Teaching and assessing competency in retinal lasers in ophthalmology residency.
The Accreditation Council for Graduate Medical Education has mandated that residency programs teach and assess six specific competencies (ie, medical knowledge, patient care, communication and interpersonal skills, professionalism, practice-based learning, and systems-based learning). To the authors' knowledge, there is no standardized and widely used curriculum for teaching and assessing resident competencies in retinal lasers. The pertinent literature on resident education in retinal lasers is reviewed and specific "good practices" for teaching and assessing laser competency are presented. Development and deployment of educational tools that teach and assess laser competency simultaneously; are reliable, reproducible, and valid; have low faculty time burden; and are affordable, generalizable, and fair are recommended. Retinal laser competency can be taught and assessed in ophthalmology residency training programs. Future research will be needed to provide evidence that these teaching and assessment tools produce improved educational and patient outcomes and provide verifiable, reliable, and valid evidence of resident competence in retinal lasers.


Computerized occlusal analysis of Essix and Hawley retainers used during the retention phase: a controlled clinical trial.
The aim of this study was to evaluate the occlusal force distribution (OFD), individual tooth force (ITF), and occlusal surface area (OSA) of Essix and Hawley retainers, using T‑Scan III (Tekscan Inc., South Boston, MA, USA) analysis. A total of 35 subjects were randomly assigned to one of the retention groups following fixed orthodontic treatment. While 18 of these subjects were provided with Essix retainers, 17 were given Hawley retainers. Computerized occlusal analysis of the patients' dentitions was performed using T‑Scan III. The evaluations were made after debonding (T0) and at month 3 (T1), month 6 (T2) and 1 year (T3) after the retention phase. The changes in OFD were significant only in the Hawley group for the left/right half jaws and the right posterior quadrants when comparing the T2-T3 time interval. Also, the differences between the groups were significant only for the left half jaw for the T0-T2 time interval and for the right half jaw when comparing the T0-T2 and the T2-T3 time intervals. The changes in ITF were insignificant within groups, but significant between the groups for tooth 11 and 22. Although there was an increase observed in OSA for both groups, the difference between the groups was insignificant. However, the OSA increase in the Essix group for the left/right anterior quadrants was significant only for the T0-T2 and the T0-T3 time intervals, while in both groups, for the posterior left quadrant, the OSA was insignificant only for the T0-T1 time interval. Although OSA increased when using both retention appliances, OFD did not change.


[The relation of fluorescein angiography in low tension glaucoma with retinal nerve fiber layer defect and visual field damage].
The fluorescein angiography, visual field and retinal nerve fiber layer defects (RNFLD) in 23 patients (35 eyes) with low tension glaucoma (LTG) showed that there was a marked positional correspondency between the fluorescein filling defect of the optic disc and the RNFLD (91.4%) or the visual field defect (77.1%). Besides, the rate of positional correspondent between the RNFLD and visual field defect was 80.0%. The study indicated that RNFLD and visual field defect of LTG are related to ischemia of the optic disc.


Inactivation of mouse liver glutathione S-transferase YfYf (Pi class) by ethacrynic acid and 5,5'-dithiobis-(2-nitrobenzoic acid).
Mouse liver glutathione S-transferase YfYf (Pi class) reacts with [14C]ethacrynic acid to form a covalent adduct with a stoichiometry of 1 mol per mol of subunit. Proteolytic digestion of the enzyme-[14C]ethacrynic acid adduct with V8 protease produced an 11 kDa fragment containing radioactivity. Sequencing revealed this to be an N-terminal peptide (minus the first 15 residues, terminating at Glu-112) which contains only one cysteine residue (Cys-47). This is tentatively identified as the site of ethacrynic attachment. Kinetic studies reveal that glutathione S-conjugates protect against inactivation by ethacrynic acid, but the level of protection is not consistent with their potency as product inhibitors. A model is proposed in which glutathione S-conjugates and ethacrynic acid compete for the free enzyme, and a second molecule of ethacrynic acid reacts covalently with the enzyme-ethacrynic acid complex. The native protein contains one thiol reactive with 5,5'-dithiobis-(2-nitrobenzoic acid) at neutral pH. The resultant mixed disulphide, like the ethacrynic acid adduct, is inactive, but treatment with cyanide (which incorporates on a mol for mol basis) restores activity to 35% of that of the native enzyme.


Proton-Assisted Mechanism of NO Reduction on a Dinuclear Ruthenium Complex.
Density-functional-theory (DFT) calculations are performed for the proposal of a plausible mechanism on the reduction of NO to N2O by a dinuclear ruthenium complex, reported by Arikawa and co-workers [J. Am. Chem. Soc. 2007, 129, 14160]. On the basis of the experimental fact that the reduction proceeds under strongly acidic conditions, the role of protons in the mechanistic pathways is investigated with model complexes, where one or two NO ligands are protonated. The reaction mechanism of the NO reduction is partitioned into three steps: reorientation of N2O2 (cis-NO dimer), O-N bond cleavage, and N2O elimination. A key finding is that the protonation of the NO ligand(s) significantly reduces the activation barrier in the rate-determining reorientation step. The activation energy of 43.1 kcal/mol calculated for the proton-free model is reduced to 30.2 and 17.6 kcal/mol for the mono- and diprotonated models, respectively. The protonation induces the electron transfer from the Ru(II)Ru(II) core to the O═N-N═O moiety to give a Ru(III)Ru(III) core and a hyponitrite (O-N═N-O)(2-) species. The formation of the hyponitrite species provides an alternative pathway for the N2O2 reorientation, resulting in the lower activation energies in the presence of proton(s). The protonation also has a marginal effect on the O-N bond cleavage and the N2O elimination steps. Our calculations reveal a remarkable role of protons in the NO reduction via N2O formation and provide new insights into the mechanism of NO reduction catalyzed by metalloenzymes such as nitric oxide reductase (NOR) that contains a diiron active site.


Distribution and functional impact of DNA copy number variation in the rat.
The abundance and dynamics of copy number variants (CNVs) in mammalian genomes poses new challenges in the identification of their impact on natural and disease phenotypes. We used computational and experimental methods to catalog CNVs in rat and found that they share important functional characteristics with those in human. In addition, 113 one-to-one orthologous genes overlap CNVs in both human and rat, 80 of which are implicated in human disease. CNVs are nonrandomly distributed throughout the genome. Chromosome 18 is a cold spot for CNVs as well as evolutionary rearrangements and segmental duplications, suggesting stringent selective mechanisms underlying CNV genesis or maintenance. By exploiting gene expression data available for rat recombinant inbred lines, we established the functional relationship of CNVs underlying 22 expression quantitative trait loci. These characteristics make the rat an excellent model for studying phenotypic effects of structural variation in relation to human complex traits and disease.


Polar-localized NPH3-like proteins regulate polarity and endocytosis of PIN-FORMED auxin efflux carriers.
PIN-FORMED (PIN)-dependent auxin transport is essential for plant development and its modulation in response to the environment or endogenous signals. A NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3)-like protein, MACCHI-BOU 4 (MAB4), has been shown to control PIN1 localization during organ formation, but its contribution is limited. The Arabidopsis genome contains four genes, MAB4/ENP/NPY1-LIKE1 (MEL1), MEL2, MEL3 and MEL4, highly homologous to MAB4. Genetic analysis disclosed functional redundancy between MAB4 and MEL genes in regulation of not only organ formation but also of root gravitropism, revealing that NPH3 family proteins have a wider range of functions than previously suspected. Multiple mutants showed severe reduction in PIN abundance and PIN polar localization, leading to defective expression of an auxin responsive marker DR5rev::GFP. Pharmacological analyses and fluorescence recovery after photo-bleaching experiments showed that mel mutations increase PIN2 internalization from the plasma membrane, but affect neither intracellular PIN2 trafficking nor PIN2 lateral diffusion at the plasma membrane. Notably, all MAB4 subfamily proteins show polar localization at the cell periphery in plants. The MAB4 polarity was almost identical to PIN polarity. Our results suggest that the MAB4 subfamily proteins specifically retain PIN proteins in a polarized manner at the plasma membrane, thus controlling directional auxin transport and plant development.


Idiopathic adulthood ductopenia: case report and review of the literature.
The clinical and pathological findings of idiopathic ductopenia were studied in a 30-year-old woman who initially manifested jaundice and pruritus. Serum biochemical tests of liver function indicated severe and progressive cholestasis. Viral hepatitis markers and circulating autoantibodies were absent. The patient had a normal cholangiogram and lacked evidence of inflammatory bowel disease. Histological examination of a liver specimen showed severe cholestasis and absence of interlobular bile ducts. Severe jaundice and intractable pruritus developed in the patient and served as the indications for liver transplantation 4 months after initial examination. Transplantation resulted in prompt and complete resolution of the jaundice and pruritus. Two types of idiopathic adulthood ductopenia associated with different prognoses are recognized. Patients with type 1 idiopathic adulthood ductopenia are asymptomatic or manifest symptoms of cholestatic liver disease. They tend to have less destruction of the intrahepatic bile ducts on liver biopsy specimens. Their clinical course ranges from spontaneous improvement to progression to biliary cirrhosis. In contrast, patients with type 2 idiopathic adulthood ductopenia generally manifest initial symptoms of decompensated biliary cirrhosis, have extensive destruction of the intrahepatic bile ducts on liver biopsy, and frequently require orthotopic liver transplantation.


"WhatsApp"ening in orthopedic care: a concise report from a 300-bedded tertiary care teaching center.
Smartphones have emerged as essential tools providing assistance in patient care, monitoring, rehabilitation, communication, diagnosis, teaching, research and reference. Among innumerable communication apps, WhatsApp has been widely popular and cost effective. The aim of our study was to report the impact of introduction of a smartphone app "WhatsApp" as an intradepartmental communication tool on (1) awareness of patient-related information, (2) efficiency of the handover process and (3) duration of traditional morning handovers among orthopedic residents in a 300-bedded tertiary care teaching center. Written handovers and paging used for communication at our center led to occasional inefficiencies among residents. Widespread use, low cost, availability and double password protection (phone lock and WhatsApp lock) made WhatsApp's group conversation feature an ideal tool for intradepartmental patient-related communication. Twenty-five consecutive admissions before and after WhatsApp (BW, AW) were included in the study. Eight orthopedic residents attempted fifty randomly arranged questions based on the twenty-five patients in each study period. A null hypothesis that introduction of WhatsApp group would neither increase the awareness of patient-related information nor improve the efficiency of the handovers among residents was assumed. A significant improvement observed in scores obtained by residents in the AW group led to rejection of the null hypothesis. The residents also reported swifter and efficient handovers after the introduction of WhatsApp. Our results indicate that the introduction of a smartphone app "WhatsApp" as an intradepartmental communication tool can bring about an improvement in patient-related awareness, communication and handovers among orthopedic residents.


Common ground: shared risk factors for type 1 diabetes and celiac disease.
Risk factors for most autoimmune diseases are multifactorial genetic variants modified by environmental risk factors. Type 1 diabetes and celiac disease share high-risk HLA haplotypes, and the prevalence of both diseases has increased in many regions during the past half century. Unknown environmental factors are suspected to have increased the disease penetrance. Celiac disease depends on immune responses to dietary gluten, whereas the environmental risk factors for type 1 diabetes are not yet clear. Here, we consider the shared heritable genetic factors and review evidence of the dietary and microbial exposures, particularly in early life, that might influence the pathogenesis of one or both diseases. A deeper mechanistic understanding of the environmental factors responsible for increased risk of these diseases should provide opportunities to manipulate exposure in children carrying defined risk markers and thus prevent and attenuate disease, as well as to identify new therapeutic strategies for patients.


Sex differences in sexuality among medical students: effects of increasing socioeconomic status.
Research has consistently shown that, compared to men, women are more cautious and selective and maintain greater marital aspirations in entering and maintaining sexual relationships. One explanation of this sex difference is that women have traditionally had inferior access to earning power and social status and consequently were forced to acquire socioeconomic status (SES) through their choice of marriage partners. A contrasting view is that this difference is a component of the basic sex difference identified in the Kinsey studies: Men are more likely than women to dissociate coitus from emotional attachment and to desire and seek coitus with a variety of partners. These two explanations were explored in open-ended interviews with matched samples of 20 male and 20 female medical students. The results were more consistent with the perspective of basic sex differences than with the differential resources explanation. Increasing female SES does not appear to eliminate or even substantially reduce this sex difference. Increasing SES tends to enlarge the pool of acceptable, available sexual and marital partners for men while it tends to reduce the pool for women. Increasing SES thus tends to have different effects on men and women and may cause sex differences in the tendency to associate coitus with emotional attachments and marital aspirations to be more, rather than less, apparent. Extensive case data with verbatim quotations are presented to reveal the emotions and desires underlying subjects' overt behavior.


Molecular characterisation of Escherichia coli from dead broiler chickens with signs of colibacillosis and ready-to-market chicken meat in the West Bank.
1. The aim of this work was to compare a group of virulence-associated characteristics of Escherichia coli isolates from broiler chickens that had died with signs of colibacillosis against E. coli isolates from ready-to-market chicken meat in the West Bank. 2. The isolates were investigated to determine the virulence factor (VF) profile, phylogenetic group and the presence of extended-spectrum beta-lactamase (ESBL). A total of 66 avian pathogenic E. coli (APEC) strains from different affected broiler farms and 21 E. coli isolates from ready-to-market chicken carcasses (hereinafter called meat strains) from 8 slaughter houses were analysed. 3. The overall content of VFs was significantly higher (P < 0.05) among APEC strains, with over 75% of APEC strains having ≥4 VFs, while over 75% of the meat strains had <4 VFs. The VFs iss, astA and iucD were frequently detected in APEC and meat strains, whereas cvi, papC, vat, tsh and irp2 occurred more significantly in APEC strains. Phylogenetic typing showed that 67% of the meat strains belonged to group B2. Phylogroup D was predominant (50%) in the APEC strains. Using double disc diffusion and polymerase chain reaction (PCR), 10.6% of the APEC and 9.5% of the meat strains were determined to be ESBL positive. 4. Our findings show that the VFs papC, vat, irp2 and to a lesser extent tsh and cvi are significantly more prevalent in APEC strains. The results demonstrate that chicken meat can be contaminated with APEC strains (≥4 VF). A significant percentage of the meat strains fall in the B2 group, which is a phylogroup largely associated with human pathogenic ExPEC strains. The results of ESBL screening indicated that broiler chicken products in Palestine represent a potential reservoir of ESBL genes and therefore could be considered a possible public health risk.


Effects of D-amphetamine on temporal discrimination in pigeons.
Two experiments used a matching to sample of durations procedure to examine changes in temporal discrimination evoked by D-amphetamine (0.75, 1.50, 2.25 and 3.0 mg/kg i.m.) in pigeons. Responses to one key color were reinforced after long (8-s) stimuli: responses to the alternative key color were reinforced after short (2-s) stimuli. Stimuli of intermediate duration were reinforced in Experiment 1 and were not reinforced in Experiment 2. Sigmoid functions relating percent of choices of the key reinforced after long-duration stimuli to the duration of stimulus presented were fit by a cumulative normal function. In addition to a parameter giving the left/right position of the sigmoid curves (which indexes temporal perception), this function also provided estimates of the range and slope of the curve (measures of stimulus control). The results showed that, contrary to many published reports, amphetamine had no effect on the left/right positioning of the sigmoid curve. There was, however, an effect of amphetamine on stimulus control, as shown by the general flattening of the psychophysical functions. Little evidence of tolerance to the drug's behavioral effects was found after 30 consecutive days of behavioral testing under amphetamine.


The effect of background music on the taste of wine.
Research concerning cross-modal influences on perception has neglected auditory influences on perceptions of non-auditory objects, although a small number of studies indicate that auditory stimuli can influence perceptions of the freshness of foodstuffs. Consistent with this, the results reported here indicate that independent groups' ratings of the taste of the wine reflected the emotional connotations of the background music played while they drank it. These results indicate that the symbolic function of auditory stimuli (in this case music) may influence perception in other modalities (in this case gustation); and are discussed in terms of possible future research that might investigate those aspects of music that induce such effects in a particular manner, and how such effects might be influenced by participants' pre-existing knowledge and expertise with regard to the target object in question.


Adapting and Developing an Academic and Community Practice Collaborative Care Model for Metastatic Breast Cancer Care (Project ADAPT): Protocol for an Implementation Science-Based Study.
Metastatic breast cancer (MBC) remains incurable despite significant treatment advances. Coordinating care for patients with MBC can be challenging given the various treatment options, available clinical trials, and frequent need for ancillary services. To optimize MBC care, we designed a project for adapting and developing an academic and community practice collaborative care model for MBC care (Project ADAPT), based on the Ending Metastatic Breast Cancer for Everyone (EMBRACE) program developed at Dana Farber Cancer Institute. We aim to describe the implementation science-based study design and innovative components of Project ADAPT. Project ADAPT uses the Dynamic Adaptation Process informed by the Exploration, Preparation, Implementation, Sustainment framework. Washington University School of Medicine (WUSM) partnered with 3 community hospitals in the St. Louis region covering rural and urban settings. The exploration and preparation phases provide patient and provider feedback on current referral practices to finalize the approach for the implementation phase. At the implementation phase, we will enroll patients with MBC at these 3 community sites to evaluate potential collaborative care at WUSM and assess the impact of this collaborative care model on referral satisfaction and acceptability for patients with MBC and their providers. Patients may then return to their community site for care or continue to receive part of their care at WUSM. We are incorporating virtual and digital health strategies to improve MBC care coordination in order to minimize patient burden. The exploration phase is ongoing. As of August 2021, we have recruited 21 patient and provider participants to complete surveys of the current collaborative care process at WUSM. Using a 2-tailed paired t test, 44 patients (including 10 patients from the exploration phase) and 32 oncologists are required to detect an effect size of 0.5 with 80% power at a level of significance of .05. Throughout this phase and in preparation for the implementation phase, we have iteratively updated and refined our surveys for the implementation phase based on testing of our data collection instruments. Our partner sites are in various stages of the single institutional review board (IRB) approval process. We have ongoing engagement with all partner sites, which has helped solidify our participant recruitment strategies and design patient-friendly recruitment materials. In addition, we have included a patient advocate on the research team. Members of the research team have launched a single IRB Support Network at WUSM to create a repository of the single IRB procedures in order to streamline the partner site onboarding process and facilitate enhanced collaboration across institutions. With this robust model, we expect that patients with MBC will receive optimal care regardless of geographical location and the model will improve patient and provider experiences when navigating the health system. DERR1-10.2196/35736.


Implementation of a PCR-based strategy to control an outbreak by Serratia marcescens in a Neonatal Intensive Care Unit.
To evaluate the clinical and epidemiological impact of a new molecular surveillance strategy based on qPCR to control an outbreak by Serratia marcescens in a Neonatal Intensive Care Unit (NICU). We design a specific qPCR for the detection of S. marcescens in rectal swabs of patients admitted to a NICU. We divided the surveillance study into two periods: (a) the pre-PCR, from the outbreak declaration to the qPCR introduction, and (b) the PCR period, from the introduction of the qPCR until the outbreak was solved. In all cases, S. marcescens isolates were recovered and their clonal relationship was analysed by PFGE. Control measures were implemented during the outbreak. Finally, the number of bloodstream infections (BSI) was investigated in order to evaluate the clinical impact of this molecular strategy. Nineteen patients colonized/infected by S. marcescens were detected in the pre-PCR period (October 2020-April 2021). On the contrary, after the PCR implementation, 16 new patients were detected. The PFGE revealed 24 different pulsotypes belonging to 7 different clonal groups, that were not overlapping at the same time. Regarding the clinical impact, 18 months after the qPCR implementation, no more outbreaks by S. marcescens have been declared in the NICU of our hospital, and only 1 episode of BSI has occurred, compared with 11 BSI episodes declared previously to the outbreak control. The implementation of this qPCR strategy has proved to be a useful tool to control the nosocomial spread of S. marcescens in the NICU.


Reverse engineering of fatty acid-tolerant Escherichia coli identifies design strategies for robust microbial cell factories.
Adaptive laboratory evolution is often used to improve the performance of microbial cell factories. Reverse engineering of evolved strains enables learning and subsequent incorporation of novel design strategies via the design-build-test-learn cycle. Here, we reverse engineer a strain of Escherichia coli previously evolved for increased tolerance of octanoic acid (C8), an attractive biorenewable chemical, resulting in increased C8 production, increased butanol tolerance, and altered membrane properties. Here, evolution was determined to have occurred first through the restoration of WaaG activity, involved in the production of lipopolysaccharides, then an amino acid change in RpoC, a subunit of RNA polymerase, and finally mutation of the BasS-BasR two component system. All three mutations were required in order to reproduce the increased growth rate in the presence of 20 mM C8 and increased cell surface hydrophobicity; the WaaG and RpoC mutations both contributed to increased C8 titers, with the RpoC mutation appearing to be the major driver of this effect. Each of these mutations contributed to changes in the cell membrane. Increased membrane integrity and rigidity and decreased abundance of extracellular polymeric substances can be attributed to the restoration of WaaG. The increase in average lipid tail length can be attributed to the RpoCH419P mutation, which also confers tolerance to other industrially-relevant inhibitors, such as furfural, vanillin and n-butanol. The RpoCH419P mutation may impact binding or function of the stringent response alarmone ppGpp to RpoC site 1. Each of these mutations provides novel strategies for engineering microbial robustness, particularly at the level of the microbial cell membrane.


Automatic Image-Based Plant Disease Severity Estimation Using Deep Learning.
Automatic and accurate estimation of disease severity is essential for food security, disease management, and yield loss prediction. Deep learning, the latest breakthrough in computer vision, is promising for fine-grained disease severity classification, as the method avoids the labor-intensive feature engineering and threshold-based segmentation. Using the apple black rot images in the PlantVillage dataset, which are further annotated by botanists with four severity stages as ground truth, a series of deep convolutional neural networks are trained to diagnose the severity of the disease. The performances of shallow networks trained from scratch and deep models fine-tuned by transfer learning are evaluated systemically in this paper. The best model is the deep VGG16 model trained with transfer learning, which yields an overall accuracy of 90.4% on the hold-out test set. The proposed deep learning model may have great potential in disease control for modern agriculture.


Continuous regional arterial infusion and laparotomic decompression for severe acute pancreatitis with abdominal compartment syndrome.
To evaluate the therapeutic effects of abdominal decompression plus continuous regional arterial infusion (CRAI) via a drug delivery system (DDS) in severe acute pancreatitis (SAP) patients with abdominal compartment syndrome (ACS). We presented our recent experience in 8 patients with SAP. The patients developed clinical ACS, which required abdominal decompression. During the operation, a DDS was inserted into the peripancreatic artery (the catheter was inserted from the right gastroepiploic artery until it reached the junction between the pancreaticoduodenal and gastroduodenal artery). Through this DDS, a protease inhibitor, antibiotics and octreotide were infused continuously. The duration of the regional artery infusion ranged from 8 to 41 d. The outcomes and the changes in the APACHE II score, computed tomography (CT) severity index and intra-abdominal pressure (IAP) of the patients were retrospectively evaluated. Eight patients with an initial APACHE IIscore of 18.9 (range, 13-27) and a Balthazar CT severity index of 9.1 (range, 7-10) developed severe local and systemic complications. These patients underwent subsequent surgical decompression and CRAI therapy because of intra-abdominal hypertension (IAH). After a mean interval of 131.9 ± 72.3 d hospitalization, 7 patients recovered with decreased APACHE II scores, CT severity indexes and IAP. The mean APACHE II score was 5.4 (range, 4-8), the CT severity index was 2.3 (range, 1-3), and IAP decreased to 7.7 mmHg (range, 6-11 mmHg) 60 d after operation. One patient died of multiple organ failure 1 wk after surgery. CRAI and laparotomic decompression might be a therapeutic option for SAP patients with ACS.


Bulk H analysis using neutrons for routine quality control of cassava and products.
Nuclear and related techniques are useful in addressing the issues of food security and safety facing the world today, via quality control of raw materials and products. In this work, experimental investigations were performed to assess the use of total hydrogen content in cassava and products as a quality control indicator of starch and cyanide contents. The work was carried out using a neutron reflection facility at the Centre for Energy Research and Training, Ahmadu Bello University, Zaria, Nigeria. Cassava samples and products were obtained from retail outlets of Ibadan, Umudike and Zaria, representing three major regions of Nigeria. In general, data obtained indicate a total hydrogen content range of 4.47±0.11-10.71±0.27wt% for the various samples, including raw, dry and processed cassava. Results show that samples having low hydrogen content are generally rich in cyanide compounds and demonstrate an inverse relationship between hydrogen content and cyanide content. The implication of this is that the neutron reflection facility can be used as a quality control setup for routine determination of hydrogen as an indicator of the cyanide content in cassava and products.


Mitochondrial DNA indicates late pleistocene divergence of populations of Heteronympha merope, an emerging model in environmental change biology.
Knowledge of historical changes in species range distribution provides context for investigating adaptive potential and dispersal ability. This is valuable for predicting the potential impact of environmental change on species of interest. Butterflies are one of the most important taxa for studying such impacts, and Heteronympha merope has the potential to provide a particularly valuable model, in part due to the existence of historical data on morphological traits and glycolytic enzyme variation. This study investigates the population genetic structure and phylogeography of H. merope, comparing the relative resolution achieved through partial DNA sequences of two mitochondrial loci, COI and ND5. These data are used to define the relationship between subspecies, showing that the subspecies are reciprocally monophyletic. On this basis, the Western Australian subspecies H. m. duboulayi is genetically distinct from the two eastern subspecies. Throughout the eastern part of the range, levels of migration and the timing of key population splits of potential relevance to climatic adaptation are estimated and indicate Late Pleistocene divergence both of the Tasmanian subspecies and of an isolated northern population from the eastern mainland subspecies H. m. merope. This information is then used to revisit historical data and provides support for the importance of clinal variation in wing characters, as well as evidence for selective pressure acting on allozyme loci phosphoglucose isomerase and phosphoglucomutase in H. merope. The study has thus confirmed the value of H. merope as a model organism for measuring responses to environmental change, offering the opportunity to focus on isolated populations, as well as a latitudinal gradient, and to use historical changes to test the accuracy of predictions for the future.


Diazonium Salt-Based Surface-Enhanced Raman Spectroscopy Nanosensor: Detection and Quantitation of Aromatic Hydrocarbons in Water Samples.
Here, we present a surface-enhanced Raman spectroscopy (SERS) nanosensor for environmental pollutants detection. This study was conducted on three polycyclic aromatic hydrocarbons (PAHs): benzo[a]pyrene (BaP), fluoranthene (FL), and naphthalene (NAP). SERS substrates were chemically functionalized using 4-dodecyl benzenediazonium-tetrafluoroborate and SERS analyses were conducted to detect the pollutants alone and in mixtures. Compounds were first measured in water-methanol (9:1 volume ratio) samples. Investigation on solutions containing concentrations ranging from 10-6 g L-1 to 10-3 g L-1 provided data to plot calibration curves and to determine the performance of the sensor. The calculated limit of detection (LOD) was 0.026 mg L-1 (10-7 mol L-1) for BaP, 0.064 mg L-1 (3.2 × 10-7 mol L-1) for FL, and 3.94 mg L-1 (3.1 × 10-5 mol L-1) for NAP, respectively. The correlation between the calculated LOD values and the octanol-water partition coefficient (Kow) of the investigated PAHs suggests that the developed nanosensor is particularly suitable for detecting highly non-polar PAH compounds. Measurements conducted on a mixture of the three analytes (i) demonstrated the ability of the developed technology to detect and identify the three analytes in the mixture; (ii) provided the exact quantitation of pollutants in a mixture. Moreover, we optimized the surface regeneration step for the nanosensor.


[Some proteins of acute phase of inflammation in differential diagnostics of rheumatoid arthritis].
Levels of lactoferrin (LF), antithrombin-III (AT-III) and beta2-macroglobulin (MG) in blood of patients with rheumatoid arthritis (RA), reactive arthritis (ReA) and systemic lupus erythematosus (SLE) were examined for assessment their importance in differential diagnostics of the diseases. It was shown that on the average, LF and AT-III levels were increased at RA, while MG level was practically unchanged. At the same time LF level was stable high regardless of RA activity and duration degree, but its concentration was significantly increased also in ReA patients (33% patients). AT-III, on the contrary, depended on process activity and duration, was more specific to RA, than LF, but its sensitivity at RA was not enough high (from 25 to 44% patients with increased levels subject to disease duration and activity). Coefficient LFE/AT-III, obtained by multiplication of these proteins concentration, had the greatest diagnostic value. Its sensitivity at RA is on the average 85%, and specificity at differential diagnostics of RA--80% vs. ReA and 92% vs. SLE. We consider that coefficient LFbetaAT-III can be used as an additional criterion at differential diagnostics at RA early stages, while other specific antibodies cannot be detected yet.


Relationship of heart rate, perceived exertion, and intra-abdominal pressure in women.
Exercise increases intra-abdominal pressure (IAP) acutely, which may impact the pelvic floor of women. IAP during exercise demonstrates high variability among women but is not routinely assessed. Assessing less invasive measures related to IAP during exercise may facilitate study of how IAP impacts the pelvic floor. The objective of this study was to investigate the relationship of heart rate and rating of perceived exertion (RPE) with IAP during a standard treadmill test. We describe the trend of IAP by predicted aerobic fitness during incremental exercise. IAP was measured using a validated transducer placed in the upper vagina. Heart rate and RPE were collected during the first 3 stages of the standard Bruce treadmill protocol. Relationships of heart rate and RPE with IAP were determined by Pearson correlation coefficients. Predicted aerobic fitness values for each participant were ranked in tertiles with IAP by treadmill stage. Twenty-four women participated in this study (mean age: 24.7 (5.4) years; body mass index: 22.5 (2.2) kg/m2). There were significant relationships between heart rate and IAP (r= 0.67, p < 0.001) and RPE and IAP (r= 0.60, p < 0.001) across treadmill stages. Tertiles of predicted aerobic fitness and IAP displayed similar trends as other exercise measures during incremental exercise, such as, heart rate and ventilation. Heart rate and RPE could be used as proxy measures of IAP during incremental exercise. Aerobic fitness may help explain IAP variability in women and provide context for future research on IAP and pelvic floor health.


Dominance of highly divergent feline leukemia virus A progeny variants in a cat with recurrent viremia and fatal lymphoma.
In a cat that had ostensibly recovered from feline leukemia virus (FeLV) infection, we observed the reappearance of the virus and the development of fatal lymphoma 8.5 years after the initial experimental exposure to FeLV-A/Glasgow-1. The goals of the present study were to investigate this FeLV reoccurrence and molecularly characterize the progeny viruses. The FeLV reoccurrence was detected by the presence of FeLV antigen and RNA in the blood and saliva. The cat was feline immunodeficiency virus positive and showed CD4+ T-cell depletion, severe leukopenia, anemia and a multicentric monoclonal B-cell lymphoma. FeLV-A, but not -B or -C, was detectable. Sequencing of the envelope gene revealed three FeLV variants that were highly divergent from the virus that was originally inoculated (89-91% identity to FeLV-A/Glasgow-1). In the long terminal repeat 31 point mutations, some previously described in cats with lymphomas, were detected. The FeLV variant tissue provirus and viral RNA loads were significantly higher than the FeLV-A/Glasgow-1 loads. Moreover, the variant loads were significantly higher in lymphoma positive compared to lymphoma negative tissues. An increase in the variant provirus blood load was observed at the time of FeLV reoccurrence. Our results demonstrate that ostensibly recovered FeLV provirus-positive cats may act as a source of infection following FeLV reactivation. The virus variants that had largely replaced the inoculation strain had unusually heavily mutated envelopes. The mutations may have led to increased viral fitness and/or changed the mutagenic characteristics of the virus.


A narrative review of supportive and end of life care considerations in advanced hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths, and case numbers continue to rise in the United States. HCC carries a poor prognosis, and management requires a multidisciplinary approach. This narrative review aims to identify opportunities for further integration of palliative care (PC) in HCC care. Given the high symptom burden faced by patients with HCC, early PC consultation can be beneficial for patients. A search of PubMed was conducted from inception of the database to March 1, 2023. The search was composed of keywords and controlled vocabulary terms for concepts related to palliative medicine and symptom management in the setting of HCC. This narrative review finds that although PC has been integrated into HCC guidelines, partnerships between PC and hepatology are still nascent in clinical practice. Treatment-related barriers pose a challenge to timely integration of PC in the care of HCC patients; evaluation or listing for transplantation can be perceived as a barrier to PC consultation, and unpredictable clinical courses make prognostication challenging. Providers may hesitate to pursue PC referral due to a lack of consensus around the role of PC, and for those that are referred, timing of consultation remains an issue, especially for those who are potential liver transplant candidates. There are few studies of PC in HCC, limiting evidence-based recommendations that can be made regarding PC involvement in this patient population. While PC is not routinely integrated into HCC care, recent guideline recommendations and a growing number of studies may change this over time. Although further evidence is needed, PC and hepatology teams partnering together can explore ways to improve the care of this patient population. PC consultation early in HCC care could assist in management of symptom relief, psychosocial and spiritual support, and caregiver support. Effective communication will be required to set parameters for referral and clarify potential outcomes of consultation. Teams should be prepared for the challenges involved in a culture change and paradigm shift in clinical practice.


Neuroendocrine regulatory peptide-1 and -2: novel bioactive peptides processed from VGF.
Neuroendocrine regulatory peptides (NERP)-1 and NERP-2 are derived from distinct regions of VGF, a neurosecretory protein that was originally identified as a product of a nerve growth factor-responsive gene in rat PC12 cells. The amino acid length of human NERP-1 is 26, and that of rat NERP-1 is 25. Human and rat NERP-2 are both 38 amino acid peptides. NERPs colocalize with vasopressin in the storage granules of the paraventricular and supraoptic nuclei in the hypothalamus of both rats and humans. Administration of NERPs suppresses hypertonic saline- or angiotensin II-induced vasopressin release from the hypothalamus and pituitary. Thus, VGF is a precursor of multiple bioactive peptides with diverse neuroendocrine functions, and NERPs are novel hypothalamic peptides involved in the control of body fluid homeostasis by regulating vasopressin release.


Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y.
Vitamin D may improve muscle strength through a highly specific nuclear receptor in muscle tissue. We investigated whether there is an association between 25-hydroxyvitamin D [25(OH)D] concentrations and lower-extremity function in ambulatory older persons, whether that association differs by activity level, and, if so, whether there is an identifiable threshold in the association. The study was a population-based survey of the ambulatory US population aged 60 to > or =90 y (n = 4100). Lower-extremity function according to serum 25(OH)D concentrations was assessed by linear regression analyses and regression plots after control for activity level (inactive or active) and several other potential confounders. Separate analyses were performed for the timed 8-foot (ie, 2.4 m) walk test and a repeated sit-to-stand test. The 8-foot walk test compared subjects in the lowest and highest quintiles of 25(OH)D; the latter group had an average decrease of 0.27 s [95% CI: -0.44, -0.09 s (or 5.6%); P for trend < 0.001]. The sit-to-stand test compared subjects in the lowest and highest quintiles of 25(OH)D; the latter group had an average decrease of 0.67 s [95% CI: -1.11, -0.23 s (or 3.9%); P for trend = 0.017]. In the 25(OH)D reference range of 22.5-94 nmol/L, most of the improvement occurred in subjects with 25(OH)D concentrations between 22.5 and approximately 40 nmol/L, and further improvement was seen in the range of 40-94 nmol/L. Stratification by activity level showed no significant effect modification. In both active and inactive ambulatory persons aged > or =60 y, 25(OH)D concentrations between 40 and 94 nmol/L are associated with better musculoskeletal function in the lower extremities than are concentrations < 40 nmol/L.


The human T-cell leukemia-lymphoma virus in the southeastern United States.
The human T-cell leukemia-lymphoma virus (HTLV) is a recently described RNA tumor virus associated with human T-cell malignant neoplasms. In two geographic areas, Japan and the Caribbean basin, clusters of adult T-cell leukemia-lymphoma are "sentinel diseases" and have suggested an underlying prevalence of HTLV infection in both family members of the index cases and in the population. Four cases of lymphoma from the United States are described as illustrative of the sentinel disease. Serological studies of families and of a small population sample suggest that HTLV infection is endemic in certain parts of the southeastern United States at rates similar to those seen in Caribbean blacks but at a lower rate than that observed in southwestern Japan.


Associations between Parenting Style and Mental Health in Children and Adolescents Aged 11-17 Years: Results of the KiGGS Cohort Study (Second Follow-Up).
Few studies from Germany have investigated the associations between parenting style and children's and adolescents' health. Little attention has been directed to whether these associations vary with familial socioeconomic or migration status. The aim of this analysis was to investigate the association between parenting style and the mental health of children and adolescents aged 11-17 years using data from the KiGGS cohort study (second follow-up). We calculated mean Strengths and Difficulties Questionnaire (SDQ) total difficulties scores stratified by parenting style (authoritative, permissive, demanding-controlling, emotional distancing). Linear regression analyses adjusted for age, gender, socioeconomic status, migration status, and family status were performed. We also analyzed moderating effects of socioeconomic and migrations status on associations between parenting style and SDQ scores. There were only small differences between the permissive and the authoritative parenting styles. Significantly higher mean scores were observed for the demanding-controlling and emotional distancing styles for both the mother and father. These associations persisted after full adjustment and did not vary by socioeconomic or migration status. Parenting behavior is an important predictor of children's and adolescents' mental health. The promotion of good relationships within families and improving parenting skills offer promising approaches for health promotion in young people.


A novel lantibiotic, nukacin ISK-1, of Staphylococcus warneri ISK-1: cloning of the structural gene and identification of the structure.
Staphylococcus warneri ISK-1, which we had previously reported as Pediococcus sp. ISK-1, produces a novel bacteriocin, nukacin ISK-1. Edman degradation of the chemically reduced nukacin ISK-1 produced a sequence of 27 amino acids, 7 of which were unidentified. Using single-specific-primer-PCR product as a probe, a 3.6-kb HindIII fragment containing the nukacin ISK-1 structural gene (nukA) was cloned and sequenced. The deduced amino acid sequence of nukacin ISK-1 had 57 amino acids, including a 30-amino acid leader region. The propeptide sequence showed significant similarity to those of lacticin-481 type lantibiotics. In the region upstream of nukA, a part of a long open reading frame (ORF), designated as nukM, encoding a putative modification enzyme was oriented in the opposite direction. In the region downstream of nukA, ORF1 was found in which the sequence of the putative translational product was similar to various response regulatory proteins.


Serum Vitamin D Concentrations Are Not Associated with Insulin Resistance in Swiss Adults.
Low vitamin D status has been associated with an increased risk of developing type 2 diabetes and insulin resistance (IR), although this has been recently questioned. We examined the association between serum vitamin D metabolites and incident IR. This was a prospective, population-based study derived from the CoLaus (Cohorte Lausannoise) study including 3856 participants (aged 51.2 ± 10.4 y; 2217 women) free from diabetes or IR at baseline. IR was defined as a homeostasis model assessment (HOMA) index >2.6. Fasting plasma insulin and glucose were measured at baseline and at follow-up to calculate the HOMA index. The association of vitamin D metabolites with incident IR was analyzed by logistic regression, and the results were expressed for each independent variable as ORs and 95% CIs. During the 5.5-y follow-up, 649 (16.9%) incident cases of IR were identified. Participants who developed IR had lower baseline serum concentrations of 25-hydroxyvitamin D3 [25(OH)D3 (25-hydroxycholecalciferol); 45.9 ± 22.8 vs. 49.9 ± 22.6 nmol/L; P < 0.001], total 25(OH)D3 (25(OH)D3 + epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3]; 49.1 ± 24.3 vs. 53.3 ± 24.1 nmol/L; P < 0.001), and 3-epi-25(OH)D3 (4.2 ± 2.9 vs. 4.3 ± 2.5 nmol/L; P = 0.01) but a higher 3-epi- to total 25(OH)D3 ratio (0.09 ± 0.05 vs. 0.08 ± 0.04; P = 0.007). Multivariable analysis adjusting for month of sampling, age, and sex showed an inverse association between 25(OH)D3 and the likelihood of developing IR [ORs (95% CIs): 0.86 (0.68, 1.09), 0.60 (0.46, 0.78), and 0.57 (0.43, 0.75) for the second, third, and fourth quartiles compared with the first 25(OH)D3 quartile; P-trend < 0.001]. Similar associations were found between total 25(OH)D3 and incident IR. There was no significant association between 3-epi-25(OH)D3 and IR, yet a positive association was observed between the 3-epi- to total 25(OH)D3 ratio and incident IR. Further adjustment for body mass index, sedentary status, and smoking attenuated the association between 25(OH)D3, total 25(OH)D3, and the 3-epi- to total 25(OH)D3 ratio and the likelihood of developing IR. In the CoLaus study in healthy adults, the risk of incident IR is not associated with serum concentrations of 25(OH)D3 and total 25(OH)D3.


Obstructive sleep apnea and cardiovascular disease.
Obstructive sleep apnea (OSA) is a common medical condition that occurs in approximately 5% to 15% of the population. The pathophysiology of OSA is characterized by repetitive occlusions of the posterior pharynx during sleep that obstruct the airway, followed by oxyhemoglobin desaturation, persistent inspiratory efforts against the occluded airway, and termination by arousal from sleep. Obstructive sleep apnea is associated with daytime sleepiness and fatigue, likely due to fragmented sleep from recurrent arousals. Substantial evidence shows that patients with OSA have an increased incidence of hypertension compared with individuals without OSA and that OSA is a risk factor for the development of hypertension. Recent studies show that OSA may be implicated in stroke and transient ischemic attacks. Obstructive sleep apnea appears to be associated with coronary heart disease, heart failure, and cardiac arrhythmias. Pulmonary hypertension may be associated with OSA, especially in patients with preexisting pulmonary disease. Although the exact cause that links OSA with cardiovascular disease is unknown, there is evidence that OSA is associated with a group of proinflammatory and prothrombotic factors that have been identified to be important in the development of atherosclerosis. Obstructive sleep apnea is associated with increased daytime and nocturnal sympathetic activity. Autonomic abnormalities seen in patients with OSA include increased resting heart rate, decreased R-R interval variability, and increased blood pressure variability. Both atherosclerosis and OSA are associated with endothelial dysfunction, increased C-reactive protein, interleukin 6, fibrinogen, and plasminogen activator inhibitor, and reduced fibrinolytic activity. Obstructive sleep apnea has been associated with enhanced platelet activity and aggregation. Leukocyte adhesion and accumulation on endothelial cells are common in both OSA and atherosclerosis. Clinicians should be aware that OSA may be a risk factor for the development of cardiovascular disease.


Association of GSTM1, GSTT1, GSTP1-ILE105VAL and ACE I/D polymorphisms with ankylosing spondylitis.
Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin. The aim of this study is to clarify the relationships between susceptibility and severity of AS and GST-mu1 (GSTM1), GST-theta1 (GSTT1), GST-pi1 (GSTP1)-Ile105Val and angiotensin-converting enzyme (ACE) I/D polymorphisms in AS patients. One hundred thirty-eight AS patients and seventy-one healthy controls were enrolled in this study. Erythrocyte sedimentation rate and C-reactive protein (CRP) levels of the AS patients were recorded. The scores of the numeric rating scale (NRS) pain, the Bath Ankylosing Spondylitis Activity Index, the Bath Ankylosing Spondylitis Metrology Index and the Bath Ankylosing Spondylitis Functional Index were calculated. The genotypes distributions and allele frequencies of GSTM1, GSTT1, GSTP1-Ile105Val and ACE I/D polymorphisms were compared between patients and healthy controls. The Multiplex polymerase chain reaction (PCR) and the PCR-restriction fragment length polymorphism methods were used to detect the polymorphisms of ACE I/D, the GSTT1 and GSTM1 genes and the GSTP1-Ile105Val polymorphism, respectively. There were significantly higher levels of the GSTT1 null and the ACE II genotypes in AS patients compared to those in healthy controls (p = 0.002 and 0.005, respectively). We found significantly higher levels of CRP and the NRS pain scores in the patients with ACE ID or DD genotypes compared to those in the patients with ACE II genotypes (p = 0.005 and 0.035, respectively). The present results showed that genes involved in protection from oxidative stress and ACE gene may influence disease development and course in AS.


[Supernumerary right pararenal spleen].
Presentation of one case report of unexpected retroperitoneal mass, since it occurred no only in a supernumerary spleen but also because of the right pararenal location. A discussion is presented on the diagnostic difficulties due to such cases being most often asymptomatic, and on the differential diagnosis with splenosis, although the possibility of an embryologic origin was also considered.


Changes in life-style after liver transplantation.
Sixty-five pediatric patients who received liver transplants between May 1981 and May 1984 were observed for as many as 5 years and examined for changes in life-style. Children were less frequently hospitalized, spent less time hospitalized, required fewer medications, and generally had excellent liver and renal function after hepatic transplantation as compared with their pretransplantation status. Most children were in age-appropriate and standard school classes or were only 1 year behind. Cognitive abilities remained unchanged. Children improved in gross motor function and patients' behavior significantly improved according to parents' perceptions. Enuresis was more prevalent, however, than in the population of children who had not received liver transplants. Parental divorce rates were no greater than those reported for other families with chronically ill children. Overall, objective changes in life-style as well as parents' perceptions of behavior of children appear to be improved after liver transplantation.


Efficacy of Presurgical Interventions to Promote Smoking Cessation: A Systematic Review.
The aim of this study was to evaluate the efficacy of presurgical interventions for promoting smoking cessation in terms of achieving smoking abstinence and reducing surgical complication rates. A systematic review of randomized clinical trials (RCTs) published from March 2009 to April 2021 was performed following the PRISMA guidelines. References were found in MEDLINE (via PubMed), Web of Science (WOS), and Cumulative Index to Nursing and Allied Health Literature (CINAHL). RCTs comparing the efficacy of a smoking cessation program directed at an intervention group (IG) versus the usual intervention or another directed at a control group (CG) were included. No language restrictions were applied in the search. All approaches to smoking cessation were admitted (face-to-face, telephone, group, individual, multicomponent, etc.), as were all methods for assessing abstinence, follow-up times, surgical specialties, definitions of smokers, and all types of surgical complications. Four hundred forty-four references were pulled out, and 79 duplicates were discarded. We excluded 346 records that were after application of the inclusion/exclusion criteria. In addition to the remaining 19 articles, 1 article obtained from citation searches was also assessed. We finally included 11 original articles in this systematic review, corresponding to 9 studies, because 2 of the RCTs had 2 different articles referring to different aspects of the same study. The results showed long-term postoperative (6 to 12 months) abstinence rates between 25.0% and 36.4% in RCTs with intensive multicomponent interventions, versus rates about 13.0% in brief interventions. Two multicomponent interventions obtained significant improvements regarding the reduction of short-term postoperative surgical complications. In conclusion, presurgical multicomponent smoking cessation interventions are more effective than brief interventions in terms of achieving abstinence and reducing surgical complications. The follow-up time and the intensity of the interventions were predictors of dropout.


Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours.
Neuropeptide Y (NPY) is found at high concentrations in neural crest-derived tumours and has been implicated as a regulatory peptide in tumour growth and differentiation. Neuroblastomas, ganglioneuromas and phaeochromocytomas with significant concentrations of NPY-like immunoreactivity were investigated for different molecular forms of NPY and for significance of proNPY processing. Gel-permeation chromatography identified intact NPY (1-36) in all tumours, whereas proNPY (69 amino acids) was detected only in control adrenal tissue and malignant neuroblastomas. Purification of NPY-like immunoreactivity in tumour extracts and structural characterization revealed that both NPY (1-36) and the truncated form NPY (3-36) was present. The degree of processing of proNPY to NPY in tumour tissue was lower in advanced neuroblastomas with regional or metastatic spread (stage 3 and 4) (n = 6), (41%, 12-100%, median, range), compared to the less aggressive stage 1, 2 and 4S tumours (n = 12), (93%; 69-100%), (P= 0.012). ProNPY processing of less than 50% was correlated with poor clinical outcome (P = 0.004). MYCN oncogene amplification was also correlated to a low degree of proNPY processing (P = 0.025). In summary, a low degree of proNPY processing was correlated to clinical advanced stage and poor outcome in neuroblastomas. ProNPY/NPY processing generated molecular forms of NPY with known differences in NPY-receptor selectivity, implicating a potential for in vivo modulation of NPY-like effects in tumour tissue.


Effect of dry needling on cubital tunnel syndrome: Three case reports.
This case series describes three patients who presented with right medial elbow pain managed unsuccessfully with conservative treatment that included medication, massage, exercise therapy, ultrasound therapy, neurodynamic mobilization, and taping. Diagnosis of cubital tunnel syndrome was based on palpatory findings, a positive elbow flexion test, and a positive Tinel's sign. Conventionally, the intervention for this entrapment has been surgical decompression, with successful outcomes. This is potentially a first-time description of the successful management of cubital tunnel syndrome with dry needling (DN) using a recently published DN grading system. The patients were seen twice a week for 2 weeks with immediate improvements noted in all the outcome measures after the first treatment session. At discharge, they were pain-free and fully functional, which was maintained up to a 6-month follow-up.


Hepatocytic globules in end-stage hepatic disease: relationship to alpha1-antitrypsin phenotype.
Hepatic explant specimens from 171 patients with cirrhosis were examined to determine the incidence of periodic acid-Schiff (PAS)-positive diastase-resistant globules (PDRGs) in end-stage hepatic disease and whether the globules bear a specific relationship to the alpha1-antitrypsin (A1AT) phenotype or to causes of hepatic disease other than A1AT deficiency. PAS-positive diastase-resistant globules were detected in 17 (10%) of the hepatic explant specimens, and the globules in all of these cases were strongly immunoreactive for A1AT. In the 17 patients with PDRGs, the cirrhosis was attributed preoperatively to A1AT deficiency (3 patients), ethanol abuse, viral hepatitis, or both (10 patients), cryptogenic cirrhosis (3 patients), and autoimmune hepatitis (1 patient). The A1AT isoelectric phenotypes classified according to the protease inhibitor (Pi) nomenclature for 16 of these patients were as follows: Pi ZZ (3 patients), Pi SS (1 patient), Pi MZ (8 patients), and Pi MM (4 patients). Because PDRGs were seen in a variety of A1AT phenotypes, serum electrophoretic analysis, not histologic examination, is required for the correct diagnosis of an A1AT abnormality. Furthermore, although PDRGs were seen in a variety of hepatic diseases, the majority of patients with globules had an undetected A1AT abnormality. Accordingly, on identification of hepatocytic PDRGs, the clinician should be alerted to the possibility of an unsuspected A1AT abnormality even in the presence of other causes of hepatic disease.


Ehrenfest Statistical Dynamics in Chemistry: Study of Decoherence Effects.
In previous works, we introduced a geometric route to define our Ehrenfest statistical dynamics (ESD) and we proved that, for a simple toy model, the resulting ESD does not preserve purity. We now take a step further: we investigate decoherence and pointer basis in the ESD model by considering some uncertainty in the degrees of freedom of a simple but realistic molecular model, consisting of two classical cores and one quantum electron. The Ehrenfest model is sometimes discarded as a valid approximation to nonadiabatic coupled quantum-classical dynamics because it does not describe the decoherence in the quantum subsystem. However, any rigorous statistical analysis of the Ehrenfest dynamics, such as the described ESD formalism, proves that decoherence exists. In this article, decoherence in ESD is studied by measuring the change in the quantum subsystem purity and by analyzing the appearance of the pointer basis to which the system decoheres, which for our example is composed of the eigenstates of the electronic Hamiltonian.


[Distribution of mitochondrial DNA markers in the European populations of Eurasia].
Results of comparative analysis of published and original data on mtDNA polymorphism in Caucasoid populations of Eurasia are presented. The study was based on choosing for analysis mitochondrial DNA markers with distinct geographical frequency gradients. Southeastern Europe was demonstrated to be an area of maximum frequencies of BamHI-1/AvaII-5(3), BamHI-3/MspI-4, and 16126(C)/16294(T) of mtDNA control region; mitogroup BamHI-2/AvaII-5(3) prevailed in populations of northwestern Europe. This distribution of mitochondrial markers was presumed to be connected to the history of European population formation and Caucasoid migrations from the Near East to Europe in the Neolithic.


Cerebrospinal fluid volume and nerve root vulnerability during lumbar puncture or spinal anaesthesia at different vertebral levels.
Cerebrospinal fluid (CSF) and nerve root volumes within the lumbosacral dural sac were estimated at various vertebral levels, in an attempt to determine any possible relevance to the incidence of nerve root trauma during lumbar puncture or spinal anaesthesia. Magnetic resonance images from seven patients were studied. Volumes were calculated by semi-automatic threshold segmentation combined with manual editing of each slice. The mean dural sac volume from S1 to T12 was 42.8±5.8 ml and the mean CSF volume 34.3±5.1 ml with the mean root volume being 10.4±2.2 cm(3). The mean CSF volume per vertebral segment ranged from 4.3±0.7 ml at L5, to 5.8±2.5 ml at L1, with high inter-individual variability. The mean root volume ranged from 0.6±0.1 cm(3) at L5 to 2.4±0.5 cm(3) at T12. The conus medullaris was located at L1 in four of the five patients scanned at upper lumbar levels, and at the lower border of L2 in the other. Vulnerability to nerve root damage was expressed as the Vulnerability Index (%), being defined as the ratio of root volume to dural sac volume (CSF volume + root volume). The value ranged between 7 and 14% at L5, increasing rostrally to 30 to 43% at T12. Caution is obviously required in high punctures to avoid contact with the conus medullaris, but the cauda equina is also vulnerable to contact with more caudal punctures and had a Vulnerability Index of about 25% at L4, that increased rostrally.


PaeA (YtfL) protects from cadaverine and putrescine stress in Salmonella Typhimurium and E. coli.
Salmonella and E. coli synthesize, import, and export cadaverine, putrescine, and spermidine to maintain physiological levels and provide pH homeostasis. Both low and high intracellular levels of polyamines confer pleiotropic phenotypes or lethality. Here, we demonstrate that the previously uncharacterized inner membrane protein PaeA (YtfL) is required for reducing cytoplasmic cadaverine and putrescine concentrations. We identified paeA as a gene involved in stationary phase survival when cells were initially grown in acidic medium, in which they produce cadaverine. The paeA mutant is also sensitive to putrescine, but not to spermidine or spermine. Sensitivity to external cadaverine in stationary phase is only observed at pH > 8, suggesting that the polyamines need to be deprotonated to passively diffuse into the cell cytoplasm. In the absence of PaeA, intracellular polyamine levels increase and the cells lose viability. Degradation or modification of the polyamines is not relevant. Ectopic expression of the known cadaverine exporter, CadB, in stationary phase partially suppresses the paeA phenotype, and overexpression of PaeA in exponential phase partially complements a cadB mutant grown in acidic medium. These data support the hypothesis that PaeA is a cadaverine/putrescine exporter, reducing potentially toxic levels under certain stress conditions.


IL-36γ induces a transient HSV-2 resistant environment that protects against genital disease and pathogenesis.
Herpes simplex virus 2 (HSV-2) causes a persistent, lifelong infection that increases risk for sexually transmitted infection acquisition. Both the lack of a vaccine and the need for chronic suppressive therapies to control infection presents the need to further understand immune mechanisms in response to acute HSV-2 infection. The IL-36 cytokines are recently identified members of the IL-1 family and function as inflammatory mediators at epithelial sites. Here, we first used a well-characterized three-dimensional (3-D) human vaginal epithelial cell (VEC) model to understand the role of IL-36γ in the context of HSV-2 infection. In 3-D VEC, IL-36γ is induced by HSV-2 infection, and pretreatment with exogenous IL-36γ significantly reduced HSV-2 replication. To assess the impact of IL-36γ treatment on HSV-2 disease pathogenesis, we employed a lethal genital infection model. We showed that IL-36γ treatment in mice prior to lethal intravaginal challenge significantly limited vaginal viral replication, delayed disease onset, decreased disease severity, and significantly increased survival. We demonstrated that IL-36γ treatment transiently induced pro-inflammatory cytokines, chemokines, and antimicrobial peptides in murine lower female reproductive tract (FRT) tissue and vaginal lavages. Induction of the chemokines CCL20 and KC in IL-36γ treated mice also corresponded with increased polymorphonuclear (PMN) leukocyte infiltration observed in vaginal smears. Altogether, these studies demonstrate that IL-36γ drives the transient production of immune mediators and promotes PMN recruitment in the vaginal microenvironment that increases resistance to HSV-2 infection and disease. Our data indicate that IL-36γ may participate as a key player in host defense mechanisms against invading pathogens in the FRT.


Imageless navigation in hip resurfacing: avoiding component malposition during the surgeon learning curve.
Studies suggest that hip arthroplasty procedures performed in specialty hospitals or by physicians in practices with a high surgical volume are associated with a decreased rate of adverse outcomes related to component malpositioning. Little is known, however, about the influence of imageless computer navigation systems on the procedural experience of the surgeon and the subsequent alignment of implants in the setting of hip resurfacing arthroplasty. Seventy-one consecutive hip resurfacing arthroplasties in which the components were placed with use of computer-assisted navigation were reviewed retrospectively. Intraoperative femoral and acetabular component parameters were compared with postoperative radiographic alignment values. Within this single surgeon series, operative time, intraoperative cup inclination and femoral stem-shaft angles, and postoperative cup inclination and femoral stem-shaft angles were measured and compared over the course of three discrete, sequential operative time periods. Patient demographic data and surgical parameters, including blood loss, surgical approach, and anesthesia time, were recorded. No significant difference was seen between the intraoperative and postoperative cup inclination angles. A significant difference was noted between the intraoperative and postoperative femoral stem-shaft angles; however, the mean angles in all groups had a valgus orientation when compared with the mean native neck angles. Over three sequential operative time periods, computer-assisted navigation produced consistent values with regard to intraoperative cup inclination (43 degrees , 44 degrees , and 40 degrees ) and postoperative radiographic alignment of the cup (46 degrees , 44 degrees , and 43 degrees ) and femoral stem (148 degrees , 147 degrees , and 144 degrees ), despite different levels of surgeon experience. Operative times significantly decreased with surgeon experience, showing the largest decrease after the first sequence interval (110, ninety-eight, and ninety-five minutes, respectively). There was a significant difference with evolving surgeon experience concerning intraoperative stem placement (144 degrees , 142 degrees , and 138 degrees , respectively) despite the mean values remaining well-clustered. No femoral notching occurred throughout the series. Computer-assisted navigation is a dependable and accurate method of positioning hip resurfacing components during arthroplasty, as measured by cup inclination, and a reliable technique for valgus stem placement and avoidance of notching. Furthermore, computer navigation allows for consistency of component alignment independent of procedural experience.


Evaluation of an advanced-practice physiotherapist in triaging patients with lumbar spine pain: surgeon-physiotherapist level of agreement and patient satisfaction.
Surgery for lumbar spine pain is indicated for specific etiologies. Given the majority of individuals referred to spine surgeons are not surgical candidates, care delivery is inefficient, with consultations being of limited value for most. Using specially trained physiotherapists in triage is a human resource strategy that may optimize surgeons' time and the patient experience. An advanced-practice physiotherapist (APP) and a surgeon assessed consecutive patients with lumbar spine pain presenting at an academic health centre's spine surgery clinic. The second assessor was blinded to the outcome of the first. We used the κ statistic to evaluate surgeon-APP level of chance-corrected agreement concerning patients' need for a surgical consultation. To assess satisfaction with the APP, patients completed a modified version of the validated Visit-specific Questionnaire. The sample included 102 participants (54 women) with a mean age of 54.3 ± 14.3 years and a mean Oswestry Disability Index score of 35.4 ± 16.6. The assessors' overall agreement was 86%. The κ coefficient for the need for a surgical consultation was 0.69 (95% confidence interval 0.54-0.84). The APP identified that 77% of patients did not require a surgical consultation. Twenty-one patients underwent surgery. Satisfaction scores for the APP were very high (mean score 92 out of 100). In triaging patients with lumbar spine pain, the APP and surgeon had a high level of agreement. An APP performing triage at a surgical centre can effectively reduce wait lists by 70%, reserving surgical consultations for those patients in whom they are indicated.


Analysis of microstructured surfaces in two dimensions.
A certain class of microstructured surfaces in 2D geometry is studied on the basis of an approximation of infinitesimal microstructure elements. The macroprofile of the surfaces is then treated as a new type of optical surface with a deflection law that differs from the law of reflection and Snell's law. We discuss the propagation of wavefronts by general microstructured surfaces and the discontinuity of the eikonal function at the microstructure. Naturally, a classification of the microstructures is obtained (regular and anomalous), and the concept of 2D ideal microstructures is also introduced, since they are used for coupling two macroscopic extended bundles.


Expression and distribution of octopus gonadotropin-releasing hormone in the central nervous system and peripheral organs of the octopus (Octopus vulgaris) by in situ hybridization and immunohistochemistry.
We recently purified a peptide with structural features similar to vertebrate gonadotropin-releasing hormone (GnRH) from the brain of Octopus vulgaris, cloned a cDNA encoding the precursor protein, and named it oct-GnRH. In the current study, we investigated the expression and distribution of oct-GnRH throughout the central nervous system (CNS) and peripheral organs of Octopus by in situ hybridization on the basis of the cDNA sequence and by immunohistochemistry using a specific antiserum against oct-GnRH. Oct-GnRH mRNA-expressing cell bodies were located in 10 of 19 lobes in the supraesophageal and subesophageal parts of the CNS. Several oct-GnRH-like immunoreactive fibers were seen in all the neuropils of the CNS lobes. The sites of oct-GnRH mRNA expression and the mature peptide distribution were consistent with each other as judged by in situ hybridization and immunohistochemistry. In addition, many immunoreactive fibers were distributed in peripheral organs such as the heart, the oviduct, and the oviducal gland. Modulatory effects of oct-GnRH on the contractions of the heart and the oviduct were demonstrated. The results suggested that, in the context of reproduction, oct-GnRH is a key peptide in the subpedunculate lobe and/or posterior olfactory lobe-optic gland-gonadal axis, an octopus analogue of the hypothalamo-hypophysial-gonadal axis. It may also act as a modulatory factor in controlling higher brain functions such as feeding, memory, movement, maturation, and autonomic functions


Batrachotoxin-induced depolarization and [3H]batrachotoxinin-a 20 alpha-benzoate binding in a vesicular preparation from guinea pig cerebral cortex.
The sodium channel-specific agent batrachotoxin (BTX) has been shown to induce a time- and concentration-dependent depolarization of a vesicular preparation from guinea pig cerebral cortex. The K0.5 for depolarization by BTX was 0.011 microM at 30 min. Membrane potential was determined by the equilibrium distribution of [3H]triphenylmethylphosphonium ion. A series of seven local anesthetics was shown to inhibit BTX-induced depolarization competitively with Ki values ranging from 0.9 microM for dibucaine to 780 microM for lidocaine ethiodide. The specific binding of labeled batrachotoxinin-A 20 alpha-benzoate ([3H]BTX-B) to voltage-sensitive channels in vesicular preparations from mouse cerebral cortex in the presence of scorpion venom was measured and found to yield a range of Kd values from 25 to 30 nM and Bmax values of 0.5 and 1.0 pmole/mg of protein; the same preparation from guinea pig cerebral cortex was found to yield Kd values from 13 to 56 nM and Bmax values of 0.8-2.2 pmoles/mg of protein. A series of 14 local anesthetics was shown to inhibit the specific binding of [3H]BTX-B with Ki values ranging from 0.6 microM for dibucaine to 400 microM for benzocaine. The rank order of potency of the local anesthetics as antagonists of [3H]BTX-B binding was as follows: dibucaine greater than tetracaine greater than bupivacaine greater than diphenhydramine greater than piperocaine greater than cocaine greater than procaine greater than lidocaine greater than benzocaine. The quaternary local anesthetic dimethyl-di(phenylcarbamoylmethyl)ammonium chloride was comparable in potency to tetracaine. The rank order and relative potency of the local anesthetics tested in both paradigms were similar with the exception of lidocaine ethiodide, which was 18 times more potent as an inhibitor of binding of [3H]BTX-B than it was as an inhibitor of BTX-elicited depolarization.


Prevalence of child and adult sexual abuse and risk taking practices among HIV serodiscordant African-American couples.
This study reports the prevalence of child (CSA) and adult (ASA) sexual abuse among 535 African American HIV serodiscordant couples from four major United State cities, and its relationship to personal and couple related vulnerabilities and HIV risk factors. As part of a randomized, clinical trial, CSA and ASA histories were obtained through face-to-face interviews. Results indicate that HIV positive women were significantly more likely to report one kind of abuse (32.32%), either before or since age 18 or both (32.6%). HIV-positive men (34.9%) were significantly more likely to report CSA than HIV-negative men (22.0%). Overall, 72% of couples reported that one or both had CSA histories. These findings underscore the heightened emotional vulnerability, and STI and HIV transmission risk taking practices, associated with sexual abuse. Sexual abuse histories among couples should be assessed to better understand how these histories may contribute to couples dynamics and risk-taking practices.


Orienting and Onboarding Clinical Nurse Specialists: A Process Improvement Project.
Clinical nurse specialists (CNSs) have a unique advanced practice role. This article describes a process useful in establishing a comprehensive orientation and onboarding program for a newly hired CNS. The project team used the National Association of Clinical Nurse Specialists core competencies as a guide to construct a process for effectively onboarding and orienting newly hired CNSs. Standardized documents were created for the orientation process including a competency checklist, needs assessment template, and professional evaluation goals. In addition, other documents were revised to streamline the orientation process. Standardizing the onboarding and orientation process has demonstrated favorable results. As of 2016, 3 CNSs have successfully been oriented and onboarded using the new process. Unique healthcare roles require special focus when onboarding and orienting into a healthcare system. The use of the National Association of Clinical Nurse Specialists core competencies guided the project in establishing a successful orientation and onboarding process for newly hired CNSs.


Finding the balance: living with memory loss.
Since the late 1980s, it has been increasingly recognized that the experiences of people with dementia have been omitted from research in the area of dementia and memory loss. More recently, it has been accepted that people with dementia have insight into their condition and, therefore, the ability to contribute to research. A qualitative research project was undertaken with nine participants to explore the experiences and coping strategies of people with dementia. Interviews were undertaken and the data analysed using thematic analysis. Three major themes emerged: coming to terms with memory loss, maintaining control and independence, and the impact of illness on relationships. Understanding the reality for people is essential given that representations of the catastrophic impact of dementia generate high levels of anxiety and depression. Implications for nurses' practice include the need for skilled, well-paced, sensitive and ongoing information about the condition, along with the need to recognize and support the active coping strategies of people with memory loss.


Size, shape and secondary structure of calponin.
The overall size and shape of the chicken gizzard calponin (CaP) h1 molecule was investigated by dynamic light scattering (DLS) measurements. From the DLS experiments, a z-averaged translational diffusion coefficient is derived (5.75 +/- 0.3) x 10(-7) cm(2) s(-1), which corresponds to a hydrodynamic radius of 3.72 nm for calponin. The frictional ratio (1.8 for the unhydrated molecule and 1.5 for the hydrated one) suggests a pronounced anisotropic structure for the molecule. An ellipsoidal model in length 19.4 nm and with a diameter of 2.6 nm used for hydrodynamic calculations was found to reproduce the DLS experimental data. The evaluation of the secondary structure of CaP h1 from the CD spectra by two independent methods has revealed that it contains, on average, 23% helix, 19% beta-strand, 18% beta-turns and loops, and 40% of remainder structures. These values are in good agreement with those predicted from the amino-acid sequence. Predictions used for CaP h1 were applied to other isoforms of known sequences and revealed that all calponins share a common secondary structure. Moreover, the predicted structure of the calponin CH domain is identical to that found by X-ray studies of the spectrin, fimbrin and utrophin CH domains.


Anti-obesity and Anti-diabetic Effect of Ursolic Acid against Streptozotocin/High Fat Induced Obese in Diabetic Rats.
Obesity is occurring due to continue taken high fat diet; this is the fast-growing problem reaching epidemic proportion globally. Ursolic acid altered the abnormal glucose metabolism in diabetic rats. In this experimental protocol, we examine ursolic acid (UA) anti-obesity effect against streptozotocin (STZ) and high-fat diet-induced obesity in rats. Orally administered the ursolic acid (2.5, 5 and 10 mg/kg) dose to the hyperglycemic rats for 8 weeks and estimated the blood glucose level at different time intervals. Biochemical, hepatic, lipid, renal and antioxidant parameters were estimated. Traf-4, Mapk-8, Traf-6 and genes such as Ins-1, ngn-3 and Pdx-1 mRNA expression were estimated using qRT-PCR to scrutinize the molecular mechanism in MAPK downstream JNK cascade and insulin pathway signalling pathways. Ursolic acid significantly (p<0.001) down-regulated the blood glucose level at dose dependent manner. Its also reduced the plasma insulin level, non-essential fatty acid and increased the level of adiponectin as compared to obese control group rats. Ursolic acid treated group rats reduced the level of total cholesterol and triglycerides. Ursolic-acid-treated rats have been shown to decrease oxidative stress in pancreatic tissue by restoring the free radical effect of scavenging, suppress the Traf-6, Mapk-8 and Traf-4 mRNA expression, enhance the expression of Pdx-1, Ins-1 and Ngn-3 and ensure the regeneration of pancreas β cells and therefore pancreas insulin. The current result suggested the anti-obese effect of ursolic acid against high fat diet (HFD) induced obese rats via alteration of insulin and JNK signaling pathway.


Common scale-invariant patterns of sleep-wake transitions across mammalian species.
Although mammals of different species have different sleep patterns, brief sleep-wake transitions commonly are observed across species and appear to occur randomly throughout the sleeping period. The dynamical patterns and functions of these brief awakenings from sleep are not well understood, and they often are viewed as disruptions (random or pathologic) of the sleep process. In this article, we hypothesize that brief awakenings from sleep may reflect aspects of the endogenous sleep control mechanism and thus may exhibit certain robust dynamical patterns across species. We analyze sleep recordings from mice, rats, cats, and humans, and we compare the distributions of sleep and wake episode durations. For all four species, we find that durations of brief wake episodes during the sleep period exhibit a scale-free power-law behavior with an exponent alpha that remains the same for all species (alpha approximately equal to 2.2). In contrast, sleep episode durations for all four species follow exponential distributions with characteristic time scales, which change across species in relation to body mass and metabolic rate. Our findings suggest common dynamical features of brief awakenings and sleep durations across species and may provide insights into the dynamics of the neural circuits controlling sleep.


Pathologic findings in patients who underwent robot-assisted radical prostatectomy following active surveillance: a prospective study in a single center.
Active surveillance is the recommended treatment of option for men with very low-risk prostate cancer. In this study, the clinicopathological results of patients who were initially treated with active surveillance and subsequently underwent robot-assisted radical prostatectomy during follow-up are described. A prospective cohort of 106 men enrolled in active surveillance was reviewed. Pathologic specimens for patients who ultimately underwent robot-assisted radical prostatectomy for progression or personal preference were analyzed. After exclusion of 14 patients who were lost to follow-up or with incomplete data collection, 92 men were included in the present analyses. Median follow-up was 27.6 months (range 3.3 to 193.1). Twenty-nine patients underwent robot-assisted radical prostatectomy. Progression occurred in 32 patients (34.8%), of which 23 men elected to undergo surgery. Robot-assisted radical prostatectomy was performed in 6 additional patients who chose definitive intervention due to anxiety. Pathologic analyses revealed organ-confined disease in 24 patients (82.8%), and Gleason score was ≥ 7 in nine (31%). Fourteen (48.3%) specimens were identified as having an advanced disease (Gleason score ≥ 7 and/or T3). In comparison to the patients with low-risk disease post-operatively (Gleason score <7 and T2), patients with advanced disease had significantly higher PSA density level and lower prostate volume. In this prospective active surveillance cohort, the progression rate was 34.8% over the follow-up period of 27.6 months. In specimens of patients who underwent robot-assisted radical prostatectomy, 48.3% displayed advanced pathologic features. Therefore we recommend that patients considering active surveillance should be counseled on risk of advanced disease as a possible hazard.


EFSA Health Claims-Based Virgin Olive Oil Shelf-Life.
The consumption of extra virgin olive oil (EVOO) has been linked to various health benefits, including a reduced risk of cardiovascular disease. EVOO contains triglycerides and unsaturated fatty acids, as well as minor compounds, such as polar phenols and tocopherols, which play a crucial nutritional and biological role. The composition of these minor compounds is affected by various factors that distinguish EVOOs from lower-quality olive oils. The European Parliament approved Regulation 1924/2006 that governs the use of health claims on food products based on EFSA reports. Currently, there are several authorized health claims related to unsaturated fatty acids, vitamin E, and polyphenol content that can be used for commercial reasons on EVOO labels. Consumers can easily take enough grams of EVOO per day to receive the beneficial effects of the nutrient in question; nevertheless, the use of these health claims is subject to a required concentration of specific nutrients throughout the shelf life of olive oil. Few studies have examined the evolution of these compounds along the shelf life of EVOO to meet health claims. This work aims to evaluate the nutritional profile of several EVOOs with potential health claims and the evolution of related nutrients during storage in darkness at different temperatures. This study proposes an accelerated method to determine the end of the EVOO shelf life based on the loss of its nutraceutical capacity and the inability to comply with the stated health claims.


Immobilization of alcohol dehydrogenase onto metal-chelated cryogels.
In this presented work, poly(HEMA-GMA) cryogel was synthesized and used for the immobilization of alcohol dehydrogenase. For this, synthesized cryogels were functionalized with iminodiacetic acid and chelated with Zn(2+). This metal-chelated cryogels were used for the alcohol dehydrogenase immobilization and their kinetic parameters were compared with free enzyme. Optimum pH was found to be 7.0 for both immobilized and free enzyme preparations, while temperature optima for free and immobilized alcohol dehydrogenase was 25 °C. Kinetic constants such as K(m), V(max), and k(cat) for free and immobilized form of alcohol dehydrogenase were also investigated. k(cat) value of free enzyme was found to be 3743.9 min(-1), while k(cat) for immobilized enzyme was 3165.7 min(-1). Thermal stability of the free and immobilized alcohol dehydrogenase was studied and stability of the immobilized enzyme was found to be higher than free form. Also, operational stability and reusability profile of the immobilized alcohol dehydrogenase were investigated. Finally, storage stability of the free and immobilized alcohol dehydrogenase was studied, and at the end of the 60 days storage, it was demonstrated that, immobilized alcohol dehydrogenase was exhibited high stability than that of free enzyme.


Nanomaterial-based barcodes.
Two-dimensional (2D) barcodes ubiquitously used to label, track and authenticate objects face increasing challenges of being damaged, altered and falsified. The past effort in nanomaterials has paved the way for controlled synthesis of nanomaterials with desired size, shape and function. Due to their extremely small sizes, these nanomaterials are promising as next generation barcodes that can be added into or mixed with objects of interest without being noticed. These barcodes can be effectively read owing to their physical properties by manufacturers, law enforcement and security agencies. Meanwhile, nanomaterial-based barcodes are hard to reverse-engineer or imitate without advanced knowledge and technical expertise. This review describes how nanomaterials can be used as barcodes, discusses advantages and limitations of each type of nanomaterial-based barcode, and points out ways that could help design and prepare better nanomaterial-based barcodes.


Antidepressant-resistant depression is characterized by reduced short- and long-interval cortical inhibition.
Major depressive disorder (MDD) is highly heterogeneous and can be classified as treatment-resistant depression (TRD) or antidepressant-responsive depression (non-TRD) based on patients' responses to antidepressant treatment. Methods for distinguishing between TRD and non-TRD are critical clinical concerns. Deficits of cortical inhibition (CI) have been reported to play an influential role in the pathophysiology of MDD. Whether TRD patients' CI is more impaired than that of non-TRD patients remains unclear. Paired-pulse transcranial magnetic stimulation (ppTMS) was used to measure cortical inhibitory function including GABAA- and GABAB-receptor-related CI and cortical excitatory function including glutamate-receptor-related intracortical facilitation (ICF). We recruited 36 healthy controls (HC) and 36 patients with MDD (non-TRD, n = 16; TRD, n = 20). All participants received evaluations for depression severity and ppTMS examinations. Non-TRD patients received an additional ppTMS examination after 3 months of treatment with the SSRI escitalopram. Patients with TRD exhibited reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI), as shown by abnormally higher estimates, than those with non-TRD or HC (F = 11.030, p < 0.001; F = 10.309, p < 0.001, respectively). After an adequate trial of escitalopram treatment, the LICI of non-TRD reduced significantly (t = - 3.628, p < 0.001), whereas the ICF remained lower than that of HC and showed no difference from pretreatment non-TRD. TRD was characterized by relatively reduced CI, including both GABAA- and GABAB-receptor-mediated neurons while non-TRD preserved partial CI. In non-TRD, SSRIs may mainly modulate GABAB-receptor-related LICI. Our findings revealed distinguishable features of CI in antidepressant-resistant and responsive major depression.


Maternal dexamethasone increases endothelin-1 sensitivity and endothelin a receptor expression in ovine foetal placental arteries.
Despite National Institutes of Health recommendations to administer antenatal steroids as a single course to women threatening preterm delivery, repeated treatments are often given. We investigated effects of repeated dexamethasone (DM) administered to the ewe on small maternal and foetal placental arteries. We hypothesized that DM would increase responsiveness to endothelin-1 (ET-1) and norepinephrine (NE) and that foetal arteries would react differently to ET-1 and NE compared to maternal arteries. Ewes received three treatments beginning at 103, 110, and 117 days of gestation (dGA). Each treatment consisted of four IM injections of 2mg DM or saline at 12-h intervals. At 119 dGA, in vitro functional studies were performed using Mulvany wire myography and endothelin receptor (ETR) expression was quantified using real-time RTPCR and receptor ligand autoradiography. Foetal placental arteries demonstrated greater maximal contractility to ET-1 and lesser maximal contractility to NE compared to maternal arteries. DM increased the maximal contraction elicited by ET-1 and NE in foetal but not maternal placental arteries. DM also increased the abundance of type-A ETR but not type-B ETR mRNA in foetal but not maternal placental arteries. However, within the whole placentome, DM increased the abundance of type-B ETR and decreased type-A ETR mRNA, which was confirmed by similar changes in ETR binding specifically within the labyrinth region. In summary, repeated DM treatment results in agonist and vascular bed specific responses within the placenta.


Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study.
The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.


Personal toilet after defaecation and the degree of hand contamination according to different methods used.
Transmission due to contaminated hands is one of the important routes by which diarrhoea pathogens spread. The hands commonly become contaminated while cleaning the anus after defaecation. This study deals with the commonly used methods of anal cleansing in a low socioeconomic community in Rangoon, Burma and with the degree of hand contamination that results according to the method used. A cross-sectional survey was employed for collection of behavioural and hand contamination data. The incidence of acute diarrhoea and dysentery among under-fives in this community was monitored for 1 month and was correlated with the cleaning method used by their mothers. Water was the principal method used for cleaning the anus in all age groups. No one used toilet paper and only 4 to 9% used paper other than toilet paper. The level of education seemed to be a factor in determining the use of paper or water. The hands of mothers using water were more contaminated than those using paper. However, thorough hand washing with soap and water was found to be effective in decontaminating the hands. Furthermore, there was a relation between the incidence of diarrhoea and dysentery and the method of cleaning.