Stratum corneum chymotryptic enzyme: a proteinase which may be generally present in the stratum corneum and with a possible involvement in desquamation.
A chymotrypsin-like proteinase that may be involved in the desquamation process in plantar stratum corneum has recently been partially characterized. The aim of the present study was to elucidate whether a similar proteinase is also present in non-palmo-plantar stratum corneum. Stratum corneum was obtained by tape stripping of volar forearm skin after the skin surface had been painted with colourless nail varnish. The adherent tissue was released from the tape strips by acetone treatment, then extracted with diethyl ether and dried. Extracts of this acetone-ether powder were analyzed with respect to proteolytic activity by means of electrophoresis under non-reducing conditions in polyacrylamide gels containing sodium dodecyl sulphate and casein. The extracts were found to contain one major chymotrypsin-like proteinase with an apparent molecular weight of around 25 kDa, and several minor proteinases with trypsin-like activity. The 25 kDa proteinase was active at pH 5.5-8, and could be inhibited by aprotinin, chymostatin and zinc ion, but not by leupeptin. No difference could be found between the 25 kDa enzyme in forearm stratum corneum and the recently described chymotrypsin-like enzyme in dissociated plantar stratum corneum cells as regards electrophoretic mobility, pH dependency, and inhibitor profile. The fact that the enzyme could degrade casein at pH 5.5 and that it appears to be present in stratum corneum in general suggests that it may play a role in the desquamation process under in vivo conditions. The tentative name "stratum corneum chymotryptic enzyme" is proposed for this newly discovered proteinase.


Nutritional Assessment in Preterm Infants: A Practical Approach in the NICU.
A practical approach for nutritional assessment in preterm infants under intensive care, based on anthropometric measurements and commonly used biochemical markers, is suggested. The choice of anthropometric charts depends on the purpose: Fenton 2013 charts to assess intrauterine growth, an online growth calculator to monitor intra-hospital weight gain, and Intergrowth-21st standards to monitor growth after discharge. Body weight, though largely used, does not inform on body compartment sizes. Mid-upper arm circumference estimates body adiposity and is easy to measure. Body length reflects skeletal growth and fat-free mass, provided it is accurately measured. Head circumference indicates brain growth. Skinfolds estimate reasonably body fat. Weight-to-length ratio, body mass index, and ponderal index can assess body proportionality at birth. These and other derived indices, such as the mid-upper arm circumference to head circumference ratio, could be proxies of body composition but need validation. Low blood urea nitrogen may indicate insufficient protein intake. Prealbumin and retinol binding protein are good markers of current protein status, but they may be affected by non-nutritional factors. The combination of a high serum alkaline phosphatase level and a low serum phosphate level is the best biochemical marker for the early detection of metabolic bone disease.


Identification of the soybean hull allergens involved in sensitization to soybean dust in a rural population from Argentina and N-terminal sequence of a major 50 KD allergen.
Sensitization to soybean hull (SH) allergens occurs in subjects from Argentina, a soybean producer country. However, the causative allergens have not been identified. The purposes of this study are to: (i) identify the SH allergens using sera of 29 subjects with asthma and/or allergic rhinitis from Argentina exposed to soybean dust who have a positive (weal with SH/weal with histamine > or = 0.5) skin prick test to SH; and (ii) determine the N-terminal amino acid sequence of a major 50 K SH allergen that sensitizes this population. All sera were assayed for specific IgE (RIA), IgG4 (ELISA), and IgE and IgG4-Western blots. A sera pool from 10 healthy subjects was a negative control. N-terminal amino acid sequencing was performed by the Edman degradation method. Positive specific IgE only was found in 12/29 (41.4%), IgG4 in 3/29 (10.3%), and both IgE and IgG4 in 14/29 (48.3%) sera. IgE-Western blot demonstrates: (i) an allergen, MW 50 K (51.7% binding); (ii) one or two distinct allergens, MW < 20.2 K (72.4% binding), depending on the sera; and (iii) 1-5 additional IgE binding proteins, MW > 20.2 to < 46.9 K (41.4% binding), depending on the sera. IgG4-Western blot demonstrates: (i) a band, MW 70K (31% binding); (ii) a band, MW 50 K (17.2% binding); (iii) one or two additional bands, MW < 20.2 K (51.7% binding), depending on the sera; and (iv) a band, MW > 20.2 to < 28.5 K (20.7% binding). The 50 K allergen N-terminal amino acid sequence of the first 17 amino acids indicates a significant homology with chlorophyll A-B binding protein precursors from tomato, spinach, and petunia. Specific IgE and IgG4 to SH are common in sera from allergic individuals living in rural areas in Argentina. SH contain an IgE binding protein, MW about 50 K, not previously described. Sensitization to this allergen is common in subjects who are repeatedly exposed to soybean dust inhalation.


Supramolecular hydrogels co-loaded with camptothecin and doxorubicin for sustainedly synergistic tumor therapy.
The co-delivery of multiple drugs has become the primary strategy in cancer therapy in recent years, because this technique could promote synergistic actions, reduce side effects and deter the development of drug resistance. To achieve a controlled and sustained release of the loaded drugs, a supramolecular hydrogel based on the host-guest interactions between a hyperbranched polyglycerol derivative and α-cyclodextrin was prepared and used to co-load camptothecin and doxorubicin for sustainedly synergistic tumor therapy. The gelation kinetics, hydrogel strength and supramolecular structure of the obtained hydrogel were studied by dynamic and steady rheometry under various concentrations of α-CD. The sustained dual drug release from the supramolecular hydrogel in vitro, and their synergistic effect in vitro and in vivo were also explored. Moreover, the supramolecular hydrogel showed receivable blood compatibility and non-cytotoxicity by in vitro and in vivo assays. Therefore, this supramolecular hydrogel could potentially be applied in sustainedly synergistic tumor therapy.


Construction of a derivative of Tn917 containing an outward-directed promoter and its use in Bacillus subtilis.
Engineered variants of the transposon Tn917 have been widely used to obtain insertion mutations and transcriptional fusions in Bacillus subtilis and other Gram-positive bacteria. We have developed a novel Tn917-based methodology useful for isolation and characterization of mutants resulting from gene over-expression. A Tn917 variant was constructed which contains a strong out-facing promoter near one end, able to promote transcription of genes in the vicinity of its insertion target. This transposon, designated Tn917PF1, was tested in model conditions. Three Tn917PF1 mutants of B. subtilis, with phenotypes presumed to result from gene over-expression, were analysed. Their phenotypes were shown to be due to transcription from the transposon promoter. In one mutant the promoter activated a deg gene, probably degQ. The other two contained different insertions decryptifying a B. subtilis gene encoding beta-galactosidase.


Carbon and hydrogen isotope analysis of parathion for characterizing its natural attenuation by hydrolysis at a contaminated site.
The applicability of compound-specific isotope analysis (CSIA) for assessing in situ hydrolysis of parathion was investigated in a contaminated aquifer at a former pesticide wastes landfill site. Stable isotope analysis of parathion extracted from groundwater taken from different monitoring wells revealed a maximum enrichment in carbon isotope ratio of +4.9‰ compared to the source of parathion, providing evidence that in situ hydrolysis took place. Calculations based on the Rayleigh-equation approach indicated that the natural attenuation of parathion was up to 8.6% by hydrolysis under neutral and acidic conditions. In degradation experiments with aerobic and anaerobic parathion-degrading microbes, no carbon and hydrogen isotope fractionation of parathion were observed. For the first time, CSIA has been applied for the exclusive assessment of the hydrolysis of phosphorothioate-containing organophosphorus pesticides at a contaminated field site.


How ATP-Competitive Inhibitors Allosterically Modulate Tyrosine Kinases That Contain a Src-like Regulatory Architecture.
Small molecule kinase inhibitors that stabilize distinct ATP binding site conformations can differentially modulate the global conformation of Src-family kinases (SFKs). However, it is unclear which specific ATP binding site contacts are responsible for modulating the global conformation of SFKs and whether these inhibitor-mediated allosteric effects generalize to other tyrosine kinases. Here, we describe the development of chemical probes that allow us to deconvolute which features in the ATP binding site are responsible for the allosteric modulation of the global conformation of Src. We find that the ability of an inhibitor to modulate the global conformation of Src's regulatory domain-catalytic domain module relies mainly on the influence it has on the conformation of a structural element called helix αC. Furthermore, by developing a set of orthogonal probes that target a drug-sensitized Src variant, we show that stabilizing Src's helix αC in an active conformation is sufficient to promote a Src-mediated, phosphotransferase-independent alteration in cell morphology. Finally, we report that ATP-competitive, conformation-selective inhibitors can influence the global conformation of tyrosine kinases beyond the SFKs, suggesting that the allosteric networks we observe in Src are conserved in kinases that have a similar regulatory architecture. Our study highlights that an ATP-competitive inhibitor's interactions with helix αC can have a major influence on the global conformation of some tyrosine kinases.


[The content of some prostanoids and status of the functional activity in the brain stem of adolescents with vegetovascular dysfunction of the hypotensive type].
A correlation analysis was performed between parameters associated with the bioelectrical activity of truncus cerebri and indices for blood level of prostanoids. Our assumption is that in adolescents suffering from hypotensive type vegetovascular dysfunction, brain truncal structures participate in regulation of hemodynamics in a relatively autonomous fashion. Regulation of vascular tone in essentially healthy juveniles and in those presenting with hypotensive type vegetovascular dysfunction has different mechanisms related to redistribution of priorities of effects of those groups of prostanoids having been studied. Autonomic regulation of hemodynamics through prostaglandins does not prevent them from exerting their influence on blood supply of the truncal structures, which fact might be a manifestation of the mechanism of closure of the feedback in the chain of regulation of arterial pressure in both healthy and sick juveniles.


Essential role for TLR9 in prime but not prime-boost plasmid DNA vaccination to activate dendritic cells and protect from lethal viral infection.
One of the requirements for efficient vaccination against infection is to achieve the best combination of an adequate adjuvant with the antigenic information to deliver. Although plasmid DNA is a promising tool bearing the unique potential to activate humoral and cellular immunity, an actual challenge is to increase plasmid immunogenicity in human vaccination protocols in which efficacy has proven rather limited. Previous work showed that the bacterial DNA backbone of the plasmid has potent adjuvant properties because it contains CpG motifs that are particular activating nucleotidic sequences. Among TLRs, which are key sensors of microbial products, TLR9 can detect CpG motifs and confer activation of APCs, such as dendritic cells. However, whether the immunogenic properties of plasmid DNA involve TLR9 signaling has not been clearly established. In the current study, we demonstrate that TLR9 determines the effectiveness of vaccination against lethal lymphocytic choriomeningitis virus infection using plasmid DNA in a prime, but not prime-boost, vaccination regimen. Furthermore, we provide evidence that the presence of TLR9 in dendritic cells is necessary for effective and functional priming of virus-specific CD8+ T cells upon plasmid exposure in vitro or single-dose vaccination in vivo. Therefore, at single or low vaccine doses that are often used in human-vaccination protocols, CpG/TLR9 interactions participate in the immunogenicity of plasmid DNA. These results suggest that the TLR9 signaling pathway is involved in the efficacy of plasmid vaccination; therefore, it should remain a focus in the development or amelioration of vaccines to treat infections in humans.


Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals.
The global prevalence of prediabetes and type 2 diabetes (T2D) is increasing, and it is contributing to the susceptibility to diabetes and its related epidemic in offspring. Although the impacts of paternal impaired fasting blood glucose and glucose intolerance on the metabolism of offspring have been well established, the exact molecular and mechanistic basis that mediates these impacts remains largely unclear. Here we show that paternal prediabetes increases the susceptibility to diabetes in offspring through gametic epigenetic alterations. In our findings, paternal prediabetes led to glucose intolerance and insulin resistance in offspring. Relative to controls, offspring of prediabetic fathers exhibited altered gene expression patterns in the pancreatic islets, with down-regulation of several genes involved in glucose metabolism and insulin signaling pathways. Epigenomic profiling of offspring pancreatic islets revealed numerous changes in cytosine methylation depending on paternal prediabetes, including reproducible changes in methylation over several insulin signaling genes. Paternal prediabetes altered overall methylome patterns in sperm, with a large portion of differentially methylated genes overlapping with that of pancreatic islets in offspring. Our study uniquely revealed that prediabetes can be inherited transgenerationally through the mammalian germ line by an epigenetic mechanism.


Prevalence of bruxism awareness in Istanbul, Turkey.
The reported prevalence of symptoms related to bruxism varies in the general population because of different investigative methodologies, operational definitions, clinical criteria, and samples of population. Awareness of bruxism in the general population is 15% to 23%, however, this rate increases to 50% to 90% in clinical studies. The aim of this study was to investigate the prevalence of self-reported symptoms associated with bruxism in Istanbul, Turkey and to analyze the correlation between bruxism and factors such as age, gender, marital status, and occupation. Seven-hundred-ninety-five (795) adult subjects who resided in the city of Istanbul were interviewed by telephone about their age, gender, marital status, occupation, and description of the prevalence of bruxism awareness. The overall prevalence of clenching teeth was 45.7% and that of grinding teeth was 21.6%. Women responded positively to the questions more often than men. The data showed significant differences between males and females, regarding clenching teeth OR: 1.41 (95% CI: 1.05-1.87), difficulty opening OR: 2.64 (95% CI: 1.63-4.26), headache on awakening OR: 2.28 (95% CI: 1.58-3.27) joint sounds OR: 1.72 (95% CI: 1.24-2.38), sore on awakening OR: 2.97 (95% CI: 1.91-4.61), influence in daily activity (OR: 2.26 CI: 1.38-3.67). Tooth wear in the married group was higher than the single group. Age distribution showed significant differences related to grinding teeth, tooth wear and joint sounds. There were statistically significant differences between bruxism and job categories. As a conclusion, this study suggest an association between bruxism and stressful events such as marital status and job problems.


A comparison of intravenous midazolam and diazepam in management of status epilepticus in children.
To compare the efficacy of intravenous midazolam and diazepam in the management of status epilepticus seizures in children. The comparative study was conducted in the paediatric neurological emergency unit of The Children's Hospital and the Institute of Child Health, Multan, Pakistan, from December 15, 2018, to May 14, 2019, and comprised paediatric patients of status epilepticus seizures which were divided into Diazepam and Midazolam groups. Data was analysed using Graph-Pad Prism 5. Of the 164 patients, 82(50%) were in each of the two groups. There was no significant difference between the groups in terms of weight, age, residence area of patients and mean duration of seizures (p>0.05). Status epilepticus seizures subsided after intravenous midazolam administration in 77(93.90%) cases, while success in the diazepam group 64(78.05%) (p<0.05). Mean time taken by midazolam to halt seizures was significantly shorter than diazepam (p<0.05) and less cases of treatment failure were observed with intravenous midazolam (p<0.05). Somnolence was observed after diazepam administration in 47(57.3%) cases (p=0.0001). Intravenous midazolam was found to be superior in efficacy than intravenous diazepam in controlling status epilepticus seizures.


Decision theory for clinicians: uses and misuses of clinical tests.
There is no clear cutoff between normal and abnormal for most clinical measurements and laboratory tests. Since normal limits for many laboratory tests are established by statistical methods, it is imperative that the clinician base his interpretation of the laboratory results on the clinical situation. In addition, a clinician should realize that the prevalence of disease is affected by the setting in which he practices, and the manner in which he uses a clinical test can affect the predictive value of the test used.


A simulation based technique to estimate intracluster correlation for a binary variable.
Cluster randomized trials have become the design of choice for evaluating the effect of selected interventions on well-known health indicators such as neonatal mortality rate, episiotomy rate, and postpartum hemorrhage rate in a community setting. Determining the sample size of a cluster randomized trial requires a reliable estimate of cluster size and the intracluster correlation (ICC), because sample size can be substantially impacted by these parameters. During the design phase of a trial, the investigators may have estimates of the valid range of the health indicator which is the primary outcome variable. Furthermore, investigators often have an estimate of the average cluster size or range of cluster sizes that exist among the proposed samples they are planning to include in the trial. We present in this article a simulation technique to estimate the ICC value and its distribution for known binary outcome variables and a varying number of clusters and cluster sizes. We applied this technique to estimate ICC values and confidence intervals for a multi-country trial assessing the effect of neonatal resuscitation to decrease seven-day neonatal mortality, where communities within a country were clusters. This simulation technique can be used to estimate the possible ranges of the ICC values and to help to design an appropriately powered trial.


Reporting of Participant Demographics in Clinical Trials Published in General Radiology Journals.
The reporting of research participant demographics provides insights into study generalizability. Our study aimed to determine the frequency at which participant age, sex/gender, race/ethnicity, and socioeconomic status (SES) are reported and used for subgroup analyses in radiology randomized controlled trials (RCTs) and their secondary analyses; as well as the study characteristics associated with, and the classification systems used for demographics reporting. RCTs and their secondary analyses published in 8 leading radiology journals between 2013 and 2021 were included. Associations between study characteristics and demographic reporting were tested with the chi-square goodness of fit test for categorical variables, Wilcoxon-Mann-Whitney test for impact factor, and logistic regression for publication year. Among 432 included articles, 89.4% (386) reported age, 90.3% (390) sex/gender, 5.6% (24) race/ethnicity, and 3.0% (13) SES. Among articles that reported these demographics and were not specific to a subgroup, results were analyzed by age in 14.2% (55/386), sex/gender in 19.4% (66/340), race/ethnicity in 13.6% (3/22), and SES in 46.2% (6/13). Journal, impact factor, and last author continent were predictors of race/ethnicity and SES reporting. Funding was associated with race/ethnicity reporting. No study reported sex and gender separately, or documented transgender, nonbinary gender spectrum or intersex participants. A single category for race/ethnicity was used in 37.5% (9/24) of studies, consisting of either "White" or "Caucasian." The reporting of participant demographics in radiology trials is variable and not always representative of the population diversity. Editorial guidelines on the reporting and analysis of participant demographics could help standardize practices.


Functional organization of repeat addition processivity and DNA synthesis determinants in the human telomerase multimer.
Human telomerase is a multimer containing two human telomerase RNAs (hTRs) and most likely two human telomerase reverse transcriptases (hTERTs). Telomerase synthesizes multiple telomeric repeats using a unique repeat addition form of processivity. We investigated hTR and hTERT sequences that were essential for DNA synthesis and processivity using a direct primer extension telomerase assay. We found that hTERT consists of two physically separable functional domains, a polymerase domain containing RNA interaction domain 2 (RID2), reverse transcriptase (RT), and C-terminal sequences, and a major accessory domain, RNA interaction domain 1 (RID1). RID2 mutants defective in high-affinity hTR interactions and an RT catalytic mutant exhibited comparable DNA synthesis defects. The RID2-interacting hTR P6.1 helix was also essential for DNA synthesis. RID1 interacted with the hTR pseudoknot-template domain and hTERT's RT motifs and putative thumb and was essential for processivity, but not DNA synthesis. The hTR pseudoknot was essential for processivity, but not DNA synthesis, and processivity was reduced or abolished in dimerization-defective pseudoknot mutants. trans-acting hTERTs and hTRs complemented the processivity defects of RID1 and pseudoknot mutants, respectively. These data provide novel insight into the catalytic organization of the human telomerase complex and suggest that repeat addition processivity is one of the major catalytic properties conferred by telomerase multimerization.


Gene repertoire of the anti-poly(Glu60Ala30Tyr10) (GAT) immune response: comparison of VH, V kappa, and D regions used by anti-GAT antibodies and monoclonal antibodies produced after anti-idiotypic immunization.
Eight monoclonal antibodies were selected from BALB/c mice immunized with two different monoclonal anti-idiotypic antibodies recognizing two discrete idiotopes characteristic of the anti-poly(Glu60Ala30Tyr10) (GAT) antibody response. These monoclonal antibodies were previously classified as Ab1 (anti-GAT-like) and Ab3 (anti-anti-idiotype) on the basis of expression of the public idiotypic specificity (p.GAT) studied with a xenogeneic serum, anti-GAT activity, and expression of various public idiotopes. All the heavy chain variable region (VH) sequences from Ab1 are nearly identical to the VH sequences of Ab1 anti-GAT monoclonal antibodies. The same type of results has been found with the Ab1 kappa light chain variable region (V kappa) sequences. Confirming our classification, Ab3 VH and V kappa sequences were found to be completely different from Ab1 VH and V kappa sequences. The Ab1 diversity (D) regions are different from one another and different from the D regions found on monoclonal anti-GAT antibodies but function similarly. These D regions are not simply derived from already described D genes. Finally, our results suggest that in the anti-GAT response VH and V kappa sequence are mainly responsible for idiotype expression.


The cold sensitivity of a mutant of Saccharomyces cerevisiae lacking a mitochondrial heat shock protein 70 is suppressed by loss of mitochondrial DNA.
SSH1, a newly identified member of the heat shock protein (hsp70) multigene family of the budding yeast Saccharomyces cerevisiae, encodes a protein localized to the mitochondrial matrix. Deletion of the SSH1 gene results in extremely slow growth at 23 degrees C or 30 degrees C, but nearly wild-type growth at 37 degrees C. The matrix of the mitochondria contains another hsp70, Ssc1, which is essential for growth and required for translocation of proteins into mitochondria. Unlike SSC1 mutants, an SSH1 mutant showed no detectable defects in import of several proteins from the cytosol to the matrix compared to wild type. Increased expression of Ssc1 partially suppressed the cold-sensitive growth defect of the SSH1 mutant, suggesting that when present in increased amounts, Ssc1 can at least partially carry out the normal functions of Ssh1. Spontaneous suppressors of the cold-sensitive phenotype of an SSH1 null mutant were obtained at a high frequency at 23 degrees C, and were all found to be respiration deficient. 15 of 16 suppressors that were analyzed lacked mitochondrial DNA, while the 16th had reduced amounts. We suggest that Ssh1 is required for normal mitochondrial DNA replication, and that disruption of this process in ssh1 cells results in a defect in mitochondrial function at low temperatures.


[Changes in various hemostasis indices during transient coronary insufficiency with different durations of myocardial ischemia].
Experiments on 93 white random-bred male rats weighing 200 +/- 10 g have shown that during myocardial ischemia under transitory coronary insufficiency, there is an increase in platelet adhesive capacity, acceleration of fibrinogenesis, staged time course of formation of the fibrin-platelet structure of the blood clot, depression of its velocity and lysis degree, as well as of fibrin polymerization. Postischemic reperfusion of the coronary blood flow is not followed by normalization of all the hemostatic indicators under study even after a short-term (10 min) myocardial ischemia. Reperfusion after a long-term (40 min) ischemia gives rise to depression of coagulation and fibrinolytic activity, while that after a still longer ischemia (120 min) is characterized by discordant changes in the parameters of the systems indicated. It is assumed that similar shifts in hemostasis can be observed in patients with different patterns of coronary insufficiency.


[Psychopathological aspects in a group of children and adolescent with insulin-dependent diabetes mellitus].
We have studied a group of children and adolescents with IDDM to evaluate their personality features and family relationship to point out elements of psychopathological risk or evident mental disorders. Our study group is composed of 30 subjects (age range 7-19 years) with IDDM for at least one year. The methods employed were interviews to patients and their parents for the attitude towards the illness (done separately), Rutter scale for parents, an anxiety scale for children and adolescents (Busnelli) and a questionnaire about knowledge of diabetes (GISED). In the interviews with parents anamnestic data were collected with particular attention to early symptoms of mental disorder. Metabolic control was tested by the HbA1c measure using high pressure column chromatography, in the same laboratory. On the basis of different results we divide our study group into three subgroups. The first (30%) present no mental disorder or at least reactive or transient disorder. The second subgroup (57%) show mild mental disorder. The third subgroup (13%) present severe mental disorder. In the first subgroup the adaptation to the illness was good, because of a normal personality, absence of past psychological disorders and good family relations. The second subgroup show a wider variability of symptomatology and 65% of these patients had some behaviour disorder in their past, which became more evident after diabetes onset. In the third subgroup diabetes seems to worsen pre-existing status of mental disorder. Metabolic control is better in the first subgroup than in the other two subgroups which do not differ too much one from the other. In conclusion, the better family relationship and personality history a patient had, the better adaptation to illness and metabolic control he had (1st Subgroup). The 2nd subgroup seems to be particularly at risk because it shows behaviour disorders and risk for future personality disorder. In the 3rd subgroup mental illness was already present even if not diagnosed at the onset of diabetes and needs to be treated anyway. As a matter of fact, it seems possible that the chronic illness points out and fixes perhaps pathological characteristics already present, which did not emerge until the traumatic onset of diabetes.


Performance of the Streamlined Quality Outcomes Database Web-based Calculator: Internal and External Validation.
With an increasing number of web-based calculators designed to provide the probabilities of an individual achieving improvement after lumbar spine surgery, there is a need to determine the accuracy of these models. To perform an internal and external validation study of the reduced Quality Outcomes Database Web-based Calculator (QOD-Calc). Observational Longitudinal cohort PATIENT SAMPLE: Patients enrolled study-wide in QOD and patients enrolled in DaneSpine at a single institution who had elective lumbar spine surgery with baseline data to complete QOD-Calc and 12-month post-operative data. Oswestry Disability Index (ODI), Numeric Rating Scales (NRS) for Back and Leg Pain, EuroQOL-5D (EQ-5D) METHODS: Baseline data elements were entered into QOD-Calc to determine the probability for each patient having Any Improvement and 30% Improvement in NRS Leg Pain, Back Pain, EQ-5D and ODI. These probabilities were compared to the actual 12-month post-op data for each of the QOD and DaneSpine cases. Receiver-Operating Characteristics Analyses were performed and Calibration plots created to assess model performance. 24,755 QOD cases and 8,105 DaneSpine lumbar cases were included in the analysis. QOD-Calc had acceptable to outstanding ability (AUC: 0.694 to 0.874) to predict Any Improvement in the QOD cohort and moderate to acceptable ability (AUC: 0.658 to 0.747) to predict 30% Improvement. QOD-Calc had acceptable to exceptional ability (AUC: 0.669 to 0.734) to predict Any improvement and moderate to exceptional ability (AUC:0.619 to 0.862) to predict 30% Improvement in the DaneSpine cohort. AUCs for the DaneSpine cohort was consistently lower that the AUCs for the QOD Validation cohort. QOD-Calc performs well in predicting outcomes in a patient population that is similar to the patients that was used to develop it. Although still acceptable, model performance was slightly worse in a distinct population, despite the fact that the sample was more homogenous. Model performance may also be attributed to the low discrimation threshold, with close to 90% of cases reporting Any Improvement in outcome. Prediction models may need to be developed that are highly specific to the characteristics of the population.


Outcome of Non-drainage Scleral Buckling in Primary Rhegmatogenous Retinal Detachment.
Scleral buckling (SB) was the principal surgical intervention for patients with rhegmatogenous retinal detachment (RRD) until the development of pars plana vitrectomy. The study aims to evaluate the outcome of SB without subretinal fluid (SRF) drainage in RRD. A retrospective observational study was conducted at a tertiary eye care center. Charts of patients operated with SB without SRF drainage for RRD between January 2014 and December 2015 were evaluated. The main outcome measure was the primary reattachment rate at 1 month after single SB surgery. Other outcome measures were final reattachment rate after further intervention, visual improvement and relation of various parameters with retinal reattachment. One hundred and seventeen patients were included of which 90 (76.9%) were men. Mean age was 26.68±12.6 years (Range 9-60). All eyes were phakic. Only 1 patient had a macula on RD. The primary reattachment rate was 84.6% (n=99). Mean LogMAR (±SD) visual acuity (VA) improved from 1.92(±0.46) to 1.02(±0.42). Extent of RD, number of breaks, and type of break was found to have no association with retinal reattachment. Association between type of PVR and status of retina post buckling was found to be significant (p=0.026) with retinal reattachment seen in 100% in PVR-A and only 60% in PVR-C2. Final reattachment rate was 98.2%. Complications encountered were postoperative diplopia (n=1), suture granuloma (n=1) and buckle infection (n=2). Scleral buckling without SRF drainage, an exclusively extra ocular procedure, is an effective and safe treatment modality for non-complicated RRD.


[Models for describing ultrasound scattering in blood].
The acoustic scattering properties of blood, which are of fundamental importance for the diagnostic utilization of ultrasonic signals backscattered by blood in Doppler-based procedures, have now been investigated using three different scattering models: the particle model, the continuum model and the hybrid model. The analysis shows the limitations of the approaches so far described in the literature, and also permits a modification of the hybrid model to produce an appreciably more accurate description of the true scattering properties of the blood. This is verified by a comparison of theoretical and experimental results obtained for a large range of haematocrits.


Risk of tuberculous infection among house staff in an urban teaching hospital.
Physicians in training in our medical center were found to have a higher risk of tuberculous infection than other hospital employees. Their annual tuberculin conversion rate was 3.96%; in two of the 15 recent converters, active disease developed. There is a significant linear relationship between the acquisition of tuberculous infection and the duration of training in an urban teaching hospital. Their compliance rate to annual tuberculin testing and chemoprophylaxis is less than 50%.


Accuracy and Reliability of Onset Detection Algorithms in Gait Initiation for Healthy Controls and Participants With Parkinson's Disease.
Accurate and reliable detection of the onset of gait initiation is essential for the correct assessment of gait. Thus, this study was aimed at evaluation of the reliability and accuracy of 3 different center of pressure-based gait onset detection algorithms: A displacement baseline-based algorithm (method 1), a velocity baseline-based algorithm (method 2), and a velocity extrema-based algorithm (method 3). The center of pressure signal was obtained during 10 gait initiation trials from 16 healthy participants and 3 participants with Parkinson's disease. Intrasession and absolute reliability of each algorithm was assessed using the intraclass correlation coefficient and the coefficient of variation of center of pressure displacement during the postural phase of gait initiation. The accuracy was evaluated using the time error of the detected onset by each algorithm relative to that of visual inspection. The authors' results revealed that although all 3 algorithms had high to very high intrasession reliabilities in both healthy subjects and subjects with Parkinson's disease, methods 2 and 3 showed significantly better absolute reliability than method 1 in healthy controls (P = .001). Furthermore, method 2 outperformed the other 2 algorithms in both healthy subjects and subjects with Parkinson's disease with an overall accuracy of 0.80. Based on these results, the authors recommend using method 2 for accurate and reliable gait onset detection.


[Chinese consensus on definition and grading of perioperative morbidities in esophageal cancer and esophagogastric junction cancer (2023 Edition)].
Surgical treatment quality dramatically affects the overall outcome of esophagogastric cancer in China, but there is currently a lack of widely accepted definitive grading criteria for evaluating perioperative safety, making it unfeasible undertaking a surgical quality improvement project nationwide. The National Cancer Center, under the commission of the National Health Commission, has recently created the "Quality Control Indicators for Standardized Diagnosis and Treatment of Esophageal Cancer in China (2022 Version)." To ensure the successful implementation of the QC standard, aligning with it more effectively is crucial. The Expert Committee on Quality Control of Esophageal Cancer at the National Cancer Center leads work teams comprised of multidisciplinary experts, particularly those in thoracic surgery, to establish a consensus on the definition and grade for perioperative morbidity. This expert consensus is developed by applying the international standardized guideline development methodology based on the latest research evidence and China's national conditions. This consensus covers the framework of 8 major categories, precisely 45 of the most common perioperative morbidities of esophagogastric cancer. This consensus aims to establish a standardization of surgical management for esophagogastric cancer in China, ultimately improving its effectiveness nationwide.


Sildenafil induces browning of subcutaneous white adipose tissue in overweight adults.
To investigate that short-term treatment of sildenafil can induce browning of subcutaneous white adipose tissue (sWAT) in human adults. A randomized, double-blinded, placebo-controlled, parallel group trial. Sixteen eligibility overweight male subjects were recruited, comparing 100mg/day sildenafil versus an identical placebo therapy for 7days. sWAT samples were collected from subjects before and after 7-day sildenafil or placebo interventions. The results showed that multilocular UCP1-positive adipocytes existed in sWAT samples from subjects after sildenafil treatment. Compared to before treatment in both group as well as after treatment in placebo, sildenafil significantly decreased adipocyte size, increased the expressions of UCP1 protein and mRNA, mitochondrial density, and leak respiratory capacity in sWAT (p<0.05). Sildenafil also increased plasma cyclic guanosine-3',5'-monophosphate (cGMP) and catecholamine concentrations (p<0.05), and consequently activated the expressions of vasodilator-stimulated phosphoprotein (VASP) and p70 ribosomal S6 kinase 1 (S6K1) (p<0.05). Sildenafil did not activate typical brown fat. The current findings demonstrate that sildenafil can induce browning of sWAT in human, and this action may be through cGMP-dependent protein kinase I and mechanistic/mammalian target of rapamycin (mTOR) signaling pathways. Sldenafil may be a promising treatment for metabolic disease.


The effect of spanking on early social-emotional skills.
Whether spanking is detrimental for social-emotional (SE) development remains controversial, mostly due to disputes around the internal and external validity of existing evidence. This study examined the effect of spanking on the SE development of Bhutanese children, using a national, longitudinal sample (N = 1377; Mage = 50.5 months old; 50% girls). Following best-practice recommendations for mitigating issues of selection bias in observational developmental research, the study employed conservative methods (i.e., child fixed-effects and lagged-dependent variables) and robustness checks to assess the internal validity of estimates. Across approaches, spanking predicted reductions in SE skills of .09-.17 SD, even after controlling for all time-invariant confounders and baseline levels of SE skills. These findings strengthen the argument that spanking might be harmful to young children's SE development.


Facetted patchy particles through entropy-driven patterning of mixed ligand SAMS.
We present a microscopic theory that describes the ordering of two distinct ligands on the surface of a facetted nanoparticle. The theory predicts that when one type of ligand is significantly bulkier than all others, the larger ligands preferentially align themselves along the edges and vertices of the nanoparticle. Monte Carlo simulations confirm these predictions. We show that the intrinsic conformational entropy of the ligands stabilizes this novel edge-aligned phase.


An Image Signal Accumulation Multi-Collection-Gate Image Sensor Operating at 25 Mfps with 32 × 32 Pixels and 1220 In-Pixel Frame Memory.
The paper presents an ultra-high-speed image sensor for motion pictures of reproducible events emitting very weak light. The sensor is backside-illuminated. Each pixel is equipped with multiple collection gates (MCG) at the center of the front side. Each collection gate is connected to an in-pixel large memory unit, which can accumulate image signals captured by repetitive imaging. The combination of the backside illumination, image signal accumulation, and slow readout from the in-pixel signal storage after an image capturing operation offers a very high sensitivity. Pipeline signal transfer from the the multiple collection gates (MCG) to the in-pixel memory units enables the sensor to achieve a large frame count and a very high frame rate at the same time. A test sensor was fabricated with a pixel count of 32 × 32 pixels. Each pixel is equipped with four collection gates, each connected to a memory unit with 305 elements; thus, with a total frame count of 1220 (305 × 4) frames. The test camera achieved 25 Mfps, while the sensor was designed to operate at 50 Mfps.


Time-resolved retardance and optic-axis angle measurement system for characterization of flexoelectro-optic liquid crystal and other birefringent devices.
A new polarimeter is presented which gives time-resolved measurements of both the optic-axis angle and the linear phase retardation for modulated birefringent optical devices. It is suitable for characterizing dynamic waveplate devices based on liquid crystal and other materials. It is fully automated and requires no angular alignment of the device under test. The system has an absolute angle error of < ± 0.3° and a retardance error of < ± 0.44°, with considerably better relative accuracy. The method has been tested with a chiral nematic liquid crystal device exhibiting flexoelectro-optic switching at 3 kHz in the uniform lying helix mode. These results represent the first time-resolved tilt-angle and phase retardation measurements for a liquid crystal device operating at fast switching frequencies.


Regional time-dependent changes in vasopressin V2 receptor expression in the rat kidney during water restriction.
Elevations of arginine vasopressin (AVP) binding to renal vasopressin V2 receptors (V2R) enhance water and urea reabsorption in the collecting duct epithelium. This study was designed to quantify the levels of V2R mRNA and protein within the distinct regions of the Sprague-Dawley rat kidney (i.e., the cortex and outer and inner medulla) during 24 and 48 h of water restriction. A competitive reverse transcription-polymerase chain reaction (RT-PCR) assay was developed to quantify changes in the V2R mRNA, in which a deletion mutant RNA transcript was used to control for the efficiency of RT-PCR. Western blot analysis was utilized for the quantification of the V2R protein. The results showed that the steady-state levels of the V2R mRNA decreased in a time-dependent manner in the cortex and outer and inner medulla throughout 48 h of water restriction. Western blot analysis revealed that the V2R protein in the renal cortex decreased after the initial 24 h of water restriction and remained decreased at 48 h. In contrast, outer medullary V2R protein decreased significantly only after 48 h of water restriction, whereas no significant change in the inner medullary V2R protein was observed throughout the 48 h of water restriction. These results suggest that water restriction leads to a regional time-dependent downregulation of the V2R mRNA and protein within the rat kidney. The stability of the plasma membrane V2R protein within the inner medulla may allow for the optimization of urine concentration and minimize water loss during periods of water restriction.


Effect of Custom Foot Insoles on Postural Stability in Figure Skaters While on Ice.
Improvements in postural stability in figure skaters can play a significant role in performance, as well as reducing fall risk. To explore the effect of custom foot insoles on postural stability in advanced figure skaters. Exploratory study. Out of laboratory. Nine advanced figure skaters were recruited and 7 completed the study (age 38 ± 18.5 y, body-mass index 25 ± 3.6 kg/m2). Custom foot insoles. Primary outcome of changes in postural stability (PS) quantified by center-of-mass sway with secondary outcomes of ankle- and hip-joint sway and joint range of motion. Sway measurements were assessed using body-worn sensors while participants wore skates on ice. PS was assessed in single-leg stance, as well as during gliding on the dominant foot. A significant improvement in static PS was observed after 6-wk use of custom insoles. Center-of-mass sway reduced significantly on average by 48.44% (P = .023), and ankle-joint sway reduced by 45.7% (P = .05) during single-leg-stance balance measurements. During the gliding maneuver nonsignificant changes were observed for both ankle- and knee-joint range of motion. The results of this study suggest proof of concept toward benefits of custom insoles in improving postural stability in advanced figure skaters. To generalize the findings, randomized controlled trials with larger sample sizes are warranted.


Production of N(epsilon)-(carboxymethyl)lysine is impaired in mice deficient in NADPH oxidase: a role for phagocyte-derived oxidants in the formation of advanced glycation end products during inflammation.
Advanced glycation end products (AGEs) derived from glucose are implicated in the pathogenesis of diabetic vascular disease. However, many lines of evidence suggest that other pathways also promote AGE formation. One potential mechanism involves oxidants produced by the NADPH oxidase of neutrophils, monocytes, and macrophages. In vitro studies have demonstrated that glycolaldehyde, a product of serine oxidation, reacts with proteins to form N(epsilon)-(carboxymethyl)lysine (CML), a chemically well-characterized AGE. We used mice deficient in phagocyte NADPH oxidase (gp91-phox(-/-)) to explore the role of oxidants in AGE production in isolated neutrophils and intact animals. Activated neutrophils harvested from wild-type mice generated CML on ribonuclease A (RNase A), a model protein, by a pathway that required L-serine. CML formation by gp91-phox(-/-) neutrophils was impaired, suggesting that oxidants produced by phagocyte NADPH oxidase contribute to the cellular formation of AGEs. To determine whether these observations are physiologically relevant, we used isotope-dilution gas chromatography/mass spectrometry to quantify levels of protein-bound CML in mice suffering from acute peritoneal inflammation. Phagocytes from the gp91-phox(-/-) mice contained much lower levels of CML than those from the wild-type mice. Therefore, oxidants generated by phagocyte NADPH oxidase may play a role in AGE formation in vivo by a glucose-independent pathway.


Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart.
Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.


Management of acute spine and spinal cord injuries. Old and new concepts.
The modern, positive approach to treatment of injuries of the cervical spine and spinal cord has produced excellent long-term survival, but less progress has been made in reversal of the neurologic defect. Injuries to the spinal column are of four types: flexion-dislocation, hyperextension, vertical compression, and rotation. Those to the spinal cord also involve four categories: morphologic damage, hemorrhage and vascular damage, structural changes, and biochemical response. Experimental work has explored new adjuncts to conservative treatment, such as norepinephrine antagonists, other drugs, and hypothermia. These results, and those of surgery on the experimental lesions, have been hopeful, but not definitive. Controversy surrounds the surgical vs nonsurgical treatment of clinical spinal cord injury. Operation is indicated for roentgenographic evidence of bone fragments in the spinal canal, for worsening neurological symptoms, and, possibly, if experimental evidence is to be followed, for surgical decompression in the very early minutes or hours after injury.


Are black Americans entitled to equal health care? a new research paradigm.
This paper analyzes the health, economic and legal implications of most major health systems' reform initiatives in the 20th century and, briefly, the 19th century. The paper suggests that models of analysis grounded in science deter the development of claims for racial equality in health care. Because race is a legal construct, the paper suggests that the 14th Amendment's Equal Protection Clause is an analytical framework that better accommodates the complexity of the health system, is at the heart of our national laws and ethos, and has political rhetorical power to further the political and policy debate. Major components of the health care system, including professional training, hospital construction, and health care financing, are analyzed for racially discriminatory purpose or impact and the extent of government participation. The paper gives particular attention to: the Flexner Report and the limited number of black physicians; the Hill-Burton program and the disproportionate assistance it gave to white controlled hospitals; and, efforts to expand health insurance coverage that also disproportionately favored the needs of the white community. Given the compounding effects of numerous policy decisions made over many years, there should not be any great wonder that such gross disparities in morbidity and mortality exist between black and white Americans. Further research and analysis of the policy decisions that have constructed the current health care system as well as framing those analyses as claims for racial fairness will better develop the policy debate than more narrowly focused analytical models from biomedical science or epidemiology. The law produced slavery and segregation, which usually determined where you lived, where you went, what work you could do, and what you learned. That legally constructed system significantly determined what you earned and what health you had. The biomedical models of analysis of our health system are too narrowly focused and temporally limited to identify the broad systemic barriers to equal health and health care. An analytical framework from law more easily accommodates the complex dynamics of our health care system. The equal protection clause of the 14th amendment has been used to analyze complex social and economic models, such as housing and education and has moved those systems to greater racial equality. The equal protection clause is at the heart of our national laws and ethos and, as a claim for fair treatment from government, has considerable rhetorical power. Menefee presents an analysis of major health policies dealing with training of physicians, construction of hospitals, and financing of personal health care. He suggests it demonstrates a health system rooted in racial discrimination and perpetuating racial discrimination in education, employment and housing. The history of successes using this analytical framework in other areas of social policy validates its consideration by health policy analysts for further research.


Dependence of morphometric allometries on the growth kinetics of body parts.
As overall size varies, the sizes of body parts of many animals often appear to be related to each other by a power law, commonly called the allometric equation. Orderly scaling relationships among body parts are widespread in the animal world, but there is no general agreement about how these relationships come about. Presumably they depend on the patterns of growth of body parts, and simple analyses have shown that exponential growth can lead to size relationships that are well-described by the allometric equation. Exponential growth kinetics also allow for a simple biological interpretation of the coefficients of the power relationship. Nevertheless, many tissues do not grow with exponential kinetics, nor do they grow for the same period of time, and the consequences of more realistic growth patterns on the resulting allometric relationships of body parts are not well understood. In this paper I derive a set of allometric equations that assume different kinetics of growth: linear, exponential and sigmoidal. In these derivations I also include differences in development times as a variable, in addition to differences in the growth rates and initial sizes of the two structures whose allometric relationship is compared. I show how these equations can be used to deduce the effect of different causes of variation in absolute size on the resulting allometry. Variation in size can be due to variation in the duration of development, variation in growth rate or variation in initial size. I show that the meaning of the coefficients of the allometric equation depends on exactly how size variation comes about. I show that if two structures are assumed to grow with sigmoidal kinetics (logistic and Gompertz) the resulting allometric equations do not have a simple and intuitive structure and produce graphs that, over a sufficiently large range of sizes, can vary from linear, to sigmoidal to hump-shaped. Over a smaller range of absolute sizes, these sigmoid growth kinetics can produce nearly linear allometries in both the arithmetic and logarithmic domains. I will argue that although growth kinetics are likely to be sigmoidal in most cases, natural selection will restrict variation in absolute size and the parameters of growth kinetics to regions where the allometric relations are linear, or nearly so.


Quality of phytoplankton deposition structures bacterial communities at the water-sediment interface.
Phytoplankton comprises a large fraction of the vertical carbon flux to deep water via the sinking of particulate organic matter (POM). However, despite the importance of phytoplankton in the coupling of benthic-pelagic productivity, the extent to which its deposition in the sediment affects bacterial dynamics at the water-sediment interface is poorly understood. Here, we conducted a microcosm experiment in which varying mixtures of diatom and cyanobacteria, representing phytoplankton-derived POM of differing quality, served as inputs to sediment cores. Characterization of 16S rRNA gene of the bacterial communities at the water-sediment interface showed that bacterial α-diversity was not affected by POM addition, while bacterial β-diversity changed significantly along the POM quality gradient, with the variation driven by changes in relative abundance rather than in taxon replacement. Analysing individual taxa abundances across the POM gradient revealed two distinct bacterial responses, in which taxa within either diatom- or cyanobacteria-favoured groups were more phylogenetically closely related to one another than other taxa found in the water. Moreover, there was little overlap in taxon identity between sediment and water communities, suggesting the minor role played by sediment bacteria in influencing the observed changes in bacterial communities in the overlying water. Together, these results showed that variability in phytoplankton-originated POM can impact bacterial dynamics at the water-sediment interface. Our findings highlight the importance of considering the potential interactions between phytoplankton and bacteria in benthic-pelagic coupling in efforts to understand the structure and function of bacterial communities under a changing climate.


miRNAs and Substances Abuse: Clinical and Forensic Pathological Implications: A Systematic Review.
Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high prevalence and social burden of addiction are indisputable; however, the available intervention is insufficient. The modulation of gene expression and aberrant adaptation of neural networks are attributed to the changes in brain functions under repeated exposure to addictive substances. Considerable studies have demonstrated that miRNAs are strong modulators of post-transcriptional gene expression in substance addiction. The emerging role of microRNA (miRNA) provides new insights into many biological and pathological processes in the central nervous system: their variable expression in different regions of the brain and tissues may play a key role in regulating the pathophysiological events of addiction. This work provides an overview of the current literature on miRNAs involved in addiction, evaluating their impaired expression and regulatory role in neuroadaptation and synaptic plasticity. Clinical implications of such modulatory capacities will be estimated. Specifically, it will evaluate the potential diagnostic role of miRNAs in the various stages of drug and substance addiction. Future perspectives about miRNAs as potential novel therapeutic targets for substance addiction and abuse will also be provided.


[Social anxiety and propranolol abuse: a case study].
A patient with severe social anxiety disorder has taken unprescribed propranolol for six years (up to 320 mg/day). In addition to the psychoanalytic treatment that had been instituted and after the diagnosis and prescription of tranilcipromine, both the social anxiety symptoms and propranolol abuse have improved; after the prescription of paroxetine she underwent a better controlled use of the betablocker. Despite the informal self-prescription for several years, the generalized social anxiety symptoms persisted. This case exemplifies the special difficulty of social phobic patients to seek for treatment. The author formulates a hypothesis that there may be an increasing informal prescription of betablockers among persons with social anxiety disorder and performance anxiety, a problem whose public health importance is still unknown.


Cartilage tissue engineering using dermis isolated adult stem cells: the use of hypoxia during expansion versus chondrogenic differentiation.
Dermis isolated adult stem (DIAS) cells, a subpopulation of dermis cells capable of chondrogenic differentiation in the presence of cartilage extracellular matrix, are a promising source of autologous cells for tissue engineering. Hypoxia, through known mechanisms, has profound effects on in vitro chondrogenesis of mesenchymal stem cells and could be used to improve the expansion and differentiation processes for DIAS cells. The objective of this study was to build upon the mechanistic knowledge of hypoxia and translate it to tissue engineering applications to enhance chondrogenic differentiation of DIAS cells through exposure to hypoxic conditions (5% O2) during expansion and/or differentiation. DIAS cells were isolated and expanded in hypoxic (5% O2) or normoxic (20% O2) conditions, then differentiated for 2 weeks in micromass culture on chondroitin sulfate-coated surfaces in both environments. Monolayer cells were examined for proliferation rate and colony forming efficiency. Micromasses were assessed for cellular, biochemical, and histological properties. Differentiation in hypoxic conditions following normoxic expansion increased per cell production of collagen type II 2.3 fold and glycosaminoglycans 1.2 fold relative to continuous normoxic culture (p<0.0001). Groups expanded in hypoxia produced 51% more collagen and 23% more GAGs than those expanded in normoxia (p<0.0001). Hypoxia also limited cell proliferation in monolayer and in 3D culture. Collectively, these data show hypoxic differentiation following normoxic expansion significantly enhances chondrogenic differentiation of DIAS cells, improving the potential utility of these cells for cartilage engineering.


Calcium currents of cardiovascular neurons isolated from adult guinea pigs.
A preparation of cells isolated from the medial and dorsal nuclei of the solitary tract of the medulla of adult guinea pigs was developed to examine the electrical properties of neurons isolated from an area of the central nervous system which is involved in the control of arterial pressure and heart rate. Bipolar cells of approximately 10 microns diameter were obtained on enzymatic dispersion. The cells were studied with the use of the patch technique for whole cell recording. Action potentials were elicited by depolarizing pulses in the presence of 10(-5) M tetrodotoxin which blocked a sodium-dependent current. These action potentials were calcium dependent and were eliminated by adding 1 mM Cd to the bath. In all cells studied, two voltage-dependent components to the calcium current were identified. In 10 mM Ca a high-threshold component activated at approximately -20 mV from holding potentials of -30 mV. A second lower threshold component was activated at -40 mV from more negative holding potentials of -80 mV. The low-threshold component was rapidly inactivating, whereas the high-threshold current slowly inactivated. The peak amplitudes of the two components were similar. Both components were blocked by 1 mM Cd. A role for the low-threshold calcium current in generating repetitive activity is postulated.


Insulin receptor of fat cells in insulin-resistant metabolic states.
A diminished response to insulin is exhibited by isolated fat cells obtained from rats that have been either starved, or treated with prednisone, or made diabetic by administration of streptozotocin. This decrease in response is not accompanied by changes in the quantity of insulin receptor of these cells or in the affinity of these receptors for insulin. Similarly, the decreased responsiveness to insulin of fat cells obtained from certain species (hamster, rabbit, mouse, guinea pig) is not explainable in terms of alterations of the insulin receptor.


Assessment of knowledge in adolescents with inflammatory bowel disease using a novel transition tool.
In the transition from pediatric to adult care, patients are expected to increase their level of self-care. Knowledge of disease characteristics, medications, and resources is crucial. This study evaluated the knowledge of adolescents with inflammatory bowel disease (IBD) and their parents in four major domains: disease characteristics, treatments, medical history, and health services resources. Patients age 14-18 years and their parents completed MyHealth Passport for IBD as a cross-sectional assessment of knowledge. Responses were evaluated for accuracy using medical records. The proportion of correct responses between patients/parents were compared. In all, 78 patients (age 16.2 ± 1.2 years, IBD duration 3.6 ± 2.5 years), and 64 parents participated. Patients and parents were equally likely to answer questions correctly regarding disease characteristics and treatment, but not health services resources. Most patients accurately identified IBD classification and listed medications. Neither patients nor parents accurately identified disease location or previous investigation results. Parents more likely correctly named insurance provider (odds ratio [OR] 6.33, 95% confidence intervals [CI] 2.68-15.0), and pharmacy location (OR 18.5, 95% CI 4.6-76.8). Multivariate regression revealed that patients with IBD type unclassified were more likely to be aware of their diagnostic classification (OR 17.2, 95% CI 2.81-105.4 compared with Crohn's disease patients). Older patients were less likely to recall if they had a small bowel x-ray (OR 0.59, 95% CI 0.35-0.996). Future educational interventions should target areas of weakness in adolescent knowledge, particularly health services resources. The MyHealth Passport for IBD (available freely online) could educate and instill independence in the transitioning adolescent.


Serum under-carboxylated osteocalcin levels in women with polycystic ovary syndrome: weight-dependent relationships with endocrine and metabolic traits.
Under-carboxylated osteocalcin (ucOC), the precursor substrate of bone biomarker OC is a potent regulator of energy metabolism by promoting insulin production and adiponectin synthesis and decreasing fat stores. The aim of the present study was to point out the potential role of ucOC in the physiopathology of polycystic ovary syndrome (PCOS), a common disorder defined by the constellation of anovulation, insulinresistance, hyperinsulinemia, obesity and androgen excess. In this prospective case-control investigation, 78 young premenopausal women, i.e. 52 PCOS patients and 26 age- and body mass index (BMI)-matched healthy controls, were successively enrolled. Recruitment of PCOS patients was performed according to Androgen Excess-Polycystic Ovary Syndrome (AE-PCOS) Society 2006 criteria. All study participants were subjected to clinical examination, whole-body composition assessment and measurements of serum ucOC, OC (1-49), glucose and lipids, insulin, total testosterone (TT), estradiol, sex-hormone binding globulin (SHBG), high-sensitivity C-reactive protein (Hs-CRP) and β-CrossLaps. BMI-stratified multivariate analysis revealed significantly higher ucOC levels in PCOS vs. controls in lean (p = 0.001) but not overweight and obese study participants (p = 0.456). Notably, a positive correlation between ucOC and TT (p = 0.018), calculated free testosterone (cFT, p = 0.028) and serum insulin (p = 0.036), respectively, was found to be confined to the lean analysis subgroup. Furthermore, in stepwise multiple regression models, β-CrossLaps and cFT were able to predict 46.71% of serum ucOC variability. (1-43/49)OC failed to be significantly associated to any PCOS trait. Circulating ucOC concentration is related to key endocrine PCOS characteristics in a weight-dependent manner. Within the bone-pancreas loop, high ucOC may favor insulin release in lean hyperandrogenic women to compensate for impaired insulin sensitivity.


[Cardio-MRT. The multimodal functional analysis of the future].
Since initial reports in the early 1990s cardiac magnetic resonance imaging (CMR) has matured and is likely to become an established method for routine cardiac diagnostics. The development of faster gradient-echo sequences and stronger magnetic fields has led to improved temporal and spatial resolution. Myocardial viability can be examined by morphological and functional analysis. Contrast enhanced MRI (ceMRI), perfusion measurements and regional wall motion analysis are the major diagnostic tools. The ability to image in arbitrary double oblique planes provides comprehensive visualization of the heart. The introduction of the MR navigator technique allowed for free-breathing motion corrected 3D coronary MR angiography with improved spatial resolution. Using this approach proximal and mid parts of the coronary arteries have been visualized. Subsequently, sensitivity and specificity for the detection of significant coronary stenoses has been evaluated in a multicenter trial demonstrating good sensitivity and specificity for the detection of significant left main and three vessel disease. However, specificity for the detection of single vessel disease was relatively low. Improved motion compensation techniques and novel imaging sequences (SSFP) are currently under investigation to further refine this technique. Despite these promising results coronary MR-angiography is not likely to replace conventional coronary angiography especially with regard to in-plane spatial resolution, coronary collateralization and in-stent restenosis. In contrast, coronary MR-angiography can provide useful morphological informations including functional analysis of the coronary vascular bed. The combination of a conventional cathlab with CMR may provide CMR-guided myocardial interventions. With further improvements in the catheter technology, CMR interventions using real-time imaging guidance will allow to take advantage of the excellent soft tissue contrast of CMR and the simultaneous visualization of the pulmonary, aortic and coronary vessels. CMR is advantageous for screening and follow-up examinations, and it offers comprehensive assessment of cardiac morphology and function in one single examination.


Significance and current approaches to vascular graft infection.
Vascular graft/endograft infection (VGEI) is a constant in cardiovascular surgery with published rates between 1 and 5%. Every graft type and anatomical location is a potential target for infectious complications. These patients are sick patients with high frailty burden. Management of VGEI entails a multidisciplinary and multimodality approach. Here we review some aspects of the problem of VGEI including prevention, diagnosis, and surgical therapy with focus on recent developments in the field.


Serum leptin is associated with the perception of palatability during a standardized high-carbohydrate breakfast test.
Leptin is an adipocyte-derived signalling molecule which plays a key role in the regulation of body weight and energy expenditure. Since its involvement in human eating behaviour is still poorly understood, we investigated whether the perception of palatability of food was related to fasting serum leptin levels. Twenty-six non-diabetic subjects, six men and twenty women of widely ranging age and body mass index, performed a standardized high-carbohydrate breakfast test. Palatability was evaluated with a visual analogue scale, body composition by bioelectrical impedance, serum leptin and plasma insulin by radioimmunoassay. Palatability was correlated to fasting serum leptin levels independently of body mass index, body fat mass and percentage of body fat (P<0.01). No significant relation was observed with peaks of insulinaemia, integrated concentrations of insulin or insulin resistance indices. A stepwise regression analysis indicated that serum leptin gave the strongest predictive association with palatability. These results suggest that the leptin system may be involved in the regulation of human eating behaviour in relation to the perception of palatability of food.


Iso-Seq analysis of Nepenthes ampullaria, Nepenthes rafflesiana and Nepenthes × hookeriana for hybridisation study in pitcher plants.
Tropical pitcher plants in the species-rich Nepenthaceae family of carnivorous plants possess unique pitcher organs. Hybridisation, natural or artificial, in this family is extensive resulting in pitchers with diverse features. The pitcher functions as a passive insect trap with digestive fluid for nutrient acquisition in nitrogen-poor habitats. This organ shows specialisation according to the dietary habit of different Nepenthes species. In this study, we performed the first single-molecule real-time isoform sequencing (Iso-Seq) analysis of full-length cDNA from Nepenthes ampullaria which can feed on leaf litter, compared to carnivorous Nepenthes rafflesiana, and their carnivorous hybrid Nepenthes × hookeriana. This allows the comparison of pitcher transcriptomes from the parents and the hybrid to understand how hybridisation could shape the evolution of dietary habit in Nepenthes. Raw reads have been deposited to SRA database with the accession numbers SRX2692198 (N. ampullaria), SRX2692197 (N. rafflesiana), and SRX2692196 (N. × hookeriana).


Expression of human membrane proteins 4.1a and 4.1b in reticulocytes and mature erythrocytes.
The erythrocyte membrane protein of band 4.1 is an essential protein of the erythrocyte cytoskeleton. Two isoforms have been detected in human erythrocytes, and six in nucleated avian erythrocytes. Multiple alternative splicing of human reticulocyte mRNA for protein 4.1 implies the possibility of even more isoforms. Structural and functional dissimilarities between isoforms, and their differential expression during the course of erythropoiesis are not well understood. Here, we show that only protein 4.1b is present in the immature reticulocytes of anaemic patients. The ratio of 4.1a to 4.1b in mature reticulocytes of healthy individuals was 1.25. This ratio was 2.0 in healty mature erythrocytes, and 0.7 in peripheral red blood cells from anaemic patients. Taking into account these and other available data, we speculate that the steady state levels of protein 4.1 isoforms change gradually in the terminal stages of erythropoiesis.


Towards the 24-hour society--new approaches for aging shift workers?
The new "24-hour society" increases night work and the diversity of flexible work-hour patterns. At the same time, the number of older shift workers is growing in most developed countries due to the general aging of the working population. Together with new experimental and epidemiologic data on the alarming relationship of shift work to fatigue, performance, accidents, and chronic health effects like coronary heart disease, there is reason to believe that shift work may become a major occupational health and safety problem in the near future. The prevention of shiftwork-related health and safety problems will be a major challenge for the employer, employees, and occupational health professionals during the next few decades. The present paper shortly summarizes the current knowledge on the relationship between shift work, aging, and health and outlines practical countermeasures and research needs to improve the health and well-being of aging shift workers.


Neural basis of interindividual variability in social perception in typically developing children and adolescents using diffusion tensor imaging.
Humans show great interindividual variability in the degree they engage in social relationship. The neural basis of this variability is still poorly understood, particularly in children. In this study, we aimed to investigate the neural basis of interindividual variability in the first step of social behavior, that is social perception, in typically developing children. For that purpose, we first used eye-tracking to objectively measure eye-gaze processing during passive visualization of social movie clips in 24 children and adolescents (10.5 ± 2.9 y). Secondly, we correlated eye-tracking data with measures of fractional anisotropy, an index of white matter microstructure, obtained using diffusion tensor imaging MRI. The results showed a large interindividual variability in the number of fixations to the eyes of characters during visualization of social scenes. In addition, whole-brain analysis showed a significant positive correlation between FA and number of fixations to the eyes,mainly in the temporal part of the superior longitudinal fasciculi bilaterally, adjacent to the posterior superior temporal cortex. Our results indicate the existence of a neural signature associated with the interindividual variability in social perception in children, contributing for better understanding the neural basis of typical and atypical development of a broader social expertise.


Demographics, socio-behavioral factors, and drug use patterns: what matters in spontaneous HCV clearance?
Hepatitis C virus (HCV), an emerging bloodborne pathogen, causes chronic liver disease frequently except in about 10-20% of infections which undergo spontaneous resolution. Investigating factors that influence viral clearance is essential to understand the natural history of this infection and establishing novel strategies for prevention and treatment. HCV clearance was estimated in a unique cohort of 1,260 HIV and HBV negative current drug users enrolled for a hepatitis B vaccination study. It was defined as the inability to detect viral RNA using a PCR method in presence of serum anti-HCV antibody EIA. Associated demographic and socio-behavioral factors including drug use patterns were identified from the enrolled subjects using multivariate regression analysis. 33.3% (420/1260) of drug users were found positive for anti-HCV antibodies and 14.8% (62/420) of these individuals achieved viral clearance (negative PCR test). Race or ethnicity of the participants was the only significant factor associated with HCV clearance. Hispanics (OR = 3.4, 95% CI: 1.3-8.5, P = 0.01) and Caucasians (OR = 3.1, 95% CI: 1.5-6.6, P = 0.003) had significantly higher odds of clearing the virus compared to African Americans when adjusted for age and gender. None of the socio-behavioral factors including alcohol intake and drug use patterns were significant determinants of HCV clearance. Racial or ethnic differences in HCV clearance were observed in this study suggesting an important role of host genetic susceptibility factors in determining the clinical course of this disease. Further research is needed to examine these genetic associations of host-virus relationships.


Viscoelastic shear properties of human vocal fold mucosa: measurement methodology and empirical results.
A standard method for the empirical rheological characterization of viscoelastic materials was adopted to measure the viscoelastic shear properties of human vocal-fold mucosal tissues (the superficial layer of lamina propria). A parallel-plate rotational rheometer was employed to measure shear deformation of viscoelastic tissue samples, which were deformed between two rigid circular plates rotating in small-amplitude sinusoidal oscillations. Elastic and viscous shear moduli of the samples were then quantified as a function of oscillation frequency (0.01 to 15 Hz) based on shear stresses and strains recorded by the rheometer. Data were obtained from 15 excised human larynges (10 male and 5 female). Results showed that the elastic shear modulus mu and the damping ratio zeta of human vocal-fold mucosa were relatively constant across the range of frequencies observed, while the dynamic viscosity eta decreased monotonically with frequency (i.e., shear thinning). Intersubject differences in mu and eta as large as an order of magnitude were observed, part of which may reflect age-related and gender-related differences. Some molecular interpretations of the findings are discussed.


Folate deficiency and aberrant expression of DNA methyltransferase 1 were associated with cervical cancerization.
DNA methyltransferase 1 (DNMT1) plays a significant role in maintaining DNA methylation. Aberrant DNA methylation is a recognized feature of human cancers and folate is directly involved in DNA methylation via one-carbon metabolism. Previous reports also have suggested that folate deficiency was associated with many cancers. The aim of the present study was to evaluate the effect of folate deficiency and aberrant expression of DNA methyltransferase 1 (DNMT1) on cervical cancerization. The expression of DNMT1 protein and mRNA and levels of serum folate were detected in 238 women with a diagnosis of normal cervix (NC,n = 53), cervical intraepithelial neoplasia (CIN I, n = 52; CIN II/III, n = 53), and squamous cell carcinoma of the cervix (SCC; n = 80). In addition, the expression of DNMT1 protein and mRNA was measured in cervical cancer cells (Caski and C33A) treated by different concentration of folate. Serum folate levels decreased and expression levels of DNMT1 protein and mRNA increased gradually with progressive severity of the cervix lesions (P<0.001). It was found that folate was able to reduce the viability of Caski or C33A cell (r=0.978, P=0.002; r=0.984, P<0.001) and regulated aberrant expression of DNMT1 protein (r=-0.859, P=0.01; r=-0.914, P<0.001) and mRNA (r=-0.297, P=0.159; r=0.433, P=0.034) in vitro. Our findings indicated that the low-level of serum folate and high-expression of DNMT1 protein or mRNA was significantly associated with cervical carcinogenesis. Folate deficiency and aberrant expression of DNA methyltransferase 1 had additive effect on cervical cancerization. Folate supplement and recovery of aberrant DNA methylation status may offer a new strategy for prevention and therapy of cancers.


Bacterial community analyses of two Red Sea sponges.
Red Sea sponges offer potential as sources of novel drugs and bioactive compounds. Sponges harbor diverse and abundant prokaryotic communities. The diversity of Egyptian sponge-associated bacterial communities has not yet been explored. Our study is the first culture-based and culture-independent investigation of the total bacterial assemblages associated with two Red Sea Demosponges, Hyrtios erectus and Amphimedon sp. Denaturing gradient gel electrophoresis fingerprint-based analysis revealed statistically different banding patterns of the bacterial communities of the studied sponges with H. erectus having the greater diversity. 16S rRNA clone libraries of both sponges revealed diverse and complex bacterial assemblages represented by ten phyla for H. erectus and five phyla for Amphimedon sp. The bacterial community associated with H. erectus was dominated by Deltaproteobacteria. Clones affiliated with Gammaproteobacteria were the major component of the clone library of Amphimedon sp. About a third of the 16S rRNA gene sequences in these communities were derived from bacteria that are novel at least at the species level. Although the overall bacterial communities were significantly different, some bacterial groups, including members of Alphaproteobacteria, Gammaproteobacteria, Acidobacteria, and Actinobacteria, were found in both sponge species. The culture-based component of this study targeted Actinobacteria and resulted in the isolation of 35 sponge-associated microbes. The current study lays the groundwork for future studies of the role of these diverse microbes in the ecology, evolution, and development of marine sponges. In addition, our work provides an excellent resource of several candidate bacteria for production of novel pharmaceutically important compounds.


Neomycin is a potent secretagogue of mast cells that directly activates a GTP-binding protein involved in exocytosis.
When loaded alongside GTP-gamma-S into ATP-permeabilized cells, neomycin, at concentrations below 1 mM, inhibits GTP-gamma-S-induced histamine secretion and phosphatidic acid formation (Cockcroft, S., and B. D. Gomperts, 1985. Nature (Lond.). 314: 534-536; Aridor, M., L. M. Traub, and R. Sagi-Eisenberg. 1990. J. Cell Biol. 111:909-917). However, at higher concentrations internally applied neomycin induces histamine secretion in a process that is: (a) dose dependent; (b) dependent on the internal application of GTP; (c) independent of phosphoinositide breakdown; and (d) inhibited by pertussis toxin (PtX) treatment. These results indicate that neomycin can stimulate histamine secretion in a mechanism that bypasses phospholipase C (PLC) activation and yet involves a PtX-sensitive GTP-binding protein (G protein). Unlike its dual effects, when internally applied, neomycin induces histamine secretion from intact mast cells in a dose-dependent manner. Half-maximal and maximal effects are obtained at 0.5 and 1 mM neomycin, respectively. This process is rapid (approximately 30 s), is independent of external Ca2+, and is associated with phosphatidic acid formation, implying that neomycin can activate histamine secretion by a mechanism similar to that utilized by other basic secretagogues of mast cells. Neomycin stimulates fourfold the GTPase activity of cholate-solubilized rat brain membranes in a PtX-inhibitable manner. In addition neomycin, as well as the basic secretagogues of mast cells, compound 48/80, and mastoparan, significantly reduce (by approximately 80%) the ADP ribosylation of PtX substrates present in rat brain membranes. Taken together these data suggest that neomycin can stimulate secretion from mast cells by directly activating G proteins that play a role in stimulus-secretion coupling. When internally applied, neomycin presumably stimulates secretion by activating a G protein that is located downstream to PLC. This G protein serves as a substrate for PtX.


[Kinetic model of micro-organism growth: the case of Xanthomonas campestris].
Microbial growth is studied and kinetic models to describe the process rate useful in the scale-up are proposed. The growth of Xanthomonas campestris NRRL B-1459, a bacterium producing xanthan, a major industrial gum, is studied. Experimental data are arranged by means of different methods, and linear and non-linear regression techniques are applied in several ways (i.e. fixing or not fixing the values of certain parameters) and they are compared. To obtain parameter values with statistical meaning, two parameters must be calculated (namely, the maximum specific growth rate and the maximum biomass concentration available) by means of a non-linear regression technique employing the logistic equation. The maximum specific growth rate is related to temperature by means of different equations, but that of Ratkowsky et al. is the most suitable for X. campestris growth. Studied variables present no tendency to error and the reproduction of experimental data is very good.


Systemic antisense therapeutics inhibiting DUX4 expression ameliorates FSHD-like pathology in an FSHD mouse model.
Aberrant expression of the double homeobox 4 (DUX4) gene in skeletal muscle causes muscle deterioration and weakness in Facioscapulohumeral muscular dystrophy (FSHD). Since the presence of a permissive pLAM1 polyadenylation signal is essential for stabilization of DUX4 mRNA and translation of DUX4 protein, disrupting the function of this structure can prevent expression of DUX4. We and others have shown promising results using antisense approaches to reduce DUX4 expression in vitro and in vivo following local intramuscular administration. Here we demonstrate that further development of the antisense chemistries enhances in vitro antisense efficacy. The optimal chemistry was conjugated to a cell-penetrating moiety and was systemically administered into the tamoxifen-inducible Cre-driver FLExDUX4 double-transgenic mouse model of FSHD. After four weekly treatments, mRNA quantities of DUX4 and target genes were reduced by 50% that led to 12% amelioration in muscle atrophy, 52% improvement in in situ muscle strength, 17% reduction in muscle fibrosis and prevention of shift in the myofiber type profile. Systemic DUX4 inhibition also significantly improved the locomotor activity and reduced the fatigue level by 22%. Our data demonstrate that the optimized antisense approach has potential of being further developed as a therapeutic strategy for FSHD.


Solanesol extraction from tobacco leaves by Flash chromatography based on molecularly imprinted polymers.
A novel solanesol extraction method based on molecularly imprinted polymer (MIP) as the Flash chromatography stationary phase was established and evaluated. Spherical MIP particles in a size range of 250-350 μm (d (0.5)=320 μm) for solanesol were synthesized by suspension polymerization, with imprinting factor of 3.9. The MIP particles (5.5 g) were packed in common Teflon column as the stationary phase while the sample solution and elution solvent were confirmed as methanol and methanol/acetic acid solution (80/20, v/v), loading at 4 ml/min and eluting 8 ml/min, respectively. Under the optimal chromatographic conditions, the adsorption capacity of the MIP-Flash column was determined as 107.3 μmol/g, and in each process, 370.8 mg purified solanesol (98.4%) could be obtained from the extract (20 mM, 40 ml) of tobacco leaves (14.7 g), and the yield of solanesol was 2.5% of the dry weight of tobacco leaves. The results reported here confirm the feasibility to extract highly purified active ingredients directly from natural products on a large scale by MIP-Flash chromatography.


Keys to cultural understanding.
Figures of speech are tangible manifestations of deeply rooted modes of perception and conceptualization. They represent categories or models for interpreting the universe-natural and supernatural, and material and non-material phenomena. These categories or models are reflected in all aspects of culture and are fundamentally determined by culture. They should not be considered universal but, rather, extremely relative and highly variable. Some students of language and culture, such as Whorf, would consider figures of speech not to be the most important organizing categories and would give precedence to grammatical constructions-that is, subject-predicate division or verb tenses. The use of figures of speech, however, is in some ways more easily investigated than grammatical categories, and their analysis can provide both unique and corroborative insights into various aspects of a culture, as has been demonstrated here with Palauan social organization.


Assessment of the Impact of Sheep and Goat Pox Lesions on Skin Quality in Selected Ware Houses of Central Ethiopia.
The study was performed from January 2016 to May 2017 with the aim of identifying the impact of sheep and goat pox in skin quality in selected localities of central Ethiopia. A total of 1360 fresh, salted and dried skins were examined and graded. Pox lesion positive skins were examined by PCR to identify the agent. The prevalence of sheep and goat in the study areas was 4.022%. From a total of 86 rejected skins, a large number of skins were in the rejected category (2.78%). There were highly statistically significant associations (p < 0.05) between sheep and goat pox and species and study areas. However, there were no statically significant associations (p > 0.05) between skin size and sheep and pox. Molecular diagnosis of the case revealed that goat pox virus was responsible for the lesion. Goat pox virus is the main cause of skin rejection and the factor that causes downgrading of skin.


Liquid chromatographic determination of residual nitrite/nitrate in foods: NMKL collaborative study.
Nitrite and nitrate are used as additives in the food industry to provide color and taste and to control undesirable gas and flavor production by anaerobic bacteria by virtue of their antimicrobial properties. The analytical method that has been widely used to determine nitrite and nitrate involves the use of toxic cadmium. In response to a request from the Nordic Committee on Food Analysis, a study was performed to obtain an alternative chromatographic method to determine residual nitrite and nitrate in meat products. The study was done in 3 stages: (1) comparative evaluation of the performance of 3 liquid chromatographic methods, (2) internal validation of the selected ion chromatographic method, and (3) a collaborative study in which 17 laboratories from European countries participated. Furthermore, the applicability of the method to matrixes other than meat and meat products was demonstrated. The results of the collaborative study show that the European Prestandard prENV 12014-4 is well suited for the determination of nitrite and nitrate in different foods (e.g., meat products, vegetables, baby food, and cheese). The limits of detection for nitrite and nitrate ions are 1 and 10 mg/kg, respectively. Recoveries of residual nitrite/nitrate ranged from 96 to 108%. Repeatability and reproducibility were satisfactory.


Induction of IgG by lipid A in the newborn mouse.
IgG of paternal allotype first becomes detectable in the serum of (BALB/c x C57BL/6)F(1) mice between day 12 and 14 after birth and reaches adult levels at an age of 5 wk. Since in mice there is a transfer of maternal IgG molecules through the placenta and via milk, F(1) heterozygous at the allotype locus were used and the concentrations of IgG with paternal allotype were measured. This was done by a sensitive method capable of detecting IgG concentrations as low as 5 x 10(-4) of normal adult serum levels. It is based on the quantitative inhibition of allotype-specific facilitation of hemolysis. When lipid A or Salmonella bacteria were injected into neonatal mice, a stimulation of IgG synthesis was observed. Thus IgG levels were enhanced 10-30-fold compared to the nontreated mice. No increase in IgG levels was obtained in adult mice after treatment with lipid A. Whether the newborns were injected at birth, on day 2, 4, or 7, IgG was first demonstrable in the treated mice at an age of 6-11 days. The increase in IgG levels was not paralleled by a demonstrable antibody activity against lipid A, SRBC, and LPS. Thus the bulk of newly induced IgG is probably a statistical distribution of different specificities.


Agriculture in West Africa in the Twenty-First Century: Climate Change and Impacts Scenarios, and Potential for Adaptation.
West Africa is known to be particularly vulnerable to climate change due to high climate variability, high reliance on rain-fed agriculture, and limited economic and institutional capacity to respond to climate variability and change. In this context, better knowledge of how climate will change in West Africa and how such changes will impact crop productivity is crucial to inform policies that may counteract the adverse effects. This review paper provides a comprehensive overview of climate change impacts on agriculture in West Africa based on the recent scientific literature. West Africa is nowadays experiencing a rapid climate change, characterized by a widespread warming, a recovery of the monsoonal precipitation, and an increase in the occurrence of climate extremes. The observed climate tendencies are also projected to continue in the twenty-first century under moderate and high emission scenarios, although large uncertainties still affect simulations of the future West African climate, especially regarding the summer precipitation. However, despite diverging future projections of the monsoonal rainfall, which is essential for rain-fed agriculture, a robust evidence of yield loss in West Africa emerges. This yield loss is mainly driven by increased mean temperature while potential wetter or drier conditions as well as elevated CO2 concentrations can modulate this effect. Potential for adaptation is illustrated for major crops in West Africa through a selection of studies based on process-based crop models to adjust cropping systems (change in varieties, sowing dates and density, irrigation, fertilizer management) to future climate. Results of the cited studies are crop and region specific and no clear conclusions can be made regarding the most effective adaptation options. Further efforts are needed to improve modeling of the monsoon system and to better quantify the uncertainty in its changes under a warmer climate, in the response of the crops to such changes and in the potential for adaptation.


Baseline Gut Metagenomic Functional Gene Signature Associated with Variable Weight Loss Responses following a Healthy Lifestyle Intervention in Humans.
Recent human feeding studies have shown how the baseline taxonomic composition of the gut microbiome can determine responses to weight loss interventions. However, the functional determinants underlying this phenomenon remain unclear. We report a weight loss response analysis on a cohort of 105 individuals selected from a larger population enrolled in a commercial wellness program, which included healthy lifestyle coaching. Each individual in the cohort had baseline blood metabolomics, blood proteomics, clinical labs, dietary questionnaires, stool 16S rRNA gene sequencing data, and follow-up data on weight change. We generated additional targeted proteomics data on obesity-associated proteins in blood before and after intervention, along with baseline stool metagenomic data, for a subset of 25 individuals who showed the most extreme weight change phenotypes. We built regression models to identify baseline blood, stool, and dietary features associated with weight loss, independent of age, sex, and baseline body mass index (BMI). Many features were independently associated with baseline BMI, but few were independently associated with weight loss. Baseline diet was not associated with weight loss, and only one blood analyte was associated with changes in weight. However, 31 baseline stool metagenomic functional features, including complex polysaccharide and protein degradation genes, stress-response genes, respiration-related genes, and cell wall synthesis genes, along with gut bacterial replication rates, were associated with weight loss responses after controlling for age, sex, and baseline BMI. Together, these results provide a set of compelling hypotheses for how commensal gut microbiota influence weight loss outcomes in humans. IMPORTANCE Recent human feeding studies have shown how the baseline taxonomic composition of the gut microbiome can determine responses to dietary interventions, but the exact functional determinants underlying this phenomenon remain unclear. In this study, we set out to better understand interactions between baseline BMI, metabolic health, diet, gut microbiome functional profiles, and subsequent weight changes in a human cohort that underwent a healthy lifestyle intervention. Overall, our results suggest that the microbiota may influence host weight loss responses through variable bacterial growth rates, dietary energy harvest efficiency, and immunomodulation.