetic Dihydrobenzofuran Synthesis and Total 1O2 Quenching.
The sensitized photooxidation of ortho-prenyl phenol is described with evidence that solvent aproticity favors the formation of a dihydrobenzofuran [2-(prop-1-en-2-yl)-2,3-dihydrobenzofuran], a moiety commonly found in natural products. Benzene solvent increased the total quenching rate constant (kT ) of singlet oxygen with prenyl phenol by ~10-fold compared to methanol. A mechanism is proposed with preferential addition of singlet oxygen to prenyl site due to hydrogen bonding with the phenol OH group, which causes a divergence away from the singlet oxygen 'ene' reaction toward the dihydrobenzofuran as the major product. The reaction is a mixed photooxidized system since an epoxide arises by a type I sensitized photooxidation.


Effect of low-intensity pulsed ultrasound on injured temporomandibular joints with or without articular disc removal in a rabbit model.
Dynamic stimulation can induce bone and cartilage growth. The purpose of this study was to examine the effect of low-intensity pulsed ultrasound (LIPUS) on injured temporomandibular joints (TMJs) in a rabbit model. Twenty-four female Japanese white rabbits (age: 12-16 weeks, weight: 2.0-2.5 kg) were equally divided into 4 groups. In two groups, discectomy was performed with (the LD group) and without (the D group) subsequent LIPUS treatment. In the other groups, a sham operation was performed with (the LC group) and without (the C group) subsequent LIPUS treatment. Two animals in each group were sacrificed at each time point (2, 4, and 8 weeks postoperatively). Mandibular measurements were made using three-dimensional computed tomography. We performed histological and immunohistochemical examination of the articular disc, and the cartilage layer and bone at the 30- and 60-degree sites in each condyle. There were no statistically significant differences among the groups in terms of thickness of the disc or the fibrous articular zone, or the number of BMP-2 positive cells. In terms of mandibular length, there were differences among the groups after 4 (P = 0.0498) and 8 weeks (P = 0.0260). Specifically, there was a difference between the LC group and the C group after 4 weeks (P = 0.014) and 8 weeks (P = 0.029). This study suggests that LIPUS has little effect on cartilage after TMJ injury. It may promote bone growth in a normal TMJ, although discectomy seems to reduce this effect.


Electrophoretic patterns of hemoglobin and oxygen binding properties of blood of anostomidae fishes from Parana-Pardo-Grande hydrographic basin (São Paulo State, Brazil).
The electrophoretic patterns of hemoglobin (Hb) and the functional properties of blood of seven migratory fish species, in two different kinds of habitat during both the rainy and dry seasons, were studied. All species showed multiple hemoglobins and very similar electrophoretic patterns except for Schizodon nasutus, which showed two cathodal components. The functional properties of blood reflect those electrophoretic patterns, since all species showed very little or no Bohr effect during each situation studied. Data on Leporinus obtusidens blood (during the rainy season), from both lotic and lentic environments, showed a normal Bohr effect (phi = -0.073). Similarly, Schizodon nasutus and Leporinus friderici from a lotic environment during the dry season were compared and showed a reverse Bohr effect (phi = 0.042). In the other 14 situations, only Leporinus elongatus from a lentic environment during the rainy season showed a statistically significant difference in log P50 values from the other fishes.


Start-up, steady state performance and kinetic evaluation of a thermophilic integrated anaerobic-aerobic bioreactor (IAAB).
Thermophilic treatment of palm oil mill effluent (POME) was studied in a novel integrated anaerobic-aerobic bioreactor (IAAB). The IAAB was subjected to a program of steady-state operation over a range of organic loading rate (OLR)s, up to 30 g COD/L day in order to evaluate its treatment capacity. The thermophilic IAAB achieved high chemical oxygen demand (COD), biochemical oxygen demand (BOD) and total suspended solids (TSS) removal efficiencies of more than 99% for OLR up to 18.5 g COD/L day. High methane yield of 0.32 LCH(4) (STP)/g COD(removed) with compliance of the final treated effluent to the discharge limit were achieved. This is higher than that of the mesophilic system due to the higher maximum specific growth rate (μ(max)) of the thermophilic microorganisms. Besides, coupling the model of Grau second order model (anaerobic system) with the model of Monod (aerobic system) will completely define the IAAB system.


ACLS interventional skills: Are we as good as we should be?
This study evaluated the competence of Advanced Cardiac Life Support certified personnel at hands-on ACLS skills. The observational, cross-sectional study assessed participants' subjective confidence and objective skills using the ACLS mega code examination. Testing was performed with a Laerdal manikin and standardized code carts. Participants had a 12% (6% to 22%, 95% CI) pass rate for the stable tachyarrhythmia scenario and a 57% (44% to 69%, 95% CI) pass rate for the unstable tachyarrhythmia scenario. The most significant skills missed were appropriate medications and postconversion maintenance in the stable scenario and appropriate energy selection and successful shock delivery for the unstable scenario. ACLS providers feel confident in their ACLS skills; however, actual performance demonstrated poor performance in the management of patients with stable and unstable tachyarrhythmias. The recommendation is to observe initial and recertification ACLS classes to investigate the standard to which these core skills are being taught and evaluated.


Progression of Physical Frailty and the Risk of All-Cause Mortality: Is There a Point of No Return?
To investigate the rate and patterns of accumulation of frailty manifestations in relationship to all-cause mortality and whether there is a point in the progression of frailty beyond which the process becomes irreversible and death becomes imminent (a.k.a. point of no return). Longitudinal observational study. Community or a non-nursing home residential care setting. Two thousand five hundred and fifty seven robust older adults identified at baseline in 2011 with follow-up for all-cause mortality between 2011 and 2018. Frailty was measured by the physical frailty phenotype. Cox models were used to study the relationships of the number of frailty criteria (0-5) at each point in time and its accumulation patterns with all-cause mortality. Markov state-transition models were used to study annual transitions between health states (i.e., frailty, recovery, and death) after becoming frail among those with frailty onset (n = 373). There was a nonlinear association between greater number of frailty criteria and increasing risk of mortality, with a notable risk acceleration after having accumulated all five criteria (hazard ratio (HR) = 32.6 vs none, 95% confidence interval (CI) = 15.7-67.5). In addition, the risk of one-year mortality tripled, and the likelihood of recovery (i.e., reverting to be robust or pre-frail) halved among those with five frailty criteria compared to those with three or four criteria. A 50% increase in mortality risk was also associated with frailty onset without (vs with) a prior history of pre-frailty (HR = 1.51, 95% CI = 1.20-1.90). Both the number and rate of accumulation of frailty criteria were associated with mortality risk. Although there was insufficient evidence to declare a point of no return, having all five-frailty criteria signals the beginning of a transition toward a point of no return. Ongoing monitoring of frailty progression could aid clinical and personal decision-making regarding timing of intervention and eventual transition from curative to palliative care.


The N-terminus of the Montano virus nucleocapsid protein possesses broadly cross-reactive conformation-dependent epitopes conserved in rodent-borne hantaviruses.
The hantavirus nucleocapsid (N) protein is an important immunogen that stimulates a strong and cross-reactive immune response in humans and rodents. A large proportion of the response to N protein has been found to target its N-terminus. However, the exact nature of this bias towards the N-terminus is not yet fully understood. We characterized six monoclonal antibodies (mAbs) against the N protein of Montano virus (MTNV), a Mexican hantavirus. Five of these mAbs recognized eight American hantaviruses and six European and Asian hantaviruses, but not the Soricomorpha-borne Thottapalayam hantavirus. The N protein-reactive binding regions of the five mAbs were mapped to discontinuous epitopes within the N-terminal 13-51 amino acid residues, while a single serotype-specific mAb was mapped to residues 1-25 and 49-75. Our findings suggest that discontinuous epitopes at the N-terminus are conserved, at least in rodent-borne hantaviruses, and that they contribute considerably to N protein cross-reactivity.


Effect of the co-administration of HCG and GnRH agonist (dual trigger) versus standard HCG trigger on morphokinetic embryo parameters.
Does dual trigger (the co-administration of triptorelin 0.2 mg and recombinant human chorionic gonadotrophin (HCG) [Decapeptyl 0.2 mg + Ovitrelle 250 µg]) versus standard recombinant HCG (Ovitrelle 250 µg) affect embryo quality and morphokinetic parameters? Morphokinetic parameters and embryo quality of embryos derived from the first gonadotrophin-releasing hormone (GnRH) antagonist IVF/intracytoplasmic sperm injection (ICSI) cycles triggered by dual trigger or standard HCG trigger in women ≤42 years. Outcome measures included time to pronucleus fading (tPNf), cleavage timings (t2-t8), synchrony of the second cycle (s2), duration of the second cycle (cc2) and known implantation data (KID) scoring for embryo quality. Multivariate linear and logistic regression analyses were performed for confounding factors. A total of 4859 embryos were analysed: 1803 embryos from 267 cycles in the dual trigger group and 3056 embryos from 463 cycles in the HCG trigger group. The groups were similar in patient and treatment characteristics apart from a higher maternal body mass index and lower maturation rate in the dual trigger group. Time to second polar body extrusion was shorter in the dual trigger group. Cleavage timings from zygote to an 8-cell embryo did not differ between the two groups. There was a higher percentage of embryos with an optimal cc2 duration in the HCG group. In multivariate logistic regression models, the trigger type was not a significant factor for cell cycle division parameters. Overall, there was no significant difference in the morphokinetic parameters or quality of embryos evaluated using a time-lapse monitoring system between embryos derived following dual trigger compared with HCG.


Relationships between genomic, cell cycle, and mutagenic responses of TK6 cells exposed to DNA damaging chemicals.
Genotoxic stress causes a variety of cellular and molecular responses in mammalian cells, including cell cycle arrest, DNA repair, and apoptosis. These responses result from the interplay between the genotoxic events themselves, and the biological context in which they occur. To better understand this interplay, we investigated cytotoxicty, mutagenesis, cell cycle profile, and global gene expression in the human TK6 lymphoblastoid cell line exposed to six genotoxicants. The six compounds have broad structural diversity and cause genotoxic stress by many different mechanisms, including covalent modification (methyl methanesulfonate, mitomycin C), reactive oxygen species (hydrogen peroxide, bleomycin), and topoisomerase II inhibition (etoposide and doxorubicin). Cell cycle analysis was performed 4 and 20 h following a 4 h chemical exposure. Cells exposed to all compounds experienced S-phase arrest at the 8h time point, but by 24 h had markedly different cell cycle responses. Cells exposed to compounds that cause covalent modification had a strong G2/M arrest at 24 h. These cells also had a robust (>25-fold) increase in mutant frequency, and had a moderate but sustained p53 response at 4, 8, and 24h, detectable as approximately 2-5-fold increases in transcript levels for p21WAF1/CIP1, GADD45alpha, BTG2, and cyclin G1. In contrast, cells exposed to the reactive oxygen compounds had little or no G2/M arrest at 24 h and no increase in mutant frequency. In addition, these compounds caused a strong but transient induction of the p53 pathway, detectable as 15-25-fold increases in p21WAF1/CIP1 transcription at 4 h that decreased dramatically by 8h and was near control levels at 24 h. Thus, the mutagenic effect of compounds was consistent with G2/M arrest and sustained kinetics of p53 pathway activation. Global gene expression data were also consistent with the mutagenesis data. Activation of genes associated with cell cycle arrest, the p53 and TNF-related pathways, and chemokines and chemokine receptors, were particularly evident for the reactive oxygen compounds. In contrast, the most mutagenic compounds caused fewer and less robust changes in global gene expression. There was therefore an inverse relationship between global gene expression and mutagenic potency.


Monitoring Ischemic Changes in Retinal Vasculitis With Optical Coherence Tomography Angiography.
This article illustrates the ability of optical coherence tomography angiography (OCTA) to aid in the diagnostic workup and management of occlusive retinal vasculitis over time. A case presentation is discussed. In this case, OCTA helped define the extent and evolution of superficial and deep retinal capillary plexus occlusion and reperfusion over the treatment course. OCTA detects blood flow and maps retinal vasculature at the capillary level without the use of intravenous dye. Serial image acquisition can reveal patterns of ischemia and reperfusion in retinal vascular conditions as they evolve and respond to therapy, providing more granular information regarding the status of the retinal microvasculature that may guide treatment.


A randomised trial of bilateral erector spinae plane block vs. no block for thoracolumbar decompressive spinal surgery.
Major spinal surgery causes significant postoperative pain. We tested the efficacy and safety of bilateral erector spinae block on quality of recovery and pain after thoracolumbar decompression. We randomly allocated 60 adults to standard care or erector spinae block. Erector spinae block improved the mean (SD) quality of recovery-15 score at 24 postoperative hours, from 119 (20) to 132 (14), an increase (95%CI) of 13 (4-22), p = 0.0044. Median (IQR [range]) comprehensive complication index was 1 (0-3 [0-5]) in the control group vs. 1 (0-1 [0-4]) after block, p = 0.4. Erector spinae block reduced mean (SD) area under the curve pain during the first 24 postoperative hours: at rest, from 78 (49) to 50 (39), p = 0.018; and on sitting, from 125 (51) to 91 (50), p = 0.009. The cumulative mean (SD) oxycodone consumption to 24 h was 27 (18) mg in the control group and 19 (26) mg after block, p = 0.20. In conclusion, erector spinae block improved recovery and reduced pain for 24 h after thoracolumbar decompression surgery.


Prevalence of asymptomatic coronary artery disease in ischemic stroke patients: the PRECORIS study.
Coronary artery disease (CAD) is a significant cause of morbidity and mortality in stroke patients. Some patients with asymptomatic CAD might benefit from specific prevention, but the prevalence of asymptomatic CAD is not well known. We assessed the prevalence of >or=50% asymptomatic CAD in patients with ischemic stroke or transient ischemic attack and whether the prevalence is related to traditional vascular risk factors and cervicocephalic atherosclerosis. From January 2006 to February 2009, consecutive patients between 45 and 75 years of age with nondisabling, noncardioembolic ischemic stroke or transient ischemic attack and no prior history of CAD were enrolled in the study. All patients had a 64-section computed tomography coronary angiography and a detailed cervicocephalic arterial workup. Risk factors were assessed individually and through the Framingham Risk Score. Among 300 patients included in the study, 274 had computed tomography coronary angiography. The prevalence of >or=50% asymptomatic CAD was 18% (95% confidence interval [CI], 14 to 23; n=50). Asymptomatic CAD was independently associated with traditional risk factors assessed individually and through the Framingham Risk Score (odds ratio [OR], 2.6; 95% CI, 1.0 to 7.6 for a 10-year risk of coronary heart disease of 10% to 19%; and OR, 7.3; 95% CI, 2.8 to 19.1 for a 10 year-risk of coronary heart disease >or=20%), the presence of at least 1 >or=50% cervicocephalic artery stenosis (OR, 4.0; 95% CI, 1.4 to 11.2), excessive alcohol consumption (OR, 3.1; 95% CI 1.3 to 7.3), and ankle brachial index <0.9 (OR, 2.2; 95% CI, 0.9 to 5.2). The prevalence of >or=50% asymptomatic CAD was also related to the extent of cervicocephalic atherosclerosis. About one fifth of patients with nondisabling, noncardioembolic ischemic stroke or transient ischemic attack have >or=50% asymptomatic CAD. In addition to vascular risk factors, the presence of >or=50% cervicocephalic artery stenosis is strongly related to >or=50% asymptomatic CAD.


Congenital anomalies of the kidney and urinary tract (CAKUT) associated with Hirschsprung's disease: a systematic review.
Congenital anomalies of the kidney and urinary tract (CAKUT), a term introduced in the late 1990 s accounts for 30-50 % of cases of end-stage renal disease in children. The association of urogenital anomalies and Hirschsprung's disease (HSCR) based on the common genetic background of enteric nervous system and human urinary tract development has been well described in the literature. However, the reported prevalence of HSCR associated with CAKUT seems to be underestimated. The aim of this systematic review was to determine the prevalence of this association and show its relationship to other syndromes. A systematic literature search was conducted for relevant articles published between 1955 and 2014. Two online databases were searched for the terms "Hirschsprung's disease", "congenital anomalies of the kidney and urinary tract", "urogenital anomalies" and "urological anomalies". All published studies containing adequate clinical data were included. Resulting publications were reviewed for epidemiology, genetic testing, operative treatment and morbidity. Reference lists were screened for additional cases. A total of 32 articles reported 222 cases of HSCR associated with either CAKUT, "urological" or "urogenital" anomalies from 1955 to 2014. Gender was reported in a total of 68 cases, with 54 (79 %) males and 14 (21 %) females. Extent of aganglionosis was reported in 67 cases and included classical rectosigmoid disease in 38, long-segment aganglionosis in 12, total colonic aganglionosis in 12 and total intestinal aganglionosis in 5 patients. 18 articles reported 204 cases of either CAKUT, "urological" or "urogenital" anomalies in a case series of 5.693 HSCR patients, resulting in an overall prevalence of 3.6 % of this association. Within this collective of 18 studies only seven were, regardless of the date of publication compatible with CAKUT criteria introduced and published in the late 1990 s. These seven studies reported a total of 72 patients with associated CAKUT among 757 HSCR patients resulting in a prevalence of 9.5 %. After introduction of the CAKUT acronym, only three studies specifically investigated the association of HSCR and CAKUT stating a prevalence of 14.3 % resulting in an almost fivefold increase compared to the reported prevalence of HSCR and associated urological and urogenital anomalies. The remaining 14 publications reported 18 single cases of HSCR patients with associated CAKUT phenotypes. Of these 18 cases, 11 (61 %) cases were associated with other syndromes or syndromatic features or reported chromosomal anomalies. This review confirms that the recognition of CAKUT in HSCR patients has been underestimated in the past. The results suggest that when confronted with HSCR in a patient, a thorough urological investigation may be indicated. The high prevalence of associated syndromes in HSCR with CAKUT may further suggest a syndromic association.


The presence of contaminations in sewage sludge - The current situation.
Sewage sludge/biosolids are by-wastes of municipal and industrial wastewater treatment. As sources of nutrients (C, N, P) they are widely used in intensive farming where large supplementation of organic matter to maintain fertility and enhance crop yields is needed. However, according to the report of European Commission published in 2010, only 39% of produced sewage sludge is recycled into agriculture in the European Union. This situation occurs mainly due to the fact, that the sewage sludge may contain a dangerous volume of different contaminants. For over decades, a great deal of attention has been focused on total concentration of few heavy metals and pathogenic bacteria Salmonella and Escherichia coli. The Sewage Sludge Directive (86/278/EEC) regulates the allowable limits of Zn, Cu, Ni, Pb, Cd, Cr and Hg and pathogens and allows for recovery of sludge on land under defined sanitary and environmentally sound conditions. In this paper, a review on quality of sewage sludge based on the publications after 2010 has been presented. Nowadays there are several papers focusing on new serious threats to human health and ecosystem occurring in sewage sludge - both chemicals (such as toxic trace elements - Se, Ag, Ti; nanoparticles; polyaromatic hydrocarbons; polychlorinated biphenyl; perfluorinated surfactants, polycyclic musks, siloxanes, pesticides, phenols, sweeteners, personal care products, pharmaceuticals, benzotriazoles) and biological traits (Legionella, Yersinia, Escherichia coli O157:H7).


Prognostic Factors Associated with Clinical and Economic Outcomes of Appendectomies in Children: A Multilevel Analysis in a National Retrospective Cohort Study.
Acute appendicitis is the most common acute surgical abdominal pathology in children, and it has a large impact on morbidity and the costs incurred by health care systems. In low- and median-income countries, national information on the clinical and economic outcomes associated with this surgery does not exist. This study aimed to identify and describe the clinical and economic outcomes for children undergoing appendectomy in Colombia's contributory system and to determine the prognostic factors associated with these outcomes. A retrospective cohort study was conducted using administrative data from patients under 18 years of age who underwent an appendectomy between July 1, 2013, and September 30, 2015, in Colombia's contributory health system. Thirty-day mortality rates, intensive care unit (ICU) admission rates, length of stay (LOS), readmission rates and median costs were estimated for the entire country by geographic region and insurer. The prognostic factors associated with these outcomes were identified using generalized multilevel mixed models. A total of 21,674 children were included. The 30-day postoperative mortality rate was 0.06% [95% CI 0.02-0.9], the ICU admission rate was 8.00% [95% CI 7.63-8.36], the mean LOS was 2.48 days (SD 5.24), the readmission rate was 1.5% [95% CI 1.33-1.66] and the median cost for Colombia was 394 USD [p25-p75: 256-555]. The prognostic factors that were associated with the 30-day ICU admission rate, LOS and readmission rate were the insurer, geographic region, age, occurrence of an appendectomy with peritoneal drainage, and certain comorbidities, such as cancer and neurological, respiratory and gastrointestinal illnesses. The prognostic factors associated with costs were those previously mentioned as well as the occurrence of a laparoscopic appendectomy. In Colombia's contributory health system, large differences in clinical outcomes and the costs incurred by the system exist, and these differences are associated with the geographic region, the insurer, and some of the clinical characteristics of the children undergoing appendectomy.


Effects of insulin in relatives of patients with type 1 diabetes mellitus.
It is unknown whether insulin therapy can delay or prevent diabetes in nondiabetic relatives of patients with diabetes. In a randomized, controlled, nonblinded clinical trial, we screened 84,228 first-degree and second-degree relatives of patients with diabetes for islet-cell antibodies; 3152 tested positive; 2103 of the 3152 underwent genetic, immunologic, and metabolic staging to quantify their risk; 372 of the 2103 had a projected five-year risk of more than 50 percent; 339 of the 372 (median age, 11.2 years) were randomly assigned to undergo either close observation or an intervention that consisted of low-dose subcutaneous ultralente insulin, administered twice daily for a total dose of 0.25 unit per kilogram of body weight per day, plus annual four-day continuous intravenous infusions of insulin. Oral glucose-tolerance tests were performed every six months. Median follow-up was 3.7 years. The primary end point was a diagnosis of diabetes. Diabetes was diagnosed in 69 subjects in the intervention group and 70 subjects in the observation group. The annualized rate of progression to diabetes was 15.1 percent in the intervention group and 14.6 percent in the observation group. The cumulative incidence of diabetes was similar in the two groups (relative risk in the intervention group as compared with the observation group, 0.96). Most subjects in whom diabetes developed were asymptomatic. Progression to diabetes occurred at a faster rate among subjects with abnormal base-line glucose tolerance (22 percent per year) than among those with normal base-line glucose tolerance (10 percent per year, P<0.001). There were no episodes of severe hypoglycemia. The incidence of chemical hypoglycemia, assessed without ascertainment bias, was similar in the two groups. In persons at high risk for diabetes, insulin at the dosage used in this study does not delay or prevent type 1 diabetes.


Diaryl Ether Containing N-Hydroxycarbamates from Nitroso Cycloadducts.
Regioselective ring opening of N-hydroxycarbamate-derived nitroso cycloadducts by a copper-catalyzed allylic alkylation reaction was achieved and applied to the synthesis of a set of substituted diaryl ether containing compounds. Use of protected 3-hydroxybenzyl bromide allowed access to a late stage phenol intermediate after protection of the N-hydroxy moiety that was generated from the ring opening reaction. The diaryl ethers were then formed by copper-mediated coupling with arylboronic acids. After selective deprotection, alumina-promoted transcarbamoylation provided the target compounds. Previous results indicate the compounds may possess significant inhibitory potency against the proinflammatory enzyme 5-lipoxygenase.


Antibodies against myoid thymic cells and striated muscle, and monoclonal gammapathy in myasthenia gravis.
The serum of a patient with myasthenia gravis contained a particularly high titer of antistriated muscle antibodies, as well as a monoclonal IgM Kappa immunoglobulin. The antibody activity was only associated with IgG fractions and not with the monoclonal IgM, when these immunoglobulins were separated by chromatography. The association of these two immunological disorders is discussed.


[Social support in the rehabilitation of mastectomized women: the role of the sexual partner].
This study identified the types of social support offered by the sexual partners of women with breast cancer and their perceptions about this support. Nine partners of women in this condition participated in the study. Data was collected through interviews and submitted to content analysis. Partners perceived themselves as important elements of social support to their wives, offering affection, stimulus to self-care and help with household chores. Difficulties faced in offering social support involved sexual relations, communication channels, the feeling of impotence and insecurity to deal with the implications of the diagnosis and to reorganize household chores.


Study on Flame Retardancy Behavior of Epoxy Resin with Phosphaphenanthrene Triazine Compound and Organic Zinc Complexes Based on Phosphonitrile.
A novel flame retardant phosphorus-containing organozinc complex (Zn-PDH) was prepared using zinc and iron as the metal center and 4-aminopyridine, with low steric hindrance, as the organic ligand, then using phosphazene to modify the organometallic complex (Zn-4APD). The flame retardant properties and mechanism of Zn-PDH/Tris-(3-DOPO-1-propyl)-triazinetrione (TAD) in epoxy resin (EP) were investigated. Flame inhibition behavior was studied by the vertical combustion test (UL94), while limiting oxygen index (LOI) measurement and flame retardant properties were studied by the cone calorimeter test (CONE). The flame retardant modes of action were explored by using the thermogravimetry-Fourier transform infrared (TG-FTIR) test, X-ray photoelectron spectrometer (XPS), and Raman spectroscopy (LRS). When TAD and Zn-PDH were added to the epoxy resin in the ratio of 3:1, the system achieved a balance between the gas-phase and condense-phase actions of the flame retardant effects, and the 3%TAD/1%Zn-PDH/EP composite system achieved not only good flame inhibition but also obtained good smoke and heat suppression performance, showing a comprehensive flame retardant performance. The gas phase and Zn-PDH mostly promoted charring with a barrier and protective effect in the condensed phase. As for the mechanism, TAD released the phosphorus-containing radicals and phenoxy radicals during decomposition and mainly exerted a gas-phase quenching effect. While in the condense phase, Zn-PDH promoted the decomposition of the polymer matrix to produce more aromatic structures and rapidly formed a complete and dense carbon layer rich in P-O-C crosslinked structures at high temperatures. Meanwhile, more N entered the gas phase in the form of inert gas, which diluted the concentration of the combustible fuel and helped to inhibit the combustion reaction.


A Systematic Review and Meta-Analysis of Stature Growth Complications in β-thalassemia Major Patients.
Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients' anemia and lifespan, but it may lead to iron overload in parenchymal tissue organs and endocrine glands that cause their dysfunctions as the iron regulatory system can't excrete excess iron from the bloodstream. To evaluate the prevalence of iron-related complications (short stature, growth retardation, and growth hormone deficiency) in β-thalassemia major (βTM) patients. We performed an electronic search in PubMed, Scopus, and Web of Sciences to evaluate the prevalence of growth hormone impairment in β-thalassemia major (βTM) patients worldwide. Qualities of eligible studies were assessed by the Joanna Briggs Institute checklist for the prevalence study. We used Comprehensive Meta-Analysis (Version 2) to calculate the event rate with 95% CIs, using a random-effects model for all analyses. Seventy-four studies were included from five continents between 1978 and 2019; 70.27% (Asia), 16.21% (Europe), 6.75% (Africa), 2.70% (America), 1.35% (Oceania), and 2.70% (Multicenter). The overall mean age of the participants was about 14 years. The pooled prevalence of short stature (ST) was 48.9% (95% CI 35.3-62.6) and in male was higher than female (61.9%, 95% CI 53.4-69.7 vs. 50.9%, CI 41.8-59.9). The pooled prevalence of growth retardation (GR) was 41.1% and in male was higher than in female (51.6%, 95% CI 17.8-84 vs. 33.1%, CI 9.4-70.2). The pooled prevalence of growth hormone deficiency (GHD) was 26.6% (95% CI 16-40.8). Our study revealed that near half of thalassemia patients suffer from growth impairments. However, regular evaluation of serum ferritin levels, close monitoring in a proper institute, suitable and acceptable treatment methods besides regular chelation therapy could significantly reduce the patients' complications.


Increased plasma homocysteine concentrations accelerate cardiac allograft vasculopathy.
A toxic and pro-oxidative effect of homocysteine on the coronary endothelium may accelerate cardiac allograft vascular disease (CAVD). In this study, we evaluated the influence of hyperhomocysteinemia on the course of CAVD. We investigated plasma homocysteine (tHCY) concentrations in 183 consecutive heart transplant recipients (158 men and 25 women, mean aged 53.1 +/- 10.0 years, at 6.7 +/- 3.2 years after transplantation) to evaluate the course of CAVD. We used serial coronary angiography to assess coronary status and graded the severity of CAVD based on the extent of luminal obstruction in the main coronary arteries (graded as 1-4). We defined progression as increased focal stenosis of >/=30% or as detection of a new coronary lesion after a mean observation period of 2.8 +/- 1.0 years. A multivariate analysis (backward logistic regression) was performed that included potential risk factors for CAVD. We excluded patients undergoing dialysis. Initially, tHCY concentrations were increased in the entire cohort (mean, 18.6 +/- 7.6 mumol/liter) and ranged from 6.6 to 46.9 mumol/liter. A total of 105 patients (57.0%) had CAVD at first angiography, and progression was detected in 52 transplant recipients (28.0%). Patients with progressive CAVD had significantly greater tHCY concentrations (21.6 +/- 6.2 mumol/liter) at baseline investigation compared with patients who had stable courses (17.4 +/- 7.7 mumol/liter; p < 0.001). These results were independent of parameters such as sex, age, dyslipoproteinemia, cyclosporine blood concentrations, and indication for transplantation. Progression of CAVD is strongly associated with increased tHCY concentrations. The intervals between routine surveillance angiography should be shortened in patients with hyperhomocysteinemia, and routine medical treatment to decrease homocysteine concentrations should be considered.


Dietary sources and levels of selenium supplements affect growth performance, carcass yield, meat quality and tissue selenium deposition in broilers.
This study examined the effects of sources and levels of selenium (Se) on performance, carcass parts yield, meat quality and tissue Se concentration in broilers. A total of 960 one-day-old male broilers were divided into 8 treatments in a 4 × 2 factorial arrangement. Chicks were penned in groups of 20 with 6 pens per group. Selenium sources were sodium selenite (SS), Se enriched yeast (SY), DL-selenomethionine (SM) and nano-selenium (NS) and dietary supplemental Se levels were 0.1 and 0.3 mg/kg diet. The average daily gain (ADG), average daily feed intake (ADFI), feed:gain ratio, mortality, and carcass parts yield were not affected by dietary treatments. The level of 0.3 mg/kg Se decreased lightness and increased yellowness of the breast and thighs (P < 0.001). Nano-selenium improved yellowness, redness and meat quality (P < 0.05). The interactive effects of sources and the levels of Se affected Se retention (P < 0.001). Inorganic Se showed poor retention compared to other sources of Se; and NS showed equal retention with the organic sources. With consideration to meat quality responses, NS had a more significant positive effect compared to SS as an inorganic source of Se. Overall, NS and organic sources of Se resulted in better meat quality compared with the inorganic source. Moreover, the highest Se retention percentage was achieved by supplementation of NS followed by organic sources at 0.1 mg/kg compared to SS.


Saline amnioinfusion for relief of repetitive variable decelerations: a prospective randomized study.
A prospective randomized study was undertaken in order to further investigate the effect of intrauterine saline amnioinfusion for the relief of repetitive variable decelerations in the first stage of labor. Intrauterine saline amnioinfusion corrects the oligohydramnios that makes the cord more vulnerable to compression during uterine contractions. Included in this study were 96 patients who had repetitive variable decelerations not relieved either by changes in position or by oxygen. Randomization resulted in 49 patients in the infusion group and 47 patients in the noninfusion group. Relief of variable decelerations was 51% in the infusion group, as compared to 4.2% in the noninfusion group. Relief of variable decelerations was more dramatic in the nulliparous infusion group (66.7%) than in the noninfusion group (0%). In the nulliparous patients there was a significant decrease in the rate of cesarean sections for fetal distress, being 14.8% in the infusion group as compared to 47.6% in the noninfusion group. This study clearly showed that saline amnioinfusion is a logical, simple, safe, and effective therapy for the relief of repetitive variable decelerations in the first stage of labor and can lower the incidence of cesarean sections for fetal distress in nulliparous patients. Furthermore, amnioinfusion was much superior to changes in position in treating repetitive variable decelerations.


Two Doses of BNT162b2 mRNA Vaccine in Patients after Hematopoietic Stem Cell Transplantation: Humoral Response and Serological Conversion Predictors.
Vaccination against SARS-CoV-2 is currently the best tool in the fight against the COVID-19 pandemic. However, there are limited data on its efficacy and safety after hematopoietic stem cell transplantation (HCT). We present the results of a prospective analysis of the humoral response to two doses of BNT162b2 mRNA vaccine in 93 adult patients, including 29 after autologous HCT (autoHCT) and 64 after allogeneic HCT (alloHCT). Positive anti-SARS-CoV-2 antibodies were detected before vaccination in 25% of patients despite a negative medical history of COVID-19. Seroconversion after vaccination was achieved in 89% of patients after alloHCT and in 96% after autoHCT, without grade 3/4 adverse events. Post-vaccination anti-SARS-CoV-2 antibody level correlated with the time from transplant and absolute B-cell count at the vaccination. In univariate analysis restricted to the alloHCT group, short time since transplantation, low B-cell count, low intensity conditioning, GvHD, and immunosuppressive treatment at the vaccination were associated with lack of seroconversion. In the multivariate model, the only negative predictor of seroconversion remained treatment with calcineurin inhibitor (CNI). In conclusion, the BNT162b2 mRNA vaccine is highly immunogenic in patients after HCT, but treatment with CNI at the time of vaccination has a strong negative impact on the humoral response.


Clinical implications of conflicting variant interpretations in the cancer genetics clinic.
The aim of this study was to describe the clinical impact of commercial laboratories issuing conflicting classifications of genetic variants. Results from 2000 patients undergoing a multigene hereditary cancer panel by a single laboratory were analyzed. Clinically significant discrepancies between the laboratory-provided test reports and other major commercial laboratories were identified, including differences between pathogenic/likely pathogenic and variant of uncertain significance (VUS) classifications, via review of ClinVar archives. For patients carrying a VUS, clinical documentation was assessed for evidence of provider awareness of the conflict. Fifty of 975 (5.1%) patients with non-negative results carried a variant with a clinically significant conflict, 19 with a pathogenic/likely pathogenic variant reported in APC or MUTYH, and 31 with a VUS reported in CDKN2A, CHEK2, MLH1, MSH2, MUTYH, RAD51C, or TP53. Only 10 of 28 (36%) patients with a VUS with a clinically significant conflict had a documented discussion by a provider about the conflict. Discrepant counseling strategies were used for different patients with the same variant. Among patients with a CDKN2A variant or a monoallelic MUTYH variant, providers were significantly more likely to make recommendations based on the laboratory-reported classification. Our findings highlight the frequency of variant interpretation discrepancies and importance of clinician awareness. Guidance is needed on managing patients with discrepant variants to support accurate risk assessment.


Impact of soluble tumor necrosis factor-related apoptosis-inducing ligand released by engineered adipose mesenchymal stromal cells on white blood cells.
The proapoptotic protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is physiologically expressed by immune cells and performs regulatory functions in infections, autoimmune diseases and cancer, where it acts as a tumor suppressor. Adipose-derived mesenchymal stromal cells (AD-MSCs) also may play immunomodulatory roles in both primary and acquired immune responses. We have previously demonstrated the efficacy of an anticancer gene therapy based on AD-MSC engineered to secrete a soluble TRAIL variant (sTRAIL) against pancreatic cancer. However, the impact of AD-MSC sTRAIL on leukocyte subsets has been not yet considered also to predict a possible immunotoxicity profile in the clinical translation of this cell-based anticancer strategy. Monocytes, polymorphonuclear cells and T lymphocytes were freshly isolated from the peripheral blood of healthy donors. Immunophenotype and functional (DR4 and DR5) and decoy (DcR1 and DcR2) TRAIL receptors were tested by flow cytometry. The viability of white blood cells treated with sTRAIL released by gene-modified AD-MSC or co-cultured with AD-MSC sTRAIL was then evaluated by both metabolic assays and flow cytometry. In addition, cytokine profile in co-cultures was analyzed by multiplex enzyme-linked immunosorbent assay. Monocytes and polymorphonuclear cells showed high positivity for DR5 and DcR2, respectively, whereas T cells revealed negligible expression of all TRAIL receptors. Irrespective of TRAIL receptors' presence on the cell membrane, white blood cells were refractory to the proapoptotic effect displayed by sTRAIL secreted by gene-modified AD-MSC, and direct cell-to-cell contact with AD-MSC sTRAIL had negligible impact on T-cell and monocyte viability. Cytokine crosstalk involving interleukin 10, tumor necrosis factor alpha, and interferon gamma secreted by T lymphocytes and vascular endothelial growth factor A and interleukin 6 released by AD-MSC was highlighted in T-cell and AD-MSC sTRAIL co-cultures. In summary, this study demonstrates the immunological safety and thus the clinical feasibility of an anticancer approach based on AD-MSC expressing the proapoptotic molecule sTRAIL.


Surgical Care in Liberia and Implications for Capacity Building.
Situational needs of health care facilities inform the optimal allocation of resources and quality improvement efforts. This study examines surgical care delivery metrics at a tertiary care institution in Liberia. We retrospectively reviewed operative and ward logbooks from January 1 to December 31, 2012. Data parameters included patients' age, diagnosis, procedure, mortality, and perioperative provider information. In 2012, 1,036 operations were performed. The breakdown of adult surgical cases reveals 452 (45.1%) general surgery operations, 192 (18.5%) orthopedic operations, and 180 (17.4%) ophthalmic operations. Other significant case volume included urologic 53 (5.1%), ENT 36 (3.5%), neurosurgical 31 (3.0%), vascular 24 (2.3%), and plastic 14 (1.4%) operations. Pediatric patients accounted for 24.5% (243) of surgical cases, and 9% of pediatric surgical cases were for hydrocephalus. General, spinal, and total intravenous anesthesia was provided by non-physician personnel, except when surgeons provided their own anesthesia. Ward logs documented 7.4% mortality among all patients admitted to the surgical ward, most of which occurred after exploratory laparotomy (44%), in burn (14%) patients, and in patients with head/neck emergencies (12%). This operative log review can be used to identify surgical practice patterns, needs, and deficits in order to inform the growth of surgical capacity at Liberia's only tertiary medical institution. Using this data to identify critical areas of high-yield operations (e.g., for pediatric hydrocephalus), or excessively high mortality rates (e.g., in burn care), can focus the direction of limited resources toward areas of need. While the heavy reliance on non-consultant surgeons reflects human capacity shortages and a pressing need for postgraduate training programs, identifying the breadth of surgical expertise demonstrated in these operative logs reveals the proficiencies required of surgeons to provide comprehensive surgical care in this setting.


Racial differences in renal sodium excretion: relationship to hypertension.
Black Americans are more susceptible to hypertension and to renal disease than white Americans. Both normotensive and hypertensive blacks are more apt to have salt-sensitive blood pressure responses to the challenge of a salt load than whites. Moreover, salt sensitivity of blood pressure in both normotensive and hypertensive subjects is associated with a decreased excretory capacity for sodium, implicating the kidney in this phenomenon. Salt sensitivity of blood pressure also is associated with increasing age and, in normotensive subjects, may predict the subsequent development of hypertension. Radical differences in a variety of humoral as well as hemodynamic responses to physical and mental stressors have been identified. The relationships between these observations and renal sodium handling require further investigation.


Notes on the genus Conocephalus Thunberg, 1815 (Orthoptera: Tettigoniidae: Conocephalinae) in Southwest China with description of one new species.
This paper reports eight species of the genus Conocephalus from Southwest China, including one new species, Conocephalus (Anisoptera) gracilicercus sp. nov., and provides the characteristic and habitus photographs.


Evaluation of a seven day course of oxytetracycline in women with chlamydial cervicitis.
In an urban clinic for sexually-transmitted diseases, 270 women with cervical swabs culture positive for Chlamydia trachomatis were treated with 250 mg oxytetracycline orally four times daily for 7 days. Chlamydial infection was found again in 17 of 220 (7.3%) women examined one month after treatment, and in 12 of 113 (9.7%) women reexamined three months after treatment. Even in cases where reinfection seemed unlikely, only 177 of 198 (89%) were cured. Most post-treatment infections were not clinically apparent, and laboratory follow-up was essential for evaluation of chemotherapy.