Hyaluronic acid hydrogels incorporating platelet lysate enhance human pulp cell proliferation and differentiation.
The restoration of dentine-pulp complex remains a challenge for dentists; nonetheless, it has been poorly addressed. An ideal system should modulate the host response, as well as enable the recruitment, proliferation and differentiation of relevant progenitor cells. Herein was proposed a photocrosslinkable hydrogel system based on hyaluronic acid (HA) and platelet lysate (PL). PL is a cocktail of growth factors (GFs) and cytokines involved in wound healing orchestration, obtained by the cryogenic processing of platelet concentrates, and was expected to provide the HA hydrogels specific biochemical cues to enhance pulp cells' recruitment, proliferation and differentiation. Stable HA hydrogels incorporating PL (HAPL) were prepared after photocrosslinking of methacrylated HA (Met-HA) previously dissolved in PL, triggered by the Ultra Violet activated photoinitiator Irgacure 2959. Both the HAPL and plain HA hydrogels were shown to be able to recruit cells from a cell monolayer of human dental pulp stem cells (hDPSCs) isolated from permanent teeth. The hDPCs were also seeded directly over the hydrogels (5 × 104 cells/hydrogel) and cultured in osteogenic conditions. Cell metabolism and DNA quantification were higher, in all time-points, for PL supplemented hydrogels (p < 0,05). Alkaline phosphatase (ALPL) activity and calcium quantification peaks were observed for the HAPL group at 21 days (p < 0,05). The gene expression for ALPL and COLIA1 was up-regulated at 21 days to HAPL, compared with HA group (p < 0,05). Within the same time point, the gene expression for RUNX2 did not differ between the groups. Overall, data demonstrated that the HA hydrogels incorporating PL increased the cellular metabolism and stimulate the mineralized matrix deposition by hDPSCs, providing clear evidence of the potential of the proposed system for the repair of damaged pulp/dentin tissue and endodontics regeneration.


Herpesvirus type 2 isolated from cervical tumor cells grown in tissue culture.
A herpesvirus has been isolated from spontaneously degenerating cultures of cervical tumor cells grown in vitro. The virus was identified as a type 2 herpesvirus on the basis of biologic properties, including plaque morphology and microtubule formation in infected HEp-2 cells, and of immunologic specificity as determined by neutralization. Herpesvirus antigens and virus particles were not seen in duplicate cultures of viable cervical tumor cells.


Impact of a Nationwide Training Program in Minimally Invasive Distal Pancreatectomy (LAELAPS).
To study the feasibility and impact of a nationwide training program in minimally invasive distal pancreatectomy (MIDP). Superior outcomes of MIDP compared with open distal pancreatectomy have been reported. In the Netherlands (2005 to 2013) only 10% of distal pancreatectomies were in a minimally invasive fashion and 85% of surgeons welcomed MIDP training. The feasibility and impact of a nationwide training program is unknown. From 2014 to 2015, 32 pancreatic surgeons from 17 centers participated in a nationwide training program in MIDP, including detailed technique description, video training, and proctoring on-site. Outcomes of MIDP before training (2005-2013) were compared with outcomes after training (2014-2015). In total, 201 patients were included; 71 underwent MIDP in 9 years before training versus 130 in 22 months after training (7-fold increase, P < 0.001). The conversion rate (38% [n = 27] vs 8% [n = 11], P < 0.001) and blood loss were lower after training and more pancreatic adenocarcinomas were resected (7 [10%] vs 28 [22%], P = 0.03), with comparable R0-resection rates (4/7 [57%] vs 19/28 [68%], P = 0.67). Clavien-Dindo score ≥III complications (15 [21%] vs 19 [15%], P = 0.24) and pancreatic fistulas (20 [28%] vs 41 [32%], P = 0.62) were not significantly different. Length of hospital stay was shorter after training (9 [7-12] vs 7 [5-8] days, P < 0.001). Thirty-day mortality was 3% vs 0% (P = 0.12). A nationwide MIDP training program was feasible and followed by a steep increase in the use of MIDP, also in patients with pancreatic cancer, and decreased conversion rates. Future studies should determine whether such a training program is applicable in other settings.


[Effect of the enzymatic treatment of erythrocyte membranes on their interaction with neutrophilic leukocytes].
The treatment of erythrocytes with different enzymes (neuraminidase, trypsin and papain) has been studied for its effect on the lipid peroxidation in their membranes, activity of antioxidant enzymes and on the ability of such erythrocytes to interact with neutrophilic leucocytes. It is shown that desialization of the membrane erythrocyte structures causes the intensification of lipid peroxidation in the membranes, decrease of their stability. Simultaneously, the interaction of neutrophils increases. The treatment with proteases causes the opposite changes. It is shown possible to split out the end molecules of sialic acids with exposure of the subterminal residues of B-galactose as a result of the effect of active oxygen forms. An assumption is advanced concerning the functional conjugation of the free-radical oxidation and proteolysis in provision of stability of the cell membranes.


Properties of Bac W42, a bacteriocin produced by Bacillus subtilis W42 isolated from Cheonggukjang.
Ten Bacillus strains with antimicrobial activities were isolated from Cheonggukjang produced at different parts in Korea. They all inhibited Listeria monocytogenes ATCC 19111 and nine inhibited Bacillus cereus ATCC 14579. Four isolates (W42, H27, SKE 12, and K21) showing strong inhibiting activities were identified as B. subtilis. B. subtilis W42 was the most inhibiting strain. The antimicrobial activity of culture supernatant from B. subtilis W42 was destroyed completely by proteinase K treatment, indicating that a bacteriocin was the responsible agent. The bacteriocin, Bac W42, was most stable at pH 7 and stable between pH 3-6 and 8-9. Bac W42 was stable up to 80°C. BHI (brain heart infusion) and TSB (tryptic soy broth) were the best media for the activity (320 AU/ml) followed by LB (160 AU/ml). Bac W42 was partially purified by column chromatographies. The specific activity was increased from 1,151.2 AU/ml to 9,043.5 AU/ml and the final yield was 26.3%. Bac W42 was 5.4 kDa in size as determined by SDS-PAGE. Bac W42 showed bactericidal activity against L. monocytogenes ATCC 19111.


Delayed-type hypersensitivity response to human papillomavirus type 16 E6 protein in a mouse model.
A mouse model incorporating the epitheliotropic nature of human papillomavirus (HPV) infections has been used to study an immune response to HPV type 16 (HPV-16) E6 protein in vivo. Using a transplantation technique, a novel immortal keratinocyte cell line expressing the E6 protein has been grafted onto syngeneic mice to re-form a differentiated epithelium overlying a granulation tissue bed. By this approach the presentation of viral antigens to the immune system can be modelled in a way analogous to the natural infection. Here we report a delayed-type hypersensitivity (DTH) reaction in grafted mice challenged intradermally with a recombinant vaccinia virus expressing the HPV-16 E6 protein. The specificity of the response was confirmed by the absence of a DTH reaction to challenge with virus expressing either HPV-16 E7 or L1 protein.


Association of miR-146a and miR196a2 genotype with susceptibility to idiopathic recurrent pregnancy loss in Iranian women: A case-control study.
Recurrent pregnancy loss (RPL) is the most common complaint of pregnancy in females with a prevalence of 5%. Numerous documents have shown that single nucleotide polymorphisms are able to change miRNA transcription and/or maturation, which may alter the incidence of disorders such as RPL. To assess the relationship of miR-146aC > G (rs2910164) and miR-196a2T > C (rs11614913) with RPL susceptibility in Iranian women. Blood samples were collected from 214 women who had experienced at least two consecutive spontaneous miscarriages (case) and 147 normal individuals without a history of miscarriage (control). MiR-146aC > G and miR-196a2T > C genotypes were evaluated via the restriction fragment length polymorphism technique. The genotypes incidence did not show a significant difference in pre-miR-146aC > G polymorphism CC vs CG + GG (p = 0.854; OR = 0.933; 95% CI) and CC + CG vs GG (p = 0.282; OR = 1.454; 95% CI). Also, no significant difference was observed between pre-miR-196a2T > C polymorphism TT vs TC + CC (p = 0.862; OR = 0.938; 95% CI) and TT + TC vs CC and (p = 0.291; OR = 1.462; 95% CI) in both the case and control groups. The results showed that although the distribution of miR-146aC > G and miR-196a2T > C was different between the unknown RPL and control groups, these variances were not statistically significant.


Optical Control of Cell Signaling with Red/Far-Red Light-Responsive Optogenetic Tools in Caenorhabditis elegans.
Optogenetic techniques have been intensively applied to the nematode Caenorhabditis elegans to investigate its neural functions. However, as most of these optogenetics are responsive to blue light and the animal exhibits avoidance behavior to blue light, the application of optogenetic tools responsive to longer wavelength light has been eagerly anticipated. In this study, we report the implementation in C. elegans of a phytochrome-based optogenetic tool that responds to red/near-infrared light and manipulates cell signaling. We first introduced the SynPCB system, which enabled us to synthesize phycocyanobilin (PCB), a chromophore for phytochrome, and confirmed the biosynthesis of PCB in neurons, muscles, and intestinal cells. We further confirmed that the amount of PCBs synthesized by the SynPCB system was sufficient for photoswitching of phytochrome B (PhyB)-phytochrome interacting factor 3 (PIF3). In addition, optogenetic elevation of intracellular Ca2+ levels in intestinal cells induced a defecation motor program. These SynPCB system and phytochrome-based optogenetic techniques would be of great value in elucidating the molecular mechanisms underlying C. elegans behaviors.


Genome-wide characterization and expression analysis of citrus NUCLEAR FACTOR-Y (NF-Y) transcription factors identified a novel NF-YA gene involved in drought-stress response and tolerance.
Nuclear factor Y (NF-Y) is a ubiquitous transcription factor found in eukaryotes. It is composed of three distinct subunits called NF-YA, NF-YB and NF-YC. NF-Ys have been identified as key regulators of multiple pathways in the control of development and tolerance to biotic and abiotic factors. The present study aimed to identify and characterize the complete repertoire of genes coding for NF-Y in citrus, as well as to perform the functional characterization of one of its members, namely CsNFYA5, in transgenic tobacco plants. A total of 22 genes coding for NF-Y were identified in the genomes of sweet orange (Citrus sinensis) and Clementine mandarin (C. clementina), including six CsNF-YAs, 11 CsNF-YBs and five CsNF-YCs. Phylogenetic analyses showed that there is a NF-Y orthologous in the Clementine genome for each sweet orange NF-Y gene; this was not observed when compared to Arabidopsis thaliana. CsNF-Y proteins shared the same conserved domains with their orthologous proteins in other organisms, including mouse. Analysis of gene expression by RNA-seq and EST data demonstrated that CsNF-Ys have a tissue-specific and stress inducible expression profile. qRT-PCR analysis revealed that CsNF-YA5 exhibits differential expression in response to water deficit in leaves and roots of citrus plants. Overexpression of CsNF-YA5 in transgenic tobacco plants contributed to the reduction of H2O2 production under dehydration conditions and increased plant growth and photosynthetic rate under normal conditions and drought stress. These biochemical and physiological responses to drought stress promoted by CsNF-YA5 may confer a productivity advantage in environments with frequent short-term soil water deficit.


Presence of neuroticism and antidepressant remission rates in late-life depression: results from the Neurobiology of Late-Life Depression (NBOLD) study.
ABSTRACTNeuroticism in older adults is common yet understudied, particularly its effects on depression treatment outcomes. We hypothesized that presence of high neuroticism would be associated with lower 12-week remission rates in older depressed sertraline-treated patients. In this longitudinal cohort study, 43 depressed older adults completed the Revised NEO Personality Inventory (NEO PI-R). A study psychiatrist administered the Montgomery Ǻsberg Depression Rating Scale (MADRS), and the Cumulative Illness Rating Scale (CIRS, a measure of medical burden) at baseline, and the MADRS at each clinical visit. All subjects began open-label sertraline treatment and were followed over 12 weeks with clinically indicated flexible dosing and an option to switch antidepressants. We used regression analyses to examine factors related to 12-week remission of depression (MADRS score < 8) and final MADRS score. We found that higher total neuroticism (odds ratio (OR) = 0.963, 95% confidence interval (CI) = 0.928-1.000) and a neuroticism subscale, stress vulnerability (OR = 0.846, 95% CI = 0.728-0.983), were associated with lower likelihood of remission among both the intention-to-treat group and sertraline completers. Findings remained significant after controlling for baseline MADRS and CIRS score. In conclusion, assessment of personality, particularly features of neuroticism, may be important in management of late-life depression. Future studies should determine if depressed patients high in neuroticism may benefit from psychotherapy focusing on emotional regulation and stress management.


General anesthetic effects on compound muscle action potentials elicited by single or dual spinal cord stimulation.
The aim of this study was to determine the optimal conditions, during general anesthesia, to obtain reproducible monitoring of compound muscle action potentials (CMAPs) as a means to evaluate motor tract integrity. The CMAPs were recorded in the soleus muscle of cats and were elicited by either single or double pulse stimulations (with various amplitudes and interpulse durations) of the spinal cord via an epidural electrode. The effects of various depths of general anesthesia with halothane, enflurane, isoflurane, or propofol on such recordings were also determined. For each agent, the CMAP amplitudes were significantly greater following double pulse stimulations (2-ms optimal interpulse duration) relative to single pulses. The CMAP amplitudes elicited by double pulse stimulations were the same at propofol concentrations of 50, 100, 150, and 200 micrograms/kg/min, whereas those for each volatile anesthetic, at all concentrations studied (0.5%, 1.0%, 1.5%, or 2.0%), were significantly lower. It was concluded that to obtain reliable CMAP amplitudes, general anesthesia with propofol should be employed and the potentials should be evoked by double pulse stimulations.


The use of nonpharmacological interventions to reduce anxiety in patients undergoing gastroscopy in a setting with an optimal soothing environment.
Patients develop anxiety before undergoing gastroscopy. By removing such distressing feelings, patients are more likely to experience gastroscopy more smoothly. This study was designed to examine changes in anxiety levels in patients undergoing gastroscopy and the effect of an optimal soothing environment (OSE) as a new nonpharmacological intervention to reduce patient anxiety prior to gastroscopy. During a 6-month period, 50 outpatients referred for gastroscopy were randomly assigned to two groups (control group, n = 24 patients; OSE group, n = 26 patients). This study was performed at the digestive endoscopy service of a 150-bed acute care hospital in Japan. The patient anxiety was assessed using the Face Scale score. Pre- and postprocedural systolic blood pressures were measured and values were compared with blood pressure upon arrival at the hospital. The tools for an OSE, including a safe essential oil burner with lavender essential oil and a digital video disk program entitled "Flow" manufactured by NHK (Japan Broadcasting Corporation) software, were provided to patients in the waiting room before gastroscopy. The score for self-assessed anxiety level just before gastroscopy was significantly higher than that on arrival at the hospital but returned to baseline after gastroscopy in the control group, whereas the score did not increase before starting gastroscopy in the OSE group. Systolic blood pressure measurements just before and after gastroscopy were significantly higher than those on arrival at the hospital and the baseline values in the control group, whereas it was not increased before starting gastroscopy in the OSE group. Providing an OSE before and during gastroscopy is useful to minimize patient anxiety regarding experiencing a gastroscopy. This nonpharmacological method is a simple, inexpensive, and safe method of minimizing anxiety before and during gastroscopy.


Dynamic Surface Modification of Metal-Organic Framework Nanoparticles via Alkoxyamine Functional Groups.
External surface engineering of metal-organic framework nanoparticles (MOF NPs) is emerging as an important design strategy, leading to optimized chemical and colloidal stability. To date, most of the MOF surface modifications have been performed either by physical adsorption or chemical association of small molecules or (preformed) polymers. However, most of the currently employed approaches cannot precisely control the polymer density, and dynamic modifications at the surfaces on demand have been a challenging task. Here, we introduce a general approach based on covalent modification employing alkoxyamines as a versatile tool to modify the outer surface of MOF nanoparticles (NPs). The alkoxyamines serve as initiators to grow polymers from the MOF surface via nitroxide-mediated polymerization (NMP) and allow dynamic attachment of small molecules via a nitroxide exchange reaction (NER). The successful surface modification and successive surface polymerization are confirmed via time-of-flight secondary ion mass spectrometry (ToF-SIMS), size exclusion chromatography (SEC), and nuclear magnetic resonance (NMR) spectroscopy. The functionalized MOF NPs exhibit high suspension stability and good dispersibility while retaining their chemical integrity and crystalline structure. In addition, electron paramagnetic resonance spectroscopy (EPR) studies prove the dynamic exchange of two different nitroxide species via NER and further allow us to quantify the surface modification with high sensitivity. Our results demonstrate that alkoxyamines serve as a versatile tool to dynamically modify the surface of MOF NPs with high precision, allowing us to tailor their properties for a wide range of potential applications, such as drug delivery or mixed matrix membranes.


Higher pH and faster decomposition in biowaste composting by increased aeration.
Composting of source separated municipal biowaste has at several plants in Scandinavia been hampered by low pH. In this study the hypothesis that increased aeration would improve the process was tested in full-scale experiments at two large composting plants. The O2 concentrations were high (>15%) even at the low aeration rates, so the prevailing low pH was not due to an anaerobic process environment. In spite of this, increased aeration rates at the start of the process resulted in higher microbial activity, increased pH and a more stable compost product. At one plant the decomposition rate varied in proportion to the aeration rate, to the extent that the temperatures and O2 concentrations were similar during the early processes even though aeration rates varied between 10 and 50 m3/(h, m3 compost). However, increased aeration caused severe drying of the compost, but at one plant the addition of water was adequate to prevent drying. In conclusion, by increasing the aeration rates and adding water to compensate for drying, it was possible to shorten the time needed to produce a stable compost product and thus to increase the efficiency of the composting plants.


Cost effectiveness of self-monitoring of blood glucose (SMBG) for patients with type 2 diabetes and not on insulin: impact of modelling assumptions on recent Canadian findings.
Canadian patients, healthcare providers and payers share interest in assessing the value of self-monitoring of blood glucose (SMBG) for individuals with type 2 diabetes but not on insulin. Using the UKPDS (UK Prospective Diabetes Study) model, the Canadian Optimal Prescribing and Utilization Service (COMPUS) conducted an SMBG cost-effectiveness analysis. Based on the results, COMPUS does not recommend routine strip use for most adults with type 2 diabetes who are not on insulin. Cost-effectiveness studies require many assumptions regarding cohort, clinical effect, complication costs, etc. The COMPUS evaluation included several conservative assumptions that negatively impacted SMBG cost effectiveness. Current objectives were to (i) review key, impactful COMPUS assumptions; (ii) illustrate how alternative inputs can lead to more favourable results for SMBG cost effectiveness; and (iii) provide recommendations for assessing its long-term value. A summary of COMPUS methods and results was followed by a review of assumptions (for trial-based glycosylated haemoglobin [HbA(1c)] effect, patient characteristics, costs, simulation pathway) and their potential impact. The UKPDS model was used for a 40-year cost-effectiveness analysis of SMBG (1.29 strips per day) versus no SMBG in the Canadian payer setting. COMPUS assumptions for patient characteristics (e.g. HbA(1c) 8.4%), SMBG HbA(1c) advantage (-0.25%) and costs were retained. As with the COMPUS analysis, UKPDS HbA(1c) decay curves were incorporated into SMBG and no-SMBG pathways. An important difference was that SMBG HbA(1c) benefits in the current study could extend beyond the initial simulation period. Sensitivity analyses examined SMBG HbA(1c) advantage, adherence, complication history and cost inputs. Outcomes (discounted at 5%) included QALYs, complication rates, total costs (year 2008 values) and incremental cost-effectiveness ratios (ICERs). The base-case ICER was $Can63 664 per QALY gained; approximately 56% of the COMPUS base-case ICER. SMBG was associated with modest risk reductions (0.10-0.70%) for six of seven complications. Assuming an SMBG advantage of -0.30% decreased the current base-case ICER by over $Can10 000 per QALY gained. With adherence of 66% and 87%, ICERs were (respectively) $Can39 231 and $Can54 349 per QALY gained. Incorporating a more representative complication history and 15% complication cost increase resulted in an ICER of $Can49 743 per QALY gained. These results underscore the importance of modelling assumptions regarding the duration of HbA(1c) effect. The current study shares several COMPUS limitations relating to the UKPDS model being designed for newly diagnosed patients, and to randomized controlled trial monitoring rates. Neither study explicitly examined the impact of varying the duration of initial HbA(1c) effects, or of medication or other treatment changes. Because the COMPUS research will potentially influence clinical practice and reimbursement policy in Canada, understanding the impact of assumptions on cost-effectiveness results seems especially important. Demonstrating that COMPUS ICERs were greatly reduced through variations in a small number of inputs may encourage additional clinical research designed to measure SMBG effects within the context of optimal disease management. It may also encourage additional economic evaluations that incorporate lessons learned and best practices for assessing the overall value of SMBG for type 2 diabetes in insulin-naive patients.


Multidisciplinary Recommendations Regarding Post-Vaccine Adenopathy and Radiologic Imaging: Radiology Scientific Expert Panel.
Vaccination-associated adenopathy is a frequent imaging finding after administration of COVID-19 vaccines that may lead to a diagnostic conundrum in patients with manifest or suspected cancer, in whom it may be indistinguishable from malignant nodal involvement. To help the medical community address this concern in the absence of studies and evidence-based guidelines, this special report offers recommendations developed by a multidisciplinary panel of experts from three of the leading tertiary care cancer centers in the United States. According to these recommendations, some routine imaging examinations, such as those for screening, should be scheduled before or at least 6 weeks after the final vaccination dose to allow for any reactive adenopathy to resolve. However, there should be no delay of other clinically indicated imaging (eg, for acute symptoms, short-interval treatment monitoring, urgent treatment planning or complications) due to prior vaccination. The vaccine should be administered on the side contralateral to the primary or suspected cancer, and both doses should be administered in the same arm. Vaccination information-date(s) administered, injection site(s), laterality, and type of vaccine-should be included in every preimaging patient questionnaire, and this information should be made readily available to interpreting radiologists. Clear and effective communication between patients, radiologists, referring physician teams, and the general public should be considered of the highest priority when managing adenopathy in the setting of COVID-19 vaccination.


Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression.
Agitation/aggression in Alzheimer disease (AD) is a major cause of patient distress, caregiver burden, and institutionalization. Enhanced behavioral responsiveness to central nervous system norepinephrine (NE) release may contribute to the pathophysiology of agitation/aggression in AD. Prazosin, a nonsedating generic medication used for hypertension and benign prostatic hypertrophy, antagonizes NE effects at brain postsynaptic alpha-1 adrenoreceptors. This pilot study examined the efficacy and tolerability of prazosin for behavioral symptoms in patients with agitation/aggression in AD. Double-blind, placebo controlled, parallel group study. A university AD center and a nursing home in Seattle, WA. Twenty-two nursing home and community-dwelling participants with agitation/aggression and probable or possible AD (mean age: 80.6 +/- 11.2). Randomization to placebo (N = 11) or prazosin (N = 11). Medication was initiated at 1 mg/day and increased up to 6 mg/day using a flexible dosing algorithm. The Brief Psychiatric Rating Scale (BPRS) and Neuropsychiatric Inventory (NPI) at Weeks 1, 2, 4, 6, and 8. The Clinical Global Impression of Change (CGIC) at Week 8. Participants taking prazosin (mean dose: 5.7 +/- 0.9 mg/day) had greater improvements than those taking placebo (mean dose: 5.6 +/- 1.2 mg/day) on the NPI (mean change: -19 +/- 21 versus -2 +/- 15, chi = 6.32, df = 1, p = 0.012) and BPRS (mean change: -9 +/- 9 versus -3 +/- 5, chi = 4.42, df = 1, p = 0.036) based on linear mixed effects models and the CGIC (mean: 2.6 +/- 1.0 versus 4.5 +/- 1.6, z = 2.57, p = 0.011 [Mann-Whitney test]). Adverse effects and blood pressure changes were similar between prazosin and placebo groups. Prazosin was well tolerated and improved behavioral symptoms in patients with agitation/aggression in AD.


Value-Based Assessment of New Medical Technologies: Towards a Robust Methodological Framework for the Application of Multiple Criteria Decision Analysis in the Context of Health Technology Assessment.
In recent years, multiple criteria decision analysis (MCDA) has emerged as a likely alternative to address shortcomings in health technology assessment (HTA) by offering a more holistic perspective to value assessment and acting as an alternative priority setting tool. In this paper, we argue that MCDA needs to subscribe to robust methodological processes related to the selection of objectives, criteria and attributes in order to be meaningful in the context of healthcare decision making and fulfil its role in value-based assessment (VBA). We propose a methodological process, based on multi-attribute value theory (MAVT) methods comprising five distinct phases, outline the stages involved in each phase and discuss their relevance in the HTA process. Importantly, criteria and attributes need to satisfy a set of desired properties, otherwise the outcome of the analysis can produce spurious results and misleading recommendations. Assuming the methodological process we propose is adhered to, the application of MCDA presents three very distinct advantages to decision makers in the context of HTA and VBA: first, it acts as an instrument for eliciting preferences on the performance of alternative options across a wider set of explicit criteria, leading to a more complete assessment of value; second, it allows the elicitation of preferences across the criteria themselves to reflect differences in their relative importance; and, third, the entire process of preference elicitation can be informed by direct stakeholder engagement, and can therefore reflect their own preferences. All features are fully transparent and facilitate decision making.


Impact of FDA Updates on Public Interest in Breast Implant-associated Anaplastic Large Cell Lymphoma.
In the United States, the Food and Drug Administration (FDA) is responsible for protecting the public health by assuring the safety, efficacy, and security of drugs, biological products, and medical devices. In that role, FDA releases timely updates with regard to medical devices and their possible adverse effects. However, the impact of such FDA updates on public interest has not been studied. The timing of multiple FDA updates regarding Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) was noted from September 2014 to September 2019. Impact on Public interest related to ALCL was measured using Google Trends and the number of YouTube video uploads. These objective markers were used to compare the public interest during FDA updates versus weeks with no FDA updates. Five major updates were released by FDA regarding BIA-ALCL during the past 5 years. Google Trends demonstrated a significant increase in public interest regarding ALCL during the week of FDA release, with a mean score of 69 ± 20.82 when compared with a mean score of 10.68 ± 4.71 (P < 0.001) during weeks with no FDA release. The mean number of YouTube videos uploaded during the period of FDA release was 11.8 ± 9.42, which was significantly higher than the mean of 2.42 ± 1.31 videos (P < 0.001) during the period of no FDA updates. FDA updates correlates with temporal increase in public interest. Plastic surgeons should be aware of FDA information releases on BIA-ALCL and anticipate an increased interest in additional information from patients and the public.


Sources of gas gangrene in hospital.
Of four cases of postoperative gas gangrene in three hospitals three followed amputation of legs with gangrenous lesions, and one followed gastrectomy. Clostridium welchii was isolated from the wounds and the faeces of each patient; small numbers of Cl. welchii were found on the floors of the theatres where the operations had been performed.Two infections occurred in one hospital on successive days. Typing of strains of Cl. welchii from these patients showed that they were serologically distinct. Further studies suggested that in each of the four cases infection was probably acquired from the patients' intestinal flora, probably through faecal contamination of skin.In 76 patients sampling of the skin with surface contact plates showed occasional heavy contamination of the thighs, groins, and buttocks with Cl. welchii, most of which were present as spores or sporing bacilli; Cl. welchii was more commonly found in patients with incontinence of faeces. Compresses of povidone-iodine applied for 30 minutes were found greatly to reduce the numbers of Cl. welchii, and swabbing with 70% alcohol was effective in some cases; washing with soap and water had no effect on the numbers of Cl. welchii on the skin.


Myocardial regeneration therapy for ischemic cardiomyopathy with cyclin A2.
Heart failure therapies ranging from revascularization to remodeling to replacement are variably effective. Theoretically, endogenous repair via myocardial regeneration would be an ideal therapy. This study examined the ability to initiate regeneration by adenoviral-mediated expression of the cell cycle regulator cyclin A2. Our prior studies have demonstrated robust cyclin A2 transgene expression and marked antiphosphorylated histone H3 activity with this strategy, indicating the induction of cardiomyocyte mitosis. Adult male, Lewis rats underwent left anterior descending coronary artery ligation followed by intramyocardial delivery of either cyclin A2 adenoviral vector (n = 8) or empty adeno-null vector as a control (n = 8) into the peri-infarct border zone. In vivo myocardial function was analyzed by echocardiography and invasive left ventricular pressure catheter at 6 weeks, when the animals are traditionally in heart failure. Hearts were explanted for immunoblotting and left ventricular geometric analysis. Cellular proliferation was assessed by proliferating cellular nuclear antigen expression. Cyclin A2 hearts exhibited improved left ventricular function as compared with controls including enhanced cardiac output (32 +/- 3.3 vs 26 +/- 5.0 mL/min, P < .05), stroke volume (0.16 +/- 0.04 vs 0.11 +/- 0.04 mL, P < .05), ejection fraction (72% +/- 7.4% vs 46.% +/- 8.5%, P < .05), fractional shortening (35% +/- 5.4% vs 19% +/- 4.3%, P < .002), maximum pressure (72 +/- 9.3 vs 61 +/- 2.9 mm Hg, P < .05), and end-systolic pressure (67 +/- 7.0 vs 55 +/- 7.0 mm Hg, P < .05). Enhanced myocardial preservation was demonstrated by enhanced left ventricular border zone wall thickness. Increased myocardial proliferation was evidenced by increased expression of proliferating cell nuclear antigen expression in cyclin A2-treated hearts. In failing hearts, targeted delivery of cyclin A2 improves hemodynamic function, as measured by echocardiography and pressure catheter analysis, preserves ventricular wall thickness, and may serve as an ideal myocardial regenerative therapy.


Involvement of cDNA in homologous recombination between Ty elements in Saccharomyces cerevisiae.
Strains carrying a marked Ty element (TyUra) in the LYS2 locus were transformed with plasmids bearing a differently marked Ty1 element (Ty1Neo) under the control of the GAL promoter. When these strains were grown in glucose, a low level of gene conversion events involving TyUra was detected. Upon growth on galactose an increase in the rate of gene conversion was seen. This homologous recombination is not the consequence of increased levels of transposition. When an intron-containing fragment was inserted into Ty1Neo, some of the convertants had the intron removed, implying an RNA intermediate. Mutations that affect reverse transcriptase or reverse transcription of Ty1Neo greatly reduce the induction of recombination in galactose. Thus, Ty cDNA is involved in homologous gene conversion with chromosomal copies of Ty elements. Our results have implications about the way families of repeated sequences retain homogeneity throughout evolution.


Small Molecule Chelators Reveal That Iron Starvation Inhibits Late Stages of Bacterial Cytokinesis.
Bacterial cell division requires identification of the division site, assembly of the division machinery, and constriction of the cell envelope. These processes are regulated in response to several cellular and environmental signals. Here, we use small molecule iron chelators to characterize the surprising connections between bacterial iron homeostasis and cell division. We demonstrate that iron starvation downregulates the transcription of genes encoding proteins involved in cell division, reduces protein biosynthesis, and prevents correct positioning of the division machinery at the division site. These combined events arrest the constriction of the cell during late stages of cytokinesis in a manner distinct from known mechanisms of inhibiting cell division. Overexpression of genes encoding cell division proteins or iron transporters partially suppresses the biological activity of iron chelators and restores growth and division. We propose a model demonstrating the effect of iron availability on the regulatory mechanisms coordinating division in response to the nutritional state of the cell.


Inhibition of androgen receptor (AR) function by the reproductive orphan nuclear receptor DAX-1.
DAX-1 (NROB1) is an atypical member of the nuclear receptor family that is predominantly expressed in mammalian reproductive tissues. While a receptor function of DAX-1 remains enigmatic, previous work has indicated that DAX-1 inhibits the activity of the orphan receptor steroidogenic factor 1 and the estrogen receptors (ERs), presumably via direct occupation of the coactivator-binding surface and subsequent recruitment of additional corepressors. In vivo evidence points at a particular role of DAX-1 for the development and maintenance of male reproductive functions. In this study, we have identified the androgen receptor (AR) NR3C4 as a novel target for DAX-1. We show that DAX-1 potently inhibits ligand-dependent transcriptional activation as well as the interaction between the N- and C-terminal activation domains of AR. We provide evidence for direct interactions of the two receptors that involve the N-terminal repeat domain of DAX-1 and the C-terminal ligand-binding and activation domain of AR. Moreover, DAX-1, known to shuttle between the cytoplasm and the nucleus, is capable of relocalizing AR in both cellular compartments, suggesting that intracellular tethering is associated with DAX-1 inhibition. These results implicate novel inhibitory mechanisms of DAX-1 action with particular relevance for the modulation of androgen-dependent gene transcription in the male reproductive system.


[Universal newborn hearing screening program in Würzburg. Experience with more than 4000 newborns and the influence of non-pathological factors on the test results].
The BERAphon(R) method employing a special headphone and the time-course step-stimulus algorithm offers a quick and reliable tool for universal hearing screening in newborns. An ABR-based universal newborn hearing screening program has been established in Würzburg since August, 1997. Until August 2001, 4115 newborns have undergone primary and/or control-screening with the BERAphon(R). The validity of this method was further examined by testing the effects of non-pathological factors such as gender, age, Apgar score, pH value of the umbilical cord, head circumference and duration of pregnancy on the ABR wave V latency in 415 infants. Out of 3930 infants who were primary screened, 27 infants were diagnosed to have hearing loss. Furthermore, hearing loss was detected in 35 out of 185 infants referred for control screening. Non-pathological factors showed a minor effect on the test results. Apgar score, gender or chronological age did not have any significant effects on the latency of wave V. Duration of pregnancy, pH value of the umbilical cord or head circumference showed a significant but weak correlation with wave V latency. Only non-pathological factors related to maturation had a minor effect on ABR measurements using the time-course-step-stimulus algorithm. The BERAphon(R) method has proven to be a reliable, robust method giving information related to the hearing threshold and accordingly can be used reliably for hearing screening in newborn infants.


Retrograde percutaneous nephrostomy.
The percutaneous approach has become an accepted procedure for the removal of kidney stones in the urinary tract. Developed initially from our method of transvenous punch biopsy and transvenous cholangiography, the "inside-out" retrograde nephrostomy technique involves either cystoscopic or fluoroscopic placement of a 9 or 10 French catheter into a selected minor calix, through which a fine 21-gauge needle passes and exists the skin. The tract is then dilated over the needle. Used in over 200 cases without any complications directly attributable to the nephrostomy, the retrograde approach is safer, more reliable, and less time consuming than the previous standard antegrade approach, particularly in the nondilated pelvicalyceal system. Also presented are several new modifications to the original procedure and further technical considerations for operators.


Using surveillance data to determine treatment rates and outcomes for patients with chronic hepatitis C virus infection.
The aim of this work was to develop and validate an algorithm to monitor rates of, and response to, treatment of patients infected with hepatitis C virus (HCV) across England using routine laboratory HCV RNA testing data. HCV testing activity between January 2002 and December 2011 was extracted from the local laboratory information systems of a sentinel network of 23 laboratories across England. An algorithm based on frequency of HCV RNA testing within a defined time period was designed to identify treated patients. Validation of the algorithm was undertaken for one center by comparison with treatment data recorded in a clinical database managed by the Trent HCV Study Group. In total, 267,887 HCV RNA test results from 100,640 individuals were extracted. Of these, 78.9% (79,360) tested positive for viral RNA, indicating an active infection, 20.8% (16,538) of whom had a repeat pattern of HCV RNA testing suggestive of treatment monitoring. Annual numbers of individuals treated increased rapidly from 468 in 2002 to 3,295 in 2009, but decreased to 3,110 in 2010. Approximately two thirds (63.3%; 10,468) of those treated had results consistent with a sustained virological response, including 55.3% and 67.1% of those with a genotype 1 and non-1 virus, respectively. Validation against the Trent clinical database demonstrated that the algorithm was 95% sensitive and 93% specific in detecting treatment and 100% sensitive and 93% specific for detecting treatment outcome. Laboratory testing activity, collected through a sentinel surveillance program, has enabled the first country-wide analysis of treatment and response among HCV-infected individuals. Our approach provides a sensitive, robust, and sustainable method for monitoring service provision across England.


Comparison of wearable sensor to traditional methods in functional outcome measures: A systematic review.
Traditional methods of collecting functional outcome measures are widely used for lower extremity arthroplasty outcome assessment. Wearable sensors are emerging as viable tools for functional outcome measures in monitoring of postarthroplasty recovery. The objective of this review was to compare the efficacy of wearable sensors with traditional methods for monitoring postarthroplasty functional recovery. Articles were searched for inclusion in this review that used both traditional and wearable sensor functional outcome measures to assess lower extremity function before and after lower extremity arthroplasty. Two independent screeners reviewed all articles, and resolved differences through consensus and consultation with the senior author. Studies that met inclusion criteria were evaluated for methodologic quality using performed risk of bias assessments. Results from several traditional and wearable sensor functional outcome measures from baseline through follow-up were normalized across studies. Fourteen articles met the inclusion criteria. Six studies used statistical methods to directly compare functional outcome measures and eight studies used qualitative description of comparisons. This review found evidence that wearable sensors detected nuanced functional outcome information on the specific biomechanics and timing of recovery, which were unaccounted for using traditional methods. Wearable sensors have shown promising utility in providing additional recovery information from lower extremity arthroplasty compared with traditional functional outcome measures, but future research is needed to assess the clinical significance of this additional information. Wearable sensor technology is an emerging clinical tool providing advanced and determinative data with the potential for advancing the assessment of lower extremity arthroplasty outcomes.


Lipid profile of type 2 diabetic and hypertensive patients in the jamaican population.
Previous studies have shown that diabetes mellitus (DM) increases the risk of cardiovascular diseases in females to a greater extent than in males. In this cross-sectional study, we evaluated the lipid profiles of type 2 diabetic males and females. The study included 107 type 2 diabetic patients (41 males and 66 females), and 122 hypertensive type 2 diabetic patients (39 males and 83 females), aged 15 years and older. Total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) and high density lipoprotein-cholesterol (HDL-C) concentrations were assayed for each group using standard biochemical methods. The mean TC, TG, VLDL-C, HDL-C and LDL-C concentrations, TG/HDL and LDL/HDL ratios were higher in type 2 diabetic and hypertensive type 2 diabetic patients compared with non-diabetic, and hypertensive non-diabetic control subjects, although these were not significant (P > 0.05). Hypertensive type 2 diabetic females had significantly higher serum TC (7.42 ± 1.63 mmol/L) than hypertensive non-diabetic males (5.76±1.57 mmol/L; P < 0.05). All the other lipid and lipoprotein parameters except HDL-C were non-significantly higher in females with type 2 DM and those with hypertension and type 2 DM, compared with type 2 diabetic and hypertensive type 2 diabetic males, respectively (P > 0.05). This study demonstrated that dyslipidemia exists in our type 2 diabetic population with greater TC in hypertensive type 2 diabetic females compared with hypertensive type 2 diabetic males. This suggests that hypertensive type 2 diabetic females are exposed more profoundly to risk factors including atherogenic dyslipidemia compared with males.


Demonstration of a flagellar antigen shared by a diverse group of spiral-shaped bacteria that colonize intestinal mucus.
Western blot analysis showed that there is little immunological cross-reactivity of the human pathogens Campylobacter jejuni and Campylobacter coli with Campylobacter pyloridis, except for a very strong cross-reaction between the flagellins. This same antigenic cross-reaction was found with two isolates of gram-negative spiral microaerophilic bacteria that are known to colonize the intestinal mucosa of rodents, but not with the flagellins of a number of other motile bacteria. It is proposed that this shared flagellin antigen may be important structurally and functionally.


Monoclonal antibodies with defined recognition sequences in the stem region of CD44: detection of differential glycosylation of CD44 between tumor and stromal cells in tissue.
CD44 is an enigmatic cell adhesion molecule acting as a major receptor for hyaluronan and playing roles in many biological and pathological processes such as lymphocyte homing, T-cell activation, wound healing, angiogenesis, and metastatic spread of tumor cells. However, the complexity of the molecule, with its alternatively spliced variants, extensive glycosylation, and processing by different proteases, has hampered detailed analysis. In this study, we prepared four monoclonal antibodies (285-2F12, 284-43F1, 268-1F5, and 294-6F2) and one polyclonal antibody (C6) that recognize defined sequences in the stem region of CD44H. Interestingly, two of the monoclonal antibodies, 268-1F5 and 294-6F2, failed to recognize the CD44 expressed in five of the seven human tumor cell lines examined by Western blotting. Treatment of the samples with a combination of neuraminidase and O-glycosidase as well as the expression of mutants with site-directed mutations at possible modification sites rendered the CD44 reactive to the antibodies. Thus, the reactivity of the antibodies is sensitive to O-glycosylation presumably near the recognition sites. Glycosylation of CD44 that affects reactivity to the antibodies was found to be regulated differentially between tumor and stromal cells in two breast and three oral carcinoma tissues. Antibody 268-1F5 reacted to the tumor cells, but not to the cells in the surrounding stroma. On the other hand, the reactivity of 294-6F2 to the cells was opposite between the two tumor types. Thus, these sets of antibodies are useful to detect and analyze the as-yet-unknown roles of site-specific glycosylation of CD44, particularly in tumors.


Significant bronchodilator responsiveness and "reversibility" in a population sample.
Chronic Obstructive Pulmonary Disease (COPD) is defined by being "not fully reversible", most guidelines recommend measurement of lung function after the administration of a bronchodilator. The objective of this study was to compare bronchodilator responsiveness (significant improvement in the FEV(1) or FVC) to full-, partial- or "inverse'" reversibility in obstruction status in a population-based sample in Southeastern Kentucky. The study population was selected using random digit dialing of an adult population in Southeastern Kentucky as part of the Burden of Lung disease (BOLD) project. Lung function was assessed using spirometry pre- and post-bronchodilation. Subjects presence and severity of COPD was classified using modified Global Obstructive Lung Disease (GOLD) criteria. We examined the relation between changes in "obstruction" status (based on the FEV(1)/ FVC of 0.7) and the presence of "significant bronchodilator responsiveness" (based on ≥ 12% improvement in the FEV(1) or the FVC). The final population with acceptable pre- and post-bronchodilator spirometry included 440 participants. 32/440 subjects (7.3%) changed from obstructed to unobstructed (full-reversibility), 19/440 (4.3%) changed from unobstructed to obstructed ("inverse"-reversibility), 389/440 (88.4%) had either no-change or partial-reversibility, and 65/440 (14.8%) had bronchodilator responsiveness. Among those with full-reversibility, only 9/32 (28.1%) had bronchodilator responsiveness, whereas among subjects with "inverse"-reversibility, 10/19 (52.6%) had bronchodilator responsiveness. Among all subjects with bronchodilator responsiveness, only 19/65 (29.2%) changed categories. Our findings suggest that significant bronchodilator responsiveness is not the same as "reversibility" of "obstruction", even though these terms are often used interchangeably.


Comparing infertility-related stress, coping, and quality of life among assisted reproductive technology and non-assisted reproductive technology treatments.
Women who undergo assisted reproductive technology (ART) treatments experience infertility-related stress and have low quality of life (QOL). However, there is limited understanding of infertility-related stress, coping, or QOL among women who undergo non-ART treatments. The purpose of this study was to examine infertility-related stress, coping, and QOL among women who undergo ART and non-ART infertility treatments. Using a descriptive correlational cross-sectional design, we recruited 200 women who underwent infertility treatments. Participants completed the Copenhagen Multi-centre Psychosocial Infertility (COMPI) Fertility Problem Stress Scale, COMPI Coping Styles Scale, Fertility Quality of Life tool, and a demographic infertility survey. Data analysis included descriptive statistics, independent t-test, chi-square, and hierarchical multiple regression. Women who underwent non-ART had more personal stress, used more active-avoidance coping, and had lower emotional, social, and treatment environment QOL compared to those in ART treatment. Women who underwent ART treatments used more meaning-based coping but had lower treatment tolerability QOL. Stress and coping contribute to core QOL differently among infertility treatment groups. Both treatment groups report low satisfaction with emotional services. Regardless of the treatment type, women who undergo infertility treatments may need care to address their psychological health.


A colony assay for in vitro transformation by human T cell leukemia viruses type I and type II.
We report here the development of a rapid and quantitative method for measuring in vitro T cell transformation by human T cell leukemia viruses type I (HTLV-I) and type II (HTLV-II). This method is based on our finding that cocultivation of lethally irradiated HTLV-producing cells with peripheral blood lymphocytes (PBLs) preactivated for 24 hours with phytohemagglutinin and interleukin-2 (IL-2) induces colony formation in methylcellulose-containing medium. Colonies of about 200 cells can be clearly distinguished from background aggregates within four to six days after cocultivation. These colonies gradually increase in size and reach 300 to 1,000 cells within 14 days after cocultivation. Cells of these colonies were infected, as evidenced by expression of viral p19 antigen and the presence of HTLV proviral sequences. These cells proved to be transformed in terms of IL-2-independent continuous growth in liquid medium. Colony formation was found to depend in a linear fashion upon the percentage of the infected cells present in the irradiated cell population and is sufficiently sensitive to detect as few as 1% of virus-producing cells.


Hormonal regulation of oligopeptide transporter pept-1 in a human intestinal cell line.
The intestinal oligopeptide transporter (cloned as Pept-1) has major roles in protein nutrition and drug therapy. A key unstudied question is whether expression of Pept-1 is hormonally regulated. In this experiment, we investigated whether insulin has such a role. We used a human intestinal cell monolayer (Caco-2) as the in vitro model of human small intestine and glycylglutamine (Gly-Gln) as the model substrate for Pept-1. Results showed that addition of insulin at a physiological concentration (5 nM) to incubation medium greatly stimulates Gly-Gln uptake by Caco-2 cells. This stimulation was blocked when genistein, an inhibitor of tyrosine kinase, was added to incubation medium. Studies of the mechanism of insulin stimulation showed the following. 1) Stimulation occurred promptly (30-60 min) after exposure to insulin. 2) There was no significant change in the Michaelis-Menten constant of Gly-Gln transport, but there was a nearly twofold increase in its maximal velocity. 3) Insulin effect persisted even when Golgi apparatus, which is involved in trafficking of newly synthesized Pept-1, was dismantled. 4) However, there was complete elimination of insulin effect by disruption of microtubules involved in trafficking of preformed Pept-1. 5) Finally, with insulin treatment, there was no change in Pept-1 gene expression, but the amount of Pept-1 protein in the apical membrane was increased. In conclusion, the results show that insulin, when it binds to its receptor, stimulates Gly-Gln uptake by Caco-2 cells by increasing the membrane population of Pept-1. The mechanism appears to be increased translocation of this transporter from a preformed cytoplasmic pool.


A longitudinal analysis of risk factors for child maltreatment: findings of a 17-year prospective study of officially recorded and self-reported child abuse and neglect.
To identify demographic, family, parent, and child factors prospectively associated with risk for child abuse and neglect among families in the community, using data on child maltreatment obtained from both official records and youth self-reports. Surveys assessing demographic variables, family relationships, parental behavior, and characteristics of parents and children were administered to a representative sample of 644 families in upstate New York on four occasions between 1975 and 1992. Data on child abuse and neglect were obtained from New York State records and retrospective self-report instruments administered when youths were > or = 18 years old. Logistic regression analyses indicated that different patterns of risk factors predicted the occurrence of physical abuse, sexual abuse, and neglect, although maternal youth and maternal sociopathy predicted the occurrence of all three forms of child maltreatment. In addition, the prevalence of child abuse or neglect increased from 3% when no risk factors were present to 24% when > or = 4 risk factors were present. State records and self-reports of child maltreatment did not correspond in most cases when maltreatment was reported through at least one data source, underlining the importance of obtaining data from both official records and self-reports. Assessment of a number of risk factors may permit health professionals to identify parents and children who are at high risk for child maltreatment, facilitating appropriate implementation of prevention and treatment interventions.


Separating the Signal from the Noise: How Psychiatric Diagnoses Can Help Discern Food Addiction from Dietary Restraint.
Converging evidence from both animal and human studies have implicated hedonic eating as a driver of both binge eating and obesity. The construct of food addiction has been used to capture pathological eating across clinical and non-clinical populations. There is an ongoing debate regarding the value of a food addiction "diagnosis" among those with eating disorders such as anorexia nervosa binge/purge-type, bulimia nervosa, and binge eating disorder. Much of the food addiction research in eating disorder populations has failed to account for dietary restraint, which can increase addiction-like eating behaviors and may even lead to false positives. Some have argued that the concept of food addiction does more harm than good by encouraging restrictive approaches to eating. Others have shown that a better understanding of the food addiction model can reduce stigma associated with obesity. What is lacking in the literature is a description of a more comprehensive approach to the assessment of food addiction. This should include consideration of dietary restraint, and the presence of symptoms of other psychiatric disorders (substance use, posttraumatic stress, depressive, anxiety, attention deficit hyperactivity) to guide treatments including nutrition interventions. The purpose of this review is to help clinicians identify the symptoms of food addiction (true positives, or "the signal") from the more classic eating pathology (true negatives, or "restraint") that can potentially elevate food addiction scores (false positives, or "the noise"). Three clinical vignettes are presented, designed to aid with the assessment process, case conceptualization, and treatment strategies. The review summarizes logical steps that clinicians can take to contextualize elevated food addiction scores, even when the use of validated research instruments is not practical.


Horizontal transmission of group B streptococcus in a neonatal intensive care unit.
The incidence of early-onset group B streptococcal (GBS) sepsis in the neonatal population has decreased substantially since the introduction of maternal intrapartum antibiotic prophylaxis and routine prenatal screening. However, these strategies have not reduced the incidence of late-onset GBS infections. Additional research pertaining to the transmission of late-onset GBS infections is required to develop effective preventive methods. The present report describes probable horizontal transmission of late-onset GBS infection among three infants in a neonatal intensive care unit. GBS strain confirmation was based on the microbiological picture, antibiogram and pulsed-field gel electrophoresis. These cases highlight the morbidity associated with late-onset GBS disease and the importance of considering horizontal transmission as an etiological factor in GBS infection in the newborn period. Further studies assessing horizontal transmission in late-onset GBS disease may improve prevention and early intervention.


Biodegradation of aromatic compounds by Escherichia coli.
Although Escherichia coli has long been recognized as the best-understood living organism, little was known about its abilities to use aromatic compounds as sole carbon and energy sources. This review gives an extensive overview of the current knowledge of the catabolism of aromatic compounds by E. coli. After giving a general overview of the aromatic compounds that E. coli strains encounter and mineralize in the different habitats that they colonize, we provide an up-to-date status report on the genes and proteins involved in the catabolism of such compounds, namely, several aromatic acids (phenylacetic acid, 3- and 4-hydroxyphenylacetic acid, phenylpropionic acid, 3-hydroxyphenylpropionic acid, and 3-hydroxycinnamic acid) and amines (phenylethylamine, tyramine, and dopamine). Other enzymatic activities acting on aromatic compounds in E. coli are also reviewed and evaluated. The review also reflects the present impact of genomic research and how the analysis of the whole E. coli genome reveals novel aromatic catabolic functions. Moreover, evolutionary considerations derived from sequence comparisons between the aromatic catabolic clusters of E. coli and homologous clusters from an increasing number of bacteria are also discussed. The recent progress in the understanding of the fundamentals that govern the degradation of aromatic compounds in E. coli makes this bacterium a very useful model system to decipher biochemical, genetic, evolutionary, and ecological aspects of the catabolism of such compounds. In the last part of the review, we discuss strategies and concepts to metabolically engineer E. coli to suit specific needs for biodegradation and biotransformation of aromatics and we provide several examples based on selected studies. Finally, conclusions derived from this review may serve as a lead for future research and applications.


Prevalence of chronic bronchitis in a rural community of the Hill Region of Nepal.
A house to house survey of everyone aged 20 years and above living in a rural community in the Hill Region of Nepal, situated about 16 km outside Kathmandu city, was conducted to determine the prevalence of chronic bronchitis and cor pulmonale. Of the total eligible population, 2826 (95.5%) were interviewed. Chronic bronchitis was diagnosed according to the British Medical Research Council criteria, and emphysema and cor pulmonale according to the World Health Organisation expert committee criteria. The crude prevalence of chronic bronchitis was found to be 18.3%. The prevalence rate of chronic bronchitis was similar in men and women, whereas in most parts of the world much lower rates have been recorded in women. Study of a random sample of 85 individuals with chronic bronchitis showed that 57.4% had evidence of airways obstruction, whereas 15.8% of a representative sample (n = 111) of the surveyed population (excluding those with chronic bronchitis) showed evidence of airway obstruction. Of 516 subjects diagnosed as having chronic bronchitis, 382 were subsequently investigated in hospital, 134 having declined further investigation. The diagnosis was confirmed in most of the patients (93.2%) who were investigated. Other diseases played an insignificant part in the production of the observed high prevalence rates of chronic bronchitis. Of the 382 patients studied in hospital, 87 had emphysema and 42 had cor pulmonale, yielding overall prevalence rates for these two conditions of at least 3.1% and at least 1.5% respectively.


Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers.
Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on specific metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas or the lung result in pancreatic ductal adenocarinoma (PDAC) or non-small cell lung carcinoma (NSCLC), respectively, but despite the same initiating events, these tumors use branched-chain amino acids (BCAAs) differently. NSCLC tumors incorporate free BCAAs into tissue protein and use BCAAs as a nitrogen source, whereas PDAC tumors have decreased BCAA uptake. These differences are reflected in expression levels of BCAA catabolic enzymes in both mice and humans. Loss of Bcat1 and Bcat2, the enzymes responsible for BCAA use, impairs NSCLC tumor formation, but these enzymes are not required for PDAC tumor formation, arguing that tissue of origin is an important determinant of how cancers satisfy their metabolic requirements.


Risk factors for surgical site infection after intracranial electroencephalography monitoring for epilepsy in the pediatric population.
OBJECTIVE Intracranial electroencephalography (iEEG) monitoring is an important method of identifying the seizure focus in patients with medically refractory epilepsy. While previous studies have demonstrated low rates of surgical complications, reported rates of surgical site infection (SSI) are highly variable. To date, no studies have specifically evaluated the patient or operative risk factors contributing to SSI. The goals of this study were to examine the rate of SSI after iEEG monitoring for epilepsy workup in pediatric patients and to determine the variables that might contribute to the development of SSI. METHODS A retrospective analysis of hospital charts at the Hospital for Sick Children was performed for all patients who had undergone iEEG monitoring between 2000 and 2016. Univariate and multivariate analyses were performed to look for statistically significant variables in relation to SSI. RESULTS Among 199 patients eligible for analysis, 8 (4.0%) developed SSIs within a period ranging from 21 to 51 days postoperatively. Univariate analysis yielded 4 factors related to SSI: number of people present in the operating room on electrode insertion (p = 0.02), length of insertion surgery (p = 0.04), previous operation at the same surgical site (p = 0.04), and number of depth electrodes inserted (p = 0.01). Multivariate analysis revealed that both the number of people present during the implant operation (OR 0.08, 95% CI 0.01-0.70) and the number of depth electrodes inserted (OR 3.52, 95% CI 1.44-8.59) independently contributed to SSI. CONCLUSIONS This is the largest case series and the first comprehensive review of both patient and operative risk factors in the development of SSI from iEEG monitoring in a pediatric population. The authors' institution had a lower rate of infection than those in most other studies, which could be explained by their protocol of administering intravenous antibiotics perioperatively and post-implant removal antibiotics for 14 days. The authors found a correlation between SSI and the number of people present during the implant operation, as well as the number of depth electrodes; both may contribute to breaks in sterility.


Bone marrow transplantation for myelodysplastic and myeloproliferative syndromes.
Twenty patients (age range, 4 to 48 years; median age, 36 years) with de novo or drug-induced myelodysplastic syndromes or myeloproliferative disorders were treated with myeloablative immunosuppressive therapy followed by bone marrow transplantation (BMT). Four preparative regimens were used; three regimens consisted of combined total body irradiation (TBI) and chemotherapy and one of combination chemotherapy only. One patient received marrow from his identical twin brother, whereas the other 19 patients were grafted with marrow from histocompatible siblings. In 19 patients the abnormal clone was at least temporarily ablated, while in one patient the congenital myelodysplasia persisted. Eight patients are alive and well for +108 to +3,359 days post-transplantation. Nine patients died of transplant-related complications (six of interstitial pneumonia, two of gastrointestinal bleeding, and one of fungal sepsis) and three patients died with persisting or recurring disease. One patient with a late recurrence has undergone a second successful bone marrow transplant procedure. Outcome of BMT was not related to French-American-British (FAB) type, marrow fibrosis, cytogenetic abnormalities, or preparation regimen. Marrow transplantation as a means of providing long-term disease-free survival and possible cure should be considered in patients if a suitable donor is available.


Rapid and Sensitive Direct Detection and Identification of Poliovirus from Stool and Environmental Surveillance Samples by Use of Nanopore Sequencing.
Global poliovirus surveillance involves virus isolation from stool and environmental samples, intratypic differential (ITD) by PCR, and sequencing of the VP1 region to distinguish vaccine (Sabin), vaccine-derived, and wild-type polioviruses and to ensure an appropriate response. This cell culture algorithm takes 2 to 3 weeks on average between sample receipt and sequencing. Direct detection of viral RNA using PCR allows faster detection but has traditionally faced challenges related to poor sensitivity and difficulties in sequencing common samples containing poliovirus and enterovirus mixtures. We present a nested PCR and nanopore sequencing protocol that allows rapid (<3 days) and sensitive direct detection and sequencing of polioviruses in stool and environmental samples. We developed barcoded primers and a real-time analysis platform that generate accurate VP1 consensus sequences from multiplexed samples. The sensitivity and specificity of our protocol compared with those of cell culture were 90.9% (95% confidence interval, 75.7% to 98.1%) and 99.2% (95.5% to 100.0%) for wild-type 1 poliovirus, 92.5% (79.6% to 98.4%) and 98.7% (95.4% to 99.8%) for vaccine and vaccine-derived serotype 2 poliovirus, and 88.3% (81.2% to 93.5%) and 93.2% (88.6% to 96.3%) for Sabin 1 and 3 poliovirus alone or in mixtures when tested on 155 stool samples in Pakistan. Variant analysis of sequencing reads also allowed the identification of polioviruses and enteroviruses in artificial mixtures and was able to distinguish complex mixtures of polioviruses in environmental samples. The median identity of consensus nanopore sequences with Sanger or Illumina sequences from the same samples was >99.9%. This novel method shows promise as a faster and safer alternative to cell culture for the detection and real-time sequencing of polioviruses in stool and environmental samples.


[Non-traumatic spinal epidural hematomas (2 cases): contribution of the CT scanner].
Two cases of non-traumatic epidural hematoma are reported. The first case, a 76 year old woman receiving anticoagulant treatment, presented with paralysis of both lower limbs and right upper limb. Myelography and CT scan showed a widespread hematoma from C4 to T2. The second patient, a 63 year old hypertensive woman, developed flaccid paraparesis with urinary retention, myelography and CT scan showed an epidural hematoma extending from T12 to L2. In both cases, surgical evacuation was followed by a fair motor recovery. The 190 published cases of non-traumatic spinal epidural hematoma include 14 of precise etiology, 69 idiopathic and 107 associated with or 2 predisposing factors. Three mechanisms are proposed to explain the spontaneous cases: alteration of peridural veins; rupture of dural vascular clusters; minimal arterial injury. CT scan imaging shows a biconvex, hyperdense epidural image and is the investigation of choice for acute, hyperalgesic myelo-radicular compression syndromes.


The coupling of blue emitting carbon dots with Eu3+/Tb3+ co-doped luminescent glasses for utilization in white light emitting diodes.
Lanthanide-doped luminescent glasses have attracted tremendous attention in modern optoelectronic applications, especially for solid-state white light-emitting diodes (WLEDs). Eu3+/Tb3+ co-doped luminescent glasses are well-known to emit intense yellowish-orange light resulting from the energy transfer from green-emitting sensitizer Tb3+ ions to red-emitting activator Eu3+ ions. Obtaining highly efficient blue light from lanthanide ions remains a challenge due to their weak down-converted emission. In this work, we attempt to use the unique characteristics of blue-emitting carbon dots (BCDs), i.e., a broad emission spectrum, ease of synthesis, and high stability, to compensate for this blue light deficiency problem. Correspondingly, a new strategy is proposed by coupling BCDs with Eu3+/Tb3+ co-doped glasses for their potential utilization in WLEDs. Hence, Eu3+/Tb3+ co-doped glasses are prepared in different thicknesses, i.e., 0.8, 1, and 1.5 mm, via the conventional melt-quenching method and subsequently spin-coated with BCDs to achieve adjustable photoluminescence quantum yield (PLQY) values. Ultimately, a proof-of-concept WLED is prepared using a 0.8 mm thick BCD-coated Eu3+/Tb3+ co-doped luminescent glass exhibiting outstanding luminescence performance with a CRI value of 92, a CCT of 4683 K, color coordinates of (x = 0.3299, y = 0.3421), a satisfying PLQY value of 55.58%, and a corresponding LER value of 316 lm W-1 under the excitation of a 375 nm UV LED. BCD-coated Eu3+/Tb3+ co-doped luminescent glasses show excellent stability against photobleaching, temperature variations, and humidity. The findings of this work indicate that the coupling of BCDs with Eu3+/Tb3+ co-doped luminescent glasses holds great potential as a substitute for traditional solid-state lighting sources.


Laparoscopic transureteroureterostomy: a novel approach.
We describe the feasibility and short-term results of laparoscopic transureteroureterostomy in children. We performed transperitoneal laparoscopic transureteroureterostomy with a 4-trocar technique in 3 children with a mean age of 63 months (range 18 to 105). Diagnoses were unilateral ureteral obstruction after cross-trigonal reimplantation for vesicoureteral reflux (1 patient), unilateral refluxing megaureter (1) and ureteral injury after bladder diverticulectomy (1). Cystoscopy, retrograde pyelogram and stent placement in the recipient ureter were performed at the beginning of each case. The anastomoses were carried out with running 6-zero reabsorbable sutures at the level of the pelvic bream. An abdominal drain and Foley catheter were left indwelling for 1 to 3 days. All cases were performed successfully. Postoperative course was uneventful except for a transient urinary leak, and patients were discharged home on postoperative day 2 to 4. At a mean followup of 6 months all patients were clinically well, with normal kidney function and blood pressure, and no significant hydronephrosis. Based on our initial experience, laparoscopic transureteroureterostomy is safe and effective, and is associated with little blood loss, minimal analgesia requirements, fast recovery and excellent cosmetic results. We believe that in selected cases in which transureteroureterostomy is the chosen technique a laparoscopic approach is advantageous.


The effects of a 10% soybean oil emulsion on lymphocyte transformation.
Free essential fatty acids (EFA) are reported to suppress cell-mediated immunity. Because Intralipid contains a high concentration of esterified EFA, the effects of this emulsion on in vitro lymphocyte transformation were studied. Intralipid concentrations of 11.5, 115, and 230 mg% in lymphocyte cultures increased phytohemagglutinin (PHA) stimulation by an average of 8.2% (not significant [NS]), 18.1% (p < 0.01), and 11.8% (NS), respectively. These same concentrations also increased Varidase stimulation in lymphocyte cultures by an average of 11.3 (p < 0.02), 18.9 (p < 0.02), and 4.4% (NS), respectively. Control wells did not demonstrate allergic reactions to Intralipid. These data demonstrate that Intralipid can significantly increase the mitogenic response of human thymic lymphocytes and the antigenic response of human lymphocytes, in vitro.


The microRNA pathway controls germ cell proliferation and differentiation in C. elegans.
The discovery of the miRNA pathway revealed a new layer of molecular control of biological processes. To uncover new functions of this gene regulatory pathway, we undertook the characterization of the two miRNA-specific Argonaute proteins in Caenorhabditis elegans, ALG-1 and ALG-2. We first observed that the loss-of-function of alg-1 and alg-2 genes resulted in reduced progeny number. An extensive analysis of the germline of these mutants revealed a reduced mitotic region, indicating fewer proliferating germ cells. We also observed an early entry into meiosis in alg-1 and alg-2 mutant animals. We detected ALG-1 and ALG-2 protein expressions in the distal tip cell (DTC), a specialized cell located at the tip of both C. elegans gonadal arms that regulates mitosis-meiosis transition. Re-establishing the expression of alg-1 specifically in the DTC of mutant animals partially rescued the observed germline defects. Further analyses also support the implication of the miRNA pathway in gametogenesis. Interestingly, we observed that disruption of five miRNAs expressed in the DTC led to similar phenotypes. Finally, gene expression analysis of alg-1 mutant gonads suggests that the miRNA pathway is involved in the regulation of different pathways important for germline proliferation and differentiation. Collectively, our data indicate that the miRNA pathway plays a crucial role in the control of germ cell biogenesis in C. elegans.


Over-the-counter antifungal drug misuse associated with patient-diagnosed vulvovaginal candidiasis.
To estimate what proportion of symptomatic women purchasing over-the-counter antifungal products for immediate treatment of presumed vulvovaginal candidiasis have vulvovaginal candidiasis or other genitourinary conditions. A time-location sample of 95 symptomatic women who purchased and presented with an over-the-counter antifungal product for immediate and personal treatment of presumed vulvovaginal candidiasis were evaluated by clinical examination and pertinent laboratory tests. The percentage of women diagnosed having vulvovaginal candidiasis or other conditions, proportions of women with vulvovaginal candidiasis compared between groups with and without a prior diagnosis of vulvovaginal candidiasis, and groups that read or did not read the over-the-counter package label were assessed. The actual diagnoses for women who self-diagnosed vulvovaginal candidiasis were: vulvovaginal candidiasis 33.7%, bacterial vaginosis 18.9%, mixed vaginitis 21.1%, normal 13.7%, other diagnoses 10.5%, and trichomonas vaginitis 2.1%. Women with a previous clinically based diagnosis of vulvovaginal candidiasis were not more accurate in diagnosing vulvovaginal candidiasis than women without a prior clinical diagnosis (chi(2) = 0.27, P =.6). Women who read the package label were no more likely to have vulvovaginal candidiasis than were women who did not read the label (Fisher exact test, P =.39). Many women who self-diagnose and use an over-the-counter product for treatment of presumed vulvovaginal candidiasis do not have vulvovaginal candidiasis. A history of a previous clinically based diagnosis of vulvovaginal candidiasis and reading the package label do not help women self-diagnose vulvovaginal candidiasis properly. Ready access to these products is associated with wasted financial expenditures, unfulfilled expectations, and a delay in correct diagnosis for a substantial number of women.


Vital dye labelling of Xenopus laevis trunk neural crest reveals multipotency and novel pathways of migration.
Although the Xenopus embryo has served as an important model system for both molecular and cellular studies of vertebrate development, comparatively little is known about its neural crest. Here, we take advantage of the ease of manipulation and relative transparency of Xenopus laevis embryos to follow neural crest cell migration and differentiation in living embryos. We use two techniques to study the lineage and migratory patterns of frog neural crest cells: (1) injections of DiI or lysinated rhodamine dextran (LRD) into small populations of neural crest cells to follow movement and (2) injections of LRD into single cells to follow cell lineage. By using non-invasive approaches that allow observations in living embryos and control of the time and position of labelling, we have been able to expand upon the results of previous grafting experiments. Migration and differentiation of the labelled cells were observed over time in individual living embryos, and later in sections to determine precise position and morphology. Derivatives populated by the neural crest are the fins, pigment stripes, spinal ganglia, adrenal medulla, pronephric duct, enteric nuclei and the posterior portion of the dorsal aorta. In the rostral to mid-trunk levels, most neural crest cells migrate along two paths: a dorsal pathway into the fin, followed by presumptive fin cells, and a ventral pathway along the neural tube and notochord, followed by presumptive pigment, sensory ganglion, sympathetic ganglion and adrenal medullary cells. In the caudal trunk, two additional paths were noted. One group of cells moves circumferentially within the fin, in an arc from dorsal to ventral; another progresses ventrally to the anus and subsequently populates the ventral fin. By labelling individual precursor cells, we find that neural tube and neural crest cells often share a common precursor. The majority of clones contain labelled progeny cells in the dorsal fin. The remainder have progeny in multiple derivatives including spinal ganglion cells, pigment cells, enteric cells, fin cells and/or neural tube cells in all combinations, suggesting that many premigratory Xenopus neural crest precursors are multipotent.


Substrate specificity and ionic regulation of GlnPQ from Lactococcus lactis. An ATP-binding cassette transporter with four extracytoplasmic substrate-binding domains.
We report on the functional characterization of GlnPQ, an ATP-binding cassette transporter with four extracytoplasmic substrate-binding domains. The first predicted transmembrane helix of GlnP was cleaved off in the mature protein and most likely serves as the signal sequence for the extracytoplasmic substrate-binding domains. Deletion analysis showed that the substrate-binding domain, in the primary sequence of GlnP nearest to the translocator domain, is used as the receptor that delivers the substrate to the translocator. Membrane reconstitution of the detergent-solubilized and purified GlnPQ complex yielded proteoliposomes that transported glutamine and glutamic acid at the expense of ATP. The transport activity of GlnPQ increased with lumenal salt concentration and internal pH, but the mechanism of ionic activation of the transporter is distinct from that of other osmoregulatory ATP-binding cassette transporters and does not depend on the presence of anionic lipids. The regulation of GlnPQ conforms to an electrostatic switch in which protein domain(s) and low molecular weight electrolytes participate.


An Investigation of Secondary Traumatic Stress and Trauma-informed Care Utilization in School Personnel.
Trauma-informed practices in schools are designed to address the impacts of trauma on students and increase supports for school personnel who are delivering this care The impact of a trauma-informed school-based intervention. Journal of Adolescence, 43, 142-147, Mendelsonet al., 2015. Research has established that professionals trained to implement the approach may have secondary traumatic stress (STS) reactions that could interfere with successful implementation (Stevens al., 2020). In this study it was hypothesized that increased use of trauma-informed care strategies would be associated with decreases in total STS scores, as well as all STS subscale scores at the end of a system's transformation initiative, controlling for sex, age, education, years worked in schools, and exposure to student trauma awareness at baseline. The Trauma Sensitive Schools Checklist (TSSC) and the Secondary Traumatic Stress Scale (STSS) were used to measure study outcomes in a sample of 205 school personnel at baseline and follow up. Statistically significant improvement in STSS scores and TSSC score were noted from Time 1 to Time 2. As hypothesized, improvements in TSSC scores were associated with decreased levels of STS over time, controlling for the covariates. However, the symptom domains of intrusion and arousal impacted this relationship in a differential manner than avoidance and alterations in cognitions and mood. This study provides evidence that increased use of trauma-informed care practices can positively impact the STS levels of school personnel, though special attention should be paid to those with high levels of intrusion or arousal.


A new locus on 3p23-p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H.
Limb-girdle muscular dystrophies (LGMDs) are a genetically heterogeneous group of neuromuscular disorders with a selective or predominant involvement of shoulder and pelvic girdles. We clinically examined 19 members in a four-generation Italian family with autosomal-dominant LGMD. A total of 11 subjects were affected. Clinical findings showed variable expressivity in terms of age at onset and disease severity. Five subjects presented with a slowly progressive proximal muscle weakness, in both upper and lower limbs, with onset during the fourth-fifth decade of life, which fulfilled the consensus diagnostic criteria for LGMD. Earlier onset of the disease was observed in a group of patients presenting with muscle weakness and/or calf hypertrophy, and/or occasionally high CK and lactate serum levels. Two muscle biopsies showed morphological findings compatible with MD associated with subsarcolemmal accumulation of mitochondria and the presence of multiple mitochondrial DNA deletions. A genome-wide scan performed using microsatellite markers mapped the disease on chromosome 3p23-p25.1 locus in a 25-cM region between markers D3S1263 and D3S3685. The highest two-point LOD score was 3.26 (theta=0) at marker D3S1286 and D3S3613, whereas non-parametric analysis reached a P-value=0.0004. Four candidate genes within the refined region were analysed but did not reveal any mutations. Our findings further expand the clinical and genetic heterogeneity of LGMDs.


Urban Early Adolescent Narratives on Sexuality: Accidental and Intentional Influences of Family, Peers, and the Media.
In this paper, we examine the ways that early adolescents talked, interacted, and made references to events in their individual and collective lives during photography-based focus groups about sexuality and relationships. Twenty-three participants (10 boys and 13 girls) were recruited from three urban schools participating in a comprehensive sex education impact evaluation in the Northeast. We analyzed conversational narratives that were elicited in a group process while sharing photos of important people, contexts, and situations, showcasing participants' exploration of sexuality and relationships. Our analysis revealed four main themes: (a) direct and indirect family communication about sexuality, (b) accidental and intentional Internet usage, (c) shared and contested peer knowledge, and (d) school as a direct and indirect learning context. Implications and future directions for practice, research, and policy are explored.


Daily, seasonal, and long-distance movements inferred from Fastloc-GPS telemetry of immature green turtles (Chelonia mydas) at a high-latitude, mid-ocean developmental site.
To characterize the movements and habitat use of juvenile green turtles (Chelonia mydas) in benthic developmental habitat, we deployed Fastloc-GPS-enabled satellite transmitters on 16 individuals captured as part of a multi-decade study of green turtles on the Bermuda Platform. We characterized residence areas, distinct use areas within them, and seasonal movements based on an average of 562 Fastloc-GPS positions and 284 tracking days per turtle. We estimated residence area sizes using traditional home range methods, e.g., 90% utilization distribution (UD) (mean 2.29 ±2.71 km2) and 50% UD (mean 0.54 ±0.69 km2). Total residence area size increased significantly over the 8-year study, from <1 km2 before 2013 to ≥3 km2 in 2018 (R2 = 0.51, F1,14 = 14.55, p = 0.0019), corresponding to a period of decline in seagrass habitat and suggesting increased foraging effort. We identified three types of distinct use areas within residence areas where tracked turtles typically exhibited behavioral fidelity: foraging, resting, and cool weather refugia. These distinct use areas were smaller than high-use areas from previous studies; e.g., seagrass meadow foraging areas averaged 0.05 km2. Most turtles made daily transits between foraging and resting sites; for some individuals, these involved crossing frequently used vessel navigation channels. Seasonal variation in behavior suggested that the overwintering strategy for green turtles on the Bermuda Platform involves "optional dormancy," during which turtles spent less time on seagrass meadows and made brief excursions to distinct deeper habitats. Four individuals made directed (mean path straightness = 0.93 ±0.02 SD) developmental migrations away from Bermuda toward known adult foraging range. Results of our study further knowledge of the green turtle life cycle at a high-latitude site; they demonstrate that green turtles show fidelity to distinct use areas within developmental habitats over many years and exhibit seasonal movements.


[Modern perimetry: automatic or manual?].
The possible applications of computer assisted static perimetry are examined after one and a half year of personal experience. The general advantage of a computer-assisted perimeter may be the elimination of the influence of the perimetrist on the results. We have employed the PERITEST perimeter because this system allows either full automatic perimetry or two types of manual perimetry with presentation of single or multiple stimuli. All perimetric examination is done after the determination of the individual visual retinal threshold. The examination is always performed at a supraliminal level relative to the individual threshold. The following conclusions can be drawn: 1 - Even after complete elimination of the perimetrist's influence fluctuations in results may be observed. Furthermore, the longer examination the more important patient cooperation becomes in automated perimetry as compared to the manual procedure. So we concluded that the best strategy should be related to the studies of the visual field defects. 2 - For perimetry of presupposed normal visual fields, the multiple stimulus procedure is quite adequate. If some problem appears, the flexibility of the PERITEST enables the use of the single manual stimulus mode. The full automatic examination is done only when there are mild field defects and in intelligent patients. 3 - These techniques enable the description of a new presentation of the classical perimetry's signs of early glaucoma: a loss of 0,5 Log. U.L. (which has the same significance as an isolated relative scotoma.


Development and validation of a high-throughput cell-based screen to identify activators of a bacterial two-component signal transduction system.
CpxRA is a two-component signal transduction system (2CSTS) found in many drug-resistant Gram-negative bacteria. In response to periplasmic stress, CpxA autophosphorylates and donates a phosphoryl group to its cognate response regulator, CpxR. Phosphorylated CpxR (CpxR-P) upregulates genes involved in membrane repair and downregulates multiple genes that encode virulence factors, which are trafficked across the cell membrane. Mutants that constitutively activate CpxRA in Salmonella enterica serovar Typhimurium and Haemophilus ducreyi are avirulent in mice and humans, respectively. Thus, the activation of CpxRA has high potential as a novel antimicrobial/antivirulence strategy. Using a series of Escherichia coli strains containing a CpxR-P-responsive lacZ reporter and deletions in genes encoding CpxRA system components, we developed and validated a novel cell-based high-throughput screen (HTS) for CpxRA activators. A screen of 36,000 compounds yielded one hit compound that increased reporter activity in wild-type cells. This is the first report of a compound that activates, rather than inhibits, a 2CSTS. The activity profile of the compound against CpxRA pathway mutants in the presence of glucose suggested that the compound inhibits CpxA phosphatase activity. We confirmed that the compound induced the accumulation of CpxR-P in treated cells. Although the hit compound contained a nitro group, a derivative lacking this group retained activity in serum and had lower cytotoxicity than that of the initial hit. This HTS is amenable for the screening of larger libraries to find compounds that activate CpxRA by other mechanisms, and it could be adapted to find activators of other two-component systems.


Reliability and validity of the Performance Recorder 1 for measuring isometric knee flexor and extensor strength.
Muscular strength is a key parameter of rehabilitation programs and a strong predictor of functional capacity. Traditional methods to measure strength, such as manual muscle testing (MMT) and hand-held dynamometry (HHD), are limited by the strength and experience of the tester. The Performance Recorder 1 (PR1) is a strength assessment tool attached to resistance training equipment and may be a time- and cost-effective tool to measure strength in clinical practice that overcomes some limitations of MMT and HHD. However, reliability and validity of the PR1 have not been reported. Test-retest and inter-rater reliability was assessed using the PR1 in healthy adults (n = 15) during isometric knee flexion and extension. Criterion-related validity was assessed through comparison of values obtained from the PR1 and Biodex® isokinetic dynamometer. Test-retest reliability was excellent for peak knee flexion (intra-class correlation coefficient [ICC] of 0.96, 95% CI: 0.85, 0.99) and knee extension (ICC = 0.96, 95% CI: 0.87, 0.99). Inter-rater reliability was also excellent for peak knee flexion (ICC = 0.95, 95% CI: 0.85, 0.99) and peak knee extension (ICC = 0.97, 95% CI: 0.91, 0.99). Validity was moderate for peak knee flexion (ICC = 0.75, 95% CI: 0.38, 0.92) but poor for peak knee extension (ICC = 0.37, 95% CI: 0, 0.73). The PR1 provides a reliable measure of isometric knee flexor and extensor strength in healthy adults that could be used in the clinical setting, but absolute values may not be comparable to strength assessment by gold-standard measures.


Freestanding bipedal posture and coordinated bimanual manipulation significantly influence lateralized hand use in rhesus monkeys (Macaca mulatta) and chimpanzees (pan troglodytes).
Investigations of behavioral lateralization in nonhuman primates yield important insights into brain-behavior relationships. In turn, they provide clues about both proximal and distal factors that shape the development and expression of association between motor asymmetries and underlying neural substrates. Nonhuman primates afford unique comparative opportunities to evaluate potential routes for the evolution of handedness, as well as to uncover relationships between behavioral lateralization and underlying neural, genetic, and physiological correlates. We examined hand preference in 22 rhesus monkeys and 79 chimpanzees using unimanual reaching tasks varying in postural stability and in a coordinated bimanual task. The majority of rhesus monkeys and chimpanzees showed significant lateral biases when reaching from a freestanding posture and when engaged in a coordinated bimanual task. Population-level directional bias was not evident for any task for rhesus monkeys and was observed only in the bimanual task for chimpanzees. We did not find consistent relationships between an individual's hand preference for different types of tasks. Both freestanding bipedal posture and coordinated bimanual hand use elicited significantly stronger lateral biases in reaching when compared with quadrupedal reaching. These data support the hypothesis that both degrees of postural instability and complex manipulation, such as bimanual coordination, may influence the expression of behavioral asymmetries in primates. These results demonstrate robust lateralization occurs at the individual level. Our results also highlight the need for greater consideration of task type and descriptive data in studies aimed at evaluating brain-behavior relationships and individual differences associated with hand preference. (PsycINFO Database Record (c) 2019 APA, all rights reserved).