The cysteine introduced into the alpha subunit of the Escherichia coli F1-ATPase by the mutation alpha R376C is near the alpha-beta subunit interface and close to a noncatalytic nucleotide binding site.
Mutation of the alpha subunit of the Escherichia coli F1-ATPase to convert Arg-376 to a Cys (alpha R376C) lowers multisite ATPase activity 400-1,000-fold while affecting unisite catalysis only around 6-fold, suggesting that the mutation is in a region important for transmission of conformational changes between catalytic sites (Soga, S., Noumi, T., Takeyama, M., Maeda, M., and Futai, M. (1989) Arch. Biochem. Biophys. 268, 643-648; this study). To learn more of the structural features of the segment of the alpha subunit around Arg-376, mutant enzyme with a Cys at this position was modified with several maleimides. N-[14C]Ethylmaleimide reacted rapidly with this Cys in one of the three alpha subunits/F1 (2,500 M-1 s-1); more slowly with a second alpha subunit (390 M-1 s-1); and the same Cys in the third copy of the alpha subunit was completely unreactive to the reagent, indicating asymmetry of alpha subunits in the ECF1 complex. The photoactivatable cross-linker N-(4-azido-2,3,5,6-tetrafluorobenzyl)-3-maleimidopropionamide++ +, when reacted via its maleimide to alpha Cys-376 of the mutant, covalently linked alpha to beta subunits upon photolysis, indicating that Cys-376 of alpha is close to an interface between the alpha and beta subunits. The EDTA-induced exchangeable noncatalytic site could be filled by TNP-ATP in both wild type and alpha R376C mutant ECF1. Occupancy of this site in the alpha R376C mutant altered the rate of reaction of the second-fastest reacting Cys-376 from 390 M-1 s-1 to below 130 M-1 s-1, suggesting that the two sites are on the same alpha subunit. TNP-ATP in the EDTA-induced exchangeable noncatalytic site was quenched by reacting Cys-376 with 4-maleimido-(2,2,6,6-tetramethylpiperidine-N(oxyl), indicating that the region around Cys-376, which is involved in transmission of conformational changes between alpha and beta, and noncatalytic sites are maximally 10-12 A from each other.


Integration of Langerhans-like cells into a human skin equivalent.
Studies regarding cellular interactions between Langerhans cells and other skin cells are somehow hampered by the difficult cultivation of these cells in vitro. Here, we show that the human MUTZ-3 cell line can be differentiated into Langerhans-like cells in the presence of a cytokine cocktail including GM-CSF, TGF-β1 and TNF-α. We used the expression of langerin, CD1a, CCR6 and the intracellular presence of Birbeck granules to identify the differentiated MUTZ-3 cells (MUTZ-3-LCs). The aim of this study was to integrate MUTZ-3-LCs into a three-dimensional full-thickness skin model. On top of fibroblast-containing collagen matrix a mixture of primary human keratinocytes and MUTZ-3-LCs were seeded and cultured for 24 h. Subsequently, the models were lifted up to the air-liquid interface. Histological evaluation featured a fully stratified epidermis with all characteristic epidermal strata. Langerin-positive cells were detected suprabasally within the epidermis indicating that keratinocytes provide environmental conditions for long-time maintenance of MUTZ-3-LCs. These skin models provide a tool to further investigate the interactions between Langerhans-like cells and other skin cells and particularly learn more about the cutaneous immune response.


Mesenchymal fusion of the palatal processes and of heterotypic explants.
Two palatal sheleves were cultured for 3 to 6 h, and palatal shelves and half lips were associated and cultured for 24, 48 or 72 h on an agar culture medium. In all cases an epithelial wall was observed between the two mesenchymes. In homotypical palatal shelf cultures, the medial palatal wall disappears and mesenchymal fusion occurs. The epithelial barrier in palate-lip associations is constituted at first by palatal and labial cells, then purely labial, the medial palatal epithelium undergoing destruction. This labial wall pushed away by the actively growing mesenchyme finally disappears so that the palatal and labial mesenchymes are continuous. This phenomenon is completely different from the mesenchymal fusion and has not the same characteristics.


Content agreement of depressive symptomatology in children and adolescents: a review of eighteen self-report questionnaires.
Identifying major depression in children and adolescents is more challenging than in adults. Questionnaires are often used for screening or guiding clinical assessment. Several instruments of different lengths are used as equivalent measures in diagnostic decisions. In this paper, we explore to what extent 18 commonly used depression scales for children and adolescents explore depression clinical symptoms as established by standard DSM-5 diagnosis criteria. We analyzed scale content adequacy by examining the overlap between scale contents and consensus clinical symptoms, the diagnostic time frame for active symptom assessment, and readability for the target age group. The 18 scales encompassed 52 distinct symptoms. These scales included just 50% of clinical symptoms required for diagnosis. The content overlap was low; on average, 29% of symptoms coincide across scales. Half of the scales did not use the standard period for active symptom appraisal, and some did not include a period for assessment. The reading levels on six scales were inappropriate for the scale's target population age group. The substantial heterogeneity in defining the depressive syndrome, the low overlap among scales, different periods of a positive diagnosis, and mismatch of reading competence for detecting may lead to heterogeneity in clinical diagnoses when using different scales. Improving the content of self-report in terms of homogeneity of diagnostic criteria would lead to better diagnostic decisions and patient management.


Campylobacter biofilms.
Campylobacter infection is one of the most widespread foodborne gastroenteritis worldwide. As a commensal microbe in the intestinal tracts of food-producing animals, Campylobacter easily enters the food chain and eventually transmits to human hosts through the consumption of contaminated food products. The survival of Campylobacter in food chain remains as a paradox considering its fastidious growth requirement in laboratory settings and ubiquitous presence in unfavorable environment. Biofilm is suggested as a key persistence mechanism used by Campylobacter during its transmission from animals to humans. This review summarizes Campylobacter biofilm characteristics, identifies biological and non-biological factors that influence biofilm formation, and discusses the control strategies. Overall, biofilm formation ability shows strain-to-strain variation in Campylobacter and is affected by the presence of other co-cultivated bacteria. Carbohydrates and eDNA are recognized as significant portions of extracellular polymeric substances (EPS) in Campylobacter biofilm. Advanced techniques such as super resolution microscopy and chemical imaging platforms can demonstrate the structure and EPS biochemical compositions. Biofilm formation relies on various biological factors (e.g., flagella, cell surface hydrophobicity, and quorum sensing) and environmental factors (e.g., substrate properties, hydrodynamic condition, and nutrients). Different biological and inorganic compounds can inactivate Campylobacter biofilm along with the feasibility of discovering specific chemicals to quench quorum sensing of this microbe so as to indirectly reduce its biofilm. Taken together, Campylobacter biofilm research is still in its infancy and future research can focus on investigating dormancy state and antimicrobial resistance evolution in biofilms as well as in vivo characterization.


Cardiac contusion in the patient with multiple injuries.
We have treated 20 patients with multiple injuries and concomitant myocardial contusion. The diagnosis of myocardial contusion was based mainly on serial ECG tracings which showed arrhythmias, dynamic ischaemic patterns or conduction disturbances. The clinical and laboratory findings of cardiac contusion are sometimes indistinguishable from those found in multiple injuries. Furthermore, they are overshadowed by the overt manifestation of cerebral, thoraco-abdominal and skeletal injuries. Awareness and prompt diagnostic measures are essential in the diagnosis of cardiac injury. Strict cardiac monitoring following multiple trauma will prevent serious or even fatal outcome of cardiac injury.


Analgesic Effects of Two Types of Spinal Manipulation in Acute Lumbar Radiculopathy Model Rats.
To compare the analgesic effects of two types of spinal manipulation (SM) in acute lumbar radiculopathy (ALR) model rats induced by self-transplantation of autologous nucleus pulposus (ANP), and clarify the therapeutic mechanism. Totally 108 male Sprague-Dawley rats were randomly divided into 6 groups by a random number table (18 rats in each group), including a blank group with no interference, a sham operation group with a surgery by making a local soft tissue incision on the left side of L5-6 vertebral segment, a model group with ALR of L5 extraforaminal nerve by ANP self-transplantation without other interference, a sham manipulation (SMA) group with simulating physical rotation, as well as a mobilization (MOB) group with simulating low-velocity and variable-amplitude rotation and a manipulation (MAN) group with simulating high-velocity and low-amplitude rotation. The interventions in SMA, MOB, and MAN groups started 1 day after modeling followed by another 5 treatments at days 3, 5, 8, 10 and 12. Rats in the other 3 groups did not receive any special intervention. Behavioral pain tests of 50% mechanical pain withdrawal threshold (50% PWT) and paw withdrawal latency (PWL) were conducted 1 day before operation followed by another 10 tests on days 1-7, 10, 12 and 14. Immunohistochemical expression of nitric oxide synthase (NOS) was investigated on days 5 and 12 after operation. After 3 experimental SM interventions, 50% PWT and PWL were higher in the MAN group than the SMA group on days 6 and 7, and higher on days 10, 12 and 14 postoperatively (P<0.05 or P<0.01), while the same indices were significantly higher in the MOB group than MAN group on days 1-4 (P<0.05 or P<0.01). The expression of NOS was lower in the MAN and MOB groups than SMA group on day 12 postoperatively (P<0.01). Both manipulation and mobilization produced better results than sham interference in relieving pain by reducing neuroinflammation possibly. At the early period, compared with manipulation, mobilization presented less sensitive response to pain until later visit. SM may inhibit the overexpression of NOS, thereby alleviating severe radiculopathy.


Seasonal influence on semen traits and freezability from locally adapted Curraleiro bulls.
Studies were conducted to characterize the effect of season of the year on testicular morphology, fresh and frozen/thawed semen quality from Curraleiro (Pé-duro) bulls in the Brazilian Central west region. Five adult, healthy bulls underwent an andrological examination and semen collection using an electroejaculator, once a month for a year. Fresh and thawed semen were evaluated for progressive sperm motility and sperm vigor, sperm morphology and acrosomal integrity. Testicular length and volume were less (P<0.05) in April than in the other months of the year. For fresh semen, the ejaculate in April had less volume and sperm concentration (P<0.05), while sperm vigor was less (P<0.05) in June, increasing in January and February. With the frozen/thawed semen, the proportion of sperm was greater (P<0.05) in April to July, decreasing from October to December. Semen collected in December had the greatest (P<0.05) proportion of major defects while that collected in February/March had the highest proportion of minor defects. The proportion of live intact sperm reduced progressively from December to April/May. The marginal influence of the time of the year on testicular biometry and fresh semen in Curraleiro bulls shows the adaptation of this breed to the environmental conditions in the region. Thus, reproduction with natural mating should be successful at any time of year. For frozen semen collection for conservation programs, the best time of year is from June to September.


Prevalence of Return to Work in Cardiovascular Patients After Cardiac Rehabilitation: A Systematic Review and Meta-analysis.
The present systematic review and meta-analysis aimed to clarify the effects of cardiac rehabilitation (CR) on the prevalence of return to work (RTW) in cardiovascular diseases (CVDs) patients. CR plays a very important role in the management of CVDs and improves the patients' physical activity, quality of life, and a decrease in the cost of healthcare. RTW is the most important goal in the rehabilitation of CVD patients. PubMed, Web of Science, Scopus, and Google scholar were searched systematically from inception up to January 2021 for English published clinical trials and observational studies. In total, 16 studies were analyzed, of them, 8 were controlled studies. Pooled results showed that the mean age of patients was 52.30 (50.04, 54.57). The prevalence of RTW in the CR attending group was 66% (60%, 71%) and in the control group was 58% (47%, 68%). Subgroup analysis showed that the proportion of RTW was higher in white-collars 76% (73%-79%) compared to. blue-collars 63% (56%-70%). Out-patient CR with 72% (61%-81%) RTW was more effective compared to in-patient CR with 62% (44%- 78%) and usual care (control). It can be concluded that CR especially out-patient CR increases the prevalence of RTW but not much. Improved and appropriate CR programs related to each individual's disease and patient condition which follow the valid guidelines might help to increase the effectiveness of CR in terms of RTW.


Diagnosing non-palpable breast disease: short-term impact on quality of life of large-core needle biopsy versus open breast biopsy.
One of the alleged advantages of stereotactic large-core needle biopsy of non-palpable breast lesions is that it entails less inconvenience for the patient. In this prospective study, the quality of life of patients undergoing large-core needle biopsy was compared with that of patients undergoing open breast biopsy prior to learning the definitive diagnosis. Thirty patients with non-palpable breast lesions underwent stereotactic large-core needle biopsy as initial diagnostic procedure (needle biopsy group). Quality of life as perceived by these patients was compared with that of 27 patients who underwent open breast biopsy as initial diagnostic procedure (control group). Both groups completed quality of life questionnaires (EuroQol and SF-36) 1 day before and 4 days after the diagnostic intervention. One day before the diagnostic procedure, the overall estimate for quality of life (measured with the EuroQol) was slightly higher in the needle biopsy group than in the control group (73 versus 69 resp.). Four days after the diagnostic procedure, the quality of life score remained approximately unchanged in the needle biopsy group, but was reduced in the control group (71 versus 61 resp.). Results of the SF-36 questionnaire demonstrated that patients in the needle biopsy group had higher quality of life scores on physical functioning, physical performance, pain and social performance after the diagnostic intervention. Stereotactic large-core needle biopsy seems to affect quality of life to a lesser extent than open breast biopsy. This difference is mainly attributable to a reduction of physical discomfort and pain.


Twice-Daily vs 4-Times-Daily Glucose Testing in Women With Gestational Diabetes Mellitus: A Pilot Study.
In women with gestational diabetes mellitus (GDM), glycemic control is typically assessed by capillary blood glucose (BG) self-monitoring. Currently, the standard method of monitoring is by 4-times-daily self-measurements. The goal of our study was to determine whether twice-daily capillary BG testing is comparable with 4-times-daily testing in women with GDM. Thirty-two women with GDM completed initial dietary counselling and recorded consecutive fasting and 2-h postprandial BG over a 14-day period. We randomly selected 2 of 4 BG measurements on each given day and compared mean (95% confidence interval [CI]) twice-daily vs 4-times-daily BG measurements using paired t tests and Bland-Altman plots. The proportion of 14-day BG measurements above glycemic targets was also compared between twice-daily vs 4-times-daily testing for fasting and postprandial readings. Comparing twice-daily vs 4-times-daily mean BG, there was a small difference for fasting BG (0.09 mmol/L; 95% CI, 0.03 to 0.14), but not for 2-h postbreakfast (-0.05 mmol/L; 95% CI, -0.17 to 0.06), 2-h postlunch (-0.03 mmol/L; 95% CI, -0.13 to 0.08) or 2-h postdinner (0.05 mmol/L; 95% CI, -0.09 to 0.19) BG. Bland-Altman plots showed general agreement and minimal bias between twice-daily vs 4-times-daily BG, whether fasting or postprandial. There was no significant difference in the proportion of 14-day BG measurements above glycemic targets comparing twice-daily vs 4-times-daily testing in the fasting or postprandial states. Twice-daily BG testing appears to generate 14-day average values similar to 4-times-daily BG testing. In women with GDM, whose BG is in target range, twice-daily BG monitoring may reduce inconvenience and cost.


[Prevention and early detection of colorectal cancer].
With 60000 new cases and approximately 31000 deaths annually the colorectal carcinoma is the second most frequent cause of death due to a tumour in Germany. In over 90% of all colorectal carcinomas the precursors (adenomas) are well known. Moreover the early carcinoma of the colorectum (pT1-carcinoma) has an exceptional benign prognosis. To detect those precursors and early stages effective methods of primary, secondary and tertiary prevention are available.


Acute pulmonary embolism.
CT pulmonary angiography has become a first-line imaging test for evaluation of PE because of its high accuracy, ease of use, and ready availability. PIOPED II supports the use of multidetector CT as a first-line test especially in outpatients. Technological advances continue to evolve, and with refinements in technology, we will continue to optimize imaging for PE detection. lonizing radiation remains a concern particularly in the young and in pregnant patients, and methods to decrease these are being advocated. SPECT V/Q may play a bigger role in PE diagnosis in the future and the role of MR is yet to be determined in the PIOPED ll study, with the potential of solving some of the issues regarding radiation in a select group of patients.


Simulated scenes: a pedagogical experiment to reflect about conflict management in nursing care.
To describe simulated scenes on conflict management in nursing care, created by university students; and to identify the skills and attitudes needed by the nursing student to manage conflicts in health care. This is a qualitative study conducted with 28 university nursing students from a public college located in the city of Boa Vista, Roraima. The strategy adopted for the production of data was the simulation of scenes of conflict. The data were analyzed according to Bardin's methodology. Four conflict scenes were produced, involving nurses and nursing technicians, health managers, multiprofessional health teams, and patient care. In this context, 274 record units were identified regarding skills and attitudes for nurses to manage conflicts. The skills and attitudes essential for conflict management were: effective verbal communication, body language observation, knowing how to listen, negotiate, make decisions, be neutral, impartial, and how to lead democratically.


Genetic variants associated with platelet count are predictive of human disease and physiological markers.
Platelets play an important role in hemostasis and other aspects of vascular biology. We conducted a meta-analysis of platelet count GWAS using data on 536,974 Europeans and identified 577 independent associations. To search for mechanisms through which these variants affect platelets, we applied cis-expression quantitative trait locus, DEPICT and IPA analyses and assessed genetic sharing between platelet count and various traits using polygenic risk scoring. We found genetic sharing between platelet count and counts of other blood cells (except red blood cells), in addition to several other quantitative traits, including markers of cardiovascular, liver and kidney functions, height, and weight. Platelet count polygenic risk score was predictive of myeloproliferative neoplasms, rheumatoid arthritis, ankylosing spondylitis, hypertension, and benign prostate hyperplasia. Taken together, these results advance understanding of diverse aspects of platelet biology and how they affect biological processes in health and disease.


Effects of cysteine and cystamine on the carbon tetrachloride induced decrease in arachidonic acid content of rat liver microsomal phospholipids.
Cystamine and cysteine inhibited the carbon tetrachloride (CCl4) prooxidant effect on rat liver microsomal preparations, at concentrations ranging from 0.001 mM to 1 mM. Cysteine exhibited a biphasic effect being an inhibitor of the prooxidant action at concentrations below 0.1 mM and acting as an enhancer at 1 mM. Cystamine but not cysteine pretreatment of the rats prevented the CCl4 induced decrease in the arachidonic acid content of liver microsomal phospholipids. However, both cystamine and cysteine led to decreases in arachidonic acid similar to that produced by CCl4 but they do not have deleterious effects on the liver. These results cast doubt on the role of lipid peroxidation in the liver cell injury by CCl4.


Activation and detoxification of dinitropyrenes by cytosol and microsomes from Aroclor-pretreated rats in the Ames and umu assays.
1,3-, 1,6-, and 1,8-Dinitropyrene (1,3-, 1,6-, and 1,8-DNP) are direct-acting mutagens in that they do not require an exogenous source of enzymes for activation to mutagens in the Ames assay. However, the addition of mammalian S9 preparations, or the microsomal and cytosolic compartments comprising S9, modulate the mutagenic response of these DNPs. In this study, we compared the mutagenic response of these DNPs in the presence of cytosol and microsomal fractions from the liver of Aroclor-pretreated (AR) and control rats, in the Ames mutagenicity assay and umu gene induction assay. 1,3- and 1,8-DNP were deactivated to a greater extent by microsomes from AR-induced and control rats than was 1,6-DNP, in both the umu and Ames assays. In the Ames assay, S9 was more potent in deactivating the DNP than an equivalent concentration of microsomes from the same S9 preparation. Also, S9 from AR-pretreated rats deactivated the isomers to a greater extent than S9 from control rats. In contrast to the constant deactivation of all the isomers in the two assays catalyzed by microsomes and S9, the response with cytosol from AR-pretreated rats differed with respect to the three isomers in the Ames and umu assays. When cytosol from AR-treated rats was added, the mutagenicity of 1,3- and 1,6-DNP, but not 1,8-DNP, was significantly (P < 0.05) increased in the Ames assay while the mutagenicity of the three DNPs was increased in the umu assay. Also, a biphasic response was observed in the umu assay with 1,6- and 1,8-DNP, in that AR-cytosol enhanced the mutagenicity at low protein concentrations (5-50 micrograms protein/reaction) but abrogated the response at higher protein concentrations. The effect of cytosol from control rats depended on the isomer tested; 1,3-DNP was activated above the background level in both assays (nearly towfold) while 1,6-DNP and 1,8-DNP were only activated at low protein concentrations in the umu assay. In the Ames assay, cytosol from AR-pretreated rats did not alter the mutagenic response with 1,8-DNP, while control cytosol significantly (P < 0.05) deactivated 1,8-DNP at all substrate concentrations tested. In summary, this study showed that the mutagenicity of 1,3-DNP was similar in the two assays but the responses with 1,6- and 1,8-DNP differed in the two assays. These isomeric differences could be due to the varying metabolic pathways of the three DNPs as well as the detectable end points of the two assays.


Selective disaccharide binding by a macrotetracyclic receptor.
A new carbohydrate receptor possesses a C3-symmetric polar cavity capable of encapsulating disaccharides; binding to beta-maltosyl is preferred, complementing previous systems which have favoured "all-equatorial" substrates.


Autonomic nervous system activity during autologous blood donation for orthognathic surgery.
The aim of this study was to assess by means of power spectral analysis the immediate response of autonomic regulation that occurs with postural change from supine to sitting position (modified head-up tilt test [m-HUT]) during autologous blood donation (ABD) and postphlebotomy infusion. We investigated 37 healthy adults who required preoperative ABD before elective orthognathic surgery. Measurements were conducted with m-HUT during ABD and postphlebotomy infusion. The data were analyzed using the maximum entropy method and the difference between supine and tilt was determined by analysis of variance. When m-HUT was conducted at the resting state, cardiac parasympathetic nervous activity was significantly decreased, whereas cardiac and vascular sympathetic nervous activities were significantly increased. When m-HUT was conducted following blood collection, cardiac parasympathetic nervous activity showed a tendency to increase, whereas vascular sympathetic nervous activity was significantly increased. These changes were not observed during postphlebotomy infusion. The m-HUT, which involves postural change from supine to sitting position, may be useful for observing autonomic nervous activity in the clinical setting. ABD carries the risk of imbalance of autonomic regulation. However, postphlebotomy infusion may reduce this imbalance.


Antibacterial photodynamic therapy mediated by 5-aminolevulinic acid on methicillin-resistant Staphylococcus aureus.
The emergence of drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), has brought great difficulties to clinical treatment. Antibacterial photodynamic therapy (aPDT) is a new non-antibiotic treatment strategy for a variety of drug-resistant bacteria. However, there are few studies on the antimicrobial mechanism of a PDT mediated by 5-aminolevulinic acid (ALA-PDT) for MRSA. In this study, we observed the bactericidal effect of ALA-PDT on MRSA. We found that ALA-PDT had the strongest bactericidal effect when ALA was at 0.05 mM, and the bactericidal activity of aPDT increased with the increase of light dose. MRSA was almost completely eliminated at 0.05 mM and 384 Jcm-2. In addition, the bactericidal morphology was also observed under a fluorescence microscope using a LIVE/DEAD® BacLight™ Bacterial Viability Kit and an electron microscope. It was also found that proteins and DNA were damaged by ALA-PDT. Finally, the transcription level of the specific gene of MRSA, nuc, was decreased by 0.74-fold (P < 0.05) after ALA-PDT treatment by qRT-PCR analysis. The findings suggest that ALA-PDT can effectively inhibit MRSA by damaging cell membrane, cytoplasm, proteins and nucleic acid.


Transfer mechanism and bioaccumulation risk of potentially toxic elements in soil-rice systems comparing different soil parent materials.
Although the accumulation of potentially toxic elements in soil and crops has attracted widespread attention, the characteristics of the transfer and accumulation of potentially toxic elements in soil-crop systems with different soil parent materials are still not clear. Soil and crop samples were collected from agricultural regions with different soil parent materials in Guangxi, China. This study analyzed the concentrations of Cd, Zn, and Fe in the roots, straws, and seeds of rice (Oryza sativa L.) and soils with Quaternary sediments and clastic rocks as the parent materials. The concentration of several potentially toxic elements in rice tissue from the two areas followed the order of Croot> Cstraw> Cseed. The transport capability of Cd and Zn from roots to straws is higher than straws to seeds, and Fe showed a strong capability for transport from straws to seeds. In general, the transfer capacity of potentially toxic elements in the soil-rice system in the Quaternary sediments area was stronger than that in the soil-rice system in the clastic rocks area. Soil pH and minerals, which were represented by major elements, were the main factors affecting the transfer of metals from soil to seeds. This approach could help to evaluate the bioaccumulation risk of potentially toxic elements in crops in different areas quantitatively.


Use of a bioabsorbable mesh in midline laparotomy closure to prevent incisional hernia: randomized controlled trial.
The objective was to assess the effectiveness and safety of a bioabsorbable mesh at the time of closure of a midline laparotomy for IH prevention. A multicenter, randomized clinical trial including patients undergoing abdominal surgical procedures through a midline laparotomy incision was designed. In the group of mesh (n = 167) the incision was closed using a continuous polydioxanone suture (PDS) plus a bioabsorbable mesh. In the control group (n = 165) a continuous PDS single layer suture was only used. Patients were randomly assigned (1:1) to the two groups. The primary outcome was the incidence of IH at 6, 12 and 24 months. Assessment of IH was done using a CT scan. At 6 months, the rates of IH were 15.2% and 24.8% in the experimental and control groups, respectively (relative risk [RR] 0.66, 95% confidence interval [CI] 0.38-0.98, P = 0.042). At 12 months, the rate of IH continued to be significantly lower in the experimental group (21.4% vs. 33.1%, P = 0.033), but at 24 months, there were no significant differences between the study groups with a follow-up rate of only 37.5%. The number needed to treat (NNT) was 11 and 9 at 6 and 12 months, respectively. The bioabsorbable mesh significantly prevented IH during the first year. Not reliable conclusions can be drawn across the second year. This may suggest that the any of the closing technique assessed in this study would have a "palliative" transient effect for preventing IH in the long-term.


Parity-preserving and magnetic field-resilient superconductivity in InSb nanowires with Sn shells.
Improving materials used to make qubits is crucial to further progress in quantum information processing. Of particular interest are semiconductor-superconductor heterostructures that are expected to form the basis of topological quantum computing. We grew semiconductor indium antimonide nanowires that were coated with shells of tin of uniform thickness. No interdiffusion was observed at the interface between Sn and InSb. Tunnel junctions were prepared by in situ shadowing. Despite the lack of lattice matching between Sn and InSb, a 15-nanometer-thick shell of tin was found to induce a hard superconducting gap, with superconductivity persisting in magnetic field up to 4 teslas. A small island of Sn-InSb exhibits the two-electron charging effect. These findings suggest a less restrictive approach to fabricating superconducting and topological quantum circuits.


Development of a fluorescent immunodot assay for Bacillus cereus enterotoxin.
A fluorescent immunodot assay has been developed for rapid, specific detection of B. cereus enterotoxin. None of the other Bacillus species tested showed cross-reactivity in the assay with antiserum to purified B. cereus enterotoxin. The assay can detect greater than or equal to 50 ng of purified enterotoxin. Using this assay system, enterotoxin was found to be produced by 25 of 25 foodborne disease-related isolates and 22 of 25 isolates not related to foodborne disease (isolates from routine surveillance foods). Because of the apparent widespread ability of isolates to produce enterotoxin the assay may have potential as a rapid identification procedure for B. cereus. The substrate gel system described may have wider application in other immunoassay systems using a membrane solid phase.


Using Non-Pharmaceutical Interventions and High Isolation of Asymptomatic Carriers to Contain the Spread of SARS-CoV-2 in Nursing Homes.
More than 40% of the deaths recorded in the first wave of the SARS-CoV-2 pandemic were linked to nursing homes. Not only are the residents of long-term care facilities (LTCFs) typically older and more susceptible to endemic infections, the facilities' high degree of connection to wider communities makes them especially vulnerable to local COVID-19 outbreaks. In 2008, in the wake of the SARS-CoV-1 and MERS epidemics and anticipating an influenza pandemic, we created a stochastic compartmental model to evaluate the deployment of non-pharmaceutical interventions (NPIs) in LTCFs during influenza epidemics. In that model, the most effective NPI by far was a staff schedule consisting of 5-day duty periods with onsite residence, followed by an 4-to-5 day off-duty period with a 3-day quarantine period just prior to the return to work. Unlike influenza, COVID-19 appears to have significant rates of pre-symptomatic transmission. In this study, we modified our prior modeling framework to include new parameters and a set of NPIs to identify and control the degree of pre-symptomatic transmission. We found that infections, deaths, hospitalizations, and ICU utilization were projected to be high and largely irreducible, even with rigorous application of all defined NPIs, unless pre-symptomatic carriers can be identified and isolated at high rates. We found that increasingly rigorous application of NPIs is likely to significantly decrease the peak of infections; but even with complete isolation of symptomatic persons, and a 50% reduction in silent transmission, the attack rate is projected to be nearly 95%.


Effect of COVID-19 on training and mental health of oral medicine residents in North America.
The objective of this study was to assess resident and faculty perception of the effect of the coronavirus disease 2019 pandemic on the training experience, education, and psychological well-being of oral medicine (OM) residents. An anonymous 16-item online questionnaire was e-mailed to faculty and residents of all Commission on Dental Accreditation-accredited OM residency programs in North America. Survey questions asked about the pandemic's effect on resident educational, clinical, and research activities and the well-being of the residents. Survey data were collected using Qualtrics XM. Forty participants (52.5% residents and 47.5% faculty members) responded to the survey. Regarding the effect on clinical activities, 67.5% reported 50% or less reduction in patient volume seen by residents at its worst during the pandemic. With respect to educational activities, most reported a complete switch of didactic training (85.3%), academic examinations (60%), and off-site resident rotations (45%) to a virtual platform. Research activities were affected the most; 55% reported complete cessation for some time. Thirty-three percent perceived a negative effect, 18% perceived no effect, 11% perceived a positive effect, and 38% were unsure regarding the effect of coronavirus disease 2019 on resident morale. Despite the interruptions in the clinical, research, and educational activities, 62.5% expected on-time resident graduation. Despite constraints due to the pandemic, OM residency programs successfully continued clinical activities, didactic training, and research productivity through virtual means and a hybrid delivery care model while supporting their residents' morale.


Late effects in long-term survivors after treatment for childhood acute leukemia.
This is a report of late effects in childhood cancer survivors seen in the follow-up clinic of a single institution. There were 324 acute leukemia survivors in the database of the Long Term Follow Up Clinic of Children's National Medical Center from January 1, 1997, through June 30, 2005. Of the 324 acute leukemia survivors, 228 were white, 48 black, 20 Hispanic, and 12 other. Their follow-up time was 0 to 25 years (mean 5.3 years). One or more adverse events occurred in 74.1% of the 324 survivors. Defective physical growth was most commonly reported, followed by disturbed neurocognitive function, emotional difficulties, cardiac abnormalities, hypertension, osteoporosis/osteopenia, fractures, and second neoplasms. More black and Hispanic children had acute myeloid leukemia, relapses, cardiac problems, and hypertension than white and other subjects. Childhood cancer survivors require lifelong monitoring, with prompt identification and treatment of adverse late effects.


Interactions of perfluorooctanoic acid with acyl-CoA thioesterase 1 (Acot1).
Perfluorooctanoic acid (PFOA), a typical representative of per- and polyfluoroalkyl substances (PFASs), is a widely utilized persistent organic pollutant (POP) known to induce liver toxicity in laboratory animals and wildlife. Evidence suggests that PFOA interacts with Acyl-CoA thioesterase 1 (Acot1) to modulate levels of β-oxidation. Specifically, PFOA accelerates β-oxidation, while Acot1 is inhibitory. Few studies have investigated the specific relationship between PFOA and Acot1 and the mechanism of their interaction remains unclear. In the following study, purified rat Acot1 protein was synthesized via bacterial recombination and the structural features that facilitate its binding to PFOA were assessed via molecular docking technology. Additionally, through use of circular dichroism spectroscopy (CD) and isothermal titration calorimetry (ITC) we demonstrate that PFOA binds to WT-Acot1 through electrostatic attraction and low strength non-covalent hydrogen bonding at a molar ratio of 1:1. Furthermore, we identify N326 and H373 amino acid residues as key regulators of the binding process. Together, these findings clarify the interaction pattern of PFOA and Acot1 proteins and provide insight into the specific molecular mechanisms that induce PFOA toxicity in humans and animals.


Cross polarization P-31 nuclear magnetic resonance of phospholipids.
P-31 single-pulse and cross-polarization (CP) nuclear magnetic resonance spectra were obtained of aqueous dispersions of pure phospholipids. Dimyristoyl phosphatidylcholine, dipalmitoylphosphatidylcholine, 1-palmitoyl-2-oleoyl phosphatidylcholine, egg phosphatidylcholine, bovine brain sphingomyelin, and transphosphatidylated (from egg phosphatidylcholine) phosphatidylethanolamine were studied. The spectra from all the phospholipids, taken in the usual single-pulse mode, showed the pseudo-axially symmetric powder pattern typical of phospholipids in a hydrated lamellar form. P-31 CP spectra of all the phosphatidylcholines and phosphatidylethanolamine revealed a decrease in intensity in the vicinity of the isotropic chemical shift as long as the lipid was above the gel-to-liquid crystalline phase transition temperature. This intensity pattern has been observed previously for C-13 CP spectra of molecules rotating rapidly about a single well-defined axis (e.g., solid benzene) (Pines, A., M.G. Gibby, and J.S. Waugh, 1973, J. Chem. Phys., 59:569-590). Pure lipid dispersions below their gel-to-liquid crystalline phase transition temperature, including dipalmitoylphosphatidylcholine and sphingomyelin, do not exhibit a local minimum in the CP spectrum at the position of the isotropic chemical shift. Thus, below the phase transition temperature, there is not the same rapid rotation of the headgroup about a well-defined axis. A dramatic change in the rate of headgroup rotation is shown to take place at the pretransition of dipalmitoylphosphatidylcholine. P-31 CP spectra were also obtained for bovine rod outer segment disk membranes, rabbit muscle sarcoplasmic reticulum membranes, a total lipid extract of the latter, and a recombined membrane containing human erythrocyte glycophorin. The CP spectra were similar to the single-pulse spectra, indicating a substantial difference in behavior from pure phospholipid dispersions. This is interpreted in terms of a slower headgroup rotation.


Traditional Chinese medicine extraction method by ethanol delivers drug-like molecules.
Traditional Chinese Medicine (TCM) is an important reservoir for bioactive natural products. TCM extraction methods by water decoction and wine tincture are an integral part of TCM and essential for their widely acknowledged efficacy. In this study, we selected 6 common TCMs that are rich in chemistry to investigate whether the TCM extraction methods deliver molecules with drug-like physical chemical properties. Six TCM herbal materials were extracted by water, 95% ethanol, and sequential hexane, dichloromethane and methanol. The extracts were analyzed by HPLC and 1H NMR. Isolation on one of the extracts yielded 32 compounds, their physical chemical properties were analyzed by Instant JChem. Our results showed that ethanol extraction, which mimics TCM wine tincture, delivered compounds with physical chemical properties compliant to Lipinski's rule of 5.


Migration of objects and inferences across episodes.
Participants viewed episodes in the form of a series of photographs portraying ordinary routines (e.g., eating at a restaurant) and later received a recognition test. In Experiment 1, it was shown that objects (e.g., a vase of flowers, a pewter lantern) that appeared in a single episode during the study phase migrated between memories of episodes described by the same abstract schema (e.g., from Restaurant Episode A at study to Restaurant Episode B at test), and not between episodes anchored by different schemas. In Experiment 2, it was demonstrated that backward causal inferences from one study episode influenced memories of other episodes described by the same schema, and that high-schema-relevant items viewed in one episode were sometimes remembered as having occurred in another episode of the same schematic type.


High-performance AEM unitized regenerative fuel cell using Pt-pyrochlore as bifunctional oxygen electrocatalyst.
The performance of fixed-gas unitized regenerative fuel cells (FG-URFCs) are limited by the bifunctional activity of the oxygen electrocatalyst. It is essential to have a good bifunctional oxygen electrocatalyst which can exhibit high activity for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). In this regard, Pt-Pb2Ru2O7-x is synthesized by depositing Pt on Pb2Ru2O7-x wherein Pt individually exhibits high ORR while Pb2Ru2O7-x shows high OER and moderate ORR activity. Pt-Pb2Ru2O7-x exhibits higher OER (η@10mAcm-2 = 0.25 ± 0.01 V) and ORR (η@-3mAcm-2 = -0.31 ± 0.02 V) activity in comparison to benchmark OER (IrO2, η@10mAcm-2 = 0.35 ± 0.02 V) and ORR (Pt/C, η@-3mAcm-2 = -0.33 ± 0.02 V) electrocatalysts, respectively. Pt-Pb2Ru2O7-x shows a lower bifunctionality index (η@10mAcm-2, OER- η@-3mAcm-2, ORR) of 0.56 V with more symmetric OER-ORR activity profile than both Pt (>1.0 V) and Pb2Ru2O7-x (0.69 V) making it more useful for the AEM (anion exchange membrane) URFC or metal-air battery applications. FG-URFC tested with Pt-Pb2Ru2O7-x and Pt/C as bifunctional oxygen electrocatalyst and bifunctional hydrogen electrocatalyst, respectively, yields a mass-specific current density of 715 ± 11 A/gcat-1 at 1.8 V and 56 ± 2 A/gcat-1 at 0.9 V under electrolyzer mode and fuel-cell mode, respectively. The FG-URFC shows a round-trip efficiency of 75% at 0.1 A/cm-2, underlying improvement in AEM FG-URFC electrocatalyst design.


The citrus flavonoid naringenin stimulates DNA repair in prostate cancer cells.
As part of a systematic study of the effects of phytochemicals beyond antioxidation on cancer prevention, we investigated whether naringenin (NR), a citrus flavonoid, stimulates DNA repair following oxidative damage in LNCaP human prostate cancer cells. The 8-hydroxydeoxyguanosine (8-OH-dG) to deoxyguanosine (dG) ratio was measured after cells were treated with 200 micromol/L of ferrous sulfate in serum-free medium followed by NR exposure for 24 h in growth medium. The results demonstrated that exposure to 10-80 micromol/L of NR led to a significant decrease in the ratio of 8-OH-dG to 10(6) dG. Because cells were treated with NR after ferrous sulfate was removed, we conclude that we demonstrated an effect on DNA repair beyond antioxidation. In support of this conclusion, we determined the induction of mRNA expression over time after oxidative stress followed by NR administration of three major enzymes in the DNA base excision repair (BER) pathway: 8-oxoguanine-DNA glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease and DNA polymerase beta (DNA poly beta). hOGG1 and DNA poly beta mRNA expression in cells after 24-h exposure to NR was increased significantly compared with control cells without NR. The intracellular concentration of NR after exposure to 80 micromol/L was 3 pmol/mg protein, which is physiologically achievable in tissues. In conclusion, the cancer-preventive effects of citrus fruits demonstrated in epidemiological studies may be due in part to stimulation of DNA repair by NR, which by stimulating BER processes may prevent mutagenic changes in prostate cancer cells.


Grade diagnosis of human glioma using Fourier transform infrared microscopy and artificial neural network.
The World Health Organization (WHO) grade diagnosis of cancer is essential for surgical outcomes and patient treatment. Traditional pathological grading diagnosis depends on dyes or other histological approaches, and the result interpretation highly relies on the pathologists, making the process time-consuming (>60 min, including the steps of dewaxing to water and H&E staining), resource-wasting, and labor-intensive. In the present study, we report an alternative workflow that combines the Fourier transform infrared (FTIR) microscopy and artificial neural network (ANN) to diagnose the grade of human glioma in a way that is faster (~20 min, including the processes of sample dewaxing, spectra acquisition and analysis), accurate (the prediction accuracy, specificity and sensitivity can reach above 99%), and without reagent. Moreover, this method is much superior to the common classification method of principal component analysis-linear discriminate analysis (PCA-LDA) (the prediction accuracy, specificity and sensitivity are only 87%, 89% and 86%, respectively). The ANN mainly learned the characteristic region of 800-1800 cm-1 to classify the major histopathologic classes of human glioma. These results demonstrate that the grade diagnosis of human glioma by FTIR microscopy plus ANN can be streamlined, and could serve as a complementary pathway that is independent of the traditional pathology laboratory.


Parental transfer of nanopolystyrene-enhanced tris(1,3-dichloro-2-propyl) phosphate induces transgenerational thyroid disruption in zebrafish.
Plastic is a globally recognized superwaste that can affect human health and wildlife when it accumulates and is amplified in the food chain. Microplastics (plastic particles < 5 mm) and nanoplastics (plastic particles < 100 nm) can interact with organic pollutants already present in the aquatic environment, potentially acting as carriers for pollutants entering organisms and thus influencing the bioavailability and toxicity of those pollutants. In this study, we investigated the transfer kinetics and transgenerational effects of exposure to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and polystyrene nanoplastics (PS-NPs) in F1 offspring. At 90 days postfertilization, zebrafish (Danio rerio) strain AB was exposed to either TDCIPP (0, 0.47, 2.64, or 12.78 μg/L) or PS-NPs (10 mg/L) or their combination for 120 days. The results showed that TDCIPP and PS-NPs accumulated in the gut, gill, head, and liver of the zebrafish in a sex-dependent manner. The presence of PS-NPs promoted the bioaccumulation of TDCIPP in the adult fish and increased the parental transfer of TDCIPP to their offspring. We demonstrate that parental exposure to TDCIPP alone or in combination with PS-NPs induces thyroid disruption in adults, and then leads to thyroid endocrine disruption in their larval offspring. Reduced thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels contributed to the observed transgenerational thyroid dysfunction, which inhibited developmental growth and disturbed the transcription of genes and expression of proteins involved in the hypothalamic-pituitary-thyroid (HPT) axis in the F1 larvae. The increased transfer of TDCIPP to the offspring in the presence of PS-NPs also enhanced transgenerational thyroid endocrine disruption, demonstrated by a further reduction in T4 and the upregulation of thyroglobulin (tg), uridine diphosphate-glucuronosyltransferase (ugt1ab), thyroid-stimulating hormone (tshβ), and thyroid hormone receptor (trα) expression in the F1 larvae compared with the effects of parental TDCIPP exposure alone. Overall, our results indicate that the presence of PS-NPs modifies the bioavailability of TDCIPP and aggravates transgenerational thyroid disruption in zebrafish.


Multiple symptomatic vertebral artery loops treated with posterior cervical fusion.
Multiple symptomatic vertebral artery (VA) loops are rare and their management is challenging. A 55-year-old man presented with a 5-year history of frequent episodes of presyncope and mild left C5 radiculopathy that was exacerbated by flexion or extension of his neck. Examination revealed complex left VA loops at C2/3 and C4. The patient underwent posterior cervical fusion which resolved his presyncope and improved his radiculopathy. Posterior cervical fusion is an option for management of patients suffering from symptoms secondary to multiple VA loops.


Dosimetric uncertainties impact on cell survival curve with low energy proton.
There is an increasing number of radiobiological experiments being conducted with low energy protons (less than 5 MeV) for radiobiological studies due to availability of sub-millimetre focused beam. However, low energy proton has broad microdosimetric spectra which can introduce dosimetric uncertainty. In this work, we quantify the impact of this dosimetric uncertainties on the cell survival curve and how it affects the estimation of the alpha and beta parameters in the LQ formalism. Monte Carlo simulation is used to generate the microdosimetric spectra in a micrometer-sized water sphere under proton irradiation. This is modelled using radiobiological experiment set-up at the Centre of Ion Beam Application (CIBA) in National University of Singapore. Our results show that the microdosimetric spectra can introduce both systematic and random shifts in dose and cell survival; this effect is most pronounced with low energy protons. The alpha and beta uncertainties can be up to 10% and above 30%, respectively for low energy protons passing through thin cell target (about 10 microns). These uncertainties are non-negligible and show that care must be taken in using the cell survival curve and its derived parameters for radiobiological models.


Orbitofrontal Extradural Hematoma: Unusual Cause of Proptosis.
Frontal extradural hematoma (EDH) extending into orbit is an uncommon entity. Clinical presentation can be subacutely progressive proptosis following head injury. We present a case of frontal EDH with orbital extension which had delayed progressive proptosis. The patient improved clinically after surgical evacuation of EDH. It is important to look for orbital roof fractures, orbital hematoma in cases of head injury. Such cases should be treated surgically at the earliest.


Nanocomposites based on halloysite nanotubes and sulphated galactan from red seaweed Gloiopeltis: Properties and delivery capacity of sodium diclofenac.
We developed novel composite films based on biocompatible components, such as halloysite clay nanotubes and sulphated galactan (Funori) from red seaweed Gloiopeltis. The filling of the nanotubes within the sulphated galactan matrix was carried out by a green protocol (aqueous casting method) assuring that Funori/halloysite nanocomposites can be totally considered as sustainable materials. The amount of halloysite in the composites was systematically changed to explore the effects of the nanofiller concentration on the mesoscopic properties of the films. We observed that the halloysite content significantly affects the initial water contact angle and the light attenuation coefficient of the Funori based films. These results were interpreted according to SEM images, which showed that the surface morphologies of the nanocomposites depend on the halloysite amounts filled within the polymeric matrix. The mechanical characterization of the nanocomposites was conducted by tensile experiments performed using a linear stress ramp. Moreover, tensile tests were conducted in oscillatory regime at variable temperature to investigate the viscoelastic properties of the nanocomposites. Finally, we filled the biopolymeric matrix with halloysite nanotubes containing sodium diclofenac. The drug release kinetics from the nanocomposites at variable halloysite contents were studied to evaluate their suitability as oral dissolving films for pharmaceutical applications.


Conducting community rehabilitation review sessions via videoconference: A feasibility study.
To determine the feasibility of conducting a single videoconferencing session (telerehabilitation) instead of a face-to-face home visit for a review appointment in a community rehabilitation program. A feasibility study based on Bowen's framework was used to determine demand, acceptability, limited efficacy and practicality of telerehabilitation. The study involved qualitative and quantitative data analysis. Two Victorian community rehabilitation programs providing services to large geographical catchment zones in the outer fringe of a metropolitan area. Ten adult clients receiving home-based therapy and 5 allied health clinicians working in the program. Clients participated in a single review therapy appointment (telerehabilitation) from physiotherapy, dietetics or speech pathology using the health network's videoconferencing platfrom and the client's own electronic device. Demand was assessed by calculating the percentage of eligible clients able to participate compared to total number of home-based clients. Acceptability, practicality and limited efficacy were explored through qualitative analysis of semi-structured interviews. Nearly one quarter of clients screened met eligibility criteria, indicating a large potential demand for telerehabilitation. Telerehabilitation was highly acceptable for clinicians and clients participating in speech pathology and dietitian sessions as these contain targeted education and talking-based therapy. It was less accepted in physiotherapy, where there is a more hands-on approach. Telerehabilitation was practical and efficient for both clinicians and clients, especially when time was allowed for training and initial troubleshooting. Telerehabilitation is a feasible modality for review sessions in community rehabilitation and helps improve efficient use of clinician and client time. It is more appropriate for disciplines that use education and talking-based therapy compared with hands-on therapy. Older clients are accepting of new technology with support and education.


Purification and properties of sterol carrier protein1.
Previous studies have demonstrated that both the 105,000 X g soluble supernatant (S105) and microsomal membranes from rat liver are required for the enzymatic conversion of squalene to cholesterol (Scallen, T.J., Dean, W.J., and Schuster, M.W. (1968) J. Biol. Chem. 243, 5202). It was postulated that S105 contained a noncatalytic carrier protein which was required for this enzymatic process (Scallen, T. J., Schuster, M.W., and Dhar, A.K. (1971) J. Biol. Chem. 246, 224). Later evidence demonstrated that S105 contained at least two proteins which were required for the microsomal conversion of squalene to cholesterol (Scallen, T.J., Srikantaiah, M.V., Seetharam, B., Hansbury, E., and Gavey, K.L. (1974) Fed. Proc. 33, 1733). This article describes the purification and properties of the first of these soluble proteins, sterol carrier protein1 (SCP1), which has been purified 575-fold from rat liver S105. While SCP1 specifically activated the enzymatic conversion of squalene to lanosterol by liver microsomal membranes, SCP1 possessed no capacity to activate the microsomal conversion of [3H-A14,4-dimethyl-delta8-cholestenol to C27 sterols or of [3H]7-dehydrocholesterol to cholesterol. Lanosterol was identified by silicic acid chromatography and mass spectrometry. The formation of lanosterol was a hyperbolic function of the concentration of SCP1 present in the incubation mixture. The Km observed for SCP1 was similar to the Km observed for squalene. The formation of lanosterol from squalene required FAD. The addition of phosphatidylserine increased enzymatic activity; however, phosphatidylserine was not required for this conversion. SCP1 was catalytically inactive when it was incubated with [3H] squalene and cofactors in the absence of microsomes. Substantial evidence supports the hypothesis that SCP1 operates as a noncatalytic carrier protein for the water-insoluble substrate squalene in the enzymatic conversion of squalene to lanosterol by liver microsomal membranes.


Is mean platelet volume a better biomarker in pre-eclampsia?
Platelet activation and destruction is a well recognized feature of pre-eclampsia, but the current literature is contradictory regarding the role of mean platelet volume (MPV) in the diagnosis of this condition. We investigated whether MPV, compared with other routine laboratory markers such as platelet count, is a more significant biomarker of pre-eclampsia, giving special attention to the intrapartum period. Biochemical and hematological markers along pregnancy including MPV were compared retrospectively between pre-eclampsia and matched controls. Laboratory marker data were compared using independent t-test. A logistic regression model was used to compare the strength of the associations of MPV and other routine markers such as platelet count with pre-eclampsia. Receiver operating characteristic curves were plotted. There were a total of 150 cases of pre-eclampsia and 297 controls. In the pre-eclampsia group, there were 60 cases of mild pre-eclampsia (40.0%); 84, severe (56.0%); and six of eclampsia (4.0%). MPV was significantly higher in the pre-eclampsia than in the control group (11.3 ± 1.0 vs 10.1 ± 0.8 fL, P = 0.002). On multivariate analysis, MPV was the only statistically significant biomarker of pre-eclampsia (OR, 4.5; 95%CI: 1.5-13.7), and severe pre-eclampsia (OR, 6.2; 95%CI: 1.6-24.6); performing superiorly to platelet count. Mean platelet volume is a more significant biomarker of pre-eclampsia. It is more significantly associated with this condition than other routinely measured laboratory markers such as platelet count. MPV is routinely obtained on complete blood cell count and its utilization in the assessment of pre-eclampsia in a clinical setting should continue to be evaluated.


Early opening of sarcolemmal ATP-sensitive potassium channels is not a key step in PKC-mediated cardioprotection.
ATP-sensitive potassium (KATP) channels are abundantly expressed in the myocardium. Although a definitive role for the channel remains elusive they have been implicated in the phenomenon of cardioprotection, but the precise mechanism is unclear. We set out to test the hypothesis that the channel protects by opening early during ischemia to shorten action potential duration and reduce electrical excitability thus sparing intracellular ATP. This could reduce reperfusion injury by improving calcium homeostasis. Using a combination of contractile function analysis, calcium fluorescence imaging and patch clamp electrophysiology in cardiomyocytes isolated from adult male Wistar rats, we demonstrated that the opening of sarcolemmal KATP channels was markedly delayed after cardioprotective treatments: ischemic preconditioning, adenosine and PMA. This was due to the preservation of intracellular ATP for longer during simulated ischemia therefore maintaining sarcolemmal KATP channels in the closed state for longer. As the simulated ischemia progressed, KATP channels opened to cause contractile, calcium transient and action potential failure; however there was no indication of any channel activity early during simulated ischemia to impart an energy sparing hyperpolarization or action potential shortening. We present compelling evidence to demonstrate that an early opening of sarcolemmal KATP channels during simulated ischemia is not part of the protective mechanism imparted by ischemic preconditioning or other PKC-dependent cardioprotective stimuli. On the contrary, channel opening was actually delayed. We conclude that sarcolemmal KATP channel opening is a consequence of ATP depletion, not a primary mechanism of ATP preservation in these cells.


An exploration of the frequency, location, and content of parents' health- and weight-focused conversations with their children and associations with child weight status.
Although parental weight-focused conversations with children have been associated with more unhealthy weight and weight-related outcomes in children and adolescents, little is known about the content and context of these conversations or conversations about healthy eating in the home environment. This study examines the frequency, location, and content of health- and weight-focused conversations in the home environment and examines the association between specific types of health- and weight-focused conversations with child overweight status. Mixed-methods data were collected from parents of children from primarily low-income, minority homes (n = 110). Quantitative data included the frequency and location (i.e., "the context") of different types of health- and weight-focused conversations, while open-ended, write-in survey questions investigated "the content" of these conversations. Parents reported having more health-focused conversations with their child compared to weight-focused conversations; parents of children who were overweight had more frequent health- and weight-focused conversations than parents of children who were not overweight. The most frequent location for these conversations was during a family meal. In addition, parental health- and weight-focused conversations were more common with overweight children (p < 0.05). Open-ended, write-in responses from parents for both health- and weight-focused conversations included conversations about moderation/portion control, unhealthy foods, and healthy foods. Open-ended, write-in results suggested that parental conversations about healthy eating were similar to conversations about weight. Results of this mixed-methods study provide an incremental next step in better understanding the nature of parental health- and weight-focused conversations with children.


Quality assessment and tracking results of cardiac surgery.
Long-standing efforts to assess quality in medical care have been intensified by the striking expansion of managed care plans. Agencies such as the Joint Commission on Accreditation of Health Care Organizations and the National Committee on Quality Assurance have formalized the evaluation of health plan quality using criteria of structure, process, and outcome. A review of attempts to apply these criteria to individual physicians and to disease-specific interventions such as myocardial revascularization demonstrates the great difficulty of reliable quality assessment in this evolving surgical field. Cardiac surgeons must continue their work in deriving valid socioeconomic and clinical conclusions from The Society of Thoracic Surgeons and Veterans Affairs databases. This may prevent the precipitate adoption of newer treatment methods driven by entrepreneurial technology companies and large group purchasers of care. These entities tend to focus on economics rather than patient welfare. New technologies may also delude patients into insisting on treatment featuring short-term convenience and comfort despite less satisfactory long-term results. "Black box" methodology providing practice profiles and physician report cards must have critical validation.


Clinical outcomes, survivorship and adverse events with mobile-bearings versus fixed-bearings in hip arthroplasty-a prospective comparative cohort study of 143 ADM versus 130 trident cups at 2 to 6-year follow-up.
The principle of dual mobility cups, often called "tripolar", has been developed to overcome the problem of instability following primary hip arthroplasty. We prospectively compared two cohorts which differed only by the type of bearings, i.e." mobile bearing hip" (MBH) in a 143-study cohort of ADM cups versus "fixed bearing hip" (FBH) of 130 Trident PSL cups, at a follow-up at 2-6years. The survival rates at 4.13-years, with instability as endpoint was significantly (P=0.0176) in favor of mobile bearings at 100% with no dislocation reported, versus 94.8% with fixed bearings. These mobile bearings, matching both "modern" dual mobility cups and annealed highly crossed polyethylene, would appear to offer at longer follow-up a valuable solution to clinical outcomes in acetabular arthroplasty.


An innovative technique of chest wall stabilization and reconstruction in traumatic flail chest: The figure-of-eight suture with polypropylene mesh and musculofascial flap.
Surgical stabilization of the flail chest is challenging and has no established guidelines. Chest wall integrity and stability are the main factors that ensure the protection of intrathoracic organs and an adequate respiratory function. Here, we report a novel chest wall reconstruction technique in a 45-year-old man with a traumatic left flail chest and open pneumothorax diagnosed both clinically and radiographically. Rib approximation and chest wall reconstruction was done using intercostal figure-of-eight suture and polypropylene mesh with vascularized musculofascial flap. The patient improved gradually and was discharged after three weeks of total hospital stay. He returned to regular working after a month with no evidence of respiratory distress or paradoxical chest movement. Follow-up visit at one year revealed no lung hernia or paradoxical chest movement. This is a novel, feasible and cost-effective modification of chest wall reconstruction that can be adopted for thoracic wall repair in case of open flail chest, which needs emergency surgical interventions even in resource constraint settings.


Neonatal hemochromatosis: diagnostic work-up based on a series of 56 cases of fetal death and neonatal liver failure.
To define an algorithm to improve diagnosis of neonatal hemochromatosis (NH) related to gestational alloimmune liver disease (GALD), which is diagnosed by immunohistochemistry demonstrating activated complement at hepatocytes (IDACH). We assessed 56 instances of fetal death or neonatal liver failure (NLF; 2006-2009), 29 (7 stillborns, 22 NLF) with NH, and 27 (5 stillborns, 22 NLF) without NH (non-NH). Immunohistochemistry was retrospectively performed in 21 cases. Cases were grouped as follows: (1) GALD as demonstrated by IDACH (n = 17); (2) indeterminate for GALD (n = 28); or (3) alternate diagnosis found (n = 11). We compared cases of immunohistochemically proven GALD with those with an alternate diagnosis. Of the 12 stillborns, 7 had NH because of GALD (NH-GALD), one was undeterminate, and 4 had alternate diagnoses (GALD excluded). Of the 22 newborns with NH, 6 had NH-GALD, one had mitochondrial respiratory chain disorder (MRCD), and 15 were indeterminate for GALD. Of 22 non-NH newborns, extrahepatic siderosis (EHS) was not assessed in 13 (3 GALD, 1 alternate diagnosis [MRCD] and 9 indeterminate GALD) and excluded in 9 (5 alternate diagnoses and 4 indeterminate GALD). The only clinical features found to be associated with GALD were intrafamilial recurrence, prematurity, and EHS. In unexplained fetal death or NLF, the diagnosis of subsets of NH requires tissue analysis (autopsy) to assess EHS. In patients with NH, if MRCD is ruled out, NH-GALD is likely. The rate of IDACH in the diagnosis of GALD in cases without NH requires further study.


Genetic factors regulate processes related to anxiety in mice.
The propensity for anxiety-related behavior has been studied by comparing two highly inbred strains of mice, ABP/Le and C57BL/6ByJ, in two behavioral procedures, open-field and light-dark preference. Their Mendelian F2 population allowed us to evaluate the putative involvement of four easily identifiable loci in anxiogenic processes. In fact, chromosomal regions containing the brown, pink-eyed dilution and short-ear loci on the 4th, 7th and 9th chromosomes respectively are associated with anxiety-related behavior patterns. In addition, binding of [3H]flumazenil to brain GABA(A) receptors was measured as a biochemical index that may be associated with observed behavior patterns.


A registration-and-fixation approach with handpiece adjustment for dynamic navigation in dental implant surgery.
The deviations between the preoperative (planned) and postoperative (actual) positions of dental implants have always been of a major concern in dental implant surgery. Dynamic computer-aided implant surgery (dCAIS) systems have been used to achieve optimal implant positioning. The method of registration is indeed an important factor that affects the implanting accuracy. Here, we propose a fast and concise registration method using a registration-and-fixation device as well as an adjustable handpiece for dynamic navigation in dental implant surgery. To the best of our knowledge, our work is the first study of such a registration method for dynamic navigation in a dental implant system.


High human herpesvirus 8 seroprevalence in populations from Western Balkan countries.
Patterns of endemicity of human herpesvirus 8 (HHV8) are still undefined in some European populations, such as those from Western Balkan countries. Serum samples from 605 human immunodeficiency virus-seronegative subjects (299 Albanians and 306 Kosovars) were tested for the presence of HHV8 antibodies to a capsid-related open reading frame (ORF65)-encoded protein and a latency-associated nuclear antigen (LANA) to determine HHV8 seroprevalence in populations from Albania and from the Kosovo region of former Yugoslavia. Levels of co- circulation with hepatitis A (HAV) and hepatitis B (HBV) viruses were also determined. HHV8 antibodies to at least one of the two antigens were detected in 28.8% of Albanians and 18% of Kosovars. The seroprevalence of HHV8 was found to be 25.0 and 16.8% in Albanian and Kosovar children (<or=15 years old), respectively. No association was found between HHV8 seropositivity and serological markers for hepatitis A (total anti-HAV) and hepatitis B (antibodies to the core antigen). HHV8 infection is widespread among Albanians and Kosovars, as is the case in populations of the Mediterranean basin. The high HHV8 seroprevalence observed in children as well as the lack of correlation with HAV and HBV infections suggest that intrafamilial, non-fecal-oral, and non-parenteral routes of HHV8 transmission may also be predominant in some populations from the Western Balkan countries.


Nanomaterials based surface plasmon resonance signal enhancement for detection of environmental pollutions.
Due to the nearby relationship between human health, socioeconomic development and environmental pollution, the detection and identification of environmental pollutants need more attention. Therefore, the development of suitable analytical devices that are sensitive, specific, precise, quick, and easy-to-use are required to resolve the increased request for legislative action on environmental pollution control and early detection of rising pollutants. Currently, the development of biosensing instruments attracted important attention because of their high selectivity, sensitivity, simplicity, reliability, low-cost and real-time response. Surface plasmon resonance (SPR) sensor as an example of portable, rapid, and smart biosensing devices widely used for qualitative and quantitative detection of multiplexed pollutant in real-time. Thus, SPR principles, assay formats, surface modification methods and signal enhancement are summarized in this review. Moreover, applications of SPR in the detection of pesticide, polycyclic aromatic hydrocarbons (PAHs), heavy metals and polychlorinated biphenyls (PCBs) over the past decade is discussed.


Aym1, a mouse meiotic gene identified by virtue of its ability to activate early meiotic genes in the yeast Saccharomyces cerevisiae.
Our understanding of the molecular mechanisms that operate during differentiation of mitotically dividing spermatogonia cells into spermatocytes lags way behind what is known about other differentiating systems. Given the evolutionary conservation of the meiotic process, we screened for mouse proteins that could specifically activate early meiotic promoters in Saccharomyces cerevisiae yeast cells, when fused to the Gal4 activation domain (Gal4AD). Our screen yielded the Aym1 gene that encodes a short peptide of 45 amino acids. We show that a Gal4AD-AYM1 fusion protein activates expression of reporter genes through the promoters of the early meiosis-specific genes IME2 and HOP1, and that this activation is dependent on the DNA-binding protein Ume6. Aym1 is transcribed predominantly in mouse primary spermatocytes and in gonads of female embryos undergoing the corresponding meiotic divisions. Aym1 immunolocalized to nuclei of primary spermatocytes and oocytes and to specific type A spermatogonia cells, suggesting it might play a role in the processes leading to meiotic competence. The potential functional relationship between AYM1 and yeast proteins that regulate expression of early meiotic genes is discussed.


Whole exome sequencing identifies three novel gene mutations in patients with the triad of diabetic ketoacidosis, hypertriglyceridemia, and acute pancreatitis.
This study aimed to analyze the genetics and treatments of the patients with the triad of diabetic ketoacidosis (DKA), hypertriglyceridemia, and acute pancreatitis (AP). We conducted a retrospective study of six patients with the triad of AP, hypertriglyceridemia, and DKA at our hospital. All patients underwent plasmapheresis as part of their treatment. The clinical characteristics of the patients were obtained from the hospital information system and analyzed. Whole exome sequencing was performed using samples of one patient (case 6) and his family members. The average triglyceride level before plasmapheresis was 3282.17 ± 2975.43 mg/dL (range: 1646-9332 mg/dL). The triglyceride levels dropped by approximately 80% after plasmapheresis. None of the patients developed complications related from plasmapheresis. During follow-up, patients 5 and 6 developed recurrent pancreatitis for several times and showed the formation of pancreatic pseudocysts. We identified three novel heterozygous missense mutations in the family of patient 6, including c.12614C > T (p.Pro4205Leu) in APOB, c.160G > C (p.Glu54Gln) in CILP2, and c.1199C > A (p.Ala400Glu) in PEPD. Three novel heterozygous missense mutations, including c.12614C > T (p.Pro4205Leu) in APOB, c.160G > C (p.Glu54Gln) in CILP2, and c.1199C > A (p.Ala400Glu) in PEPD were first identified in a patient with the triad of DKA, hypertriglyceridemia, and AP. The combination of plasmapheresis, hydration, and insulin therapy may have the greatest clinical benefits for these patients.


The impact of a universal human papilloma virus (HPV) vaccination program on lower genital tract dysplasia and genital warts.
Assess Ontario's school-based human papillomavirus (HPV) vaccination program on reducing rates of cervical dysplasia, colposcopy services and treatment for genital warts, cervical conization, cryotherapy and laser vaporization of the lower genital tract. Women born in 1995 in Ontario, Canada were the first cohort of students to receive the vaccine. We followed these women from age 18-23 and identified pap test cytology results, referral and attendance at colposcopy, treatment of HPV related warts and treatment of lower-genital tract dysplasia using administrative databases. We compared the incidence of these outcomes to women born in 1985, followed during the same age period prior to access to the HPV vaccine. We calculated relative risk ratios for all outcomes over the 5-year period for the unvaccinated group compared to the vaccinated group. Results were stratified at the income and geographic level. A total of 221,039 women were included. Among vaccinated women, 5.2% percent had cytologic abnormalities and 2.7% required treatment for pre-invasive disease or warts compared to 9.2% and 5.2%, respectively among unvaccinated women. The relative risk of developing a low-grade cytologic abnormality if unvaccinated was 1.69 and 3.74 for high-grade abnormalities. The relative risk of requiring colposcopy if unvaccinated was 1.94 and they were 6.15 times more likely to require treatment. There were no differences between socio-economic groups and geographic regions. Vaccination programs are effective at decreasing rates of cervical dysplasia, lead to reduced need for colposcopy, treatment of HPV related warts and pre-invasive disease even at early ages.


Recommendations and Clinical Validation of Inguinal Clinical Target Volume Delineation in Penile Cancer.
This study determined the patterns of distribution of inguinal nodes and the optimal margin needed around the femoral vessels to propose guidelines for inguinal clinical target volume (CTV) delineation in penile cancer. Patients with biopsy-proven penile squamous cell carcinoma with inguinal node metastases were identified on a computed tomography scan. Distribution of nodes and distance of nodes to the nearest femoral vessel and inferior edge of pubic symphysis (IPS) were obtained. A 3-dimensional CTV margin to cover 95% of the nodes was estimated to evolve contouring guidelines. A comprehensive contouring guide with a visual atlas for inguinal CTV delineation was created. The proposed CTV was prospectively validated in 14 consecutive patients with penile squamous cell carcinoma treated with post-operative radiation therapy to the inguino-femoral region. Of the 222 inguinal lymph nodes analyzed in 33 patients, 99% were located anterior (81% antero-medial, 18% antero-lateral) to femoral vessels. A majority (95%) of the antero-laterally located nodes were superior to IPS. Margin around the femoral vessels to cover 95% of the nodes for supra-IPS region in anterior, medial, and lateral directions was 29, 23, and 21 mm, respectively, and for infra-IPS region in anterior and medial directions was 21 and 23 mm, respectively. Cranial and caudal extent of CTV delineation with respect to IPS was at 48 and 50 mm, respectively for 95% nodal coverage. On prospective validation, after a median follow-up of 24 months (range, 5-31), none of the patients developed marginal recurrences. Grade 1 and grade 2 lymphedema was seen in 6 (42.8%) and 4 (28.5%) patients, respectively. This study analyzed pattern of distribution of inguinal nodes and proposes guidelines for inguinal CTV delineation in penile cancer. The proposed guidelines were validated prospectively in a small cohort of patients and found to be implementable and safe.


Study of distribution and interaction of arsenic and selenium in rat thyroid.
Seventy-eight Wistar weanling rats were pretreated with arsenate (100 mg/L As), selenite (1 mg/L Se), and arsenate (100 mg/L As) plus selenite (1 mg/L Se) added to the drinking water. After 4 w, all the animals were sacrificed and serum T3 and T4 were determined by double-antibody radioimmunoassay. Thyroid tissue concentrations of As and Se were determined in female rats by neutron activation analysis, and tissue specimens were examined histopathologically. For both sexes, the measurements indicated that T4/T3 was lowest in the Se group, intermediate in the As group, and highest in the controls. Corrected for the mean value of the controls, mean As concentration of thyroid tissue was of the same magnitude in the group pretreated with As + Se as the sum of the mean As concentration in the groups pretreated with As or Se alone. The outcome was symmetric with regard to the Se concentration: In the As + Se pretreated group, the mean Se concentration was of the same magnitude as the sum of the mean Se concentration in the groups pretreated with As or Se alone. Thus, As and Se tended to accumulate in the thyroid tissue. Postmortem examination showed that the thyroid tissue of rats pretreated with As alone exhibited obvious, toxic changes, whereas only minor or no changes were found in the tissues of the groups pretreated with Se or As + Se, and in the tissues of the controls. Multivariate analyses demonstrated that s-T4 and s-T3 were significantly correlated with sex, that s-T3 was positively correlated (p < or = 0.001) with Se pretreatment, and that the T4/T3 ratio was negatively correlated with both As (p < or = 0.012) and Se pretreatment (p < or = 0.001). The results were discussed in relation to the cancer preventive effect of Se.


Small-angle neutron scattering of long-wavelength magnetic modulations in reduced sample dimensions.
Magnetic small-angle neutron scattering (SANS) is ideally suited to providing direct reciprocal-space information on long-wavelength magnetic modulations, such as helicoids, solitons, merons or skyrmions. SANS of such structures in thin films or micro-structured bulk materials is strongly limited by the tiny scattering volume vis a vis the prohibitively high background scattering by the substrate and support structures. Considering near-surface scattering just above the critical angle of reflection, where unwanted signal contributions due to substrate or support structures become very small, it is established that the scattering patterns of the helical, conical, skyrmion lattice and fluctuation-disordered phases in a polished bulk sample of MnSi are equivalent for conventional transmission and near-surface SANS geometries. This motivates the prediction of a complete repository of scattering patterns expected for thin films in the near-surface SANS geometry for each orientation of the magnetic order with respect to the scattering plane.


Determination of dose enhancement caused by AuNPs with Xoft® Axxent® Electronic (eBx™) and conventional brachytherapy: in vitro study.
The purpose of this study was to determine dose enhancement (DE) and the possible clinical benefits associated with the inclusion of gold nanoparticles (AuNPs) in cancer cells irradiated by either an 192Ir brachytherapy source or a Xoft® Axxent® Electronic (eBx™) Brachytherapy. Brachytherapy DE caused by AuNPs is investigated using two methods, namely 192Ir and eBx™ Brachytherapy. The second method, which was recently introduced clinically, operates at ~50 kV, which is also the optimal beam energy for DE. In this in vitro study, two cancer cell lines, lung (A549) and prostate (DU145), were used. Cells were incubated with 1 mM (2% w/w) concentration of AuNPs of ~15 nm in size. The control groups were exposed to a range of doses from 0 (control) to 6 Gy, with eBx™ and 192Ir sources separately. A clonogenic assay was conducted to determine cell survival curves. High dose enhancement factor (DEF) values were achieved in treated groups with low concentration of AuNPs with the 50 kV energy associated with the eBx™. The DE levels in eBx™ for Du145 and A549 cells were found to be 2.90 and 2.06, respectively. The results showed DEFs measured for the same cell lines using 192Ir brachytherapy to be 1.67 and 1.54 for Du145 and A549 cancer cells, respectively. This clearly indicates that much higher DE values are obtained in the case of eBx™ X-ray brachytherapy compared to 192Ir gamma brachytherapy. The higher DE values obtained with eBx™ compared to 192Ir brachytherapy can be attributed to the lower average energy of the former and being closer to the optimal energy for DE. This could potentially be utilized by medical practitioners and clinicians to achieve the same tumor control with a significantly lower dose from the eBx™ compared to the 192Ir brachytherapy treatment, thus bringing huge benefits to the brachytherapy-treated patients.


Stem cell fate in hypoxic root apical meristems is influenced by phytoglobin expression.
Root survival to flooding-induced hypoxic stress is dependent upon maintaining the functionality of the root apical meristem quiescent center (QC), a process that is governed by the basipetal flow of auxin leading to the formation of an auxin maximum, which is needed for the establishment of a highly oxidized environment specifying the QC niche. Perturbations in auxin flow and distribution along the root profile occurring during hypoxia can shift the redox state of the QC towards a more reduced environment, leading to the activation of the QC, degradation of the meristem, and root abortion. The maize phytoglobin gene ZmPgb1.1 is involved in minimizing these damaging effects during hypoxia in processes that result in sustaining the PIN-mediated auxin maximum and an oxidized environment in the QC. The oxidized environment is accomplished by maintaining the activity of redox enzymes oxidizing ascorbate and glutathione. These events, compromised in QCs suppressing ZmPgb1.1, ensure the functionality of the QC and root meristems under conditions of low oxygen, resulting in stable root performance.


Influence of copper on the early post-implantation mouse embryo: An in vivo and in vitro study.
Female mice were injected intravenously with copper sulphate on either the 7th day (early egg cylinder stage of development), the 8th day (late egg cylinder stage), or the 9th day (early somite stage of development), and examined on the 10th day of gestation. Injection on the 7th day was found to be embryo-lethal; when females were injected on the 8th day, the majority of the surviving embryos exhibited anomalies of the neural tube and/or the heart, while injection on the 9th day resulted in a very low incidence of anomalies. The most common malformations seen on the 10th day involved failure of closure of the neural tube in the head region of the embryo, and various types of anomalies of cardiac rotation and shape. When additional females injected on the 8th day were examined on the 12th day, a high proportion of the fetuses examined had developed exencephaly.A further group of embryos from untreated females were explanted on the 9th day and cultured in vitro in various concentrations of copper sulphate. The lowest levels tested had little obvious effect on neural tube closure. Intermediate doses resulted in, retarded and anomalous embryonic development, while the highest levels employed resulted in neural tube and cardiac anomalies similar to those produced in vivo.The results demonstrate both the direct toxic effect of copper on embryonic development and that the stage of embryonic development at the time of exposure determines both the nature and the extent of the effect.


[Evaluation of the urinary tract in children with renal agenesis].
The condition of urinary tract in 24 children with kidney agenesia was estimated. 14 out of 24 children had additionally renal abnormalities or different renal diseases. It was detected that more than 50% of patients developed chronic failure of this single kidney, but renal function of normal single kidney remains many years correct.


Balloon Bronchoplasty for the Treatment of Bronchial Stenosis After Lung Transplantation: A Single-Center 10-Year Experience.
To assess the safety and efficacy of balloon dilatation under dual guidance using fluoroscopy and bronchoscopy for treating bronchial stenosis following lung transplantation (LT), and to elucidate the factors associated with patency after the procedure. From September, 2012, to April, 2021, 50 patients (mean age ± standard deviation, 54.4 ± 12.2 years) with bronchial stenosis among 361 recipients of LT were retrospectively analyzed. The safety of balloon dilatation was assessed by evaluating procedure-related complications. Efficacy was assessed by evaluating the technical success, primary patency, and secondary patency. Primary and secondary cumulative patency rates were calculated using the Kaplan-Meier method. The factors associated with patency after the procedure were evaluated using multivariable Cox hazard proportional regression analysis. In total, 65 bronchi were treated with balloon dilatation in 50 patients. The total number of treatment sessions was 277 and the technical success rate was 99.3% (275/277 sessions). No major procedure-related complications were noted. During the mean follow-up period of 34.6 ± 30.8 months, primary patency was achieved in 12 of 65 bronchi (18.5%). However, the patency rate improved to 76.9% (50 of 65 bronchi) after repeated balloon dilatation (secondary patency). The 6-month, 1-year, 3-year, and 5-year secondary patency rates were 95.4%, 90.8%, 83.1%, and 78.5%, respectively. The presence of clinical symptoms was a significant prognostic factor associated with reduced primary patency (adjusted hazard ratio [HR], 0.465; 95% confidence interval [CI], 0.220-0.987). Early-stage treatment ≤ 6 months (adjusted HR, 3.588; 95% CI, 1.093-11.780) and prolonged balloon dilatation > 5 min (adjusted HR, 3.285; 95% CI, 1.018-10.598) were associated with significantly higher secondary patency. Repeated balloon dilatation was determined to be safe and effective for treating bronchial stenosis following LT. Early-stage treatment and prolonged balloon dilatation could significantly promote long-term patency.


Morphine-induced tail erection: site of action.
Acute ablation techniques were used to localize morphine-induced tail erection (MITE) within the central nervous system of mice. Morphine produced no elevation of tails in mice whose spinal cord had been transected at the lower thoracic or lumbar levels. Decortication and high-level precollicular decerebration did not prevent MITE while morphine caused no tail response at all in low-level inferior collicular decerebrate mice. Lesions in various portions of the mesencephalon revealed that the degree of MITE was closely related to the size of the lesions of the central gray matter. The larger the lesion, the smaller the degree of tail elevation. MITE could not be elicited in mice when the mesencephalic central gray matter had been completely destroyed. Results indicate that morphine acts on the mesencephalic central gray matter producing tail erection and the pathway responsible for the reaction descends from the midbrain downward to the spinal cord.


Temporal-Spatial-Color Multiresolved Chemiluminescence Imaging for Multiplex Immunoassays Using a Smartphone Coupled with Microfluidic Chip.
Chemiluminescence (CL) bioassays have become a main technology in clinical diagnosis. However, multiplex analysis for sensitive and simultaneous determination of multiple biomarkers related to one disease in one detection run on a single chip in order to achieve fast and accurate diagnosis of diseases remains a great challenge. Herein, we report temporal-spatial-color multiresolved CL imaging strategy for multiplex label-free immunoassays using a smartphone coupled with a microfluidic chip. Temporal-spatial-color multiresolved CL imaging signals were produced by sequentially transporting coreactant H2O2 to the detection zones to initiate cobalt-based zeolitic imidazolate frameworks ZIF-67 catalyzed luminol-H2O2 CL and CL resonance energy transfer reactions. As proof-of-concept, a ZIF-67 regulated sensing strategy was developed for multiplex analysis of three model cancer biomarkers with a low detection limit of pg/mL to fg/mL, good selectivity, and low-cost, avoiding complicated labeling procedures and interferences from adjacent detection zones. This work opens a door for temporal-spatial-color multiresolved imaging for multiplex analysis.


Factors influencing psychosocial adjustment to forced geographical relocation: the Israeli withdrawal from the Sinai.
The evacuation of an Israeli community in the Sinai peninsula afforded an unusual opportunity to study the relationships among individual coping styles, social network characteristics, and parameters of psychosocial adjustment manifested by community residents immediately prior to their forced relocation. Key variables affecting adjustment are highlighted and directions for future research are suggested.


Self-Perception of Teeth Alignment and Colour in Adolescents: A Cross-sectional Study.
This study aimed to evaluate the prevalence and factors associated with self-perception of teeth alignment and colour in adolescents. This cross-sectional study was carried out in public and private schools in Passo Fundo, Brazil. A representative sample of students aged 15 to 19 years were included. The outcome of this study was self-perception of teeth alignment and colour according to selected items from a structured and validated questionnaire (the Child's and Parent's Questionnaire about Teeth Appearance). Bivariate and multivariable analysis, using Poisson regression with robust variance, were used. A P value <.05 was established for statistical significance. The study included 736 adolescents. The worst self-perception of teeth alignment and colour was observed in 46.5% (n = 342) of the adolescents. Nonsmokers presented a prevalence ratio (PR) 29% lower (95% CI, 0.57-0.89) for the worst self-perception of teeth alignment and colour when compared to smokers/former smokers. Adolescents with highly educated mothers presented a lower prevalence of negative self-perception than those with mothers with a low level of education (PR: 0.66; 95% CI, 0.51-0.86). Presence of orthodontic treatment with (PR: 0.76; 95% CI, 0.62-0.94) or without (PR: 0.61; 95% CI, 0.46-0.76) tooth whitening were associated with better self-perception of teeth alignment and colour. Exposure to smoking and lower maternal level of education were associated with worse self-perception of teeth alignment and colour in adolescents. A history of orthodontic treatment with or without tooth whitening was associated with a lower concern with aesthetics.


Deep-Sea Misconceptions Cause Underestimation of Seabed-Mining Impacts.
Scientific misconceptions are likely leading to miscalculations of the environmental impacts of deep-seabed mining. These result from underestimating mining footprints relative to habitats targeted and poor understanding of the sensitivity, biodiversity, and dynamics of deep-sea ecosystems. Addressing these misconceptions and knowledge gaps is needed for effective management of deep-seabed mining.


Sense of responsibility in ICU end-of-life decision-making: Relatives' experiences.
Relatives of intensive care unit patients who lack or have reduced capacity to consent are entitled to information and participation in decision-making together with the patient. Practice varies with legislation in different countries. In Norway, crucial decisions such as withdrawing treatment are made by clinicians, usually morally justified to relatives with reference to the principle of non-maleficence. The relatives should, however, be consulted about whether they know what the patient would have wished in the situation. To examine and describe relatives' experiences of responsibility in the intensive care unit decision-making process. A secondary analysis of interviews with bereaved relatives of intensive care unit patients was performed, using a narrative analytical approach. In all, 27 relatives of 21 deceased intensive care unit patients were interviewed about their experiences from the end-of-life decision-making process. Most interviews took place in the participants' homes, 3-12 months after the patient's death. Based on informed consent, the study was approved by the Data Protection Official of the Norwegian Social Science Data Services and by the Regional Committee for Medical and Health Research Ethics. The results show that intensive care unit relatives experienced a sense of responsibility in the decision-making process, independently of clinicians' intention of sparing them. Some found this troublesome. Three different variants of participation were revealed, ranging from paternalism to a more active role for relatives. For the study participants, the sense of responsibility reflects the fact that ethics and responsibility are grounded in the individual's relationship to other people. Relatives need to be included in a continuous dialogue over time to understand decisions and responsibility. Nurses and physicians should acknowledge and address relatives' sense of responsibility, include them in regular dialogue and help them separate their responsibility from that of the clinicians.