Specific methods to identify plasma binding abnormalities in euthyroid hyperthyroxinemia.
Methods to identify the plasma T4-binding abnormalities that can cause euthyroid hyperthyroxinemia were evaluated in patients with excess T4-binding globulin, familial dysalbuminemic hyperthyroxinemia, prealbumin-associated hyperthyroxinemia, and autoantibody binding of T4. Familial dysalbuminemic hyperthyroxinemic serum showed a unique persistence of abnormal [125I]T4 binding when diluted 1:100 in phosphate buffer with added 1000-fold excess of unlabeled T4 (10(-6) M T4). Immunoprecipitation of [125I]T4 by antibody to prealbumin, precipitation of [125I]T4 by polyethylene glycol 6000 19%, and in vitro resin uptake of T3 were specific for prealbumin-associated hyperthyroxinemia, autoantibody binding of T4, and T4-binding globulin excess, respectively. These simple methods facilitate investigation of patients with euthyroid hyperthyroxinemia and will identify individuals and families at risk of misdiagnosis by standard methods. Use of these techniques rules out the known binding abnormalities in hyperthyroxinemic patients and may make the diagnosis of generalized hormone resistance more specific.


Normal and abnormal pulmonary arteriovenous shunting: occurrence and mechanisms.
Severe cyanosis due to pulmonary arteriovenous fistulas occurs often after a bidirectional superior cavopulmonary anastomosis (Glenn operation) and also in some congenital anomalies in which hepatic venous blood bypasses the lungs in the first passage. Relocation of hepatic flow into the lungs usually causes these fistulas to disappear. Similar pulmonary arteriovenous fistulas are observed in hereditary haemorrhagic telangiectasia, and in liver disease (hepatopulmonary syndrome). There is no convincing identification yet of a responsible hepatic factor that produces these lesions. Candidates for such a factor are reviewed, and the possibility of angiotensin or bradykinin contributing to the fistulas is discussed.


Microfluidic platform for the generation of organic-phase microreactors.
Rapid prototyping photolithography of a thiolene-based resin was used to fabricate microfluidic devices stable to aliphatic and aromatic organic solvents. The swelling of the cross-linked polymer matrix in various organic solvents was quantified, and the solvent resistance properties of these microfluidic devices are described. Discrete droplets of hexanes and toluene of uniform size were generated in microfluidic devices inside a water matrix containing SDS surfactant (SDS = sodium dodecyl sulfate). Variation of water and organic flow rates in the fluidic channels was used to control droplet size and separation. Droplet composition could be controlled by varying flow rates of two joined organic streams. Organic-phase synthetic reactions within the droplets were demonstrated with the bromination of alkenes inside benzene droplets.


Efficacy and safety of different interventions in castration resistant prostate cancer progressing after docetaxel-based chemotherapy: Bayesian network analysis of randomized controlled trials.
Background: Most patients receiving docetaxel-based chemotherapy for castration resistant prostate cancer (CRPC) will eventually progress, and the optimal interventions for these patients are controversial. The objective of our study is to evaluate the clinical efficacy and safety of pharmacological interventions for CRPC patients progressing after docetaxel-based chemotherapy. Methods: A systematic review and Bayesian network meta-analysis of the literature was carried out according to standard methods. Major electronic databases including PubMed, Web of Science and Embase were searched until Jan 2017. Hazard ratios (HRs) and odds ratios (ORs) with corresponding 95% credible intervals (CrIs) were used to estimate the association. Results: 17 Randomized Controlled Trials (RCTs) comprising 14 different interventions with 12347 patients were enrolled. Compared with control arms, Abiraterone Acetate (HR: 0.70, 95%CrI: 0.63-0.79), Cabazitaxel (HR: 0.70, 95%CrI: 0.51-0.95) and Enzalutamide (HR: 0.63, 95%CrI: 0.53-0.75) presented similar benefits in term of OS. Enzalutamide showed superiority over PFS and PSA response with a highest probability to rank 1. Moreover, sensitivity analysis showed that Abiraterone Acetate (HR: 0.71, 95%CrI: 0.63-0.78) exhibited the most efficacious intervention of being rank 1 in term of OS compared with control arms, followed by Cabazitaxel and Cetuximab. On the other hand, Abiraterone Acetate (OR: 0.86, 95%CrI: 0.35-2.03) presented no significant toxicities compared with control arms. Conclusions: Our results demonstrated that Abiraterone Acetate might be the optimal intervention for CRPC patients after docetaxel failure with acceptable tolerability. Future well-designed RCTs and systematic reviews are needed to validate these findings.


HLA associations in three mutually exclusive autoantibody subgroups in UK systemic sclerosis patients.
Systemic sclerosis (SSc) is characterized by the presence of autoantibodies, mostly IgG, which target a limited set of nuclear proteins. These antinuclear antibodies (ANA) associate with disease subgroups and specific organ involvement. Here we show that there is mutual exclusivity of individual ANA in 130 UK SSc patients, confirm clinical associations with antibody profile and extend the analysis to include genetic data. The ANA mutual exclusivity observed leads to the possibility that SSc, in these patients, is in fact three separate diseases. An alternative explanation for exclusivity relates to the fact that optimal production of IgG antibody requires T-cell help, a process restricted by the HLA class II presentation of antigen peptide. If each autoantibody has a different and tight MHC restriction, then there is a possibility that these groups arose from a common pathway and were modified by genetics into the mutually exclusive groups observed, making the separate disease theory less tenable. In order to answer this question, we have determined MHC class II restriction precisely using high-resolution HLA genotyping (SSP) coupled with an amino acid analysis program in our 130 UK SSc patients. DRB1*11 was associated with anti-topoisomerase-I antibody (ATA)-positive patients (P = 0.007) and when combined with ATA (RR = 15.82), dcSSc (RR = 11.45), or both (RR = 21.9), represented the strongest risk factor for pulmonary fibrosis. Patients with antibodies to RNA polymerases I, II and III were associated with DQB1*0201. At the amino acid level, 20 positions in DRB1 and 20 positions in DQB1 showed some significant correlation with an ANA group. Clearly, however, the linkages to MHC class II alleles are not nearly strong enough to explain the mutually exclusive nature of the autoantibody groups and our results support, but do not prove, the separate disease theory.


Diesel exhaust enhances allergic airway inflammation and hyperresponsiveness in mice.
We previously reported that the intratracheal instillation of diesel exhaust particles enhances allergic airway inflammation and hyperresponsiveness in mice. However, it is not known whether the effects of such instillation differ from those obtained with the daily inhalation of diesel exhaust. We therefore examined whether the inhalation of diesel exhaust would also enhance allergic reactions. Mice were exposed to diesel exhaust or clean air for 5 wk. After the first week, the animals were sensitized to ovalbumin by intraperitoneal injection. At the end of the exposure period, they underwent an ovalbumin challenge. Control animals received saline instead of ovalbumin. Independently of ovalbumin sensitization, diesel exhaust caused an increase in the numbers of neutrophils and macrophages in bronchoalveolar lavage fluid, whereas a significant increase in eosinophil numbers occurred only after antigen challenge combined with diesel exhaust exposure. Furthermore, ovalbumin alone caused an increase in eosinophil numbers in lung tissue, and this was enhanced by diesel exhaust. Exposure to diesel exhaust combined with ovalbumin sensitization, but not diesel exhaust inhalation alone, enhanced the number of goblet cells in lung tissue, respiratory resistance, production of ovalbumin-specific immunoglobulin E and G1 in the serum, and expression of interleukin-5 in lung tissue.


The effect of solid surface tension and exposure to elevated hydrodynamic shear on Pseudomonas fluorescens biofilms grown on modified titanium surfaces.
The solid surface tension of titanium was varied by using organosilane monolayers of various terminations, minimising differences in other material properties. Both the quantity of Pseudomonas fluorescens biofilms grown on the modified surfaces, and the percentage of biofilm remaining after exposure to hydrodynamic shear stress, varied significantly as a function of solid surface tension. The quantity of biofilm was less on chloropropyl-terminated surfaces than on an alkyl-terminated surfaces. However, the percentage of biofilm remaining after exposure to hydrodynamic shear stress (which depends on the adhesion and cohesion strengths of the biofilm) was less for the alkyl-terminated surface than for the chloropropyl-terminated surface, for one of the two sample sets analysed. These results demonstrate the importance of differentiating between the quantity of biofilm on a surface and the adhesion and cohesion strength of the biofilm, and may help explain discrepancies in the existing literature regarding the effect of solid surface tension on the propensity of a surface for microfouling.


Observational "go-alongs" of follow-up HIV care visits of two virally suppressed Black sexual minority men.
This study explored potentially underreported healthcare contexts, clinical experiences, and motivations for adherence in care among virally suppressed Black sexual minority men (BSMM) living with HIV (LWHIV) in Baltimore, MD. Go-alongs with two virally suppressed BSMM LWHIV supplemented 27 in-depth interviews of a larger qualitative study guided by Positive Deviance and Life Course Theory. The go-alongs involved accompanying participants' follow-up HIV care visit to obtain a better account of contextual healthcare factors. Observations focused on (1) clinic location and resources, (2) sources of HIV and sexuality stigma or support in the clinic, and (3) patient-provider interactions. We found that facilitators and barriers to viral suppression for BSMM LWHIV included structural factors (i.e., healthcare setting, facility, and services), quality of patient-provider interactions, and personal motivations to achieve viral suppression. Clinic accessibility, co-located clinical services, and rapport with clinicians and healthcare staff could be key contextual conditions that facilitate retention in care among BSMM LWHIV.


Bipolar disorder: clinical perspectives and implications with cognitive dysfunction and dementia.
Introduction. Cognitive dysfunction as a core feature in the course of bipolar affective disorder (BPD) is a current subject of debate and represents an important source of psychosocial and functional burden. Objectives. To stand out the connection and clinical implications between cognitive dysfunction, dementia, and BPD. Methods. A nonsystematic review of all English language PubMed articles published between 1995 and 2011 using the terms "bipolar disorder," "cognitive dysfunction," and "dementia". Discussion. As a manifestation of an affective trait or stage, both in the acute phases and in remission, the domains affected include attention, executive function, and verbal memory. The likely evolution or overlap with the behavioural symptoms of an organic dementia allows it to be considered as a dementia specific to BPD. This is named by some authors, as BPD type VI, but others consider it a form of frontotemporal dementia. It is still not known if this process is neurodevelopmental or neurodegenerative in nature, or both simultaneously. The assessment should consider the iatrogenic effects of medication, the affective symptoms, and a neurocognitive evaluation. Conclusion. More specific neuropsychological tests and functional imaging studies are needed and will assume an important role in the near future for diagnosis and treatment.


The bHLH transcription factor hand2 is essential for noradrenergic differentiation of sympathetic neurons.
The basic helix-loop-helix transcription factor Hand2, together with Ascl1, Phox2a, Phox2b and Gata2/Gata3, is induced by bone morphogenetic proteins in neural crest-derived precursor cells during sympathetic neuron generation. Hand2 overexpression experiments and the analysis of its function at the Dbh promotor implicated Hand2 in the control of noradrenergic gene expression. Using the zebrafish hand2 deletion mutant hands off, we have now investigated the physiological role of hand2 in the development of sympathetic ganglia. In hands off mutant embryos, sympathetic precursor cells aggregate to form normal sympathetic ganglion primordia characterized by the expression of phox2b, phox2a and the achaete-scute family member zash1a/ascl1. The expression of the noradrenergic marker genes th and dbh is strongly reduced, as well as the transcription factors gata2 and tfap2a (Ap-2alpha). By contrast, generic neuronal differentiation seems to be unaffected, as the expression of elavl3 (HuC) is not reduced in hands off sympathetic ganglia. These results demonstrate in vivo an essential and selective function of hand2 for the noradrenergic differentiation of sympathetic neurons, and implicates tfap2a and gata2 as downstream effectors.


MEC3, MEC1, and DDC2 are essential components of a telomere checkpoint pathway required for cell cycle arrest during senescence in Saccharomyces cerevisiae.
When telomerase is absent and/or telomeres become critically short, cells undergo a progressive decline in viability termed senescence. The telomere checkpoint model predicts that cells will respond to a damaged or critically short telomere by transiently arresting and activating repair of the telomere. We examined the senescence of telomerase-deficient Saccharomyces cerevisiae at the cellular level to ask if the loss of telomerase activity triggers a checkpoint response. As telomerase-deficient mutants were serially subcultured, cells exhibited a progressive decline in average growth rate and an increase in the number of cells delayed in the G2/M stage of the cell cycle. MEC3, MEC1, and DDC2, genes important for the DNA damage checkpoint response, were required for the cell cycle delay in telomerase-deficient cells. In contrast, TEL1, RAD9, and RAD53, genes also required for the DNA damage checkpoint response, were not required for the G2/M delay in telomerase-deficient cells. We propose that the telomere checkpoint is distinct from the DNA damage checkpoint and requires a specific set of gene products to delay the cell cycle and presumably to activate telomerase and/or other telomere repair activities.


Plastic Surgery and the COVID-19 Pandemic: A Review of Clinical Guidelines.
A novel coronavirus disease (COVID-19) was first reported in December 2019 in China and was soon declared a pandemic by the World Health Organization. Many elective and nonessential surgeries were postponed worldwide in an effort to minimize spread of disease, as well as to conserve resources. Our goal with this article is to review current practice guidelines in setting of the COVID-19 pandemic, based on available data and literature. Websites pertaining to surgical and medical societies, and government agencies were reviewed, along with recently published literature to identify recommendations related to COVID-19 and plastic surgery procedures. Clinical practice modifications are recommended during the pandemic in outpatient and perioperative settings. Use of personal protective equipment is critical for aerosol-generating procedures, such as surgery in the head and neck area. Care for trauma and malignancy should continue during the pandemic; however, definitive reconstruction could be delayed for select cases. Specific recommendations were made for surgical treatment of cancer, trauma, and semiurgent reconstructive procedures based on available data and literature. The risk and benefit of each reconstructive procedure should be carefully analyzed in relation to necessary patient care, minimized COVID-19 spread, protection of health care personnel, and utilization of resources. Recommendations in this article should be taken in the context of each institute's resources and prevalance of COVID-19 in the region. It should be emphasized that the guidelines provided are a snapshot of current practices and are subject to change as the pandemic continues to evolve.


Extended magnesium and calcium force field parameters for accurate ion-nucleic acid interactions in biomolecular simulations.
Magnesium and calcium play an essential role in the folding and function of nucleic acids. To correctly describe their interactions with DNA and RNA in biomolecular simulations, an accurate parameterization is crucial. In most cases, the ion parameters are optimized based on a set of experimental solution properties such as solvation free energies, radial distribution functions, water exchange rates, and activity coefficient derivatives. However, the transferability of such bulk-optimized ion parameters to quantitatively describe biomolecular systems is limited. Here, we extend the applicability of our previous bulk-optimized parameters by including experimental binding affinities toward the phosphate oxygen on nucleic acids. In particular, we systematically adjust the combination rules that are an integral part of the pairwise interaction potentials of classical force fields. This allows us to quantitatively describe specific ion binding to nucleic acids without changing the solution properties in the most simple and efficient way. We show the advancement of the optimized Lorentz combination rule for two representative nucleic acid systems. For double-stranded DNA, the optimized combination rule for Ca2+ significantly improves the agreement with experiments, while the standard combination rule leads to unrealistically distorted DNA structures. For the add A-riboswitch, the optimized combination rule for Mg2+ improves the structure of two specifically bound Mg2+ ions as judged by the experimental distance to the binding site. Including experimental binding affinities toward specific ion binding sites on biomolecules, therefore, provides a promising perspective to develop a more accurate description of metal cations for biomolecular simulations.


Visualization of Endolymphatic Hydrops in Patients With Unilateral Idiopathic Sudden Sensorineural Hearing Loss With Four Types According to Chinese Criterion.
Objective: The aim of this study is to evaluate the possible value of endolymphatic hydrops (EH) in patients with unilateral idiopathic sudden sensorineural hearing loss (UISSNHL) with four types according to audiometry. Methods: Seventy-two patients (40 men and 32 women; age range, 28-78 years; mean age: 50.0 ± 12.9 years) with UISSNHL were admitted retrospectively into this study. Based on the pure tone audiometry before treatment, the hearing loss of all these patients were categorized into four types: low-frequency group (LF-G), high-frequency group (HF-G), flat group (F-G), and total deafness group (TD-G). The average time from symptom onset to the first examination was 6.9 ± 4.4 days (1-20 days). 3D-FLAIR MRI was performed 24 h after intratympanic injection of gadolinium (Gd) within 1 week after the UISSNHL onset. The incidence of EH in the affected ears based on four types of hearing loss were analyzed using the Chi-square test, and the possible relationship with vertigo and prognosis were also assessed. Results: Eleven of 21 patients (52.4%) in LF-G had the highest EH-positive rate, followed by 18.2% in HF-G, 11.8% in F-G, and 17.4% in TD-G. The significant difference was found in the four groups (P = 0.018). The EH rate of LF-G was statistically significantly higher than that of F-G and TD-G (P = 0.009, P =0.014), respectively. After being valued by the volume-referencing grading system (VR scores), the EH level was represented by the sum scores of EH. In LF-G, no statistically significant difference was found in the prognosis of ISSNHL patients between with the EH group and the no EH group (P = 0.586). The symptom "vertigo" did not correlate with EH and prognosis. Conclusions: EH was observed in UISSNHL patients by 3D-FLAIR MRI. EH may be responsible for the pathology of LF-G but not related to prognosis. It might be meaningless to assess EH in other hearing loss types, which might be more related to the blood-labyrinth dysfunction.


Efficacy and safety of laparoscopic liver resection for hepatocellular carcinoma in segment 8: a propensity score-matched two-center study.
The safety and efficacy of laparoscopic liver resection (LLR) have been reported worldwide. However, those of LLR for tumors located in Couinaud's segment 8 are not sufficiently investigated. We retrospectively analyzed 108 patients who underwent liver resection for hepatocellular carcinoma (HCC) in segment 8 at Kobe University Hospital and Hyogo Cancer Center between January 2010 and December 2021. The patients were categorized in LLR and open liver resection (OLR) groups, and 1:1 propensity score matching (PSM) was performed to compare surgical outcomes between the groups. Forty-seven and 61 patients underwent LLR and OLR, respectively. After PSM, each group contained 34 patients. There was no significant difference in operation time between the groups (331 min vs. 330 min, P = 0.844). Patients in the LLR group had significantly less blood loss (30 mL vs. 468 mL, P < 0.001) and shorter length of postoperative hospital stay (10 days vs. 12 days, P = 0.015) than those in the OLR group. There was no significant difference in the occurrence of postoperative complications between the groups (12% vs. 9%, P = 0.690). Further, the 1-year cumulative incidence of recurrence was not significantly different between the groups (16% vs. 19%, P = 0.734). The surgical outcomes and short-term prognosis of LLR were similar or better than those of OLR. LLR could be an effective and safe procedure, even for lesions located in segment 8, which is considered a difficult anatomical location for LLR.


Technological aptitude and applications of Leuconostoc mesenteroides bioactive strains isolated from Algerian raw camel milk.
Two strains (B7 and Z8) of the Leuconostoc mesenteroides subspecies mesenteroides that were isolated from Algerian camel milk from an initial pool of 13 strains and demonstrated a high ability to inhibit the growth of Listeria spp. were selected and characterised at the phenotypic and genotypic levels. Probiotic profiling and inhibition spectra against food borne pathogens in mixed cultures were also investigated. The bacteriocin produced by L. mesenteroides strain B7 was identified as leucocin B by specific PCR. In vitro studies demonstrated that both Leuconostoc mesenteroides strains exhibited a marked probiotic profile, showing high survival at low pH (2-3 and 4) in the presence of 0.5%, 1%, and 2% of bile salts and at pH 3 in the presence of 3 mg/mL pepsin. Susceptibility testing against antimicrobial agents was also performed for both strains. When tested in a mixed culture with Listeria innocua, Listeria ivanovii, or Staphylococcus aureus, strain B7 reduced the numbers of these species by 1.87, 1.78, and 1.38 log units, respectively. Consequently, these two strains were found to possess good probiotic properties in vitro and a high capacity for Listeria spp. inhibition in mixed cultures. Therefore, these strains have a favourable technological aptitude and a potential application as novel probiotic starters.


Disenecioyl dehydroretronecine--synthesis and acute hepatic toxicity of a pyrrolizidine alkaloid pyrrole analog.
Disenecioyl dehydroretronecine (DSDR), a semi-synthetic analog of the highly reactive pyrrole metabolites of the pyrrolizidine alkaloids, has been synthesized from disenecioyl retronecine. Rats which received 40 mg DSDR/kg body weight via the mesenteric vein showed multiple depressed areas (less than 2 mm in diameter) on the surface of the median lobe of the liver. Microscopically these areas consisted of hepatic venous occlusion, necrosis, and proliferation of fibroblasts and bile ducts in and around the portal triad. These hepatic lesions were similar to those produced by dehydroretrorcine.


Genomic epidemiology of SARS-CoV-2 in the UAE reveals novel virus mutation, patterns of co-infection and tissue specific host immune response.
To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world and that defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host-pathogen interaction investigation.


Open Talar Neck Fracture With Medial Subtalar Joint Dislocation: A Case Report.
We present a unique case of an open talar neck fracture with medial subtalar joint dislocation. This rare and traumatic injury was treated with immediate open reduction of the subtalar joint and open reduction internal fixation of the talar neck fracture. After a follow-up of 2.2 years, highlighted by numerous complications including posttraumatic arthritis, soft tissue abscess, and fibrotic adhesions, the patient recovered sufficiently to return full activity.


Genetic modulation of PPARgamma phosphorylation regulates insulin sensitivity.
Obesity-associated diabetes is epidemic in industrialized societies. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is highly expressed in adipose tissue and the presumed molecular target for antidiabetic thiazolidinedione drugs that reverse insulin resistance but also promote weight gain. Phosphorylation reduces the activity of PPARgamma in vitro, but physiological relevance has not been demonstrated. We have studied mice homozygous for a mutation (S112A) that prevents PPARgamma phosphorylation. Surprisingly, the weights and adipose mass of PPARgamma-S112A mice are not greater than wild-type. Remarkably, however, genetic prevention of PPARgamma phosphorylation preserves insulin sensitivity in the setting of diet-induced obesity. Underlying this protection are smaller fat cells, elevated serum adiponectin, and reduced free fatty acid levels. Thus, the phosphorylation state of PPARgamma modulates insulin sensitivity. Compounds that prevent PPARgamma phosphorylation or ligands that induce the conformation of nonphosphorylated PPARgamma may selectively enhance insulin sensitivity without increasing body weight.


Epigenetic control of gene regulation during development and disease: A view from the retina.
Complex biological processes, such as organogenesis and homeostasis, are stringently regulated by genetic programs that are fine-tuned by epigenetic factors to establish cell fates and/or to respond to the microenvironment. Gene regulatory networks that guide cell differentiation and function are modulated and stabilized by modifications to DNA, RNA and proteins. In this review, we focus on two key epigenetic changes - DNA methylation and histone modifications - and discuss their contribution to retinal development, aging and disease, especially in the context of age-related macular degeneration (AMD) and diabetic retinopathy. We highlight less-studied roles of DNA methylation and provide the RNA expression profiles of epigenetic enzymes in human and mouse retina in comparison to other tissues. We also review computational tools and emergent technologies to profile, analyze and integrate epigenetic information. We suggest implementation of editing tools and single-cell technologies to trace and perturb the epigenome for delineating its role in transcriptional regulation. Finally, we present our thoughts on exciting avenues for exploring epigenome in retinal metabolism, disease modeling, and regeneration.


[Does arteriosclerotic calcinosis of vessel walls imitate osteogenesis? Pathomorphological studies of arteriosclerotic plaque].
For it is supposed that calcification of arteriosclerotic plaques imitates osteogenesis, it was studied whether the morphology of different stages of calcification supports such an assumption. Investigations were performed on one operation specimen of a dissecting aneurysm of the aorta and five human autopsy aortas. From different arteriosclerotic plaques, paraffin sections without and after EDTA-decalcification were prepared. Light microscopic, scanning (SEM) and transmission electron microscopic (TEM) investigations as well as X-ray microanalysis were performed. By light microscopy, it became obvious that the intensity of calcification of arteriosclerotic plaques is not reflected by the conventional H&E stain--the real amount of calcium-phosphorus deposits becomes only evident by using a special stain, such as the alizarin red S reaction. In the SEM, arteriosclerotic plaques with granular calcification were characterized by accumulations of isolated calcified globules often reflecting the structure of necrotic cells. TEM exhibited even accumulations of calcified bodies corresponding to the shape of cells; cell remnants were present in the neighborhood. X-ray microanalysis of the granules detected calcium and phosphorus and a relative high content of magnesium, reflecting the composition of calcospherites in granular media calcification (71). By SEM, solid calcifications exhibited associations of calcified bodies resembling those of the isolated granules in early calcification but with one stuck onto the other. X-ray microanalysis revealed that these deposits are characterized by high amounts of calcium and phosphorus and a minor component of magnesium in comparison to the isolated granules. From the investigations it is concluded that calcification of arteriosclerotic plaques imitates the process of granular media calcification which is assumed as "dystrophic" calcification of fragments of necrotic cells. The hypothesis of a "regulated" calcification as it occurs in cartilage or bone cannot be supported for the development of the calcified plaques; however, it cannot be excluded that proteins that are associated with osteogenesis participate in the transition of calcification to ossification in the vessel wall.


Taking the business continuity programme to a corporate leadership role.
The paper discusses a process to raise the awareness and value of your continuity programme to higher levels by leveraging existing data. It gives examples of how to utilise the structure of the Business Impact Analysis tool to develop an enterprise level of information capture, and then utilise that data to generate an enterprise level 'group think' which results in incorporation of business continuity as a part of the business-as-usual model.


[Screening of Panax notoginsenoside water in oil microemulsion formulations and their evaluation in vitro and in vivo].
Water in oil (W/O) microemulsion formulation was developed to enhance intestinal absorption of ginsenoside Rb1 (Rb1) of panax notoginseng (PNS). Effects of W/O microemulsions on pharmacokinetics after intraduodenal administration, membrane fluidity and membrane transport of Rb, were studied in rats, liposomes and parallel artificial membrane permeability assay (PAMPA), respectively. Soybean phospholipids/ethanol (SP/EtOH) was selected as surfactant/cosurfactant, together with PNS 400 mg x mL(-1) solution and various kinds of oils, to prepare 11 W/O microemulsions. Most of the microemulsions can enhance Rb1 intestinal absorption significantly. Besides surfactant/cosurfactant, oil also had an effect on the enhanced absorption and the order of enhancement was as follows: glyceryl laurate approximately = isopropyl myristate > isopropyl palmitate > 2-ethylhexanol palmitate. The effection of absorption enhancement by the long chain glyceride ( > C14) is lower than that by the medium chain glyceride (C8 - C14). Most of W/O microemulsions were found to enhance the membrane fluidity of liposomes to different extents. In PAMPA analysis, efficient permeability coefficient (Pe) of diluted-microemulsion (D-ME) is mostly higher than that of PNS solution, which indicated the components of microemulision can facilitate the membrane permeability of the drug. Meanwhile, linearity correlation between Pe and ratio of relative bioavailability (Fr) was acquired for undiluted microemulison (ME). Therefore, W/O microemulsions can enhance intestinal absorption of Rbr, and this effect may be attiributed to its enhancement on membrane fluidity to a certain degree. PAMPA analysis could be brought into not only the investigation of membrane transport of crude drug, but also conditioned preformulation research (e.g. absorption enhancer etc.).


Analysis of the epidemiological burden of age-related macular degeneration in China based on the data of global burden of disease.
Age-related macular degeneration (AMD) is one of the 3 major eye diseases recognized by WHO to prevent blindness, and which is the main cause of irreversible visual impairment in the elderly. This study aims to analyze the disease epidemiological burden, and provide a theoretical foundation for the prevention and control of AMD in China based on the data in global burden of disease (GBD) 2019. The prevalent cases/prevalence, disability-adjusted life year (DALYs)/DALY rate of AMD and socio-demographic index (SDI) for global and China were searched from the GBD 2019 database to analyze the epidemiological trend, age-period-gender trend of AMD in China from 1990 to 2019, and to evaluate the relations between the prevalence and SDI. In 2019, the prevalence of AMD in China was at a high level in the world, and the number of prevalent cases were 1.93 times of that in 1990. The prevalence and DALY rates continued to rise. The age trend of AMD in China was high at the middle of the age stages and low at the two ends, and which was higher in the female than in the male. With the increase of SDI, the prevalence of AMD was increased linearly. The disease burden of AMD in China is increased significantly and is positively correlated with the social development from 1990 to 2019. It is of great significance to study the relationship between epidemilolgical data of AMD and social development level for diagnosis treatment and policy of AMD.


Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe heart failure.
Treatment of decompensated heart failure often includes the use of intravenous vasoactive medications, but the effect on outcome has not been clearly defined. Data from 433 patients enrolled in the ESCAPE trial were analyzed to determine 6-month risks of all-cause mortality and all-cause mortality plus rehospitalization associated with the use of vasodilators, inotropes, and their combination. Patients had a mean left ventricular ejection fraction of 19%, 6-minute walk distance of 414 ft, and systolic blood pressure of 106 mm Hg. The main outcome measure was multivariable risk-adjusted 6-month hazard ratios (HRs). Overall 6-month mortality was 19%. Risk-adjusted HRs were not statistically significant for vasodilators (1.39, 95% CI 0.64-3.00), but were significant for inotropes (2.14, 95% CI 1.10-4.15) and the combination (4.81, 95% CI 2.34-9.90). Risk-adjusted 6-month mortality plus rehospitalization HRs were not significant for vasodilators (1.20, 95% CI 0.81-1.78, P = .37), but were significant for inotropes (1.96, 95% CI 1.37-2.82, P < .001) and their combination (2.90, 95% CI 1.88-4.48, P = .001). The decision to use vasodilators or inotropes was determined by hemodynamic parameters and renal function, but the main factor was treatment site. In ESCAPE, the choice of medications was mainly determined by the treatment site. Use of inotropic agents was associated with adverse outcomes, whereas the use of vasodilators was not. Inotropes in combination with vasodilators identified a group with the highest mortality. Prospective studies are needed to establish the appropriate use of vasoactive medications in this population.


Mental Health Providers' Attitudes About Criminal Justice-Involved Clients With Serious Mental Illness.
Community mental health providers' attitudes toward criminal justice-involved clients with serious mental illness were examined. A total of 627 Maryland psychiatric rehabilitation program providers responded to a survey (83% response rate). Measures assessed providers' experience with, positive regard for, and perceptions of similarity, with their clients with serious mental illness. Chi-square tests were used to compare providers' attitudes toward clients with and without criminal justice involvement. Providers reported lower regard for criminal justice-involved clients than for clients without such involvement. Providers were less likely to report having a great deal of respect for clients with (79%) versus without (95%) criminal justice involvement. On all items that measured providers' perceived similarity with their clients, less than 50% of providers rated themselves as similar, regardless of clients' criminal justice status. Future research should explore how providers' attitudes toward criminal justice-involved clients influence service delivery for this group.


Agranulocytosis: A Rare Complication of Infectious Mononucleosis and Recovery After IVIG Therapy.
A six-year-old boy was admitted with acute agranulocytosis four weeks after the onset of infectious mononucleosis. His bone marrow aspiration revealed maturation arrest of myeloid series. He was hospitalized for agranulocytosis and he was put on intravenous immunoglobulin (IVIG) (400 mg/kg/day) on the third day of hospitalization for two days. His white blood cell count increased to 4200/mm3 (1176 PMNL absolutely) on the fifth day. This may suggest that IVIG therapy may be effective for early recovery from agranulocytosis which is a very rare complication of infectious mononucleosis.


The effectiveness of psychosocial modalities in the treatment of alcohol problems in adults: a review of the evidence.
Our objectives were to review the effectiveness of psychosocial modalities in the treatment of alcohol use disorders and problems, and to examine the impact of therapists on treatment outcome, the evidence on best practices for comorbid conditions, and the evidence on treatment matching. We based our review on published systematic reviews of this topic after 2000. There is strong evidence that some, but not all, psychosocial treatments are effective in treating alcohol problems. Those with the strongest empirical support are motivational enhancement therapy, various cognitive-behavioural interventions, and brief interventions. Meta-analyses for several of these modalities suggest typical effect sizes in the low-to-moderate range. When these modalities have been compared with one another in well-designed clinical trials, they have been shown to be of comparable effectiveness. There is little basis on which to recommend one of these modalities over another but good reason to select from among them.


Coupling regularizes individual units in noisy populations.
The regularity of a noisy system can modulate in various ways. It is well known that coupling in a population can lower the variability of the entire network; the collective activity is more regular. Here, we show that diffusive (reciprocal) coupling of two simple Ornstein-Uhlenbeck (O-U) processes can regularize the individual, even when it is coupled to a noisier process. In cellular networks, the regularity of individual cells is important when a select few play a significant role. The regularizing effect of coupling surprisingly applies also to general nonlinear noisy oscillators. However, unlike with the O-U process, coupling-induced regularity is robust to different kinds of coupling. With two coupled noisy oscillators, we derive an asymptotic formula assuming weak noise and coupling for the variance of the period (i.e., spike times) that accurately captures this effect. Moreover, we find that reciprocal coupling can regularize the individual period of higher dimensional oscillators such as the Morris-Lecar and Brusselator models, even when coupled to noisier oscillators. Coupling can have a counterintuitive and beneficial effect on noisy systems. These results have implications for the role of connectivity with noisy oscillators and the modulation of variability of individual oscillators.


Time-resolved spectroscopic study on photoinduced electron-transfer processes in Zn(II)porphyrin-Zn(II)chlorin-fullerene triad.
Femtosecond time-resolved transient absorption studies have been performed to investigate the photoinduced energy and electron-transfer processes in Zn(II)porphyrin-Zn(II)chlorin-fullerene triad in which energy and oxidation potential gradients are directed along the donor-acceptor-linked arrays. Fast energy transfer (approximately 450 fs) from photoexcited Zn(II)porphyrin to Zn(II)chlorin was observed upon selective photoexcitation of Zn(II)porphyrin unit in the triad. In a nonpolar solvent such as toluene, the energy transfer from the excited singlet state of Zn(II)chlorin to fullerene occurs and is followed by the formation of an intermediate state with a time constant of nanoseconds, which was attributed to the intramolecular exciplex between Zn(II)chlorin and fullerene. In benzonitrile, on the other hand, the photoexcitation of the triad results in the fast electron transfer (< 1 ps) from photoexcited Zn(II)chlorin to fullerene. The generated charge-separated species recombine with a time constant of approximately 12 ps. The relatively fast charge separation and charge recombination rates imply that the strong electronic coupling between Zn(II)chlorin and fullerene moieties is probably induced by the folded conformation between Zn(II)chlorin and fullerene moieties which enhances direct through-space interaction between the approximately contacted pi systems.


β-Cyclodextrin covalent organic framework supported by polydopamine as stationary phases for electrochromatographic enantioseparation.
In this work, a new open-tubular capillary electrochromatography (OT-CEC) column was prepared using β-cyclodextrin covalent organic framework (β-CD COF) as a stationary phase. Polydopamine was used to assist fabrication of β-CD COF on an inner wall of a fused-silica capillary. The coating layer on the capillary was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Electroosmotic flow (EOF) was also studied to evaluate the variation of the inner wall of immobilized columns. Furthermore, the chiral separation effectiveness of the fabricated capillary column was evaluated by CEC using enantiomers of several related proton pump inhibitors as model analytes, including omeprazole, lansoprazole, pantoprazole and tenatoprazole. The effects of bonding time and concentration of β-CD COF, the type, concentration and pH of buffer, applied voltage were investigated to obtain satisfactory enantioselectivity. In the optimum conditions, the enantiomers of four analytes were resolved within 15 min with resolutions of 1.63-2.62. The relative standard deviation values for migration times and resolutions of the analytes representing intraday and interday were less than 6.75% and 4.24%, respectively. The results reveal that β-CD COF has great potential as chiral-stationary phases for enantioseparation in CEC.


Management of difficult intra-articular fractures or fracture dislocations of the proximal interphalangeal joint.
Intra-articular fractures or fracture dislocations of the proximal interphalangeal joint are difficult clinically because the bone and soft tissue structures are small and intricate. Suboptimal treatment of intra-articular fractures typically leads to functional impairment of the hand. This article reviews the current methods of treatment, together with the senior author's experience in treating difficult proximal interphalangeal joint fractures and dislocations. Besides conservative treatments, surgical treatments include open or closed reduction with traditional Osteosynthesis, such as K-wires, screws or plates. Among recent developments are the percutaneous application of thin cannulated compression screws and novel dynamic external fixators. After a preferred minimally invasive treatment with stable reconstruction of the articular surface, sufficient aftercare is necessary to improve surgical outcomes.


Methionine- and Choline-Deficient Diet-Induced Nonalcoholic Steatohepatitis Is Associated with Increased Intestinal Inflammation.
Inflammation drives the pathogenesis of nonalcoholic steatohepatitis (NASH). The current study examined changes in intestinal inflammation during NASH. In male C57BL/6J mice, feeding a methionine- and choline-deficient diet (MCD) resulted in severe hepatic steatosis and inflammation relative to feeding a chow diet (CD). MCD-fed mice exhibited characteristics of mucosal and submucosal inflammatory responses compared with CD-fed mice. Moreover, intestinal phosphorylation states of c-Jun N-terminal protein kinase p46 and mRNA levels of IL-1B, IL-6, tumor necrosis factor alpha, and monocyte chemoattractant protein-1 were significantly higher and intestinal mRNA levels of IL-4 and IL-13 were significantly lower in MCD-fed mice compared with those in CD mice. Surprisingly, upon treatment with MCD-mimicking media, the proinflammatory responses in cultured intestinal epithelial CMT-93 cells did not differ significantly from those in CMT-93 cells treated with control media. In contrast, in RAW264.7 macrophages, MCD-mimicking media significantly increased the phosphorylation states of c-Jun N-terminal protein kinase p46 and mitogen-activated protein kinases p38 and mRNA levels of IL-1B, IL-6, IL-10, and tumor necrosis factor alpha under either basal or lipopolysaccharide-stimulated conditions. Collectively, these results suggest that increased intestinal inflammation is associated with NASH phenotype. Thus, elevated proinflammatory responses in macrophages likely contribute to, in large part, increased intestinal inflammation in NASH.


Drug-Drug Interactions Between PA-824 and Darunavir Based on Pharmacokinetics in Rats by LC-MS-MS.
Currently, patients with co-infection with HIV and tuberculosis are treated with more than one drug. PA-824 a new chemical entity and a member of a class of compounds known as nitroimidazo-oxazines, has significant antituberculosis activity and a unique mechanism of action. Darunavir (PrezistaTM) is a new protease inhibitor of HIV-1. A simple, sensitive and rapid LC-MS-MS method has been developed and validated for simultaneous determination of PA-824 and darunavir. Chromatographic separation was achieved on Agilent Eclipse plus C18 column (100 mm × 2.1 mm, 3.5 μm) using gradient elution of acetonitrile-water (90:10, v/v) with fast gradient elution at a flow rate of 0.6 mL/min and run time of 4.5 min. The mass spectrometer was run in positive electrospray ionization mode using multiple reaction monitoring to monitor the mass transitions. The method was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification, recovery and matrix effect. All validation parameters met the acceptance criteria according to regulatory guidelines. The method had been successfully applied to a pharmacokinetic study of fixed dose administration of PA-824, darunavir and their combination in rats. The results indicated that when co-administration of darunavir could decrease the amount of PA-824 in vivo and extend the elimination half-life.


All-Intra-articular Arthroscopic Rotator Cuff Repair.
This Technical Note presents an arthroscopic technique to repair rotator cuff tears using a constant intra-articular (glenohumeral) portal for visualization. The smoothness of both the humeral head cartilage and the articular side of the rotator cuff offers a cleaner arthroscopic approach, while the absence of a subacromial bursa also reduces bleeding, turbidity, and the need for iterative soft tissue debridement. It also facilitates the recognition and repair of certain tear patterns. The intra-articular perspective allows the surgeon to visualize how stitches pierce the tissue in a desired and resistant area of the tendon. During knot tying, instead of watching the knot compressing against the bursal side of the tendon, the surgeon monitors how the articular side of the tendon is compressed and attached against the footprint while pushing the knot until the desired level of reduction is achieved.


Incidence of neural tube defects of Lucknow over a 10 year period from 1982-1991.
Open neural tube defects (NTD) in babies, occurring over a 10 yr period (1982-91), in four major maternity hospitals of Lucknow, were identified to analyse the incidence of this disorder. The overall incidence of NTD was found to be 3.9/1000. It was significantly higher in the teaching hospital compared to non-teaching hospitals. But there was no significant difference in the incidence of NTD between the Government and Private hospitals. During the decade (1982-91) under study there was no decline in NTD births. These data could serve as base-line for the incidence of NTD in north India, as NTD is expected to decline with the introduction of folic acid for the prevention of NTD.


Molecular Research Comparing the Probabilities of Burkholderia Cepacia Bacterium Diagnosis Procedures.
Burkholderia cepacia is found as part of the B. cepacia complex (Bcc), a collection of highly pathogenic organisms. The Bcc is present almost everywhere in nature; however, it is most prevalent in damp settings, plant roots, and soils. Moreover, Bcc is a major source of morbidity and death in patients due to its high intrinsic antibiotic resistance. The present study aims to isolate and identify gram-negative aerobic bacteria from clinical samples derived from a variety of pathological diseases and investigate the bacterium's virulence factors and genes. The current study included 250 specimens collected from patients suffering from diabetic foot ulcers, urine, burn, wound, sputum, and discharge from the eyes. The samples were collected from both sexes with the age range of 1-75 years. The recorded data showed that males had a higher frequency of infection (79.2%) than females (52%). The results revealed that 7.6% of infected females were between 1-15 years old, while 22% of infected males were aged between 31-45 years. In addition, 26.8% of infected patients (both males and females) were aged between 31-45 years.


Highly selective terahertz bandpass filters based on trapped mode excitation.
We present two types of metamaterial-based spectral bandpass filters for the terahertz (THz) frequency range. The metamaterials are specifically designed to operate for waves at normal incidence and to be independent of the field polarization. The functional structures are embedded in films of benzocyclobutene (BCB) resulting in large-area, free-standing and flexible membranes with low intrinsic loss. The proposed filters are investigated by THz time-domain spectroscopy and show a pronounced transmission peak with over 80% amplitude transmission in the passband and a transmission rejection down to the noise level in the stopbands. The measurements are supported by numerical simulations which evidence that the high transmission response is related to the excitation of trapped modes.


Publication of sports medicine-related randomized controlled trials registered in ClinicalTrials.gov.
There is increasing evidence that a significant proportion of randomized trials in medicine, and recently in orthopaedics, do not go on to publication. The objectives of this study were (1) to determine publication rates of randomized controlled trials in sports medicine that have been registered with ClinicalTrials.gov (CTG) and (2) to compare the registration summaries of randomized trials on CTG with final published manuscripts on pertinent methodological variables. Systematic review. Two independent investigators searched ClinicalTrials.gov for all closed and completed trials related to sports medicine until June 2009 using a text search strategy. The authors then searched for publications resulting from these registered trials in peer-reviewed journals that are indexed with MEDLINE and/or EMBASE as of February 2012 based on study authors and key words provided in the study protocol. Details of primary outcomes and secondary outcomes, study sponsors, and sample size were extracted and compared between registrations and publications. Of 34 closed and completed trials registered on CTG, there were 20 resultant publications in peer-reviewed journals (58.8%). There was no significant relationship between source of funding and rate of publication (P > .05). The authors found a discrepancy between the CTG registration summary and the manuscript in at least one methodological variable (primary/secondary outcomes, inclusion/exclusion criteria, sample size) in 16 of 20 (80.0%) articles and a discrepancy in the primary outcome in 8 of 20 (40.0%) published trials. Although registration of sports medicine trials in CTG does not consistently result in publication or disclosure of results at 32 months from the time of study completion, observed publication rates are higher than in other orthopaedic subspecialties. Changes are also frequently made to the final presentation of eligibility criteria and primary and secondary outcomes that are not reflected in the registered trial data.


Coexistence of neurons integrating urinary bladder activity and pelvic nerve activity in the same cardiovascular areas of the pontomedulla in cats.
The present study examines the coexistence of neurons in the same cardiovascular point of the pontomedulla that integrates urinary bladder (UB) motility, and pelvic nerve activity (PNA). Microinjection of monosodium L-glutamate (Glu) into the locus coeruleus (LC), the gigantocellular tegmental field (FTG), the rostral ventrolateral medulla (RVLM), and the dorsomedial medulla (DM) produced pressor responses, whereas injection into the lateral tegmental field (FTL), the nucleus of tractus solitarii (NTS), and the caudal ventrolateral medulla (CVLM) produced depressor responses. However, microinjection of Glu into the dorsomotor nucleus of the vagus (DMV) and the ambiguus nucleus (AN), where the vagus nerve originates, produced marked bradycardia. Many of these cardiovascular responses were accompanied by increased, or decreased parasympathetic PNA. In six animals, sympathetic renal nerve activity (RNA) and PNA also increased simultaneously during the pressor response. The present study also examines the connection between the DMV-AN and the sacral intermediolateral column (IML), where parasympathetic preganglionic neurons (PGNs) of the pelvic nerve located. Biotinylated dextran amine (BDA), an anterograde tracer, was iontophoretically injected into the DMV or AN. No labelled terminal or neuron was detected in the sacral IML, but labelled terminals were observed in the bilateral LC, and also in the bilateral sides of the FTG, FTL, RVLM, DM, and CVLM. These results suggest that neurons of the DMV and/or AN may indirectly regulate the sacral parasympathetic PGNs through the LC for supraspinal control of the pelvic nerve. Furthermore, these results also suggest the coexistence of multiple autonomic integrating mechanisms of different kinds within various cardiovascular areas of the pontomedulla.


Molecular Characteristics and Antibiotic Resistance Profiles of Klebsiella Isolates in Mthatha, Eastern Cape Province, South Africa.
The increase in the incidence of extended-spectrum β-lactamase- (ESBL-) producing Klebsiella species has become a serious problem worldwide, because of their incrimination in antibiotic resistance. The objective of this study is to investigate the resistance genes responsible for ESBL-producing Klebsiella species and carbapenemase-producing Klebsiella (CRE) isolated in Mthatha and to study their epidemiology. A prospective, descriptive study of 202 nonrepetitive samples from patients was obtained from Nelson Mandela Academic Hospital. The cultured Klebsiella isolates were subjected to antimicrobial susceptibility tests and the polymerase chain reaction of blaCTX-M, blaTEM, blaSHV, blaKPC, and blaNDM genes. Overall K. pneumoniae were the majority with 169 (83.7%) species isolates, followed by K. oxytoca with 29 (14.4%), while K. ozaenae and Raoultella ornithinolytica were 2 (0.9%) each. The prevalence of ESBL production in all Klebsiella species was 117 (57.9%). ESBL-genotypic resistance is driven in Mthatha by blaSHV 121 (77.1%) followed by blaTEM 105 (66.9%) and blaCTX-M at 89 (56.7%). The most common ESBL genotype combination among the Klebsiella was blaTEM + blaSHV + blaCTX-M at 79 (50.3%). There is a steady increase in the rate of ESBL genes in the last five years.


Atlantoaxial intraspinal juxtafacet cyst.
A 69-year-old man presented with progressive paralysis of the right arm and leg with a past history of metastatic rectal cancer. Magnetic resonance imaging showed a cystic mass lesion posterior to the odontoid process. Under a preoperative diagnosis of intradural extramedullary tumor, partial transcondylectomy and C1 hemilaminectomy were performed, and the cyst was removed through a transdural approach, decompressing the medulla oblongata and the cervical spinal cord. The histological diagnosis was juxtafacet cyst (ganglion cyst). An atlantoaxial intraspinal juxtafacet cyst at the level of the odontoid process is extremely rare. In our case, the cyst was removed using a posterior approach, resulting in rapid improvement in symptoms.


Effects of various gait speeds on the latissimus dorsi and gluteus maximus muscles associated with the posterior oblique sling system.
[Purpose] This study investigated the effect of different gait speeds on the muscle activities of the latissimus dorsi and gluteus maximus muscles in relation to the posterior oblique sling system. [Subjects] We recruited 14 young adult males. [Methods] We measured the left latissimus dorsi muscle activity and right gluteus maximus muscle activity of all subjects while they walked on a treadmill at speeds of 1.5 km/h, 3.5 km/h and 5.5 km/h. [Results] There was a significant increase in latissimus dorsi muscle activity with a treadmill speed of 5.5 km/h compared with 1.5 km/h and 3.5 km/h. The gluteus maximus muscle activity significantly increased in the order of 1.5 km/h < 3.5 km/h < 5.5 km/h. [Conclusion] The present results indicate that arm swing connected to increasing gait speed influences the muscle activity of the lower limbs through the posterior oblique sling system.


Determination of residual clopidol in chicken muscle by capillary gas chromatography/mass spectrometry.
Clopidol was extracted from chicken with acetonitrile, and the extract was evaporated to about 5 mL. The concentrated solution was centrifuged and applied to a glass column filled with basic alumina. The column was eluted with methanol and the methanol was evaporated to dryness. The residue was derivatized with Sylon BFT and analyzed by gas chromatography/mass spectrometry (GC/MS). Mass characteristics of trimethylsilyl derivative of clopidol were interpreted manually. The selected-ion monitoring mode was performed at m/z 191, 248, 263, and 265. A sensitive, reproducible GC/MS method was developed for monitoring residues of clopidol in chickens. All recoveries of the drug from chicken muscle fortified at 1, 10, and 100 ng/g were > 65%, and relative standard deviations were < 15%. The detection limit was about 0.5 ng/g, and the quantitation limit was the lower limit of the standard curve, which was about 1 ng/g.


Symposium review: Integration of postweaning nutrient requirements and supply with composition of growth and mammary development in modern dairy heifers.
To optimize first lactation and lifetime milk yield, growth benchmarks were established to help meet the appropriate growth objectives of breeding weight and age at an economically viable time and to achieve the optimum body size and composition at first calving. These guidelines provide a framework that helps to minimize overfeeding and, thus, potential overconditioning of heifers, which can lead to postpartum metabolic issues and reduced milk yield. Concerns still exist that mammary development is impaired when body weight gain exceeds a certain threshold, which would negatively affects milk yield. The objective of this review was to integrate concepts of nutrient requirements, body growth and composition, mammary development, and milk yield to provide a systems-based perspective on first-lactation milk differences that have been associated with mammary development. Work in the early 1980s described the effect of high energy intake on mammary development and the relationship with circulating growth hormone linked the relationship between prepubertal growth, mammary development, and future milk yield. The primary outcome of that research was to provide an intuitive mechanism to explain why rapid growth during the prepubertal phase resulted in reduced milk yield. The observation of reduced mammary development could be repeated in almost every experiment, leading to the conclusion that high energy intake and increased average daily gain reduced mammary development through altered hormone status or some signaling processes. However, further work that looked at mammary development over the entire prepubertal growth phase recognized that mammary development was not reduced by high energy intake, and instead accumulated at a constant rate; thus, overall mammary parenchymal growth was a function of the time to reach puberty and the associated signals to change from allometric mammary growth. The mammary gland, similar to most reproductive organs, grows in proportion to the size of the body and not in proportion to nutrient intake during the postweaning, prepubertal phase. First-lactation milk yield, mammary development, and body composition will be further discussed in the context of mechanisms and opportunities.


Effects of Systemic Therapy on Mental Health of Children and Adolescents: A Meta-Analysis.
Systemic therapy is a frequently used form of psychotherapy for the treatment of mental disorders in children and adolescents. The present study reports the results of the first meta-analysis on the effects of systemic treatment of mental disorders and behavior problems in children and adolescents. Based on systematic search in electronic databases (PsycINFO, Psyndex, PubMed, ISI Web of Knowledge, CINAHL), k = 56 randomized, controlled trials met the inclusion criteria. We computed a random-effects meta-analysis. Systemic therapy showed small-to-medium effects in comparison with an untreated control group (posttest: k = 7, g = .59 standard deviation units, follow-up: k = 2, g = .27) and alternative treatment (posttest: k = 43, g = .32, follow-up: k = 38, g = .28). At follow-up, longer interventions produced larger effect sizes. No other moderator effects were identified. Although available randomized, controlled trials show convincing results, their effects refer to a limited number of systemic approaches and mental disorders, and also pertain to adolescents rather than younger children. Thus, more research is needed before more general conclusions about the effects of systemic therapy can be drawn.


Irritable bowel syndrome in twins: genes and environment.
Both environmental and genetic factors may contribute to irritable bowel syndrome (IBS). Nutrition in fetal life, an early environmental factor, seems to influence the development of chronic diseases later in life, such as coronary heart disease, hypertension, and non-insulin diabetes. This population based twin study evaluated the association between intrauterine growth, measured by weight and gestational age, and IBS. Structural equation analyses were conducted to analyse genetic and environmental sources of variation in liability to IBS. A postal questionnaire was sent to 12 700 Norwegian twins born between 1967 and 1979. The questionnaire included a checklist of 31 illnesses and symptoms, including IBS. The influence of birth weight on developing IBS was tested in four weight groups. Disease discordant monozygotic (MZ) pairs were analysed to test the association between intrauterine growth and IBS. Concordance for IBS was significantly greater (p = 0.011) in monozygotic (22.4%) than in dizygotic (9.1%) twins. The heritability of IBS was estimated to be 48.4% among females. Birth weight below 1500 g (adjusted odds ratio 2.4 (95% confidence interval 1.1, 5.3)) contributed significantly to the development of IBS, which appeared 7.7 years earlier than in higher weight groups. In the MZ group with birth weights lower than 2500 g, twins with IBS were significantly lighter than twins without disease (190.6 g; p = 0.02). The present study demonstrates that restricted fetal growth has a significant influence on the development of IBS later in life. Weight below 1500 g influences age at onset. Genetic contribution appears to be important for IBS among females.


Isomers of C(20): an energy profile.
Semiempirical calucaltions, at the PM 3 level, are used to geometrically optimize and determine the absolute energies (heats of formation) of a variety of C(20) isomers. Based on the geometrically optimized Cartesian coordinates of the ring and the bowl isomers, and the subsequent saddle-point calculation, a two-dimensional energy profile between these two isomers is generated. Performing geometry optimization on the Cartesian coordinates that correspond to energy minima within the ring-bowl profile, we have been able to identify several more isomers of C(20) that are predicted to be energitically stable. With these additional stable structures, we have identified pairs of isomers that lie adjacent to one another on the potential energy surface, as is evidenced by the form of their respective energy profiles. These adjacent pairs of isomers establish a step-wise transformation between the ring and the bowl. This process, which extends out over the three-dimensional surface, is predicted to require less energy than that of the direct, two-dimensional transformation predicted in the ring-bowl profile.


Cochlear implantation in otosclerosis: a unique positioning and programming problem.
A case is reported in which a Nucleus 22 channel cochlear implant was inserted into the basal turn of the cochlea of a patient with advanced otosclerosis. It then passed out of the anterior end of the basal turn into an otospongiotic cavity related to the cochlea. Seven electrodes were located in the basal turn and it was possible to map them sufficiently well for the patient to derive considerable benefit from the implant. The problem of implant induced facial nerve stimulation in otospongiosis is also discussed.


Generation of remote adaptive torsional shear waves with an octagonal phased array to enhance displacements and reduce variability of shear wave speeds: comparison with quasi-plane shear wavefronts.
A method based on adaptive torsional shear waves (ATSW) is proposed to overcome the strong attenuation of shear waves generated by a radiation force in dynamic elastography. During the inward propagation of ATSW, the magnitude of displacements is enhanced due to the convergence of shear waves and constructive interferences. The proposed method consists in generating ATSW fields from the combination of quasi-plane shear wavefronts by considering a linear superposition of displacement maps. Adaptive torsional shear waves were experimentally generated in homogeneous and heterogeneous tissue mimicking phantoms, and compared to quasi-plane shear wave propagations. Results demonstrated that displacement magnitudes by ATSW could be up to 3 times higher than those obtained with quasi-plane shear waves, that the variability of shear wave speeds was reduced, and that the signal-to-noise ratio of displacements was improved. It was also observed that ATSW could cause mechanical inclusions to resonate in heterogeneous phantoms, which further increased the displacement contrast between the inclusion and the surrounding medium. This method opens a way for the development of new noninvasive tissue characterization strategies based on ATSW in the framework of our previously reported shear wave induced resonance elastography (SWIRE) method proposed for breast cancer diagnosis.


gamma-Preprotachykinin-(72-92)-peptide amide: an endogenous preprotachykinin I gene-derived peptide that preferentially binds to neurokinin-2 receptors.
The presence of N-terminally extended forms of neurokinin A has recently been reported in the mammalian brain. Among them, gamma-preprotachykinin-(72-92)-peptide amide [gamma-PPT-(72-92)-NH2], a peptide derived by posttranslational processing of gamma-preprotachykinin, is most prominent. We report here that this peptide most likely acts on neurokinin-2 receptor sites since neurokinin A (a putative neurokinin-2 agonist) and gamma-PPT-(72-92)-NH2 are potent competitors of 125I-labeled gamma-PPT-(72-92)-NH2 binding whereas selective neurokinin-1 and -3 agonists are not. Moreover, the distribution of 125I-labeled gamma-PPT-(72-92)-NH2 and 125I-labeled neurokinin A binding sites are very similar in rat brain. On the other hand, 125I-labeled Bolton-Hunter-substance P (a neurokinin-1 ligand) and 125I-labeled Bolton-Hunter-eledoisin (a neurokinin-3 ligand) binding sites are differentially located in this tissue. Thus, it appears that gamma-PPT-(72-92)-NH2 binds to neurokinin-2 receptors and should be considered as a putative endogenous ligand for this receptor class.


A CMOS application-specified-integrated-circuit for 40 GHz high-electron-mobility-transistors automatic biasing.
This paper presents the design and the experimental results of a CMOS Automatic Control System (ACS) for the biasing of High-Electron-Mobility-Transistors (HEMT). The ACS is the first low-power mixed-signal Application-Specified-Integrated-Circuit (ASIC) able to automatically set and regulate the operating point of an off-chip 6 HEMT Low-Noise-Amplifiers (LNAs), hence it composes a two-chip system (the ACS+LNAs) to be used in the Large Scale Polarization Explorer (LSPE) stratospheric balloon for Cosmic Microwave Background (CMB) signal observation. The hereby presented ACS ASIC provides a reliable instrumentation for gradual and very stable LNAs characterization, switching-on, and operating point (<4 mV accuracy). Moreover, it simplifies the electronic instrumentation needed for biasing the LNAs, since it replaces several off-the-shelf and digital programmable device components. The ASIC prototype has been implemented in a CMOS 0.35 μm technology (12 mm2 area occupancy). It operates at 4 kHz clock frequency. The power consumption of one-channel ASIC (biasing one LNA) is 3.6 mW, whereas 30 mW are consumed by a single LNA device.


Hypnosis, suggestions, and altered states of consciousness: experimental evaluation of the new cognitive-behavioral theory and the traditional trance-state theory of "hypnosis".
Sixty-six subjects were tested on a new scale for evaluating "hypnotic-like" experiences (The Creative Imagination Scale), which includes ten standardized test-suggestions (e.g. suggestions for arm heaviness, finger anesthesia, time distortion, and age regression). The subjects were randomly assigned to one of three treatment groups (Think-With Instructions, trance induction, and Control), with 22 subjects to each group. The new Cognitive-Behavioral Theory predicted that subjects exposed to preliminary instructions designed to demonstrate how to think and imagine along with the suggested themes (Think-With Instructions) would be more responsive to test-suggestions for anesthesia, time distortion, age regression, and so on, than subjects exposed to a trance-induction procedure. On the other hand, the traditional Trance State Theory predicted that a trance induction would be more effective than Think-With Instructions in enhancing responses to such suggestions. Subjects exposed to the Think-With Instructions obtained significantly higher scores on the test-suggestions than those exposed either to the traditional trance-induction procedure or to the control treatment. Scores of subjects who received the trance-induction procedure were not significantly different from those of the subjects who received the control treatment. The results thus supported the new Cognitive-Behavioral Theory and contradicted the traditional Trance State Theory of hypnosis. Two recent experiments, by De Stefano and by Katz, confirmed the above experimental results and offered further support for the Cognitive-Behavioral Theory. In both recent experiments, subjects randomly assigned to a "Think-With Instructions" treatment were more responsive to test-suggestions than those randomly assigned to a traditional trance-induction treatment.


Psoriasis in children.
The clinical presentation, disease associations, and diverse treatment modalities in overcoming the challenges of managing pediatric psoriasis have been extensively summarized in this article. An extensive literature review revealed the differences in presentation of psoriasis during infancy, childhood, and adolescence. We also summarized the latest topical, systemic, and biological modalities in treating recalcitrant psoriasis. The association of psoriasis with juvenile arthritis and obesity and the significant influence of the disease on the children's quality of life were explored. The clinical presentation of psoriasis can evolve during the child's lifespan. While many treatment modalities already exist for treating pediatric psoriasis, some of the new biologics that are approved for adult patients have not been investigated in the pediatric population and no algorithm exists for their use in this population. Large clinical studies in the future will enhance our understanding with regards to their safety and potential implications in pediatric populations.


Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy.
Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. RNA-LPX triggers interferon-α (IFNα) release by plasmacytoid DCs and macrophages. Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated. We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFNα-dependent rejection of progressive tumours. A phase I dose-escalation trial testing RNA-LPX that encode shared tumour antigens is ongoing. In the first three melanoma patients treated at a low-dose level, IFNα and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency. As any polypeptide-based antigen can be encoded as RNA, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-I-IFN-mediated innate immune mechanisms for cancer immunotherapy.


Coincident Hfq binding and RNase E cleavage sites on mRNA and small regulatory RNAs.
The Escherichia coli RNA chaperone Hfq was discovered originally as an accessory factor of the phage Qbeta replicase. More recent work suggested a role of Hfq in cellular physiology through its interaction with ompA mRNA and small RNAs (sRNAs), some of which are involved in translational regulation. Despite their stability under certain conditions, E. coli sRNAs contain putative RNase E recognition sites, that is, A/U-rich sequences and adjacent stem-loop structures. We show herein that an RNase E cleavage site coincides with the Hfq-binding site in the 5'-untranslated region of E. coli ompA mRNA as well as with that in the sRNA, DsrA. Likewise, Hfq protects RyhB RNA from in vitro cleavage by RNase E. These in vitro data are supported by the increased abundance of DsrA and RyhB sRNAs in an RNase E mutant strain as well as by their decreased stability in a hfq(-) strain. It is commonly believed that the RNA chaperone Hfq facilitates or promotes the interaction between sRNAs and their mRNA targets. This study reveals another role for Hfq, that is, protection of sRNAs from endonucleolytic attack.


TNM classification of gynaecological malignant tumours, eighth edition: changes between the seventh and eighth editions.
The staging classification of gynaecological malignancies has been revised by the International Federation of Gynecology and Obstetrics (FIGO) and has been subsequently reviewed by the FIGO Committee on Gynecologic Oncology, the International Union for Cancer Control TNM Committee and the American Joint Committee on Cancer. The major change in the eighth edition of TNM classification of gynaecological malignant tumours is integrated staging for ovarian, fallopian tube and primary peritoneal carcinoma, whereas the seventh edition distinguished 'ovary and primary peritoneal carcinoma' and 'Fallopian tube carcinoma'. Furthermore, the new edition describes a prognostic factor grid for vulvar, cervical, endometrial and ovarian, fallopian tube and primary peritoneal carcinoma. If these factors contribute strongly to the prognosis, they may be incorporated into future staging classifications. This paper reviews the staging system for gynaecological malignancies, how it was developed, and current problems to be resolved.


Ribophorin I regulates substrate delivery to the oligosaccharyltransferase core.
Protein N-glycosylation is widespread among biological systems, and the fundamental process of transferring a lipid-linked glycan to suitable asparagine residues of newly synthesized proteins occurs in both prokaryotes and eukaryotes. The core reaction is mediated by Stt3p family members, and in many organisms this component alone is sufficient to constitute the so called oligosaccharyltransferase (OST). However, eukaryotes typically have a more elaborate OST with several additional subunits of poorly defined function. In the mammalian OST complex one such subunit, ribophorin I, is proposed to facilitate the N-glycosylation of certain precursors during their biogenesis at the endoplasmic reticulum. Here, we use cell culture models to show that ribophorin I depletion results in substrate-specific defects in N-glycosylation, clearly establishing a defined physiological role for ribophorin I. To address the molecular mechanism of ribophorin I function, a cross-linking approach was used to explore the environment of nascent glycoproteins during the N-glycosylation reaction. We show for the first time that ribophorin I can regulate the delivery of precursor proteins to the OST complex by capturing substrates and presenting them to the catalytic core.


Regulation of Serine, Glycine, and One-Carbon Biosynthesis.
The biosynthesis of serine, glycine, and one-carbon (C1) units constitutes a major metabolic pathway in Escherichia coli and Salmonella enterica serovar Typhimurium. C1 units derived from serine and glycine are used in the synthesis of purines, histidine, thymine, pantothenate, and methionine and in the formylation of the aminoacylated initiator fMet-TRNAfMet used to start translation in E. coli and serovar Typhimurium. The need for serine, glycine, and C1 units in many cellular functions makes it necessary for the genes encoding enzymes for their synthesis to be carefully regulated to meet the changing demands of the cell for these intermediates. This review discusses the regulation of the following genes: serA, serB, and serC; gly gene; gcvTHP operon; lpdA; gcvA and gcvR; and gcvB genes. Threonine utilization (the Tut cycle) constitutes a secondary pathway for serine and glycine biosynthesis. L-Serine inhibits the growth of E. coli cells in GM medium, and isoleucine releases this growth inhibition. The E. coli glycine transport system (Cyc) has been shown to transport glycine, D-alanine, D-serine, and the antibiotic D-cycloserine. Transport systems often play roles in the regulation of gene expression, by transporting effector molecules into the cell, where they are sensed by soluble or membrane-bound regulatory proteins.


PEGylated helper-dependent adenoviral vector expressing human Apo A-I for gene therapy in LDLR-deficient mice.
Helper-dependent adenoviral (HD-Ad) vectors have great potential for gene therapy applications; however, their administration induces acute toxicity that impairs safe clinical applications. We previously observed that PEGylation of HD-Ad vectors strongly reduces the acute response in murine and primate models. To evaluate whether PEGylated HD-Ad vectors combine reduced toxicity with the correction of pathological phenotypes, we administered an HD-Ad vector expressing the human apolipoprotein A-I (hApoA-I) to low-density lipoprotein (LDL)-receptor-deficient mice (a model for familial hypercholesterolemia) fed a high-cholesterol diet. Mice were treated with high doses of HD-Ad-expressing apo A-I or its PEGylated version. Twelve weeks later, LDL levels were lower and high-density lipoprotein (HDL) levels higher in mice treated with either of the vectors than in untreated mice. After terminal killing, the areas of atherosclerotic plaques were much smaller in the vector-treated mice than in the control animals. Moreover, the increase in pro-inflammatory cytokines was lower and consequently the toxicity profile better in mice treated with PEGylated vector than in mice treated with the unmodified vector. This finding indicates that the reduction in toxicity resulting from PEGylation of HD-Ad vectors does not impair the correction of pathological phenotypes. It also supports the clinical potential of these vectors for the correction of genetic diseases.


Feasibility of spacers to facilitate postoperative radiotherapy for retroperitoneal sarcomas.
The role and timing of postoperative radiotherapy (PORT) in the management of retroperitoneal sarcoma (RPS) remains controversial. This is a retrospective cohort review of patients undergoing curative resection for RPS at a single institution between January 2011 and July 2016. Patient selection was through the South Australian Soft Tissue Tumour Multidisciplinary Group (MDT) based at Royal Adelaide Hospital. An individualised approach, including assessment of resectability, histopathological grade and subtype, and radiotherapy considerations, was taken for each patient. Patients offered preoperative radiotherapy or palliation were excluded. A saline-filled spacer was inserted following operative resection. Radiotherapy commenced postoperatively. Patients underwent laparotomy to remove the device approximately 6 weeks post completion of PORT. Primary endpoints were technical feasibility, perioperative morbidity and radiation toxicity. Secondary endpoints were local recurrence (LR), distant recurrence (DR) and death. During the study period, 40 patients with RPS were managed through the MDT. Twelve patients (ages 33-78) underwent PORT utilising spacers. Radiotherapy toxicity was reported in four patients and extensive adhesions observed in another four patients during spacer removal. Median follow-up was 35 months (range 4-60). Seven patients remain alive and disease free. Four patients developed LR, three developed DR. Three patients died; two with DR and one with LR. Two patients with recurrent/progressive disease are alive; one with DR and one with LR. Use of intraoperative spacers to facilitate PORT is feasible, with acceptable toxicity following resection of RPS. Patient selection for this approach remains to be determined.


The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review.
Cancer is a multi-stage process resulting from aberrant signaling pathways driving uncontrolled proliferation of transformed cells. The development and progression of cancer from a premalignant lesion towards a metastatic tumor requires accumulation of mutations in many regulatory genes of the cell. Different chemopreventative approaches have been sought to interfere with initiation and control malignant progression. Here we present research on dietary compounds with evidence of cancer prevention activity that highlights the potential beneficial effect of a diet rich in cruciferous vegetables. The Brassica family of cruciferous vegetables such as broccoli is a rich source of glucosinolates, which are metabolized to isothiocyanate compounds. Amongst a number of related variants of isothiocyanates, sulforaphane (SFN) has surfaced as a particularly potent chemopreventive agent based on its ability to target multiple mechanisms within the cell to control carcinogenesis. Anti-inflammatory, pro-apoptotic and modulation of histones are some of the more important and known mechanisms by which SFN exerts chemoprevention. The effect of SFN on cancer stem cells is another area of interest that has been explored in recent years and may contribute to its chemopreventive properties. In this paper, we briefly review structure, pharmacology and preclinical studies highlighting chemopreventive effects of SFN.


Observational study: microgravity testing of a phase-change reference on the International Space Station.
Orbital sensors to monitor global climate change during the next decade require low-drift rates for onboard thermometry, which is currently unattainable without on-orbit recalibration. Phase-change materials (PCMs), such as those that make up the ITS-90 standard, are seen as the most reliable references on the ground and could be good candidates for orbital recalibration. Space Dynamics Lab (SDL) has been developing miniaturized phase-change references capable of deployment on an orbital blackbody for nearly a decade. Improvement of orbital temperature measurements for long duration earth observing and remote sensing. To determine whether and how microgravity will affect the phase transitions, SDL conducted experiments with ITS-90 standard material (gallium, Ga) on the International Space Station (ISS) and compared the phase-change temperature with earth-based measurements. The miniature on-orbit thermal reference (MOTR) experiment launched to the ISS in November 2013 on Soyuz TMA-11M with the Expedition 38 crew and returned to Kazakhstan in March 2014 on the Soyuz TMA-10 spacecraft. MOTR tested melts and freezes of Ga using repeated 6-h cycles. Melt cycles obtained on the ground before and after launch were compared with those obtained on the ISS. To within a few mK uncertainty, no significant difference between the melt temperature of Ga at 1 g and in microgravity was observed.


Antibiotic resistance patterns of pediatric community-acquired urinary infections.
Knowledge about antimicrobial resistance patterns of the etiological agents of urinary tract infections (UTIs) is essential for appropriate therapy. Urinary isolates from symptomatic UTI cases attended at Santa Casa University Hospital of São Paulo from August 1986 to December 1989 and August 2004 to December 2005 were identified by conventional methods. Antimicrobial resistance testing was performed by Kirby Bauer's disc diffusion method. Among the 257 children, E. coli was found in 77%. A high prevalence of resistance was observed against ampicillin and TMP/SMX (55% and 51%). The antibiotic resistance rates for E. coli were: nitrofurantoin (6%), nalidixic acid (14%), 1st generation cephalosporin (13%), 3rd generation cephalosporins (5%), aminoglycosides (2%), norfloxacin (9%) and ciprofloxacin (4%). We found that E. coli was the predominant bacterial pathogen of community-acquired UTIs. We also detected increasing resistance to TMP/SMX among UTI pathogens in this population.


The state of leadership education in US medical schools: results of a national survey.
Over the past two decades, there have been increasing calls for physicians to develop the capabilities to lead health care transformation. Many experts and authors have suggested that leadership education should begin during medical school; however, little information exists regarding the presence or nature of undergraduate medical education leadership curricula in the USA. This study sought to determine the prevalence of formal leadership education in US undergraduate medical schools, as well as the delivery methods and degree of student participation. A web-based survey of medical education deans from US allopathic medical schools (N = 144) was administered from November 2014 to February 2015. The survey included questions on the presence of leadership curricula, delivery format, student participation rates, and forms of recognition. Eighty-eight surveys were completed; the majority (85%) of respondents were associate or assistant deans for medical education. Approximately half (54.5%) of respondents reported leadership curricula within their medical schools. Of those, 34.8% (16/46) were required; 32.6% (15/46) were elective; and 32.6% (15/46) indicated both required and elective components. Of schools with formal leadership curricula (n = 48), the common forms of content delivery were: mentoring programs (65.1%); dual degree programs (54.5%); workshops (48.8%); seminar/lecture series (41.9%); courses (41.9%); or single seminars (18.6%). Nineteen percent of institutions offer longitudinal leadership education throughout medical school. Common forms of recognition for leadership education were: course credit (48.8%); dual degrees (37.2%); certificates of completion (18.6%); and transcript notations (7.0%). This study indicates that formal leadership education exists in more than half of US allopathic medical schools, suggesting it is an educational priority. Program format, student participation, delivery methods, and recognition varied considerably. Further study is needed to identify the optimal content, competencies, and pedagogy for leadership education. Identifying best practices may help guide standards for leadership curricula across UME and fill this educational need..


Sustained impairment of IFN-gamma secretion in suppressed HIV-infected patients despite mature NK cell recovery: evidence for a defective reconstitution of innate immunity.
The impairment of NK cell functions in the course of HIV infection contributes to a decreased resistance against HIV and other pathogens. We analyzed the proportion of mature and immature NK cell subsets, and measured subsets of IFN-gamma and TNF-alpha-producing NK and T cells in viremic or therapy-suppressed HIV-infected subjects, and noninfected control donors. Viremic HIV(+) individuals had significantly lower proportions of mature CD3(-)/CD161(+)/CD56(+) NK cells and of IFN-gamma-producing NK cells compared with noninfected donors, independent of CD4(+) T cell counts. HIV-infected subjects with undetectable viral load recovered mature CD3(-)/CD161(+)/CD56(+) NK cells and cytotoxicity against tumor (K562) and HSV-infected target cells to percentages comparable with those of uninfected individuals, but their NK cells remained impaired in their ability to produce IFN-gamma. In parallel to these ex vivo findings, in vitro NK cell differentiation of CD34-positive cord blood precursors in the presence of R5 or X4 HIV-1 resulted in the production of NK cells with a normal mature phenotype, but lacking the ability to produce IFN-gamma, whereas coculture of uninfected PBMC with HIV failed to affect mature NK cell properties or IFN-gamma secretion. Altogether, our findings support the hypothesis that mature NK cell phenotype may be uncoupled from some mature functions following highly active antiretroviral therapy-mediated suppression of HIV-1, and indicate that relevant innate immune functions of NK cell subsets may remain altered despite effective viral suppression following antiretroviral treatment.


Benzodiazepine problems.
Benzodiazepines present problems related to both unwanted and withdrawal effects. Dosage adjustments usually obviate unwanted effects except for paradoxical reactions such as hostility. Patients with apparent benzodiazepine dependence need careful assessment with respect to personality, social situation and psychiatric disorder. The patient must be motivated and carefully prepared for withdrawal and taught anxiety management techniques. Withdrawal must always be gradual over at least 6 weeks but very prolonged schedules are counter-productive. Substituting a long-acting for a medium-acting benzodiazepine may be helpful in the more intractable cases. An antidepressant may be needed if a depressive disorder supervenes, but other adjunctive therapies are usually unhelpful.


Alum Adjuvant and Built-in TLR7 Agonist Synergistically Enhance Anti-MUC1 Immune Responses for Cancer Vaccine.
The tumor-associated antigen mucin 1 (MUC1) is an attractive target of antitumor vaccine, but its weak immunogenicity is a big challenge for the development of vaccine. In order to enhance immune responses against MUC1, herein, we conjugated small molecular toll-like receptor 7 agonist (TLR7a) to carrier protein BSA via MUC1 glycopeptide to form a three-component conjugate (BSA-MUC1-TLR7a). Furthermore, we combined the three-component conjugate with Alum adjuvant to explore their synergistic effects. The immunological studies indicated that Alum adjuvant and built-in TLR7a synergistically enhanced anti-MUC1 antibody responses and showed Th1-biased immune responses. Meanwhile, antibodies elicited by the vaccine candidate effectively recognized tumor cells and induced complement-dependent cytotoxicity. In addition, Alum adjuvant and built-in TLR7a synergistically enhanced MUC1 glycopeptide-specific memory CD8+ T-cell immune responses. More importantly, the vaccine with the binary adjuvant can significantly inhibit tumor growth and prolong the survival time of mice in the tumor challenge experiment. This novel vaccine construct provides an effective strategy to develop antitumor vaccines.


Fine structural changes of peripheral cystoid degenerations during life.
Peripheral cystoid degeneration is the result of malnutrition of the retinal tissue, already observed in postnatal development. The morphological substrate for a disturbance in the function of the blood-retinal barrier at the ora is the presence of a perivascular space around the capillaries.


[Nuclear medicine: current aspects and future].
A survey of the range and progress of nuclear medicine procedures is presented and the accuracy of the modalities is described. The priority in nuclear medicine diagnosis has shifted from proof of the non-functioning nodule to localization of biochemical lesions with the aid of new bioindicators and single photon and positron emission computer tomography. Diagnosis has extended to subcellular regions with the introduction of immunoscintigraphy as well as enzyme and receptor scintigraphy. This is a new dimension to which Swiss nuclear medicine specialists have contributed a great deal.


Nanoclusters with specific DNA overhangs: modifying configurability, engineering contrary logic pairs and the parity generator/checker for error detection.
The most promising alternative for next-generation molecular computers is biocomputing, which uses DNAs as its primary building blocks to perform a Boolean operation. DNA nanoclusters (NCs) have emerged as promising candidates for biosensing applications due to their unique self-assembly properties and programmability. It has been demonstrated that adding DNA overhangs to DNA NCs improves their adaptability in identifying specific biomolecular interactions. A recent proposal in DNA computing is the concept of "contrary logic pairs (CLPs)" executed by employing a DNA hybrid architecture as a universal platform. We have designed thymine overhang-modified DNA-templated NCs (T-Au/Ag NCs). These NCs serve as a chemosensing ensemble platform, where the presence of HgII ions mediates the formation of M-Au/Ag NCs. The resulting NCs exhibit the capability to drive elementary CLPs (YES, NOT, OR, NOR, INH and IMP) as well as complex logic operations (XOR and XNOR). Additionally, they can be utilized for advanced non-arithmetic DNA logic devices like a parity generator (pG) and a parity checker (pC) for "error detection". Bit errors are an unavoidable and common occurrence during any computing. A cascade of XOR operations was used to evaluate these errors by introducing the pG and pC at the transmitting (TX) and receiving (RX) ends in binary transmission, respectively, which has devastating implications for reliable logic circuits, especially in advanced logic computation. Moreover, an even/odd natural number from 0 to 9 distinguishable pC was designed based on a dual-source responsive computing platform. This work offers inspiring avenues for a cost-effective strategy to construct highly-intelligent DNA computing devices by enhancing the multi-input responsive single DNA platform concept.