Pneumococcal bacteriology after pneumococcal otitis media with special reference to pneumococcal antigens.
Fifty-four ears with evidence of pneumococcus (Pn) in the first acute otitis media (AOM) in 38 infants and with prolongation or recurrence of the MEF during the follow-up were observed for 7-22 months for the presence of Pn by culture or of pneumococcal antigen (Pn-ag) by counterimmunoelectrophoresis or latex agglutination methods in their MEFs. During the first three 1-month observation periods, Pn and/or Pn-ags were detected in 24% to 9% of these ears, always of the initial type/group. Later on new Pn types/groups appeared also. In two of the 9 MEFs persisting for greater than or equal to 3 months, initial Pn-ag, with culturable Pn, was repeatedly found but not for longer than 5 months. Of the 12 ears resulting in secretory otitis media (SOM) only one showed initial Pn-ag (and Pn) in the MEF of SOM. Pneumococcal type/group pattern associated with prolongation or recurrence of infection did not differ from that of initial AOM. In another series of 151 SOM ears in 97 children, Pn-ags were detected in 7 MEFs. Four of them grew Pn, each of the corresponding group. Our studies suggest that the persistence of Pn-ags in the middle ear after AOM is limited and their occurrence in the MEFs of SOM is rare. Thus, the role of the persistence of Pn-ags in prolonged, recurrent or secretory otitis media seems questionable.


The effect of family integrated care on the prognosis of premature infants.
The purpose of this study was to investigate the effect of family integrated care (FICare) on the prognosis of children hospitalized with preterm infants. Two hundred thirty preterm infants admitted to our hospital from January 2019 to April 2021 were enrolled in a prospective randomized study and divided into 115 cases in the intervention group and 115 cases in the control group according to the random number table method, and given the FICare and the conventional care, respectively. The duration of nasogastric tube retention, time to achieve total enteral nutrition, rate of weight gain, exclusive breastfeeding rate, length of hospital stay, growth and development, readmission rate, parental self-efficacy, family functioning and complications related to prematurity were compared between the two groups. Compared with the control group, the intervention group had shorter nasogastric tube retention time, shorter time to achieve total enteral nutrition, higher exclusive breastfeeding rate, shorter time of hospital stay and better growth rate. Before the intervention, there was no difference in parental self-efficacy and family functioning between the two groups; after the intervention, the intervention group had higher parental self-efficacy and higher ratings of family functioning, and the difference was statistically significant. Compared with the control group, the intervention group had a lower readmission rate and significantly lower incidence of infection and choking. The FICare can shorten the time of nasogastric tube retention, shorten time to achieve total enteral nutrition and hospital stay, increase the rate of exclusive breastfeeding and the rate of weight gain, finally improve the prognosis of preterm infants and have a positive effect on parents.


Crystal structures of methyl (E)-3-(2-chloro-phen-yl)-2-({2-[(E)-2-nitro-vin-yl]phen-oxy}meth-yl)acrylate and methyl (E)-2-({4-chloro-2-[(E)-2-nitro-vin-yl]phen-oxy}meth-yl)-3-(2-chloro-phen-yl)acrylate.
The title compounds, C19H16ClNO5, (I), and C19H15Cl2NO5, (II), both crystallize in the monoclinic space group P21/n. They differ essentially in the orientation of the methyl acetate group, with the C=O bond directed towards the NO2 group in (I) but away from it in (II). In compound (I), the mean plane of the methyl acrylate unit is planar, with a maximum deviation of 0.0044 (2) Å for the methyl C atom, while in (II) this deviation is 0.0147 Å. The inter-planar angles between the two aromatic rings are 74.87 (9) and 75.65 (2)° for compounds (I) and (II), respectively. In both compounds, the methyl acrylate and nitro-vinyl groups each adopt an E conformation about the C=C bond. In the crystal of (I), mol-ecules are linked by C-H⋯O hydrogen bonds forming chains along the b axis. The chains are linked via C-H⋯Cl hydrogen bonds, forming sheets parallel to the ab plane. The sheets are linked via C-H⋯π inter-actions, forming a three-dimensional structure. In the crystal of (II), mol-ecules are linked by pairs of C-H⋯O hydrogen bonds, forming inversion dimers with an R 2 (2)(30) ring motif. The dimers are linked via C-H⋯O hydrogen bonds, forming sheets parallel to the ac plane and enclosing R 4 (4)(28) ring motifs. The sheets are linked via parallel slipped π-π inter-actions (inter-centroid distances are both ca 3.86 Å), forming a three-dimensional structure.


Specific Inhibition of Tumor Growth by T Cell Receptor-Drug Conjugates Targeting Intracellular Cancer-Testis Antigen NY-ESO-1/LAGE-1.
Despite the significant therapeutic advances in T-cell immunotherapy, many malignancies remain unresponsive, which might be because of the negative regulation of T cells by the tumor microenvironment (TME). T cells discriminate tumor cells and normal cells through T-cell receptors (TCRs); therefore, we generated a novel type of TCR-drug conjugates (TDCs) by referring antibody-drug conjugations (ADCs) to overcome the effects of the TME on T cells while preserving the specificity of TCR for tumor recognition. We selected HLA-A2/NY-ESO-1157-165 (peptide NY-ESO-1157-165 in complex with human leukocyte antigen serotype HLA-A*02:01) as the antigen and the antigen-specific TCR (1G4113) as the carrier. By sortase A-mediated ligation, we obtained three NY-TCR-vcMMAEs and further studied their properties, antitumor activity, and toxicity in vitro and in vivo. We found that all the NY-TCR-vcMMAEs had high endocytosis efficiency and specifically killed HLA-A2/NY-ESO-1157-165 positive tumor cells. In xenograft models, one of the TDCs, NY-TCR-2M, was effectively and specifically distributed into tumor tissues and inhibited tumor growth without inducing obvious toxicity. Our results demonstrated that TCRs can be carriers of toxic payloads and that the TDCs thus formed can specifically inhibit tumor growth, neglecting the immune microenvironment.


The trouble with reporting and utilization of workplace violence data in health care.
The study aimed to evaluate the reporting, monitoring and use of workplace violence data in Victorian health services. Surveillance of workplace violence is important in understanding the circumstances in which workplace violence occurs and development of relevant and appropriate prevention and intervention strategies. A descriptive exploratory approach was used. Fifteen staff from occupational health and safety, quality and safety, and nurse unit managers, from five major metropolitan health services were interviewed. Recorded interviews were transcribed verbatim and thematically analysed. Three themes were identified: (a) "under-reporting of workplace violence," (b) "inconsistent guidance" caused subjective and variable data coding and (c) "application of data" described how health services used the data available to them, to inform the development and implementation of systems designed to prevent workplace violence. Improved reporting systems may increase consistency in reporting, enable data sharing across organisations and assist in planning of prevention strategies. Staff should be encouraged to complete incident reports for each episode of workplace violence. Incident reporting systems must be simplified to reduce the burden of reporting. Nurse managers should advocate for the sharing of health service workplace violence data, to enable improved prevention across all services.


Effect of the Asn52----Ile mutation on the redox potential of yeast cytochrome c. Theory and experiment.
Theoretical methods for correlation of sequence changes and redox potential of electron transport proteins are examined using the Asn52----Ile mutation in cytochrome c as a test case. The first approach uses the protein dipoles Langevin dipoles (PDLD) method and the high resolution X-ray structures of the native and the mutant proteins. This approach is found to give reliable results where all the solvent molecules are represented by Langevin dipoles and also when some bound water molecules are represented explicitly. A free energy perturbation method is also found to give reasonable results but at the expense of much more computer time. Finally, an approach that generates mutant structures from the native structure by molecular dynamics simulation and then uses these configurations in PDLD calculations is found to give a reasonable estimate of the effect of the mutation on the corresponding redox potential. The encouraging results obtained here and in a preliminary test case of the Phe82----Ser mutation indicates that the present strategies can provide a useful tool for structure-redox and sequence-redox correlation in proteins.


A Comparative Pharmacokinetic Study of Fexuprazan 10 mg: Demonstrating Bioequivalence with the Reference Formulation and Evaluating Steady State.
Fexuprazan is a potassium-competitive acid blocker approved for treating gastric-acid-related diseases. Although the effectiveness of the recent formulation fexuprazan 10 mg has been demonstrated in Phase 3 clinical trials, data on the pharmacokinetics (PKs) of administering fexuprazan 10 mg twice daily at a 12 h interval are lacking. Moreover, it is imperative to ensure the bioequivalence of the new formulation with the previously approved 40 mg formulation. This study evaluated the pharmacokinetics (PKs) of the single- and multiple-dose oral administration of fexuprazan 10 mg tablets in healthy participants (Part 1) and investigated their bioequivalence with 40 mg tablets (Part 2). Part 1 comprised a single- and multiple-dose, one-sequence, two-period design and eight participants, while Part 2 comprised a single-dose, 2 × 2 crossover design and 24 participants. In Part 1, in Periods 1 and 2, participants received single and multiple doses (twice daily) of fexuprazan 10 mg, respectively. The maximum plasma concentration (Cmax) area under the concentration-time curve from 0 to 12 h (AUC0-12h) of the multiple-dose participants was approximately double that of the single-dose participants. In Part 2, the geometric mean ratios (90% confidence intervals) for Cmax and AUC from zero to the time of the last quantifiable concentration (AUClast) of the use of four fexuprazan 10 mg tablets to those of one fexuprazan 40 mg tablet were 1.0290 (0.9352-1.1321) and 1.0290 (0.9476-1.1174), respectively, meeting the bioequivalence criteria. Favorable PKs were observed after single and multiple administrations of one fexuprazan 10 mg tablet, and four fexuprazan 10 mg tablets were pharmacokinetically equivalent to one fexuprazan 40 mg tablet.


Cluster formation as a measure of interpretability in multiple testing.
Multiple test procedures are usually compared on various aspects of error control and power. Power is measured as some function of the number of false hypotheses correctly identified as false. However, given equal numbers of rejected false hypotheses, the pattern of rejections, i.e. the particular set of false hypotheses identified, may be crucial in interpreting the results for potential application.In an important area of application, comparisons among a set of treatments based on random samples from populations, two different approaches, cluster analysis and model selection, deal implicitly with such patterns, while traditional multiple testing procedures generally focus on the outcomes of subset and pairwise equality hypothesis tests, without considering the overall pattern of results in comparing methods. An important feature involving the pattern of rejections is their relevance for dividing the treatments into distinct subsets based on some parameter of interest, for example their means. This paper introduces some new measures relating to the potential of methods for achieving such divisions. Following Hartley (1955), sets of treatments with equal parameter values will be called clusters. Because it is necessary to distinguish between clusters in the populations and clustering in sample outcomes, the population clusters will be referred to as P -clusters; any related concepts defined in terms of the sample outcome will be referred to with the prefix outcome. Outcomes of multiple comparison procedures will be studied in terms of their probabilities of leading to separation of treatments into outcome clusters, with various measures relating to the number of such outcome clusters and the proportion of true vs. false outcome clusters. The definitions of true and false outcome clusters and related concepts, and the approach taken here, is in the tradition of hypothesis testing with attention to overall error control and power, but with added consideration of cluster separation potential.The pattern approach will be illustrated by comparing two methods with apparent FDR control but with different ways of ordering outcomes for potential significance: The original Benjamini-Hochberg (1995) procedure (BH), and the Newman-Keuls (Newman, 1939; Keuls, 1952) procedure (NK).


The fate of injected trigger fingers.
Patients who were scheduled for surgical release of their trigger fingers underwent an injection of the involved tendon sheath prior to surgery. In thirty-six patients the injection of methylene blue was undertaken in a proximal-distal direction and in forty-three the direction of the injection was reversed. The success rate of the injections was 61 per cent. in the proximal distal group and 37 per cent in the second group. There was no significant statistical difference with regard to age, but duration of the disorder and mode of injection regarding the different fingers did have statistical significance.


Complementary expression and repulsive signaling suggest that EphB receptors and ephrin-B ligands control cell positioning in the gastric epithelium.
Eph receptors and ephrin ligands are membrane-bound cell-cell communication molecules with well-defined roles in development. However, their expression and functions in the gastric epithelium are virtually unknown. We detected several EphB receptors and ephrin-Bs in the gastric corpus mucosa of the adult rodent stomach by RT-PCR amplification. Immunostaining showed complementary expression patterns, with EphB receptors preferentially expressed in the deeper regions and ephrin-Bs in the superficial regions of the gastric units. EphB1, EphB2 and EphB3 are expressed in mucous neck, chief and parietal cells, respectively. In contrast, ephrin-B1 is in pit cells and proliferating cells of the isthmus. In a mouse ulcer model, EphB2 expression was upregulated in the regenerating epithelium and expanded into the isthmus. Thus, EphB/ephrin-B signaling likely occurs preferentially in the isthmus, where receptor-ligand overlap is highest. We show that EphB signaling in primary gastric epithelial cells promotes cell retraction and repulsion at least in part through RhoA activation. Based on these findings, we propose that the EphB-positive progeny of gastric stem cells migrates from the isthmus toward the bottom of the gastric glands due to repulsive signals arising from contact with ephrin-Bs, which are preferentially expressed in the more superficial regions of the isthmus and gastric pits.


Fifty-four Shigella sonnei colicin types and their typing by specific indicator strains.
Fifty-four S. sonnei colicin types and 92 indicator strains used for their determination are listed. Most of the indicators were prepared by conjugational transfer of Col factors from shigellae to the recipient strains of E. coli K13 HfrR nalr and E. coli K12 ROW or by selection of resistant mutants of these strains or by combination of both methods. Ten indicators are S. sonnei strains. The indicator strains are suitable for E. coli colicin typing.


Performance and granulation in an upflow anaerobic sludge blanket (UASB) reactor treating saline sulfate wastewater.
An upflow anaerobic sludge blanket reactor was employed to treat saline sulfate wastewater. Mesophilic operation (35 ± 0.5 °C) was performed with hydraulic retention time fixed at 16 h. When the salinity was 28 g L(-1), the chemical oxygen demand and sulfate removal efficiencies were 52 and 67 %, respectively. The salinity effect on sulfate removal was less than that on organics removal. The methane productions were 887 and 329 cm(3) L(-1) corresponding to the NaCl concentrations of 12 and 28 g L(-1), respectively. High salinity could stimulate microbes to produce more extracellular polymeric substances (EPSs) and granulation could be performed better. Besides, with the high saline surroundings, a great deal of Na(+) compressed the colloidal electrical double-layer, neutralized the negative charge of the sludge particles and decreased their electrostatic repulsion. The repulsion barrier disappeared and coagulation took place. The maximum size of granules was 5 mm, which resulted from the coupled triggering forces of high EPSs and Na(+) contents. Sulfate-reducing bacteria (SRB) were dominant in the high saline surroundings while the methane-producing archaea dominated in the low saline surroundings. The SRB were affected least by the salinity.


Serum beta human chorionic gonadotropin levels and preeclampsia.
Preeclampsia is one of the most common complications of pregnancy. It is a trophoblastic disorder. Since human chorionic gonadotropin (hCG) is secreted by trophoblast, the purpose of the study was to determine the levels of beta (hCG) in preeclampsia and normal cases. This study was conducted on 40 term pregnant women with preeclampsia (case group) and 40 normal pregnant cases (control group) in the Department of Obstetrics and Gynecology, Medical University, Babol, Iran, from 2004 to 2005. Serum beta-hCG in all cases were measured by radioimmunoassay. The mean beta-hCG level in preeclampsia (mild and severe) was compared with normal cases. The maternal serum, beta-hCG level in patients with preeclampsia (39840 +/- 24630 IU/L) was higher than in the control group (27460 +/- 25862 IU/L) (p=0.031). In mild preeclampsia (34 cases), the mean serum beta-hCG level was 31991 +/- 16758 IU/L while in severe preeclampsia (6 cases) 84312 +/- 9257 IU/L (p<0.0001). The mean serum beta-hCG level in mild and severe preeclampsia was higher compared to the normal cases. The results of this study show that the levels of beta-hCG in severe form of preeclampsia is higher compared to the milder ones.


Laparoscopic duplication of the uterosacral ligaments following hysterectomy for stage III-IV apical pelvic organ prolapse.
Different techniques have been proposed over the last decades to avoid the vaginal vault prolapse following hysterectomy for severe (stage III-IV) apical pelvic organ prolapse. In this scenario, the laparoscopic duplication of the uterosacral ligaments to the vaginal apex might represent a simple alternative procedure, associated with low morbidity and optimal surgical outcomes. In this paper, we present the preliminary results of 25 consecutive patients, who underwent total laparoscopic hysterectomy followed by uterosacral ligament duplication for stage III-IV apical pelvic organ prolapse. A detailed description of the surgical procedure is also provided.


Assessing the implementation of a patient navigation intervention for colonoscopy screening.
A recent study demonstrated the effectiveness of the New Hampshire Colorectal Cancer Screening Program's (NHCRCSP) patient navigation (PN) program. The PN intervention was delivered by telephone with navigators following a rigorous, six-topic protocol to support low-income patients to complete colonoscopy screening. We applied the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework to examine implementation processes and consider potential scalability of this intervention. A mixed-methods evaluation study was conducted including 1) a quasi-experimental, retrospective, comparison group study examining program effectiveness, 2) secondary analysis of NHCRCSP program data, and 3) a case study. Data for all navigated patients scheduled and notified of their colonoscopy test date between July 1, 2012 and September 30, 2013 (N = 443) were analyzed. Researchers were provided in-depth call details for 50 patients randomly selected from the group of 443. The case study included review of program documents, observations of navigators, and interviews with 27 individuals including staff, patients, and other stakeholders. Program reach was state-wide, with navigators serving patients from across the state. The program successfully recruited patients from the intended priority population who met the established age, income, and insurance eligibility guidelines. Analysis of the 443 NHCRCSP patients navigated during the study period demonstrated effectiveness with 97.3% completing colonoscopy, zero missed appointments (no-shows), and 0.7% late cancellations. Trained and supervised nurse navigators spent an average of 124.3 min delivering the six-topic PN protocol to patients. Navigators benefited from a real-time data system that allowed for patient tracking, communication across team members, and documentation of service delivery. Evaluators identified several factors supporting program maintenance including consistent funding support from CDC, a strong program infrastructure, and partnerships. Factors supporting implementation included funding for colonoscopies, use of registered nurses, a clinical champion, strong partnerships with primary care and endoscopy sites, fidelity to the PN protocol, significant intervention dose, and a real-time data system. Further study is needed to assess scalability to other locations.


Effect of a disulfide bond on mevalonate kinase.
Mevalonate kinase is one of ATP-dependent enzymes in the mevalonate pathway and catalyzes the phosphorylation of mevalonate to form mevalonate 5-phosphate. In animal cells, it plays a key role in regulating biosynthesis of cholesterol, while in microorganisms and plants, it is involved in the biosynthesis of isoprenoid derivatives that are one of the largest groups of natural products. Crystal structure and sequence alignment show that a unique disulfide bond exists in mevalonate kinase of thermostable species Methanococcus jannaschii, but not in rat mevalonate kinase. In the present study, we investigated the effect of the disulfide bond in M. jannaschii mevalonate kinase and an engineered disulfide bond in rat mevalonate kinase mutant A141C on the properties of enzymes through characterization of their wild-type and variant enzymes. Our result suggests that the Cys107-Cys281 disulfide bond is important for maintaining the conformation and the thermal activity of M. jannaschii mevalonate kinase. Other interactions could also have contributions. The thiol-titration and fluorescence experiment further indicate that rat mevalonate kinase A141C variant enzyme has a new disulfide bond, which makes the variant protein enhance its thermal activity and resist to urea denaturation.


Decoy receptor 3 (DcR3) induces osteoclast formation from monocyte/macrophage lineage precursor cells.
Recent evidence indicates that the decoy receptor 3 (DcR3) of the TNF receptor superfamily, which initially though prevents cytokine responses of FasL, LIGHT and TL1A by binding and neutralization, can modulate monocyte function through reverse signaling. We show in this work that DcR3 can induce osteoclast formation from human monocytes, murine RAW264.7 macrophages, and bone marrow cells. DcR3-differentiated cells exhibit characteristics unique for osteoclasts, including polynuclear giant morphology, bone resorption, TRAP, CD51/61, and MMP-9 expression. Consistent with the abrogation of osteoclastogenic effect of DcR3 by TNFR-Fc, DcR3 treatment can induce osteoclastogenic cytokine TNF-alpha release through ERK and p38 MAPK signaling pathways. We conclude that DcR3 via coupling reverse signaling of ERK and p38 MAPK and stimulating TNF-alpha synthesis is a critical regulator of osteoclast formation. This action of DcR3 might play an important role in significant osteoclastic activity in osteolytic bone metastases.


Self-reported neck and shoulder pain in adolescents is associated with episodic and chronic migraine.
The aim of this study was to verify the association between self-reported neck/shoulder pain and migraine and to compare findings of chronic and episodic migraine in adolescents. In this cross-sectional study, 601 secondary-school students filled in questionnaires about headache appearance, type and frequency, neck and shoulder pain and lifestyle factors. The adjusted strength of the association between reported neck and shoulder pain and migraine (assessed in multinomial regression models) increased with the frequency of migraine: less than once a week (OR = 1.40; 95% CI = (0.85-2.30)), weekly (OR = 2.14; 95% CI = (1.42-3.24)), and at least 15 days/month (OR = 7.27; 95% CI = (3.42-15.44)). In adolescents the association between self-reported neck and shoulder pain and migraine is most pronounced in migraine with a high attack frequency.


Optimal timing and indications for cholecystectomy in cardiac transplant patients.
Cardiac transplant is performed with increasing frequency as the treatment for end-stage cardiac disease. Although cholelithiasis is more frequent in both pretransplant and posttransplant patients, no standard management approach exists. Because many such patients are cared for outside the transplant center, it is important that general surgeons develop an appropriate strategy to manage this entity. We present our experience with 11 patients from our institution who underwent cholecystectomy before or after cardiac transplantation. In addition, we have reviewed the 76 reported cases of cholecystectomy performed in precardiac or postcardiac transplant patients from centers throughout the world. Any procedure in this patient group requires critical consideration in regard to the timing and type of procedure. Pretransplant patients are well recognized cardiac risks, and posttransplant immunosuppressed patients are at considerable risk for septic complications. Six patients underwent cholecystectomy prior to heart transplant. Five were performed laparoscopically, one as an open procedure. We also report five laparoscopic cholecystectomies in patients after cardiac transplant. One patient in the pretransplant group died 7 days after surgery from an uncontrollable arrhythmia. There were no hemodynamic or septic complications in either group. Current summated experience (87 cases) indicates that the mortality rate for urgent cholecystectomy in the posttransplant group is at least 36%. Because the first presentation of gallstones in this population is often acute cholecystitis, asymptomatic calculi cannot be considered benign. Elective cholecystectomy, laparoscopic or open, is tolerated well both before and after transplant. Given these facts, it seems reasonable to recommend pretransplant screening and posttransplant surveillance for gallstones.(ABSTRACT TRUNCATED AT 250 WORDS)


Maternal serum alpha fetoprotein in monozygotic and dizygotic twin pregnancies.
Maternal serum alpha-fetoprotein (MSAFP) values in the second trimester have been related to pregnancy outcome for 100 normal twin pairs, 42 monozygous (MZ) and 58 dizygous (DZ), liveborn after 28 weeks gestation. The median MSAFP value was 1.9 multiples of the median value (MOM) for uncomplicated singleton pregnancies. Both very low and very high MSAFP values were associated with twins of low birthweight. MSAFP values were higher in MZ than DZ twin pregnancies particularly those with dizygotes of like-sex. This effect was even more marked when only dichorionic like-sex twin pairs were compared.


The discovery of the nature of ferredoxin in photosystems: a recollection.
I describe here my recollection of the story of the discovery of the nature of ferredoxin in photosystems that began in 1965: this story involved the EPR measurements by a young physicist J.H.M. Thornley, using samples provided by J.F. Gibson and D. Hall, and in collaboration with F.R. Whatley.


[Nutritional support with parenteral nutrition. Course and associated complications].
Parenteral nutrition (PN) is an integral part of medical management of patients who do not have a functioning or accessible gastrointestinal tract. This paper discusses the clinical characteristics of patients receiving PN in a 420-bed hospital from 2009 to 2011. In addition, nutritional parameters were assessed at the start and end of PN and associated complications were analyzed. retrospective, observational study of PN episodes in adults conducted at the Nutrition Unit of Hospital Universitario de Guadalajara. Variables collected included epidemiological and clinical data, number and type of routes used, anthropometric data, analytical data, number of days on PN, reason for withdrawal, caloric provision, prevalence of phlebitis, metabolic complications (hypertriglyceridemia, abnormal liver function tests, hyperglycemia, and refeeding syndrome), and prevalence of bacteremia associated with central venous catheter (BAC). There were 312 episodes of PN. The immediate indication was postoperative ileus in 53.8% of the episodes. There was a statistically significant improvement in all analytical parameters assessed (albumin, prealbumin, retinol binding protein, transferrin, cholesterol, and lymphocytes). Caloric provision (kcal per kg) was 25.1±6.6. No metabolic complication occurred in 16.3% of the episodes, and hyperglycemia was the most common complication (79.8%). There were 10 cases of phlebitis (32.2%) and 30 episodes of BAC (8.7%). Bacteriemia rate was 8.1 per 1000 days of PN. Although PN is an effective nutritional support technique, it is associated with complications of varying severity. Use of PN should therefore comply with the instructions accepted in the main clinical practice guidelines and requires careful monitoring by experienced professionals.


Effect of oral vitamin A supplementation on host immune response to infectious bronchitis virus infection in specific pathogen-free chicken.
Vitamin A is a fat-soluble vitamin that is a crucial mediator of the immune system. In this study, we evaluated the effect of oral vitamin A supplementation on host immune responses to infectious bronchitis virus (IBV) infection in chickens. Forty 1-day-old specific pathogen-free (SPF) chickens were fed a basal diet and randomly divided into 2 groups (n = 20 birds per group). Chickens in the experimental group were treated orally with vitamin A (dissolved in 0.1 mL soybean oil, at a dose of 8,000 IU per kg diet) daily. Birds in the control group were orally administered 0.1 mL soybean oil without vitamin A until 21 d of age. On d 21 after birth, all chickens were infected with 0.1 mL of 106.5 50% median embryo infectious dose of a pathogenic IBV strain (CK/CH/LDL/091022) by intraocular and intranasal routes. The results demonstrated that oral vitamin A supplementation did not affect the clinical course of disease and growth performance of SPF chickens. However, vitamin A supplementation increased the IBV-specific IgG serum levels and decreased the viral load in some tissues of IBV-infected chickens. In addition, the results demonstrated that vitamin A supplementation decreased the expression levels of most immune-related molecules in some tissues of IBV-infected chickens. Vitamin A supplementation decreased the mRNA expression levels of some avian β-defensins (AvBD2, 3, 6, 7, 11, and 13) and increased the expression levels of AvBD9 and AvBD12 in some tissues of IBV-infected chickens. Similarly, vitamin A supplementation decreased the mRNA expression levels of some cytokines (interferon-γ, interleukin-1β [IL-1β], and IL-6) and increased the mRNA expression levels of IL-2 in some tissues of IBV-infected chickens. Furthermore, vitamin A supplementation decreased the mRNA expression levels of myeloid differentiation primary response protein 88, nuclear factor-κB p65, toll-like receptor 3, toll-like receptor 7, and CD4. In summary, the present study suggests that vitamin A supplementation enhances the immune function of SPF chickens against IBV infection by inhibiting viral replication, increasing the IBV-specific antibody titer, and suppressing the excessive inflammatory responses to IBV infection.


Curiosity to kill the KAT (kynurenine aminotransferase): structural insights into brain kynurenic acid synthesis.
Kynurenine aminotransferases are pyridoxal-5'-phosphate-dependent enzymes, which catalyze the synthesis of kynurenic acid, a highly neuroactive metabolite whose impairment is associated with a number of severe brain disorders. Crystallographic studies of these enzymes from different organisms, including humans, have revealed distinctive structural traits of type I and type II kynurenine aminotransferases. A striking difference concerns domain swapping of the N-terminal regions, which play equivalent key functional roles in both an unswapped and swapped structure in type I and type II isozymes. Different conformational changes during catalysis create divergent active sites in the two isozymes and affect substrate specificity. Structural investigations indicate intriguing evolutionary relationships and pave the way for the design of isozyme-specific inhibitors, which are of interest for the treatment of catastrophic brain diseases such as Alzheimer's disease and schizophrenia.


Incidence and factors associated with falls in independent ambulatory individuals with spinal cord injury: a 6-month prospective study.
Sensorimotor impairments following spinal cord injury (SCI) affect mobility and subsequently increase the risk of falls to patients. However, most of the fall data for these patients were retrospectively gathered. This study prospectively assessed falls and intrinsic factors associated with falls in 89 independent ambulatory individuals with SCI over the course of 6 months. In addition, functional ability between participants who did and did not fall was compared. Participants were interviewed and assessed for their baseline data and functional ability using the Timed "Up & Go" Test and the Six-Minute Walk Test. Then they were interviewed by telephone to complete a self-report questionnaire once per week to gather fall data for 6 months. A stepwise multiple logistic regression was utilized to determine the effects of demographics and SCI characteristics on occurrence of falls. The functional data between participants who fell and those who did not fall were compared using the Mann-Whitney U test. Thirty-five participants (39%) experienced at least 1 fall during 6 months (range=1-11). Two participants required medical attention due to patellar and sternum fractures after falling. Participants with an educational level of high school graduate or greater, an American Spinal Injury Association Impairment Scale C (AIS-C) classification, and a fear of falling (FOF) significantly increased their risk of falls approximately 4 times more than those who graduated primary education, had an AIS-D classification, and did not have FOF. Moreover, the functional abilities of participants who fell were significantly poorer than those who did not fall. The sample size was calculated based on the primary objective (incidence of falls), which may not be sufficient to clearly indicate factors associated with falls for the participants. More than one third of the independent ambulatory participants with SCI experienced at least 1 fall during the 6-month period of the study. The findings suggest the importance of functional improvement on the reduction of fall risk in these individuals.


[Congenital hypothyroidism].
Congenital hypothyroidism (CH) occurs in 1/3 500 newborn infants. Interest in newborn screening for CH has been widely demonstrated in most countries. It was introduced in France in the last 70's; by the measurement of serum TSH level from an eluate of whole blood collected on filter paper on 3 days of life. It allows earlier diagnosis and treatment preventing most of the serious sequelae of the disease such as postnatal neurological damage. Their neuropsychological evaluation has shown normal mental development in most cases. Although CH with eutopic gland (15% of the cases) has recently been recognized as associated with different molecular defect, the cause of thyroid agenesis (85% of the cases with athyreosis or ectopic gland) remains unknown. These latter forms are usually sporadic but familial cases are described.


Antibacterial and anticancer activity of ε-poly-L-lysine (ε-PL) produced by a marine Bacillus subtilis sp.
A marine Bacillus subtilis SDNS was isolated from sea water in Alexandria and identified using 16S rDNA sequence analysis. The bacterium produced a compound active against a number of gram negativeve bacteria. Moreover, the anticancer activity of this bacterium was tested against three different human cell lines (Hela S3, HepG2 and CaCo). The highest inhibition activity was recorded against Hela S3 cell line (77.2%), while almost no activity was recorded towards CaCo cell line. HPLC and TLC analyses supported evidence that Bacillus subtilis SDNS product is ε-poly-L-lysine. To achieve maximum production, Plackett-Burman experimental design was applied. A 1.5 fold increase was observed when Bacillus subtilis SDNS was grown in optimized medium composed of g/l: (NH(4))(2) SO(4), 15; K(2)HPO(4), 0.3; KH(2)PO(4), 2; MgSO(4) · 7 H(2)O, 1; ZnSO(4) · 7 H(2)O, 0; FeSO(4) · 7 H(2)O, 0.03; glucose, 25; yeast extract, 1, pH 6.8. Under optimized culture condition, a product value of 76.3 mg/l could be obtained. According to available literature, this is the first announcement for the production of ε-poly-L-lysine (ε-PL) by a member of genus Bacillus.


Review article: coagulation disorders in chronic liver disease.
The liver is the site for synthesis of the vast majority of proteins that play a central role in maintaining hemostasis, by participating in the regulation of coagulation and fibrinolysis. To summarize the available data on the impact of coagulation disorders in patients with chronic liver disease. Hepatocellular damage in patients with severe liver disease can lead to abnormalities in the production and function of coagulation and fibrinolytic factors, disrupting the balance between coagulation and anticoagulation systems. Hemostatic abnormalities (eg. impaired synthesis of clotting factors, heightened fibrinolysis, disseminated intravascular coagulation, thrombocytopenia, and platelet dysfunction) can increase the risk of bleeding in cirrhotic patients.


German S3 guideline: anal abscess.
The incidence of anal abscess is relatively high, and the condition is most common in young men. A systematic review of the literature was undertaken. This abscess usually originates in the proctodeal glands of the intersphincteric space. A distinction is made between subanodermal, intersphincteric, ischioanal, and supralevator abscesses. The patient history and clinical examination are diagnostically sufficient to establish the indication for surgery. Further examinations (endosonography, MRI) should be considered in recurrent abscesses or supralevator abscesses. The timing of the surgical intervention is primarily determined by the patient's symptoms, and acute abscess is generally an indication for emergency treatment. Anal abscesses are treated surgically. The type of access (transrectal or perianal) depends on the abscess location. The goal of surgery is thorough drainage of the focus of infection while preserving the sphincter muscles. The wound should be rinsed regularly (using tap water). The use of local antiseptics is associated with a risk of cytotoxicity. Antibiotic treatment is only necessary in exceptional cases. Intraoperative fistula exploration should be conducted with extreme care if at all; no requirement to detect fistula should be imposed. The risk of abscess recurrence or secondary fistula formation is low overall, but they can result from insufficient drainage. Primary fistulotomy should only be performed in case of superficial fistulas and by experienced surgeons. In case of unclear findings or high fistulas, repair should take place in a second procedure. In this clinical S3 guideline, instructions for diagnosis and treatment of anal abscess are described for the first time in Germany.


Serum-free conditioned medium of human diploid fibroblast cells contains an activity that stimulates prostacyclin production by cultured bovine aortic endothelial cells.
Serum-free culture medium conditioned by human diploid fibroblast cells stimulated prostacyclin production by cultured bovine aortic endothelial cells. Gel filtration chromatography using Sephacryl S-100HR revealed at least three peaks of prostacyclin-stimulating activity. This factor was relatively heat-stable, acid-labile, trypsin-sensitive and bound to heparin Sepharose CL-6B. This factor was completely inhibited by indomethacin.


Characterization of metalloproteinases, oxidative status and inflammation levels in the different stages of fibrosis in HCV patients.
This study was aimed at searching noninvasive markers of the transition from mild to severe fibrosis stage in HCV patients undergoing hepatic fibrosis. Thirty-three patients affected by chronic HCV vs. twenty healthy donors were evaluated for the serum levels of several circulating matrix metalloproteinases (MMPs), TRAIL and β-NGF by multiplex biometric ELISA based immunoassay and anti- and pro-oxidant status (d-ROMs, BAP and NO) using a Diacron automated method. HCV patients displayed increased expression levels of MMP-8, MMP-9, TRAIL and β-NGF, and an imbalance between pro- and antioxidant status, that contribute to liver fibrosis. Since the determination of these parameters represents a reliable and easily applicable method, these parameters are suggested as serum surrogate markers for HCV patients in the routine clinical practice.


Efficacy of a repeat testing protocol for cognitive fatigue assessment: a preliminary study in postconcussive syndrome participants.
A small but notable number of individuals who suffer a concussion report ongoing cognitive difficulties. This preliminary study investigated the efficacy of repetitive test application to discern cognitive impairment in those with ongoing symptoms. Participants (n = 17) with continuing self-reported symptoms following a concussion (∼9 months postinjury) were compared with 17 age group matched controls for working memory and word-list learning. Both groups performed similarly after the first trial for both assessments. However, in subsequent trials, the postconcussion group performed significantly worse than controls. While further studies to understand the mechanisms are warranted, data from this preliminary study suggest that a repetitive test application may be useful to discern cognitive fatigue in individuals who report ongoing concerns following a concussion.


Genome-wide association study signal at the 12q12 locus for Crohn's disease may represent associations with the MUC19 gene.
Genome-wide association studies (GWAS) in Crohn's disease (CD) have identified associations with single-nucleotide polymorphism (SNP) rs11175593 at chromosome 12q12. The MUC19 and LRRK2 genes reside close to the GWAS signal, but it is as yet unclear which of the 2 genes represent the CD susceptibility genes. We studied associations between nonsynonymous coding variants in the MUC19 (5) and LRRK2 (3) genes in a case-control sample comprising CD cases aged <18 years at diagnosis. The GWAS lead SNP rs11175593 was also investigated. Allelic, genotype, and haplotype associations were examined assuming different models of inheritance. A total of 530 cases and 600 controls were studied. The mean (±SD) age at diagnosis was 12.4 (±3.3). Most cases were male (57.4%). Most patients had ileocolonic disease location (48.8%) and inflammatory behavior at diagnosis (87.0%). Three MUC19 SNPs were nominally significantly associated with CD (rs11564245, Asp→His: P = 0.02; rs4768261, Ser→Phe: P = 0.0008; and rs2933353, Glu→Ala: P = 0.01). Associations with rs4768261 were maintained after corrections for multiple comparisons (permuted, P = 0.007). None of the LRRK2 SNPs were associated with CD. Haplotype analysis supported the single SNP associations noted with the MUC19 gene. GWAS signal at chromosome 12q12 for CD may represent associations with the MUC19 gene.


[External carotid arteriography in Horton's disease. A report on 11 observations (author's transl)].
Highly selective angiography was used to study eleven cases of Horton's arteritis. The results showed the presence of segmental vascular abnormalities which, though mainly affecting the temporal artery region, were also present in that of the internal maxillary artery. This examination procedure can be of great value by assisting the surgeon in his choice of biopsy sample, which is essential for diagnostic purposes.


Transcriptional regulation of N-acetylglutamate synthase.
The urea cycle converts toxic ammonia to urea within the liver of mammals. At least 6 enzymes are required for ureagenesis, which correlates with dietary protein intake. The transcription of urea cycle genes is, at least in part, regulated by glucocorticoid and glucagon hormone signaling pathways. N-acetylglutamate synthase (NAGS) produces a unique cofactor, N-acetylglutamate (NAG), that is essential for the catalytic function of the first and rate-limiting enzyme of ureagenesis, carbamyl phosphate synthetase 1 (CPS1). However, despite the important role of NAGS in ammonia removal, little is known about the mechanisms of its regulation. We identified two regions of high conservation upstream of the translation start of the NAGS gene. Reporter assays confirmed that these regions represent promoter and enhancer and that the enhancer is tissue specific. Within the promoter, we identified multiple transcription start sites that differed between liver and small intestine. Several transcription factor binding motifs were conserved within the promoter and enhancer regions while a TATA-box motif was absent. DNA-protein pull-down assays and chromatin immunoprecipitation confirmed binding of Sp1 and CREB, but not C/EBP in the promoter and HNF-1 and NF-Y, but not SMAD3 or AP-2 in the enhancer. The functional importance of these motifs was demonstrated by decreased transcription of reporter constructs following mutagenesis of each motif. The presented data strongly suggest that Sp1, CREB, HNF-1, and NF-Y, that are known to be responsive to hormones and diet, regulate NAGS transcription. This provides molecular mechanism of regulation of ureagenesis in response to hormonal and dietary changes.


Quantification of [Ca2+]i in perfused hearts. Critical evaluation of the 5F-BAPTA and nuclear magnetic resonance method as applied to the study of ischemia and reperfusion.
Calcium has been implicated as a mediator of cell injury in ischemia and reperfusion, but direct measurements of Ca2+ are required to refine this idea. We used nuclear magnetic resonance spectroscopy and the Ca2+ indicator 5F-BAPTA to measure [Ca2+]i in perfused ferret hearts. Several lines of evidence are presented to show that loading with the acetoxymethyl ester of 5F-BAPTA is not significantly complicated by accumulation of partially de-esterified metabolites, compartmentalization into mitochondria, or disproportionate uptake into endothelial cells. During 20 minutes of total global ischemia at 30 degrees C, time-averaged [Ca2+]i increased significantly, reaching peak values roughly three times control at 15-20 minutes. Reperfusion resulted in a persistent elevation of [Ca2+]i during the first 5 minutes, but not afterward. Although the nonlinear response of 5F-BAPTA to [Ca2+] leads to underestimation of the true time-averaged [Ca2+]i, the measured alterations of intracellular Ca2+ homeostasis during ischemia are large compared with the likely errors in quantification. Phosphorus nuclear magnetic resonance spectroscopy of 5F-BAPTA-loaded hearts reveals changes during ischemia similar to those recorded previously in hearts not containing a Ca2+ indicator. Developed pressure recovers to only 50% of control values during reflow, indicating that the presence of 5F-BAPTA in the cytosol does not protect against stunning, at least when the extracellular calcium concentration has been raised to 8 mM. We conclude that 5F-BAPTA provides useful measurements that reveal that time-averaged [Ca2+]i rises during ischemia and returns to control levels soon after reperfusion.


Non-acidic pyrazole EP1 receptor antagonists with in vivo analgesic efficacy.
Replacement of the carboxylic acid group in a series of previously described methylene-linked pyrazole EP(1) receptor antagonists led to the discovery of amide, reversed amide and carbamate derivatives. Two compounds, 10a and 10b, were identified as brain penetrant compounds and both demonstrated efficacy in the CFA model of inflammatory pain.


Injury mechanisms and electromyographic changes after injury of the recurrent laryngeal nerve: Experiments in a porcine model.
Recurrent laryngeal nerve (RLN) injury during surgery may reveal differences in electromyographic (EMG) changes after sustained compression or traction. In 20 pigs with the NIM-FLEX EMG-endotracheal tube, EMG was recorded at baseline, during sustained RLN compression, or traction until 70% amplitude decrease and during 30 minutes of recovery. Seventy percent amplitude decrease from baseline was reached after 110 ± 98 seconds (compression group) and 2034 ± 2108 seconds (traction group). Traction induced a pronounced latency increase, peaking at 122 ± 8% in contrast to compression with 106 ± 5% (P < .001). The EMG amplitude recovery to ≥50% of baseline failed in 7 nerves after compression and 8 nerves after traction. Compression caused a fast decrease of EMG amplitude with minor effects on latency. In contrast, RLN traction showed early and significant latency increase preceding a delayed amplitude decrease. Recovery rate of the EMG signals were similar in both groups.


Sensitivity differences to 5-HT and carbachol in subsections of the isolated rat stomach fundus strip: an improved preparation.
The rat stomach fundus strip has often been used as a sensitive assay of pharmacological activity at 5-HT receptors. In the present study, we describe an improved preparation based on the finding that the majority of the contractile response to 5-HT and carbachol was present in one particular longitudinal quartile of the tissue. The fundi were dissected into four anatomically consistent sections and labelled accordingly (left ventral = LV; right ventral = RV; left dorsal = LD; right dorsal = RD). A distinct pattern of responsiveness (contraction) to 5-HT and carbachol was observed. For carbachol, the maximum contraction ratios of the sections (LV:LD:RV:RD) were 7.2(+/-0.8):5.8(+/-1.4):4.2(+/-0.46):3.0 (+/-0.22), respectively. For 5-HT, the differences were more pronounced with maximum contraction ratios of 5.6 (+/-0.94): 3.6(+/-0.58):1.4(+/-0.30):1.6(+/-0.22), respectively. When the sections were dissected along the submucosa, the mucosal section responded to carbachol and 5-HT, while the muscularis externa did not respond to these agonists. Selection of the LV section allowed the use of smaller bath volumes, and subsequent bisection facilitated the design of more effective paired experiments.


Minimally Invasive Treatments of Benign Thyroid Nodules: A Network Meta-Analysis of Short-Term Outcomes.
Background: Image-guided thermal ablation interventions are novel thermal-based modalities used for the treatment of benign thyroid nodules. Methods: We conducted a systematic review and a Bayesian network meta-analysis, examining studies using thermal ablation interventions in the treatment of benign nodular thyroid disease (PROSPERO CRD42022367680). The primary endpoints included volume reduction rate (VRR), and symptomatic score and cosmetic score improvement. Secondary endpoints included vocal disturbances, laryngeal nerve palsy, hypothyroidism, and nodular regrowth (defined by increased nodular volume of >50% for thermal ablation or new nodules arising in remaining thyroid tissue conventional surgery [CS]). Results: We included 16 studies (3 randomized controlled trials [RCTs] and 13 comparative case series), describing radiofrequency ablation (RFA), laser ablation (LA), microwave ablation (MWA), high-intensity focus ultrasound (HIFU), and CS, respectively. The review included data from 4112 patients followed for a mean of 11.9 months. Meta-analyses showed no significant differences among RFA, LA, MWA, HIFU, and CS regarding any of the primary endpoints of VRR, symptomatic score, and cosmetic score. In examining the surface under the cumulative ranking area (SUCRA) ranking, CS (SUCRA, 98.49), LA (SUCRA, 51.58), and MWA (SUCRA, 57.0) were identified as the three interventions that were most likely to result in the largest VRR, symptomatic and cosmetic score reduction. RFA, relative risk (RR) 0.19 [95% credibility interval (CI): 0.06 to 0.48], LA RR 0.23 [CI: 0.06 to 0.79], and MWA RR 0.25 [CI: 0.09 to 0.60] were associated with the greatest reduction in risk for postintervention vocal complications compared with CS, with RFA (SUCRA, 61.62) being ranked as the highest in safety. RFA RR 0.05 [CI: 0.00 to 0.40] and MWA RR 0.16 [CI: 0.02 to 0.73] were associated with a reduced risk of transient laryngeal nerve injury compared with CS. RFA RR 0.00 [CI: 0.00 to 0.00] and MWA RR 0.00 [CI: 0.00 to 0.03] were associated with a reduced risk of hypothyroidism occurrence compared with CS, with RFA (SUCRA, 99.86) yielding the highest safety ranking. RFA was associated with a reduced risk for nodular regrowth RR 0.09 [CI: 0.00 to 0.85], compared with CS. Conclusion: We have comprehensively reviewed the published literature on the efficacy and safety of thermal ablation modalities for benign thyroid nodules. Important research gaps remain regarding a paucity of both long-term data and high-quality RCTs.


Baboon (Papio ursinus) model to study deep vein thrombosis using 111-indium-labeled autologous platelets.
This study evaluates the chacma baboon as a model for investigations on deep vein thrombosis (DVT). There is a good correlation of the baboon and human thrombelastographic parameters (r-time, k-time, ma). Investigation on the diagnostic efficacy of 111 In-labeled platelets as an imaging agent for DVT cast considerable doubt on the procedure, owing to the age of the thrombus.


Equilibrium thermodynamics of cell-cell adhesion mediated by multiple ligand-receptor pairs.
In many situations, cell-cell adhesion is mediated by multiple ligand-receptor pairs. For example, the interaction between T cells and antigen-presenting cells of the immune system is mediated not only by T cell receptors and their ligands (peptide-major histocompatibility complex) but also by binding of intracellular adhesion molecules. Interestingly, these binding pairs have different resting lengths. Fluorescent labeling reveals segregation of the longer adhesion molecules from the shorter T cell receptors in this case. Here, we explore the thermal equilibrium of a general cell-cell interaction mediated by two ligand-receptor pairs to examine competition between the elasticity of the cell wall, nonspecific intercellular repulsion, and bond formation, leading to segregation of bonds of different lengths at equilibrium. We make detailed predictions concerning the relationship between physical properties of the membrane and ligand-receptor pairs and equilibrium pattern formation, and suggest experiments to refine our understanding of the system. We demonstrate our model by application to the T cell/antigen-presenting-cell system and outline applications to natural killer cell adhesion.


German pathologist Walter Büngeler (1900-1987)-Nazi victim or political influencer in Brazil?
One of the most wellknown German pathologists of the twentieth century, Walter Büngeler became internationally known for his elemental research on leukemia and the pathology of tumors. In 1936, Büngeler left Nazi Germany for Brazil, but returned to Germany in 1942. After the war ended in 1945, Büngeler portrayed himself as a political victim who had been expelled first by the National Socialists and later by the Brazilian government, and in fact, he was able to successfully perpetuate this image and emerged unscathed from his de-Nazification procedure, continuing on to a successful university career with stations in Kiel and Munich as both professor and dean, as well as a term as DGP president. Up until very recently, Büngeler was portrayed in literature as a victim and critic of Nazism. Does this self-portrayal stand up to a critical examination of the facts? It is precisely this question that is the focus of this article. The analysis draws upon primary sources; namely, Büngeler's own claims from a curriculum vitae filled out in 1943 as well as his de-Nazification file from the post-war period. This article exposes significant contradictions between these two sources. The statements Büngeler made in his de-Nazification file can be verified as false in all relevant aspects. Nevertheless, Büngeler managed to create a wide-reaching and successful version of himself; a picture which persisted until only very recently.


[Proteins of the basal plate of bacteriophage T4 participating in the contractile impulse].
Reversible linking of proteins with Cu2+ and Ni2+ ions was used to study the topography of the structural proteins of bacteriophage T4 basal plate. Gene products (GP) 9 and 10 were found to directly contact the proximal part of long fibrils (GP34). GP27, GP54 and GP5 interact with the lower disk of the contractive sheath (GP18), while GP48 and GP54 are in contact with the core (GP19). The proteins of the sheath (GP18) and the core (GP19) were found to have contact over the whole tail length.


Klebsiella pneumoniae ST258 producing KPC-3 identified in italy carries novel plasmids and OmpK36/OmpK35 porin variants.
A carbapenemase-resistant Klebsiella pneumoniae strain, clone ST258 producing KPC-3, was fully characterized. The entire plasmid content was investigated, thereby identifying plasmids of the IncFII(k) (two of them similar to pKPQIL and pKPN3, respectively), IncX, and ColE types, carrying a formidable set of resistance genes against toxic compounds, metals, and antimicrobial drugs and a novel iron(III) uptake system.


Decoherence optimized tilted-angle cross polarization: A novel concept for sensitivity-enhanced solid-state NMR using ultra-fast magic angle spinning.
Ultra-fast magic-angle spinning (UFMAS) at a MAS rate (ωR/2π) of 60 kHz or higher has dramatically improved the resolution and sensitivity of solid-state NMR (SSNMR). However, limited polarization transfer efficiency using cross-polarization (CP) between 1H and rare spins such as 13C still restricts the sensitivity and multi-dimensional applications of SSNMR using UFMAS. We propose a novel approach, which we call decoherence-optimized tilted-angle CP (DOTA CP), to improve CP efficiency with prolonged lifetime of 1H coherence in the spin-locked condition and efficient band-selective polarization transfer by incorporating off-resonance irradiation to 1H spins. 13C CP-MAS at ωR/2π of 70-90 kHz suggested that DOTA CP notably outperformed traditional adiabatic CP, a de-facto-standard CP scheme over the past decade, in sensitivity for the aliphatic-region spectra of 13C-labeled GB1 protein and N-formyl-Met-Leu-Phe samples by up to 1.4- and 1.2-fold, respectively. 1H-detected 2D 1H/13C SSNMR for the GB1 sample indicated the effectiveness of this approach in various multidimensional applications.


The prediction of protein-ligand unbinding for modern drug discovery.
Drug-target thermodynamic and kinetic information have perennially important roles in drug design. The prediction of protein-ligand unbinding, which can provide important kinetic information, in experiments continues to face great challenges. Uncovering protein-ligand unbinding through molecular dynamics simulations has become efficient and inexpensive with the progress and enhancement of computing power and sampling methods. In this review, various sampling methods for protein-ligand unbinding and their basic principles are firstly briefly introduced. Then, their applications in predicting aspects of protein-ligand unbinding, including unbinding pathways, dissociation rate constants, residence time and binding affinity, are discussed. Although various sampling methods have been successfully applied in numerous systems, they still have shortcomings and deficiencies. Most enhanced sampling methods require researchers to possess a wealth of prior knowledge of collective variables or reaction coordinates. In addition, most systems studied at present are relatively simple, and the study of complex systems in real drug research remains greatly challenging. Through the combination of machine learning and enhanced sampling methods, prediction accuracy can be further improved, and some problems encountered in complex systems also may be solved.


A novel method for improving laccase activity by immobilization onto copper ferrite nanoparticles for lignin degradation.
In this paper, a novel method for simultaneous enhancement of catalytic activity and reusability of laccase was carried out to overcome the limitations on industrial application of laccase. The immobilization of laccase onto copper ferrite magnetic nanoparticles (CuMNPs) and ferrite magnetic nanoparticles (MNPs) were optimized at 50 mM glutaraldehyde concentration and 1:5 enzyme:nanoparticles (NPs) ratio for 9 h of cross-linking time, yielding a maximum activity recovery of 94.68 ± 0.92% and 89.78 ± 1.24%, respectively. The laccase immobilized NPs were characterized using physico-chemical methods such as SEM-EDAX, FTIR, XRD, TGA and VSM and the laccase immobilized CuMNPs showed 18% higher activity as compared to free enzyme. The prepared CuMNPs and MNPs showed superior thermal stability (50-70 °C) with t1/2 increased by 5.7 and 4.1 folds, respectively, as compared to free laccase. The laccase in immobilized forms exhibited higher kinetic potential and stable at wide temperature and pH range. In addition, laccase immobilized NPs retained more than 70% residual activity during reuse up to 6 cycles and storing for 20 days at 4 °C. The laccase immobilized CuMNPs showed higher delignification (43.28 ± 1.46%) on Ipomoea carnea than laccase immobilized MNPs.


The wolf will live with the lamb.
Maestripieri et al. pit evolutionary psychology against social psychological and economic perspectives in a winner-take-all empirical battle. In doing so, they risk positioning evolutionary psychology as an antagonistic subdisciplinary enterprise. We worry that such a framing may exacerbate tensions between "competing" scientific perspectives and limit evolutionary psychology's potential to serve as a unifying core theory.


Ohtahara syndrome: with special reference to its developmental aspects for differentiating from early myoclonic encephalopathy.
Ohtahara syndrome (OS) is well known as a peculiar early onset epileptic syndrome with serious prognosis. The outline of OS, mainly in relation to the evolution with age, and differentiation from related conditions, particularly early myoclonic encephalopathy (EME) were mentioned. Etiologically, structural brain lesions are most probable in OS, and non-structural/metabolic disorders in EME. Clinically, tonic spasms are the main seizures in OS, while myoclonia and frequent partial motor seizures in EME. Another difference is noted in EEG findings: suppression-bursts (SB) are consistently observed in both waking and sleeping states in OS, but suppression-bursts become more apparent in sleep in EME. The course observation clarifies differences between both syndromes; SBs evolve to hypsarrhythmia around 3-4 months of age, and sometimes further to diffuse slow spike-waves in OS. In contrast, in EME suppression-bursts may persist up to late childhood after a transient evolution to hypsarryhtmia in the middle to late infancy. Transition between syndromes is also specific; OS evolves to West syndrome, and further to Lennox-Gastaut syndrome with age, but EME persists long without such evolution excepting a transient phase of West syndrome. These clinicoelectrical characteristics and differential points strongly indicate the efficiency of the developmental study to delineate both syndromes.


Predictive value of the TyG index and rheumatoid factor for cardiovascular disease risk in a rheumatoid arthritis population: data from a survey of 418 patients.
To investigate the correlation between the triglyceride-glucose (TyG) index and rheumatoid factor levels and the existence of cardiovascular disease in patients in the rheumatoid arthritis population and to analyze their potential value in predicting the risk of cardiovascular disease. Patients with rheumatoid arthritis treated by the Traditional Chinese Medicine Department of Rheumatism of the China-Japan Friendship Hospital from 2019-01 to 2021-12 were included in this retrospective study. Regression analysis was performed with multifactor-corrected multimodal logistic models to observe the correlation between the TyG index and rheumatoid factor and cardiovascular disease risk, construct predictive models and assess the potential predictive value of the variables on cardiovascular disease risk with receiver operating characteristic curves. The results were further corrected by sensitivity analysis and trend tests. A total of 418 patients with rheumatoid arthritis were included in the study. In the rheumatoid arthritis population, high rheumatoid factor (OR = 1.002, 95% CI = 1.001-1.002, P < 0.001), high TyG index (OR = 1.057, 95% CI = 1.008-1.109, P = 0.022), advanced age (OR = 1.080, 95% CI = 1.050-1.112, P < 0.001), and low physical activity (OR = 2.848, 95% CI = 1.195-6.785, P = 0.018) were independent risk factors for the existence of cardiovascular disease in patients. The combined coefficient calculated on the basis of the TyG index and rheumatoid factor was used to plot the receiver operating characteristic curve with an area under the curve of 0.791, which can be used to predict the potential risk of cardiovascular disease in patients with rheumatoid arthritis. Further sensitivity analysis found that the marker of focus remained associated with cardiovascular disease risk in a high-physical activity population with rheumatoid arthritis. The final trend test found a linear trend between the TyG index, rheumatoid factor levels and the risk of cardiovascular disease. In the rheumatoid arthritis population, the TyG index and rheumatoid factor have some potential predictive value in determining the risk of cardiovascular disease, and the predictive efficacy is better when the two tests are combined.


Antioxidant properties of magnesium lithospermate B contribute to the cardioprotection against myocardial ischemia/reperfusion injury in vivo and in vitro.
To determine the cardioprotective effect of magnesium lithospermate B (MLB) on myocardial ischemia/reperfusion (MI/R) injury and to investigate the antioxidant potential in vivo and in vitro. MI/R injury was induced by the occlusion of left anterior descending coronary artery for 30 min followed by reperfusion for 3 h in rats. After reperfusion, hearts were harvested to assess infarct size, histopathological damages, the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and malondialdehyde (MDA). Blood samples were collected to determine serum levels of creatine kinase-MB (CK-MB), cardiac troponin (cTnl) and lactate dehydrogenase (LDH). Furthermore, simulated ischemia/reperfusion (SI/R) injury in vitro was established by oxygen and glucose deprivation (OGD) for 2 h followed by 24-hour recovery period in cardiomyocytes. The activity of LDH in the cultured supernatant and the levels of intracellular reactive oxygen species (ROS), SOD and MDA in cardiomyocytes were also measured. Finally, cardiomyocytes apoptosis was determined with flow cytometry. MLB significantly limited infarct size, ameliorated histopathological damages and prevented leakage of CK-MB, cTnI and LDH. Additionally, SOD, CAT, GPx and GSH activities were notably increased by MLB, along with the MDA content decreased as compared with the model group in rats. In vitro study, MLB also decreased LDH activity in the cultured supernatant, increased SOD activity in cardiomyocytes, reduced intracellular ROS and MDA levels, and significantly suppressed cardiomyocytes apoptosis. MLB possessed remarkably cardioprotective effects on MI/R injury in vivo and in vitro. The protection of MLB may contribute to its antioxidant properties.


Unskilled and unaware in the classroom: College students' desired grades predict their biased grade predictions.
People tend to be overconfident when predicting their performance on a variety of physical and mental tasks (i.e., they predict they will perform better than they actually do). Such a pattern is commonly found in educational settings, in which many students greatly overestimate how well they will perform on exams. In particular, the lowest-performing students tend to show the greatest overconfidence (i.e., the "unskilled-and-unaware" effect). Such overconfidence can have deleterious effects on the efficacy of students' short-term study behaviors (i.e., underpreparing for exams) and long-term academic decisions (i.e., changing one's academic major to an "easier" topic or dropping out of school completely). To help understand why students' grade predictions are often overconfident, we examined the hypothesis that students' grade predictions are biased by their desired levels of performance, which are often much higher than their actual levels of performance. Across three studies in which actual students made predictions about their exam performance in their courses, we demonstrated that students' grade predictions are highly biased by their desired grades on those exams. We obtained this result when students predicted their exam grades over a week before the exam (Study 1), immediately after taking the exam (Study 2), and across the four course exams in a single semester (Study 3). These results are informative for understanding why the "unskilled-and-unaware" pattern of performance predictions occurs, and why people in general tend to be overconfident when making both physical and mental performance predictions.


Infection-induced seroconversion and seroprevalence of SARS-CoV-2 among a cohort of children and youth in Montreal, Canada.
The EnCORE study is a prospective serology study of SARS-CoV-2 in a cohort of children from Montreal, Canada. Based on data from our fourth round of data collection (May-October 2022), we estimated SARS-CoV-2 seroprevalence and seroconversion. Using multivariable regression, we identified factors associated with seroconversion. Our results show that previously seronegative children were approximately 9-12 times more likely to seroconvert during the early Omicron-dominant period compared to pre-Omicron rounds. Unlike the pre-Omicron rounds, the adjusted rate of seroconversion among 2- to 4-year-olds was higher than older age groups. As seen previously, higher seroconversion rates were associated with ethnic/racial minority status.


Spontaneous remission of infantile spasms and hypsarrhythmia following acute infection with high-grade fever.
To elucidate the pathogenesis of spontaneous remission of infantile spasms (ISs) and hypsarrhythmia following infection, we reviewed 58 patients with ISs from 1986 through 2006 in our hospital. Five patients showed spontaneous remission of spasms or hypsarrhythmia following infections with high-grade fever (SR group). In control, we analyzed five patients with complete improvement of ISs for ACTH therapy (ACTH group). In the SR group, ISs stopped in an average of 4.0 days after the onset of infection. In three patients performing EEG during the infection, hypsarrhythmia disappeared within an average of 8 days after the onset of infection. In the ACTH group, ISs stopped an average of 4.6 days and hypsarrhythmia disappeared within an average of 10 days after ACTH therapy. During the remission course of ISs, low-voltage background activity (BGA) on EEG showed in one patient of the SR group and in all patients of the ACTH group. ACTH is known to the efficacy for ISs and suppression of cortical activity on human EEG. This similar remission course between in the SR group and in the ACTH group suggest neuroendocrinal products in response to infection, which is resembled ACTH-related cascade, may play a role for spontaneous remission following infection.


Welsh Government proposals: organ and tissue donation reforms.
In November 2011, the Welsh Government published a consultation document setting out proposals for legislation on organ and tissue donation. The scheme would introduce a notable change in the law from a consent-based 'opt-in' scheme for transplantation to an 'opt-out' one. This article explores the scope of the current law concerning organ transplantation. It considers the proposals for reform and some of the challenges which might arise in implementing the legislation.


Highly cytotoxic iron(II) complexes with pentadentate pyridyl ligands as a new class of anti-tumor agents.
The iron(II) complexes and with pentadentate pyridyl ligands are stable under physiological conditions and exhibit higher cytotoxicities toward a series of human carcinoma cell lines than cisplatin; can significantly increase intracellular oxidant levels, cleave supercoiled plasmid DNA in vitro without addition of a reductant and induce apoptotic cell death in human cervical epithelioid carcinoma cells (HeLa) as observed in flow cytometric studies.


PFKFB3 promotes sepsis-induced acute lung injury by enhancing NET formation by CXCR4hi neutrophils.
CXCR4hi neutrophils, which are a subset of neutrophils with high CXCR4 expression, are important contributors to sepsis-induced acute lung injury (ALI). PFKFB3, a key glycolysis gene, plays an essential role in neutrophil inflammatory activation. However, the specific involvement of PFKFB3 in sepsis-induced ALI remains unclear. Here, we observed that PFKFB3 was upregulated in CXCR4hi neutrophils and facilitated sepsis-induced ALI. Mechanistically, we observed that PFKFB3 promoted sepsis-induced ALI by enhancing neutrophil extracellular trap (NET) formation by CXCR4hi neutrophils. Further study indicated that PFKFB3 promoted NET formation by upregulating glycolytic metabolism in CXCR4hi neutrophils. In summary, our study uncovered a new mechanism by which CXCR4hi neutrophils trigger sepsis-induced ALI by promoting NET formation, which is supported by PFKFB3-mediated glycolytic metabolism.


Comparative Characterization of Vibrio cholerae O1 from Five Sub-Saharan African Countries Using Various Phenotypic and Genotypic Techniques.
We used standardized methodologies to characterize Vibrio cholerae O1 isolates from Guinea, Democratic Republic of the Congo (DRC), Togo, Côte d'Ivoire and Mozambique. We investigated 257 human isolates collected in 2010 to 2013. DRC isolates serotyped O1 Inaba, while isolates from other countries serotyped O1 Ogawa. All isolates were biotype El Tor and positive for cholera toxin. All isolates showed multidrug resistance but lacked ciprofloxacin resistance. Antimicrobial susceptibility profiles of isolates varied between countries. In particular, the susceptibility profile of isolates from Mozambique (East-Africa) included resistance to ceftriaxone and was distinctly different to the susceptibility profiles of isolates from countries located in West- and Central-Africa. Molecular subtyping of isolates using pulsed-field gel electrophoresis (PFGE) analysis showed a complex relationship among isolates. Some PFGE patterns were unique to particular countries and clustered by country; while other PFGE patterns were shared by isolates from multiple countries, indicating that the same genetic lineage is present in multiple countries. Our data add to a better understanding of cholera epidemiology in Africa.


Respiratory muscle strength and pulmonary function in unvaccinated athletes before and after COVID-19 infection: A prospective cohort study.
We investigated abnormalities and recovery in respiratory function after COVID-19 infection in an unvaccinated elite athlete population. Measurements included maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF). The most frequent reported symptoms were fatigue with 80% and muscle/joint pain and headache with 50%, whereas only 10% reported dyspnoea and 30% cough. During follow-up, MIP was up to 13% and MEP up to 8% lower following COVID-19 infection. Likewise, FEV1 was up to 2% and FVC up to 5% lower. While MEP and FEV1 rapidly normalised, MIP and FVC still remained abnormal after 52 days of COVID-19 infection, thereby leading to a restrictive ventilatory pattern. PEF seemed unaffected during follow-up. COVID-19 decreases respiratory function in unvaccinated athletes despite reporting few respiratory symptoms and having mild disease. An initiative aimed at reducing the long-term adverse effects following COVID-19 infection seems warranted, which perhaps may be avoided through vaccination.


External cephalic version with tocolysis: factors associated with success.
Data were collected prospectively on factors that might affect the success or failure of external cephalic version, using a protocol including fetal monitoring, ultrasound, tocolysis, and external version after 37 weeks' gestation. Patients were accepted into the protocol whether or not risk factors for failure were present. Sixty-seven patients were admitted to the study and 40 (60%) underwent successful version. Using chi 2 analysis, we found that failure of external version was significantly associated with obesity, descent of the breech into the pelvis, decreased fluid, and fetal back positioned posteriorly. Thirteen women were in active labor; this had no effect on the success rate providing that descent had not occurred. Two factors, descent of the breech into the pelvis and posterior position of the fetal back, had an independent effect on success after controlling for other variables.


A Comparative Study on the Impact of Lexical Inferencing, Extended Audio Glossing, and Frequency Mode of Input Instruction on EFL Learners' Lexical Collocation Knowledge.
This study shed light on the effects of four modes of vocabulary instruction, i.e., extended audio glossing, lexical inferencing, lexical translation, and frequency manipulation of input on the learning of lexical collocations by Iranian intermediate EFL learners. In so doing, 80 L1 Persian EFL students were divided into four 20-participant comparison groups: Lexical Inferencing (LI), Extended Audio Glossing (EAG), Frequency Manipulation of Input (FM), and the Lexical Translation group (LT). LI, EAG, FM, and LT were treated through lexical inferencing, extended audio glossing, skewed frequency of input, and lexical translation techniques, respectively. The participants were pretested and posttested through a piloted multiple-choice lexical collocation test and instructed for ten instructional sessions. The results of the data, analyzed through repeated measures ANCOVA, showed that all the techniques examined in this study were effective on learners' achievement in lexical collocations. Comparatively, FM treated through frequency manipulation of input, significantly outperformed the other groups in lexical collocation improvement. The ANCOVA results and paired comparisons also indicated that EAG had the least achievement in lexical collocation compared to the other three groups. These results can hopefully inform language teachers, learners, and syllabus designers.


Relative Effectiveness of Cell-Based Versus Egg-Based Quadrivalent Influenza Vaccines in Adults During the 2019-2020 Influenza Season in the United States.
Mutations occurring during egg-based influenza vaccine production may affect vaccine effectiveness. The mammalian cell-based quadrivalent inactivated influenza vaccine (IIV4c) demonstrated improved protection relative to egg-based vaccines in prior seasons. This study estimated the relative vaccine effectiveness (rVE) of IIV4c versus standard-dose egg-based quadrivalent inactivated influenza vaccine (IIV4e) in preventing influenza-related medical encounters (IRMEs) in the 2019-2020 US influenza season. This retrospective cohort study was conducted using a dataset linking electronic medical records with medical and pharmacy claims data among individuals ≥18 years vaccinated with IIV4c or IIV4e during 2019-2020. A doubly robust inverse probability of treatment weighting model was used to obtain odds ratios (ORs) adjusted for age, sex, race, ethnicity, region, vaccination week, health status, frailty, and baseline healthcare resource utilization. rVE was calculated by (1 - OR) × 100. An exploratory analysis evaluated IRMEs in inpatient and outpatient settings separately. The final study cohort included 1 499 215 IIV4c and 4 126 263 IIV4e recipients ≥18 years of age. Fewer IRMEs were reported in individuals with recorded IIV4c versus IIV4e. The rVE for IIV4c versus IIIV4e for any IRME was 9.5% (95% confidence interval [CI], 7.9%-11.1%). Inpatient and outpatient rVEs were 5.7% (95% CI, 2.1%-9.2%) and 11.4% (95% CI, 9.5%-13.3%), respectively. In age subgroup analyses, rVEs favored IIV4c except in adults aged ≥65 years. Adults vaccinated with IIV4c had a lower risk of IRMEs versus IIV4e recipients in the 2019-2020 US influenza season. These results support IIV4c as a potentially more effective public health measure against influenza than egg-based vaccines.


Human bocavirus is detected in human placenta and aborted tissues.
To date, four human bocaviruses (HBoV) have been described. The most closely related viruses (bovine and canine parvoviruses) are associated with miscarriage in their hosts. The objective of this retrospective study was to determine the frequency of HBoV DNA in miscarriage. Tissue samples from 172 patients, in which miscarriage occurred, were included and tested with a published qPCR protocol. Positive PCRs were mutually confirmed by sequencing. 43 patients (25%) were positive for HBoV DNA. Of those, the majority of HBoV-positive samples were tissues from miscarriage (placenta: 6; aborted tissue products of conception: 37 specimens). The samples were not paired; either placental or aborted tissue was available. The results show that, as long as no animal model is available, the role of HBoV in the occurrence of miscarriage requires additional prospective studies in order to investigate its significance and causal involvements of this pathogen.


Morin attenuates blood pressure and oxidative stress in deoxycorticosterone acetate-salt hypertensive rats: a biochemical and histopathological evaluation.
The present study was designed to evaluate the antihypertensive and antioxidant effect of morin, a flavonoid against deoxycorticosterone acetate (DOCA)-salt induced hypertension in male Wistar rats. Hypertension was induced in uninephrectomized rats (UNX) by weekly twice subcutaneous injection of DOCA (25mg/kg) and 1% NaCl in the drinking water for six consecutive weeks. The DOCA-salt hypertensive rats showed significant (P < .05) increase in the systolic and diastolic blood pressure, heart rate, water intake and organ weights (kidney, heart, aorta and liver). DOCA-salt hypertensive rats also showed significant (P < .05) increase in the levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes in plasma and tissues (kidney, heart, aorta and liver), and significant (P < .05) decrease in the body weight, nitrite and nitrate levels in plasma and heart. Furthermore, the activities of enzymic antioxidants such as superoxide dismutase, catalase and glutathione peroxidase in erythrocyte and tissues and the levels of non-enzymic antioxidants such as reduced glutathione, vitamin C and vitamin E in plasma and tissues were significantly (P < .05) decreased in DOCA-salt rats. Morin supplementation (50mg/kg) daily for six weeks brought back all the above parameters to near normal level. The above findings were confirmed by the histopathological examination. No significant (P < .05) effect was observed in UNX-rats treated with morin (50mg/kg). These results suggest that morin acts as an antihypertensive and antioxidant agent against DOCA-salt induced hypertension.


An electric-field induced dynamical state in dispersions of highly charged colloidal rods: comparison of experiment and theory.
Concentrated dispersions of highly charged rod-like colloids (fd-virus particles) in isotropic-nematic coexistence exhibit a dynamical state when subjected to low-frequency electric fields [Soft Matter, 2010, 6, 273]. This dynamical state consists of nematic domains which persistently melt and form on time scales typically of the order of seconds. The origin of the dynamical state has been attributed to a field-induced, cyclic dissociation and association of condensed ions [Soft Matter, 2014, 10, 1987, Soft Matter, 2015, 11, 2893]. The ionic strength increases on dissociation of condensed ions, rendering the nematic domains unstable, while the subsequent decrease of the ionic strength due to association of condensed ions leads to a recurrent stabilization of the nematic state. The role of dissociation/association of condensed ions in the phase/state behaviour of charged colloids in electric fields has not been addressed before. The electric field strength that is necessary to dissociate sufficient condensed ions to render a nematic domain unstable, depends critically on the ambient ionic strength of the dispersion without the external field, as well as the rod-concentration. The aim of this paper is to compare experimental results for the location of transition lines and the dynamics of melting and forming of nematic domains at various ionic strengths and rod-concentrations with the ion-dissociation/association model. Phase/state diagrams in the field-amplitude versus frequency plane at two different ambient ionic strengths and various rod-concentrations are presented, and compared to the theory. The time scale on which melting and forming of the nematic domains occurs diverges on approach of the transition line where the dynamical state appears. The corresponding critical exponents have been measured by means of image time-correlation spectroscopy [Eur. Phys. J. E, 2009, 30, 333], and are compared to the theoretical values predicted by the ion-dissociation/association model.


Hygroma following endovascular femoral aneurysm exclusion: A case report.
Endovascular treatment of aneurysms in the superficial femoral artery (SFA) and popliteal segments is a suggested alternative to open surgical repair. Careful selection of patients for endovascular treatment of SFA aneurysms is mandatory. A complication due to endovascular stent-graft treatment in an 80-year old male with a 6 cm aneurysm in the SFA is presented. Hygroma developed after a partially unintended extravascular placed stent-graft. Two consecutive explorations resulted in a femoro-popliteal Polytetrafluoro-ethylene (PTFE) by-pass graft as the final solution. Several explanations for the patient's complications are suggested. A primary femoral-femoral/popliteal by-pass might be the best solution in SFA aneurysms due to risk of stent complications.


Clinical responses to the combination of estradiol and drospirenone in symptomatic postmenopausal Thai women.
To investigate the efficacy and tolerability of the oral hormone replacement therapy (HRT) containing 1 mg estradiol (E2) plus 2 mg drospirenone (DRSP) in Thai women with postmenopausal symptoms. Fifty-five Thai women with postmenopausal symptoms participated in this multicenter, open-label, non-comparative Phase IV study. The primary endpoint was the reduction of hot flushes after 12 weeks of treatment. Secondary endpoints included changes infrequency and intensity of menopausal symptoms as well as safety assessments after 4, 8, and 12 weeks of treatment. Treatment with 1 mg E2 plus 2 mg DRSP reduced the frequency of hot flushes in 94.6% of women at the end of the 12-week treatment period. In 60% of women, the frequency of hot flushes was reduced to 10% or less, compared to baseline findings and 49.1% of women had no remaining hot flushes. Other postmenopausal symptoms such as vaginal dryness, urinary incontinence, dysuria, and dyspareunia improved The most common adverse events were vaginal bleeding or spotting and breast tenderness. The oral HRT of 1 mg E2 plus 2 mg DRSP was effective and well tolerated by Thai women suffering from postmenopausal symptoms.


[Priapism: Diagnosis and management].
Our aim was to present a synthesis on the diagnosis and treatment of priapism. For this purpose, a literature search was performed through PubMed to analyze literature reviews and guidelines regarding priapism. Priapism is an erection that persists more than 4hours. There are 3 types of priapism: ischemic priapism, non-ischemic priapism and recurrent (stuttering) priapism. Ischemic priapism, often idiopathic, is the most frequent. When diagnosed, an urgent management is required to limit erectile dysfunction. Sickle-cell patients are prone to have ischemic and stuttering priapism. Non-ischemic priapism usually occurs after perineal trauma. Priapism management depends on the type of priapism. Medical treatment (corporal aspiration and injection of sympathomimetics) then if failed, surgery are indicated for ischemic priapism. The persistence of a non-ischemic priapism most likely requires a radiologic embolization. Priapism is a condition that often requires emergency treatment to spare erectile function. It appears crucial to know this condition and its management.


Regulation of heart creatine kinase.
Magnetization transfer nuclear magnetic resonance (NMR) provides measurement of the velocity of the creatine kinase reaction in the intact heart. Standard one-pulse NMR spectroscopy coupled with conventional biochemical analyses provides information about the average cytosolic concentrations of ATP, creatine phosphate (CrP), creatine (Cr) and H+ in the heart. By combining these techniques, we tested the hypothesis that the velocity of the creatine kinase reaction in vivo was regulated by changes in cytosolic concentrations of its substrates. We found that the reaction velocity cannot always be predicted from its metabolite levels. We interpreted these observations as support for the hypothesis that flux through the creatine kinase reaction is regulated by metabolite levels in microcompartments formed by localization of creatine kinase isozymes.


Gene expression profiling in fetal rat lung during gestational perfluorooctane sulfonate exposure.
Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in the tissues of humans and wildlife. It has been reported that gestational exposure to PFOS causes neonatal death of rats. However, the mechanism is still unclear. In this study, we investigated the effects of gestational PFOS exposure on the gene expression profiling of fetal rat lung at pseudoglandular stage. Adult Sprague Dawley dams were dosed orally from gestational day 12-18 with 0 (control), 5 mg/kg/day or 20 mg/kg/day PFOS. Animals were euthanized on day 18.5, fetal lung samples were collected for histochemical staining and RNA profiling analysis. PFOS did not cause apparent microscopic changes of fetal lungs. Gene expression profiling revealed that PFOS dose-dependently up-regulated the expression of 21 (5 mg/kg) and 43 (20 mg/kg) genes. These genes include five PPARα target genes (Acot1, Hmgcs2, Fabp4, Fabp1 and Myh7), and 4 of them are involved in lipid metabolism. The other genes were primarily included in the categories of cytoskeletal structure (Tpm1, Tnnt2, Actn3, Myoz2, Tmod1, and Mfap5), extracellular matrix (Ckm, Lum, Tnnc1, Art3, Dcn, Col17a1, Aspn, Ctsk, Itm2a, Spock2 and Orm1), transporting (Cox8h, Cox6a2 and Scnn1a) and secreted proteins (Scgb3a1, Nppb and Spp1). Our study demonstrates that in utero PFOS exposure resulted in the alteration of a set of genes which are involved in significant cytoskeletal, extracellular matrix remodeling, lipid metabolism and secreted proteins in the fetal rat lung.


Socio-demographic, Behavioral and Health Characteristics of Underage Female Sex Workers in Mozambique: The Need to Protect a Generation from HIV Risk.
Characteristics, HIV risk, and program coverage for underage female sex workers (FSW) are rarely systematically described worldwide. We compared characteristics of underage (15-17 years old) and adult (≥18 years old) FSW in three main urban areas of Mozambique (Maputo, Beira and Nampula) using data from three respondent-driven sampling surveys implemented in 2011-2012. Among survey participants, 9.8 % (39/400) in Maputo, 17.0 % (70/411) in Beira and 25.6 % (110/429) in Nampula were underage. Over half reported performing sex work to afford daily living, and 29.7-50.0 % had unprotected sex with their last client. The proportion of underage FSW having accessed care and prevention services was lower compared to adult FSW. While HIV prevalence among underage FSW was lower than in adults, it increased markedly with age. Our results point to the urgency of expanding prevention and care programs geared towards underage FSW.


Evolving spectrum of HIV-associated rheumatic syndromes.
At the end of 2013, 35 million people worldwide were infected with HIV. The prognosis of HIV has been transformed by combination antiretroviral therapy (cART). Providing compliance is good, the use of cART has normalised the life expectancy of HIV-infected people leading to a growing population of people with chronic infection. Management of HIV patients has therefore needed to adapt in order to not only control viral activity but also manage long-term complications of HIV and cART. Rheumatological manifestations of HIV were first described in 1989. Since then, there have been case reports, case series and epidemiological studies describing different clinical manifestations of HIV in the musculoskeletal system. This review will encompass musculoskeletal pain, fibromyalgia, systemic lupus erythematosus (SLE) and inflammatory arthritis in HIV. We will aim to report on the prevalence of these conditions and the risk factors, explore the impact of the virus on the clinical presentations and discuss implications for diagnosis and management.


Differential sensitivity to humidity of daily photosynthesis in the field in C3 and C4 species.
Net photosynthesis was measured under field conditions in Maryland, U.S.A. on several days in the C4 species Amaranthus hybridus and Portulaca oleracea, and the C3 species Chenopodium album. Two similar fully exposed canopy leavesof the same specieswere measured each day, following ambient patterns of air temperature and irradiance. One leaf of the pair was exposed to air at the ambient humidity, while the other leaf was exposed to wetter air, such that the leaf to air water vapor pressure difference was 0.5 to 0.6 of that of the leaf at ambient humidity. Daily totals of net photosynthesis were consistently higher for leaves at increased humidity in C. album, with a mean ratio of 1.17. In contrast, daily totals of net photosynthesis in the two C4 species were at most 1.06 times higher for leaves at increased humidity, with a mean ratio of 1.03. Leaf conductance to water vapor increased as water vapor pressure differences decreased in C. album and A. hybridus. In A. hybridus increased sub-stomatal CO2 concentrations resulting from increased humidity only slightly increased net photosynthesis.


Tissue oxygen tension as a predictor of colonic anastomotic healing.
Inadequate blood flow causing tissue hypoxia can result in failure of anastomotic healing. Tissue oxygen tension (ptO2) measurement has been used to predict anastomotic leakage in animals, but its use in humans has not been described previously. A Clark-type oxygen electrode was used to measure ptO2 on the colon of 50 patients undergoing colonic resection and anastomosis. Baseline ptO2 levels were lowest on the descending colon (31.8 +/- 7.4 mmHg, mean +/- SD) and tended to increase at all sites with increasing arterial paO2 (r greater than .76, P less than .001). Perianastomotic ptO2 levels were predictive of subsequent anastomotic leakage when they were less than either 20 mmHg; 50 percent of the preresection ptO2; 15 percent of the arterial paO2; or 40 percent of the ptO2 at a control site (ileum). It is concluded that perioperative ptO2 measurements are of value in the prediction of anastomotic leakage.


Atomistic autophagy: the structures of cellular self-digestion.
Autophagy is directed by numerous distinct autophagy-related (Atg) proteins. These transmit starvation-induced signals to lipids and regulatory proteins and assemble a double-membrane autophagosome sequestering bulk cytoplasm and/or selected cargos destined for degradation upon autophagosome fusion with a vacuole or lysosome. This Review discusses the structural mechanisms by which Atg proteins sense membrane curvature, mediate a PI(3)P-signaling cascade, and utilize autophagy-specific ubiquitin-like protein cascades to tether proteins to autophagosomal membranes. Recent elucidation of molecular interactions enabling vesicle nucleation, elongation, and cargo recruitment provides insights into how dynamic protein-protein and protein-membrane interactions may dictate size, shape, and contents of autophagosomes.