Diagnostic efficiency of abattoir meat inspection service in Ethiopia to detect carcasses infected with Mycobacterium bovis: implications for public health.
Bovine Tuberculosis (BTB) is a widespread and endemic disease of cattle in Ethiopia posing a significant threat to public health. Regular surveillance by skin test, bacteriology and molecular methods is not feasible due to lack of resource. Thus, routine abattoir (RA) inspection will continue to play a key role for national surveillance. We evaluated efficiency of RA inspection for diagnosis of Mycobacterium bovis infection and discussed its public health implications in light of a high risk of human exposure. The study was conducted in five abattoirs: Addis Ababa, Adama, Hawassa, Yabello and Melge-Wondo abattoirs. The efficiency of routine abattoir (RA) inspection was validated in comparison to detailed abattoir (DA) inspection, followed by culture and microscopy (CM) and region of difference (RD) deletion analysis. Diagnostic accuracies (with corresponding measures of statistical uncertainty) were determined by computing test property statistics (sensitivity and specificity) and likelihood estimations using web-based SISA diagnostic statistics software. Post-test probability of detecting TB infected carcasses was estimated using nomograms. Agreement between RA and DA inspections was measured using kappa statistics. The study was conducted and reported in accordance with standards for reporting of diagnostic accuracy (STARD) requirements. Both routine and detailed meat inspection protocols were performed on a subpopulation of 3322 cattle selected randomly from among 78,269 cattle slaughtered during the study period. Three hundred thirty seven carcasses identified through detailed meat inspection protocols were subjected to culture and microscopy; of the 337, a subset of 105 specimens for culture and microscopy were subjected to further molecular testing. There was a substantial agreement between RA and DA inspections in Addis Ababa (Kappa = 0.7) and Melge-Wondo abattoirs (Kappa = 0.67). In Adama, Hawassa and Yabello abattoirs, the agreement was however poor (Kappa <or= 0.2). RA inspection was able to detect only 117 of the total 3322 carcasses inspected (3.5%). The sensitivity (Sn) and specificity (Sp) of RA inspection were 28.2% (95/337) [95%CI: 23.4-33.0] and 99.3% (2963/2985) [95%CI: 99.0-99.6], respectively, when DA inspection was considered as reference test. When culture and microscopy (CM) was considered as reference test, the Sn and Sp of RA were 55.2% (58/105) [95%CI: 45.7-64.7] and 84.1% (195/232) [95%CI: 79.3-88.8]. RA inspection failed to detect 71.8% (242/337) and 44.8% (47/105) of TB infected carcasses as judged by DA inspection and CM, respectively. On the other hand, a much higher sensitivity of DA was obtained when CM and RD deletion analysis were considered as reference tests (96.3% (105/109) and 100.0% (24/24), respectively). The study results indicate that meat inspection protocols currently utilized in abattoirs are insufficient to detect the majority of TB lesions at the gross level. DA inspection protocols were demonstrated to improve the detection level by approximately 3-fold. The failure of current inspection techniques to detect approximately 70% of carcasses presented with grossly-visible lesions of TB at the slaughter-plants indicates the magnitude of meat-borne zoonotic TB as an on-going risk to public health. Standardization of abattoir inspection protocols (in line with international sanitary requirements), enhanced training and proficiency testing of meat inspections, and raising public awareness are recommended as essential and cost-effective interventions to improve meat inspection service in Ethiopia, with subsequent protection of consumers' health.


Endoscopic versus open microvascular decompression for trigeminal neuralgia: a systematic review and comparative meta-analysis.
OBJECTIVEMicrovascular decompression (MVD) is commonly used in the treatment of trigeminal neuralgia (TN) with positive clinical outcomes. Fully endoscopic MVD (E-MVD) has been proposed as an effective minimally invasive alternative, but a comparative review of the two approaches has not been conducted. The authors performed a meta-analysis of studies, comparing patient outcome rates and complications for the open versus the endoscopic technique.METHODSThe PubMed/MEDLINE and Ovid databases were searched for studies published from database inception to 2017. The search terms used included, but were not limited to, "open microvascular decompression," "microvascular decompression for trigeminal neuralgia," and "endoscopic decompression for trigeminal neuralgia." Criteria for inclusion of studies in the meta-analysis were established as follows: adult patients, clinical studies with ≥ 10 patients (excluding case studies to obtain a higher volume of outcome rates), utilization of open MVD or E-MVD to treat TN, craniotomy and retrosigmoid incision, English-language studies, and articles that listed pain relief outcomes (complete, very good, partial, or absent), recurrence rate (number of patients), and complications (paresis, hearing loss, CSF leakage, cerebellar damage, infection, death). Relevant references from the chosen articles were also included.RESULTSFrom a larger pool of 1039 studies, 23 articles were selected for review: 13 on traditional MVD and 10 on E-MVD. The total number of patients was 6749, of which 5783 patients (and 5802 procedures) had undergone MVD and 993 patients (and procedures) had undergone E-MVD. Analyzed data included postoperative pain relief outcome (complete or good pain relief vs partial or no pain relief), and rates of recurrence and complications including facial paralysis, weakness, or paresis; hearing loss; auditory and facial nerve damage; cerebrospinal fluid leakage; infection; cerebellar damage; and death.Good pain relief was achieved in 81% of MVD patients and 88% of E-MVD patients, with a mean recurrence rate of 14% and 9%, respectively. Average rates of reported complications were statistically lower in E-MVD than in MVD approaches, including facial paresis or weakness, hearing loss, cerebellar damage, infection, and death, whereas cerebrospinal fluid leakage was similar. The overall incidence of complications was 19% for MVD and 8% for E-MVD.CONCLUSIONSThe reviewed literature revealed similar clinical outcomes with respect to pain relief for MVD and E-MVD. The recurrence rate was lower in E-MVD studies, though not significantly so, and the incidence of complications, notably facial paresis and hearing loss, were statistically higher for MVD than for E-MVD. Based on these results, the use of endoscopy to perform MVD for TN appears to offer at least as good a surgical outcome as the more commonly used open MVD, with the possible added advantages of having a shorter operative time, smaller craniotomy, and lower recurrence rates. The authors advise caution in interpreting these data given the asymmetry in the sample size between the two groups and the relative novelty of the E-MVD approach.


Facile synthesis and potential application of Ni0.6Zn0.4Fe2O4 and Ni0.6Zn0.2Ce0.2Fe2O4 magnetic nanocubes as a new strategy in sewage treatment.
Disinfection using chlorine has paramount importance in the treatment of either drinking water or sewage since it can kill and inhibit all waterborne pathogens, but it may result in carcinogenic substances when interacting with organic matter. An eco-friendly sol-gel process with citrate was used to prepare the nano-cubic activated nickel-zinc ferrite magnetic nanostructures (Ni0.6Zn0.4Fe2O4 and Ni0.6Zn0.2Ce0.2Fe2O4). The activated nanomagnetic samples were characterized using XRD, HR-TEM, HR-SEM, FTIR, and VSM techniques. The structural and magnetic results showed that the nano-cubes magnetic-structures exhibited higher crystalline degrees and an increase in the total magnetization, enabling spinel nano-ferrite to possess potentials for excellent industry various applications. Likewise, the VSM results reveal that Ce2O3 had a significant influence on the magnetic behavior such as the coercivity (Hc; 69.226-133.15) saturation and magnetization (Ms; 24.562-52.174). The results revealed that all Magnetic nanoparticles (MNPs) had an outstanding inhibitory effect on microbes tested. The manufactured particles showed a remarkable ability to eliminate pathogenic bacteria in real sewage samples. The results obtained endorsed that the manufactured magnetic nanoparticles (MNPs) are powerful nano-weapons with an excellent anticipated output for the deactivation of pathogenic microbes during sewage treatment, with, nickel-zinc-cerium ferrite being more effective in inhibiting microbial growth than nickel-zinc-cerium ferrite.


Mechanism for the suppression of the mammalian stress response by genistein, an anticancer phytoestrogen from soy.
Soy products contain high levels of genistein, a phytoestrogen that is a potent inhibitor of cell proliferation and angiogenesis. Genistein has been found to inhibit the growth of carcinogen-induced cancers in rats and human leukemia cells transplanted into mice. The induction of stress proteins (e.g., glucose-related proteins and heat shock proteins) in tumor cells has been shown to protect them against programmed cell death; this stress response is inhibited by genistein. The mechanism(s) by which genistein affects certain stress response genes was explored in this study. Mammalian cell cultures were treated with azetidine, a proline analog, which elicits a stress response that includes the induction of the expression of glucose-regulated protein GRP78 and heat shock protein HSP70. The effects of azetidine and/or genistein treatment on cellular levels of grp78 and hsp70 messenger RNAs and proteins were measured by northern blot hybridization and western blot analyses, respectively, and the binding of nuclear factors to sequence motifs in the upstream (promoter) regions of these two genes were examined by electrophoretic mobility shift assays. Genistein antagonized the binding of a specific transcription factor, nuclear factor-Y/CCAAT binding factor (NF-Y/CBF), to the CCAAT sequence element most proximal to the transcription start sites in the hsp70 and grp78 promoters; this CCAAT element was previously shown to be necessary for full-stress inducibility of both genes. Treatment of cells with genistein converted NF-Y/CBF into a nonbinding, transcriptionally inactive form. The anticancer effects of genistein may be related to its ability to reduce the expression of stress response-related genes.


The significance of historical troponin elevation in acute heart failure: Not as reassuring as previously assumed.
Historical cardiac troponin (cTn) elevation is commonly interpreted as lessening the significance of current cTn elevations at presentation for acute heart failure (AHF). Evidence for this practice is lacking. Our objective was to determine the incremental prognostic significance of historical cTn elevation compared to cTn elevation and ischemic heart disease (IHD) history at presentation for AHF. A total of 341 AHF patients were prospectively enrolled at five sites. The composite primary outcome was death/cardiopulmonary resuscitation, mechanical cardiac support, intubation, new/emergent dialysis, and/or acute myocardial infarction (AMI)/percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG) at 90 days. Secondary outcomes were 30-day AMI/PCI/CABG and in-hospital AMI. Logistic regression compared outcomes versus initial emergency department (ED) cTn, the most recent electronic medical record cTn, estimated glomerular filtration rate, age, left ventricular ejection fraction, and IHD history (positive, negative by prior coronary workup, or unknown/no prior workup). Elevated cTn occurred in 163 (49%) patients, 80 (23%) experienced the primary outcome, and 29 had AMI (9%). cTn elevation at ED presentation, adjusted for historical cTn and other covariates, was associated with the primary outcome (adjusted odds ratio [aOR] 2.39, 95% confidence interval [CI] 1.30-4.38), 30-day AMI/PCI/CABG, and in-hospital AMI. Historical cTn elevation was associated with greater odds of the primary outcome when IHD history was unknown at ED presentation (aOR 5.27, 95% CI 1.24-21.40) and did not alter odds of the outcome with known positive (aOR 0.74, 95% CI 0.33-1.70) or negative IHD history (aOR 0.79, 95% CI 0.26-2.40). Nevertheless, patients with elevated ED cTn were more likely to be discharged if historical cTn was also elevated (78% vs. 32%, p = 0.025). Historical cTn elevation in AHF patients is a harbinger of worse outcomes for patients who have not had a prior IHD workup and should prompt evaluation for underlying ischemia rather than reassurance for discharge. With known IHD history, historical cTn elevation was neither reassuring nor detrimental, failing to add incremental prognostic value to current cTn elevation alone.


CD93 and related family members: their role in innate immunity.
CD93 belongs to a newly described family of transmembrane glycoproteins which also includes endosialin and thrombomodulin. These cell surface proteins are grouped into a family based on similar ectodomain architecture consisting of a C-type lectin-like domain, a series of EGF-like repeats and a highly glycosylated mucin-like domain. However, recent studies suggest overlapping functions in the regulation of processes involving innate immunity and inflammation. CD93 regulates phagocytosis of apoptotic cells in vivo, a function critical to development, tissue repair and maintenance of tissue homeostasis. In addition, in vitro studies have demonstrated a role for CD93 in phagocytosis of antibody and complement opsonized particles and also in leukocyte and endothelial cell adhesion. Analysis of CD93 expression on endothelial cells in the developing mouse embryo correlates with the remodeling of blood vessels suggesting a role for CD93 in regulating angiogenesis, a process tightly linked to acute and chronic inflammation and also required for tumor metastasis. Endosialin has been characterized as a tumor specific antigen and functions in angiogenesis. Thrombomodulin is best characterized as a natural anticoagulant; however, more recent reports have illuminated the importance of thrombomodulin in the regulation of inflammation. This review discusses similarities and differences in the family members, and focuses on known and speculated functions in regulation of innate immunity.


Pituitary specific retinoid-X receptor ligand interactions with thyroid hormone receptor signaling revealed by high throughput reporter and endogenous gene responses.
Disruption of thyroid hormone (TH) signaling can compromise vital processes both during development and in the adult. We previously reported on high-throughput screening experiments for man-made TH disruptors using a stably integrated line of rat pituitary cells, GH3.TRE-Luc, in which a thyroid hormone receptor (TR) response element drives luciferase (Luc) expression. In these experiments, several retinoid/rexinoid compounds activated the reporter. Here we show that all-trans and 13-cis retinoic acid appear to function through the heterodimer partners of TRs, retinoid-X receptors (RXRs), as RXR antagonists abrogated retinoid-induced activation. The retinoids also induced known endogenous TR target genes, showing good correlation with Luc activity. Synthetic RXR-specific agonists significantly activated all tested TR target genes, but interestingly, retinoid/rexinoid activation was more consistent between genes than the extent of T3-induced activation. In contrast, the retinoids neither activated the Luc reporter construct in transient transfection assays in the human hepatocarcinoma cell line HuH7, nor two of the same T3-induced genes examined in pituitary cells. These data demonstrate the suitability and sensitivity of GH3.TRE-Luc cells for screening chemical compound libraries for TH disruption and suggest that the extent of disruption can vary on a cell type and gene-specific bases, including an underappreciated contribution by RXRs.


[Preventable hospital acquired infections are common].
Preventable hospital acquired infections are common A modified GTT (Global trigger tool) was used for 480 patient records from 15 departments at Linköping University Hospital. Sixty-three hospital-acquired infections (HAI) were detected at 59 admissions. Postoperative wound infections were most common (44.4 %). Catheter-related urinary infections occurred in 15.9 %, infections associated with a central venous catheter in 7.9 % and hospital-acquired pneumonia in 6.3 % of all HAI. Other types of HAI consisting of any abscess or oral Candida infection composed 17.5 %. Some 221 patients were operated (46.0 %). Postoperative wound infections were diagnosed in 28 of them (12.7 %), the majority after discharge from hospital. Most urinary infections were diagnosed in emergency patients (8/10). Prolonged hospital stay or unplanned return to hospital occurred in 54 %. Out of 63 HAI some 76.2 % were judged as probably preventable, and 11.1 % as preventable.


Nitric oxide: an antioxidant and neuroprotector.
Indirect evidence, including neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-neurotoxicity by nitric oxide synthase (NOS) inhibitors and resistance of transgenic animals deficient in NOS, is controversial. We have reviewed evidence in favor of oxidative stress during the development of MPTP-neurotoxicity and the influence of antioxidants, including nitric oxide (NO) and NO donors, on MPTP-induced dopaminergic neurotoxicity. Systemic administration of MPTP causes dose-dependent generation of hydroxyl radicals (OH) in vivo in the striatum in mice; OH scavengers protect dopaminergic neurons from this insult. On the other hand the role of NO in MPTP-neurotoxicity is controversial. Hitherto, no direct evidence for the involvement of NO in MPTP neurotoxicity has been available. MPTP does not affect inducible-NOS mRNA level or its expression in SN or the striatum. Nitroglycerine, a NO donor, can attenuate MPTP-induced dopamine depletion in the striatum by virtue of its OH scavenging action. Several other NO donors have also been shown to scavenge the OH generated, following Fenton chemistry in vitro, and to protect against in vivo dopaminergic neurotoxicity by small mass iron complex formation. This evidence suggests that NO renders protection against MPTP-induced OH-mediated nigrostriatal lesions, acting as an antioxidant.


Localization of a Mr 52,000 keratin in basal epithelial cells of the mouse bladder and expression throughout neoplastic progression.
In this study, we report the isolation of a Mr 52,000 keratin from a nontumorigenic bladder epithelial cell line and its localization, by immunofluorescence, in bladder frozen sections at different stages of neoplastic progression and in various carcinogen-transformed bladder epithelial cells and human bladder carcinoma-derived cell lines. The results showed that: (a) the Mr 52,000 keratin is present in basal epithelial cells of the normal bladder but absent from the intermediate and superficial epithelial cell layers; (b) hyperplastic bladder lesions, induced in mice after the administration of butyl-(4-hydroxybutyl)-nitrosamine, resulted primarily from the proliferation of cells in the basal compartment; (c) butyl-(4-hydroxybutyl)nitrosamine-induced bladder carcinomas displayed differential staining with the anti-Mr 52,000 keratin antiserum reflecting divergent differentiated status within a tumor and a subpopulation of cells with reduced overall keratin expression; (d) primary cultures of bladder carcinomas revealed a subpopulation of cells with limited filamentous keratin as was observed in vivo; (e) mouse bladder epithelial cell lines transformed in culture by a chemical carcinogen showed a loss or reduction in expression of the Mr 52,000 keratin; (f) two human bladder carcinoma cell lines displayed very limited expression of the Mr 52,000 keratin. Although the loss or reduction in expression of a specific keratin is unlikely to be responsible for transformation, it may contribute to the heterogeneity in the differentiated state and morphology of bladder epithelial cells during neoplastic progression both in vivo and in culture.


Sampling protein form and function with the atomic force microscope.
To study the structure, function, and interactions of proteins, a plethora of techniques is available. Many techniques sample such parameters in non-physiological environments (e.g. in air, ice, or vacuum). Atomic force microscopy (AFM), however, is a powerful biophysical technique that can probe these parameters under physiological buffer conditions. With the atomic force microscope operating under such conditions, it is possible to obtain images of biological structures without requiring labeling and to follow dynamic processes in real time. Furthermore, by operating in force spectroscopy mode, it can probe intramolecular interactions and binding strengths. In structural biology, it has proven its ability to image proteins and protein conformational changes at submolecular resolution, and in proteomics, it is developing as a tool to map surface proteomes and to study protein function by force spectroscopy methods. The power of AFM to combine studies of protein form and protein function enables bridging various research fields to come to a comprehensive, molecular level picture of biological processes. We review the use of AFM imaging and force spectroscopy techniques and discuss the major advances of these experiments in further understanding form and function of proteins at the nanoscale in physiologically relevant environments.


Parametric and genetic analysis of Drosophila appetitive long-term memory and sugar motivation.
Distinct forms of memory can be highlighted using different training protocols. In Drosophila olfactory aversive learning, one conditioning session triggers memory formation independently of protein synthesis, while five spaced conditioning sessions lead to the formation of long-term memory (LTM), a long-lasting memory dependent on de novo protein synthesis. In contrast, one session of odour-sugar association appeared sufficient for the fly to form LTM. We designed and tuned an apparatus that facilitates repeated discriminative conditioning by alternate presentations of two odours, one being associated with sugar, as well as a new paradigm to test sugar responsiveness (SR). Our results show that both SR and short-term memory (STM) scores increase with starvation length before conditioning. The protein dependency of appetitive LTM is independent of the repetition and the spacing of training sessions, on the starvation duration and on the strength of the unconditioned stimulus. In contrast to a recent report, our test measures an abnormal SR of radish mutant flies, which might initiate their STM and LTM phenotypes. In addition, our work shows that crammer and tequila mutants, which are deficient for aversive LTM, present both an SR and an appetitive STM defect. Using the MB247-P[switch] system, we further show that tequila is required in the adult mushroom bodies for normal sugar motivation.


Identifying and distinguishing treatment effects and complications from malignancy at FDG PET/CT.
Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is increasingly used in the initial staging, evaluation of treatment response, and surveillance of many malignancies. Uptake of FDG is substantially increased in most malignancies, compared with its uptake in normal tissues, and the finding of FDG avidity often leads to cancer detection earlier than abnormalities can be seen at anatomic imaging. However, FDG is not a cancer-specific agent, and FDG avidity can be seen in many benign processes. It can be particularly challenging to discriminate malignancy from benign FDG-avid changes caused by surgery and procedures, radiation therapy, and chemotherapy. FDG-avid abnormalities caused by surgery and procedures include inflammation at sites of incision or dissection, inflammation from vascular compromise or surgical retraction, surgical transposition of structures with physiologic FDG avidity (such as ovaries or testes), and pleurodesis inflammation. Radiation therapy may induce FDG-avid pneumonitis, esophagitis, or hepatitis, as well as osteoradionecrosis or fractures. FDG-avid chemotherapy complications include pneumonitis, osteonecrosis, enterocolitis, and pancreatitis. Use of granulocyte colony stimulating factor for treatment of bone marrow suppression after chemotherapy induces temporary increases of FDG avidity in the bone marrow and spleen. Familiarity with common and unusual iatrogenic causes of FDG avidity that can confound interpretation of FDG PET/CT results will improve the accuracy of distinguishing treatment effects and complications from residual or recurrent malignancy at FDG PET/CT examinations.


Gene frequency comparisons between taxa: support for the natural selection of protein polymorphisms.
The hypothesis has been advanced that the pervasive protein variation found in natural populations of many organisms is adaptively neutral, and thus not subject to natural selection. This neutrality hypothesis predicts that at polymorphic gene loci different configurations of allelic frequencies will occur in different species. Results of an extensive study of protein variation in several species of Drosophila show that any two species have very similar allelic frequencies at a substantial proportion of all gene loci, while at many other loci the species have very different sets of alleles. Genetic distances have been calculated between pairs of subspecies, morphologically similar species, and morphologically different species. The distribution of genetic distances is strikingly different from the predictions of the neutrality theory. Protein variation appears to be maintained by natural selection.


Urinary excretion of 1-hydroxypyrene as a marker for exposure to urban air levels of polycyclic aromatic hydrocarbons.
A cross-sectional study was conducted among 94 traffic police officers from the Municipality Police of Genoa, Italy, exposed to airborne pollutants and 52 referent subjects exposed to indoor air pollution levels to investigate the relationships between exposure to ambient air polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 1-hydroxypyrene (1-OH-P). The effects of smoking, lifestyle factors such as exposure to ETS, and diet, along with the role played by the cytochrome P4501A1 (CYP1A1), and glutathione S-transferase M1 and theta metabolic susceptibility gene polymorphisms were examined. The geometric mean of benzo(a)pyrene air measurements (an index compound of PAH levels) was 70 times higher in traffic police officers (3.67 ng/m3) than in referents (0.05 ng/m3). The urinary concentration of 1-OH-P was clearly associated with cigarette smoking and, to a lesser extent, with exposure to ETS and particulate PAH pollution. No association was detected between 1-OH-P excretion and diet. Women exhibited a higher excretion level than did men, and an apparent effect of age was due to differences in cigarette smoking habits. Exposure to PAHs resulted in higher levels of 1-OH-P excretion in all groups except heavy smokers. Overall, no significant role of any metabolic polymorphism was detected. However, stratification of study subjects according to their smoking habits revealed higher levels of excretion of 1-OH-P in subjects smoking < or =15 cigarettes/day carrying the CYP1A1 polymorphism. No such effect was seen either with nonsmokers or with people smoking more than 15 cigarettes/day. These findings are suggestive of a gene-environment interaction, in which subjects with the CYP1A1 polymorphism, relative to subjects without it, have higher levels of 1-OH-P in their urine at low doses of exposure to PAHs.


Economic evaluation of individualized nutritional support in medical inpatients: Secondary analysis of the EFFORT trial.
Existing guidelines support the importance of nutritional interventions for medical inpatients at malnutrition risk to alleviate the impact of malnutrition on outcomes. While recent studies have reported positive effects of nutritional support on health outcomes, limited evidence exists on whether in-hospital nutritional support also results in economic advantages. We report the results of the economic evaluation of EFFORT-a pragmatic, investigator-initiated, open-label, multicenter trial. A total of 2028 medical inpatients at nutritional risk were randomly assigned to receive individualized nutritional support to reach protein and energy goals (intervention group; n = 1015) or standard hospital food (control group; n = 1013). To calculate the economic impact of nutritional support, a Markov model was developed with relevant health states. Costs were estimated for days in normal hospital ward and in the Intensive Care Unit (ICU), hospital-acquired complications, and nutritional support. We used a Euro conversion rate of 0.93216 Euro for 1 Swiss Franc (CHF). The estimated per-patient cost was CHF90 (83.78 €) for the in-hospital nutritional support and CHF283.85 (264.23 €) when also considering dietitian consultation time. Overall costs of care within 30 days of admission averaged CHF29,263 (27,240 €) per-patient in the intervention group versus CHF29,477 (27,439 €) in the control group resulting in per-patient cost savings of CHF214 (199 €). Per-patient cost savings was CHF19.56 (18.21 €) when also accounting for dietician costs (full cost analysis). These cost savings were mainly due to reduced ICU length of stay and fewer complications. We also calculated costs to prevent adverse outcomes, which were CHF276 (256 €) for one severe complication, CHF2,675 (2490 €) for one day in ICU, and CHF7,975 (7423 €) for one death. For the full cost analysis, these numbers were CHF872 (811 €), CHF8,459 (7874 €) and CHF25,219 (23,475 €). Sensitivity analyses confirmed the original findings. Our evaluation demonstrates that in-hospital nutritional support for medical inpatients is a highly cost-effective intervention to reduce risks for ICU admissions and hospital-associated complications, while improving patient survival. The positive clinical and economic benefits of nutritional support in at-risk medical inpatients calls for comprehensive nutrition programs, including malnutrition screening, consultation, and nutritional support. ClinicalTrials.gov number, NCT02517476.


Rural inpatient telepharmacy consultation demonstration for after-hours medication review.
Medication errors contribute to a significant number of fatal and nonfatal adverse medical events each year. Many actions, from both a policy and innovation standpoint, have been taken to reduce medication errors in the inpatient setting; yet, these actions often target larger urban hospitals. Rural hospitals face many more challenges in implementing these changes due to fewer resources and lower patient volumes. Our article discusses the implementation and results of a telepharmacy demonstration implemented between the University of California Davis Health System and six rural hospitals. A retrospective chart review obtained baseline medication errors for comparison with the prospective review of medication orders through telepharmacy. Medication orders from rural hospitals were transmitted via fax to the University of California Davis Pharmacy for after-hours review. If a medication required after-hours removal from the pharmacy, it was requested that video verification by a telepharmacist be used to verify that the correct medication was removed from the pharmacy. Baseline findings from the retrospective chart review indicated that 30.0% of patients had one or more medication errors and that these errors occurred in 7.2% of the medication orders. None of these errors were found to have resulted in harm to the patients. During the telepharmacy demonstration, 2,378 medication orders were screened from 504 independent order review requests. In total, 58 (19.2%) patients had one or more medication errors. The errors from the telepharmacy demonstration represented potential errors that were identified through telepharmacy medication review. Telepharmacy represents a potential alternative to around-the-clock on-site pharmacist medication review for rural hospitals.


Intranasal supernumerary tooth in a child: a case report.
Ectopic eruption of supernumerary teeth in the nasal cavity is extremely rare, and most cases usually involve the maxillary sinus or are accompanied by dental cysts. It is usually discovered during adulthood. A 5-year-old patient presented with an intranasal mass and intermittent nasal bleeding that lasted for 1 year. He was taking medication for symptoms of allergic rhinitis, such as nasal obstruction and intermittent epistaxis, without any endoscopic evaluation for 1 year. On nasal endoscopy, a needlelike whitish mass was observed on the left nasal floor. On paranasal sinus computed tomography, it appeared as a pointed highdensity mass covered by soft tissue. The intranasal mass which was a supernumerary tooth was completely removed using a pediatric endoscope. Detection of supernumerary teeth in the nasal cavity of children without symptoms is difficult, and it can be delayed; although the child, in this case, had nonspecific nasal symptoms, supernumerary teeth was not considered in the diagnosis. This case report raises awareness and provides evidence for the clinical characterization and optimal treatment of supernumerary teeth in children.


Assessment of heavy metal distribution, risk, and sourcing in mangrove sediments from three Saudi Arabian Red Sea locations.
This work measured the concentration of heavy metal cations (V, Cr, Ni, Cu, Zn, Cd, and Pb) and associated anionic ligands (SOM, carbonate, and silicate) in mangrove sediment samples from the Red Sea of Saudi Arabia to set a biogeochemical baseline within these as yet poorly constrained sensitive ecosystems. Sediments were collected from three regions along the Saudi Arabian coast: Yanbu, Jeddah, and the Farasan Islands. Risk indices and statistical analyses were applied to assess contamination levels and potential sourcing. Results show that Yanbu is at environmental risk as it shows higher concentrations and anthropogenic signatures for most metals (Cr, Cu, Zn, Cd and Pb) compared to the other two regions. Jeddah metal concentrations are similar to the Islands; however, the statistical analyses suggest that a singular anthropogenic source controls heavy metal delivery to its environment.


Brachial plexus variations in human fetuses.
We examined the anatomic variations of the brachial plexus (BP) in human fetuses. This study was performed with 200 BPs from spontaneously aborted fetuses without detectable malformations. The plexuses were dissected, and the normal position and/or morphological variations of the BP were determined and photographed. There were no variations in 93 plexuses, and 107 plexuses were observed to have different variations. Morphological variations were observed more frequently among female fetuses and right sides. The BPs were composed mostly of the C5, C6, C7, and C8 nerves and the T1 nerve (71.5%). A prefixed plexus was observed in 25.5% of cases, and a postfixed plexus was observed in 2.5% of cases. In one case (0.5%), the C4 and T2 nerves joined the formation. The inferior trunk was not formed in 9% of cases. The superior trunk was not formed in 1% of cases. In one plexus, the superior trunk was formed by the ventral rami of the C4 and C5 nerves. In one case, the inferior trunk was formed by the ventral rami of the T1 and T2 nerves. Division variations were observed most frequently. There were also variations in the terminal branches, such as the roots of the median nerve joining in the distal part of the arm (8.5%), the axillary nerve being separate from the posterior division of the superior trunk (2.5%), and a connection existing between the median and musculocutaneous nerves (1%). Knowledge of BP variations is important for surgeons who perform surgical procedures in the cervical and axillary regions.


GmRAV1 regulates regeneration of roots and adventitious buds by the cytokinin signaling pathway in Arabidopsis and soybean.
The division and differentiation of cells are the basis of growth and development. Cytokinin plays an active role in cell growth division and differentiation. The Related to ABI3/VP1 (RAV) family comprises transcription factors in plants and all contain both AP2- and B3-like domains. In this study, GmRAV1 (Glycine max), which belongs to the AP2/ERF transcription factor family, was isolated and functionally characterized. Subcellular localization showed that GmRAV1 was localized to the nucleus and quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that GmRAV1 was induced by cytokinin. Furthermore, compared with wild-type plants, plants overexpressing GmRAV1 showed dwarfism and late maturity. In contrast, the mutant of TEMPRANILLO (tem1) and GmRAV-i plants had an opposite phenotype. More interestingly, a root and shoot regeneration experiment indicated that GmRAV1 is one of the most important positive regulators of the cytokinin signaling pathway, which is involved in promoting root and shoot regeneration. In addition, RNA-seq and qRT-PCR results indicated that GmRAV1 is related to the key factors involved in the cytokinin signaling pathway, namely, cytokinin oxidase (GmCKX6 and GmCKX7), purine permease (GmPUP1), cell cyclin-related genes (GmCycA2;4, GmCycD3 and GmCYC1), cyclin-dependent kinase (GmCDKB2), cell division cycle (GmCDC20), E2F transcription factors (GmE2FE) and authentic response regulator (GmARR9). In conclusion, GmRAV1, one of the most important positive regulators involved in promoting root and shoot regeneration, was induced by cytokinin and is related to the key factors of the cytokinin signaling pathways.


Protective effect of breastfeeding on invasive Haemophilus influenzae infection: a case-control study in Swedish preschool children.
In Orebro County a 2.5-fold increase in the incidence of Haemophilus influenzae (HI) meningitis was found between 1970 and 1980, an observation that initiated the present study. In order to search for associations between morbidity in invasive HI infection and possible risk factors, a case-control study was conducted over a 6-year period from 1987 to 1992, before general Hib vaccination was introduced in Sweden. Fifty-four cases with invasive HI infection 139 matched controls were studied for possible risk factors such as day-care outside the home, short duration of breastfeeding, passive smoking, low socioeconomic level of the household, many siblings in the family, allergy, frequent, infections, repeated antibiotic treatments and immunoglobulin deficiency. Multivariate analysis showed a significant association between invasive HI infection and two independent factors, i.e. short duration (< 13 weeks) of exclusive breastfeeding, odds ratio (OR) 3.79 (95% confidence interval [CI] 1.6-8.8) and history of frequent infections, OR 4.49 (95% CI : 1.0-21.0). For the age at onset 12 months or older, the associations were stronger, OR 7.79 (95% CI : 2.4-26.6) and 5.86 (95% CI : 1.1-30.6), respectively. When breastfeeding duration in weeks was analysed as a continuous variable the OR was 0.95 (95% CI : 0.92-0.99), indicating a decreased risk with each additional week. Increased OR were observed for other risk factors as well but not of the magnitude found for short duration of breastfeeding. The association of decreased risk for invasive HI infection and long duration of breastfeeding was persisting beyond the period of breastfeeding itself. This finding supports the hypothesis of a long-lasting protective effect of breastfeeding on the risk for invasive HI infection. A decreased risk for invasive HI infection with long duration of breastfeeding was found. Our results do have implications for strategies in breastfeeding promotion, especially in countries where Hib vaccination is too costly and not yet implemented.


Genetic ME-a visualization application for merging and editing pedigrees for genetic studies.
In order to study the genetics of diseases more accurately and effectively, one often collects large families. Different members of a large family may provide differing information about the structure and make-up of their pedigree. Thus, software is needed to facilitate reconciliation of pedigrees collected independently from multiple informants from a single large family to create a unified pedigree that is based on the best composite information available. Our implementation demonstrates that Genetic ME performs merging in terms of adding, replacing and combining information from two pedigrees. Through a tracking process, all of the changes made to the data set for the individuals can be traced back to their original source material. A new pedigree structure can be easily visualized while reconciling disparate information from multiple pedigrees. We developed the Genetic Merging & Editing (Genetic ME) program, an open source Java application built on top of CraneFoot and Ghostscript, to support comparing, editing and merging of pedigrees collected from multiple sources in a visually-oriented manner. Genetic ME constitutes an ideal addition to software packages for reconciling pedigree information from multiple sources. Genetic ME provides a friendly graphical user interface, traces the changes made by users, and produces viewable merged pedigree structures able to be further used by other popular analysis programs.


Breast cancer survival and its prognostic factors in the United Arab Emirates: A retrospective study.
Data on breast cancer survival and its prognostic factors are lacking in the United Arab Emirates (UAE). Sociodemographic and pathologic factors have been studied widely in western populations but are very limited in this region. This study is the first to report breast cancer survival and investigate prognostic factors associated with its survival in the UAE. This is a retrospective cohort study involving 988 patients who were diagnosed and histologically confirmed with breast cancer between January 2008 and December 2012 at Tawam hospital, Al Ain, UAE. Patient were followed from the date of initial diagnosis until the date of death from any cause, lost-to-follow up or the end of December 2018. The primary outcome is overall survival (OS). The Kaplan-Meier method was used to estimate the survival curve along with the 2- and 5-year survivals. Different group of patients categorized according to prognostic factors were compared using the log-rank test. Multiple Cox proportional hazards models was used to examine the impact of several prognostic factors on the overall survival. The median study follow-up was 35 months. Of the 988 patients, 62 had died during their follow-up, 56 were lost to follow-up and 870 were still alive at the end of the study. The average age of patients was 48 years. The majority of patients presented to the hospital with grade II or III, 24% with at least stage 3 and 9.2% had metastasis. The 2-year and 5-year survivals were estimated to 97% and 89% respectively. Results of the multiple Cox proportional hazard model show that tumor grade, and stage of cancer at presentation are jointly significantly associated with survival. The 2- and 5-year survival are within the norms compared to other countries. Significant clinical and pathological prognostic factors associated with survival were tumor grade, and the stage of cancer at presentation.


Role of executive function in ADHD.
Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder characterized by inattention, hyperactivity, and impulsivity. ADHD is commonly treated with behavioral therapy and noradrenergic and dopaminergic pharmacotherapy with psychostimulants such as methylphenidate and dextroamphetamine. Stimulants primarily have dopaminergic and noradrenergic mechanisms of action, with blockade at the dopamine transporter reducing reuptake, resulting in an increase in these neurotransmitters at the synapse. Theoretically, inattention, hyperactivity, and impulsivity in ADHD may be due to underlying executive functioning, alerting, and orienting deficits, and the nonstimulant modafinil could be beneficial in managing symptoms of ADHD by improving these components of attention that accompany wakefulness. Although modafinil exhibits a small degree of dopaminergic action by blocking the dopamine transporter, the major effect of modafinil may be attributable to neuronal activity in the hypothalamus, particularly pertaining to the recently discovered peptides hypocretin 1 and 2 (also known as orexin A and B). However, further placebo-controlled and flexible-dose studies are needed to determine the efficacy of modafinil in treating the symptoms of ADHD in children and adults.


An improved model of acute liver failure based on transient ischemia of the liver.
A reproducible and potentially reversible model of acute liver failure in the pig is feasible based on transient ischemia of the liver. To determine the shortest period of liver ischemia sufficient to cause 100% mortality, ischemia of the liver was induced for different lengths of time, starting with 6 hours. If the pig survived, ischemia time was prolonged for 2 hours in the next animal. In the first group, the common bile duct was not tightened. In the second group, the common bile duct was tightened. The Laboratory for Hepatopathophysiology, Catholic University, Leuven, Belgium. Female stress-negative Belgian Landrace pigs weighing 18 to 22 kg. During preparatory surgery, all ligaments around the liver and connective tissue around the liver hilum were transected and an end-to-side portacaval shunt was made. Vessel loops were placed around the branches of the hepatic artery and bile duct. Three days later, in fully awake pigs, the loops were tightened. Mortality. Development of acute liver failure was determined based on neurologic, biochemical, and pathological variables. When occluded for 10 hours, all pigs in group 2 (n = 5) [corrected] died between 12 and 17 hours after the induction of ischemia. All pigs developed typical acute liver failure. Tissue specimens showed 90% necrosis of the liver parenchyma. A highly reproducible and potentially reversible model of acute liver failure in the large animal has been established.


Myasthenia in a patient with sarcoidosis and schizophrenia.
A 44-year-old male patient was hospitalised with paranoid schizophrenia in 1985. Depot neuroleptic treatment was started which successfully prevented further psychotic relapses for the next ten years. His myasthenia gravis started with bulbar signs in 1997 and the symptoms soon became generalized. The diagnosis of myasthenia gravis was confirmed by electromyography, by positive anticholinesterase test and by the detection of anti-acetylcholine receptor antibodies in the serum. Mediastinal CT examination showed enlarged hilar lymph nodes on the left but no thymic pathology was observed. Mediastinoscopy was performed and biopsies were obtained from the affected nodes. Histology revealed sarcoidosis. The patient suffered respiratory crisis following the thoracic intervention (in September 1998). Combined oral corticosteroid (64 mg methylprednisolone/e.o.d.) and azathioprine (150 mg/day) treatment regimen was initiated and complete remission took place in both the myasthenic symptoms and the sarcoidosis. The follow-up CT scans showed no mediastinal pathology (January 2000). During steroid treatment a transient psychotic relapse occurred which was successfully managed by supplemental haloperidol medication added to his regular depot neuroleptics. The patient currently takes 150 mg/day azathioprine and receives 40 mg/month flupentixol depot i.m. His physical and mental status are stable and he has been completely symptom free in the last 24 months. The association of myasthenia gravis and sarcoidosis is very rare. To our best knowledge no case has been reported of a patient suffering from myasthenia gravis, sarcoidosis, and schizophrenia at the same time.


"I feel I have no voice": hospital doctors' workplace silence in Ireland.
Workplace silence impedes productivity, job satisfaction and retention, key issues for the hospital workforce worldwide. It can have a negative effect on patient outcomes and safety and human resources in healthcare organisations. This study aims to examine factors that influence workplace silence among hospital doctors in Ireland. A national, cross-sectional, online survey of hospital doctors in Ireland was conducted in October-November 2019; 1,070 hospital doctors responded. This paper focuses on responses to the question "If you had concerns about your working conditions, would you raise them?". In total, 227 hospital doctor respondents (25%) stated that they would not raise concerns about their working conditions. Qualitative thematic analysis was carried out on free-text responses to explore why these doctors choose to opt for silence regarding their working conditions. Reputational risk, lack of energy and time, a perceived inability to effect change and cultural norms all discourage doctors from raising concerns about working conditions. Apathy arose as change to working conditions was perceived as highly unlikely. In turn, this had scope to lead to neglect and exit. Voice was seen as risky for some respondents, who feared that complaining could damage their career prospects and workplace relationships. This study highlights the systemic, cultural and practical issues that pressure hospital doctors in Ireland to opt for silence around working conditions. It adds to the literature on workplace silence and voice within the medical profession and provides a framework for comparative analysis of doctors' silence and voice in other settings.


Inhibition of fried meat-induced colorectal DNA damage and altered systemic genotoxicity in humans by crucifera, chlorophyllin, and yogurt.
Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100°C) or high temperature (250°C), each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs) and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated carcinogenesis. ClinicalTrials.gov NCT00340743.


Incidental Cardiovascular Abnormalities in the Abdominal Aortic Aneurysm (AAA) Surveillance Population During the AAA Get Fit Trial: A Case Series and Review of the Literature.
Background The prevalence of cardiovascular disease and incidence of major adverse cardiovascular events (MACEs) is very high among the abdominal aortic aneurysm (AAA) surveillance population. Formal assessments of and interventions to reduce cardiovascular risk are not a routine part of the surveillance programme at present. However, its potential importance is highlighted by incidental findings during the AAA Get Fit Trial, a randomised controlled trial which included baseline cardiopulmonary exercise testing (CPET). We speculate that CPET can act as an opportunistic screening programme to identify cardiovascular disease in AAA surveillance patients. Methods The AAA Get Fit Trial was a prospective, randomised controlled trial at a tertiary vascular centre, Manchester University NHS Foundation Trust, conducted between November 2017 and August 2019. Patients underwent CPET at baseline, 8, 16, 24 and 36 weeks as well as clinical history and examination and blood tests. We report on incidental cardiovascular abnormalities diagnosed during the trial. Results Of the 59 participants in the trial, four (6.8%) were identified to have abnormal findings suggestive of unstable cardiovascular disease. On subsequent further investigation, two patients were diagnosed and treated for severe coronary artery disease after abnormal ECG findings were noted during CPET. One patient was diagnosed with unstable angina after obtaining a detailed history on baseline assessment which was treated medically before going on to have a successful elective AAA repair. Conclusions There is a high incidence of MACEs among this high-risk population both pre and perioperatively. Identifying and treating cardiovascular disease among the AAA surveillance population must be a focus of the future AAA screening programme.


Identification of a beta-cell-specific HLA class I restricted epitope in type 1 diabetes.
Type 1 diabetes is an autoimmune disease in which pancreatic beta-cells are destroyed by cytotoxic T-cells that recognize peptide epitopes presented by HLA class I molecules. The identification of human beta-cell epitopes may significantly improve the prospects for immunodiagnosis and immunotherapy in type 1 diabetes. Using algorithms to predict nonameric beta-cell peptides that would bind to the common HLA allele, HLA-A*0201, we identified a potential epitope from the leader sequence of islet amyloid polypeptide (human islet amyloid polypeptide [IAPP] precursor protein [preproIAPP] 5-13: KLQVFLIVL). Peripheral blood mononuclear cells (PBMCs) were isolated from 18 HLA-A*0201 patients with type 1 diabetes (9 with recent-onset [<180 days; range, 1-120 days] and 9 with long-standing diabetes [>180 days; range, 183-3,273 days]) and 9 healthy, nondiabetic control subjects. PBMCs were screened for peptide recognition using interferon-gamma enzyme-linked immunospot (ELISpot) assays. Of the nine patients with recent-onset type 1 diabetes, six had ELISpot responses to preproIAPP 5-13 that were >3 SDs above the mean of the nondiabetic control subjects (P = 0.002). In contrast, no patients with type 1 diabetes for >180 days had a response above this threshold. In summary, preproIAPP 5-13 is a novel HLA class I epitope recognized by a significant proportion of cytotoxic T-cells from HLA-A*0201 patients with recent-onset type 1 diabetes and may prove to be a useful tool for the prediction and/or prevention of this disease.


Experimental study of dielectrophoresis and liquid dielectrophoresis mechanisms for particle capture in a droplet.
This work presents a microfluidic system that can transport, concentrate, and capture particles in a controllable droplet. Dielectrophoresis (DEP), a phenomenon in which a force is exerted on a dielectric particle when it is subjected to a non-uniform electric field, is used to manipulate particles. Liquid dielectrophoresis (LDEP), a phenomenon in which a liquid moves toward regions of high electric field strength under a non-uniform electric field, is used to manipulate the fluid. In this study, a mechanism of droplet creation presented in a previous work that uses DEP and LDEP is improved. A driving electrode with a DEP gap is used to prevent beads from getting stuck at the interface between air and liquid, which is actuated with an AC signal of 200 V(pp) at a frequency of 100 kHz. DEP theory is used to calculate the DEP force in the liquid, and LDEP theory is used to analyze the influence of the DEP gap. The increment of the actuation voltage due to the electrode with a DEP gap is calculated. A set of microwell electrodes is used to capture a bead using DEP force, which is actuated with an AC signal of 20 V(pp) at a frequency of 5 MHz. A simulation is carried out to investigate the dimensions of the DEP gap and microwell electrodes. Experiments are performed to demonstrate the creation of a 100-nL droplet and the capture of individual 10-μm polystyrene latex beads in the droplet.


Multi-view singular value decomposition for disease subtyping and genetic associations.
Accurate classification of patients with a complex disease into subtypes has important implications for medicine and healthcare. Using more homogeneous disease subtypes in genetic association analysis will facilitate the detection of new genetic variants that are not detectible using the non-differentiated disease phenotype. Subtype differentiation can also improve diagnostic classification, which can in turn inform clinical decision making and treatment matching. Currently, the most sophisticated methods for disease subtyping perform cluster analysis using patients' clinical features. Without guidance from genetic information, the resultant subtypes are likely to be suboptimal and efforts at genetic association may fail. We propose a multi-view matrix decomposition approach that integrates clinical features with genetic markers to detect confirmatory evidence for a disease subtype. This approach groups patients into clusters that are consistent between the clinical and genetic dimensions of data; it simultaneously identifies the clinical features that define the subtype and the genotypes associated with the subtype. A simulation study validated the proposed approach, showing that it identified hypothesized subtypes and associated features. In comparison to the latest biclustering and multi-view data analytics using real-life disease data, the proposed approach identified clinical subtypes of a disease that differed from each other more significantly in the genetic markers, thus demonstrating the superior performance of the proposed approach. The proposed algorithm is an effective and superior alternative to the disease subtyping methods employed to date. Integration of phenotypic features with genetic markers in the subtyping analysis is a promising approach to identify concurrently disease subtypes and their genetic associations.


Comparing the Efficacy and Safety of Metacarpal Neck Fracture Treatments: A Systematic Review and Network Meta-Analysis.
Metacarpal neck fractures may perform well without operative intervention, but the current literature on this topic is fragmented and guidance on managing these injuries needs further refinement. We conducted a systematic review and network meta-analysis to provide a comprehensive evaluation of the various treatments available for these injuries. We searched 3 electronic databases and included any study comparing interventions for metacarpal neck fractures. We conducted a Bayesian network meta-analysis for each outcome. We identified a total of 14 studies comparing: antegrade (AIMP) or retrograde (RIMP) intramedullary pinning, buddy strapping, transverse pinning (TP), functional bracing, plating, retrograde cross-pinning, a combination of retrograde cross-pinning and plating, and placement of an orthosis or casting. Although the results were not statistically significant, the effect estimates suggested more favorable pain reduction and functional improvement with AIMP compared with nonsurgical therapies and RIMP in the short term (3 months or less). However, differences between interventions at later follow-up were less extreme; data on short-term pain and function with surgical options outside AIMP and RIMP were unavailable. In addition, compared with both plating and TP, AIMP was associated with significantly higher risks for implant migration and neurological events. There were contrasting findings in union-related outcomes. Plating showed the earliest time to union (not statistically significant) but TP demonstrated the lowest risk for a delayed union. This review demonstrated that although AIMP may be a viable surgical option for early symptomatic relief after a metacarpal neck fracture, it may also be associated with a greater likelihood of certain postoperative complications. Clinicians should consider patient preferences for the time frame of symptomatic relief when selecting the optimal treatment, and patients should weigh the advantages and disadvantages of each available option, especially when considering invasive surgery. Considering the lack of high-quality primary research investigating these interventions, future studies are needed to make more definitive conclusions. Therapeutic II.


Femoral nerve transfers for restoring tibial nerve function: an anatomical study and clinical correlation: a report of 2 cases.
Sciatic nerve injuries cause debilitating functional impairment, particularly when the injury mechanism and level preclude reconstruction with primary grafting. The purpose of this study was to demonstrate the anatomical feasibility of nerve transfers from the distal femoral nerve terminal branches to the tibial nerve and to detail the successful restoration of tibial function using the described nerve transfers. Six cadaveric legs were dissected for anatomical analysis and the development of tension-free nerve transfers from femoral nerve branches to the tibial nerve. In 2 patients with complete tibial and common peroneal nerve palsies following sciatic nerve injury, terminal branches of the femoral nerve supplying the vastus medialis and vastus lateralis muscles were transferred to the medial and lateral gastrocnemius branches of the tibial nerve. Distal sensory transfer of the saphenous nerve to the sural nerve was also performed. Patients were followed up for lower-extremity motor and sensory recovery up to 18 months postoperatively. Consistent branching patterns and anatomical landmarks were present in all dissection specimens, allowing for reliable identification, neurolysis, and coaptation of donor femoral and saphenous nerve branches to the recipients. Clinically, the patients obtained Medical Research Council Grade 3 and 3+ plantar flexion by 18 months postoperatively. Improved strength was accompanied by improved ambulation in both patients and by a return to competitive sports in 1 patient. Sensory recovery was demonstrated by an advancing Tinel sign in both patients. This study illustrates the clinical success and anatomical feasibility of femoral nerve to tibial nerve transfers after proximal sciatic nerve injury.


In search of true autonomy.
Patient autonomy is discussed in medical care now both because this is an appropriate ethical practice and also as a reaction against the emphasis that was placed in the past on the medical profession 'always knowing best'. This article examines where our present understanding and practice of the ethical concept of autonomy may be flawed. It examines both doctors' and patients' responsibilities for this flaw and how they may be rectified.


[The reactivity of the mononuclear phagocytes in the acute period of craniocerebral trauma].
The article analyses the condition of one of the main links of the defence status--the cells of the mononuclear phagocytotic system in the acute period of craniocerebral trauma (CCT). The authors established the existence of a dependence of the functional condition of the peripheral blood monocytes on the CCT severity. Disorders of the monocyte functional condition (phagocytosis, monocyte test) were most marked in a severe CCT. Early (in the first 24 hours after the trauma) activation of mononuclears develops in such case. Standard nonspecific response of monocytes to traumatic damage is maintained in mild CCT.


BK virus and cancer in Uganda.
As part of an epidemiological study of cancer in Uganda, we investigated the titre of antibodies against BK virus among 821 people with different cancer types and benign tumours. Among study participants, 790 were considered seropositive for anti-BK virus antibodies and all analyses were conducted on transformed data. The mean optical density (a measure of antibody titre) for all patients combined (including the 31 who were considered seronegative) was 1.03 (standard error 0.01), but was 5% higher in women than in men (P=0.05), and 8% higher among HIV seropositive than seronegative people (P=0.002). Otherwise, there were few consistent associations between anti-BK virus antibodies and any social and lifestyle factor investigated. Differences in the mean optical density for each cancer type were estimated using multivariate analysis of variance with adjustment for sex, age group and HIV serostatus, using all other patients as controls. The mean optical density was about 17% lower among those with oral cancer (optical density 0.86, standard error 0.06; P=0.01, based on 30 patients) and about 20% higher among those with prostate cancer (optical density 1.22, standard error 0.09; P=0.01, based on 11 cases) than among all other patients combined. The number of cases of each cancer was too small to exclude the possibility of these findings arising by chance. No other cancer site or type was significantly associated with low, or with high anti-BK virus antibody titres.


A synthetic rainbow trout linkage map provides new insights into the salmonid whole genome duplication and the conservation of synteny among teleosts.
Rainbow trout is an economically important fish and a suitable experimental organism in many fields of biology including genome evolution, owing to the occurrence of a salmonid specific whole-genome duplication (4th WGD). Rainbow trout is among some of the most studied teleosts and has benefited from substantial efforts to develop genomic resources (e.g., linkage maps. Here, we first generated a synthetic map by merging segregation data files derived from three independent linkage maps. Then, we used it to evaluate genome conservation between rainbow trout and three teleost models, medaka, stickleback and zebrafish and to further investigate the extent of the 4th WGD in trout genome. The INRA linkage map was updated by adding 211 new markers. After standardization of marker names, consistency of marker assignment to linkage groups and marker orders was checked across the three different data sets and only loci showing consistent location over all or almost all of the data sets were kept. This resulted in a synthetic map consisting of 2226 markers and 29 linkage groups spanning over 3600 cM. Blastn searches against medaka, stickleback, and zebrafish genomic databases resulted in 778, 824 and 730 significant hits respectively while blastx searches yielded 505, 513 and 510 significant hits. Homology search results revealed that, for most rainbow trout chromosomes, large syntenic regions encompassing nearly whole chromosome arms have been conserved between rainbow trout and its closest models, medaka and stickleback. Large conserved syntenies were also found between the genomes of rainbow trout and the reconstructed teleost ancestor. These syntenies consolidated the known homeologous affinities between rainbow trout chromosomes due to the 4th WGD and suggested new ones. The synthetic map constructed herein further highlights the stability of the teleost genome over long evolutionary time scales. This map can be easily extended by incorporating new data sets and should help future rainbow trout whole genome sequence assembly. Finally, the persistence of large conserved syntenies across teleosts should facilitate the identification of candidate genes through comparative mapping, even if the occurrence of intra-chromosomal micro-rearrangement may hinder the accurate prediction their genomic location.


Levamisole therapy in atopic dermatitis: randomized double-blind evaluation.
A randomized double-blind study of levamisole hydrochloride therapy in atopic dermatitis is reported. No improvement was noted in any of several assessments, which included patients' subjective impressions; physicians' clinical impressions; comparison of clinical extent and severity scores; and incidence of cutaneous infections or lessening of serum IgE levels. A trend toward improvement was seen in a majority of cases, whether treatment was with a placebo or an active drug. This study emphasizes the need for double-blind techniques for therapeutic trial in the management of patients with atopic dermatitis.


Effect of Ligand Attachment at Ag11 for CO Oxidation: A Computational Investigation.
Heterogeneous CO oxidation is a demanding reaction at room temperature due to the high activation energy required to break the O=O bond. While several metal clusters are reported to oxidize CO successfully, they fall short of their selectivity for the reaction and recyclability. In this regard, there is a need for economic catalysts with high catalytic activity, low activation barrier, and reusability. In this study, we have investigated the catalytic activity of the neutral pristine and ligated Ag11 cluster toward CO oxidation. We investigated the attachment effect of three organic donor ligands: trimethylphosphine, triethylphosphine, and N-ethyl pyrrolidone to the Ag11 cluster. Our results show that including donor ligands on the Ag11 cluster surface can significantly reduce the barrier heights for CO oxidation. The minimum barrier heights with the system coordinated with triethylphosphine showed the lowest activation barrier of 1.06 kcal/mol compared to the high activation barrier of 14.77 kcal/mol recorded for the pristine cluster. Exploration of the reaction mechanism and charge analysis showed that the electron donor ligands activate O2 via charge donation, thereby reducing the barrier heights of CO oxidation.


Room-temperature study of iron gall ink impregnated paper degradation under various oxygen and humidity conditions: time-dependent monitoring by viscosity and X-ray absorption near-edge spectrometry measurements.
Many western manuscripts were written using iron gall inks. These inks can damage the paper via two major mechanisms: (a) acid hydrolysis, enhanced by humidity, and (b) oxidative depolymerization provoked by the presence of oxygen and free iron(II) ions. The degradation of unsized Whatman paper impregnated with different combinations of iron sulfate, gallic acid, and gum arabic was studied at room temperature in order to assess the relative importance of each mechanism. The samples were stored in various environments including a dry and/or an oxygen-free atmosphere. The cellulose depolymerization was monitored by viscometry and related to changes in the oxidation state of iron, determined by X-ray absorption near-edge spectrometry. The results indicate that residual amounts of oxygen (less than 0.1%) promote cellulose depolymerization, whereas the level of relative humidity has no impact. The cellulose depolymerization also appears closely correlated to oxidative mechanisms. Regarding the oxidation of iron, it only occurs in the simultaneous presence of oxygen and moisture, suggesting the occurrence of rustlike oxidative mechanisms. Finally, the presence of gallic acid has a strong influence, which is only partially explained by its capacity to reduce iron(III) to iron(II).


Children's physical activity and sedentary behaviour in before school care: An observational study.
In Australia, less than one quarter of children aged 5-12 years meet national physical activity (PA) guidelines. Before school care operates as part of Out of School Hours Care (OSHC) services and provide opportunities for children to meet their daily PA recommendations. The aim of this study was to explore factors associated with children meeting 15 min of moderate-to-vigorous-intensity physical activity (MVPA) while attending before school care. A cross-sectional study was conducted in 25 services in New South Wales, Australia. Each service was visited twice between March and June 2021. Staff behaviours and PA type and context were captured using staff interviews and the validated System for Observing Staff Promotion of Physical Activity and Nutrition (SOSPAN) time sampling tool. Child PA data were collected using Actigraph accelerometers and associations between program practices and child MVPA analysed. PA data were analysed for 654 children who spent an average of 39.2% (±17.6) of their time sedentary; 45.4% (±11.4) in light PA; and 14.9% (±11.7) in MVPA. Only 17% of children (n = 112) reached ≥15 min MVPA, with boys more likely to achieve this. Children were more likely to meet this recommendation in services where staff promoted and engaged in PA; PA equipment was available; children were observed in child-led free play; and a written PA policy existed. Before school care should be supported to improve physical activity promotion practices by offering staff professional development and guidance on PA policy development and implementation practices.


Up to 100-fold increase of apparent gene expression in the presence of Epstein-Barr virus oriP sequences and EBNA1: implications of the nuclear import of plasmids.
A 100-fold increase in luciferase activity was observed in 293 cells, stably expressing Epstein-Barr nuclear antigen 1 (EBNA1; 293-EBNA1 cells), that had been transiently transfected with plasmids carrying Epstein-Barr virus (EBV) oriP sequences. This increase was observed in comparison to reporter gene activity obtained after transfection with a plasmid carrying no oriP sequences. The luciferase gene on these plasmids was under the control of either the cytomegalovirus immediate-early 1 gene enhancer-promoter (CMV IE1) or the Rous sarcoma virus promoter. The increase of reporter gene activity was not due to plasmid replication, since a similar enhancement was observed in the presence of aphidicolin, an inhibitor of replicative DNA synthesis, or after deletion of the dyad symmetry (DS) element within oriP. Luciferase production was not increased in the presence of only the DS element. Microinjection of plasmids carrying the CMV IE1 promoter-driven luciferase gene with or without oriP sequences into the nuclei of 293-EBNA1 cells resulted in a 17-fold increase in luciferase activity. Cytoplasmic injection of these plasmids led to an enhancement of luciferase activity of up to 100-fold. This difference in the factor of activation after nuclear or cytoplasmic injection could be ascribed to increased transport of plasmids carrying oriP from the cytoplasm to the nucleus in the presence of EBNA1. These data suggest the possibility of substantially increasing the apparent expression of a gene under the control of a strong constitutive promoter in the presence of oriP sequences and EBNA1. This improvement in expression is due to intranuclear enhancement of gene expression. oriP-specific transport of plasmid DNA from the cytoplasm of 293-EBNA1 cells to the nucleus seems to contribute to the observed effect.


Preclinical tissue distribution and metabolic correlations of vigabatrin, an antiepileptic drug associated with potential use-limiting visual field defects.
Vigabatrin (VGB; (S)-(+)/(R)-(-) 4-aminohex-5-enoic acid), an antiepileptic irreversibly inactivating GABA transaminase (GABA-T), manifests use-limiting ocular toxicity. Hypothesizing that the active S enantiomer of VGB would preferentially accumulate in eye and visual cortex (VC) as one potential mechanism for ocular toxicity, we infused racemic VGB into mice via subcutaneous minipump at 35, 70, and 140 mg/kg/d (n = 6-8 animals/dose) for 12 days. VGB enantiomers, total GABA and β-alanine (BALA), 4-guanidinobutyrate (4-GBA), and creatine were quantified by mass spectrometry in eye, brain, liver, prefrontal cortex (PFC), and VC. Plasma VGB concentrations increased linearly by dose (3 ± 0.76 (35 mg/kg/d); 15.1 ± 1.4 (70 mg/kg/d); 34.6 ± 3.2 μmol/L (140 mg/kg/d); mean ± SEM) with an S/R ratio of 0.74 ± 0.02 (n = 14). Steady state S/R ratios (35, 70 mg/kg/d doses) were highest in eye (5.5 ± 0.2; P < 0.0001), followed by VC (3.9 ± 0.4), PFC (3.6 ± 0.3), liver (2.9 ± 0.1), and brain (1.5 ± 0.1; n = 13-14 each). Total VGB content of eye exceeded that of brain, PFC and VC at all doses. High-dose VGB diminished endogenous metabolite production, especially in PFC and VC. GABA significantly increased in all tissues (all doses) except brain; BALA increases were confined to liver and VC; and 4-GBA was prominently increased in brain, PFC and VC (and eye at high dose). Linear correlations between enantiomers and GABA were observed in all tissues, but only in PFC/VC for BALA, 4-GBA, and creatine. Preferential accumulation of the VGB S isomer in eye and VC may provide new insight into VGB ocular toxicity.


Cancer-Associated, Stimuli-Driven, Turn on Theranostics for Multimodality Imaging and Therapy.
Advances in bioinformatics, genomics, proteomics, and metabolomics have facilitated the development of novel anticancer agents that have decreased side effects and increased safety. Theranostics, systems that have combined therapeutic effects and diagnostic capabilities, have garnered increasing attention recently because of their potential use in personalized medicine, including cancer-targeting treatments for patients. One interesting approach to achieving this potential involves the development of cancer-associated, stimuli-driven, turn on theranostics. Multicomponent constructs of this type would have the capability of selectively delivering therapeutic reagents into cancer cells or tumor tissues while simultaneously generating unique signals that can be readily monitored under both in vitro and in vivo conditions. Specifically, their combined anticancer activities and selective visual signal respond to cancer-associated stimuli, would make these theranostic agents more highly efficient and specific for cancer treatment and diagnosis. This article focuses on the progress of stimuli-responsive turn on theranostics that activate diagnostic signals and release therapeutic reagents in response to the cancer-associated stimuli. The present article not only provides the fundamental backgrounds of diagnostic and therapeutic tools that have been widely utilized for developing theranostic agents, but also discusses the current approaches for developing stimuli-responsive turn on theranostics.


Endoscopic image-guided odontoidectomy for decompression of basilar invagination via a standard anterior cervical approach. Technical note.
Symptomatic irreducible basilar invagination has traditionally been approached through a transoral-transpharyngeal route with resection of the anterior portion of C-1 and the odontoid. Modification of this exposure with either a Le Fort osteotomy or a transmandibular osteotomy and circumglossal approach has increased the access to pathological conditions in this region. These traditional routes all require traversing the oral cavity and accepting the associated potential complications. The authors have developed a novel surgical approach, an endoscopic transcervical odontoidectomy, which allows access for resection of the odontoid and for brainstem and spinal cord decompression without traversing the oral cavity. In this paper they describe the technique and its advantages and present three cases in which patients underwent the endoscopic transcervical odontoidectomy for basilar invagination. Three consecutive patients (age range 42-74 years) who had irreducible basilar invagination underwent the endoscopic transcervical odontoidectomy. All were symptomatic and had neck pain and myelopathy. All were evaluated preoperatively and postoperatively with computed tomography and magnetic resonance imaging. In all cases the procedure resulted in complete decompression. There were no serious complications. No patient required prolonged intubation, tracheostomy, or enteral tube feeding. One patient had an intraoperative cerebrospinal fluid leak, which had no postoperative sequelae. The authors present an alternative surgical approach for treating ventral compression of the brainstem and spinal cord. The technique is safe and effective for decompression and provides a surgical route that can be added to the armamentarium of treatments for pathological conditions in this region.


SR;NI Atom Transfer Radical Random Copolymerization of Styrene and Methyl Methacrylate:Incorporation of Diatomite Platelets.
Mesoporous diatomite platelets were employed to prepare various random poly (styrene-co-methyl methacrylate)/diatomite composites by in situ simultaneous reverse and normal initiation technique for atom transfer radical random copolymerization (SR&NI ATRP) technique. Nitrogen adsorption/desorption isotherm, SEM and TEM were employed for evaluating some inherent properties of the pristine diatomite platelets. Conversion and molecular weight determinations were carried out using GC and SEC respectively. Addition of 3 wt% diatomite platelets leads to increase of conversion from 76 to 92%. Molecular weight of poly (styrene-co-methyl methacrylate) chains increases from 12893 to 14907 g mol-1 by addition of 3 wt% mesoporous diatomite; however, polydispersity index values increases from 1.18 to 1.44. Copolymers composition was evaluated using 1H NMR spectroscopy. Increasing thermal stability of the nanocomposites is demonstrated by TGA. Differential scanning calorimetry shows an increase in glass transition temperature from 67.6 to 73.4 °C by adding 3 wt% of mesoporous diatomite platelets.


Neuronal Ca2+ sensor-1/frequenin functions in an autocrine pathway regulating Ca2+ channels in bovine adrenal chromaffin cells.
NCS-1/frequenin belongs to a family of EF-hand-containing Ca(2+) sensors expressed mainly in neurons. Overexpression of NCS-1/frequenin has been shown to stimulate neurotransmitter release but little else is known of its cellular roles. We have constructed an EF-hand mutant, NCS-1(E120Q), as a likely dominant inhibitor of cellular NCS-1 function. Recombinant NCS-1(E120Q) showed an impaired Ca(2+)-dependent conformational change but could still bind to cellular proteins. Transient expression of this mutant, but not NCS-1, in bovine adrenal chromaffin cells increased non-L-type Ca(2+) channel currents. Cells expressing NCS-1(E120Q) no longer responded effectively to the removal of autocrine purinergic/opioid inhibition of Ca(2+) currents but still showed voltage-dependent facilitation. These data are consistent with the existence of both voltage-dependent and voltage-independent pathways for Ca(2+) channel inhibition in chromaffin cells. Our results suggest a novel function for NCS-1 specific for the voltage-independent autocrine pathway that negatively regulates non-L-type Ca(2+) channels in chromaffin cells.


[Study of genetic models of maize kernel traits].
Two sets of NCII mating design including 21 different maize inbreds were used to study the genetic models of five maize kernel traits--kernel length, width, ratio of kernel length and width, kernel thickness and weight per 100 kernels. Ten generations including P1, P2, F1, F2, B1, B2 and their reciprocal crosses RF1, RF2, RB1, RB2 were obtained. Three years' data were obtained and analyzed using mainly two methods: (1) precision identification for single cross and (2) mixed liner model MINQUE approach for diallel design. Method 1 showed that kernel traits were primarily controlled by maternal dominance, endosperm additive and dominance effect (maternal dominance > endosperm additive > endosperm dominance). Cytoplasmic effect was detected in one of the two crosses studied. Method 2 revealed that in the total variance of kernel traits, maternal genotypic effect contributed more than 60%, endosperm genotypic effect contributed less than 40%. Cytoplasmic effect only existed in kernel length and 100 kernel weight, with the range of 10% to 30%. The results indicated that kernel genetic performance was quite largely controlled by maternal genotypic effect.


[Treatment of splenic trauma in paediatric age].
The splenic trauma in children presents some peculiarity that differentiates it from that one in adult age. Therefore we have see again our relative experience on splenic trauma, in the period 2001-2006, confronting two groups of patients, one of inferior age to fourteen years (A Group) and one of advanced age (B Group). We have estimated the following parameters: aetiology, type of lesion, association with others trauma, type of treatment, compliance, mortality, number of transfusions and hospital stay. On a total of 75 splenic trauma (M:52, F:23 of age comprised between 5 and 71 years) 18 belongs to the A group (medium age of 9.2 years) and 57 to the B group (medium ages of 47.4 years). The prevailing aetiology in the A group is domestic accident (39%) and the fall from bicycle (33%), while in the B group it is the street accident (69%). The lesions found in pediatric age are of smaller gravity if compared with B group, for lesion gravity and for association with abdominal and/or extra-abdominal others trauma. In the children group we have performed nonoperative management or conservative surgery in the 83% of cases versus the 26% in the B group. The rate of conversion from a nonoperative treatment in to an operative treatment has been of 7%. The post-operative complicance are absent in the A group and of 5.5% in the B group. The mortality rate in the surgical patients has been of the 14.3% for serious toraco-abdominal trauma in A group and of 11.1% in B group. No mortality is detected in the groups with nonoperative treatment. The medium number of transfusions is of 1.8 units in the paediatric patients and of 2.5 units in the adults. The medium stay in hospital is of eighteen days in the A group and of thirteen days in the B group. In conclusion the marked difference in the two groups examines stays in the type of treatment, more often nonoperative or conservative in the children group.


Doppler-derived percentage systolic window and the quantitation of arterial stenosis.
Peak systolic frequency (PSF) and percentage systolic window (%SW) are spectral parameters used to characterize poststenotic flow velocity patterns. The PSF, obtained using a continuous-wave (CW) Doppler velocimeter, has been used more frequently, however, in the quantitation of carotid occlusive disease. The authors have employed a microprocessor-driven pulsatile flow model to evaluate more completely the relationship between stenosis and the %SW. Using an 8 MHz CW Doppler probe, the Doppler-shifted frequencies were recorded at 1, 2, 3, 4, and 5 diameters distal to a variable, nonaxisymmetric stenosis, which reduced the cross-sectional area (CSA) 25, 40, 50, 60, 70, 85, and 97 per cent. Four sets of observations were made and the %SW derived using a spectrum analyzer. At one diameter from the stenosis, the relationship between the %SW (Y) and the reduction in CSA (X) is best described by two first-order regressions (Y = MX + B). The slope of the relationship from 0 to 60 per cent reduction in CSA is nearly flat, -0.052, while there is a significant (P less than 0.05) decrease in the slope, -1.538, when the CSA is further reduced from 60 to 97 per cent. Beyond 1 diameter, the relationship is best described by a single linear regression, the gradual slope of which does not permit clinically useful comparisons. These data explain the lack of strong correlation between CSA and %SW when the data are evaluated over the entire range of stenoses. However, they do indicate that the %SW may be a useful correlate if it is obtained within one diameter of the stenosis.


Identification of bacterial isolates from commercial poultry feed via 16S rDNA.
The study's objective was to identify typical aerobic isolates from commercial, corn-soybean meal poultry diets utilizing 16S rDNA, assign them their corresponding taxonomy, and compare the data with the previously published WGS analysis of these same isolates. Ten grams of a commercial corn-soybean meal poultry diet was homogenized in 100 mL of tryptic soy broth for 2 min, serially diluted, plated onto tryptic soy agar (TSA), and incubated aerobically for 24 h at 37 °C. Subsequently, 20 unique colonies were streaked for isolation on TSA and incubated aerobically for 24 h at 37 °C. This process was repeated three consecutive times for purification of isolates until only 11 morphologically distinct colonies were obtained. DNA was extracted using Qiagen's DNeasey® Blood and Tissue Kit. The 16S rRNA V4 region was targeted using an Illumina MiSeq and analyzed via QIIME2-2020.2. Alpha diversity and Beta diversity metrics were generated, and taxa were aligned using Silva in Qiime2-2020.2. Twenty-five distinct genera were identified within the 11 different colonies. Because 16S rDNA identification can provide an understanding of pathogen associations and microbial niches within an ecosystem, the information may present a potential method to establish and characterize the hygienic indicator microorganisms associated with poultry feed.


Metabolic correction in the management of diabetic peripheral neuropathy: improving clinical results beyond symptom control.
Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications. In USA alone, it has been estimated that there are more than 5,000,000 patients suffering from DPN and the total annual cost of treating the disease and its complications is over $10,000 million dollars. In order to be able to reduce complications of DPN, it is crucial to improve or correct the metabolic conditions that lead to the pathology present in this condition. Pathophysiologic mechanisms implicated in diabetic neuropathy include: increased polyol pathway with accumulation of sorbitol and reduced Na+/K+-ATPase activity, microvascular damage and hypoxia due to nitric oxide deficit and increased oxygen free radical activity. Moreover, there is a decrease in glutathione and increase in homocysteine. Clinical trials in the last two decades have demonstrated that the use of specific nutrients can correct some of these metabolic derangements, improving symptom control and providing further benefits such as improved sensorium, blood flow and nerve regeneration. We will discuss the evidence on lipoic acid, acetyl-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metformin, an important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk of developing DPN and how metabolic correction can reduce these risks.


The antigenic binding site(s) of antibodies to factor XII associated with the antiphospholipid syndrome.
Phospholipid binding proteins, including factor XII (FXII), are known to be targeted by antiphospholipid antibodies (aPA). Factor XII antibodies (FXIIab) have been described in some patients with the antiphospholipid syndrome (APS) and have been shown to lead to reduced levels of FXII. The antigenic binding site(s) and the pathophysiological effects of FXIIab are unknown. In an attempt to elucidate the binding site of these antibodies, immobilized plasma kallikrein was used to cleave FXII into its 52-kDa heavy-chain (HCFXII) and 28-kDa light-chain (LCFXII) components. Plasma samples from 12 female patients with definite APS and FXIIab were investigated for the presence of antibodies to FXII, HCFXII and LCFXII. All but one patient's plasma reacted to FXII, HCFXII and LCFXII in a similar manner. One patient gave markedly reduced positivity to HCFXII and LCFXII, suggesting that the FXIIab in this patient had a higher affinity for the intact FXII molecule. To further investigate the antigenic binding site(s) of FXII, 150 biotinylated peptides of the known FXII sequence were synthesized using a Multipin(TM) peptide synthesis procedure. The IgG and IgM fractions of the 12 patients' plasma were purified by affinity chromatography. The synthesized peptides were captured on streptavidin plates and individual patients' purified FXIIab assayed against the peptides in a modified enzyme-linked immunosorbent assay (ELISA). Two regions were identified as possible antigenic binding site(s) for FXIIab: one in the growth factor domain and the other in the catalytic domain.


Finite-size scaling in random K-satisfiability problems.
We provide a comprehensive view of various phase transitions in random K-satisfiability problems solved by stochastic-local-search algorithms. In particular, we focus on the finite-size scaling (FSS) exponent, which is mathematically important and practically useful in analyzing finite systems. Using the FSS theory of nonequilibrium absorbing phase transitions, we show that the density of unsatisfied clauses clearly indicates the transition from the solvable (absorbing) phase to the unsolvable (active) phase as varying the noise parameter and the density of constraints. Based on the solution clustering (percolation-type) argument, we conjecture two possible values of the FSS exponent, which are confirmed reasonably well in numerical simulations for 2 ≤ K ≤ 3.


Development of a Simple RP-HPLC-UV Method for Determination of Azithromycin in Bulk and Pharmaceutical Dosage forms as an Alternative to the USP Method.
The present study was designed to develop a simple, validated liquid chromatographic method for the analysis of azithromycin in bulk and pharmaceutical dosage forms using ultraviolet detector. The best stationary phase was determined as C18 column, 5 μm, 250 mm × 4.6 mm. Mobile phase was optimized to obtain a fast and selective separation of the drug. Flow rate was 1.5 mL/min, Wavelength was set at 210 nm and the volume of each injection was 500 μL. An isocratic methanol/buffer mobile phase at the ratio of 90:10 v/v gave the best separation and resolution. The proposed method was accurate, precise, sensitive, and linear over a wide range of concentration of azithromycin. The developed method has the advantage of using UV detector compared to the USP method in which electrochemical detector has been used. The validated method was successfully applied to the determination of azithromycin in bulk and pharmaceutical dosage forms.


L1CAM: a major driver for tumor cell invasion and motility.
The L1 cell adhesion molecule (L1CAM) plays a major role in the development of the nervous system and in the malignancy of human tumors. In terms of biological function, L1CAM comes along in two different flavors: (1) a static function as a cell adhesion molecule that acts as a glue between cells; (2) a motility promoting function that drives cell migration during neural development and supports metastasis of human cancers. Important factors that contribute to the switch in the functional mode of L1CAM are: (1) the cleavage from the cell surface by membrane proximal proteolysis and (2) the ability to change binding partners and engage in L1CAM-integrin binding. Recent studies have shown that the cleavage of L1CAM by metalloproteinases and the binding of L1CAM to integrins via its RGD-motif in the sixth Ig-domain activate signaling pathways distinct from the ones elicited by homophilic binding. Here we highlight important features of L1CAM proteolysis and the signaling of L1CAM via integrin engagement. The novel insights into L1CAM downstream signaling and its regulation during tumor progression and epithelial-mesenchymal transition (EMT) will lead to a better understanding of the dualistic role of L1CAM as a cell adhesion and/or motility promoting cell surface molecule.


Chronic pancreatitis.
As in our previous reviews, we endeavor to review important new observations in chronic pancreatitis made in the past year. Topics recently reviewed were truncated to accommodate a surge in publications on clinical aspects of chronic pancreatitis, which contained new observations or insights into new or old concepts. Cystic fibrosis carriers have been found to be at increased risk of pancreatitis. Autoimmune pancreatitis may belong to a multiorgan immunoglobulin G4-related autoimmune disease, and the natural history of chronic pancreatitis differs among the etiologies. Diffusion-weighted magnetic resonance imaging improves upon previous methodologies for diagnosing reduced pancreatic exocrine secretion, and fecal elastase-1 has been found to be a poor test for diagnosing pancreatic malabsorption. Visceral hyperalgesia or heightened central pain perception may contribute to pain in chronic pancreatitis. Instruments are evolving to assess quality of life in chronic pancreatitis, and fibrolytic agents have been found to have therapeutic promise. Researchers this past year have further characterized genetic, molecular and clinical aspects of chronic pancreatitis. Advancing the understanding of fibrogenesis, mechanisms of exocrine insufficiency, calcification, and pain and continuing development/modification of diagnostic tests should lead to improved prevention, detection and treatment of the condition. More accurate quantification of outcomes is critical for translating potential therapies from bench to bedside.