A quantum mechanical "jack in the box": rapid rearrangement of a tetrahedryl-tetrahedrane via heavy atom tunneling.
A bridged tetrahedryl-tetrahedrane ("TT") was, theoretically, recognized as the holder of the chemical record for the shortest C-C single bond in a stable molecule. However, owing to its strained nature, this molecule is prone to rearrange to a carbene via ring contraction. Although TT was predicted to be stable to rearrangement at very low temperatures, our calculations find that, due to carbon quantum mechanical tunneling, even at 0 K it will immediately rearrange, with a half-life of only 4 ms. TT provides an excellent example of why tunneling effect should be considered in the stability analysis of a theoretically conceived molecule, even at cryogenic temperatures.


Superimposed Skilled Performance in a Virtual Mirror Improves Motor Performance and Cognitive Representation of a Full Body Motor Action.
Feedback is essential for skill acquisition as it helps identifying and correcting performance errors. Nowadays, Virtual Reality can be used as a tool to guide motor learning, and to provide innovative types of augmented feedback that exceed real world opportunities. Concurrent feedback has shown to be especially beneficial for novices. Moreover, watching skilled performances helps novices to acquire a motor skill, and this effect depends on the perspective taken by the observer. To date, however, the impact of watching one's own performance together with full body superimposition of a skilled performance, either from the front or from the side, remains to be explored. Here we used an immersive, state-of-the-art, low-latency cave automatic virtual environment (CAVE), and we asked novices to perform squat movements in front of a virtual mirror. Participants were assigned to one of three concurrent visual feedback groups: participants either watched their own avatar performing full body movements or were presented with the movement of a skilled individual superimposed on their own performance during movement execution, either from a frontal or from a side view. Motor performance and cognitive representation were measured in order to track changes in movement quality as well as motor memory across time. Consistent with our hypotheses, results showed an advantage of the groups that observed their own avatar performing the squat together with the superimposed skilled performance for some of the investigated parameters, depending on perspective. Specifically, for the deepest point of the squat, participants watching the squat from the front adapted their height, while those watching from the side adapted their backward movement. In a control experiment, we ruled out the possibility that the observed improvements were due to the mere fact of performing the squat movements-irrespective of the type of visual feedback. The present findings indicate that it can be beneficial for novices to watch themselves together with a skilled performance during execution, and that improvement depends on the perspective chosen.


A study on the role of apoptotic human umbilical cord mesenchymal stem cells in bleomycin-induced acute lung injury in rat models.
We sought to determine whether normal human umbilical cord mesenchymal stem cells and apoptotic human umbilical cord mesenchymal stem cells play any role in the lung repair following bleomycin-induced lung injury in rat models. Umbilical cord mesenchymal stem cells were obtained from the umbilical cord following caesarian section from healthy normal babies. Plasmin deprivation method was used for culture of human umbilical cord mesenchymal stem cells and flow cytometry was used to identify cell surface antigen and activity of stem cells and apoptosis. The animal model of acute lung injury was established by a one-off intratracheal instillation of bleomycin (BLM) (5 mg/kg) and then normal stem cells and apoptotic stem cells were separately injected. Alveolar lavage fluid and lung tissue were collected for further analysis prior to the injury and at days 3, 7, 14 after administration of BLM. The number of neutrophils in the broncho alveolar lavage fluid (BALF) was counted; Bicinchoninic Acid (BCA) method was used for estimation of total protein content in alveolar lavage fluid; biochemical assay was used for estimation of myeloperoxidase (MPO) activity; hematoxylin and eosin (HE) staining of lung tissue was used for histopathology analysis; reverse transcription-polymerase chain reaction (RT-PCR) assay was used for the determination of interferon-gamma (INF-γ) and mRNA changes of interleukin-4 (IL-4) in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used for the determination of cytokines TNF-α in the lung tissue. Apoptotic human umbilical cord mesenchymal stem cells were more effective in reducing lung neutrophil infiltration and total protein leakage in rat models of acute lung injury (ALI). There was also an improvement in the degree of vascular permeability, reduction in the level of proinflammatory cytokines, INF-γ gene level and boost in anti-inflammatory cytokine IL-4 levels which also helps in more effectively reducing the degree of injury in ALI. Human umbilical cord mesenchymal stem cell transplantation may have a bright future in the clinical setting for the treatment of ALI/acute respiratory distress syndrome (ARDS). Apoptotic human umbilical cord mesenchymal stem cells may have more effective than normal human umbilical cord mesenchymal stem cells in the treatment of acute lung injury.


First Record of Stephanostomum Sp. Looss, 1899 (Digenea: Acanthocolpidae) Metacercariae Parasitising the Pleasure Oyster Crassostrea Corteziensis (Hertlein) from the Mexican Pacific Coast.
The aim of this investigation was to identify the parasites present in the largely understudied pleasure oyster Crassostrea corteziensis in Sinaloa state in the northwestern Mexican Pacific coast. Inspection of twenty-eight oysters collected on "Ceuta" lagoon revealed the presence of the digenean Stephanostomum sp. (Digenea: Acanthocolpidae) cysts. Metacercariae were found encapsulated and embedded in the digestive gland and mantle tissue of oysters. The prevalence of infection revealed that 84.6 % were infected, the abundance was 13.62, with a mean intensity of 16.09 per host. The members of this genus are characterized by a double crown of spines in the cephalic region surrounding the buccal opening of the worm. Significantly, we report the first incidence of the digenean Stephanostomum sp of the family Acanthocolpidae parasitizing Crassostrea corteziensis. Further we report that this bivalve is now considered a new intermediate host, and the northwestern Mexican Pacific coast is a new geographical distribution area for this digenean. The findings contribute to our understanding of the biology, biodiversity and host preference of these parasites, with implications for health risks posed by human consumption of the pleasure oyster.


Assessment and Diagnostic Classification Using DC:0-5 in Early Childhood Mental Health Clinics: The Protocol for the Developmental Psychiatry Diagnostic Challenges Study (DePsy).
Mental health problems in early childhood are common, but there is a lack of psychiatric research on this age group. DC:0-5 is a multiaxial classification system for mental disorders in early childhood, providing a framework for standardizing clinical practice and research. However, research on the validity of DC:0-5 is scarce. The Developmental Psychiatry Diagnostic Challenges Study (DePsy) is a multi-site, prospective clinical study including six German early childhood mental health (ECMH) clinics. The main objective of the study is to contribute to the validation of Axis I and Axis II of DC:0-5. A second aim of the study is to describe the population of the participating clinics regarding diagnoses, family context, and treatment outcomes. Additionally, the impact of environmental risk factors, including parental Adverse Childhood Experiences (ACEs) and media use, on child psychopathology and caregiver-child relationships will be examined. Over two years, patients aged 0.0-5.9 years old will be enrolled in the study. Assessments include ICD-10 and DC:0-5 diagnoses, developmental tests, video-based observations of caregiver-child interactions, and questionnaires on child psychopathology, media use, parental stress, and treatment satisfaction. Study results will promote the standardization of assessment and treatment in ECMH clinics aiming to improve the development of patients and their families.


Microfluidics in flow cytometry and related techniques.
Technological advances in laboratory automation are now well understood and applied as they considerably improved the speed and robustness of haematological laboratory data, in the companion fields of blood analyzers and flow cytometry. Still rather confidential is the field of microfluidics, mostly confined so far to academic settings and research laboratories. The literature in the field of microfluidics is growing and applications in hematology range from cell counting to flow cytometry, cell sorting, or ex vivo testing. A literature search allows to identify many innovative solutions developed to master the specific physics of fluid movements in microchips. Miniaturization also dwells on findings that have emerged from different areas such as electronics and nanoengineering. This review proposes an overview of the major principles guiding developments in microfluidics and describes a necessarily limited and nonexhaustive series of specific applications. Readers are strongly encouraged to consult the documents referred to in the references section to learn more about this world knocking at our door and possibly liable to revolutionize our profession of hematology biologists in a not so far future.


Transcriptomics of Temporal- versus Substrate-Specific Wood Decay in the Brown-Rot Fungus Fibroporia radiculosa.
Brown-rot fungi lack many enzymes associated with complete wood degradation, such as lignin-attacking peroxidases, and have developed alternative mechanisms for rapid wood breakdown. To identify the effects of culture conditions and wood substrates on gene expression, we grew Fibroporia radiculosa in submerged cultures containing Wiley milled wood (5 days) and solid wood wafers (30 days), using aspen, pine, and spruce as a substrate. The comparative analysis revealed that wood species had a limited effect on the transcriptome: <3% of genes were differentially expressed between different wood species substrates. The comparison between gene expression during growth on milled wood and wood wafer conditions, however, indicated that the genes encoding plant cell wall-degrading enzymes, such as glycoside hydrolases and peptidases, were activated during growth on wood wafers, confirming previous reports. On the other hand, it was shown for the first time that the genes encoding Fenton chemistry enzymes, such as hydroquinone biosynthesis enzymes and oxidoreductases, were activated during submerged growth on ground wood. This illustrates the diversity of wood-decay reactions encoded in fungi and activated at different stages of this process.


Chronic alcohol consumption shifts learning strategies and synaptic plasticity from hippocampus to striatum-dependent pathways.
The hippocampus and striatum have dissociable roles in memory and are necessary for spatial and procedural/cued learning, respectively. Emotionally charged, stressful events promote the use of striatal- over hippocampus-dependent learning through the activation of the amygdala. An emerging hypothesis suggests that chronic consumption of addictive drugs similarly disrupt spatial/declarative memory while facilitating striatum-dependent associative learning. This cognitive imbalance could contribute to maintain addictive behaviors and increase the risk of relapse. We first examined, in C57BL/6 J male mice, whether chronic alcohol consumption (CAC) and alcohol withdrawal (AW) might modulate the respective use of spatial vs. single cue-based learning strategies, using a competition protocol in the Barnes maze task. We then performed in vivo electrophysiological studies in freely moving mice to assess learning-induced synaptic plasticity in both the basolateral amygdala (BLA) to dorsal hippocampus (dCA1) and BLA to dorsolateral striatum (DLS) pathways. We found that both CAC and early AW promote the use of cue-dependent learning strategies, and potentiate plasticity in the BLA → DLS pathway while reducing the use of spatial memory and depressing BLA → dCA1 neurotransmission. These results support the view that CAC disrupt normal hippocampo-striatal interactions, and suggest that targeting this cognitive imbalance through spatial/declarative task training could be of great help to maintain protracted abstinence in alcoholic patients.


Phytochemicals in Chronic Disease Prevention.
Chronic diseases, also known as noncommunicable diseases (NCD), are characterized by long durations and a slow progression of the associated medical conditions [...].


Anabolic androgenic steroids--use and correlates among gym users--an assessment study using questionnaires and observations at gyms in the Stockholm region.
The purpose of this study was to estimate the prevalence of anabolic androgenic steroid (AAS) use and offers to use among gym users in Stockholm County (Sweden), and to conduct a comparison of concordance in estimates of AAS and supplements at gyms between two data collection methods. A questionnaire was distributed to members at 36 training facilities and 1,752 gym users participated in the study. An observation study was conducted as covert participant observations at 64 gyms. According to the questionnaire, 3.9% of men reported life time use of AAS, 1.4% use during the past 12 months and 0.4% AAS use during past 30 days. Not only were there similar patterns found in the two methods, i.e., similar age and gender distributions for AAS use, but analyses of concordance showed that gyms with a higher prevalence of self-reported AAS-use and supplement use (questionnaire) showed a significantly higher proportion of observer-assessed AAS users. Analyses of individual predictors showed that AAS users were almost always young men, regular weight trainers and more often users of drugs and nutritional supplements. The higher prevalence of AAS use among gym users than in the general population makes the former an appropriate target group for AAS prevention. The connection between supplements, drugs and AAS use suggests that effective AAS prevention need to focus on several risk factors for AAS use. The clear resemblance in estimates between the observation and questionnaire data strengthen the credibility of the two methods.


CB1 agonist ACEA protects neurons and reduces the cognitive impairment of AβPP/PS1 mice.
The present study shows that chronic administration of the cannabinoid receptor type 1 (CB1) receptor agonist arachidonyl-2-chloroethylamide (ACEA) at pre-symptomatic or at early symptomatic stages, at a non-amnesic dose, reduces the cognitive impairment observed in double AβPP(swe)/PS1(1dE9) transgenic mice from 6 months of age onwards. ACEA has no effect on amyloid-β (Aβ) production, aggregation, or clearance. However, ACEA reduces the cytotoxic effect of Aβ42 oligomers in primary cultures of cortical neurons, and reverses Aβ-induced dephosphorylation of glycogen synthase kinase-3β (GSK3β) in vitro and in vivo. Reduced activity of GSK3β in ACEA-treated mice is further supported by the reduced amount of phospho-tau (Thr181) in neuritic processes around Aβ plaques. In addition, ACEA-treated mice show decreased astroglial response in the vicinity of Aβ plaques and decreased expression of the pro-inflammatory cytokine interferon-γ in astrocytes when compared with age-matched vehicle-treated transgenic mice. Our present results show a beneficial effect of ACEA at both the neuronal, mediated at least in part by GSK3β inhibition, and glial levels, resulting in a reduction of reactive astrocytes and lower expression of interferon-γ. As a consequence, targeting the CB1 receptor could offer a versatile approach for the treatment of Alzheimer's disease.


Gitools: analysis and visualisation of genomic data using interactive heat-maps.
Intuitive visualization of data and results is very important in genomics, especially when many conditions are to be analyzed and compared. Heat-maps have proven very useful for the representation of biological data. Here we present Gitools (http://www.gitools.org), an open-source tool to perform analyses and visualize data and results as interactive heat-maps. Gitools contains data import systems from several sources (i.e. IntOGen, Biomart, KEGG, Gene Ontology), which facilitate the integration of novel data with previous knowledge.


Long-term outcome of autoimmune disease following allogeneic bone marrow transplantation.
To investigate the long-term outcome of autoimmune disease following allogeneic bone marrow transplantation (BMT), and its relationship to hemopoietic chimerism. Three previously described patients with rheumatoid arthritis (RA) who underwent allogeneic BMT for therapy-related severe aplastic anemia and 1 new patient with psoriasis who received BMT for chronic myeloid leukemia (CML) were followed up. Molecular studies were performed to assess hemopoietic and immune reconstitution in 3 cases. In 2 of the RA patients, the RA remained in remission without treatment, with nonprogressive disease, 11 and 13 years after BMT. The third patient with RA had a relapse 2 years after BMT, although the previously aggressive disease subsequently ran an attenuated course with treatment-free remission for the last 11 years. Comparison with other cases of RA suggests that graft-versus-host disease may influence the long-term outcome, perhaps through ongoing inhibition of the immune system. In the patient with psoriasis, BMT was followed by remission, but the psoriatic rash recurred and arthropathy developed 12 months later. The psoriasis and arthropathy remained active 4.5 years post-BMT, although the CML remained in remission. Molecular studies in the 2 patients whose RA remained in continued remission and in the patient with psoriasis that relapsed confirmed complete donor hemopoietic reconstitution. Long-term followup of autoimmune disease after allogeneic transplantation confirmed cure of the autoimmune disease in some, but eventual relapse in others. The occurrence of relapse despite complete donor hemopoietic reconstitution is evidence for the development of de novo, as opposed to persistent, disease, and is possibly related to intrinsic susceptibility of the transplanted stem cells or to host factors. There may be a relationship between remission of autoimmune disease and graft-versus-host reaction. These findings have relevance for the evolving application of stem cell transplantation as a therapy for autoimmune diseases.


Current approaches for the assessment of in situ biodegradation.
Considering the high costs and technical difficulties associated with conventional remediation strategies, in situ biodegradation has become a promising approach for cleaning up contaminated aquifers. To verify if in situ biodegradation of organic contaminants is taking place at a contaminated site and to determine if these processes are efficient enough to replace conventional cleanup technologies, a comprehensive characterization of site-specific biodegradation processes is essential. In recent years, several strategies including geochemical analyses, microbial and molecular methods, tracer tests, metabolite analysis, compound-specific isotope analysis, and in situ microcosms have been developed to investigate the relevance of biodegradation processes for cleaning up contaminated aquifers. In this review, we outline current approaches for the assessment of in situ biodegradation and discuss their potential and limitations. We also discuss the benefits of research strategies combining complementary methods to gain a more comprehensive understanding of the complex hydrogeological and microbial interactions governing contaminant biodegradation in the field.


Diabetes and Hypertension Differentially Affect Renal Catecholamines and Renal Reactive Oxygen Species.
Patients with diabetic hypertensive nephropathy have accelerated disease progression. Diabetes and hypertension have both been associated with changes in renal catecholamines and reactive oxygen species. With a specific focus on renal catecholamines and oxidative stress we examined a combined model of hypertension and diabetes using normotensive BPN/3J and hypertensive BPH/2J Schlager mice. Induction of diabetes (5 × 55 mg/kg streptozotocin i.p.) did not change the hypertensive status of BPH/2J mice (telemetric 24 h avg. MAP, non-diabetic 131 ± 2 vs. diabetic 129 ± 1 mmHg, n.s at 9 weeks of study). Diabetes-associated albuminuria was higher in BPH/2J vs. diabetic BPN/3J (1205 + 196/-169 versus 496 + 67/-59 μg/24 h, p = 0.008). HPLC measurement of renal cortical norepinephrine and dopamine showed significantly greater levels in hypertensive mice whilst diabetes was associated with significantly lower catecholamine levels. Diabetic BPH/2J also had greater renal catecholamine levels than diabetic BPN/3J (diabetic: norepinephrine BPN/3J 40 ± 4, BPH/2J 91 ± 5, p = 0.010; dopamine: BPN/3J 2 ± 1; BPH/2J 3 ± 1 ng/mg total protein, p < 0.001 after 10 weeks of study). Diabetic BPH/2J showed greater cortical tubular immunostaining for monoamine oxidase A and cortical mitochondrial hydrogen peroxide formation was greater in both diabetic and non-diabetic BPH/2J. While cytosolic catalase activity was greater in non-diabetic BPH/2J it was significantly lower in diabetic BPH/2J (cytosolic: BPH/2J 127 ± 12 vs. 63 ± 6 nmol/min/ml, p < 0.001). We conclude that greater levels of renal norepinephrine and dopamine associated with hypertension, together with diabetes-associated compromised anti-oxidant systems, contribute to increased renal oxidative stress in diabetes and hypertension. Elevations in renal cortical catecholamines and reactive oxygen species have important therapeutic implications for hypertensive diabetic patients.


Why is African swine fever still present in Sardinia?
African swine fever (ASF) is an infectious disease of swine that has been present in Sardinia since 1978. Soon after introduction of the disease, several control and eradication programmes were established with limited success. Some researchers attributed the persistence of the disease in central and eastern areas to certain socio-economic factors, the existence of some local and traditional farming practices (i.e., unregistered free-ranging pigs known as brado animals) and the high density of wild boar in the region. In the past, scarcity of swine data in Sardinia complicated the evaluation and study of ASF on the island. More complete, accurate and reliable information on pig farms has become available as a result of the most recent eradication programmes. Here, we perform statistical modelling based on these data and the known distribution of domestic pig and wild boar to identify the main risk factors that have caused ASF persistence in Sardinia. Our results categorized, identified and quantified nine significant risk factors, six of which have not been previously described. The most significant factors were the number of medium-sized farms, the presence of brado animals and the combination of estimated wild boar density and mean altitude above sea level. Based on these factors, we identified regions in eastern and central Sardinia to be at greatest risk of ASF persistence; these regions are also where the disease has traditionally been endemic. Based on these risk factors, we propose specific control measures aimed at mitigating such risks and eradicating ASF from the island.


Neuraxial opioids as analgesia in labour and postoperative after caesarean section and hysterectomy: A questionnaire survey in Sweden.
Background: Neuraxial opioids improve labour analgesia and analgesia after caesarean section (CS) and hysterectomy. Undesirable side effects and difficulties in arranging postoperative monitoring might influence the use of these opioids. The aim of the present survey was to assess the use of intrathecal and epidural morphine in gynaecology and obstetrics in Sweden. Methods: A questionnaire was sent to 47 anaesthesiologists at obstetric units in Sweden concerning the use and postoperative monitoring of morphine, sufentanil and fentanyl in spinal/epidural anaesthesia. Results: A total of 32 units responded representing 83% of annual CS in Sweden. In CS spinal anaesthesia, 20/32 units use intrathecal morphine, the most common dose of which was 100 μg (17/21). Intrathecal fentanyl (10-20 μg) was used by 21 units and sufentanil (2.5 -10 μg) by 9/32 of the responding units. In CS epidural anaesthesia, epidural fentanyl (50-100 μg) or sufentanil (5-25 μg) were commonly used (25/32), and 12/32 clinics used epidural morphine, the majority of units used a 2 mg dose. Intrathecal morphine for hysterectomy was used by 20/30 units, with 200 μg as the most common dose (9/32). Postoperative monitoring was organized in adherence to the National Guidelines; the patient is in postoperative care or an obstetrical ward over 2-6 hours and up-to 12 hours in an ordinary surgical ward. Risk of respiratory depression/difficult to monitor was a reason for not using intrathecal opioids. Conclusions: Neuraxial morphine is used widely in Sweden in CS and hysterectomy, but is still restricted in some units because of the concern for respiratory depression and difficulties in monitoring.


Preprocessing and downstream analysis of microarray DNA copy number profiles.
Analysis of DNA copy number profiles requires methods tailored to the specific nature of these data. The number of available data analysis methods has grown enormously in the last 5 years. We discuss the typical characteristics of DNA copy number data, as measured by microarray technology and review the extensive literature on preprocessing methods such as segmentation and calling. Subsequently, the focus narrows to applications of DNA copy number in cancer, in particular, several downstream analyses of multi-sample data sets such as testing, clustering and classification. Finally, we look ahead: what should we prepare for and which methodology-related topics may deserve attention in the near future?


Testing strategies to detect acute and prevalent HIV infection in adult outpatients seeking healthcare for symptoms compatible with acute HIV infection in Kenya: a cost-effectiveness analysis.
Detection of acute and prevalent HIV infection using point-of-care nucleic acid amplification testing (POC-NAAT) among outpatients with symptoms compatible with acute HIV is critical to HIV prevention, but it is not clear if it is cost-effective compared with existing HIV testing strategies. We developed and parametrised a decision tree to compare the cost-effectiveness of (1) provider-initiated testing and counselling (PITC) using rapid tests, the standard of care; (2) scaled-up provider-initiated testing and counselling (SU-PITC) in which all patients were tested with rapid tests unless they opted out; and (3) opt-out testing and counselling using POC-NAAT, which detects both acute and prevalent infection. The model-based analysis used data from the Tambua Mapema Plus randomised controlled trial of a POC-NAAT intervention in Kenya, supplemented with results from a stochastic, agent-based network model of HIV-1 transmission and data from published literature. The analysis was conducted from the perspective of the Kenyan government using a primary outcome of cost per disability-adjusted life-year (DALY) averted over a 10-year time horizon. After analysing the decision-analytical model, the average per patient cost of POC-NAAT was $214.9 compared with $173.6 for SU-PITC and $47.3 for PITC. The mean DALYs accumulated per patient for POC-NAAT were 0.160 compared with 0.176 for SU-PITC and 0.214 for PITC. In the incremental analysis, SU-PITC was eliminated due to extended dominance, and the incremental cost-effectiveness ratio (ICER) comparing POC-NAAT to PITC was $3098 per DALY averted. The ICER was sensitive to disability weights for HIV/AIDS and the costs of antiretroviral therapy. POC-NAAT offered to adult outpatients in Kenya who present for care with symptoms compatible with AHI is cost-effective and should be considered for inclusion as the standard of HIV testing in this population. Tambua Mapema ("Discover Early") Plus study (NCT03508908) conducted in Kenya (2017-2020) i.e., Post-results.


The 2013 HIV Continuum of Care in Tennessee: Progress Made, but Disparities Persist.
We measured patient engagement in the human immunodeficiency virus (HIV) continuum of care in Tennessee after implementation of enhanced surveillance activities to assess progress toward 2015 statewide goals. We also examined subgroup disparities to identify groups at risk for poor outcomes. We estimated linkage to care, retention in care, and viral suppression among HIV-infected people in Tennessee in 2013, overall and by subgroup, after implementation of enhanced laboratory reporting, address verification, and death-matching procedures. Of 792 people newly diagnosed with HIV infection in 2013, 632 (79.8%) were linked to care, close to the 2015 goal of ≥80%. Of 15 473 people living and diagnosed with HIV infection before 2013, 8458 (54.7%) were retained in care, approaching the 2015 goal of ≥64.0%. A total of 8640 (55.8%) were virally suppressed, surpassing the 2015 goal of ≥51.0%. Compared with people living and diagnosed with HIV infection before 2013, newly diagnosed people were more likely to be younger, male, non-Hispanic black, and men who have sex with men (MSM). For linkage to care, retention in care, and viral suppression, younger and non-Hispanic black people fared worse, whereas females and those enrolled in the Ryan White program fared better. For retention in care and viral suppression, Hispanic people, injection drug users, and East Tennessee residents fared worse than those in Memphis, whereas MSM fared better. Nashville residents fared worse in retention in care than Memphis residents. Tennessee's HIV continuum of care in 2013 showed progress toward 2015 goals. Future efforts to improve the HIV continuum of care should be directed toward vulnerable groups and regions, particularly young, non-Hispanic black, and Hispanic people; injection drug users; and residents of the East Tennessee and Nashville regions.


Comparison of safety between individualized and empiric dose regimen of amitriptyline in the treatment of major depressive episode.
To accomplish therapeutic goal it is necessary to adjust the dose of medication to be right for every single patient. This procedure of dose adjustment is individualized dose regimen. First of all, pharmacokinetic aspects should be revised, including parameters such as resorption, distribution, metabolism and secretion of drug. For these purposes, the authors developed and clinically assessed the modified Bayesian method supported by original basic computer program. The aim of research was to compare frequency of adverse events in cases of individualized and empiric dose regimens of amitriptyline in the treatment of major depressive episode. Sixty subjects (32- 65 years old), with major depressive disorder (International Classification of Disease, 10th revision), were randomly assigned and single- blinded to take individualized (experimental group, n=30) or empiric (control group, n=30) doses of amitriptyline for 8 weeks. CGI scale and originally designed questionnaire were used for adverse events assessment. In experimental group, 69 complaints on nine different types of adverse effects were recorded during eight-week treatment period. Severe adverse events, such as confusion or arrhythmia, were not registered in this subgroup. In control group, 111 complaints on twelve different types of adverse effects were recorded. Most common were anticholinergic effects, but during the third and fourth week from baseline, some severe adverse events were observed: tremor (16%), fatigue (16%), in one of the subjects confusion occurred and arrhythmia in another. Analyzing of the results according to CGI scale for adverse events showed that, during the treatment period, adverse events were less frequent in experimental group. This was particularly obvious in the first four weeks of treatment, when statistically significant difference (p<0.05) was observed.


Enhancing the dental histology curriculum using computer technology.
The predominant difference between the histology offered to dental students and that taken by other health care professionals is the emphasis placed on the oral tissues. The oral histology component of the dental curriculum is commonly handled in one of three ways, all delivering far more detailed information than the often less than one hour that a typical medical histology course spends on the oral cavity and its component tissues. Overall, three general curricular styles can be defined: 1) dental histology is taught by medical or dental faculty as a separate course, the oral histology component being a separate course taught by either faculty group; 2) medical and dental students take histology together in a single class with the oral histology component taught separately by faculty from either college; and 3) both basic and oral histology is taught within a single semester, the format used at the University of Kentucky College of Dentistry. The oral histology topics are similar in all of the course formats, regardless of whether they occur as a stand-alone course or are merged with basic histology. The main portion of this paper will describe a self-study, non-microscope-based laboratory experience designed to complement this fused topic course. Self-study labs using digital media are becoming more popular across both medical and dental histology curricula, specifically with the oral histology component where the histological skills for preparing these tissues are rapidly disappearing from many schools. This paper describes a typical syllabus for a fused course, outlining the topics for basic and oral histology, and demonstrates how the laboratory portion has been enhanced using digital technology.


[Standardization in forensic medicine].
It is for the first time that an issue is raised on the need to introduce a system of standardization into the forensic medical field. A general scheme is suggested of how to do it.


A rapid method for detecting extracellular proteinase activity in Cryptococcus neoformans and a survey of 63 isolates.
A rapid method to detect extracellular proteolytic activity around colonies of Cryptococcus neoformans was developed with tannic acid used to complex with residual protein in a solid medium. A survey was conducted with 32 isolates of C. neoformans var. gattii and 31 isolates of C. neoformans var. neoformans which were cultured on medium containing gelatin as the sole nitrogen source. The annulus of clearing around fungal colonies was > 1.2 mm in 24 (77%) isolates of C. neoformans var. neoformans compared with only 7 (22%) isolates of C. neoformans var. gattii. There was no difference in proteolytic activity between environmental and human clinical isolates of C. neoformans. However, there was a difference between the size of the annulus around animal isolates of C. neoformans var. neoformans and isolates of the same variety from other sources. The annuli around the 14 animal isolates were all >1.2 mm, while 7 (70%) of 10 human clinical isolates and only 3 (43%) of 7 environmental isolates were scored in the high proteinase range. A difference between the genetic types (as characterised by RAPD typing) of C. neoformans var. gattii was also evident with 17 (77%) of 22 VG-I isolates having a small annulus compared with only 1 (17%) of 6 VG-II and VG-III isolates with annuli of similar size. Relatively low proteinase production by C. neoformans var. gattii may reduce local and systemic spread of infection in mammalian hosts.


Inhibition Gets a New KAR Smell.
Ionotropic and metabotropic kainate receptor signaling regulates Cl- homeostasis and GABAergic inhibition Garand D, Mahadevan V, Woodin MA. J Physiol. 2018. doi:10.1113/JP276901 Potassium chloride cotransporter 2 (KCC2) plays a critical role in the regulation of chloride (Cl-) homeostasis within mature neurons. The KCC2 is a secondarily active transporter that extrudes Cl- from the neuron, which maintains a low intracellular Cl-concentration [Cl-]. This results in a hyperpolarized reversal potential of GABA ( EGABA), which is required for fast synaptic inhibition in the mature central nervous system. Potassium chloride cotransporter 2 also plays a structural role in dendritic spines and at excitatory synapses and interacts with "excitatory" proteins, including the GluK2 subunit of kainate receptors (KARs). Kainate receptors are glutamate receptors that display both ionotropic and metabotropic signaling. We show that activating KARs in the hippocampus hyperpolarizes EGABA, thus strengthening inhibition. This hyperpolarization occurs via both ionotropic and metabotropic KAR signaling in the CA3 region, whereas it is absent in the GluK1/2-/- mouse, and is independent of zinc release from mossy fiber terminals. The metabotropic signaling mechanism is dependent on KCC2, although the ionotropic signaling mechanism produces a hyperpolarization of EGABA even in the absence of KCC2 transporter function. These results demonstrate a novel functional interaction between a glutamate receptor and KCC2, a transporter critical for maintaining inhibition, suggesting that the KAR:KCC2 complex may play an important role in excitatory:inhibitory balance in the hippocampus. Additionally, the ability of KARs to regulate chloride homeostasis independently of KCC2 suggests that KAR signaling can regulate inhibition via multiple mechanisms. Activation of kainate-type glutamate receptors could serve as an important mechanism for increasing the strength of inhibition during periods of strong glutamatergic activity.


[New aspects in the treatment of puerperal mastitis (author's transl)].
36 women with postpartal breast engorgement were treated with a single oral dose of 2.5 mg bromocriptine (Pravidel). Significant relief was recorded in 28 patients, 6 patients required a second dose of 2.5 mg bromocriptine, whereas 2 patients failed to respond. Antibiotics were at first avoided in the treatment of puerperal mastitis. 26 patients with all characteristics of breast inflammation were treated exclusively with bromocriptine: for 3 days 2.5 mg t.i.d., for the following 11 days 2.5 mg twice daily. The temperature dropped below 37C in 25 patients within 12-24 hours, tension and pain disappearing simultaneously. One patient did not respond after 36 hours, so that an antibiotic was administered additionally; in another patient who had been admitted to the hospital six days after the onset of the clinical symptoms of breast inflammation, bromocriptine failed to prevent abscess formation. The results indicate that in most cases of puerperal breast inflammation no antibiotics are required. Puerperal mastitis can be treated effectively by the exclusive administration of bromocriptine.


Laser scanner for direct writing lithography.
A laser scanner and a stepping xy stage have been developed for direct writing lithography in the micron and the submicron range. System design is described and examples of exposed photoresist with a structure size of 1 microm are presented.


Calcium action potentials and potassium permeability activation in pancreatic beta-cells.
Ionic control mechanisms of mouse pancreatic beta-cell action potentials ("spikes"), in response to glucose, were studied by measuring membrane potentials with intracellular microelectrodes. The curve relating the peaks of the spikes to the log of the external calcium concentration above 10 mM has a slope of 25 mV/10-fold increase of Ca2+. This approaches the value predicted by the Nernst equation for a pure Ca2+ electrode. Increasing the external [Ca2+]o from 0 to 42.5 mM caused an increase in rates of spike depolarization and repolarization. Lowering [Ca2+]o or applying Ca2+ conductance blockers, including Co2+ (1.25 mM), Mn2+ (2mM), and D-600 (2 X 10(-4) M), caused a decrease in rates of spikes depolarization and repolarization, with an increase of [Ca2+]o reversing this effect. Higher concentrations of these Ca2+-conductance blockers eliminated the spike activity. Quinidine at a high concentration (10(-3) M) blocked spike repolarization. Tetraethylammonium (TEA, 25 mM) increased spike amplitude and duration. Therefore, it is concluded that Ca2+ entry during the spike affects potassium permeability, which is inhibited by TEA. Also, there is a competitive binding between Co2+, Mn2+, Mg2+, and Ca2+, the charge carrier. These cations may have an additional action of substituting for Ca2+ to "stabilize" the membrane.


Omics methods for probing the mode of action of natural and synthetic phytotoxins.
For a little over a decade, omics methods (transcriptomics, proteomics, metabolomics, and physionomics) have been used to discover and probe the mode of action of both synthetic and natural phytotoxins. For mode of action discovery, the strategy for each of these approaches is to generate an omics profile for phytotoxins with known molecular targets and to compare this library of responses to the responses of compounds with unknown modes of action. Using more than one omics approach enhances the probability of success. Generally, compounds with the same mode of action generate similar responses with a particular omics method. Stress and detoxification responses to phytotoxins can be much clearer than effects directly related to the target site. Clues to new modes of action must be validated with in vitro enzyme effects or genetic approaches. Thus far, the only new phytotoxin target site discovered with omics approaches (metabolomics and physionomics) is that of cinmethylin and structurally related 5-benzyloxymethyl-1,2-isoxazolines. These omics approaches pointed to tyrosine amino-transferase as the target, which was verified by enzyme assays and genetic methods. In addition to being a useful tool of mode of action discovery, omics methods provide detailed information on genetic and biochemical impacts of phytotoxins. Such information can be useful in understanding the full impact of natural phytotoxins in both agricultural and natural ecosystems.


[New data on morphogenesis of gunshot bone injuries].
Studies with the use of atomic-force and scanning electron microscopy yielded new data that extend our knowledge of the complicated process underlying bone tissue degeneration as a result of its interaction with a high-speed injurious projectile. These data open up good prospects for the study of gunshot wounds and provide novel opportunities for forensic medical examination and diagnostics including confirmation of gunshot origin of the injury, elucidation of the properties (in the first place, energetic characteristics) of the injurious projectile, and determination of the wound size.


Experience with the SynCardia total artificial heart in a Canadian centre.
The SynCardia total artificial heart (TAH) provides complete circulatory support by replacing both native ventricles. Accepted indications include bridge to transplantation and destination therapy. We review our experience with TAH implantation during a period when axial flow pump became available. We retrospectively analyzed the demographics, clinical characteristics and survival of all patients receiving the TAH. From September 2004 to November 2016, 13 patients (12 men, mean age 45 ± 13 yr) received the TAH for refractory cardiogenic shock secondary to idiopathic (56%) or ischemic (17%) cardiomyopathy and to other various causes (33%). Before implantation, mean ejection fraction was 14% ± 4%, 7 (54%) patients had previous cardiac surgery, 4 (31%) were on mechanical ventilation, and 3 (23%) patients were on dialysis. The mean duration of TAH support was 46 ± 40 days. Three (23%) patients died while on support after a mean of 15 days. Actuarial survival on support was 77% ± 12% at 30 days after implantation. Complications on support included stroke (n = 1, 8%), acute respiratory distress syndrome requiring prolonged intubation (n = 5, 38%) and acute renal failure requiring temporary dialysis (n = 5, 38%). Ten (77%) patients survived to be transplanted after a mean of 52 ± 42 days of support. Actuarial survival rates after transplant were 67% ± 16% at 1 month and 56% ± 17% at 1 year after transplantation. The TAH provides an alternative with low incidence of neurologic events in extremely fragile and complex patients waiting for heart transplantation. Complex and unusual anatomic conditions explained the current use of TAH.


Laryngeal and hypopharyngeal cancer and occupation: results of a case control-study.
To ascertain whether certain occupations are associated with laryngeal or hypopharyngeal cancer. A hospital based case-control study was carried out in 15 hospitals in France. It included 528 male cases diagnosed between January 1989 and April 1991, and 305 male controls with various other types of cancer. Interviews were carried out to obtain lifetime job histories and information on potential confounders. Logistic regression was used to compute the odds ratios (OR) for each of about 80 occupations and industries. There was an excess risk of laryngeal and hypopharyngeal cancer among service workers (OR 2.2, 95% confidence interval (95% CI) 1.3 to 3.9), agricultural and animal husbandry workers (OR 1.6, 95% CI 0.9 to 2.8), miners and quarrymen (OR 2.0, 95% CI 0.9 to 4.3), plumbers and pipe fitters (OR 2.6, 95% CI 0.8 to 8.1), glass formers and potters (OR 4.3, 95% CI 1.0 to 18) transport equipment operators (OR 1.5, 95% CI 1.0 to 2.5), and unskilled workers (OR 1.7, 95% CI 1.0 to 2.9). Analysis by industrial branch showed an excess risk for coal mining (OR 2.1, 95% CI 1.1 to 4.1), manufacture of metal products (OR 1.9, 95% CI 1.0 to 3.3), and administration and sanitary services (OR 1.7, 95% CI 1.1 to 2.5). These results suggest that occupational exposure might have a role in generating laryngeal and hypopharyngeal cancer, and indicate the need for further evaluation of these findings, an for the identification of the carcinogens which might account for the excess risks found for certain occupations.


Localization of symbiotic mutations in Rhizobium meliloti.
A total of 5 Nod- and 57 Fix- symbiotic mutants of Rhizobium meliloti strain 41 have been isolated after either nitrosoguanidine or Tn5 transposition mutagenesis. Chromosomal locations of mutations in 1 Nod- and 11 Fix- derivatives were ascertained by transferring the chromosome (mobilized by plasmid R68.45), in eight fragments, into symbiotically effective recipients and testing the recombinants for symbiotic phenotype. Alternatively, the kanamycin resistance marker of Tn5 was mapped. In five mutants the fix alleles were localized on different chromosomal regions, but six other fix mutations and one nod mutation tested did not map onto the chromosome. It was shown that the chromosome-mobilizing ability (Cma+) of R68.45 was not involved in the mobilization of genes located extrachromosomally. Moreover, Cma- derivatives of R68.45 could mobilize regions of the indigenous plasmid pRme41b but not chromosomal genes. Thus, mobilization of a marker by Cma- R68.45 indicates its extrachromosomal location. With a 32P-labeled DNA fragment carrying Tn5 as a hybridization probe, it was shown that in five extrachromosomally located Tn5-induced fix mutants and one nod mutant Tn5 was localized on plasmid pRme41b. This is in agreement with the genetic mapping data.


Selective distribution of mu-opioid receptors in C1 adrenergic neurons and their afferents.
Agonists of the mu-opioid receptor (MOR) have profound effects on blood pressure, heart rate, and respiration that may be mediated by C1 adrenergic neurons in the rostral ventrolateral medulla (RVL). C1 neurons are sympathoexcitatory and are involved in both tonic and reflex regulation of sympathetic outflow. This study was designed to determine whether C1 neurons, or their afferents, contain MOR. C1 neurons were identified by using an antibody against the epinephrine synthesizing enzyme phenylethanolamine-N-methyl transferase (PNMT), whereas MOR was localized by using an antipeptide antibody that recognizes the cloned MOR, MOR1. Combined immunoperoxidase and immunogold methods were used to examine the cellular distribution of MOR1 relative to PNMT-containing neurons in the RVL. MOR1 was found in 22% of PNMT-containing dendrites (n = 392), whereas MOR1-containing axons or axon terminals contacted 14% of PNMT-containing dendrites. This distribution was heterogenous with regard to dendritic size: PNMT-labeled dendrites containing MOR1 were usually large (60% were >1.2 microm), whereas PNMT-containing dendrites that received MOR1-labeled afferents were usually small (79% were <1.2 microm). Individual dendrites rarely contained MOR1 at both pre- and postsynaptic sites. Together these results suggest that MOR agonists may directly influence the activity of C1 neurons, as well as the activity of select afferents to these cells. Plasmalemmal membrane labeling for MOR1 was more frequent in smaller PNMT-containing dendrites, suggesting that postsynaptic receptors are more readily available for ligand binding in small dendrites, although the receptor was more frequently detected in larger PNMT dendrites. The selective distribution of MORs to specific pre- and postsynaptic sites suggests the receptor may be selectively trafficked to positions where it may regulate afferent activity that is heterogeneously distributed along the dendritic tree of C1 neurons.


Statistical manipulation for normalization of data: in vitro thyroid function tests.
Interest in chemical and statistical methods chosen to define "normal" populations for the clinical significance of tests has grown recently. Because few clinical values are distributed in gaussian fashion, recommendations for smoothing of data by transforms have been prepared. In this paper we examine mathematical transformations as they are applied to in vitro tests of thyroid function and evaluate the use of multivariate regression analysis. Mathematical transforms used included square root, two parameter log, three parameter log, and inverse hyperbolic sine methods. Multivariate regression analysis was obtained by comparing test data for the T3 uptake, T4, and effective thyroxine ratio with clinical diagnoses as individual and aggregate weighting values for decision. None of the mathematical transforms resulted in complete elimination of diagnostic errors when compared with clinical diagnoses. The effective thyroxine ratio by itself had the highest correlation with patient findings. Additions of other commonly used in vitro function tests added little diagnostic accuracy.


Denervation of the radiocarpal joint. A follow-up study in 22 patients.
Denervation surgery has been a mainstay of our management of chronic pain in the wrist. If there is useful movement at the wrist we prefer denervation to arthrodesis. We have reviewed 22 patients at a mean of 50 months after such denervation surgery at the wrist. This was the only treatment in 16 patients; the other six also had other treatments. Pain was reduced in 16 patients, and 17 were satisfied or improved. None of the patients wished to have a supplementary arthrodesis. We stress the importance of preoperative blockade tests and of a very detailed knowledge of the local anatomy.


Rational design and latest advances of polysaccharide-based hydrogels for wound healing.
Acute and chronic wounds cause severe physical trauma to patients and also bring an immense socio-economic burden. Hydrogels are considered to be effective wound dressings. Polysaccharides possessing distinctive properties such as biocompatibility, biodegradability, and nontoxicity are promising candidates to structure hydrogels for wound healing. Polysaccharide-based hydrogels can provide suitable moisture for the wound and act as a shield against bacteria. Adequate mechanical properties, degradability, and therapeutic agent controlled release of polysaccharide-based hydrogels have been already characterized for effective utilization. This review presented several crucial design considerations about hydrogels for wound healing, and the current state of polysaccharide (chitosan, alginate, hyaluronic acid, cellulose, dextran, and starch)-based hydrogels as wound dressings was also summarized. The commonly used crosslinking techniques, including physical, chemical, and enzymatic crosslinking, are discussed in detail. Finally, we outline the challenges and perspectives about the improvement of polysaccharide-based hydrogels.


Approach for evaluating inundation risks in urban drainage systems.
Urban inundation is a serious challenge that increasingly confronts the residents of many cities, as well as policymakers. Hence, inundation evaluation is becoming increasingly important around the world. This comprehensive assessment involves numerous indices in urban catchments, but the high-dimensional and non-linear relationship between the indices and the risk presents an enormous challenge for accurate evaluation. Therefore, an approach is hereby proposed to qualitatively and quantitatively evaluate inundation risks in urban drainage systems based on a storm water management model, the projection pursuit method, the ordinary kriging method and the K-means clustering method. This approach is tested using a residential district in Guangzhou, China. Seven evaluation indices were selected and twenty rainfall-runoff events were used to calibrate and validate the parameters of the rainfall-runoff model. The inundation risks in the study area drainage system were evaluated under different rainfall scenarios. The following conclusions are reached. (1) The proposed approach, without subjective factors, can identify the main driving factors, i.e., inundation duration, largest water flow and total flood amount in this study area. (2) The inundation risk of each manhole can be qualitatively analyzed and quantitatively calculated. There are 1, 8, 11, 14, 21, and 21 manholes at risk under the return periods of 1-year, 5-years, 10-years, 20-years, 50-years and 100-years, respectively. (3) The areas of levels III, IV and V increase with increasing rainfall return period based on analyzing the inundation risks for a variety of characteristics. (4) The relationships between rainfall intensity and inundation-affected areas are revealed by a logarithmic model. This study proposes a novel and successful approach to assessing risk in urban drainage systems and provides guidance for improving urban drainage systems and inundation preparedness.


Cellular effects and epistasis among three determinants of adaptation in experimental populations of Saccharomyces cerevisiae.
Epistatic interactions in which the phenotypic effect of an allele is conditional on its genetic background have been shown to play a central part in various evolutionary processes. In a previous study (J. B. Anderson et al., Curr. Biol. 20:1383-1388, 2010; J. R. Dettman, C. Sirjusingh, L. M. Kohn, and J. B. Anderson, Nature 447:585-588, 2007), beginning with a common ancestor, we identified three determinants of fitness as mutant alleles (each designated with the letter "e") that arose in replicate Saccharomyces cerevisiae populations propagated in two different environments, a low-glucose and a high-salt environment. In a low-glucose environment, MDS3e and MKT1e interacted positively to confer a fitness advantage. Also, PMA1e from a high-salt environment interacted negatively with MKT1e in a low-glucose environment, an example of a Dobzhansky-Muller incompatibility that confers reproductive isolation. Here we showed that the negative interaction between PMA1e and MKT1e is mediated by alterations in intracellular pH, while the positive interaction between MDS3e and MKT1e is mediated by changes in gene expression affecting glucose transporter genes. We specifically addressed the evolutionary significance of the positive interaction by showing that the presence of the MDS3 mutation is a necessary condition for the spread and fixation of the new mutations at the identical site in MKT1. The expected mutations in MKT1 rose to high frequencies in two of three experimental populations carrying MDS3e but not in any of three populations carrying the ancestral allele. These data show how positive and negative epistasis can contribute to adaptation and reproductive isolation.


Instrumentation of the infected and unstable spine: a review of 17 cases from the thoracic and lumbar spine with pyogenic infections.
A retrospective review of 17 consecutive cases of spinal instrumentation for pyogenic vertebral osteomyelitis (PVO) with follow-up of > 2 years was undertaken, to describe the clinical course and outcomes in patients with instrumentation of actively infected spines. In 17 patients with PVO, instrumentation of the spine was performed during the period of clinical infection. Twelve of 17 patients were immunocompromised because of systemic or iatrogenic factors. Five patients had a history of malignancy and four had had spinal irradiation. In all 17 cases, the infection appeared to clinically be controlled after instrumentation. All patients were mobilized directly after instrumentation. The erythrocyte sedimentation rate returned to normal in 15 patients without rheumatic disease and decreased by more than half in two patients with inflammatory arthritis. Four patients had died at follow-up, and none of these had signs of persistent infection. Eight cases had significant postoperative complications (47%), including two instrumentation failures and one wound dehiscence. Spinal instrumentation in selected cases of PVO allows early mobilization and did not seem to compromise the ability to clear infection. In certain recalcitrant cases, stabilization seemed to promote clinical resolution of the infection.


Deoxynucleotide-polymerizing enzyme activities in T- and B-cells of acute lymphoblastic leukemia origin.
All 5 thymus-dependent cell (T-cell) lines (Molt-3; Molt-4; RPMI-8402; CCRF-CEM; CCRF-HSB-2) and 7 thymus-independent cell (B-cell) lines (RPMI-8382, RPMI-8392, RPMI-8412, RPMI-8422, RPMI-8432, RPMI-8442, CCRF-SB) established so far from acute lymphoblastic leukemia patients were examined for deoxynucleotide polymerizing enzymes. All T- and B-cells had DNA polymerase gamma, DNA polymerase beta, and terminal deoxynucleotidyl transferase both in the soluble (the latter 2 enzymes only in small amounts) and chromatin fraction, whereas DNA polymerase alpha was found only in the soluble fraction. With respect to their sedimentation and chromatographic behavior, template-primer requirements, Km for deoxythymidine triphosphate or deoxyguanosine triphosphate divalent cation preference, effect of NaCI and inhibitors, the enzymes from T- and B-cells resembled each other and those from other mammalian cells. DNA polymerase alpha, beta, and gamma from T-cells like those from "fresh" acute lymphoblastic leukemia cells, were more thermolabile than those from B-cells or phytohemagglutinin-stimulated normal lymphocytes. In addition, the terminal deoxynucleotidyl transferase from the above cells was completely inactivated in 5 to 6 min at 50 degrees, whereas the DNA polymerase alpha, beta, and gamma retained considerable activity even after heating for 25 min at 50 degrees. DNA polymerase activity of the soluble fraction from T-cells was of the same magnitude as in B-cells when expressed on a DNA basis but twice that of B-cells when expressed on a protein basis. High terminal deoxynucleotidyl transferase activity, equivalent to that observed in acute lymphoblastic leukemia cells, was found in all T-cell lines that, when expressed on a DNA basis, was 30 to 100 times higher than the B-cell lines tested. These results support the suggestion of earlier investigators that T-cell lines examined here may have originated from leukemic cells.


[Age-specific morphological-functional characteristics of the rabbit's hippocampal neurons during conditioning].
Formation of trace rhythm recruitment (an analogue of conditioned time reflex) was studies in CA3 hippocampal neurons of alert young (less than one year), old (54-65 months), and very old rabbits after a prolonged (10-20 min) electro-cutaneous stimulation of a forelimb with the frequency of 0.5-1 Hz. Comparative analysis of neuronal spike activity in young and old rabbits showed that in the late ontogeny the number of spontaneously active neurons was significantly decreased, the proportion of slowly firing neurons increased, the interspike intervals and intervals between spike groups became longer, the number of spikes in a group reduced. The ability of hippocampal neurons to acquire and reproduce the rhythm of the previous stimulation declined with age. No appropriate rhythms were found in neurons of very old animals. A nonspecific increase in neuronal baseline activity was observed in old rabbits after the stimulation. Deterioration of morphological structures of hippocampal neurons and glial cells may explain the impairment of mnestic processes in late ontogeny.


Intraprocedural and long-term incomplete occlusion of the left atrial appendage following placement of the WATCHMAN device: a single center experience.
Transcatheter left atrial appendage (LAA) closure with the WATCHMAN device has become one of the therapeutic options in atrial fibrillation (AF) patients who are at high risk for ischemic stroke. However, the incidence and evolution of incomplete occlusion of the LAA during and after placement of the WATCHMAN device has not been reported. Fifty-eight consecutive patients who had undergone WATCHMAN device implant were included in the study. Intraprocedural, 45-day and 12-month transesophageal echocardiogram images were reviewed and analyzed. Peridevice gap was noted in 16 (27.6%), 17 (29.3%), and 20 (34.5%) patients across the 3 time points. Intraprocedural gaps are more likely to be persistent until 12 months and become larger in size over time. New gap also occurs during follow-up even if the LAA was completely sealed at implantation. One patient had an ischemic stroke 4.7 months after implant; another patient developed a left atrial thrombus over the device 21.6 months after implant. Both patients had intraprocedural gap and discontinued warfarin therapy after the 45-day evaluation. Incomplete LAA occlusion with a gap between the WATCHMAN device surface and the LAA wall is relatively common. Intraprocedural gaps are more likely to become bigger over time and persist, while new gaps also occur during follow-up. Further studies are warranted to verify whether the presence and persistence of a peridevice gap is associated with increased risk of thromboembolic event in AF patients implanted with a WATCHMAN device.


Risky sexual behaviours among adolescents in Owerri Municipal: predictors of unmet family health needs.
This study examined the risky sexual behaviours (RSBs) of adolescents in Owerri Municipal in Imo State. Adopting the descriptive Survey research design, a stratified sampling technique was used to enroll 1008 adolescents aged 10 - 19 from 4 secondary schools into the study. A structured questionnaire was used for data collection. Result shown that majority of the adolescent (47.4%) have had sex and many have engaged in one form of RSBs or another. Peer group seem to be major source of the sexuality information (55.6%) and influencing factor (52.3%). Significant association was found to exist between adolescents RSBs and age at first sexual experience or adolescent perception of parental rearing pattern (p<.05). The study challenged the stake holders involved in the inculcation of values, curriculum design or policy formulation to provide appropriate, time sensitive and scientifically sound sexuality information for adolescents.


[Tumors of the footbones- a report from the Hamburg Bone Tumor Registry].
Aim of the present study was a systematic examination of the tumors of the foot registered in the Hamburg Bone Tumor Registry regarding age, sex, location, diagnosis and morphological characteristics. The registry files and histological specimens of 367 tumors and tumor-like lesions of the foot were reviewed. Males were more frequently affected (ratio 4 : 3). Some 20.4 % of all mass forming tumors were malignant. Cartilage tumors (146 cases), cystic (132 cases) and osteoblastic lesions (33 cases) were most common. Several tumors showed a strong predilection for certain parts of the foot. In the calcaneus a solitary bone cyst was the most common lesion. Lesions in the talus and metatarsals with a similar morphology mostly represented intraosseous ganglion cysts. Other tumors in the calcaneus were mainly cartilaginous. Besides chondroblastoma, chondrosarcoma was regularly diagnosed. Chondroma was extremely rare at this site. Contrary to that chondroma was regularly found at the metatarsal and phalangeal bones, it was 4 times more common than chondrosarcoma. An even distribution showed aneurysmal bone cysts and osteoidosteoma. Very rare lesions were fibrous dysplasia, eosinophilic granuloma and intraosseous lipoma. The knowledge of the distribution of tumors in the foot is important for an exact differential diagnosis and thereby for biopsy planning, diagnosis and therapy.


A randomised placebo controlled trial of pegylated interferon alpha in active ulcerative colitis.
Pilot studies of interferon alpha (IFN-alpha) suggest a high remission rate in the treatment of active ulcerative colitis. We evaluated the safety of pegylated interferon alpha (PegIFN) and its role in induction of remission in patients with active ulcerative colitis, in a multicentre placebo controlled trial. Sixty patients with a clinical activity score (CAI) of >6 were randomised to receive placebo (n=20), PegIFN 0.5 microg/kg (n=19), or PegIFN 1.0 microg/kg body weight (n=21) once weekly (PegIntron; Schering-Plough, USA) over 12 weeks. Patients receiving 5-aminosalicylates, steroids, and/or azathioprine in stable dosages were included. Serious adverse events were seen in none of the placebo patients, in 3/19 patients in the PegIFN 0.5 microg/kg group (hospitalisation due to disease flare up n=3), and in 3/21 in the PegIFN 1.0 microg/kg group (hospitalisation due to disease flare up n=1; thrombosis n=1; grand mal seizure n=1). Otherwise, we observed only minor IFN-alpha side effects. Clinical remission rates at week 12 (CAI < or =4) were 7/20 (35%) in the placebo, 9/19 (47%) in the PegIFN 0.5 microg/kg group, and 7/21 (33%) in the PegIFN 1.0 microg/kg group (NS). Early withdrawal from the study was observed in 11/20 placebo patients, in 6/19 in the PegIFN 0.5 microg/kg group, and in 10/21 in the PegIFN 1.0 microg/kg group, mainly due to lack of efficacy. The higher PegIFN dose was associated with a significant decrease in levels of C reactive protein (p=0.003, day 0 v 85). PegIFN is safe but not effective, at the dosages used, in patients with ulcerative colitis.


Expression of HTRA Genes and Its Association with Microsatellite Instability and Survival of Patients with Colorectal Cancer.
HtrA proteases regulate cellular homeostasis and cell death. Their dysfunctions have been correlated with oncogenesis and response to therapeutic treatment. We investigated the relation between HtrA1-3 expression and clinicopathological, and survival data, as well as the microsatellite status of tumors. Sixty-five colorectal cancer patients were included in the study. The expression of HTRA1-3 was estimated at the mRNA and protein levels by quantitative PCR and immunoblotting. Microsatellite status was determined by high-resolution-melting PCR. We found that the HTRA1 mRNA level was higher in colorectal cancer tissue as compared to the unchanged mucosa, specifically in primary lesions of metastasizing cancer. The levels of HtrA1 and HtrA2 proteins were reduced in tumor tissue when compared to unchanged mucosa, specifically in primary lesions of metastasizing disease. Moreover, a decrease in HTRA1 and HTRA2 transcripts' levels in cancers with a high level of microsatellite instability compared to microsatellite stable ones has been observed. A low level of HtrA1 or/and HtrA2 in cancer tissue correlated with poorer patient survival. The expression of HTRA1 and HTRA2 changes during colorectal carcinogenesis and microsatellite instability may be, at least partially, associated with these changes. The alterations in the HTRA1/2 genes' expression are connected with metastatic potential of colorectal cancer and may affect patient survival.


A novel subcutaneous counterpulsation device: acute hemodynamic efficacy during pharmacologically induced hypertension, hypotension, and heart failure.
The miniaturization of mechanical assist devices and less invasive implantation techniques may lead to earlier intervention in patients with heart failure. As such, we evaluated the effectiveness of a novel, minimally invasive, implantable counterpulsation device (CPD) in augmenting cardiac function during impaired hemodynamics. We compared the efficacy of a 32-mL stroke volume CPD with a standard 40-mL intra-aortic balloon pump (IABP) over a range of clinically relevant pathophysiological conditions. Male calves were instrumented via thoracotomy, the CPD was anastomosed to the left carotid artery, and the IABP was positioned in the descending aorta. Hemodynamic conditions of hypertension, hypotension, and heart failure were pharmacologically simulated and data were recorded during CPD and IABP support (off, 1:2, 1:1 modes) for each condition. In all three pathophysiological conditions, the CPD and IABP produced similar and statistically significant (P < 0.05) increases in coronary artery blood flow normalized to the left ventricular (LV) workload. During hypotension and heart failure conditions, however, the CPD produced significantly greater reductions in LV workload and myocardial oxygen consumption as compared with the IABP. A novel 32-mL CPD connected to a peripheral artery produced equivalent or greater hemodynamic benefits than a standard 40-mL IABP during pharmacologically induced hypertension, hypotension, and heart failure conditions.


Switching from cetrorelix to dydrogesterone in an IVF cycle - a new strategy for unexpected freeze-all cycles.
Preventing a luteinizing hormone (LH) surge is a major concern in controlled ovarian stimulation (COS). Several strategies have been developed over the years, including protocols with Gonadotrophin Releasing Hormone agonists and antagonists. More recently Progestin Primmed Ovarian Stimulation (PPOS) has shown to be equally effective in pituitary suppression, with comparable clinical and laboratorial outcomes. This is the case of a 34 year old female, with a previous diagnosis of primary infertility due to tubal factor and high ovarian reserve markers. The initial plan was to perform IVF/ICSI. followed by fresh blastocyst transfer. The chosen COS strategy was to use Alfacorifolitropin 150mg (Elonva®) and Cetrorelix acetate 0,25mg (Cetrotide®) in a flexible pituitary suppression protocol. However, because of elevated risk for Ovarian Hyper-stimulation Syndrome (OHSS) detected during ultrasound and hormonal monitoring, in order to diminish financial burden and to have a more patient friendly protocol, we switched cetrorelix acetate to oral dydrogesterone. COS was successful and resulted in 24 retrieved oocytes (16 metaphase 2 oocytes) without any premature LH peak. No OHSS symptoms occurred. Our main goal with this case report is to reinforce the feasibility and efficacy of this innovative approach, especially in patients aiming for a fresh embryo transfer, who present alert sings of OHSS during the stimulation. Developing friendlier and cheaper protocols in assisted reproduction makes the treatment more accessible and affordable.


Modelling the bulk properties of ambient pressure polymorphs of zirconia.
We report a detailed survey of the calculated bulk properties of zirconia using GGA and meta-GGA functionals (PBE, PBEsol, RPBE, and TPSS), dispersion (Grimme's D2 and D3 approach), and on-site Coulomb repulsion correction (U = 2-8 eV). Structural, elastic, mechanical, and dielectric properties, as well as energetics, electronic structure, and phonon dispersion curves were computed and compared to previous investigations to identify the best DFT approach for a consistent in silico description of zirconia polymorphs. In general, inclusion of dispersion corrections led to only small changes in the calculated properties, whereas DFT+U (U = 2 or 4 eV) reduced the deviations of calculated properties from the experimental results, although deterioration of the structure and relative stabilities may be observed in some cases. Standard PBEsol, RPBE+U, and PBE+U were the best methodologies for a simultaneous description of the three polymorphs of ZrO2. RPBE+U, however, was the only functional to conserve the distinct structures and stabilities of c-, t-, and m-ZrO2 when U = 4 eV was used, resulting in the best in silico replication of the band gaps of ZrO2, whilst outperforming the other methodologies in the description of elastic, mechanical, and dielectric properties of this material. Overall, these results provide insight into the most appropriate DFT methodology for in silico investigations of ZrO2, and show that simultaneous description of all three ambient pressure zirconia polymorphs by DFT techniques with acceptable levels of accuracy can be achieved only when the correct choice of methodology is applied.


Patients with Atopic Dermatitis Colonized with Staphylococcus aureus Have a Distinct Phenotype and Endotype.
Patients with atopic dermatitis (AD) are commonly colonized with Staphylococcus aureus (AD S. aureus+), but what differentiates this group from noncolonized AD patients (AD S. aureus-) has not been well studied. To evaluate whether these two groups have unique phenotypic or endotypic features, we performed a multicenter, cross-sectional study enrolling AD S. aureus+ (n = 51) and AD S. aureus- (n = 45) participants defined by the presence or absence of S. aureus by routine culture techniques and nonatopic, noncolonized control individuals (NA S. aureus-) (n = 46). Filaggrin (FLG) genotypes were determined, and disease severity (Eczema Area and Severity Index, Rajka-Langeland Severity Score, Investigator's Global Assessment score, Numerical Rating Scale, and Dermatology Life Quality Index) was captured. Skin physiology was assessed (transepidermal water loss [TEWL], stratum corneum integrity, hydration, and pH), and serum biomarkers were also measured. We found that AD S. aureus+ patients had more severe disease based on all scoring systems except itch (Numerical Rating Scale), and they had higher levels of type 2 biomarkers (eosinophil count, tIgE, CCL17, and periostin). Additionally, AD S. aureus+ patients had significantly greater allergen sensitization (Phadiatop and tIgE), barrier dysfunction (TEWL and stratum corneum integrity), and serum lactate dehydrogenase (LDH) than both the AD S. aureus- and NA S. aureus- groups. FLG mutations did not associate with S. aureus+ colonization. In conclusion, adult patients with AD who are colonized on their skin with S. aureus have more severe disease, greater type 2 immune deviation, allergen sensitization, barrier disruption, and LDH level elevation than noncolonized patients with AD.


RIP1 Kinase Is an Oncogenic Driver in Melanoma.
Although many studies have uncovered an important role for the receptor-binding protein kinase RIP1 in controlling cell death signaling, its possible contributions to cancer pathogenesis have been little explored. Here, we report that RIP1 functions as an oncogenic driver in human melanoma. Although RIP1 was commonly upregulated in melanoma, RIP1 silencing inhibited melanoma cell proliferation in vitro and retarded the growth of melanoma xenografts in vivo. Conversely, while inducing apoptosis in a small proportion of melanoma cells, RIP1 overexpression enhanced proliferation in the remaining cells. Mechanistic investigations revealed that the proliferative effects of RIP1 overexpression were mediated by NF-κB activation. Strikingly, ectopic expression of RIP1 enhanced the proliferation of primary melanocytes, triggering their anchorage-independent cell growth in an NF-κB-dependent manner. We identified DNA copy-number gain and constitutive ubiquitination by a TNFα autocrine loop mechanism as two mechanisms of RIP1 upregulation in human melanomas. Collectively, our findings define RIP1 as an oncogenic driver in melanoma, with potential implications for targeting its NF-κB-dependent activation mechanism as a novel approach to treat this disease.


A commonly used Drosophila model of Alzheimer's disease generates an aberrant species of amyloid-β with an additional N-terminal glutamine residue.
Expression of human amyloid-β (Aβ) in Drosophila is frequently used to investigate its toxicity in vivo. We expressed Aβ1-42 in the fly using a secretion signal derived from the Drosophila necrotic gene, as described in several previous publications. Surface-enhanced laser desorption/ionization TOF MS analysis revealed that the Aβ produced contained an additional glutamine residue at the N-terminus. AβQ+1-42 was found to have increased protein abundance and to cause more severe neurodegenerative effects than wild type Aβ1-42 as assessed by locomotor activity and lifespan assays. These data reveal that a commonly used model of Alzheimer's disease generates incorrect Aβ peptide.


Cross-cultural adaptation and validation for central sensitization inventory: based on Chinese patients undergoing total knee arthroplasty for knee osteoarthritis.
This study was conducted to develop a simplified Chinese version of the central sensitization inventory (CSI-CV) and to evaluate its reliability and validity. The CSI-CV was developed through a process involving the translation and back translation of the original CSI. Subsequently, experts reviewed and revised the content of the items to ensure their appropriateness. A total of 325 patients with knee osteoarthritis (KOA), who were scheduled to undergo total knee arthroplasty (TKA), completed the CSI-CV at a prominent orthopedic center in Xi'an, China. Afterward, a random selection of 100 participants was chosen for retesting after one week. The reliability and validity of the inventory were evaluated through exploratory factor analysis, correlation coefficient calculation and other methods. The CSI-CV consists of 25 items in five dimensions (emotional distress, headache and jaw symptoms, physical symptoms, urological symptoms, and fatigue and sleep problems). The cumulative variance contribution rate was 75.3%, the Cronbach's α coefficient was 0.83, the Guttman split-half reliability coefficient was 0.88 and the intraclass correlation coefficient was 0.965. The CSI-CV scores correlated moderately with the total scores of the brief pain inventory (r = 0.506), Western Ontario and McMaster Universities Osteoarthritis Index (r = 0.466) and EuroQoL Group's five-dimension questionnaire (r = 0.576). The findings demonstrate that the CSI was successfully trans-culturally adapted into a simplified Chinese version (CSI-CV) that was reliable and valid for Chinese-speaking patients who awaiting TKA for KOA.


Proteoglycans and Glycosaminoglycans in Stem Cell Homeostasis and Bone Tissue Regeneration.
Stem cells maintain a subtle balance between self-renewal and differentiation under the regulatory network supported by both intracellular and extracellular components. Proteoglycans are large glycoproteins present abundantly on the cell surface and in the extracellular matrix where they play pivotal roles in facilitating signaling transduction and maintaining stem cell homeostasis. In this review, we outline distinct proteoglycans profiles and their functions in the regulation of stem cell homeostasis, as well as recent progress and prospects of utilizing proteoglycans/glycosaminoglycans as a novel glycomics carrier or bio-active molecules in bone regeneration.


Morphologic and biochemical evidence for a contractile cell network within the rat intestinal mucosa.
Subepithelial and pericryptal fibroblastlike cells form a two-dimensional network immediately subjacent to the epithelial basal lamina in the small intestine and colon in several mammalian species. Stellate-shaped cells with similar, but not identical characteristics, form a three-dimensional network deep within the villar lamina propria. Electron microscopic studies indicate that these cells contain a putative contractile apparatus, are attached to each other and to apparently organized elements of the extracellular matrix by typical adhesive devices, and form gap junctions with each other. Comparative in situ immunoperoxidase localization studies document the presence in these cells of four contraction-associated proteins (smooth muscle isotropomyosin, cyclic guanosine monophosphate-dependent protein kinase, both nonmuscle and smooth muscle isomyosin, and actin) in amounts generally greater than those found in connective tissue fibroblasts, but less than in smooth muscle cells. Taken together, these results strongly suggest a smooth muscle-like, contractile function for these cells and indicate that this cellular network may provide a supportive tonus for the epithelium, as well as provide the force needed for active movement of the villus, expulsion of crypt secretion products, and propulsion of absorption products in the lamina propria, the microvasculature, and lacteals of the intestinal villus.


A method to estimate the serial interval distribution under partially-sampled data.
The serial interval of an infectious disease is an important variable in epidemiology. It is defined as the period of time between the symptom onset times of the infector and infectee in a direct transmission pair. Under partially sampled data, purported infector-infectee pairs may actually be separated by one or more unsampled cases in between. Misunderstanding such pairs as direct transmissions will result in overestimating the length of serial intervals. On the other hand, two cases that are infected by an unseen third case (known as coprimary transmission) may be classified as a direct transmission pair, leading to an underestimation of the serial interval. Here, we introduce a method to jointly estimate the distribution of serial intervals factoring in these two sources of error. We simultaneously estimate the distribution of the number of unsampled intermediate cases between purported infector-infectee pairs, as well as the fraction of such pairs that are coprimary. We also extend our method to situations where each infectee has multiple possible infectors, and show how to factor this additional source of uncertainty into our estimates. We assess our method's performance on simulated data sets and find that our method provides consistent and robust estimates. We also apply our method to data from real-life outbreaks of four infectious diseases and compare our results with published results. With similar accuracy, our method of estimating serial interval distribution provides unique advantages, allowing its application in settings of low sampling rates and large population sizes, such as widespread community transmission tracked by routine public health surveillance.


Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer.
Intravenous platinum-based chemotherapy is the standard primary therapy for advanced ovarian cancer. We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated, stage III, epithelial ovarian cancer. The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm. Within four weeks after surgery, six courses of intravenous cyclophosphamide (600 mg per square meter of body-surface area per course) plus either intraperitoneal cisplatin (100 mg per square meter) or intravenous cisplatin (100 mg per square meter) were administered at three-week intervals. Of 654 randomized patients, 546 were eligible for the study. The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months; 95 percent confidence interval, 42 to 56) than in the group receiving intravenous cisplatin (41 months; 95 percent confidence interval, 34 to 47). The risk of death was lower in the intraperitoneal group than in the intravenous group (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Moderate-to-severe tinnitus, clinical hearing loss, and neuromuscular toxic effects were significantly more frequent in the intravenous group. As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less.


Chronic toxicity of biodegradable microplastic (Polylactic acid) to Daphnia magna: A comparison with polyethylene terephthalate.
The increase in the usage of biodegradable microplastics (MPs) as an alternative to conventional plastics has necessitated comprehensive ecotoxicity assessments of biodegradable MPs alongside conventional MPs. This study aimed to assess ecotoxicity of biodegradable polylactic acid (PLA) MPs at concentration of 1 and 5 mgL-1 including a genetic analysis of Daphnia magna, and compared to effects of conventional polyethylene terephthalate (PET) MPs. The survival rate for D. magna exposed to 5 mg L-1 of PLA-MPs declined to 52.4 %, signifying a higher rate of mortality when contrasted with PET-MPs, which exhibited 85.7 % survival rate. Chronic exposure to 1 and 5 mgL-1 PLA-MPs resulted in a decrease of offspring, while increasing the sex ratio and deformed embryo. Interestingly, down-regulation of the SOD and AK genes was observed in D. magna after exposure to 5 mgL-1 of PLA-MPs, while 1 mgL-1 of PLA-MPs up-regulated. These results means that 5 mgL-1 PLA-MP could not produce energy and cope with oxidative stress, resulting in high mortality, and 1 mgL-1 of MP was maintained survival due to energy production and antioxidant action. This study contributes to our understanding of biodegradable microplastics (BMPs) toxic effects on D. magna which could be similar to conventional MPs and provide the importance of ecotoxicological data for risk assessment of BMPs in aquatic organisms.


Time-motion analysis of health care workers' contact with patients and workers' hand hygiene: open vs closed units.
The effects of open (care provided by general medicine teams with a pulmonary intensivist consultant) vs closed (care provided by a dedicated critical care team) intensive care units on health care workers' contact with patients and their hand hygiene is uncertain. To determine if closed intensive care units have fewer visits of patients by health care providers and greater hand-washing compliance among providers than do open units. Time-motion analysis was used to observe 2 rooms in a medical intensive care unit at a teaching hospital affiliated with Indiana University School of Medicine, Indianapolis, for 96 hours before and after closure of the unit. The main outcome measures were frequency of health care providers' visits and their hand-washing hygiene compliance rates. Mean number of visits per room per hour by physicians (1.53 in the open unit vs 1.27 in the closed unit; P = .93) and nurses (3.98 in open unit vs 4.14 in closed unit; P = .60) did not differ. No differences were observed in gold-standard hand washing among physicians (0.00% in open unit vs 2.63% in closed unit; P = .11) or nurses (2.50% in open unit vs 3.49% in closed unit; P = .51). However, hand washing decreased significantly in nurses in the closed unit (40.94% in open unit vs 29.84% in closed unit; P = .002). Closing the intensive care unit did not decrease the number of contacts between health care providers and patients nor did it increase the providers' compliance with hand hygiene.


Management of skin ageing: how to combine cosmetic procedures.
Skin ageing may be physiological and/or a result of photoageing. To provide comprehensive management of ageing skin, it is essential to make a thorough diagnosis before any therapeutic decision is made. The most appropriate treatment(s) may then be offered to the patient. This comprehensive approach to care requires knowledge of the mechanisms of skin ageing and the advantages and drawbacks of the different therapeutic approaches available, in order to arrive at the best therapeutic strategy and to meet patient expectations. There are very many different therapeutic approaches, and in the context of work by a group of European experts it seems appropriate to propose a therapeutic strategy for the overall management of skin ageing to help dermatologists in their daily work with patients. This therapeutic strategy is based both on an analysis of the literature and the personal experience of the experts.


Prevalence of self-reported poor odor detection sensitivity: the Skövde population-based study.
To enable adequate planning of ENT healthcare it is important to know the prevalence of olfactory dysfunction in the general population. Whether an individual will actually seek medical attention for olfactory dysfunction is likely to depend predominantly on his/her self-evaluation of the sense of smell. This motivated an investigation of the prevalences of self-reported poorer- and better-than-normal odor detection sensitivity in the general population. A random sample of 1900 adult inhabitants, stratified for age and gender, was drawn from the municipal population register of Skövde, Sweden. Subjects were asked to attend a structured interview concerning their self-evaluation of their odor detection sensitivity. In total, 1387 volunteers (73% of the sample) were investigated. The overall prevalences of self-reported poorer- and better-than normal odor detection sensitivity were 15.3% and 17.4%, respectively. The prevalence of poorer sensitivity was found to increase with age, and the prevalence of better sensitivity was lower in men than women. Considering the fairly high participation rate in this study and the fact that the population of Skövde is representative of the general Swedish population, the obtained prevalences can be considered representative of the general Swedish adult population.


Gold-catalyzed annulations of 2-alkynyl benzaldehydes with vinyl ethers: synthesis of dihydronaphthalene, isochromene, and bicyclo[2.2.2]octane derivatives.
With the suitable selection of a gold catalyst as well as the appropriate control of the reaction conditions, various new gold-catalyzed cyclizations of 2-alkynyl benzaldehyde with acyclic or cyclic vinyl ethers have been developed. Acetal-tethered dihydronaphthalene and isochromenes were obtained from the reactions of 2-alkynyl benzaldehydes with acyclic vinyl ethers under mild conditions. And, more interestingly, the gold-catalyzed reactions of 2-alkynyl benzaldehyde with a cyclic vinyl ether afforded the bicyclo[2.2.2]octane derivative involving two molecules of cyclic vinyl ethers. These products contain interesting substructures that have been found in many biologically active molecules and natural products. In addition, a gold-catalyzed homo-dimerization of 2-phenylethynyl benzaldehyde 1a was observed when the reaction was carried out in the absence of vinyl ether, affording a set of separable diastereomeric products. Plausible mechanisms for these transformations are discussed; a gold-containing benzopyrylium was regarded as the crucial intermediate by which a number of these new transformations took place.


Long live the health care system in Japan.
In Japan, a cost-containment policy has been implemented with health care system reform. Increasing medical expenses are inevitable due to aging of the population, health transitions, and expanded and advanced medical services. Policies such as the introduction of regressive reimbursement for inpatient services as part of social insurance, the reduction in the number of hospital beds, fewer medical examinations, and curtailed usage of medical tests have jeopardized the accessibility and quality of medical services, especially for the elderly. Compared to other developed countries, both the proportion of the government's payment of health expenses and the proportion of health expenses in proportion to GDP are lower in Japan. To confront the challenges of an aging society in terms of finances and the health care system, policymakers from the Ministry of Health should take a comprehensive approach instead of a mere cost-containment policy.


miR-122-5p Inhibits the Proliferation, Invasion and Growth of Bile Duct Carcinoma Cells by Targeting ALDOA.
Bile duct cancer, although not among the most common tumors, still accounts for more and more worldwide deaths each year. By attempting to verify an overexpression of ALDOA in cholangiocarcinoma tissues and cells and explore the underlying molecular mechanism regulated by miR-122-5p, this study was designed to provide a potential molecular target in bile duct cancer treatment. Western blot and immunohistochemistry were performed to detect the ALDOA protein level in duct carcinoma tissues. The transfection efficiency was confirmed by western blot and/or RT-qPCR assay. The proliferation of bile duct carcinoma cells was determined by MTT and colony formation assay. The invasion ability of bile duct carcinoma cells was evaluated with Transwell invasion assay. Flow cytometry detected cell apoptosis of bile duct carcinoma cells. The miRNAs which modulate ALDOA were filtrated from bioinformatics software and clinical specimens. The target relationship was confirmed by dual luciferase reporter assay. Furthermore, a xenograft model was completed to verify the impact of miRNA on inhibition growth of bile duct carcinoma cells. ALDOA was found up-regulated in bile duct carcinoma tissues and cells. Knockdown of ALDOA promoted the apoptosis of cells and inhibited the proliferation and invasion of bile duct carcinoma cells. Bioinformatics and clinical specimens indicated the negative correlation and targeted regulation between miR-122-5p and ALDOA. By down-regulating ALDOA, overexpression of miR-122-5p appeared to promote cell apoptosis and significantly inhibit cell proliferation, invasion in vitro and suppress the tumor growth in vivo. miR-122-5p inhibited proliferation and invasion of bile duct carcinoma cells and promoted cell apoptosis by targeting ALDOA expression.


Macroscopic and histological variations in the cellular tapetum in dogs.
We aimed to document macroscopic variations in the cellular tapetum in the dog, to provide a histologic description of the macroscopic results and to evaluate the correlation between the macroscopic appearance and aging. Fifty three dogs including 5 beagles, 1 Chihuahua and 47 mixed breeds of each gender were used. For a macroscopic study, the fresh tapetal fundi were photographed using digital camera. For a histological study, the glutaraldehyde-formalin fixed eyes were embedded in nitrocellulose and stained with hematoxylin-eosin or thionine. The normal tapetum was triangular with the rounded angles and the smooth contour. The atypical tapetum was smaller and more variable in shape, contour and color than the normal one. In severe cases, the fundus was devoid of the tapetum. The atypical tapetum tended to increase in frequency with aging. Retinal pigment epithelial cells on the normal tapetum were unpigmented. In the eye with the atypical tapetum, regardless of tapetal size and shape, unpigmented retinal pigment epithelial cells showed a similar distribution to that on the normal tapetum, even in a dog without a tapetum. Although there is a congenitally hypoplastic tapetum, the atypical tapetum tends to increase in incidence and severity with aging.


Introgression reshapes recombination distribution in grapevine interspecific hybrids.
In grapevine interspecific hybrids, meiotic recombination is suppressed in homeologous regions and enhanced in homologous regions of recombined chromosomes, whereas crossover rate remains unchanged when chromosome pairs are entirely homeologous. Vitis rotundifolia, an American species related to the cultivated European grapevine Vitis vinifera, has a high level of resistance to several grapevine major diseases and is consequently a valuable resource for grape breeding. However, crosses between both species most often lead to very few poorly fertile hybrids. In this context, identifying genetic and genomic features that make cross-breeding between both species difficult is essential. To this end, three mapping populations were generated by pseudo-backcrosses using V. rotundifolia as the donor parent and several V. vinifera cultivars as the recurrent parents. Genotyping-by-sequencing was used to establish high-density genetic linkage maps and to determine the genetic composition of the chromosomes of each individual. A good collinearity of the SNP positions was observed between parental maps, confirming the synteny between both species, except on lower arm of chromosome 7. Interestingly, recombination rate in V. rotundifolia × V. vinifera interspecific hybrids depends on the length of the introgressed region. It is similar to grapevine for chromosome pairs entirely homeologous. Conversely, for chromosome pairs partly homeologous, recombination is suppressed in the homeologous regions, whereas it is enhanced in the homologous ones. This balance leads to the conservation of the total genetic length of each chromosome between V. vinifera and hybrid maps, whatever the backcross level and the proportion of homeologous region. Altogether, these results provide new insight to optimize the use of V. rotundifolia in grape breeding and, more generally, to improve the introgression of gene of interest from wild species related to crops.


A study of scalds in Birmingham.
The causes of serious domestic scald injuries in Birmingham were studied for one year. Seventy-eight people sustained such scalds, 11 adults and 67 children. Only 51 of the patients received satisfactory first aid. Most accidents could have been avoided and the severity of the injury would have been less if appropriate first aid had been given.