[Prognosis of the thyroid carcinomas after surgery (author's transl)].
The authors review 140 cases and show the prime importance of the patient's age and the histological type in the prognosis of the operations of thyroid carcinoma (with the exception of solitary malignant cold nodule). The survival rate is higher with the papillary carcinoma of young patients, even though an extensive development of lymph nodes occurs, whereas metastases are encountered in the evolution of follicular carcinoma with increased risks. The anaplastic carcinoma which occurs mainly in aged people, is the worst of all. The medullary carcinoma is quite different from the others and is almost as malignant as the differentiated and anaplastic carcinomas. Surgery has to be adapted to anatomical lesions and requires the presence of an experienced histopathologist, the extension of the gland excision depending on the histological type and whether the isthmic area has been touched or not; in the same way a microscopic examination of lymph nodes, which are systematically excised, reveals whether a lymph nodes dissection has to be done at the same time. In this way extensive excisions together with their sequels can be avoided when the best prognosis can be forecasted with these lesions.


Hospital Preparedness for COVID-19: The Known and The Known Unknown.
In late March 2020, we faced a nosocomial outbreak of novel coronavirus disease 2019 (COVID-19) at Keio University Hospital, Tokyo, Japan. Presently, COVID-19 is an unprecedented worldwide biohazard, and a nosocomial outbreak can occur in any hospital at any time. Therefore, we reviewed the literature regarding hospital preparedness, the initial management of COVID-19, and the surveillance of healthcare workers (HCWs) to find information that would be generally useful for physicians when confronted with COVID-19. In terms of hospital preparedness, each hospital should develop an incident management system and establish a designated multidisciplinary medical team. To initiate case management, COVID-19 should be suspected based on patient symptoms and/or high-risk history and then should be confirmed by viral testing, such as reverse transcription polymerase chain reaction (RT-PCR) analysis. Although some patients will become critically ill, the guidelines for respiratory failure and septic shock for non-COVID-19 cases can be followed for supportive treatment. Antiviral medications should be carefully selected because the available information is confused by the large volume of preprint literature and unreliable data. HCWs who have come into contact with patients with COVID-19 can generate new in-hospital clusters of COVID-19 cases. Quarantine following contact tracking with risk stratification is effective in preventing transmission, and the essentials of medical surveillance include monitoring different types of symptoms, delegation of supervision, and continuation of surveillance regardless of the RT-PCR results. Preparation for COVID-19 is recommended before the first COVID-19 case is encountered.


Induction of the second exopolysaccharide (EPSb) in Rhizobium meliloti SU47 by low phosphate concentrations.
In previous work, Rhizobium meliloti SU47 produced its alternative exopolysaccharide (EPSb [also called EPS II]) only in strains that were genetically altered to activate EPSb synthesis. Here we report that EPSb synthesis is not entirely cryptic but occurred under conditions of limiting phosphate. This was shown in several different exo mutants that are blocked in the synthesis of the normal exopolysaccharide, succinoglycan. In addition, EPSb biosynthetic gene expression was markedly increased by limiting phosphate. An apparent regulatory mutant that does not express alkaline phosphatase activity was unable to produce EPSb under these conditions. A mucR mutant that was previously shown to produce EPSb instead of the normal exopolysaccharide, succinoglycan, was not sensitive to phosphate inhibition of EPSb synthesis. No evidence was found to indicate that exoX, which affects succinoglycan synthesis, had any influence on EPSb synthesis. In contrast to limiting phosphate, limiting nitrogen or sulfur did not stimulate EPSb synthesis as it does succinoglycan.


[[14C] Alanine incorporation into proteins and their contents in the tissue of intact and adrenalectomized rabbits after hydrocortisone and cortitropin administration].
A single administration of hydrocortisone to intact rabbits increases the incorporation of [14C] alanine into proteins of the brain and liver tissue homogenates and soluble fractions as well as in blood plasma proteins and reduces the label incorporation into the brain tissue proteins and reduces its incorporation into the blood plasma proteins. Adrenalcetomy is followed by an increase in the incorporation of [14C] alanine into proteins of the brain and muscle tissue homogenates and soluble fraction and into proteins of blood plasma and liver tissue homogenates as well as by reducing the label incorporation into the spleen soluble fraction proteins. ACTH administered to adrenalectomized rabbits reduces incorporation of [14C] alanine into the brain and muscle tissue proteins, total proteins of liver tissue homogenate and increases it into the proteins of the spleen tissue soluble fraction. Multiple administration of the soluble fraction hormones both to intact and adrenalectomized rabbits inhibits the label incorporation into the studied tissue proteins. Parallel with the change in [14C] alanine incorporation into proteins under the hormones effect certain shifts in their contents were also established.


Acetyl-coenzyme A synthase: the case for a Ni(p)(0)-based mechanism of catalysis.
Acetyl-CoA synthase (also known as carbon monoxide dehydrogenase) is a bifunctional Ni-Fe-S-containing enzyme that catalyzes the reversible reduction of CO(2) to CO and the synthesis of acetyl-coenzyme A from CO, CoA, and a methyl group donated by a corrinoid iron-sulfur protein. The active site for the latter reaction, called the A-cluster, consists of an Fe(4)S(4) cubane bridged to the proximal Ni site (Ni(p)), which is bridged in turn to the so-called distal Ni site. In this review, evidence is presented that Ni(p) achieves a zero-valent state at low potentials and during catalysis. Ni(p) appears to be the metal to which CO and methyl groups bind and then react to form an acetyl-Ni(p) intermediate. Methyl group binding requires reductive activation, where two electrons reduce some site on the A-cluster. The coordination environment of the distal Ni suggests that it could not be stabilized in redox states lower than 2+. The rate at which the [Fe(4)S(4)](2+) cubane is reduced is far slower than that at which reductive activation occurs, suggesting that the cubane is not the site of reduction. An intriguing possibility is that Ni(p)(2+) might be reduced to the zero-valent state. Reinforcing this idea are Ni-organometallic complexes in which the Ni exhibits analogous reactivity properties when reduced to the zero-valent state. A zero-valent Ni stabilized exclusively with biological ligands would be remarkable and unprecedented in biology.


Human rights and psychiatric care in Africa with particular reference to the Ethiopian situation.
Around 700 million people are estimated to live in the continent of Africa. The majority live far from health facilities and are short of basic supplies. Most African people believe that diseases in general, and mental illness in particular, are afflictions caused by supernatural evil forces. Traditional methods are preferred sources of help for health problems by most people in the continent. Modern psychiatric services are far from adequate. The available asylums are located in the capital cities and very few patients have access to them. There is no mental health legislation in some African countries. In Ethiopia, where the population is 55 million, there is only one mental hospital; and a total of 390 beds for psychiatric inpatients. There are 11 psychiatrists in the country. In the regions of the country, mental health services are provided by psychiatric nurses. Patients usually come to medical services having tried the available local means. Psychotic patients almost always are forced to come to the mental hospital by their families, friends, neighbours, work-mates (and very seldom by the police). Consent is not usually required to initiate treatment or admit such patients. Alleged offenders, who come to the hospital for assessment, stay in the same ward as other patients. Armed prison guards assigned to watch the prisoners also stay in the same room with the prisoners. Care providing procedures in Ethiopia do not seem to be in accordance with the declarations of human rights. However, in a country where the economy cannot provide its citizens with basic needs for survival, it is unlikely that the standard of mental health care will change much in the foreseeable future.


Antipsychotic drug use is correlated with CRP40/mortalin mRNA expression in the dorsolateral prefrontal cortex of human postmortem brain specimens.
Heat shock proteins act as intracellular chaperones by assisting with proper protein folding in response to various cellular stresses. In doing so, these proteins protect the cell from unwanted protein aggregation, which in turn, plays an important role in the pathogenesis of numerous disorders. Previous reports from our laboratory have described a 40 kDa catecholamine regulated heat shock-like protein (CRP40), an alternate gene product of the 70 kDa mitochondrial heat shock protein, mortalin. CRP40 shares an intimate association with dopaminergic activity, specifically as it pertains to dopamine dysregulation in schizophrenia. This study investigates human CRP40/mortalin mRNA expression within dorsolateral prefrontal cortex postmortem specimens from normal control, schizophrenic and bipolar patients obtained from the Stanley Medical Research Institute. Real-time polymerase chain reaction was carried out for all patient samples (n=105; n=35 per group) in a blinded manner. No significant alterations in CRP40/mortalin mRNA expression levels were observed between control, bipolar and schizophrenic patients. However, multiple regression demonstrated a distinct positive correlation between CRP40/mortalin mRNA expression and lifetime use of antipsychotic drugs within the schizophrenic patient profile, after controlling for important confounding factors. Thus, the data suggest that human CRP40/mortalin is modulated by dopaminergic activity and may act to protect neurons from excess catecholamine activity in regions of the brain associated with psychosis.


Guanosine-Mediated Anxiolytic-Like Effect: Interplay with Adenosine A1 and A2A Receptors.
Acute or chronic administration of guanosine (GUO) induces anxiolytic-like effects, for which the adenosine (ADO) system involvement has been postulated yet without a direct experimental evidence. Thus, we aimed to investigate whether adenosine receptors (ARs) are involved in the GUO-mediated anxiolytic-like effect, evaluated by three anxiety-related paradigms in rats. First, we confirmed that acute treatment with GUO exerts an anxiolytic-like effect. Subsequently, we investigated the effects of pretreatment with ADO or A1R (CPA, CCPA) or A2AR (CGS21680) agonists 10 min prior to GUO on a GUO-induced anxiolytic-like effect. All the combined treatments blocked the GUO anxiolytic-like effect, whereas when administered alone, each compound was ineffective as compared to the control group. Interestingly, the pretreatment with nonselective antagonist caffeine or selective A1R (DPCPX) or A2AR (ZM241385) antagonists did not modify the GUO-induced anxiolytic-like effect. Finally, binding assay performed in hippocampal membranes showed that [3H]GUO binding became saturable at 100-300 nM, suggesting the existence of a putative GUO binding site. In competition experiments, ADO showed a potency order similar to GUO in displacing [3H]GUO binding, whereas AR selective agonists, CPA and CGS21680, partially displaced [3H]GUO binding, but the sum of the two effects was able to displace [3H]GUO binding to the same extent of ADO alone. Overall, our results strengthen previous data supporting GUO-mediated anxiolytic-like effects, add new evidence that these effects are blocked by A1R and A2AR agonists and pave, although they do not elucidate the mechanism of GUO and ADO receptor interaction, for a better characterization of GUO binding sites in ARs.


Factors associated with increased mortality and prolonged length of stay in an adult intensive care unit.
The intensive care unit is synonymous of high severity, and its mortality rates are between 5.4 and 33%. With the development of new technologies, a patient can be maintained for long time in the unit, causing high costs, psychological and moral for all involved. This study aimed to evaluate the risk factors for mortality and prolonged length of stay in an adult intensive care unit. The study included all patients consecutively admitted to the adult medical/surgical intensive care unit of Hospital das Clínicas da Universidade Estadual de Campinas, for six months. We collected data such as sex, age, diagnosis, personal history, APACHE II score, days of invasive mechanical ventilation orotracheal reintubation, tracheostomy, days of hospitalization in the intensive care unit and discharge or death in the intensive care unit. Were included in the study 401 patients; 59.6% men and 40.4% women, age 53.8±18.0. The mean intensive care unit stay was 8.2±10.8 days, with a mortality rate of 13.5%. Significant data for mortality and prolonged length of stay in intensive care unit (p <0.0001), were: APACHE II>11, OT-Re and tracheostomy. The mortality and prolonged length of stay in intensive care unit intensive care unit as risk factors were: APACHE>11, orotracheal reintubation and tracheostomy.


Brittle solid collapse to simple liquid for a waxy suspension.
We show that thanks to the existence of a continuous (percolating) network of weak interparticle bonds in a liquid, wax suspensions behave as "soft breakable (brittle) solids". It appears that, under the action of either a large stress over a short time or oscillating low stress (fatigue test), the initially solid network of these materials is broken and dispersed in the liquid, which makes them turn abruptly ("collapse") and irreversibly into a low viscous fluid. This collapse is more dramatic as the concentration increases. These phenomena are related to the evolution of the microstructure directly observed after different flow histories. The interpretation of these results provides new perspectives for understanding the physical origin of the brittleness or plasticity of solid or pasty materials, and suggests such materials might be used as model systems to simulate and explain natural catastrophic events such as landslides and avalanches.


How cognitive psychology changed the face of medical education research.
In this article, the contributions of cognitive psychology to research and development of medical education are assessed. The cognitive psychology of learning consists of activation of prior knowledge while processing new information and elaboration on the resulting new knowledge to facilitate storing in long-term memory. This process is limited by the size of working memory. Six interventions based on cognitive theory that facilitate learning and expertise development are discussed: (1) Fostering self-explanation, (2) elaborative discussion, and (3) distributed practice; (4) help with decreasing cognitive load, (5) promoting retrieval practice, and (6) supporting interleaving practice. These interventions contribute in different measure to various instructional methods in use in medical education: problem-based learning, team-based learning, worked examples, mixed practice, serial-cue presentation, and deliberate reflection. The article concludes that systematic research into the applicability of these ideas to the practice of medical education presently is limited and should be intensified.


Liquid-liquid phase transition and structure inheritance in carbon films.
Molecular dynamics simulations are performed to study the cooling process of quasi-2D liquid carbon. Our results show an obvious liquid-liquid phase transition (LLPT) from the twofold coordinated liquid to the threefold coordinated liquid with the decrease of temperature, followed by a liquid-solid phase transition (LSPT). The LLPT can be regarded as the preparation stage of LSPT. During the cooling process, the chain structures firstly self-assemble into some ring structures and then aggregate into some stable islands which can further connect together to form a complete polycrystalline film. The threefold coordinated structures play an important role in the formation of atomic rings. The inheritance of the threefold coordinated structures provides essential condition to form rings and islands.


Variation of microcystins, cyanobacterial hepatotoxins, in Anabaena spp. as a function of growth stimuli.
Cyanobacterial hepatotoxins, microcystins, are specific inhibitors of serine/threonine protein phosphatases and potent tumor promoters. They have caused several poisonings of animals and also pose a health hazard for humans through the use of water for drinking and recreation. Different strains of the same cyanobacterial species may variously be nontoxic, be neurotoxic, or produce several microcystin variants. It is poorly understood how the amount of toxins varies in a single strain. This laboratory study shows the importance of external growth stimuli in regulating the levels and relative proportions of different microcystin variants in two strains of filamentous, nitrogen-fixing Anabaena spp. The concentration of the toxins in the cells increased with phosphorus. High temperatures (25 to 30 degrees C), together with the highest levels of light studied (test range, 2 to 100 mumol m-2 s-1), decreased their amount. Different structural variants of microcystins responded differently to growth stimuli. Variants of microcystin (MCYST)-LR correlated with temperatures below 25 degrees C, and those of MCYST-RR correlated with higher temperatures. Nitrogen added into the growth medium and increasing temperatures increased the proportion of microcystin variants demethylated in amino acid 3. All variants remained mostly intracellular. Time was the most important factor causing the release of the toxins into the growth medium. Time, nitrogen added into the growth medium, and light fluxes above 25 mumol m-2 s-1 significantly increased the concentrations of the dissolved toxins. According to the results, it thus seems that the reduction of phosphorus loads in bodies of water might play a role in preventing the health hazards that toxic cyanobacterial water blooms pose, not only by decreasing the cyanobacteria but also by decreasing their toxin content.


Salivary Gland Neoplasms in Children and Adolescents.
Salivary gland neoplasms (SGNs) in children are uncommon. Epithelial SGNs (ESGNs) comprise the majority (95%), with the remaining being mesenchymal SGNs (MeSGNs). Pleomorphic adenoma is the most frequently encountered benign neoplasm, mucoepidermoid carcinoma is the most frequent malignant ESGN, and rhabdomyosarcoma is the most frequent malignant MeSGN. ESGN presents in the second decade, whereas MeSGN presents in the first and second decades. Swelling without pain or neurological signs is the main presentation of both benign and malignant neoplasms. Making an accurate preoperative histological diagnosis is important, so a needle biopsy or a perioperative frozen section is useful when there is doubt about the disease status of the patient; the excised tumour margin is also important. Surgical excision should aim to achieve clear margin excision in benign and malignant ESGNs, minimising the need for adjuvant radiotherapy and maximising the long-term likelihood of patient cure. Benign ESGNs are uncommon, and excision is curative, whereas malignant ESGN and MeSGN should be managed by a multidisciplinary paediatric oncology team.


Climate effects on archaic human habitats and species successions.
It has long been believed that climate shifts during the last 2 million years had a pivotal role in the evolution of our genus Homo1-3. However, given the limited number of representative palaeo-climate datasets from regions of anthropological interest, it has remained challenging to quantify this linkage. Here, we use an unprecedented transient Pleistocene coupled general circulation model simulation in combination with an extensive compilation of fossil and archaeological records to study the spatiotemporal habitat suitability for five hominin species over the past 2 million years. We show that astronomically forced changes in temperature, rainfall and terrestrial net primary production had a major impact on the observed distributions of these species. During the Early Pleistocene, hominins settled primarily in environments with weak orbital-scale climate variability. This behaviour changed substantially after the mid-Pleistocene transition, when archaic humans became global wanderers who adapted to a wide range of spatial climatic gradients. Analysis of the simulated hominin habitat overlap from approximately 300-400 thousand years ago further suggests that antiphased climate disruptions in southern Africa and Eurasia contributed to the evolutionary transformation of Homo heidelbergensis populations into Homo sapiens and Neanderthals, respectively. Our robust numerical simulations of climate-induced habitat changes provide a framework to test hypotheses on our human origin.


Mechano-transduction in periodontal ligament cells identifies activated states of MAP-kinases p42/44 and p38-stress kinase as a mechanism for MMP-13 expression.
Mechano-transduction in periodontal ligament (PDL) cells is crucial for physiological and orthodontic tooth movement-associated periodontal remodelling. On the mechanistic level, molecules involved in this mechano-transduction process in PDL cells are not yet completely elucidated. In the present study we show by western blot (WB) analysis and/or indirect immunofluorescence (IIF) that mechanical strain modulates the amount of the matrix metalloproteinase MMP-13, and induces non-coherent modulation in the amount and activity of signal transducing molecules, such as FAK, MAP-kinases p42/44, and p38 stress kinase, suggesting their mechanistic role in mechano-transduction. Increase in the amount of FAK occurs concomitant with increased levels of the focal contact integrin subunits beta3 and beta1, as indicated by WB or optionally by IIF. By employing specific inhibitors, we further identified p42/44 and p38 in their activated, i.e. phosphorylated state responsible for the expression of MMP-13. This finding may point to the obedience in the expression of this MMP as extracellular matrix (ECM) remodelling executioner from the activation state of mechano-transducing molecules. mRNA analysis by pathway-specific RT-profiler arrays revealed up- and/or down-regulation of genes assigning to MAP-kinase signalling and cell cycle, ECM and integrins and growth factors. Up-regulated genes include for example focal contact integrin subunit alpha3, MMP-12, MAP-kinases and associated kinases, and the transcription factor c-fos, the latter as constituent of the AP1-complex addressing the MMP-13 promotor. Among others, genes down-regulated are those of COL-1 and COL-14, suggesting that strain-dependent mechano-transduction may transiently perturbate ECM homeostasis. Strain-dependent mechano-/signal-transduction in PDL cells involves abundance and activity of FAK, MAP-kinases p42/44, and p38 stress kinase in conjunction with the amount of MMP-13, and integrin subunits beta1 and beta3. Identifying the activated state of p42/44 and p38 as critical for MMP-13 expression may indicate the mechanistic contribution of mechano-transducing molecules on executioners of ECM homeostasis.


High levels of imported asymptomatic malaria but limited local transmission in KwaZulu-Natal, a South African malaria-endemic province nearing malaria elimination.
KwaZulu-Natal, one of South Africa's three malaria endemic provinces, is nearing malaria elimination, reporting fewer than 100 locally-acquired cases annually since 2010. Despite sustained implementation of essential interventions, including annual indoor residual spraying, prompt case detection using malaria rapid diagnostics tests and treatment with effective artemisinin-based combination therapy, low-level focal transmission persists in the province. This malaria prevalence and entomological survey was therefore undertaken to identify the drivers of this residual transmission. Malaria prevalence as well as malaria knowledge, attitudes and practices among community members and mobile migrant populations within uMkhanyakude district, KwaZulu-Natal were assessed during a community-based malaria prevalence survey. All consenting participants were tested for malaria by both conventional and highly-sensitive falciparum-specific rapid diagnostic tests. Finger-prick filter-paper blood spots were also collected from all participants for downstream parasite genotyping analysis. Entomological investigations were conducted around the surveyed households, with potential breeding sites geolocated and larvae collected for species identification and insecticide susceptibility testing. A random selection of households were assessed for indoor residual spray quality by cone bioassay. A low malaria prevalence was confirmed in the study area, with only 2% (67/2979) of the participants found to be malaria positive by both conventional and highly-sensitive falciparum-specific rapid diagnostic tests. Malaria prevalence however differed markedly between the border market and community (p < 0001), with the majority of the detected malaria carriers (65/67) identified as asymptomatic Mozambican nationals transiting through the informal border market from Mozambique to economic hubs within South Africa. Genomic analysis of the malaria isolates revealed a high degree of heterozygosity and limited genetic relatedness between the isolates supporting the hypothesis of limited local malaria transmission within the province. New potential vector breeding sites, potential vector populations with reduced insecticide susceptibility and areas with sub-optimal vector intervention coverage were identified during the entomological investigations. If KwaZulu-Natal is to successfully halt local malaria transmission and prevent the re-introduction of malaria, greater efforts need to be placed on detecting and treating malaria carriers at both formal and informal border crossings with transmission blocking anti-malarials, while ensuring optimal coverage of vector control interventions is achieved.


Increased Prognostic Value of Query Amyloid Late Enhancement Score in Light-Chain Cardiac Amyloidosis.
Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665-13.497; P<0.001) and log N-terminal pro-brain natriuretic peptide (HR, 1.525; 95% CI: 1.112-2.092; P=0.009) were the only 2 independent predictors of all-cause mortality. On Kaplan-Meier analysis, patients with subendocardial LGE can be further risk stratified using QALE score ≥9. The QALE scoring system provides powerful independent prognostic value in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.


The complexity of searching the literature.
The science of systematically reviewing literature has become a research process in its own right. The key word of course, is systematic. In the context of a systematic review this indicates that all possible sources have been comprehensively searched using a pre-defined search strategy designed to identify all relevant published and unpublished work. This paper illustrates the components of a comprehensive search, examines the yield of this approach and discusses the time and resource requirements for conducting the search. It uses as an example a recently completed systematic review. The paper goes on to discuss ways in which nurses can become more involved in conducting and using the results of good quality reviews.


An evaluation of community-acquired urinary tract infection and appropriateness of treatment in an emergency department in Saudi Arabia.
Urinary tract infection (UTI) is a serious health problem affecting millions of people every year. Inappropriate antibiotic prescriptions put patients at risk and lead to bacterial resistance and elevated costs. Study aims were to assess the prevalence and antibiotic-treatment patterns of community acquired UTIs, prevalence and types of antibiotic-prescribing errors, and the cost of inappropriate antibiotic use. This was a retrospective cross-sectional study conducted over a 3-month period in an emergency department in Saudi Arabia. During the study period, 1,449 patients were diagnosed with UTIs, including pediatric (18.6%), adult (59.2%), and elderly (22.2%) patients. The overall prevalence of UTIs was 9.9% of total visits. Broad-spectrum antibiotics were prescribed for 85% of patients. Three main antibiotics were prescribed: cephalosporin (39%), penicillin (26%), and fluoroquinolone (22%). The overall prevalence of inappropriate antibiotic prescription with at least one type of error was 46.2% (pediatrics 51%, adults 46%, elderly 47%). Errors were dose (37%), duration (11%), frequency (6%), and antibiotic selection (2.4%). Dose error was significantly greater in pediatric patients (P=0.001). Duration error was higher among adults and the elderly (P=0.014). Significantly more inappropriate cephalosporin prescriptions were seen in adults (P=0.001), while penicillin had significantly higher errors in pediatric patients. Positive urine culture was seen in 34.9% of patients, and the most common microorganism was Escherichia coli (51%). The mean cost of care for one episode of UTI was US$134.56±$31.34 (95% CI $132.94-$136.17). Treatment of UTI was more costly in women (63.9% of total cost), adults (59.2%), and those using broad-spectrum antibiotics (86.5%). There were statistically significant associations among sex, age, spectrum of antibiotic, category of antibiotic, and inappropriate cost. The results revealed a significant level of inappropriate use of antibiotics in the treatment of UTIs in the emergency department.


Dipole models for the EEG and MEG.
The current dipole is a widely used source model in forward and inverse electroencephalography and magnetoencephalography applications. Analytic solutions to the governing field equations have been developed for several approximations of the human head using ideal dipoles as the source model. Numeric approaches such as the finite-element and finite-difference methods have become popular because they allow the use of anatomically realistic head models and the increased computational power that they require has become readily available. Although numeric methods can represent more realistic domains, the sources in such models are an approximation of the ideal dipole. In this paper, we examine several methods for representing dipole sources in finite-element models and compare the resulting surface potentials and external magnetic field with those obtained from analytic solutions using ideal dipoles.


Transient architectonic features in the basolateral amygdala of the human fetal brain.
The architectonical differentiation in the basolateral nuclei of the human fetal amygdala - with special reference to transient structures - was studied using series of relatively thick Nissl-stained sections. These architectonic features were correlated with the process of migration. Radial glial fibers providing the scaffold of migratory routes can reliably be marked with the aid of antivimentin. In the 5th gestational month a transient feature is conspicuous in the inferior portions of the basolateral nuclei bordering upon the ganglionic eminence (proliferative zone): columnar cell clusters, separated by cell-sparse septa, extend from the poliferative zone to the nuclei. The width of the cell columns vary considerably between the different nuclei. In vimentin immunopreparations fibers are found inside these cell columns. So they most probably reflect clustered migratory streams. Two months later, instead of this merging area between the ganglionic eminence and the amygdaloid nuclei a cell-free capsule envelopes the nuclei and clearly separates them from the ganglionic eminence. Changes in cytoarchitectonics are accompanied by a distinct rearrangement of radial glial fibers. A basket-like arrangement of the vimentin-immunoreactive fibers around the cell columns inside the cell sparse septa is found. Towards the end of pregnancy radial glial fibers gradually vanish. A comparison of Nissl and vimentin preparations reveals that transient architectonic characteristics as visible in relatively thick Nissl sections may be correlated with migrational routes.


Myotonic Myopathy With Secondary Joint and Skeletal Anomalies From the c.2386C>G, p.L769V Mutation in SCN4A.
The phenotypic spectrum associated with the skeletal muscle voltage-gated sodium channel gene (SCN4A) has expanded with advancements in genetic testing. Autosomal dominant SCN4A mutations were first linked to hyperkalemic periodic paralysis, then subsequently included paramyotonia congenita, several variants of myotonia, and finally hypokalemic periodic paralysis. Biallelic recessive mutations were later identified in myasthenic myopathy and in infants showing a severe congenital myopathy with hypotonia. We report a patient with a pathogenic de novo SCN4A variant, c.2386C>G p.L769V at a highly conserved leucine. The phenotype was manifest at birth with arthrogryposis multiplex congenita, severe episodes of bronchospasm that responded immediately to carbamazepine therapy, and electromyographic evidence of widespread myotonia. Another de novo case of p.L769V has been reported with hip dysplasia, scoliosis, myopathy, and later paramyotonia. Expression studies of L796V mutant channels showed predominantly gain-of-function changes, that included defects of slow inactivation. Computer simulations of muscle excitability reveal a strong predisposition to myotonia with exceptionally prolonged bursts of discharges, when the L796V defects are included. We propose L769V is a pathogenic variant, that along with other cases in the literature, defines a new dominant SCN4A disorder of myotonic myopathy with secondary congenital joint and skeletal involvement.


[Diagnosis and treatment of chondromyxoid fibroma of bones].
Under observation were 23 patients, aged from 9 to 57 years, with chondromyxoid fibroma of bones. All patients were treated surgically. In 5 cases the involved bone was resected, in 6--edge resection with homoplasty and in 7--segmental resection with automoplasty were employed, in 4--amputation, in 1--exarticulation in the coxa. 20 patients are being kept under observation for 1-7 years without any recurrence and metastases, one patients is still being treated. Two patients died as a result of lung metastases.


A simplified wall-based model for regional innervation/perfusion mismatch assessed by cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT to predict arrhythmic events in ischaemic heart failure.
Cardiac 123iodine-meta-iodobenzylguanidine (123I-mIBG) single-photon emission computed tomography (SPECT) imaging provides information on regional myocardial innervation. However, the value of the commonly used 17-segment summed defect score (SDS) as a prognostic marker is uncertain. The present study examined whether a simpler regional scoring approach for evaluation of 123I-mIBG SPECT combined with rest 99mTc-tetrofosmin SPECT myocardial perfusion imaging could improve prediction of arrhythmic events (AEs) in patients with ischaemic heart failure (HF). Five hundred and two ischaemic HF subjects of the ADMIRE-HF study with complete cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT studies were included. Both SPECT image sets were read together by two experienced nuclear imagers and scored by consensus. In addition to standard 17-segment scoring, the readers classified walls (i.e. anterior, lateral, inferior, septum and apex) as normal, matched defect, mismatched (innervation defect > perfusion defect), or reverse mismatched (perfusion defect > innervation defect). Cox proportional hazards ratios (HRs) were used to determine if age, body mass index, functional class, left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), norepinephrine, 123I-mIBG SDS, 99mTc-tetrofosmin SDS, innervation/perfusion mismatch SDS, and our simplified visual innervation/perfusion wall classification were associated with occurrence of AEs (i.e. sudden cardiac death, sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate implantable cardioverter-defibrillator therapy). At 2-year median follow-up, 52 subjects (10.4%) had AEs. Subjects with 1 or 2 mismatched walls were twice as likely to have AEs compared with subjects with either 0 or 3-5 mismatched walls (16.3% vs. 8.3%, P = 0.010). Cox regression analyses showed that patients with a visual mismatch in 1-2 walls had an almost two times higher risk of AEs [HR 2.084 (1.109-3.914), P = 0.001]. None of the other innervation, perfusion and mismatch scores using standard 17 segments were associated with AEs. BNP (ng/L) was the only non-imaging parameter associated with AEs. A visual left ventricular wall-level based scoring method identified highest AE risk in ischaemic HF subjects with intermediate levels of innervation/perfusion mismatches. This simple technique for the evaluation of SPECT studies, which are often challenging in HF subjects, seems to be superior to the 17-segment scoring method.


On being dependent on home mechanical ventilation: depictions of patients' experiences over time.
In this study, the authors describe the meanings of experiences of being dependent on a ventilator (HMV) and living at home as narrated by 13 people who had been using a ventilator via a mask or tracheostomy for half a year. The analyses revealed various movements across time toward the goal of using the ventilator successfully, and some narratives depicted suffering caused by care. The analyses also yielded different representations of embodiment. These findings were abstracted into two contrasting meanings of the experience of using HMV over time: a closing in or an opening up of the lived body, oneself, to other people and to the world. The authors illustrate this interpretation with two images. Ignorance and negative attitudes on the part of professionals working and/or managing care in the patients' homes are interpreted as causing suffering and intensifying a closed-in mode of being.


Surgical treatment of lesions involving the supplementary motor area: clinical results of 12 patients.
Surgical resection of lesions involving the dominant supplementary motor area (SMA) may result in immediate postoperative motor and speech deficits which in most cases are reversible.We report 12 patients with frontal lesions involving the SMA and aim to analyse the clinical data and the correlation of neurological deficit with the extent of SMA resection. 12 patients (5M/7F, mean age 30.5) harbouring lesions involving the SMA who underwent surgery between 2002-2007 were evaluated retrospectively. Eloquent cortical areas were determined by functional MRI studies and/or invasive monitoring with subdural grids and depth electrodes and/or awake craniotomy with continuous intraoperative monitoring. The evaluation of postoperative MRI's revealed total and subtotal resection of the lesion in 9(75%) and 3(25%) patients respectively. The extent of SMA resection was complete in 5 patients (41,6%) and incomplete in 7 patients (58,3%). Immediately postoperatively, all patients where the resection of SMA was complete displayed the typical characteristics of SMA syndrome. The degree of deficits was consistent with the extent of the SMA resection in all patients. Proper diagnostic methods aiming to localise the sensorimotor area can minimize the risk of deficit in the surgical treatment of SMA lesions. The results suggest a relationship between the incidence of SMA syndrome and the extent of SMA resection.


Inverse Correlation of Venous Brain Natriuretic Peptide Levels with Body Mass Index Is due to Decreased Production.
The aim of this paper was to study the association between body mass index (BMI) and coronary sinus (CS) brain natriuretic peptide (BNP) levels in patients with heart failure and reduced systolic function (HFrEF). There is an inverse relationship between systemic venous BNP (V-BNP) levels and BMI in patients with HFrEF. It is unclear whether this finding is due to decreased production or due to an increased metabolism of BNP. Since CS-BNP levels reflect BNP production, we hypothesized that assessing the correlation of CS-BNP levels with BMI would provide insight into the mechanism of this inverse relationship of V-BNP and BMI. We prospectively enrolled 54 subjects with HFrEF who were to undergo cardiac resynchronization device implantation. CS-BNP, V-BNP, and arterial BNP (A-BNP) levels were measured during the implant procedure. Subjects were divided into 2 groups based on their BMI (group 1: BMI <30 and group 2: BMI ≥30). The mean age of the overall study group was 64 ± 10 years. Average BMI for group 1 was 25.8 ± 2.8 and 36.8 ± 4.6 for group 2 (p < 0.03). A history of hypertension was present in 55% (n = 26) of the subjects, while diabetes was reported in 31% (n = 15). Serum creatinine was 1.0 ± 0.2 mg/dL and TSH 2.1 ± 1.4 mIU/L. 79% of the subjects were receiving β-blockers, while 94% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The mean CS-BNP, V-BNP, and A-BNP levels in group 2 were significantly lower than in group 1 (286.2 ± 170.5 vs. 417.5 ± 247.5 pg/mL, p = 0.04; 126.6 ± 32.5 vs. 228 ± 96.4 pg/mL, p = 0.01; and 151.9 ± 28.6 vs. 242 ± 88.8 pg/mL, p = 0.04, respectively). Univariate analysis and multivariate regression adjusted for age, diabetes mellitus, sex, glomerular filtration rate, and left atrial size confirmed BMI as an independent predictor of CS-BNP levels (β = -0.372, p = 0. 03) in our study. In this study, we demonstrate an inverse relationship between CS-BNP levels and BMI in patients with HFrEF. These findings suggest that the previously established inverse relationship between V-BNP and BMI is due to a decreased cardiac production of BNP in obese patients rather than from increased peripheral metabolism.


Oxygen-derived radicals: a link between reperfusion injury and inflammation.
Oxygen-derived free radicals (superoxide and hydroxyl) and related species (hydrogen peroxide and hypohalous acids) have well-defined roles in the inflammatory process. Their actions include the killing of microorganisms as well as participation in cell-to-cell communication among phagocytes via the activation of a superoxide-dependent chemoattractant. The active oxygen species also have roles in postischemic injury brought about by the conversion during ischemia of the enzyme xanthine dehydrogenase (EC 220.127.116.11) to the radical-producing xanthine oxidase (EC 18.104.22.168). Although the enzymes responsible for producing superoxide in inflammation and ischemia are quite distinct, and are triggered by very different events, there are points of interplay in the two mechanisms whereby an ischemia/reperfusion-induced injury would lead to inflammation, and conversely whereby inflammation could lead to impairment of the circulation and hence to ischemic injury.


Long-term mortality burden trends attributed to black carbon and PM2·5 from wildfire emissions across the continental USA from 2000 to 2020: a deep learning modelling study.
Long-term improvements in air quality and public health in the continental USA were disrupted over the past decade by increased fire emissions that potentially offset the decrease in anthropogenic emissions. This study aims to estimate trends in black carbon and PM2·5 concentrations and their attributable mortality burden across the USA. In this study, we derived daily concentrations of PM2·5 and its highly toxic black carbon component at a 1-km resolution in the USA from 2000 to 2020 via deep learning that integrated big data from satellites, models, and surface observations. We estimated the annual PM2·5-attributable and black carbon-attributable mortality burden at each 1-km2 grid using concentration-response functions collected from a national cohort study and a meta-analysis study, respectively. We investigated the spatiotemporal linear-regressed trends in PM2·5 and black carbon pollution and their associated premature deaths from 2000 to 2020, and the impact of wildfires on air quality and public health. Our results showed that PM2·5 and black carbon estimates are reliable, with sample-based cross-validated coefficients of determination of 0·82 and 0·80, respectively, for daily estimates (0·97 and 0·95 for monthly estimates). Both PM2·5 and black carbon in the USA showed significantly decreasing trends overall during 2000 to 2020 (22% decrease for PM2·5 and 11% decrease for black carbon), leading to a reduction of around 4200 premature deaths per year (95% CI 2960-5050). However, since 2010, the decreasing trends of fine particles and premature deaths have reversed to increase in the western USA (55% increase in PM2·5, 86% increase in black carbon, and increase of 670 premature deaths [460-810]), while remaining mostly unchanged in the eastern USA. The western USA showed large interannual fluctuations that were attributable to the increasing incidence of wildfires. Furthermore, the black carbon-to-PM2·5 mass ratio increased annually by 2·4% across the USA, mainly due to increasing wildfire emissions in the western USA and more rapid reductions of other components in the eastern USA, suggesting a potential increase in the relative toxicity of PM2·5. 100% of populated areas in the USA have experienced at least one day of PM2·5 pollution exceeding the daily air quality guideline level of 15 μg/m3 during 2000-2020, with 99% experiencing at least 7 days and 85% experiencing at least 30 days. The recent widespread wildfires have greatly increased the daily exposure risks in the western USA, and have also impacted the midwestern USA due to the long-range transport of smoke. Wildfires have become increasingly intensive and frequent in the western USA, resulting in a significant increase in smoke-related emissions in populated areas. This increase is likely to have contributed to a decline in air quality and an increase in attributable mortality. Reducing fire risk via effective policies besides mitigation of climate warming, such as wildfire prevention and management, forest restoration, and new revenue generation, could substantially improve air quality and public health in the coming decades. National Aeronautics and Space Administration (NASA) Applied Science programme, NASA MODIS maintenance programme, NASA MAIA satellite mission programme, NASA GMAO core fund, National Oceanic and Atmospheric Administration (NOAA) GEO-XO project, NOAA Atmospheric Chemistry, Carbon Cycle, and Climate (AC4) programme, and NOAA Educational Partnership Program with Minority Serving Institutions.


Treatment of intracranial aneurysms using flow-diverting silk stents (BALT): a single centre experience.
The Silk stent (Balt, Montmorency, France) is a retractable device designed to achieve curative reconstruction of the parent artery associated with an intracranial aneurysm. We present our initial experience with the Silk flow-diverting stent in the management and follow-up of 25 patients presenting with intracranial aneurysms.Twenty-five patients (age range, 34-81 years; 24 female) were treated with the Silk flow-diverting device. Aneurysms ranged in size from small (5), large (10) and giant (10) and included wide-necked aneurysms, multiple, nonsaccular, and recurrent intracranial aneurysms. Nine aneurysms were treated for headache, 14 for mass effect. None presented with haemorrhage. All patients were pretreated with dual antiplatelet medications for at least 72 hours before surgery and continued taking both agents for at least three months after treatment. A total of 25 Silk stents were used. Control MR angiography and/or CT angiography was typically performed prior to discharge and at one, three, six and 12 months post treatment. A follow-up digital subtraction angiogram was performed between six and 19 months post treatment.Complete angiographic occlusion or subtotal occlusion was achieved in 15 patients in a time frame from three days to 12 months. Three deaths and one major complication were encountered during the study period. Two patients, all with cavernous giant aneurysms, experienced transient exacerbations of preexisting cranial neuropathies and headache after the Silk treatment. Both were treated with corticosteroids, and symptoms resolved completely within a month.In our experience the Silk stent has proven to be a valuable tool in the endovascular treatment of intracranial giant partially thrombosed aneurysms and aneurysms of the internal carotid artery cavernous segment presenting with mass effect. The time of complete occlusion of the aneurysms and the risk of the bleeding is currently not predictable.


"Spike" in acute asthma exacerbations during enterovirus D68 epidemic in Japan: A nation-wide survey.
In September 2015, Japan experienced an unusual increase in acute asthma hospitalizations of children that coincided with an enterovirus D68 (EV-D68) epidemic. The objective of this study is to investigate whether EV-D68 had a causal relationship with the spike in asthma hospitalizations. A nation-wide retrospective survey of asthma hospitalizations of children was performed for the period from January 2010 through October 2015. The Japanese Society of Pediatric Allergy and Clinical Immunology asked its affiliated hospitals to report monthly numbers of hospitalizations, ICU admissions and mechanical ventilations due to acute asthma exacerbation. The data were retrieved from medical databases using predefined search criteria: diagnosis of asthma or asthmatic bronchitis, admission, and age <20 years. Monthly numbers of EV-D68 detection were also obtained from the Infectious Disease Surveillance Center of Japan. A Granger causality test was used to analyze the association of EV-D68 detections for asthma exacerbation. A total of 157 hospitals reported 87,189 asthma hospitalizations, including 477 ICU admissions and 1193 mechanical ventilations, during the survey period of 5 years and 10 months. The numbers of these events increased drastically in September 2015. The Granger causality test verified the association between EV-D68 and asthma hospitalizations/mechanical ventilations. The most-affected age group was 3-6 years old. The spike in pediatric asthma hospitalizations in Japan in September 2015 was found to be associated with the EV-D68 epidemic. Respiratory pathogens can cause "epidemics" of asthma exacerbation. Coordinated surveillance of infectious diseases and asthma may be beneficial for prevention and better control of both illnesses.


Application of Artificial Neural Network to Preoperative 18F-FDG PET/CT for Predicting Pathological Nodal Involvement in Non-small-cell Lung Cancer Patients.
Purpose: To evaluate the performance of artificial neural networks (aNN) applied to preoperative 18F-FDG PET/CT for predicting nodal involvement in non-small-cell lung cancer (NSCLC) patients. Methods: We retrospectively analyzed data from 540 clinically resectable NSCLC patients (333 M; 67.4 ± 9 years) undergone preoperative 18F-FDG PET/CT and pulmonary resection with hilo-mediastinal lymphadenectomy. A 3-layers NN model was applied (dataset randomly splitted into 2/3 training and 1/3 testing). Using histopathological reference standard, NN performance for nodal involvement (N0/N+ patient) was calculated by ROC analysis in terms of: area under the curve (AUC), accuracy (ACC), sensitivity (SE), specificity (SP), positive and negative predictive values (PPV, NPV). Diagnostic performance of PET visual analysis (N+ patient: at least one node with uptake ≥ mediastinal blood-pool) and of logistic regression (LR) was evaluated. Results: Histology proved 108/540 (20%) nodal-metastatic patients. Among all collected data, relevant features selected as input parameters were: patients' age, tumor parameters (size, PET visual and semiquantitative features, histotype, grading), PET visual nodal result (patient-based, as N0/N+ and N0/N1/N2). Training and testing NN performance (AUC = 0.849, 0.769): ACC = 80 and 77%; SE = 72 and 58%; SP = 81 and 81%; PPV = 50 and 44%; NPV = 92 and 89%, respectively. Visual PET performance: ACC = 82%, SE = 32%, SP = 94%; PPV = 57%, NPV = 85%. Training and testing LR performance (AUC = 0.795, 0.763): ACC = 75 and 77%; SE = 68 and 55%; SP = 77 and 82%; PPV = 43 and 43%; NPV = 90 and 88%, respectively. Conclusions: aNN application to preoperative 18F-FDG PET/CT provides overall good performance for predicting nodal involvement in NSCLC patients candidate to surgery, especially for ruling out nodal metastases, being NPV the best diagnostic result; a high NPV was also reached by PET qualitative assessment. Moreover, in such population with low a priori nodal involvement probability, aNN better identify the relatively few and unexpected nodal-metastatic patients than PET analysis, so supporting the additional aNN use in case of PET-negative images.


A surface plasmon resonance sensor based on 3,5-diaminopyrazine with a high selectivity for thymine in AP site-containing DNA duplex.
We here report on a surface plasmon resonance (SPR) sensor carrying small organic ligands for the detection of single-nucleotide polymorphisms (SNPs). Two kinds of ligands are prepared, both of which have a hydrogen-bond forming site suitable for nucleobase recognition, and have an active amino group for the immobilization to the sensor chip. While the sensor immobilized flavin does not show any useful responses, the sensor based on 3,5-diaminopyrazine shows a highly selective response to thymine over other nucleobases opposite an abasic site in DNA duplexes (5'-GTT GGA GCT GXG GGC GTA GGC-3'/3'-CAA CCT CGA CNC CCG CAT CCG-5', X = AP site, N = target; G, C, A, T). In PBS buffer (pH 6.4, 0.25 M NaCl, at 5 degrees C), the sensor can detect 10 nM of the sample solution, and the SPR signal for thymine is linear in the concentration range from 10 nM to 100 nM. These sensing functions of the present sensor are discussed for the development of SNPs detection chemistry based on DNA-binding small molecules.


Arthroscopic Dorsal Ligamentocapsulodesis in the Treatment of Occult Dorsal Wrist Ganglion Cysts Associated with Scapholunate Instability: Surgical Technique and Preliminary Clinical Results.
Background: This study aimed to evaluate our preliminary results and experience with the arthroscopic dorsal ligamentocapsulodesis in managing occult dorsal wrist ganglion cysts (ODGCs) associated with scapholunate (SL) instability. Methods: All patients who underwent arthroscopic dorsal ligamentocapsulodesis due to an ODGC with concomitant SL ligament tear were retrospectively reviewed. In addition to demographic data and length of follow-up, outcomes data that included range of motion, grip strength, modified Mayo wrist score (MMWS), complications and radiographs were collected. Results: The study included 18 patients (18 wrists; 10 female and 8 male). The mean age was 32 years (range: 19-48) and the mean follow-up was 34 months (range: 24-48). The mean preoperative extension deficit decreased from 5.5° (range: 0°-20°) to 2.7° (range: 0°-15°) at the final follow-up (p = 0.004). The mean preoperative flexion deficits decreased from 4.4° (range: 0°-15°) to 2.2° (range: 0°-10°) postoperatively (p = 0.003). The mean hand grip strength significantly increased from 27.7 kg (range: 22-36) to 38.3 kg (range: 31-46) at the final follow-up assessment (p < 0.001). The mean MMWS improved from 46 (range: 25-65) pre-operatively to 91 (range: 70-100) at the final follow-up (p = 0.0002). No major intra- or postoperative complications were observed. Conclusions: SL instability may have an important role in the aetiology of ODGCs, and arthroscopic dorsal ligamentocapsulodesis can provide pain relief and functional improvement without recurrence at the short- to mid-term follow-up in the treatment of ODGCs. Level of Evidence: Level IV (Therapeutic).


Phosphoproteomic Analysis of Rat Neutrophils Shows the Effect of Intestinal Ischemia/Reperfusion and Preconditioning on Kinases and Phosphatases.
Intestinal ischemia reperfusion injury (iIRI) is a severe clinical condition presenting high morbidity and mortality worldwide. Some of the systemic consequences of IRI can be prevented by applying ischemic preconditioning (IPC), a series of short ischemia/reperfusion events preceding the major ischemia. Although neutrophils are key players in the pathophysiology of ischemic injuries, neither the dysregulation presented by these cells in iIRI nor the protective effect of iIPC have their regulation mechanisms fully understood. Protein phosphorylation, as well as the regulation of the respective phosphatases and kinases are responsible for regulating a large number of cellular functions in the inflammatory response. Moreover, in previous work we found hydrolases and transferases to be modulated in iIR and iIPC, suggesting the possible involvement of phosphatases and kinases in the process. Therefore, in the present study, we analyzed the phosphoproteome of neutrophils from rats submitted to mesenteric ischemia and reperfusion, either submitted or not to IPC, compared to quiescent controls and sham laparotomy. Proteomic analysis was performed by multi-step enrichment of phosphopeptides, isobaric labeling, and LC-MS/MS analysis. Bioinformatics was used to determine phosphosite and phosphopeptide abundance and clustering, as well as kinases and phosphatases sites and domains. We found that most of the phosphorylation-regulated proteins are involved in apoptosis and migration, and most of the regulatory kinases belong to CAMK and CMGC families. An interesting finding revealed groups of proteins that are modulated by iIR, but such modulation can be prevented by iIPC. Among the regulated proteins related to the iIPC protective effect, Vamp8 and Inpp5d/Ship are discussed as possible candidates for control of the iIR damage.


[The medical organizational aspects of decreasing of preventable mortality in the case of traffic accident in municipal district].
The article deals with the results of the study of such actual issue as decreasing of preventable mortality in the case of traffic accident in municipal district. The analysis was based on the mortality statistical data and the expertise of causes of lethal outcomes of traffic accidents. The results are used to develop the measures of improving the organization and quality of medical care of victims of road accident on the pre-hospital and hospital stages on the level of municipal health care to decrease the human losses caused by traffic accident.


The Effect of Changes in Cannabis Exposure on Psychotic Symptoms in Patients With Comorbid Cannabis Use Disorder.
It remains unclear whether there is an association between severity of cannabis use and psychotic symptom severity over time. Shedding light on this under-researched matter could have clinical implications for this patient group. This was a secondary analysis of a randomized, parallel-group, superiority, assessor-blinded trial. We followed 60 patients with dually diagnosed psychosis and cannabis use disorders from the Danish CapOpus trial, which included assessments at baseline, post-treatment (6 months) and 10 months. Cannabis use was registered by self-report assisted by timeline follow-back. Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) positive, negative, and general symptoms scores. Analyses were adjusted for potential confounders. Patients were classified into four categories: minor use (0-30 joints at baseline and 0-9 joints at follow-up; n = 19), moderate use (0-30 joints at baseline and 10-196 joints at follow-up; n = 11), high (reducing) use (31-240 joints at baseline and 0-9 joints at follow-up; n = 9), and severe use (31-240 joints at baseline and 10-196 joints at follow-up; n = 21). Those with severe and persistent cannabis use (severe use group) had significantly higher scores, as compared to those with minor use, on the positive symptom (17.0, 95% CI [4.7-19.2] vs. 12.7, 95% CI [10.4-15.0], respectively, adjusted p < .009) and general symptom (37.4, 95% CI [34.0-40.8] vs. 29.8, 95% CI [26.3-33.3], respectively, adjusted p < .003) scales at follow-up. The severe use group had significantly higher scores, as compared to the moderate use group, on the negative symptom scale at follow-up (17.4, 95% CI [15.1-19.7] vs. 12.5, 95% CI [9.3-15.6], respectively, adjusted p < .02). On the other hand, patients in the high (reducing) use group demonstrated the greatest improvement in psychotic symptoms on all three measures. These findings are preliminary and more research must be done to elucidate the relationship between cannabis use and psychosis. Treatment of psychosis and comorbid cannabis use disorder could in the future incorporate treatment strategies emphasising encouragement to reduce cannabis use. CapOpus is registered at clinicaltrials.gov (NCT00484302).


A biomimetic platform to study the interactions of bioelectroactive molecules with lipid nanodomains.
In this work, we developed a biomimetic platform where the study of membrane associated redox processes and high-resolution imaging of lipid nanodomains can be both performed, based on a new functional gold modification, l-cysteine self-assembled monolayer. This monolayer proved to be ideal for the preparation of defect-free planar supported lipid bilayers (SLBs) where nanodomains with height difference of ∼1.5 nm are clearly resolved by atomic force microscopy. Single and multicomponent lipid compositions were used, leading to the formation of different phases and domains mimicking the lateral organization of cellular membranes, and in all cases stable and continuous bilayers were obtained. These platforms were tested toward the interaction with bioelectroactive molecules, the antioxidant quercetin, and the hormone epinephrine. Despite the weak interaction detected between epinephrine and lipid bilayers, our biomimetic interface was able to sense the redox process of membrane-bound epinephrine, obtain its surface concentration (9.36 × 10(-11) mol/cm(2) for a fluid bilayer), and estimate a mole fraction membrane/water partition coefficient (Kp) from cyclic voltammetric measurements (1.13 × 10(4) for a fluid phase membrane). This Kp could be used to quantitatively describe the minute changes observed in the photophysical properties of epinephrine intrinsic fluorescence upon its interaction with liposome suspensions. Moreover, we showed that the lipid membrane stabilizes epinephrine structure, preventing its oxidation, which occurs in neutral aqueous solution, and that epinephrine partition and mobility in membranes depends on lipid phase, expanding our knowledge on hormone membrane interactions.


Process for Assembly and Transformation into Saccharomyces cerevisiae of a Synthetic Yeast Artificial Chromosome Containing a Multigene Cassette to Express Enzymes That Enhance Xylose Utilization Designed for an Automated Platform.
A yeast artificial chromosome (YAC) containing a multigene cassette for expression of enzymes that enhance xylose utilization (xylose isomerase [XI] and xylulokinase [XKS]) was constructed and transformed into Saccharomyces cerevisiae to demonstrate feasibility as a stable protein expression system in yeast and to design an assembly process suitable for an automated platform. Expression of XI and XKS from the YAC was confirmed by Western blot and PCR analyses. The recombinant and wild-type strains showed similar growth on plates containing hexose sugars, but only recombinant grew on D-xylose and L-arabinose plates. In glucose fermentation, doubling time (4.6 h) and ethanol yield (0.44 g ethanol/g glucose) of recombinant were comparable to wild type (4.9 h and 0.44 g/g). In whole-corn hydrolysate, ethanol yield (0.55 g ethanol/g [glucose + xylose]) and xylose utilization (38%) for recombinant were higher than for wild type (0.47 g/g and 12%). In hydrolysate from spent coffee grounds, yield was 0.46 g ethanol/g (glucose + xylose), and xylose utilization was 93% for recombinant. These results indicate introducing a YAC expressing XI and XKS enhanced xylose utilization without affecting integrity of the host strain, and the process provides a potential platform for automated synthesis of a YAC for expression of multiple optimized genes to improve yeast strains.


Inferring Causal Gene Regulatory Networks from Coupled Single-Cell Expression Dynamics Using Scribe.
Here, we present Scribe (https://github.com/aristoteleo/Scribe-py), a toolkit for detecting and visualizing causal regulatory interactions between genes and explore the potential for single-cell experiments to power network reconstruction. Scribe employs restricted directed information to determine causality by estimating the strength of information transferred from a potential regulator to its downstream target. We apply Scribe and other leading approaches for causal network reconstruction to several types of single-cell measurements and show that there is a dramatic drop in performance for "pseudotime"-ordered single-cell data compared with true time-series data. We demonstrate that performing causal inference requires temporal coupling between measurements. We show that methods such as "RNA velocity" restore some degree of coupling through an analysis of chromaffin cell fate commitment. These analyses highlight a shortcoming in experimental and computational methods for analyzing gene regulation at single-cell resolution and suggest ways of overcoming it.


Measuring the glomerular filtration rate in obese individuals without overt kidney disease.
Identifying methods to accurately measure the glomerular filtration rate (GFR) in obese individuals without kidney overt kidney disease is necessary to understanding the pathophysiology and natural history of obesity-related kidney disease. Using a cross-sectional design, iohexol clearance and disposition was measured, an optimal sampling schedule was identified, and the reliability of GFR-estimating methods was described in 29 obese individuals with normal serum creatinine levels. Iohexol disposition was measured using population pharmacokinetics. The agreement with GFR-estimating equations was assessed by intraclass coefficients. Mean age was 44 ± 10 years, body mass index 45 ± 10, creatinine 0.7 ± 0.2 mg/dl (62 ± 18 μmol/l) , and cystatin C 0.83 ± 0.18 mg/dl (8.3 ± 1.8 mg/l). Iohexol disposition fit a two-compartment model and 5 sampling windows were identified over a 4-hour period to optimize model accuracy and minimize blood draws. Precision was not compromised with this sampling design. Neither creatinine nor cystatin C were linearly correlated with the measured GFR though cystatin C was independent of body composition. Agreement was fair to poor between the measured GFR and GFR-estimating equations. This study offers a rigorous method to study obesity-related kidney disease and improve upon suboptimal GFR-estimating methods.


Cleavage of hemagglutinin-bearing lentiviral pseudotypes and their use in the study of influenza virus persistence.
Influenza A viruses (IAVs) are a major cause of infectious respiratory human diseases and their transmission is dependent upon the environment. However, the role of environmental factors on IAV survival outside the host still raises many questions. In this study, we used lentiviral pseudotypes to study the influence of the hemagglutinin protein in IAV survival. High-titered and cleaved influenza-based lentiviral pseudoparticles, through the use of a combination of two proteases (HAT and TMPRSS2) were produced. Pseudoparticles bearing hemagglutinin proteins derived from different H1N1, H3N2 and H5N1 IAV strains were subjected to various environmental parameters over time and tested for viability through single-cycle infectivity assays. We showed that pseudotypes with different HAs have different persistence profiles in water as previously shown with IAVs. Our results also showed that pseudotypes derived from H1N1 pandemic virus survived longer than those derived from seasonal H1N1 virus from 1999, at high temperature and salinity, as previously shown with their viral counterparts. Similarly, increasing temperature and salinity had a negative effect on the survival of the H3N2 and H5N1 pseudotypes. These results showed that pseudotypes with the same lentiviral core, but which differ in their surface glycoproteins, survived differently outside the host, suggesting a role for the HA in virus stability.


The vanilloid receptor: a molecular gateway to the pain pathway.
The detection of painful stimuli occurs primarily at the peripheral terminals of specialized sensory neurons called nociceptors. These small-diameter neurons transduce signals of a chemical, mechanical, or thermal nature into action potentials and transmit this information to the central nervous system, ultimately eliciting a perception of pain or discomfort. Little is known about the proteins that detect noxious stimuli, especially those of a physical nature. Here we review recent advances in the molecular characterization of the capsaicin (vanilloid) receptor, an excitatory ion channel expressed by nociceptors, which contributes to the detection and integration of pain-producing chemical and thermal stimuli. The analysis of vanilloid receptor gene knockout mice confirms the involvement of this channel in pain sensation, as well as in hypersensitivity to noxious stimuli following tissue injury. At the same time, these studies demonstrate the existence of redundant mechanisms for the sensation of heat-evoked pain.


Serotonergic 5-HT2A receptor stimulation induces steroid 5alpha-reductase gene expression in rat C6 glioma cells via transcription factor Egr-1.
Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment of depressive mood disorders and well known to inhibit the reuptake of neurotransmitter serotonin into nerve terminals. Thus, it seems conceivable that these drugs may induce the outflow of serotonin from the synapse as a consequence of inhibiting the reuptake, resulting in the stimulation of glial cells surrounding nerve terminals. On this hypothesis, the effect of serotonin on steroid 5alpha-reductase type 1 (5alpha-R) gene expression in rat C6 glioma cells was examined as one of the in vitro model experiments for investigating the indirect influence of SSRIs on glial cells. Serotonin elevated 5alpha-R mRNA and protein levels through the stimulation of serotonin 5-HT2A receptors, and also elevated Egr-1 mRNA and protein levels prior to 5alpha-R gene expression in the glioma cells. Furthermore, serotonin failed to significantly increase 5alpha-R mRNA levels in the cells preloaded with the antisense oligodeoxynucleotide targeted on Egr-1 gene. These results indicate that serotonin may stimulate 5alpha-R gene expression via transcription factor Egr-1 in glial cells, thus suggesting that serotonin flowing out of the serotonergic synapse may be implicated in SSRI-induced changes in neurosteroid metabolism in brain.


Cancer-Cell Deep-Learning Classification by Integrating Quantitative-Phase Spatial and Temporal Fluctuations.
We present a new classification approach for live cells, integrating together the spatial and temporal fluctuation maps and the quantitative optical thickness map of the cell, as acquired by common-path quantitative-phase dynamic imaging and processed with a deep-learning framework. We demonstrate this approach by classifying between two types of cancer cell lines of different metastatic potential originating from the same patient. It is based on the fact that both the cancer-cell morphology and its mechanical properties, as indicated by the cell temporal and spatial fluctuations, change over the disease progression. We tested different fusion methods for inputting both the morphological optical thickness maps and the coinciding spatio-temporal fluctuation maps of the cells to the classifying network framework. We show that the proposed integrated triple-path deep-learning architecture improves over deep-learning classification that is based only on the cell morphological evaluation via its quantitative optical thickness map, demonstrating the benefit in the acquisition of the cells over time and in extracting their spatio-temporal fluctuation maps, to be used as an input to the classifying deep neural network.


[Detecting antibiotics in milk: a public health problem].
Determining the presence of antibiotics in raw and processed milk in the city of Monteria. Three samplings were three samples were taken in a dairy company in the city of Monteria at two-month intervals. Pasteurised milk samples were taken from six trademarks. All milk samples were tested for acidity by alcoholometry; the presence of antiseptic H2O2 was determined by using 35 % KI and 1 % V2O5 diluted in H2SO4. The incidence of antibiotics (Total antibiotic Bio K 331 (Diagnostic Jemelle dioxide, Belgique) was then determined. The test's sensitivity limit was determined by using 0.004 UI/ml penicillin, 0.100 mg/ml oxytetracycline and 5,000 mg/ml chloramphenicol as positive controls in two-fold serial dilutions. Aliquots of milk were used as positive and negative controls for each sample. The first sampling evaluated 212 samples of milk, the second 167 and the third 66, for a total of 445 samples. All samples were negative for alcoholometry acidity. Antibiotics were detected in 111 (25 %) samples of raw milk; however, no antibiotics were detected in the pasteurised milk. The test's sensitivity revealed that penicillin was detectable in a maximum 0.002UI/ml dilution, oxytetracycline in 0.005ìg/ml and chloramphenicol in 1.25 mg/ml. Traces of antibiotics being found in 25 % of milk samples revealed a lack of public health controls, as well as evidence of the indiscriminate use of antibiotics in the livestock industry and a risk to public health.


[Study on functions and mechanism of curcumin in inducing gastric carcinoma BGC apoptosis].
discuss the biological function and regulation mechanism of curcumin in promoting human gastric carcinoma BGC-823 apoptosis. Conventional in virto culture in logarithmic phase gastric carcinoma BGC-823 cells; cells are divided into four groups: control group, low treatment group, middle treatment group and high treatment group, with curcumin concentration being 0 mg/L, 5 mg/L, 10 mg/L, and 20 mg/L, respectively. 24 hours after curcumin is treated, cell proliferation level and apoptosis rate are measured with MTT colorimetry and flow cytometry, Bax, Bcl-2 protein expression is measured with immunohistochemistry; mRNA of Caspase-3 is tested by means of PCR. MTT test indicates that curcumin can inhibit human gastric carcinoma BGC-823 cell proliferation, showing concentration dependency; flow cytometry shows that curcumin can effectively induce apoptosis, showing concentration dependency, where the apoptosis rate is 48.3% 24 hours after 20 mg/L curcumin is treated; immunohistochemistry test shows that curcumin treatment enables Bax expression level in human gastric carcinoma BGC-823 cells to go up, meanwhile, the Bcl-2 protein expression level to go down, besides, the mRNA expression level of Caspase-3 in cells increases through induction of curcumin. Curcumin has obvious inhibitory effect on human gastric carcinoma BGC-823 cell proliferation, showing concentration dependency to promote apoptosis. Such biological effect may be associated with activating Caspase-3 signal channel by activating Bax protein expression and inhibiting Bcl-2 protein. This study lays an important foundation for further discussing the mechanism of curcumin in inducing human gastric carcinoma BGC-823 apoptosis.


Bromobenzene-induced hepatotoxicity at the transcriptome level.
Rats were exposed to three levels of bromobenzene, sampled at 6, 24, and 48 h, and liver gene expression profiles were determined to identify dose and time-related changes. Expression of many genes changed transiently, and dependent on the dose. Few changes were identified after 6 h, but many genes were differentially expressed after 24 h, while after 48 h, only the high dose elicited large effects. Differentially expressed genes were involved in drug metabolism (upregulated GSTs, mEH, NQO1, Mrps, downregulated CYPs, sulfotransferases), oxidative stress (induced HO-1, peroxiredoxin, ferritin), GSH depletion (induced GCS-l, GSTA, GSTM) the acute phase response, and in processes like cholesterol, fatty acid and protein metabolism, and intracellular signaling. Trancriptional regulation via the electrophile and sterol response elements seemed to mediate part of the response to bromobenzene. Recovery of the liver was suggested in response to BB by the altered expression of genes involved in protein synthesis and cytoskeleton rearrangement. Furthermore, after 48 h, rats in the mid dose group showed no toxicity, and gene expression patterns resembled the normal situation. For certain genes (e.g., CYP4A, metallothioneins), intraday variation in expression levels was found, regardless of the treatment. Selected cDNA microarray measurements were confirmed using the specific and sensitive branched DNA signal amplification assay.


Dietary relationships with fatal colorectal cancer among Seventh-Day Adventists.
Associations between fatal colon or colorectal cancer and frequency of use of meat, cheese, milk, eggs, green salad, and coffee, as well as percent desirable weight, are described with the use of 21 years of follow-up for 25,493 white California Seventh-Day Adventists. Associations are presented in terms of relative risk (RR) of colorectal cancer for heavy or light exposure versus rare exposure. There were no clear relationships evident between colon or rectal cancer and meat, cheese, milk, or green salad use. Egg use was positively associated with risk of fatal colon cancer in both males (RR = 1.6) and females (RR = 1.7). Coffee use was positively associated with both colon and rectal cancer mortality in males and females, particularly for colon cancer during the last 11 years of follow-up (male RR = 3.5; female RR = 1.9). Overweight (percent of desirable weight greater than or equal to 125) was associated with an increased risk of fatal rectal cancer in both sexes combined (RR = 2.8) and colon cancer in males only (RR = 3.3). Furthermore, eggs, coffee, and overweight appear to be independently associated with risk of both colon and colorectal cancer. These three factors may explain a substantial portion of the colorectal cancer mortality differential between Adventists and U.S. whites (62% for males; 30% for females).


[Administration of two uroselective alpha-adrenoblockers in pharmacological treatment of acute urinary retention in patients with prostatic adenoma].
Acute urinary retention in males is often caused by infravesical obstruction due to enlargement of the prostatic gland. Recently it was found that alpha-adrenoblockers promote recovery of physiological voiding in patients with benign prostatic hyperplasia. In our study urinary bladder draining with urethral catheter in 136 patients with acute urinary retention was immediately followed by simultaneous administration of two alpha1-adrenoblockers--alfuzosine (10 mg once a day) (dalfaz CP) and tamsulosine (0.4 mg once a day) (omnik okas). The control group of 96 patients received monotherapy with alfuzosine. Physiological voiding recovered in 42.7% patients on alfuzosine monotherapy and in 64% patients on alfuzosine+tamsulosine.


Perceptions and Definitions of Power Within the Context of HIV-Negative Male Couples' Relationships.
Examining dynamics within relationships is critical for development of effective HIV prevention interventions for male couples. The dynamic of power has received little attention in research with male couples, though power has been reported to affect HIV risk among heterosexual couples. To help address this knowledge gap, the present cross-sectional analysis used mixed methods with dyadic data from 142 HIV-negative male couples to (1) assess partnered men's perception of who has the most power in their relationship and why, (2) examine whether partners concur about who has the most power and their reasoning for this selection, and (3) assess whether male couples' concurrence about who has the most power is associated with their engagement of condomless anal sex within and/or outside the relationship, type of relationship, and aspects of their sexual agreement. Individual- and couple-level responses about who has the most power were quantitatively assessed, whereas for why, their responses were coded qualitatively. Fifty-six percent of couples concurred about who has the most power in their relationship and of these, many said it was equal. Regarding why, themes of responses ranged from "compromise" and "shared responsibility" for those who concurred about who has the most power versus "dominant/compliant personality" and "money" among the couples who disagreed about who has the most power in their relationship. Concordance about who has the most power was only associated with condomless anal sex within the relationship. Further research is warranted to examine how power may affect other dynamics of male couples' relationships and risk-related behaviors.


Cytotoxic CD4 T cells in viral hepatitis.
CD4+ T cells are thought to contribute to antiviral immune responses by secretion of cytokines thereby providing help to CD8+ T and B cells. However, perforin-positive cytotoxic CD4+ T cells have been described in human immunodeficiency virus-positive patients suggesting a role not only of CD8+ but also of CD4+ T cells for killing virus-infected cells. We investigated 76 patients with viral hepatitis [15 hepatitis B virus (HBV), 22 HBV/hepatitis D virus and 17 hepatitis C virus (HCV)] for cytotoxic CD4+ T cells. The frequency of perforin-positive CD4+ T cells in viral hepatitis was highly variable ranging from < 1% to more than 25%. Perforin-positive CD4+ T cells displayed the phenotype of terminally differentiated effector cells (CD28-, CD27-). The highest frequencies of CD4+ cytotoxic T lymphocytes (CTLs) were found in patients with delta hepatitis (P = 0.04 vs HBV and HCV patients), and the presence of CD4+ CTLs was associated with elevated aspartate aminotransferase levels (P = 0.01) and decreased platelet counts (P = 0.03). Perforin-positive CD4+ T cells decreased in two individuals during spontaneous clearance of acute hepatitis C. Significant associations were found between the frequency of perforin-expressing CD4+ cells and age (P = 0.04), perforin-positive CD8+ cells (P < 0.001) and perforin-positive CD4-/CD8- lymphoid cells (P = 0.002). Differentiated CD27- effector CD4+ CTLs can be detected in patients with viral hepatitis. In particular in patients with more advanced liver disease, the accumulation of perforin-positive T cells with age could be one correlate for the more severe course of viral hepatitis in elderly individuals.


Dentinal tubule invasion and adherence by Enterococcus faecalis.
To investigate dentinal tubule invasion and the predilection of Enterococcus faecalis for dentinal tubule walls. The invasion of dentinal tubules in extracted human teeth by E. faecalis was measured ex vivo after 8 weeks of incubation. The canal walls of 16 root sections were either intact or instrumented with or without smear layer present. Extent and maximum depth of tubule invasion were assessed histologically and compared between groups. In the adherence study, 44 vertically split root samples were prepared to expose longitudinally aligned dentinal tubules and fractured orthodentine (OD). Surfaces were exposed to E. faecalis (erythromycin resistant strain, JH2-2 carrying plasmid pGh9:ISS1) and incubated aerobically for 2 h. Samples were processed for analysis using scanning electron microscopy. Bacterial adhesion to tubule walls versus fractured OD was calculated as number of cells per 100 microm(2). The strain of E. faecalis used in this study showed moderate to heavy tubule invasion after 8 weeks. In the adhesion studies, significantly more bacteria adhered to fractured OD than to dentinal tubule walls (ANOVA, P < 0.001). With respect to the tubule wall, adherence was greater in inner versus outer dentine (P = 0.02) and greater when bacterial adhesion was tested in chemically defined medium than in phosphate-buffered saline (ANOVA, P < 0.001). Although E. faecalis readily invaded tubules, it did not adhere preferentially to tubule walls. Initial colonization of dentinal tubules by E. faecalis may depend primarily on other factors.


Autologous chondrocyte transplantation for reconstruction of isolated joint defects: the Assaf Harofeh experience.
Articular cartilage is incapable of undergoing self-repair since chondrocytes lose their mitotic ability as early as the first year of life. Defects in articular cartilage, especially in weight-bearing joints, will predictably deteriorate toward osteoarthritis. No method has been found to prevent this deterioration. Drilling of the subchondral bone can lead to fibrocartilage formation and temporary repair that slowly degrades. Animal experiments indicate that introducing proliferating chondrocytes such as cultured articular chondrocytes can reliably reconstruct joint defects. To describe our clinical experience in culturing and transplanting autologous chondrocytes. Biopsies were obtained from 10 patients, aged 18-45, undergoing a routine arthroscopy in which a cartilage defect was identified with indications for cartilage transplantation. The biopsies were further processed to establish chondrocyte cultures. ACT was performed in 8 of the 10 patients because of persistent symptoms for at least 2 months post-arthroscopy. All patients (6 men and 2 women) had a grade IV cartilage defect in the medial or lateral femoral condyle, and three had a defect in the trochlear region as well. Biopsies were removed from the lateral rim of the superior aspect of the femur, and cells were cultured in a clean room. Following a 2 order of magnitude expansion, cells were implanted under a periosteal flap. The eight patients implanted with autologous cells were followed for 6 months to 5 years (average 1 year). Complaints of giving-way, effusion and joint locking resolved in all patients, and pain as assessed by the visual analogue score was reduced by an average of 50%. Follow-up magnetic resonance imaging studies in all patients revealed that the defects were filled with tissue having similar signal characteristics to cartilage. Chondrocyte implantation is a procedure capable of restoring normal articular cartilage in cases with isolated joint defects. Pain can be predictably reduced, while joint locking and effusion are eliminated. The effect on osteoarthritis progression in humans has not yet been elucidated.


Treadmill Exercise before and during Pregnancy Improves Bone Deficits in Pregnant Growth Restricted Rats without the Exacerbated Effects of High Fat Diet.
Growth restriction programs adult bone deficits and increases the risk of obesity, which may be exacerbated during pregnancy. We aimed to determine if high-fat feeding could exacerbate the bone deficits in pregnant growth restricted dams, and whether treadmill exercise would attenuate these deficits. Uteroplacental insufficiency was induced on embryonic day 18 (E18) in Wistar Kyoto (WKY) rats using bilateral uterine vessel ligation (restricted) or sham (control) surgery. The F1 females consumed a standard or high-fat (HFD) diet from 5 weeks, commenced treadmill exercise at 16 weeks, and they were mated at 20 weeks. Femora and plasma from the pregnant dams were collected at post-mortem (E20) for peripheral quantitative computed tomography (pQCT), mechanical testing, histomorphometry, and plasma analysis. Sedentary restricted females had bone deficits compared to the controls, irrespective of diet, where such deficits were prevented with exercise. Osteocalcin increased in the sedentary restricted females compared to the control females. In the sedentary HFD females, osteocalcin was reduced and CTX-1 was increased, with increased peak force and bending stress compared to the chow females. Exercise that was initiated before and continued during pregnancy prevented bone deficits in the dams born growth restricted, whereas a HFD consumption had minimal bone effects. These findings further highlight the beneficial effects of exercise for individuals at risk of bone deficits.


[Mechanisms of development of long-periodicity oscillations in activity in nerve nets. Stochastically uniform nerve nets].
The possibility of generation of long-term activity in the stochastic uniform networks consisting of neuron-like threshold elements was analyzed by the mathematical simulation model. It was shown that the long-term (hundreds of milliseconds) self-stopping activity in the networks with a positive feed-back between units can be generated. Termination of the activity was based on the following factors: 1) stochastic properties of network processes which determine the fluctuations of the activity level; 2) neuronal interaction leading either to synchronization of neuronal discharges and respectively to postactivation inhibitory processes, or to reconstruction of the microstructure of the neuronal network activity when weak-connected neurons are predominantly excited. Basing on the data obtained possible participation of the mechanism involved in formation of the long-term self-stopping activity of interneuronal networks of the spinal cord realizing different types of programmed rhythmical activity (generators) is discussed.


AIDS-related tuberculosis in Rio de Janeiro, Brazil.
We studied the incidence of tuberculosis, AIDS, AIDS deaths and AIDS-TB co-infection at the population level in Rio de Janeiro, Brazil where universal and free access to combination antiretroviral therapy has been available since 1997. This was a retrospective surveillance database match of Rio de Janeiro databases from 1995-2004. Proportions of tuberculosis occurring within 30 days and between 30 days and 1 year after AIDS diagnosis were determined. Generalized additive models fitted with cubic splines with appropriate estimating methods were used to describe rates and proportions over time. Overall, 90,806 tuberculosis cases and 16,891 AIDS cases were reported; 3,125 tuberculosis cases within 1 year of AIDS diagnosis were detected. Tuberculosis notification rates decreased after 1997 from a fitted rate (fR per 100,000) of 166.5 to 138.8 in 2004. AIDS incidence rates increased 26% between 1995 and 1998 (30.7 to 38.7) followed by a 33.3% decrease to 25.8 in 2004. AIDS mortality rates decreased dramatically after antiretroviral therapy was introduced between 1995 (27.5) and 1999 (13.4). The fitted proportion (fP) of patients with tuberculosis diagnosed within one year of AIDS decreased from 1995 (24.4%) to 1998 (15.2%), remaining stable since. Seventy-five percent of tuberculosis diagnoses after an AIDS diagnosis occurred within 30 days of AIDS diagnosis. Our results suggest that while combination ART should be considered an essential component of the response to the HIV and HIV/tuberculosis epidemics, it may not be sufficient alone to prevent progression from latent TB to active disease among HIV-infected populations. When tuberculosis is diagnosed prior to or at the same time as AIDS and ART has not yet been initiated, then ART is ineffective as a tuberculosis prevention strategy for these patients. Earlier HIV/AIDS diagnosis and ART initiation may reduce TB incidence in HIV/AIDS patients. More specific interventions will be required if HIV-related tuberculosis incidence is to continue to decline.


School health systems under strain: an example of COVID-19 experiences & burnout among school health staff in Pima County, Arizona.
School health staff lead and provide a variety of care for children in schools. As school districts have navigated the COVID-19 pandemic, school health staff have faced unprecedented challenges in protecting the health of students and school staff. Our objective was to qualitatively characterize these pandemic challenges and experiences of school health staff in Pima County, Arizona to identify gaps in school health staff support for improving future emergency preparedness. We conducted two focus group discussions (FGDs) with 48 school health staff in Pima County, Arizona in two school districts using a discussion guide including ten open-ended questions. The FGDs were audio recorded and transcribed verbatim. We used the socioecological model (SEM) to organize the thematic analysis and generate codes and themes; data were analyzed using Atlas.ti software. The pandemic has significantly challenged school health staff with new pandemic-related job tasks: managing isolation, vaccination, and developing/implementing new and evolving COVID-19 guidelines. School health staff also reported increased stress related to interactions with parents and school administration as well as frustrations with rapid changes to guidance from the health department and policy makers. A common issue was not having enough staff or resources to complete regular job responsibilities, such as providing care for students with non-COVID-19 related health issues. Increased workload for school health staff resulted in physical burnout, mental distress, and disruption of core functions with long term implications for children's health. These focus groups highlight the need for improved emergency preparedness in schools during pandemics or infectious disease outbreaks. These include basic infrastructure changes (e.g., personnel support from health departments for tasks such as contact tracing to enable school nurses to continue core functions), and increased funding to allow for hazard pay and more school health personnel during emergency situations. In addition, basic school health infrastructure is lacking, and we should include a licensed school health nurse in every school.


Genomic comparison of herpes simplex virus type 1 isolates from Japan, Sweden and Kenya.
One-hundred and seventy-two epidemiologically unrelated herpes simplex virus type 1 (HSV-1) strains isolated in Japan (104 strains) and Sweden (68 strains) were compared by analysis of their genome structures using four restriction endonucleases, BamHI, KpnI, SalI and HindIII. In addition, 32 Kenyan HSV-1 isolates previously compared to Japanese isolates were included for further comparison with the Swedish isolates. Remarkable and statistically significant differences were found between the HSV-1 isolates from the three countries. One-hundred and thirty cleavage sites were examined, and it was shown that isolates from two of the three countries were statistically distinguishable at 27 of these loci. Pairwise comparison between isolates from Japan and Sweden, Kenya and Sweden, and Japan and Kenya revealed variation in 18, 16 and 23 sites, respectively. By considering gains and losses of 19 sites, the total of 204 strains could be classified into 92 distinct cleavage patterns. Isolates from the three countries could be distinguished from each other by the pattern, except for one Swedish and two Kenyan isolates which shared a pattern. Twenty-one fragments that were present or absent only in individual isolates from one or other of the three countries could be detected. These results show that HSV-1 strains from geographically separate countries or anthropologically different races have distinct distributions of endonuclease recognition sites.


Surgical outcome information and the media.
There is increased media attention to healthcare outcome in the current reform atmosphere. Surgical care is a natural target for both print and electronic coverage. Hospital public relations departments often will be the interface with media representatives. Because surgical care outcome interpretation requires thoughtful evaluation of both single-patient and grouped-patient data, as well as knowledge of realistic risk-benefit ratios, it always is prudent to work with your local surgeon when the request for a story comes to the public relations department.