The epidemiological trend of monkeypox and monkeypox-varicella zoster viruses co-infection in North-Eastern Nigeria.
Monkeypox (MPX) is endemic in Nigeria, but it was first reported in Adamawa state, North-Eastern Nigeria, in January 2022. There are currently 172 cases of MPX in Nigeria, with four reported deaths, and Adamawa has the second-highest case count. Therefore, this study was undertaken to evaluate the epidemiological profile of this viral disease. This is a cross-sectional study. The skin and blood samples were screened for the presence for Monkeypox virus (MPXV) and Varicella Zoster virus (VZV) DNA by real-time PCR; the clinical diagnosis was based on symptoms of visual signs of skin lesions and other clinical symptoms from January to July 2022. A total of 33 suspected cases aged 1-57 years [26 (79%) males vs. 7 (21%) females] were screened for MPX and VZV. Twenty-four (72.7%) were positive (6.1% were MPX only, 39% were VZV only, and 27% were both MPX and VZV). Most cases of MPX (82%), VZV (69%) and MPX-VZV co-infection (78%) occurred in males. More than half (54%) of those infected were children and adolescents between 0 and 19 years. All patients experienced body rashes and itching, and other clinical symptoms included fever, headache, mouth sores, muscle aches and lymphadenopathy. Over 64 and 86% of patients had contact with livestock and rodents, respectively. MPXV, VZV and MPXV-VZV co-infections occurred predominantly among males and children in Adamawa state, Nigeria. Given the patient contact with rodents and livestock, further research on the animal reservoir is needed to highlight the transmission of MPXV in Adamawa.


FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome.
Mutations in FBXL4 have recently been recognized to cause a mitochondrial disorder, with clinical features including early onset lactic acidosis, hypotonia, and developmental delay. FBXL4 sequence analysis was performed in 808 subjects suspected to have a mitochondrial disorder. In addition, 28 samples from patients with early onset of lactic acidosis, but without identifiable mutations in 192 genes known to cause mitochondrial diseases, were examined for FBXL4 mutations. Definitive diagnosis was made in 10 new subjects with a total of 7 novel deleterious variants; 5 null and 2 missense substitutions. All patients exhibited congenital lactic acidemia, most of them with severe encephalopathic presentation, and global developmental delay. Overall, FBXL4 defects account for at least 0.7% (6 out of 808) of subjects suspected to have a mitochondrial disorder, and as high as 14.3% (4 out of 28) in young children with congenital lactic acidosis and clinical features of mitochondrial disease. Including FBLX4 in the mitochondrial diseases panel should be particularly important for patients with congenital lactic acidosis.


A blinded, randomized, palatability study comparing variations of 2 popular field water disinfection tablets.
Halogen-based water disinfection tablets may render an unpleasant taste to treated water. Proposed safe additives such as ascorbic acid may reduce this objectionable taste. We compared the palatability of 2 field water disinfectants: iodine-based tetraglycine hydroperiodide (TGHP) and chlorine-based chlorine dioxide (CD) both with and without the concomitant use of an ascorbic acid taste neutralizer. Blinded participants randomly sampled 5 different distilled water samples containing combinations of disinfectant tablets and ascorbic acid: 1) water; 2) water with TGHP; 3) water with CD; 4) water with TGHP plus ascorbic acid; and 5) water with CD plus ascorbic acid. Participants rated beverage taste via a 100 mm visual analogue scale (VAS) and ranked the samples from "most pleasant" to "least pleasant." Sixty participants evaluated the samples. On the VAS, water with TGHP tasted worst and water with CD tasted second worst. Water with TGHP plus ascorbic acid, water alone, and water with CD plus ascorbic acid measured similarly as significantly best tasting. Water with TGHP was ranked by 58% as "least pleasant" tasting, while water with TGHP and ascorbic acid was ranked by 40% as "most pleasant" tasting. Participants found halogen-based disinfected water significantly less palatable prior to the addition of ascorbic acid. Addition of ascorbic acid to treated water created a beverage of similar preference to distilled water. These results may increase compliance with the use of disinfecting tablets by increasing the palatability of drinking water made potable via addition of ascorbic acid to halogen-based chemical disinfection.


THE RELATION OF THE STABILITY OF PROTOPLASMIC FILMS IN NOCTILUCA TO THE DURATION AND INTENSITY OF AN APPLIED ELECTRIC POTENTIAL.
1. The experiments demonstrate that when a constant electric potential of sufficient intensity is applied to Noctiluca, the protoplasmic films which represent a part of the visible continuous phase of the cytoplasm and plasma membrane at the surface of the cell, become unstable and break down, thus releasing the acid contents of one of the internal discontinuous phases present in the cytoplasm of Noctiluca. This process which occurs first at anode then at the cathode side of the cell, appears to be a selective deemulsification or coalescence similar to that at the surface of an emulsion having a viscous continuous phase. 2. The experiments demonstrate that Nernst's equation See PDF for Equation which expresses approximately the relation of duration and intensity of a constant electric current to threshold stimulation of striated muscle, applies equally well to the process of anodal coalescence in Noctiluca. 3. Anodal and cathodal coalescence have different thresholds, due to the fact that the semipermeable plasma film at the surface of the cell is asymmetric with respect to the direction of the applied current. Attention is called to the possible relation between this phenomenon and the conditions occurring at the synapse between neurons. 4. The stability of the protoplasmic films in relation to the applied electric potential is greater in young cells than in old cells, or in other words the threshold intensity of the stimulus is higher for young than for old cells. 5. Attention is called to the occurrence in the same cell of different receptor-affector mechanisms having a corresponding difference in intensity threshold when an electric current is acting as a stimulus.


Thermoplasmonic Vesicle Fusion Reveals Membrane Phase Segregation of Influenza Spike Proteins.
Many cellular processes involve the lateral organization of integral and peripheral membrane proteins into nanoscale domains. Despite the biological significance, the mechanisms that facilitate membrane protein clustering into nanoscale lipid domains remain enigmatic. In cells, the analysis of membrane protein phase affinity is complicated by the size and temporal nature of ordered and disordered lipid domains. To overcome these limitations, we developed a method for delivering membrane proteins from transfected cells into phase-separated model membranes that combines optical trapping with thermoplasmonic-mediated membrane fusion and confocal imaging. Using this approach, we observed clear phase partitioning into the liquid disordered phase following the transfer of GFP-tagged influenza hemagglutinin and neuraminidase from transfected cell membranes to giant unilamellar vesicles. The generic platform presented here allows investigation of the phase affinity of any plasma membrane protein which can be labeled or tagged with a fluorescent marker.


Cocaine and chest pain: clinical features and outcome of patients hospitalized to rule out myocardial infarction.
To investigate the clinical features, electrocardiographic findings, and hospital course in patients admitted with acute chest pain temporally related to cocaine use. Retrospective data analysis. A 485-bed county hospital. One hundred and one consecutive patients with cocaine-related chest pain admitted to the hospital to rule out myocardial infarction. The quality of the chest pain frequently suggested myocardial ischemia. Dyspnea was common (56%). The onset of chest pain occurred during cocaine use in 21% of patients, within 1 hour of use in 37%, and after 1 hour of use in 42%. Admission electrocardiographic findings were interpreted as normal in 32% of patients; as acute myocardial injury in 8%; as early repolarization variant in 32%; as left ventricular hypertrophy in 16%; and as "other" in 12%. Forty-three percent of patients had ST-segment elevation meeting the electrocardiographic criteria for use of thrombolytic therapy, but such elevation was usually due to the early repolarization variant. The initial total creatine kinase was elevated more than 3.3 mu kat/L (200 U/L) in 43% of patients, and an elevated total creatine kinase was recorded at some time during the hospital course in 47% of patients. The creatine kinase MB fraction was less than 0.02 in all patients. Myocardial infarction was ruled out in all patients. No patient experienced in-hospital cardiovascular complications. The quality of acute chest pain related to cocaine use is indistinguishable from that experienced in acute myocardial ischemia. Abnormal or normal variant electrocardiographic findings are common in patients with chest pain related to cocaine use, but nevertheless the incidence of acute myocardial infarction is low. The ST-segment and T-wave changes can mimic acute myocardial injury and are most likely normal findings in young black men that can be readily recognized in the emergency department. Most of these patients do not require admission to an intensive care unit.


Patient education and preventive care in Malaysian dental practice.
A questionnaire survey was conducted to examine the attitudes of Malaysian dentists toward patient education and preventive dentistry and the level of preventive care adopted in Malaysian dental practice. An adjusted response rate of 73.1% was obtained. Generally the Malaysian dentists had positive attitudes towards patient education and preventive dentistry including fluoridation. However, a sizable proportion of them considered that preventive measures were no challenge for the dentist. The common preventive measures given to patients were scaling, dental health education, prophylaxis and instruction in correct brushing and flossing in as much as 40 to 50 percent of the queried dentist claimed that these preventive items were provided to most or all of their new patients. In spite of the fact that the majority of the dentists had good knowledge about the application and effects of sealants only about 41 percent of the dentists claimed to have used sealants. More dentists in the private sector reportedly having done so. Also many Malaysian dentists (18.5%) did not use leaded protection for any of their new patients when taking radiographs.


Hybrid Gibbs-sampling algorithm for challenging motif discovery: GibbsDST.
The difficulties of computational discovery of transcription factor binding sites (TFBS) are well represented by (l, d) planted motif challenge problems. Large d problems are difficult, particularly for profile-based motif discovery algorithms. Their local search in the profile space is apparently incompatible with subtle motifs and large mutational distances between the motif occurrences. Herein, an improved profile-based method called GibbsDST is described and tested on (15,4), (12,3), and (18,6) challenging problems. For the first time for a profile-based method, its performance in motif challenge problems is comparable to that of Random Projection. It is noteworthy that GibbsDST outperforms a pattern-based algorithm, WINNOWER, in some cases. Effectiveness of GibbsDST using a biological dataset as an example and its possible extension to more realistic evolution models are also introduced.


Multicanonical Monte Carlo study and analysis of tails for the order-parameter distribution of the two-dimensional Ising model.
The tails of the critical order-parameter distribution of the two-dimensional Ising model are investigated through extensive multicanonical Monte Carlo simulations. Results for fixed boundary conditions are reported here, and compared with known results for periodic boundary conditions. Clear numerical evidence for "fat" stretched exponential tails exists below the critical temperature, indicating the possible presence of fat tails at the critical temperature. Our work suggests that the true order-parameter distribution at the critical temperature must be considered to be unknown at present.


A Randomized Trial of Collaborative Care for Perinatal Depression in Socioeconomically Disadvantaged Women: The Impact of Comorbid Posttraumatic Stress Disorder.
The comorbidity of posttraumatic stress disorder (PTSD) with antenatal depression poses increased risks for postpartum depression and may delay or diminish response to evidence-based depression care. In a secondary analysis of an 18-month study of collaborative care for perinatal depression, the authors hypothesized that pregnant, depressed, socioeconomically disadvantaged women with comorbid PTSD would show more improvement in the MOMCare intervention providing Brief Interpersonal Psychotherapy and/or antidepressants, compared to intensive public health Maternity Support Services (MSS-Plus). A multisite randomized controlled trial with blinded outcome assessment was conducted in the Seattle-King County Public Health System, July 2009-January 2014. Pregnant women were recruited who met criteria for a probable diagnosis of major depressive disorder (MDD) on the Patient Health Questionnaire-9 and/or dysthymia on the MINI-International Neuropsychiatric Interview (5.0.0). The primary outcome was depression severity at 3-, 6-, 12-and 18-month follow-ups; secondary outcomes included functional improvement, PTSD severity, depression response and remission, and quality of depression care. Sixty-five percent of the sample of 164 met criteria for probable comorbid PTSD. The treatment effect was significantly associated with PTSD status in a group-by-PTSD severity interaction, controlling for baseline depression severity (Wald χ²₁ = 4.52, P = .03). Over the 18-month follow-up, those with comorbid PTSD in MOMCare (n = 48), versus MSS-Plus (n = 58), showed greater improvement in depression severity (Wald χ²₁ = 8.51, P < .004), PTSD severity (Wald χ²₁ = 5.55, P < .02), and functioning (Wald χ²₁ = 4.40, P < .04); higher rates of depression response (Wald χ²₁ = 4.13, P < .04) and remission (Wald χ²₁ = 5.17, P < .02); and increased use of mental health services (Wald χ²₁ = 39.87, P < .0001) and antidepressant medication (Wald χ²₁ = 8.07, P < .005). Participants without comorbid PTSD in MOMCare (n = 33) and MSS-Plus (n = 25) showed equivalent improvement on these outcomes. Collaborative depression care had a greater impact on perinatal depressive outcomes for socioeconomically disadvantaged women with comorbid PTSD than for those without PTSD. Findings suggest that a stepped care treatment model for high-risk pregnant women with both MDD and PTSD could be integrated into public health systems in the United States. ClinicalTrials.gov identifier: NCT01045655.


Exhalative Breath Markers Do Not Offer for Diagnosis of Interstitial Lung Diseases: Data from the European IPF Registry (eurIPFreg) and Biobank.
Background: New biomarkers are urgently needed to facilitate diagnosis in Interstitial Lung Diseases (ILD), thus reducing the need for invasive procedures, and to enable tailoring and monitoring of medical treatment. Methods: In this study we investigated if patients with idiopathic pulmonary fibrosis (IPF; n = 21), non-IPF ILDs (n = 57) and other lung diseases (chronic obstructive pulmonary disease (COPD) n = 24, lung cancer (LC) n = 16) as well as healthy subjects (n = 20) show relevant differences in exhaled NO (FeNO; Niox MINO), or in eicosanoid (PGE2, 8-isoprostane; enzyme-linked immunosorbent assay (ELISA)) levels as measured in exhaled breath condensates (EBC) and bronchoalveolar lavage fluids (BALF). Results: There was no significant difference in FeNO values between IPF, non-IPF ILDs and healthy subjects, although some individual patients showed highly elevated FeNO. On the basis of the FeNO signal, it was neither possible to differentiate between the kind of disease nor to detect exacerbations. In addition, there was no correlation between FeNO values and lung function. The investigation of the eicosanoids in EBCs was challenging (PGE2) or unreliable (8-isoprostane), but worked out well in BALF. A significant increase of free 8-isoprostane was observed in BALF, but not in EBCs, of patients with IPF, hypersensitivity pneumonitis (HP) and sarcoidosis, possibly indicating severity of oxidative stress. Conclusions: FeNO-measurements are not of diagnostic benefit in different ILDs including IPF. The same holds true for PGE2 and 8-isoprostane in EBC by ELISA.


New tuberculosis drugs on the horizon.
Tuberculosis (TB) remains a major global health concern whose control has been exacerbated by HIV and the emergence of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains of Mycobacterium tuberculosis. The demand for new and faster acting TB drugs is thus greater than ever. In the past decade intensive efforts have been made to discover new leads for TB drug development using both target-based and cell-based approaches. Here, we describe the most promising anti-tubercular drug candidates that are in clinical development and introduce some nitro-aromatic compounds that inhibit a new target, DprE1, an essential enzyme involved in a crucial step in mycobacterial cell wall biosynthesis.


Large-scale sequestration of atmospheric carbon via plant roots in natural and agricultural ecosystems: why and how.
The soil holds twice as much carbon as does the atmosphere, and most soil carbon is derived from recent photosynthesis that takes carbon into root structures and further into below-ground storage via exudates therefrom. Nonetheless, many natural and most agricultural crops have roots that extend only to about 1 m below ground. What determines the lifetime of below-ground C in various forms is not well understood, and understanding these processes is therefore key to optimising them for enhanced C sequestration. Most soils (and especially subsoils) are very far from being saturated with organic carbon, and calculations show that the amounts of C that might further be sequestered (http://dbkgroup.org/carbonsequestration/rootsystem.html) are actually very great. Breeding crops with desirable below-ground C sequestration traits, and exploiting attendant agronomic practices optimised for individual species in their relevant environments, are therefore important goals. These bring additional benefits related to improvements in soil structure and in the usage of other nutrients and water.


13C NMR relaxation and conformational flexibility of the deoxyribose ring.
13C T1's and NOE's have been measured for all protonated carbons of 2'-deoxy-D-ribose (2'-d-ribose), 2'-deoxyadenosine-5'-monophosphate (5'-dAMP), thymidine-3'-monophosphate (3'-TMP) and thymidine-5'-monophosphate (5'-TMP) in D2O solutions. In all of the deoxy sugars examined, NT1 values for C-2' are significantly larger than the values for the remaining carbons. This result is interpreted in terms of rapid puckering motion of C-2'. By contrast, NT1 values measured in ribose are found to be equal, within experimental error. The results are compared with analogous data obtained for the five membered pyrrolidine ring of proline and with results for DNA itself.


ADHD and reading disability in male adults: is there a connection?
The present study examined the comorbidity between attention-deficit/hyperactivity disorder (ADHD) and reading disability (RD) in male adults. Participants were 120 men, of whom 24 were classified as having ADHD. The basis for the diagnosis was two self-report scales validated by interviews and background data. An extensive battery was used to assess phonological abilities and various aspects of reading skills. No differences were obtained between adults with and without ADHD on measures of either phonological processing skills or word decoding, indicating a low comorbidity with RD. This finding was valid even when different criteria were used to diagnose RD. However, the two groups differed in reading comprehension, with individuals with ADHD performing poorly in tests of reading comprehension. These results are compatible with the view that reading comprehension involves many of the higher cognitive control functions assumed to be impaired in ADHD. However, these attentional control functions are not critical to word recognition, which is determined by a more encapsulated phonological processing module. The pattern of associations between ADHD and RD observed in the present study is explained with reference to the differential attentional demands of the two aspects of reading.


Pharmacotherapeutic management of atopic keratoconjunctivitis.
Atopic keratoconjunctivitis (AKC) is a form of allergic eye disease that can have sight threating implications. Prevalence is underestimated due to scarce published data and treatment is expanding as a result of limitations of current strategies. This article aims to provide an up-to-date overview of AKC and summarize current and upcoming management. The authors provide history, immunopathogenesis, and summary of the clinical manifestations of AKC as well as presenting a review of the evidence in relation to treatment options including mast cell stabilizers, antihistamines, corticosteroids, and immunomodulatory drugs based on clinical trials. Future trends, drug targets, and novel delivery drug systems are also highlighted in this review. Previously established treatment strategies of AKC had relied on corticosteroids, but the side effects of long-term therapy resulted in the expansion into the use of immunomodulatory drugs such as tacrolimus and ciclosporin. However, these too provide limited success due to the suboptimal structural properties of the current molecules. The ideal molecule should generate maximum permeability across the multi-layered structure of the cornea, be able to be formulated into eye drops for ease of application with minimal dosing and for maximal clinical effect.


Cochlear Implantation in Inner Ear Malformations: Considerations Related to Surgical Complications and Communication Skills.
There are particular challenges in the implantation of malformed cochleae, such as in cases of facial nerve anomalies, cerebrospinal fluid (CSF) leaks, erroneous electrode insertion, or facial stimulation, and the outcomes may differ depending on the severity of the malformation. The aim of this study was to assess the impact of inner ear malformations (IEMs) on surgical complications and outcomes of cochlear implantation. In order to assess the impact of IEMs on cochlear implant (CI) outcomes, 2 groups of patients with similar epidemiological parameters were selected from among 863 patients. Both the study group (patients with an IEM) and control group (patients with a normal inner ear) included 25 patients who received a CI and completed at least 1 year of follow-up. Auditory performance, receptive and expressive language skills, and production and use of speech were evaluated preoperatively and at least 1 year after implantation. Types of surgical complications and rates of revision surgeries were determined in each group. In the study group, the most common malformation was an isolated enlarged vestibular aqueduct (EVA) (44.8%). Overall, the patients with IEMs showed significant improvement in auditory-verbal skills. In general, the patients who had normal cochleae scored significantly better compared to patients with IEMs (p < 0.05). The complication rate was significantly lower in the control group compared to the study group (p = 0.001), but the rate of revision surgeries did not differ significantly (p = 0.637). It is possible to improve communication skills with CIs in patients with IEMs despite the variations in postoperative performances. Patients with EVA, incomplete partition type 2, and cochlear hypoplasia type 2 were the best performers in terms of auditory-verbal skills. Patients with IEMs scored poorly compared to patients with normal cochleae. CSF leak (gusher or oozing) was the most common complication during surgery, which is highly likely in cases of incomplete partition type 3.


A five-year assessment of clinical incidents requiring transfer in a dental hospital day surgery unit.
Previous studies regarding general anaesthesia related morbidity and mortality rates for dental surgery have taken the form of a retrospective survey. The Australian and New Zealand College of Anaesthetists also do not record morbidity and mortality for dental/oral and maxillofacial procedures. The aim of this study was to document the clinical incidents requiring transfer to another hospital and mortality. Records from patients transferred to another hospital after having treatment under general anaesthesia performed at the Royal Dental Hospital of Melbourne between 1 January 2005 and 31 December 2009 were prospectively reviewed. There were 17,557 general anaesthesia procedures performed during the review period, including paediatric, special needs and minor oral and maxillofacial surgery procedures. The incidence of morbidity requiring transfer to a hospital with overnight stay facilities was 0.13%. There were no cases of mortality recorded. The most common complication was low oxygen saturation. The low incidence of morbidity seen is most likely attributed to the safety of modern anaesthesia and appropriate patient selection. Dentists and dental specialists performing general anaesthesia procedures should be aware of the complications that arise so that informed consent can be obtained. This study also provides a benchmark for general anaesthesia morbidity/mortality for dental procedures.


Expression of Otx Genes in Müller Cells Using an In Vitro Experimental Model of Retinal Hypoxia.
Müller glial cells typically activate to react to hypoxic tissue damage in several retinal diseases. We evaluated the in vitro response to a hypoxia-mimicking stimulus on the expression of a set of genes, known to contribute to eye morphogenesis and cell differentiation. A MIO-M1 Müller cell line was cultured in a hypoxia-mimicking environment by the addition of cobalt chloride to the culture medium, followed by a recovery time in which we mimic restoration from the hypoxic insult. The HIF-1α protein and VEGF-A gene expression were quantified to verify the induction of a hypoxia-like state. Among the genes under study, we did not observe any difference in the expression levels of Otx1 and Otx2 during treatment; conversely, Otx1 was overexpressed during recovery steps. The VEGF-A gene was strongly upregulated at both the CoCl2 and recovery time points. The transactivated isoform (TA) of the TP73 gene showed an overexpression in long-term exposure to the hypoxic stimulus with a further increase after recovery. Discussion. Our molecular analysis is able to describe the activation of a set of genes, never before described, that can drive the response to a hypoxia-like status. The improved comprehension of these cellular events will be useful for designing new therapeutical approaches for retinal pathologies.


YcaO domains use ATP to activate amide backbones during peptide cyclodehydrations.
Thiazole/oxazole-modified microcins (TOMMs) encompass a recently defined class of ribosomally synthesized natural products with a diverse set of biological activities. Although TOMM biosynthesis has been investigated for over a decade, the mechanism of heterocycle formation by the synthetase enzymes remains poorly understood. Using substrate analogs and isotopic labeling, we demonstrate that ATP is used to directly phosphorylate the peptide amide backbone during TOMM heterocycle formation. Moreover, we present what is to our knowledge the first experimental evidence that the D-protein component of the heterocycle-forming synthetase (YcaO/domain of unknown function 181 family member), formerly annotated as a docking protein involved in complex formation and regulation, is able to perform the ATP-dependent cyclodehydration reaction in the absence of the other TOMM biosynthetic proteins. Together, these data reveal the role of ATP in the biosynthesis of azole and azoline heterocycles in ribosomal natural products and prompt a reclassification of the enzymes involved in their installation.


Spontaneous Rhabdomyosarcomas in (A/J x CBA/J)Fl Mice.
Spontaneous rhabdomyosarcoma is rare in laboratory rodents. Incidence was estimated as 2.4/100,000 in BALB/c mice; incidence of <0.5% for rodents is generally accepted. We describe spontaneous rhabdomyosarcoma in 2 aged, female ([A/J x CBA/ J]F1) mice. Part of a small breeding colony, these mice were experimentally naive; incidence was estimated as 12.5%. Tumors were located in the muscles of the thoracic wall and muscles of the dorsolumbar region. Cross-striations were detected, using phosphotung- stic acid hematoxylin stain; presence of cross-striations within the neoplasm are diagnostic for rhabdomyosarcoma.


Out-of-Pocket Health Care Spending at Older Ages: Do Caregiving Arrangements Matter?
Identifying the correlates of out-of-pocket (OOP) health care spending is an important step for ensuring the financial security of older adults. Whether or not someone has a family member providing assistance is one such factor that could be associated with OOP spending. If family caregivers facilitate better health, health care spending could be reduced. On the other hand, costs would be higher if family members facilitate more (or more costly) care for loved ones. This paper explores the relationship between caregiving arrangements and OOP spending using data from 5045 individuals in the 2000-2016 Health and Retirement Study with Medicare coverage and caregiving needs. We do not find a relationship between family caregiving and OOP health care costs, overall. However, among those with Medicare HMO insurance, having a family caregiver is associated with more spending than having no helper. This is mainly due to differences in spending on prescription medications.


An integrated environmental risk assessment framework for coal-fired power plants: A fuzzy logic approach.
This study quantifies the environmental risk of a coal-fired thermal power plant during operation by using environmental monitoring data, site surveys, and documented evidence. The following criteria are assessed: emissions (CO, SO2 , NOx , PM10 ), impact on aquatic ecosystem (fish protection at cooling water intake and cooling water discharge temperature), and waste management (fly ash and bottom ash). Fuzzy sets were defined for each criterion, taking environmental regulatory context as an expert judgment. A survey was conducted with multiple stakeholders to determine the relative importance of risk factors. The survey results showed that the most concerned risks are SO2 and NOx emissions. The proposed method estimates the risk of each environmental criterion separately and then accumulates them into an environmental risk index (ERI). Accordingly, we assessed the Catalagzi coal-fired power plant, which has been in operation on the Black Sea coast in northwestern Turkey. For this case study, the ERI resulted in a value of 0.78 (on a scale of 0-1), showing high environmental risk to the facility. Moreover, the applicability of the proposed framework was tested in several existing coal-fired power plants using simultaneous measurements. All studied coal-fired power plants in Turkey have unacceptable pollutants (PM10 , SO2 , and NOx ) concentration levels indicating high health risk potential. The application of the integrated environmental risk assessment framework showed that new environmental regulations are needed in Turkey to specify more strict emission limits and to monitor CO2 , fine particulate matter emissions, cooling water discharge, and fish protection at cooling water intake.


Passage of bacterial DNA into host cells during in vitro transformation of Nicotiana tabacum by Agrobacterium tumefaciens.
Tumorigenic and non-tumorigenic strains of Agrobacterium tumefaciens were labelled with tritiated thymidine and added separately to suspension cultures of X-D line habituated tobacco cells. The subsequent association of bacteria with plant host cells and the passage of bacteria and bacterial DNA into these cells was examined by conventional light and electron microscopy and light microscope autoradiography. The results suggest that both strains of bacterium enter damaged host cells (via wall lesions), where they remain restricted to cell vacuoles. By 48 h, the radioactive label has spread from the vacuoles of infiltrated cells to the non-vacuolar cytoplasm of the whole callus tissue. Tumorigenic bacteria differ from the non-tumorigenic strain in promoting a significant increase in host cell nuclear volume, which is paralleled by clear and specific nuclear labelling. It is proposed that tumorigenic DNA, but not non-tumorigenic DNA, is specifically incorporated into, and activates, the host cell nucleus.


Characterization of nuclear mitochondrial insertions in the whole genomes of primates.
The transfer and integration of whole and partial mitochondrial genomes into the nuclear genomes of eukaryotes is an ongoing process that has facilitated the transfer of genes and contributed to the evolution of various cellular pathways. Many previous studies have explored the impact of these insertions, referred to as NumtS, but have focused primarily on older events that have become fixed and are therefore present in all individual genomes for a given species. We previously developed an approach to identify novel Numt polymorphisms from next-generation sequence data and applied it to thousands of human genomes. Here, we extend this analysis to 79 individuals of other great ape species including chimpanzee, bonobo, gorilla, orang-utan and also an old world monkey, macaque. We show that recent Numt insertions are prevalent in each species though at different apparent rates, with chimpanzees exhibiting a significant increase in both polymorphic and fixed Numt sequences as compared to other great apes. We further assessed positional effects in each species in terms of evolutionary time and rate of insertion and identified putative hotspots on chromosome 5 for Numt integration, providing insight into both recent polymorphic and older fixed reference NumtS in great apes in comparison to human events.


Pharmacokinetics of tetrabenazine and its major metabolite in man and rat. Bioavailability and dose dependency studies.
The pharmacokinetics of tetrabenazine (TBZ), a catecholamine and serotonin depletor, and its major metabolite, dihydrotetrabenazine (HTBZ), were studied in four patients affected by tardive dyskinesia, who were under treatment with different doses of TBZ (12.5-37.5 mg, t.i.d.), and in the rat. In the patients, the steady-state area under the plasma concentration-time curves (AUCs) of the metabolite were 82.6-199-fold higher than those of TBZ. The drug showed a small and erratic bioavailability (F = 0.06 +/- 0.026, mean +/- SD). It appears to be extensively metabolized, as no unchanged TBZ could be detected in the urine of the patients. Single oral doses of 0.5-10 mg/kg and single iv dose of 1 mg/kg of TBZ were each administered to four to six rats. The clearance of the drug following iv administration to the rat (mean +/- SD, 58.9 +/- 6.01 ml X min-1 X kg-1) was very close to the rat hepatic blood flow indicating a perfusion-limited clearance. An F value of 0.17 was obtained following iv and po doses of 1 mg/kg TBZ in the rat. The oral absorption of TBZ seems to be rapid and almost complete. Plots of the AUCs of TBZ and HTBZ vs. five different po doses (0.5-10 mg/kg) were linear with correlation coefficients of 0.998 and 0.986 for TBZ and HTBZ, respectively, suggesting linear kinetics in the examined dosage range. In both the patients and rats, the plasma profile of TBZ followed characteristics of a multiexponential pharmacokinetic model.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of a mitochondrial protein associated with cytoplasmic male sterility in petunia.
The petunia fused gene (pcf), which is associated with cytoplasmic male sterility (CMS), is composed of sequences derived from atp9, coxII, and an unidentified reading frame termed urfS. To determine whether the pcf gene is expressed at the protein level, we produced antibodies to synthetic peptides specified by the coxII and urfS portions of the pcf gene. Anti-COXII peptide antibodies recognized petunia COXII but no other mitochondrial proteins. Anti-URF-S peptide antibodies recognized a 20-kilodalton protein present in both cytoplasmic male sterile and fertile lines and a protein with an apparent molecular mass of 25 kilodaltons present only in cytoplasmic male sterile lines. The 25-kilodalton protein was found to be synthesized by isolated mitochondria and to fractionate into both the soluble and membrane portions of disrupted mitochondria, whereas the 20-kilodalton protein was found only in the membrane fraction. The abundance of the 25-kilodalton protein was much lower in fertile plants carrying the cytoplasmic male sterile cytoplasm and a single dominant nuclear fertility restorer gene, Rf. Thus, the pcf gene is correlated with cytoplasmic male sterility not only by its co-segregation with the phenotype in somatic hybrids, but also by the modification of its expression at the protein level through the action of a nuclear gene that confers fertility.


Human platelet-specific antigen, Siba, is associated with the molecular weight polymorphism of glycoprotein Ib alpha.
Platelet-specific antigen Sib(a) has been highly implicated in the pathogenesis of refractoriness to human leukocyte antigen (HLA)-matched platelet transfusions in Japan. We provide evidence that the Sib(a) antigen is located on the glycoprotein (GP) Ib alpha and has a close association with the molecular weight (mol wt) polymorphism of GPIb. In modified antigen-capture ELISA (MACE), anti-Sib(a) antibody reacted only with GPIb/IX held by a murine anti-GPIb/IX monoclonal antibody (MoAb). The reactivity of anti-Sib(a) antibody to Sib(a)-positive (Sib(a+)) platelets was abolished after they were treated with Serratia marcescens protease. Platelets from 50 healthy volunteers were semiquantitatively phenotyped for Sib(a) antigen by MACE and divided into three distinct groups: strongly positive, positive, and negative. They were also analyzed by sodium dodeyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and periodic acid-silver staining for mol wt polymorphism of GPIb, phenotyped as A, B, C, or D. Without exception, Sib(a+) platelets showed larger phenotypes (A or B). Removal of sialic acid from Sib(a+) platelets did not reduce the binding of anti-Sib(a). Finally, anti-Sib(a) antibody specifically immunoprecipitated A and B phenotypes of GPIb from Sib(a+) platelets. Thus, Sib(a) antigen evidently is located in the region of glycocalicin that is present only on the A and B phenotypes of GPIb.


Clinical Outcomes of Geriatric Care in Cipto Mangunkusumo Hospital, Before and After the Implementation of National Health Insurance Program.
the National Health Insurance (NIH/JKN) has been enacted since January 2014. Various outcomes of geriatric patient care, such as improved functional status and quality of life have not been evaluated. Prolonged hospitalization and re-hospitalization are potentially affecting the efficiency care of this vulnarable group. This study aimed to identify the differences of functional status improvement, quality of life improvement, length of stay, and hospitalization of geriatric patients admitted to CMH between prior to and after NHI implementation. a cohort study with historical control was conducted among geriatric patients admitted to Acute Geriatric Ward CMH Hospital on two periods of time: January-December 2013 (pre-NHI implementation) and June 2014-May 2015 (after NHI implementation). Patients who died within 24 hours of hospital admission, those with APPACHE II score >24, advance stage cancer, transfer to other wards before they were discharged or have incomplete record were excluded from the study. Data on demographical and clinical characteristics, functional status, quality of life, length of stay, and re-hospitalization were taken from patient's medical record. The differences of studied outcomes were analyzed using t-test or Mann-Whitney test. there were 102 subjects in pre-NHI and 135 subjects in NHI groups included in the study. Median lengths of stay were not different between two groups (12.5 days in pre-NHI and 10 days in NHI groups, p=0.087), although the proportion of patients with in-hospital stay less than 14 days was higher in NHI group. The difference of functional status of discharged patients in pre-NHI and NHI groups were 3 and 3 (p=0.149) respectively, whereas for health-related quality of life, although NHI group in the beginning showed a lower quality of life compared to the pre-NHI (0.163 [0.480] vs. 0.243 [0.550]; p=0.012). However, after incorporating comprehensive geriatric assessment (CGA) the quality of life improved significantly by the end of in-hospital care in both groups. Re-hospitalization incidence in NHI group was lower compared to pre-NHI (7 [5.2%] vs. 13 [12.7%]; p=0.038). our study shows that there was no significant difference regarding length of stay, functional status, and health-related quality of life between prior to and after national health insurance implementation on admitted geriatric patients. Rehospitalization incidence showed better results in NHI group and hence NHI implementation is favored.


Chemical evolution from simple inorganic compounds to chiral peptides.
Numerous experiments performed in the past 50 years have strongly changed ideas of how life could have emerged on the primitive Earth. This review deals with the synthesis of biomolecule precursors under the conditions prevailing on the primordial Earth, and describes possible scenarios for their combination and elongation to form peptides and proteins. Furthermore it proposes different answers to one of the big secrets of nature: why DNA-coded biohomochiral life emerged using amino acids in their l-form?


Diversity in adjustment to a leg amputation: case illustrations of common themes.
To provide in-depth case descriptions that illustrate the common themes in the research literature on psychological adjustment to a lower-extremity amputation as well as capture the uniqueness of each individual's response to this prevalent acquired disability. Four cases were chosen based on the diversity of adjustment issues they represented. These case presentations were reconstructed from evaluations completed by the authors, all psychologists, as part of routine care on an inpatient rehabilitation service. Identifying information was changed to protect confidentiality. Taken together, these four cases serve to underscore the importance attending to common issues such as post-amputation depression and anxiety, body image, feelings of vulnerability, social support changes, grief, pre-amputation psychological issues and phantom limb pain and sensations. Psychological assessment and referrals for treatment should be included as part of the routine care provided to individuals with amputations, irrespective of the length of time that has passed since the amputation.


Innovative regenerative medicine in the management of knee OA: The role of Autologous Protein Solution.
Osteoarthritis (OA) is one of the most common causes of chronic disability in adults due to pain and altered joint function. Although most patients report pain and functional limitation, symptoms, age of onset and disease progression are extremely variable. While inflammation could play a central role in the OA pathogenesis and progression, many underpinning mechanisms are still unclear. A number of proinflammatory mediators have been found in OA joints and could play a role, such as IL-1, IL-6, IL-7, IL-8, IL-15, IL-17, IL-18, TNF-alpha, macrophage chemotactic protein (MCP)-1, interferon-induced protein (IP)-10, monokine induced by interferon (MIG), oncostatin M (OSM), growth-related oncogene (GRO)-alpha, chemokine (C-C-motif) ligand 19 (CCL19), macrophage inflammatory protein (MIP)-1beta, and TGF-alpha. Biological approaches have recently got increasing interest due to their anti-inflammatory and immunomodulatory properties, regenerative potential, and high tolerability. The primary aim of this paper is to report the current concepts on regenerative medicine for knee OA with a particular focus on Autologous Protein solution (APS). APS is a blood derived product obtained by using a proprietary device, made of APS Separator, which isolates WBCs and platelets in a small volume of plasma, and APS Concentrator, which further concentrates platelets, WBCs and plasma proteins. The result is a peculiar formulation differing from other biologic products as it contains high levels of growth factors (EGF, IGF-1, PDGF-AB, PDGF-BB, VEGF, TGF-β1) along with high concentrations of anti-inflammatory mediators (IL-1ra, sIL-1RII, sTNF-RI, sTNF-RII) and low levels of pro-inflammatory cytokines (Il-1β and TNF-α). While emerging evidence supports the use of APS, as confirmed by in vitro studies and preliminary clinical results, the real clinical potential of APS and its benefits are still under investigation.


The model-specific Markov embedding problem for symmetric group-based models.
We study model embeddability, which is a variation of the famous embedding problem in probability theory, when apart from the requirement that the Markov matrix is the matrix exponential of a rate matrix, we additionally ask that the rate matrix follows the model structure. We provide a characterisation of model embeddable Markov matrices corresponding to symmetric group-based phylogenetic models. In particular, we provide necessary and sufficient conditions in terms of the eigenvalues of symmetric group-based matrices. To showcase our main result on model embeddability, we provide an application to hachimoji models, which are eight-state models for synthetic DNA. Moreover, our main result on model embeddability enables us to compute the volume of the set of model embeddable Markov matrices relative to the volume of other relevant sets of Markov matrices within the model.


Genetic analysis of the upper phenylacetate catabolic pathway in the production of tropodithietic acid by Phaeobacter gallaeciensis.
Production of the antibiotic tropodithietic acid (TDA) depends on the central phenylacetate catabolic pathway, specifically on the oxygenase PaaABCDE, which catalyzes epoxidation of phenylacetyl-coenzyme A (CoA). Our study was focused on genes of the upper part of this pathway leading to phenylacetyl-CoA as precursor for TDA. Phaeobacter gallaeciensis DSM 17395 encodes two genes with homology to phenylacetyl-CoA ligases (paaK1 and paaK2), which were shown to be essential for phenylacetate catabolism but not for TDA biosynthesis and phenylalanine degradation. Thus, in P. gallaeciensis another enzyme must produce phenylacetyl-CoA from phenylalanine. Using random transposon insertion mutagenesis of a paaK1-paaK2 double mutant we identified a gene (ior1) with similarity to iorA and iorB in archaea, encoding an indolepyruvate:ferredoxin oxidoreductase (IOR). The ior1 mutant was unable to grow on phenylalanine, and production of TDA was significantly reduced compared to the wild-type level (60%). Nuclear magnetic resonance (NMR) spectroscopic investigations using (13)C-labeled phenylalanine isotopomers demonstrated that phenylalanine is transformed into phenylacetyl-CoA by Ior1. Using quantitative real-time PCR, we could show that expression of ior1 depends on the adjacent regulator IorR. Growth on phenylalanine promotes production of TDA, induces expression of ior1 (27-fold) and paaK1 (61-fold), and regulates the production of TDA. Phylogenetic analysis showed that the aerobic type of IOR as found in many roseobacters is common within a number of different phylogenetic groups of aerobic bacteria such as Burkholderia, Cupriavidis, and Rhizobia, where it may also contribute to the degradation of phenylalanine.


The nature and extent of college student hazing.
This study explored the nature and extent of college student hazing in the USA. Hazing, a form of interpersonal violence, can jeopardize the health and safety of students. Using a web-based survey, data were collected from 11,482 undergraduate students, aged 18-25 years, who attended one of 53 colleges and universities. Additionally, researchers interviewed 300 students and staff at 18 of the campuses. Results reveal hazing among USA college students is widespread and involves a range of student organizations and athletic teams. Alcohol consumption, humiliation, isolation, sleep-deprivation and sex acts are hazing practices common across student groups. Furthermore, there is a large gap between the number of students who report experience with hazing behaviors and those that label their experience as hazing. To date, hazing prevention efforts in post-secondary education have focused largely on students in fraternities/sororities and intercollegiate athletes. Findings from this study can inform development of more comprehensive and research-based hazing prevention efforts that target a wider range of student groups. Further, data can serve as a baseline from which to measure changes in college student hazing over time.


Effect of intraportal glucagon-like peptide-1 on glucose metabolism in conscious dogs.
Arteriovenous difference and tracer ([3-(3)H]glucose) techniques were used in 42-h-fasted conscious dogs to identify any insulin-like effects of intraportally administered glucagon-like peptide 1-(7-36)amide (GLP-1). Each study consisted of an equilibration, a basal, and three 90-min test periods (P1, P2, and P3) during which somatostatin, intraportal insulin (3-fold basal) and glucagon (basal), and peripheral glucose were infused. Saline was infused intraportally in P1. During P2 and P3, GLP-1 was infused intraportally at 0.9 and 5.1 pmol. kg(-1). min(-1) in eight dogs, at 10 and 20 pmol. kg(-1). min(-1) in seven dogs, and at 0 pmol. kg(-1). min(-1) in eight dogs (control group). Net hepatic glucose uptake was significantly enhanced during GLP-1 infusion at 20 pmol. kg(-1). min(-1) [21.8 vs. 13.4 micromol. kg(-1). min(-1) (control), P < 0.05]. Glucose utilization was significantly increased during infusion at 10 and 20 pmol. kg(-1). min(-1) [87.3 +/- 8.3 and 105.3 +/- 12.8, respectively, vs. 62.2 +/- 5.3 and 74.7 +/- 7.4 micromol. kg(-1). min(-1) (control), P < 0.05]. The glucose infusion rate required to maintain hyperglycemia was increased (P < 0.05) during infusion of GLP-1 at 5.1, 10, and 20 pmol. kg(-1). min(-1) (22, 36, and 32%, respectively, greater than control). Nonhepatic glucose uptake increased significantly during delivery of GLP-1 at 5.1 and 10 pmol. kg(-1). min(-1) (25 and 46% greater than control) and tended (P = 0.1) to increase during GLP-1 infusion at 20 pmol. kg(-1). min(-1) (24% greater than control). Intraportal infusion of GLP-1 at high physiological and pharmacological rates increased glucose disposal primarily in nonhepatic tissues.


A large-scale national study of gambling severity among immigrant and non-immigrant adolescents: The role of the family.
The primary aim of the present study was to examine the association between immigrant generation, family sociodemographic characteristics, and problem gambling severity in a large-scale nationally representative sample of Italian youth. Data from the 2013-2014 Health Behaviour in School-aged Children (HBSC) Survey were used for cross-sectional analyses of adolescent problem gambling. Self-administered questionnaires were completed by a representative sample of 20,791 15-year-old students. Respondents' problem gambling severity, immigrant status, family characteristics (family structure, family affluence, perceived family support) and socio-demographic characteristics were individually assessed. Rates of adolescent at-risk/problem gambling were twice as high among first generation immigrants than non-immigrant students; the odds of being at-risk/problem gamblers were higher among first-generation immigrants than adolescents of other immigrant generations or non-immigrant. Not living with two biological or adoptive parents appears to be a factor that increases the risk of becoming a problem gambler in first generation immigrants. Immigrant status and family characteristics may play a key role in contributing to adolescent problem gambling.


[Comparative characteristics of glucose metabolism in the liver of rats under acute alcohol and morphine intoxication].
The comparative analysis effect of acute alcohol and morphine intoxications on rats on hepatic glycolysis and pentose phosphate pathway was done. The dose-dependent inhibitory effect of ethanol on activity of limiting enzymes of these metabolic ways, as well as anaerobic reorientation of glucose metabolism was recognised with the increase of the dose of the intake alcohol. Morfine (10 mg/kg) activated enymes of glycolysis and pentose phosphate pathway, but in contrast to ethanol it did not influence these parameters at the dose 20 or 40 mg/kg.


Structural basis of nanobody-mediated blocking of BtuF, the cognate substrate-binding protein of the Escherichia coli vitamin B12 transporter BtuCD.
Bacterial ABC importers catalyze the uptake of essential nutrients including transition metals and metal-containing co-factors. Recently, an IgG antibody targeting the external binding protein of the Staphylococcus aureus Mn(II) ABC importer was reported to inhibit transport activity and reduce bacterial cell growth. We here explored the possibility of using alpaca-derived nanobodies to inhibit the vitamin B12 transporter of Escherichia coli, BtuCD-F, as a model system by generating nanobodies against the periplasmic binding protein BtuF. We isolated six nanobodies that competed with B12 for binding to BtuF, with inhibition constants between 10-6 and 10-9 M. Kinetic characterization of the nanobody-BtuF interactions revealed dissociation half-lives between 1.6 and 6 minutes and fast association rates between 104 and 106 M-1s-1. For the tightest-binding nanobody, we observed a reduction of in vitro transport activity of BtuCD-F when an excess of nanobody over B12 was used. The structure of BtuF in complex with the most effective nanobody Nb9 revealed the molecular basis of its inhibitory function. The CDR3 loop of Nb9 reached into the substrate-binding pocket of BtuF, preventing both B12 binding and BtuCD-F complex formation. Our results suggest that nanobodies can mediate ABC importer inhibition, providing an opportunity for novel antibiotic strategies.


Medullary thyroid carcinoma: a 30-year experience at one institution in Korea.
The objective of this study was to review the clinical outcome and prognosis of patients with sporadic and hereditary medullary thyroid cancer (MTC) who were treated at a single tertiary hospital in Korea. We retrospectively reviewed the case files of 85 patients treated from August 1982 to February 2012. In all, 65 patients (76.5%) had sporadic MTC and 20 patients (23.5%) had hereditary MTC. Patients in the sporadic group were older than in the hereditary group (P < 0.001). However, the hereditary group had more tumor multiplicity (P < 0.001) and bilaterality (P < 0.001). Neither survival rate was significantly different between the sporadic and hereditary groups (P = 0.775 and P = 0.866). By multivariate analysis, distant metastasis was a significant prognostic factor for overall and progression-free survival. In general, patients with MTC have favorable outcomes. Distant metastasis appears to be the strongest predictor of overall and progression-free survival.


Two-Level Anterior Cervical Discectomy and Fusion Versus Cervical Disc Arthroplasty-Long-Term Evidence Update.
Multiple studies have highlighted the motion-sparing benefits of single-level cervical disc arthroplasty (CDA) compared with anterior cervical discectomy and fusion (ACDF). However, few studies have reviewed multilevel ACDF versus CDA. Several recent studies have midterm and even long-term data available comparing 2-level ACDF versus CDA. We reviewed 3 reports from 2 large randomized, prospective Food and Drug Administration investigational drug exemption trials looking at 2-level CDA versus ACDF, which provide the bulk of the available midterm to long-term, high-level evidence for the topic. We also present several smaller and/or shorter-term studies. One 5-year study showed that, while both CDA and ACDF showed significant improvement in patient-reported outcome scores, CDA demonstrated greater improvement in Neck Disability Index (NDI) scores than ACDF (mean = -37 versus mean = -28, P = .0003), were more likely to be satisfied (96.4% versus 89.5%, P = .04), had fewer secondary surgeries (4% versus 16.2%, P = .0003), had fewer adjacent level reoperations (3.1% versus 11.4%), and developed less adjacent segment degeneration (50.7% versus 90.5%, P < .0001). Adverse events occurred more frequently with ACDF (8.6% versus 4.4%).Similarly, Lanman et al [Lanman TH, Burkus JK, Dryer RG, Gornet MF, McConnell J, Hodges SD. Long-term clinical and radiographic outcomes of the Prestige LP artificial cervical disc replacement at 2 levels: results from a prospective randomized controlled clinical trial. J Neurosurg Spine. 2017;27(1):7-19] showed that, at 7 years, while both groups demonstrated improvement in patient-reported outcomes, CDA had greater improvement in regard to NDI, neck pain, and Short Form (36) Physical Component Summary scores (each P < .001), had higher rates of satisfaction (94.8% versus 92.6%), had lower rate of secondary surgery at treated levels (4.2% versus 14.7%), and had a lower, albeit not statistically significant, rate of secondary surgeries at adjacent levels (6.5% versus 12.5%). Adverse events were more common with ACDF (7.2% versus 3.2%).More recently, Gornet et al [Gornet MF, Lanman TH, Burkus JK, et al. Two-level cervical disc arthroplasty versus anterior cervical discectomy and fusion: 10-year outcomes of a prospective, randomized investigational device exemption clinical trial. J Neurosurg Spine. 2019;31:508-518.] in 2019 reported 10-year data from the same clinical trial as the Lanman et al report comparing 2-level CDA (209 patients) versus ACDF (188 patients). With >84% follow-up for both groups at 10 years, they found that CDA demonstrated a statistically significantly improved rate of overall success (84% versus 62%) as compared with ACDF. Greater improvements were seen in several other outcome measures for CDA, including NDI, neurological success, and neck pain scores. The CDA group had a lower rate of serious implant-related adverse events and demonstrated a lower rate of needing a secondary surgery at an adjacent level, 9% versus 18% in the ACDF group. Results of 2 large randomized trials suggest similar-to-improved patient reported outcomes for multilevel CDA versus ACDF maintained out to midterm to long-term follow-up of 5-10 years, with lower rates of revision surgery at index and adjacent levels and lower rates of serious adverse device-related events. 5. Comparison of the safety and efficacy of multi-level cervical disc arthroplasty and cervical discectomy and fusion.


Effects of all-trans retinol and cigarette smoke condensate on hamster tracheal epithelium in organ culture. I. A cell proliferation study.
The effects of cigarette smoke condensate (CSC) and all-trans retinol on the cell proliferative activity of vitamin A-deprived hamster tracheal epithelium have been studied in vitamin A-deficient, serum-free, hormone-supplemented medium in organ culture. In the absence of retinol, CSC induced a dose-dependent increase in labeling index (LI) during 12 days of culture. The basal cells were more sensitive to CSC exposure than non-basal cells during the first 6 to 8 culture days. However, in squamous metaplastic foci developing after culture day 6, both basal and non-basal cells in the mid-part of the epithelium were labeled. Physiological concentrations of all-trans retinol stimulated the non-basal LI and inhibited the basal cell LI. Compared with dimethylsulfoxide (DMSO), all retinol concentrations used in the present study inhibited the basal cell LI at each time point examined (4-12 days culture). Exposure of tracheal rings to retinol, either before or after exposure to CSC, or simultaneous exposure to retinol and CSC, clearly decreased the CSC-induced basal cell proliferative activity depending on the retinol concentration used. It is concluded from the present study that squamous metaplasia induced by vitamin A-deficiency or by CSC originates mainly from basal cells and that for the maintenance of these lesions, both basal and non-basal cells play a role. Furthermore, all-trans retinol inhibited CSC-induced basal cell proliferation.


Multidimensional Sexual Perfectionism and Female Sexual Function: A Longitudinal Investigation.
Research on multidimensional sexual perfectionism differentiates four forms: self-oriented, partner-oriented, partner-prescribed, and socially prescribed. Self-oriented sexual perfectionism reflects perfectionistic standards people apply to themselves as sexual partners; partner-oriented sexual perfectionism reflects perfectionistic standards people apply to their sexual partner; partner-prescribed sexual perfectionism reflects people's beliefs that their sexual partner imposes perfectionistic standards on them; and socially prescribed sexual perfectionism reflects people's beliefs that society imposes such standards on them. Previous studies found partner-prescribed and socially prescribed sexual perfectionism to be maladaptive forms of sexual perfectionism associated with a negative sexual self-concept and problematic sexual behaviors, but only examined cross-sectional relationships. The present article presents the first longitudinal study examining whether multidimensional sexual perfectionism predicts changes in sexual self-concept and sexual function over time. A total of 366 women aged 17-69 years completed measures of multidimensional sexual perfectionism, sexual esteem, sexual anxiety, sexual problem self-blame, and sexual function (cross-sectional data). Three to six months later, 164 of the women completed the same measures again (longitudinal data). Across analyses, partner-prescribed sexual perfectionism emerged as the most maladaptive form of sexual perfectionism. In the cross-sectional data, partner-prescribed sexual perfectionism showed positive relationships with sexual anxiety, sexual problem self-blame, and intercourse pain, and negative relationships with sexual esteem, desire, arousal, lubrication, and orgasmic function. In the longitudinal data, partner-prescribed sexual perfectionism predicted increases in sexual anxiety and decreases in sexual esteem, arousal, and lubrication over time. The findings suggest that partner-prescribed sexual perfectionism contributes to women's negative sexual self-concept and female sexual dysfunction.


Collaboration between dental faculties and National Dental Associations (NDAs) within the World Dental Federation-European Regional Organization zone: an NDAs perspective.
Although improvements in certain oral health measures have been achieved, many global oral health matters and challenges exist. Collaborations and partnerships among various institutions are crucial in solving such problems. The main aim of the present study was to analyse the nature and extent of the partnership between dental faculties and National Dental Associations (NDAs). A questionnaire was developed, focusing on the relationship between NDAs and dental faculties within the World Dental Federation-European Regional Organization (FDI-ERO) zone with regard to major professional activities, such as dental education (both undergraduate and continuing education), workforce issues, improvement of national oral health, and science and knowledge transfer. The questionnaire was sent to all member NDAs within the ERO zone. The response rate was 21/41 (53.65%). The major activities in which NDAs were found to be involved were improvement of national oral health (100%), followed by continuing education activities (90%), whereas the activity which received least involvement was the development of an undergraduate dental curriculum (52%). The NDAs perceived their relationship with dental faculties to be quite satisfactory in the fields of continuing education, science and knowledge transfer, and the implementation of new technologies into daily dental practice. However, it was suggested that their relationship needed significant improvement with regard to the development of an undergraduate dental education curriculum, dental workforce issues and negotiations with the authorities regarding professional matters/issues. As the two important elements of organised dentistry, NDAs and dental faculties have a significant role to play in the improvement of oral health and in finding solutions to global oral health challenges; therefore, their collaboration and partnership are crucial for this purpose. On the basis of the perceptions of NDAs regarding their relationship with dental faculties, it can be concluded that their partnership can and should be further improved.


Induction of pemphigus phenotype by a mouse monoclonal antibody against the amino-terminal adhesive interface of desmoglein 3.
Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering disease that is caused by IgG autoantibodies against the cadherin-type adhesion molecule desmoglein (Dsg)3. Previously, we have generated an active mouse model for PV by adoptive transfer of Dsg3(-/-) splenocytes. In this study, we isolated eight AK series, anti-Dsg3 IgG mAbs from the PV mouse model, and examined their pathogenic activities in induction of blister formation. Intraperitoneal inoculation of the AK23 hybridoma, but not the other AK hybridomas, induced the virtually identical phenotype to that of PV model mice or Dsg3(-/-) mice with typical histology of PV. Epitope mapping with domain-swapped and point-mutated Dsg1/Dsg3 molecules revealed that AK23 recognized a calcium-dependent conformational epitope on Dsg3, which consisted of the V3, K7, P8, and D59 Dsg3-specific residues that formed the adhesive interface between juxtaposed Dsg, as predicted by the crystal structure. The epitopes of the mAbs that failed to show apparent pathogenic activity were mapped in the middle to carboxyl-terminal extracellular region of Dsg3, where no direct intermolecular interaction was predicted. These findings demonstrate the pathogenic heterogeneity among anti-Dsg3 IgG Abs due to their epitopes, and suggest the direct inhibition of adhesive interaction of Dsg as an initial molecular event of blister formation in pemphigus.


Prevention of DNA double-strand breaks induced by radioiodide-(131)I in FRTL-5 thyroid cells.
Radioiodine-131 released from nuclear reactor accidents has dramatically increased the incidence of papillary thyroid cancer in exposed individuals. The deposition of ionizing radiation in cells results in double-strand DNA breaks (DSB) at fragile sites, and this early event can generate oncogenic rearrangements that eventually cause cancer. The aims of this study were to develop a method to show DNA DSBs induced by (131)I in thyroid cells; to test monovalent anions that are transported by the sodium/iodide symporter to determine whether they prevent (131)I-induced DSB; and to test other radioprotective agents for their effect on irradiated thyroid cells. Rat FRTL-5 thyroid cells were incubated with (131)I. DSBs were measured by nuclear immunofluorescence using antibodies to p53-binding protein 1 or γH2AX. Incubation with 1-10 μCi (131)I per milliliter for 90 min resulted in a dose-related increase of DSBs; the number of DSBs increased from a baseline of 4-15% before radiation to 65-90% after radiation. GH3 or CHO cells that do not transport iodide did not develop DSBs when incubated with (131)I. Incubation with 20-100 μm iodide or thiocyanate markedly attenuated DSBs. Perchlorate was about 6 times more potent than iodide or thiocyanate(.) The effects of the anions were much greater when each was added 30-120 min before the (131)I. Two natural organic compounds recently shown to provide radiation protection partially prevented DSBs caused by (131)I and had an additive effect with perchlorate. In conclusion, we developed a thyroid cell model to quantify the mitogenic effect of (131)I. (131)I causes DNA DSBs in FRTL-5 cells and had no effect on cells that do not transport iodide. Perchlorate, iodide, and thiocyanate protect against DSBs induced by (131)I.


Characterization of the isocitrate lyase gene from Corynebacterium glutamicum and biochemical analysis of the enzyme.
Isocitrate lyase is a key enzyme in the glyoxylate cycle and is essential as an anaplerotic enzyme for growth on acetate as a carbon source. It is assumed to be of major importance in carbon flux control in the amino acid-producing organism Corynebacterium glutamicum. In crude extracts of C. glutamicum, the specific activities of isocitrate lyase were found to be 0.01 U/mg of protein after growth on glucose and 2.8 U/mg of protein after growth on acetate, indicating tight regulation. The isocitrate lyase gene, aceA, was isolated, subcloned, and characterized. The predicted gene product of aceA consists of 432 amino acids (M(r), 47,228) and shows up to 57% identity to the respective enzymes from other organisms. Downstream of aceA, a gene essential for thiamine biosynthesis was identified. Overexpression of aceA in C. glutamicum resulted in specific activities of 0.1 and 7.4 U/mg of protein in minimal medium containing glucose and acetate, respectively. Inactivation of the chromosomal aceA gene led to an inability to grow on acetate and to the absence of any detectable isocitrate lyase activity. Isocitrate lyase was purified to apparent homogeneity and subjected to biochemical analysis. The native enzyme was shown to be a tetramer of identical subunits, to exhibit an ordered Uni-Bi mechanism of catalysis, and to be effectively inhibited by 3-phosphoglycerate, 6-phosphogluconate, phosphoenolpyruvate, fructose-1,6-bisphosphate, and succinate.


Variations in inpatient mortality for AIDS in a national sample of hospitals.
In this project, we examined the spectrum of AIDS-related conditions and variations in associated inpatient mortality for AIDS patients treated in a national sample of hospitals. We identified 10,538 adult discharges with a diagnosis indicating AIDS from 258 hospitals from a national sample of 438 acute-care hospitals with 6 million discharges in 1986-1987. Opportunistic and other infections occurred in 55.9 and 37.9%, respectively, of AIDS discharges, and inpatient fatality rates varied considerably depending on complication type(s) and comorbidities. Clinical conditions were more important predictors of inpatient death than demographic or treatment site characteristics. Among opportunistic infections, odds of inpatient death were significantly increased for progressive multifocal leukoencephalopathy (odds ratio [OR] = 2.8), Pneumocystis carinii pneumonia (OR = 2.4), cryptococcosis (OR = 1.6), atypical mycobacterial infections (OR = 1.6), and toxoplasmosis (OR = 1.3). Odds of inpatient death were also significantly increased by non-AIDS-defining infections causing septicemia (OR = 3.1) or CNS involvement (OR = 1.6) or pulmonary involvement (OR = 1.5). After controlling for clinical conditions, significant differences in odds of death persisted across regions, age, and ethnic groups. Increases in hospitals' AIDS treatment experience were associated with a significant decrease in odds of inpatient death. These analyses provide a national perspective on the diversity of AIDS-related clinical conditions and their relative effects on inpatient mortality.


Heterogeneity and clonal variation related to cell surface expression of a mouse lung tumor-associated antigen quantified using flow cytometry.
Previous reports have established that line 1, a spontaneous BALB/c lung carcinoma, expresses a Mr 180,000 tumor-associated surface antigen (TSP-180). In this study, using a monoclonal antibody and flow cytometry to quantify cell surface TSP-180 expression, we found that essentially all cells in a tissue culture-adapted line 1 population express TSP-180, but that the amount of TSP-180 expressed by cells is quite heterogeneous. Variation in amount of TSP-180 was found to be in part related to cell size heterogeneity, and to the expression of TSP-180 being cell cycle-dependent. The amount of surface-expressed TSP-180 correlated somewhat with cell size, and was greater on the average for cells in the G2 cell cycle compartment. However, cells of a defined size and specific cell cycle stage still showed marked heterogeneity of expression. Even though the average amount of TSP-180 expressed per cell decreased during in vitro propagation, little change in heterogeneity was observed. To explore whether any TSP-180-related heterogeneity resulted from heritable variation of expression, 263 limiting dilution-derived line 1 clones were analyzed. The majority displayed, shortly after cloning, heterogeneous TSP-180 profiles and mean TSP-180 levels similar to those observed for the parent tumor. Occasionally, however, clones were isolated that again appeared as heterogeneous as the parent, but differed by as much as 3-fold in mean TSP-180 expression. Extensive passage did not substantially increase the low probability of isolating clones which differed in expression of TSP-180. Differences in TSP-180 expression among clones were found to be relatively stable upon passage, typically maintained after recloning, and large enough to influence clonal susceptibility to TSP-180-directed antibody and complement-mediated lysis. Heritable variation in TSP-180 expression among some clones was also shown to be independent of differences related to cell size, cell cycle, or expression of another line 1 surface antigen (P-100). We concluded that although clones demonstrating large heritable differences in TSP-180 expression can occasionally be isolated, line 1 TSP-180 heterogeneity is predominantly nonheritable, being similar to that present in recently cloned lines, quite stable during in vitro passage, and not totally accounted for by cell cycle or cell size variation.


In vitro killing activities of antibiotics at clinically achievable concentrations in cerebrospinal fluid against penicillin-resistant Streptococcus pneumoniae isolated from children with meningitis.
We evaluated the in vitro killing activities of ceftriaxone, imipenem, vancomycin, gentamicin, fosfomycin, and rifampin, alone and in combination, against 26 Streptococcus pneumoniae strains (penicillin G MICs, > 0.125 to 2 micrograms/ml) isolated from the cerebrospinal fluid of children with meningitis. The antibiotics were tested at clinically achievable concentrations in cerebrospinal fluid. After 5 h of incubation, imipenem was the most effective drug. None of the combinations had synergistic activity. Killing by beta-lactam antibiotics or vancomycin was enhanced by the addition of gentamicin, reduced by the addition of rifampin, and unaffected by the addition of fosfomycin.


Molecular imaging of musculoskeletal diseases.
Chronic musculoskeletal diseases such as arthritis, malignancy, chronic injury/ inflammation, and chronic musculoskeletal pain often pose challenges for current clinical imaging modalities. There is hope that a growing field, referred to as "molecular imaging," will shed new light on these chronic phenomenon as it aims to noninvasively detect special molecular and physiologic effects such as metabolism rate, specific proteins, cell death, and particular gene-related events. Molecular imaging represents recent advances in imaging technology, engineering, chemistry, molecular biology, and genetics that have coalesced into a multidisciplinary and multimodality effort. Molecular probes are currently being developed not only in radionuclide-based techniques but also in magnetic resonance imaging, magnetic resonance spectroscopy, ultrasound, and the emerging field of optical imaging. Furthermore, molecular imagers are fueling the development of novel molecular therapies and gene therapy, as tracking these efforts in living subjects is now possible with molecular imaging protocols.


Evaluation of Brainstorming Session as a Teaching-learning Tool among Postgraduate Medical Biochemistry Students.
The thrust for postgraduate teaching should be self-directed learning with equal participation by all students in academic discussions. Group discussions involve conduction of the discourse by a leader who guides the discussion as well as points out any wrong information. This discourages quieter students from participation with the fear of rebuke. Brainstorming is devoid of all such fallacies with no judgment and reprimand. The aim of this study was to use brainstorming as a teaching-learning tool among postgraduate students of medical biochemistry. The project was commenced after due approvals from the research and ethical committee. The participants were enrolled after informed consent and sensitization. All the pro forma and questionnaires were duly validated by experts. After piloting and incorporation of the suggestions for improvisation, the main sessions were planned and implemented. The response was judged by posttest scores and feedback forms. There was an improvement of understanding of the biochemical concepts as assessed by the posttest scores and solving of a similar clinical problem. The students expressed satisfaction with the conduction, timing, and discussion of the clinical problems. The drawbacks of traditional teaching as expressed during the feedback stage were also taken care of by the brainstorming sessions. Our project made the students and the faculty aware about the utility of brainstorming for teaching purposes in medical education which till now was considered efficacious only for troubleshooting in advertising and management institutions. The students were satisfied with this technique for understanding of biochemical concepts.


Real-time functional architecture of visual word recognition.
Despite a century of research into visual word recognition, basic questions remain unresolved about the functional architecture of the process that maps visual inputs from orthographic analysis onto lexical form and meaning and about the units of analysis in terms of which these processes are conducted. Here we use magnetoencephalography, supported by a masked priming behavioral study, to address these questions using contrasting sets of simple (walk), complex (swimmer), and pseudo-complex (corner) forms. Early analyses of orthographic structure, detectable in bilateral posterior temporal regions within a 150-230 msec time frame, are shown to segment the visual input into linguistic substrings (words and morphemes) that trigger lexical access in left middle temporal locations from 300 msec. These are primarily feedforward processes and are not initially constrained by lexical-level variables. Lexical constraints become significant from 390 msec, in both simple and complex words, with increased processing of pseudowords and pseudo-complex forms. These results, consistent with morpho-orthographic models based on masked priming data, map out the real-time functional architecture of visual word recognition, establishing basic feedforward processing relationships between orthographic form, morphological structure, and lexical meaning.


Alveolar macrophages are required for protective pulmonary defenses in murine Klebsiella pneumonia: elimination of alveolar macrophages increases neutrophil recruitment but decreases bacterial clearance and survival.
To study the in vivo role of alveolar macrophages (AM) in gram-negative bacterial pneumonia in mice, AM were eliminated by the intratracheal (i.t.) administration of dichloromethylene diphosphonate encapsulated liposomes. Subsequently, the AM-depleted mice were infected i.t. with 100 CFU of Klebsiella pneumoniae, and the effects of AM depletion on survival, bacterial clearance, and neutrophil (polymorphonuclear leukocyte [PMN]) recruitment were assessed. It was shown that depletion of AM decreases survival dramatically, with 100% lethality at day 3 postinfection, versus 100% long-term survival in the control group. This increased mortality was accompanied by 20- to 27- and 3- to 10-fold increases in the number of K. pneumoniae CFU in lung and plasma, respectively, compared to those in nondepleted animals. This decreased bacterial clearance was not due to an impaired PMN recruitment; on the contrary, the K. pneumoniae-induced PMN recruitment in AM-depleted lungs was sevenfold greater 48 h postinfection than that in control infected lungs. Together with an increased PMN infiltration, 3- and 10-fold increases in lung homogenate tumor necrosis factor alpha (TNF-alpha) and macrophage inflammatory protein 2 (MIP-2) levels, respectively, were measured. Neutralization of TNF-alpha or MIP-2, 2 h before infection, reduced the numbers of infiltrating PMN by 41.6 and 64.2%, respectively, indicating that these cytokines mediate PMN influx in infected lungs, rather then just being produced by the recruited PMN themselves. Our studies demonstrate, for the first time, the relative importance of the AM in the containment and clearance of bacteria in the setting of Klebsiella pneumonia.


Hybrid III-V/silicon single-mode laser with periodic microstructures.
In this Letter, a III-V/silicon hybrid single-mode laser operating at C band for photonic integration circuit is presented. The InGaAlAs gain structure is bonded onto a patterned silicon-on insulator through wafer to wafer directly. The mode selected mechanism based on a hybrid III-V/silicon straight cavity with periodic microstructures is applied, which only need low cost i-line projection photolithography in the whole technological process. At room temperature, we obtain 0.62 mW output power in continuous-wave. The side mode suppression ratio of larger than 20 dB is obtained from experiments. [corrected].


Vestibular nerve regeneration in the bullfrog, Rana catesbeiana: peripheral dendrites.
Three experiments were conducted on healthy adult bullfrogs (Rana catesbeiana) for the purpose of investigating three characteristics of centrifugal vestibular afferent regeneration after complete transection of the anterior division of the vestibular nerve (AVN). In experiment 1 total fiber count and axon diameter measurements were obtained from the anterior canal nerve at three different time periods and compared with normal. The normal group (n = 3) demonstrated a total fiber count of 1001 +/- 76 (SEM). The early time period (1 to 2 weeks, n = 3) did not completely regenerate as demonstrated by a total fiber count of 282 +/- 23. The intermediate (4 to 6 weeks, n = 3) and late (8 to 16 weeks, n = 3) groups exhibited total fiber counts of 907 +/- 29 and 946 +/- 50, respectively, which were not different from normal (Mann-Whitney U, p > 0.2). Evaluation of fiber diameter distribution of the intermediate and late regenerated nerves revealed a reduction in axon diameter caliber compared with normal (analysis of variance, p < 0.0001). Thus transection of the AVN results in regeneration of all afferents that exhibit a reduction in axon diameter. In experiment 2 fibers innervating the anterior canal crista (ACC) were prelabeled before nerve transection. After the labeling procedure the AVN (n = 3) was sectioned at a location that resulted in denervation of three vestibular receptors: the ACC, horizontal canal cristae (HCC), and utricular macula. After 4 weeks of regeneration the ACC fibers that were prelabeled were observed innervating all three denervated vestibular receptors. This result demonstrated that reinnervation of the peripheral vestibular end organs after AVN transection is a nonspecific process. In experiment 3, 167 regenerated canal afferents were evaluated for functional recovery 16 weeks after transection. Both spontaneous and rotation-induced discharge characteristics were obtained and compared with those obtained from a sample of 254 normal afferents in a previous study (Hoffman LF. Factors affecting the response dynamics of canalicular primary afferent neurons in the bullfrog. St. Petersburg (FL): Association for Research in Otolaryngology; 1989). The mean spontaneous discharge coefficient of variation (CV) +/- standard deviation was 0.60 +/- 0.32 and 0.49 +/- 0.33 for ACC and HCC regenerated afferents, respectively, which did not differ from the normal means of 0.63 +/- 0.33 and 0.54 +/- 0.36 (Mann-Whitney, p > 0.2). Response gains and phases obtained during 0.05 Hz sinusoid rotations at 15 degrees/second maximum horizontal table velocity also demonstrated normal discharge characteristics. The mean phases were -28.2 +/- 25.2 degrees and -55.9 +/- 21.5 degrees for regenerated ACC and HCC afferents, respectively, which were not different from the normal means of -33.77 +/- 24.31 degrees and -58.0 +/- 23.3 degrees (Mann-Whitney U). Furthermore, regenerated afferents exhibited a positive association between phase and CV, which was also true for normal afferents (correlation analysis, p > 0.001). Although the mean gains for regenerated ACC and HCC (7.13 +/- 5.5 and 3.3 +/- 2.4 spikes x sec(-1)/degrees x sec(-2), respectively) afferents were reduced from normal ACC and HCC (14.8 +/- 12.52 and 7.76 +/- 6.58 spikes x sec(-1)/degrees x sec(-2), respectively) afferents (Mann-Whitney U, p > 0.0001), a positive association between gain and CV was also demonstrated by regenerated afferents, as was the case for normal afferents (correlation analysis, p < 0.001). Thus the overall response discharges of regenerated afferents were comparable with normal afferents. Normally, large fibers innervate central regions of the receptor, and smaller fibers innervate the peripheral regions. However, the data from experiments 1 and 2 demonstrate that vestibular nerve regeneration results in a dissociation between the normal topographic organization of fiber size and regional innervation of the receptor epithelium. (ABSTRACT TRUNCATED)


[Usefulness of the Biofeedback Diacontrol module in the automatic programming of plasmatic conductivity and ionic mass transfer].
Programmed variable sodium in the dialysate can improve hypotension during hemodialysis but may also alter sodium balance and thus resulting in a increase of water intake and weight gain between dialysis sessions. The aim of this study was to evaluate the changes on plasma volume (PV), Ionic Mass Transfer (IMT) and plasma conductivity (PC) with two different hemodialysis techniques. We studied 10 patients during a four-period protocol (one week each: PF1-DC1-DC2PF2): 120 dialysis sessions. During periods PF1 and PF2, the dialysis procedure was as usual, with exponential decrease of dialysate conductivity (DC) profile (15.7 mS/cm at start, 14.4 mS/cm at middle and 13.8 mS/cm at the end of the session) and UF profile (1.7 1/h at start and 0.1 1/h at the end). During periods DC1 and DC2, DC was automatically determined by a biofeedback modulae (Diacontrol) in order to reach a plasma water conductivity fixed at 14 mS/cm. All hemodialysis parameters were the same for the four periods: duration, blood and dialysate flow rates, dialysis membrane. A lower reduction of PV was evident on PF1 and PF2 (104 +/- 3.26% and -4.36 +/- 2.7%) compared with DC 1 and DC2 (-6.53 +/- 3.31% and -6.67 +/- 3.12%) (p < 0.001). No significant differences were seen in systolic, mean and diastolic blood pressure pre-HD or post-HD, UF, and weight gain, between the four periods. Hypotensive episodes were seen in 33.3% of PF1, 20% of DC1, 23.3% of DC2 and 26.6% of PF2 sessions (NS). PF1 and PF2 periods resulted in a significantly higher 30', mid and post-dialysis PC as compared to DC1 and DC2 periods (p < 0.001). The mean difference between the actual value and the prescribed value of PC at the end of the session was -0.01 +/- 0.07 mS/cm (n: 60). There was a negative correlation between the mean DC during session and the PC at 30' of session. IMT was 420.73 +/- 126.9 mEq in PF1, 311.96 +/- 161.75 in DC1, 278.34 +/- 153.14 in DC2 and 417.66 +/- 152.17 in PF2 (p > 0.001 PF1 and PF2 vs. DC1 and DC2). Diacontrol determines automatically an individualized DC profile for each patient, and accurately reaches the prescribed PC target. By reaching both the dry weight and PC settings, the water and sodium pool is maintained lower in the hemodialysis session using a biofeedback module. Clinical tolerance was similar in the two different dialysis procedures.


Flexible infrared photodetector based on indium antimonide nanowire arrays.
Narrow bandgap semiconductors like indium antimonide (InSb) are very suitable for high-performance room temperature infrared photodetectors, but the fragile nature of the wafer materials hinders their application as flexible/wearable devices. Here, we present a method to fabricate a photodetector device of assembled crystalline InSb nanowire (NW) arrays on a flexible substrate that balances high performance and flexibility, facilitating its application in wearable devices. The InSb NWs were synthesized by means of a vapor-liquid-solid technique, with gold nanoclusters as seeding particles. The morphological and crystal properties were investigated using scanning electron microscopy, x-ray diffraction and high-resolution transmission electron microscopy, which revealed the unique spike shape and high crystallinity with (111) and (220) planes of InSb NWs. The flexible infrared photodetector devices were fabricated by transferring the NWs onto transparent and stretchable polydimethylsiloxane substrate with pre-deposited gold electrodes. Current versus time measurement of the photodetector devices under light showed photoresponsivity and sensitivity to mid-infrared at bias as low as 0.1 V while attached to curved surfaces (suitable for skin implants). A high-performance NW device yielded efficient rise and decay times down to 1 s and short time lag for infrared detection. Based on dark current, calculated specific detectivity of the flexible photodetector was 1.4 × 1012Jones. The performance and durability render such devices promising for use as wearable infrared photodetectors.


Severe placental abruption: clinical definition and associations with maternal complications.
Placental abruption traditionally is defined as the premature separation of the implanted placenta before the delivery of the fetus. The existing clinical criteria of severity rely exclusively on fetal (fetal distress or fetal death) and maternal complications without consideration of neonatal or preterm delivery-related complications. However, two-thirds of abruption cases are accompanied by fetal or neonatal complications, including preterm delivery. A clinically meaningful classification for abruption therefore should include not only maternal complications but also adverse fetal and neonatal outcomes that include intrauterine growth restriction and preterm delivery. The purpose of this study was to define severe placental abruption and to compare serious maternal morbidity profiles of such cases with all other cases of abruption (ie, mild abruption) and nonabruption cases. We performed a retrospective cohort analysis using the Premier database of hospitalizations that resulted in singleton births in the United States between 2006 and 2012 (n = 27,796,465). Severe abruption was defined as abruption accompanied by at least 1 of the following events: maternal (disseminated intravascular coagulation, hypovolemic shock, blood transfusion, hysterectomy, renal failure, or in-hospital death), fetal (nonreassuring fetal status, intrauterine growth restriction, or fetal death), or neonatal (neonatal death, preterm delivery or small for gestational age) complications. Abruption cases that did not qualify as being severe were classified as mild abruption cases. The morbidity profile included amniotic fluid embolism, pulmonary edema, acute respiratory or heart failure, acute myocardial infarction, cardiomyopathy, puerperal cerebrovascular disorders, or coma. Associations were expressed as rate ratios with 95% confidence intervals that were derived from fitting log-linear Poisson regression models. The overall prevalence rate of abruption was 9.6 per 1000, of which two-thirds of cases were classified as being severe (6.5 per 1000). Serious maternal complications occurred in 15.4, 33.3, and 141.7 per 10,000 among nonabruption cases and mild and severe abruption cases, respectively. In comparison with no abruption, the rate ratio for serious maternal complications were 1.52 (95% confidence interval, 1.35-1.72) and 4.29 (95% confidence interval, 4.11-4.47) in women with mild and severe placental abruption, respectively. Rate ratios for the individual complications were 2- to 7-fold higher among severe abruption cases. Furthermore, the rate ratios for serious maternal complications among severe abruption cases compared with mild abruption cases was 3.47 (95% confidence interval, 3.05-3.95). This association was considerably stronger for virtually all maternal complications among cases with severe abruption compared with mild abruption. Annual rates of mild and severe abruption were fairly constant during the study period. Although the maternal complication rate among non-abruption births was stable from 2006-2012, the rate of complications among mild abruption cases dropped from 2006-2008 and then leveled off thereafter. In contrast, the rate of serious complications among severe abruption cases remained fairly stable from 2006-2010 and increased sharply thereafter. Severe abruption was associated with a distinctively higher morbidity risk profile compared with the other 2 groups. The clinical characteristics and morbidity profile of mild abruption were more similar to those of women without an abruption. These findings suggest that the definition of severe placental abruption based on the proposed specific criteria is clinically relevant and may facilitate epidemiologic and genetic research.


Basic optokinetic-ocular reflex pathways in the frog.
Frogs (Rana temporaria) have two midbrain nuclei that receive contralateral retinal afferents, and whose neurons respond to optokinetic stimulation. The basal optic nucleus is composed of direction-selective neurons with different response types. One type is activated exclusively by upward moving optokinetic targets; another type is activated only by downward moving targets. Two other types of basal optic neurons show this vertical preference, but each is also activated by patterns moved horizontally from the nasal to temporal visual field. No activation of these cells was found with patterns moved horizontally from the temporal to nasal visual fields. Rather, cells in a discrete pretectal region have this type of sensitivity: they increase their resting rate with temporal to nasal stimulation and decrease it with nasotemporal stimulation. Oculomotor neurons (antidromically identified) have similar optokinetic sensitivities. As with basal optic neurons, these cells have exclusively upward or downward sensitivity, and some also have nasotemporal sensitivity. An additional type of oculomotor neuron and abducens motoneurons are activated by temporonasal pattern movement. In general, the extraocular motoneurons have similar velocity and pattern size preferences, as have the sensory nuclei. Investigations of the connectivity between the sensory and motor nuclei were primarily restricted to the relation between the pretectum and the abducens. A monosynaptic connection between the pretectum and the abducens is suggested by four points: (1) excitatory postsynaptic potential onset latency in antidromically identified abducens motoneurons, following optic nerve stimulation, is consistent with the interpretation of a disynaptic pathway to the abducens from the retina; (2) pretectal cells, sensitive to optokinetic stimulation, can be activated antidromically from stimulation of the abducens nucleus; (3) horseradish peroxidase injections into the pretectum result in labeling of axons, which terminate in the abducens nucleus; (4) horseradish peroxidase injections into the abducens result in labeling of cells in the pretectal region, where optokinetically sensitive cells are found. In the frog, there seem to be three-neuronal retino-ocular reflexes mediating optokinetic slow phase behavior as there are three-neuronal vestibulo-ocular reflexes that also mediate compensatory spatial behavior. It is suggested that these direct connections act to initiate ocular movements and accelerate the eye, whereas more indirect pathways may act to maintain eye position.


Histamine avoidance through three gustatory receptors in Drosophila melanogaster.
Histamine is a fermented food product that exerts adverse health effects on animals when consumed in high amounts. This biogenic amine is fermented by microorganisms from histidine through the activity of histidine decarboxylase. Drosophila melanogaster can discriminate histidine and histamine using GR22e and IR76b in bitter-sensing gustatory receptor neurons (GRNs). In this study, RNA interference screens were conducted to examine 28 uncharacterized gustatory receptor genes using electrophysiology and behavioral experiments, including the binary food choice and proboscis extension response assays. GR9a and GR98a were first identified as specific histamine receptors by evaluating newly generated null mutants and recovery experiments by expressing their wild-type cDNA in the bitter-sensing GRNs. We further determined that histamine sensation was mainly mediated by the labellum but not by the legs, as demonstrated by the proboscis extension response assay. Our findings indicated that toxic histamine directly activates bitter-sensing GRNs in S-type sensilla, and this response is mediated by the GR9a, GR22e, and GR98a gustatory receptors.