Continuous Pneumatic Regulation of Tracheal Cuff Pressure to Decrease Ventilator-associated Pneumonia in Trauma Patients Who Were Mechanically Ventilated: The AGATE Multicenter Randomized Controlled Study.
Ventilator-associated pneumonia (VAP) is the most frequent health care-associated infection in severely ill patients, and aspiration of contaminated oropharyngeal content around the cuff of the tracheal tube is the main route of contamination. Is continuous regulation of tracheal cuff pressure using a pneumatic device superior to manual assessment three times daily using a portable manometer (routine care) in preventing VAP in patients with severe trauma? In this open-label, randomized controlled superiority trial conducted in 13 French ICUs, adults (age ≥ 18 years) with severe trauma (Injury Severity Score > 15) and requiring invasive mechanical ventilation for ≥ 48 h were enrolled. Patients were randomly assigned (1:1) via a secure Web-based random number generator in permuted blocks of variable sizes to one of two groups according to the method of tracheal cuff pressure control. The primary outcome was the proportion of patients developing VAP within 28 days following the tracheal intubation, as determined by two assessors masked to group assignment, in the modified intention-to-treat population. This study is closed to new participants. A total of 434 patients were recruited between July 31, 2015, and February 15, 2018, of whom 216 were assigned to the intervention group and 218 to the control group. Seventy-three patients (33.8%) developed at least one episode of VAP within 28 days following the tracheal intubation in the intervention group compared with 64 patients (29.4%) in the control group (adjusted subdistribution hazard ratio, 0.96; 95% CI, 0.76-1.20; P = .71). No serious adverse events related to the use of the pneumatic device were noted. Continuous regulation of cuff pressure of the tracheal tube using a pneumatic device was not superior to routine care in preventing VAP in patients with severe trauma. ClinicalTrials.gov; No.: NCT02534974; URL: www.clinicaltrials.gov.


Analysis of the transgenerational iron deficiency stress memory in Arabidopsis thaliana plants.
We investigated the existence of the transgenerational memory of iron (Fe) deficiency stress, in Arabidopsis thaliana. Plants were grown under Fe deficiency/sufficiency, and so were their offspring. The frequency of somatic homologous recombination (SHR) events, of DNA strand breaks as well as the expression of the transcription elongation factor TFIIS-like gene increase when plants are grown under Fe deficiency. However, SHR frequency, DNA strand break events, and TFIIS-like gene expression do not increase further when plants are grown for more than one generation under the same stress, and furthermore, they decrease back to control values within two succeeding generations grown under control conditions, regardless of the Fe deficiency stress history of the mother plants. Seedlings produced from plants grown under Fe deficiency evolve more oxygen than control seedlings, when grown under Fe sufficiency: however, this trait is not associated with any change in the protein profile of the photosynthetic apparatus and is not transmitted to more than one generation. Lastly, plants grown for multiple generations under Fe deficiency produce seeds with greater longevity: however, this trait is not inherited in offspring generations unexposed to stress. These findings suggest the existence of multiple-step control of mechanisms to prevent a genuine and stable transgenerational transmission of Fe deficiency stress memory, with the tightest control on DNA integrity.


Pretreatment with rivaroxaban attenuates stroke severity in rats by a dual antithrombotic and anti-inflammatory mechanism.
Stroke outcome is more favourable in patients receiving oral anticoagulants compared with non-anticoagulated patients. The reasons for this "stroke-attenuating" property of oral anticoagulants are largely unknown. This study examined whether prestroke anticoagulation with rivaroxaban, a novel direct factor Xa inhibitor, influences stroke severity, thrombin-mediated intracerebral thrombus formation and pro-inflammatory processes in a rat model of brain ischaemia/reperfusion injury. Male Wistar rats were anticoagulated with rivaroxaban and subjected to 90 minutes of transient middle cerebral artery occlusion. Infarct size, functional outcome and the occurrence of intracranial haemorrhage (ICH) were assessed until day 7. Thrombin generation was determined by measuring the amount of thrombin/antithrombin complex. Intracerebral thrombus formation was evaluated by histology and Western blot. CD68-immunoreactivity and the expression of cytokines and adhesion molecules were investigated to assess postischaemic inflammation. The integrity of the blood-brain barrier was analysed using fluorescein isothiocyanate-dextran. Rats pretreated with rivaroxaban developed significantly smaller strokes and less severe functional deficits compared with controls. Although rivaroxaban strongly reduced thrombin-mediated thrombus formation, this was not accompanied by an increased risk of ICH. In addition, rivaroxaban dampened the inflammatory response in the ischaemic brain by downregulating ICAM-1 expression and the activation of CD68+-immune cells. In contrast, rivaroxaban had no effect on the integrity of the blood-brain barrier after stroke. Here, we identified reduced thrombo-inflammation as a major determinant of the stroke-protective property of rivaroxaban in rats. Further studies are needed to assess the therapeutic potential of novel oral anticoagulants in the acute phase after a stroke.


Designing of rapid assay for the detection of RdRp/Orf1ab specific to SARS-CoV-2.
SARS-CoV-2 is still threat and mostly used detection method is real time reverse transcriptase polymerase chain reaction (rRT-PCR) for the open reading frame (Orf1ab), RNA-dependent RNA polymerase (RdRp), nucleocapsid (N) and envelope (E) genes of virus. However, rRT-PCR may have false negative rate for the nucleic acid detection. Since the RdRp/Orf1ab has high sensitivity for the molecular detection, two sandwich models, Model 1A-Model 1B, based on hybridization on lateral flow assay (LFA) were designed here and applied with the synthetic and clinical samples of RdRp/Orf1ab. In this purpose colloidal gold nanoparticles (AuNPs) were used as label. Membranes having different flow rate, three oligonucleotide probe concentrations and running buffers were used. Although synthetic target sequence was recognized by all the LFAs, PCR products obtained from either the synthetic plasmid DNA or oro/nasopharyngeal swabs were detected by Model 1 A using W12 membrane. Designed strip assays detected the RdRp/Orf1ab of the clinical samples as 100% sensitivity and specifity. It means that they might be used for the detection of virus and can be modified for the recognition of mutant genes of virus. These findings also demonstrated the importance of membranes, sandwich models, probe concentrations and sample contents for developing LFAs for viral detection.


A case report of PVOD patient combined with pulmonary embolism: Anticoagulation or not?
Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary arterial hypertension (PAH). Oral anticoagulation is confined to patients with idiopathic PAH (IPAH), but no oral anticoagulation has been recommended for PVOD, because occult pulmonary hemorrhage was a common finding in PVOD. We report a case of PVOD, who was misdiagnosed as IPAH for 5 years with worsening dyspnea and two episodes of pulmonary embolism (PE). He was confirmed as PVOD combined with PE by biopsy of the explanted lung specimen. He took oral anticoagulation, warfarin, to treat his first-time PE in July 2010, and his disease was kept stable for about 4 years, until he discontinued the anticoagulation therapy by himself sometime in 2014. Later on, a life-threatening PE recurred in January 2015, so he resumed the anticoagulation therapy. Fortunately, the bilateral sequential lung transplantation that was performed in July 2015 in time saved his life. He has been living well without dyspnea and the echocardiography showed the normalizations of the once increased pulmonary arterial pressure and the once enlarged right ventricle of his heart. In addition, to the best of my knowledge, he was the first PVOD patient receiving lung transplantation in China. We recommend that PVOD patients combined with PE should be treated with anticoagulation therapy indefinitely to prevent the recurrence of life-threatening PE until they get a chance for lung transplantation.


[Physiotherapeutic service of the Irkutsk region: present status, problems, and prospect].
Improving the organizational forms of physiotherapy services in the context of the formation of the novel specialty of physical and rehabilitation medicine poses urgent tasks for practical public health. At the same time, ensuring the proper quality of medical care, the high level of safety, customer satisfaction from the new service presents a multifaceted and complex problem that cannot be solved without analyzing the current situation in the units of the physiotherapy network. To study the parameters of the activity of physiotherapy units of treatment-and-prophylactic facilities in the Irkutsk Region to assess the dynamics of their development and further prospects. The authors analyzed the data of state statistical annual reporting on the work of physiotherapy departments (PTDs) and physiotherapy rooms (PTRs), which had been submitted to the Medical Information Analysis Center, Ministry of Health of the Irkutsk Region, and information on physiotherapeutic medical care in the treatment-and-prophylactic facilities of the Irkutsk Region in the period 2010 to 2017. The quantitative indicators of the activities of PTD and PTR employees were investigated; the qualitative components of their activities were assessed; the problems of physiotherapeutic management were revealed and the ways of their solution were defined. Since 2014, there have been negative changes in the development of physiotherapy: the material and technical base is worsening; the number of doctors and nurses is being reduced; the specialists' qualification is decreasing, and the coverage of patients with physiotherapies is reducing. Physiotherapy is currently undergoing a period of stagnation. Along with the existing systemic economic problems of modern public health, the deepening of this negative situation in physiotherapy is promoted by the protracted period of the formation of the new specialty of physical and rehabilitation medicine physician, the absence of its legal base, federal state educational standards, which creates a number of misunderstandings of its promises and demand for physiotherapists in near future.


Pharmacogenomics Implementation: Considerations for Selecting a Reference Laboratory.
One of the initial steps for implementing pharmacogenomics into routine patient care is selecting an appropriate clinical laboratory to perform the testing. With the rapid advances in genotyping technologies, many clinical laboratories are now performing pharmacogenomic testing. Selection of a reference laboratory depends on whether a particular genotype assay is already performed by an internal health care organization laboratory or only available externally. Other factors for consideration are coverage of genomic variants important for the patient population, technical support, and cost. In some instances, the decision to select a particular reference laboratory may be the responsibility of the clinician who is recommending genomic interrogation. Only limited guidance is available that describes the laboratory characteristics to consider when selecting a reference laboratory. We provide practical considerations for selecting a clinical laboratory for pharmacogenomic testing broadly categorized into four domains: pharmacogene and variant selection; logistics; reporting of results; and test costs along with reimbursement.


ZB-16, a Novel GPR119 Agonist, Relieves the Severity of Streptozotocin-Nicotinamide-Induced Diabetes in Rats.
GPR119 is involved in the regulation of incretin and insulin secretion, so the GPR119 agonists have been suggested as novel antidiabetic medications. The purpose of this work was to assess the influence of novel GPR119 agonist ZB-16 on the glucose utilization, insulin, and glucagon-like peptide-1 (GLP-1) secretion and the morphology of pancreas in rats with streptozotocin-nicotinamide-induced diabetes. 45 male Wistar rats were used in the study. The criteria of streptozotocin-nicotinamide-induced diabetes were blood glucose levels of 9-14 mmol/l measured in fasting conditions on the third day since administration of streptozotocin (65 mg/kg) and nicotinamide (230 mg/kg). Animals failed to reach the criteria were excluded from the experiment. The substances were administered per os once per day for 28 days. Measurements included blood glucose monitoring (every 7 days), glucose tolerance test (every 14 days), the assessment of insulin and GLP-1 levels in blood plasma (28 days after beginning), and the results of immunohistochemical staining of pancreas. It was found that ZB-16 (1 mg/kg per os, once a day) decreases the blood glucose levels under fasting conditions and improves the glucose utilization. These changes were associated with the increase in stimulated secretion of GLP-1 and insulin, accompanied by the growth of insulin-positive cells in pancreas. Thus, ZB-16 could be a promising antidiabetic drug for oral administration.


Does the Intersectionality of Race/Ethnicity and Type 2 Diabetes Increase the Odds of a Cervical Cancer Diagnosis? A Nested Case-Control Study of a Florida Statewide Multisite EHR Database.
Cervical cancer and Type 2 Diabetes (T2D) share common demographic risk factors. Despite this, scarce research has examined the relationship between race/ethnicity, having T2D, and cervical cancer incidence. We analyzed statewide electronic health records data between 2012 and 2019 from the OneFlorida+ Data Trust. We created a 1:4 nested case-control dataset. Each case (patient with cervical cancer) was matched with four controls (patients without cervical cancer) without replacement by year of encounter, diagnosis, and age. We used conditional logistic regression to estimate the unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to examine the association between race/ethnicity, T2D, and cervical cancer incidence. A total of 100,739 cases and 402,956 matched controls were identified. After adjusting for sociodemographic characteristics, non-Hispanic Black women with T2D had higher odds of cervical cancer compared with non-Hispanic White women with T2D (OR: 1.58, 95% CI 1.41-1.77). Living in a rural area, having Medicaid/Medicare insurance, and having high social vulnerability were associated with higher odds of having a cervical cancer diagnosis. Our findings imply the need to address the higher burden of cervical cancer diagnosis among non-Hispanic Black women with T2D and in underserved populations.


[Reader survey of the Journal of the Norwegian Medical Association 2007].
Upon request, The Research Institute of the Norwegian Medical Association conducted a reader survey for the Journal of the Norwegian Medical Association (JNMA) during the autumn of 2007. Three probability samples of 1,500 active doctors, 250 medical students and 250 retired doctors were given a questionnaire that could be completed and returned by ordinary mail or electronically. 48% of the students, 54% of the doctors, and 76% of the retired doctors responded. 54% of the readers spend 30 min or more on each issue. 20% of the retired doctors, 9% of the active doctors, and 7% of the students spend two hours or more. The declared aims of being a membership journal and a source for professional update were fulfilled significantly better than the other three declared aims; to stimulate research, support professional attitudes and promote health policy debate. The readers wanted more review articles, news from other journals and situations to learn from; and fewer advertisements, articles on "medicine and art" and a shorter language column. The website was particularly used to search for previously published articles, but also to read articles on screen. 32% of the students, 19% of the doctors, and 59% of the retired doctors did not use the JNMA's website. With regard to layout, the paper quality and the quality of the illustrations were praised. All in all the readers found many interesting articles in the JNMA and did not think it was too compact.


The role of perceived control for the perception of health by patients with persistent mental illness.
Perceived control has been found to be of significance for patients with psychiatric disorders and may be regarded as an aspect of empowerment. Moreover, a sense of control has been identified as important for occupational performance, both in empirical research and in occupational therapy theory. This study aimed at investigating factors that might be of importance for perceived control: sociodemographic, clinical, and well-being variables. Another aim was to investigate whether perceived control served as a mediator between clinical variables, in terms of psychopathology, and well-being variables, in terms of perceived health. Sociodemographic data were collected from 177 subjects, most of them with psychosis diagnoses. They were also assessed regarding perceived control (locus of control and self-mastery) and different aspects of health and well-being. The findings showed that both clinical and well-being variables were consistently related to both aspects of perceived control. Moreover, the roles of self-mastery and locus of control as mediators of perceived health were identified. The results also identified some important sociodemographic factors that might promote a sense of control and empowerment, mainly educational level and friends. This study provided detailed knowledge of the role of perceived control for well-being among people with mental disorders. Strategies for how occupational therapists may promote a sense of control in this group are discussed.


Exploration of the Quorum-Quenching Mechanism in Pseudomonas nitroreducens W-7 and Its Potential to Attenuate the Virulence of Dickeya zeae EC1.
Quorum quenching (QQ) is a novel, promising strategy that opens up a new perspective for controlling quorum-sensing (QS)-mediated bacterial pathogens. QQ is performed by interfering with population-sensing systems, such as by the inhibition of signal synthesis, catalysis of degrading enzymes, and modification of signals. In many Gram-negative pathogenic bacteria, a class of chemically conserved signaling molecules named N-acyl homoserine lactones (AHLs) have been widely studied. AHLs are involved in the modulation of virulence factors in various bacterial pathogens including Dickeya zeae. Dickeya zeae is the causal agent of plant-rot disease of bananas, rice, maize, potatoes, etc., causing enormous economic losses of crops. In this study, a highly efficient AHL-degrading bacterial strain W-7 was isolated from activated-sludge samples and identified as Pseudomonas nitroreducens. Strain W-7 revealed a superior ability to degrade N-(3-oxododecanoyl)-l-homoserine lactone (OdDHL) and completely degraded 0.2 mmol/L of OdDHL within 48 h. Gas chromatography-mass spectrometry (GC-MS) identified N-cyclohexyl-propanamide as the main intermediate metabolite during AHL biodegradation. A metabolic pathway for AHL in strain W-7 was proposed based on the chemical structure of AHL and intermediate products. In addition to the degradation of OdDHL, this strain was also found to be capable of degrading a wide range of AHLs including N-(3-oxohexanoyl)-l-homoserine lactone (OHHL), N-(3-oxooctanoyl)-l-homoserine lactone (OOHL), and N-hexanoyl-l-homoserine lactone (HHL). Moreover, the application of strain W-7 as a biocontrol agent could substantially attenuate the soft rot caused by D. zeae EC1 to suppress tissue maceration in various host plants. Similarly, the application of crude enzymes of strain W-7 significantly reduced the disease incidence and severity in host plants. These original findings unveil the biochemical aspects of a highly efficient AHL-degrading bacterial isolate and provide useful agents that exhibit great potential for the control of infectious diseases caused by AHL-dependent bacterial pathogens.


Acute renal vein thrombosis and nephrotic syndrome in the setting of retroperitoneal fibrosis.
Idiopathic retroperitoneal fibrosis (RPF) is a rare disease that involves non-specific inflammation and fibrosis surrounding the aorta. As a result, RPF is a challenging diagnosis to make; patients often seek medical attention after complications arise, such as nephrotic syndrome. The patient in our case report initially complained of flank pain. Laboratory evaluation revealed acute renal failure and nephrotic syndrome with substantial proteinuria. Multiple imaging modalities demonstrated a large, ill-defined, infiltrative retroperitoneal soft tissue mass that encased the great vessels. The patient was also noted to have acute left renal vein thrombosis. Although the patient was eventually diagnosed with RPF of unknown etiology, his clinical course is particularly unique given the rarity of the renal vein thrombosis. This case report adds a value to the medical community by helping to elucidate RPF and exposing its potentially life-threatening complications.


Analysis of the relapse of imported Plasmodium vivax and Plasmodium ovale in five provinces of China.
The global battle against malaria is facing formidable challenges, particularly in controlling Plasmodium vivax and Plasmodium ovale, whose cases have not been reduced as effectively as Plasmodium falciparum because of their relapse. This study investigates the current situation and underlying factors contributing to relapse or recrudescence of imported cases of P. vivax and P. ovale, and seeks to provide a reference for reducing relapse or recrudescence in malaria-free areas and offers a scientific basis for designing strategies to prevent imported re-transmission. This study analysed imported P. vivax and P. ovale in Anhui, Zhejiang, Henan, Hubei, and Guangxi provinces during 2014-2021 by retrospective analysis. A case-control study was conducted on patients who experienced relapse or recrudescence. From 2014 to 2021, 306 cases of P.vivax and 896 cases of P.ovale were included in the study, while 75 cases had relapse or recrudescence, including 49 cases of P. ovale (65.33%) and 26 cases of P. vivax (34.67%). Within less than 5 weeks after returning to the country, 122 cases of P. vivax (39.87%, 122/306) and 265 cases of P. ovale (29.58%, 265/896) occurred. Within less than 53 weeks, the ratio of P. vivax was 94.77% (290/306), and that of P. ovale was 89.96% (806/896). Among the cases experiencing relapse or recrudescence, only 1 case of P. vivax (1/26 3.85%) and 3 cases of P. ovale (3/49 6.12%) occurred within less than 5 weeks after the first onset, whereas 21 cases of P. vivax (21/26 80.77%) and 42 cases of P. ovale (42/49 85.71%) occurred within less than 53 weeks after the first onset. The difference in relapse or recrudescence due to different drugs and medication regimens and medical activities at various levels of medical institutions was statistically significant. In areas where malaria has been eliminated, routine health screening in a scientific time frame for people returning from at-risk areas can effectively improve the efficiency of preventing re-transmission, thereby reducing prevention costs and disease burden. Preventing patients from self-treating and strengthening medication regulations in health facilities are key measures to reduce relapse or recrudescence.


Measles seroconfirmation using dried capillary blood specimens in filter paper.
Because the incidence of measles has declined in recent years, the potential for confusion of measles with other morbilliform rashes has increased. Routine serologic testing of suspected cases of measles is recommended but it has been hampered, particularly in young infants and children, by the requirement of performing venipuncture. We have compared measles hemagglutination inhibition antibody testing performed on dried capillary whole blood collected on filter paper strips with testing of serum specimens obtained simultaneously by venipuncture. We assessed overall comparability, diagnostic sensitivity and specificity and acceptability and practicality for field use. Of the 125 capillary-venous sets compared, there was a 4-fold difference in hemagglutination inhibition titer between the two types of specimens in only one set (0.8%). Diagnostic sensitivity using capillary blood was 100% and specificity was 96%. Immunoglobulin M assessments on six capillary-venous sets were in complete agreement (three positive in both, three negative in both). In a pilot program of field use, filter paper blood collection was associated with a 97% (36 of 37) success rate in obtaining specimens from individuals with suspected cases of measles. This method of blood collection and testing is an accurate, feasible and acceptable means for seroconfirmation of measles.


Cerebrovascular carbon dioxide reactivity in children anaesthetized with sevoflurane.
To determine the effects of sevoflurane on cerebrovascular carbon dioxide reactivity (CCO2R), middle cerebral artery blood flow velocity (CBFV) was measured at different levels of PE'CO2 by transcranial Doppler sonography in 16 ASA I or II children, aged 18 months to 7 yr undergoing elective urological surgery. Anaesthesia comprised 1.0 MAC sevoflurane and air in 30% oxygen delivered through an Ayre's T piece by intermittent positive-pressure ventilation, and a caudal epidural block with 0.25% bupivacaine 1.0 ml kg(-1) without epinephrine. PE'CO2 was randomly adjusted to 25, 35, 45 and 55 mm Hg (3.3, 4.6, 5.9 and 7.2 kPa) with an exogenous source of CO2, while maintaining ventilation variables constant. CBFV increased as PE'CO2 increased from 25 to 35, and to 45 mm Hg (P<0.001), but did not increase significantly with an increase in PE'CO2 from 45 to 55 mm Hg. Mean heart rate and arterial pressure remained constant. CCO2R is preserved in healthy children anaesthetized with 1.0 MAC sevoflurane.


[Protective effects and its mechanisms of total alkaloids from rhizoma Coptis chinensis on Helicobacter pylori LPS induced gastric lesion in rats].
To study the effects and its possible mechanisms of total alkaloids (TA) from rhizoma Coptis chinensis on H. pylori LPS induced gastric lesion in rats. H. pylori lipopolysaccharide was applied to rat intragastrically for 4 days to induce a pattern of mucosal responses resembling that of acute gastritis. After treatment with 50, 100, 200 mg x kg(-1) TA, we identified the changes on gastric histopathology, the effects on the activities of cNOS and NOS-2, the contents of TNF-alpha and the gastric mucus epithelial cell apoptosis. H. pylori LPS could significantly induce the epithelial cell apoptosis of gastric mucus, increase the expression of NOS-2 and decline the expression of cNOS, and enhance the content of TNF-alpha in serum. Treatment with 50, 100, 200 mg x kg(-1) TA led to reduction in the extent of mucosal inflammatory changes elicited by H. pylori LPS and decrease in epithelial cell apoptosis. Furthermore, this effect of TA was associated with decrease in content of TNF-alpha in serum, decline in NOS-2, and increase in cNOS. The findings suggest that TA is a potent protective agent against H. pylori LPS induced gastric mucosal inflammation. The concerned mechanisms may be related to its inhibition on epithelial cell apoptosis, and the suppression of the inflammatory responses by upregulating cNOS and interfering with the events propagated by NOS-2, and reducing the content of TNF-alpha.


Cardiac arrest triggers hippocampal neuronal death through autophagic and apoptotic pathways.
The mechanism of neuronal death induced by ischemic injury remains unknown. We investigated whether autophagy and p53 signaling played a role in the apoptosis of hippocampal neurons following global cerebral ischemia-reperfusion (I/R) injury, in a rat model of 8-min asphyxial cardiac arrest (CA) and resuscitation. Increased autophagosome numbers, expression of lysosomal cathepsin B, cathepsin D, Beclin-1, and microtubule-associated protein light chain 3 (LC3) suggested autophagy in hippocampal cells. The expression of tumor suppressor protein 53 (p53) and its target genes: Bax, p53-upregulated modulator of apoptosis (PUMA), and damage-regulated autophagy modulator (DRAM) were upregulated following CA. The p53-specific inhibitor pifithrin-α (PFT-α) significantly reduced the expression of pro-apoptotic proteins (Bax and PUMA) and autophagic proteins (LC3-II and DRAM) that generally increase following CA. PFT-α also reduced hippocampal neuronal damage following CA. Similarly, 3-methyladenine (3-MA), which inhibits autophagy and bafilomycin A1 (BFA), which inhibits lysosomes, significantly inhibited hippocampal neuronal damage after CA. These results indicate that CA affects both autophagy and apoptosis, partially mediated by p53. Autophagy plays a significant role in hippocampal neuronal death induced by cerebral I/R following asphyxial-CA.


Development of a highly sensitive methodology for quantitative determination of fexofenadine in a microdose study by multiple injection method using ultra-high performance liquid chromatography with tandem mass spectrometry.
An ultra high-sensitivity method for quantifying fexofenadine concentration in rat plasma samples by multiple injection method (MIM) was developed for a microdose study. In this study, MIM involved continuous injections of multiple samples containing the single compound into a column of the ultra-HPLC (UHPLC) system, and then, temporary trapping of the analyte at the column head. This was followed by elution of the compound from the column and detection by mass spectrometer. Fexofenadine, used as a model compound in this study, was extracted from the plasma samples by a protein precipitation method. Chromatographic separation was achieved on a reversed-phase C18 column by using a gradient method with 0.1% formic acid and 0.1% formic acid in acetonitrile as the mobile phase. The analyte was quantified in the positive-ion electrospray ionization mode using selected reaction monitoring. In this study, the analytical time per fexofenadine sample was approximately 2 min according to the UHPLC system. The method exhibited the linear dynamic ranges of 5-5000 pg/mL for fexofenadine in rat plasma. The intra-day precisions were from 3.2 to 8.7% and the accuracy range was 95.2-99.3%. The inter-day precisions and accuracies ranged from 3.5 to 8.4% and from 98.6 to 102.6%, respectively. The validated MIM was successfully applied to a microdose study in the rats that received oral administration of 100 µg/kg fexofenadine. We suggest that this method might be beneficial for the quantification of fexofenadine concentrations in a microdose clinical study.


[The Laurence-Moon-Bardet-Biedl syndrome].
The Laurence-Moon-Bardet-Biedl syndrome consists of: retinitis pigmentosa, adiposo-genital dystrophy, syndactyly, mental retardation. It is presented a patient with atypical retinitis pigmentosa--unilateral, sectorial and hypopigmentary form, as part of the Laurence-Moon-Bardet-Biedl syndrome.


A Continuum Model for the Unfolding of von Willebrand Factor.
von Willebrand Factor is a mechano-sensitive protein circulating in blood that mediates platelet adhesion to subendothelial collagen and platelet aggregation at high shear rates. Its hemostatic function and thrombogenic effect, as well as susceptibility to enzymatic cleavage, are regulated by a conformational change from a collapsed globular state to a stretched state. Therefore, it is essential to account for the conformation of the vWF multimers when modeling vWF-mediated thrombosis or vWF degradation. We introduce a continuum model of vWF unfolding that is developed within the framework of our multi-constituent model of platelet-mediated thrombosis. The model considers two interconvertible vWF species corresponding to the collapsed and stretched conformational states. vWF unfolding takes place via two regimes: tumbling in simple shear and strong unfolding in flows with dominant extensional component. These two regimes were demonstrated in a Couette flow between parallel plates and an extensional flow in a cross-slot geometry. The vWF unfolding model was then verified in several microfluidic systems designed for inducing high-shear vWF-mediated thrombosis and screening for von Willebrand Disease. The model predicted high concentration of stretched vWF in key regions where occlusive thrombosis was observed experimentally. Strong unfolding caused by the extensional flow was limited to the center axis or middle plane of the channels, whereas vWF unfolding near the channel walls relied upon the shear tumbling mechanism. The continuum model of vWF unfolding presented in this work can be employed in numerical simulations of vWF-mediated thrombosis or vWF degradation in complex geometries. However, extending the model to 3-D arbitrary flows and turbulent flows will pose considerable challenges.


C-Phycocyanin: A Phycobiliprotein from Spirulina with Metabolic Syndrome and Oxidative Stress Effects.
Spirulina maxima is a cyanobacterium considered a "superfood" due to its metabolites and nutrient content. These include a complex mixture of minerals, vitamins, fatty acids, proteins, and accessory pigments. In recent years, it has positioned itself as a promising source of bioactive molecules for the treatment of several diseases, including metabolic syndrome, coronary diseases, cancer, and the improvement of health modulating oxidative stress. C-Phycocyanin (C-PC) is a photosynthetic pigment from green-blue cyanobacterium and the most abundant phycobiliprotein in the Spirulina genus with various pharmacological properties attributed due to its antioxidant capacity but has no specific cellular target. This has made it a molecule of great interest in biomedical research. This review focuses on the pharmacological effects and the benefits on metabolic syndrome and oxidative stress of C-PC.


Leptomeningeal carcinomatosis in a young patient with obstructive colorectal signet- ring cell adenocarcinoma.
We present the case report of a twenty-five-year-old Moroccan male patient who suffered from leptomeningeal carcinomatosis related to a signet-ring cell carcinoma of the rectum. He presented to the emergency department with abdominal pain, constipation, weight loss and rectal bleeding. The rectal examination showed a rectal tumor and a CT scan revealed a large bowel obstruction due to rectal diffuse thickening. An emergency transverse colostomy was performed, with a rectal biopsy and a cytological sample collection. The pathology analysis showed a signet-ring cell carcinoma from the rectum. The staging evaluation was completed and neoadjuvant chemotherapy and radiotherapy were offered to the patient. Two months later, he developed neurological signs of leptomeningeal involvement which was confirmed by a lumbar puncture. Then, the patient received systemic and intrathecal chemotherapy but later died. This case shows the tendency of colorectal signet-ring cell carcinomas to cause leptomeningeal metastasis, even in young patients.


Hot flashes during androgen deprivation therapy with luteinizing hormone-releasing hormone agonist combined with steroidal or nonsteroidal antiandrogen for prostate cancer.
To investigate hot flashes and quality of life during combined androgen blockade (CAB) therapy using steroidal or nonsteroidal antiandrogens. A total of 151 patients with prostate cancer, who were enrolled into this study from May 2001 to June 2003, were randomized to receive CAB therapy using a luteinizing hormone-releasing hormone agonist (leuprorelin) combined with a steroidal antiandrogen (chlormadinone) or a nonsteroidal antiandrogen (bicalutamide). The incidence of, frequency of, and distress due to hot flashes were evaluated with a self-administered questionnaire during a 2-year period. The general and disease-specific quality-of-life outcomes were also measured using the Functional Assessment of Cancer Therapy-Prostate questionnaire. Data were available for analysis from 124 patients. Although the incidence of hot flashes largely tended to be greater in the bicalutamide group than in the chlormadinone group, no significant difference was noted in the cumulative incidence of hot flashes at 2 years. The median frequency of hot flashes daily was 1.3 and 2.2 for warmth/flushing (P = .16) and 1.0 and 3.6 for sweating (P = .021) in the chlormadinone and bicalutamide groups, respectively. Patients in the chlormadinone group were significantly less likely to be distressed by warmth/flushing (odds ratio 0.47, P < .001) and sweating (odds ratio 0.61, P = .01) than were those in the bicalutamide group. The Functional Assessment of Cancer Therapy-Prostate scores over time showed no intergroup differences. Our results suggest that CAB using a steroidal antiandrogen such as chlormadinone might induce fewer and less-distressing hot flashes than CAB with bicalutamide.


Application of the enzyme-linked immunoelectrotransfer blot to filter paper blood spots to estimate seroprevalence of cysticercosis in Bolivia.
An enzyme-linked immunoelectrotransfer blot (EITB) assay was used to study the prevalence of cysticercosis in rural Bolivia. Dried blood spots on filter paper from fingersticks were used as assay samples. Before the serosurvey, experiments were performed to show that samples eluted from dried whole blood on filter paper exhibited no decrease in sensitivity when compared with the more traditional serum samples used in the EITB. Fingerstick blood dried on filter paper is a convenient, economical way of transporting and storing field samples for epidemiologic surveys of cysticercosis in developing countries. This report shows the utility of this sample collection method in underdeveloped countries where refrigeration is not possible and where venipuncture is a problem. Blood was obtained from randomly selected residents in three rural regions of Bolivia: Chuquisaca (n = 1,859), Cochabamba (n = 1,516), and Tarija (n = 1,010). The estimated seroprevalence on 10% of the sample collected for the three regions were 9%, 4.5%, and 2%, respectively.


Epidemiological study of muscular disorders in Assiut, Egypt.
Few comprehensive epidemiological studies of the prevalence of muscle diseases have been undertaken, and none has been carried out in our locality. The present cross-sectional study was conducted in Assiut Governorate (Upper Egypt) to estimate the prevalence of different types of primary muscular disorder in 1997. The study involved 52,203 subjects, 15,617 (30%) from the rural community and 36,586 (70%) from the urban community. Patients were identified from a door-to-door survey, and all were subjected to a full clinical examination, with confirmation of the diagnosis through electrophysiological, and biochemical investigations. Histopathological studies were performed for the classification of muscular dystrophies. Forty patients with muscular disorders were identified, with a point prevalence of 76.6 per 100,000 in the total community with no significant differences between the rural and urban communities. The creatine kinase level was abnormally high (>225 IU/l) in 80% of the cases, increased in all patients with muscular dystrophy or myositis, in 88.8% of patients with systemic myopathy and 66.6% of patients with myotonia. None of the cases of myasthenia showed an increase in the creatine kinase level. The lifetime prevalence per 100,000 was 26.8 for muscular dystrophy, 11.49 for myotonia, 11.49 for myositis, 17.24 for systemic myopathy and 9.57 for myasthenia.


MoS2 Quantum Dots as New Electrochemiluminescence Emitters for Ultrasensitive Bioanalysis of Lipopolysaccharide.
Cd-based semiconductor quantum dots (QDs) with size-tunable luminescence and high quantum yield have become the most promising electrochemiluminescence (ECL) emitters. However, their unavoidable biotoxicity limited their applications in bioassays. Here, the nontoxic and economical MoS2 QDs prepared by chemical exfoliation from the bulk MoS2 were first investigated as new ECL emitters, and then the possible luminescence mechanism of MoS2 QDs was studied using ECL-potential curves and differential pulse voltammetry (DPV) methods in detail. With MoS2 QDs as the ECL emitters and triethylamine (TEA) as the efficient coreactant, a practical and label-free aptasensor for lipopolysaccharide (LPS) detection was constructed based on aptamer recognition-driven target-cycling synchronized rolling circle amplification. Comparing to conventional stepwise reactions, this target-cycling synchronized rolling circle amplification achieved more efficient signal amplification and simpler operation. The developed assay for LPS detection demonstrated a wide linear range of 0.1 fg/mL to 50 ng/mL with limit of detection down to 0.07 fg/mL. It is worth mentioning that MoS2 QDs with stable ECL emission exhibited a great application potential in ECL bioanalysis and imaging as a new type of excellent emitter candidates.


An Investigation of the Effect of Transfected Defective, Ebola Virus Genomes on Ebola Replication.
As the ongoing outbreak in the Democratic Republic of Congo illustrates, Ebola virus disease continues to pose a significant risk to humankind and this necessitates the continued development of therapeutic options. One option that warrants evaluation is that of defective genomes; these can potentially parasitize resources from the wild-type virus and may even be packaged for repeated co-infection cycles. Deletion and copy-back defective genomes have been identified and reported in the literature. As a crude, mixed preparation these were found to have limiting effects on cytopathology. Here we have used synthetic virology to clone and manufacture two deletion defective genomes. These genomes were tested with Ebola virus using in vitro cell culture and shown to inhibit viral replication; however, and against expectations, the defective genomes were not released in biologically significant numbers. We propose that EBOV might have yet unknown mechanisms to prevent parasitisation by defective interfering particles beyond the known mechanism that prevents sequential infection of the same cell. Understanding this mechanism would be necessary in any development of a defective interfering particle-based therapy.


Bioremediation of Copper-Ions by Polymer Encapsulated and Immobilized Micrococcus Luteus.
Bioremediation of copper (Cu2+ ) with immobilized Micrococcus luteus in polymer matrices has been broadly studied for a wide range of applications including wastewater treatment. Herein, the bioremediation efficiency based on modified immobilization techniques and by the addition of Cu2+ is investigated. Porous composite nonwovens with living M. luteus (living polymer composites) are prepared by encapsulation of the bacterial cells in poly(vinyl alcohol) (PVA) microparticles (M. luteus/PVA microparticles) produced by spray drying method. The M. luteus/PVA microparticles are chemically cross-linked. The hydrogel microparticles with encapsulated M. luteus are embedded in a nonwoven of poly (lactic acid) (PLA) electrospun short fibers provided by wet-laid method. Two different models of composite nonwovens are reported, in which the place position of the hydrogel PVA microparticles with encapsulated M. luteus and PLA nonwoven can affect the bioremediation process.


Lepidopterism caused by the puss caterpillar.
Lepidopterism is a term inclusive of cutaneous and systemic reactions resulting from moths, butterflies, and larva. The puss caterpillar is the larval form of the southern flannel moth, Megalopyge opercularis. A case presentation is reviewed and treatment options presented for contact with puss caterpillars and other stinging caterpillars encountered in the primary care setting. Contact with the puss caterpillar causes a characteristic rash and can produce extreme symptoms of pain for its victims. Accurate and early diagnosis can expediate treatment to alleviate symptoms and decrease morbidity in those affected and aid in differential diagnosis of various stinging caterpillars.


[Transitory hepatic peliosis in a child].
A case of hepatic peliosis in a 4 year old child is reported. The exceptional character of such a presentation in a child, along with its reversibility, are emphasized. The hepatogram performed during splenoportography showed numerous little granular pictures, which probably corresponded to the opacification of "peliotic" cavities. The mechanism of hepatic peliosis remains unknown in this case, except that it occurred in a child with poor general condition.


Treponema zioleckii sp. nov., a novel fructan-utilizing species of rumen treponemes.
During studies on fructan degradation in the rumen, a Treponema-like bacterium able to utilize Timothy grass fructan, commercial inulin and sucrose as the sole carbon source was recovered from sheep rumen. At least two different fructanolytic enzymes were identified in cell-free extracts of the isolated bacterium. Characterization of the strain by a polyphasic approach indicated that it can be regarded as a representative of a new bacterial species within the genus Treponema. Electron microscopy showed that the bacterium exhibited all of the features typical of spirochetes. The helical cells measured 5.4-11.5 microm x 0.42-0.51 microm and possessed up to seven regular coils. The bacterium utilized various plant mono- and disaccharides as fermentable substrates. Formate, acetate and ethanol in a molar ratio of 16 : 10 : 1 were the end products of glucose fermentation. The major cellular fatty acids were C(13:0), C(14:0), C(14:1), C(15:0), C(15:1) and C(16:0). The nearly complete 16S rRNA gene sequence was obtained, and phylogenetic analysis of the 16S rRNA gene showed the highest similarity to rumen Treponema strain CA. We propose the name Treponema zioleckii sp. nov. for this novel rumen spirochete with strain kT as the type strain.


Neurochemical and behavioral profiling of the selective GlyT1 inhibitors ALX5407 and LY2365109 indicate a preferential action in caudal vs. cortical brain areas.
Selective inhibitors of the glycine transporter 1 (GlyT1) have been implicated in central nervous system disorders related to hypoglutamatergic function such as schizophrenia. The selective GlyT1 inhibitors ALX5407 (NFPS) and LY2365109 {[2-(4-benzo[1,3]dioxol-5-yl-2-tert-butylphenoxy)ethyl]-methylamino}-acetic acid increased cerebrospinal fluid levels of glycine and potentiated NMDA-induced increases in dialysate levels of neurotransmitters in the prefrontal cortex (PFC) and the striatum. However, higher doses produced both stimulatory and inhibitory effects on motor performance and impaired respiration, suggesting significant involvement of cerebellar and brain stem areas. A dual probe microdialysis study showed that ALX5407 transiently elevated extracellular levels of glycine in the PFC with more sustained increases in the cerebellum. In support of these findings, immuno-staining with pan-GlyT1 and GlyT1a antibodies showed a higher abundance of immunoreactivity in the brain stem/cerebellum as compared to the frontal cortical/hippocampal brain areas in four different species studied, including the mouse, rat, monkey and human. In addition, the inhibitory effects of ALX5407 on cerebellar levels of cGMP in the mouse could be reversed by the glycine A receptor antagonist strychnine but not the glycine B receptor antagonist L-701324. We propose that the adverse events seen with higher doses of ALX5407 and LY2365109 are the result of high GlyT1 inhibitory activity in caudal areas of the brain with sustained elevations of extracellular glycine. High levels of glycine in these brain areas may result in activation of strychnine-sensitive glycine A receptors that are inhibitory on both motor activity and critical brain stem functions such as respiration.


A comparative analysis of family-based and population-based association tests using whole genome sequence data.
The revolution in next-generation sequencing has made obtaining both common and rare high-quality sequence variants across the entire genome feasible. Because researchers are now faced with the analytical challenges of handling a massive amount of genetic variant information from sequencing studies, numerous methods have been developed to assess the impact of both common and rare variants on disease traits. In this report, whole genome sequencing data from Genetic Analysis Workshop 18 was used to compare the power of several methods, considering both family-based and population-based designs, to detect association with variants in the MAP4 gene region and on chromosome 3 with blood pressure. To prioritize variants across the genome for testing, variants were first functionally assessed using prediction algorithms and expression quantitative trait loci (eQTLs) data. Four set-based tests in the family-based association tests (FBAT) framework--FBAT-v, FBAT-lmm, FBAT-m, and FBAT-l--were used to analyze 20 pedigrees, and 2 variance component tests, sequence kernel association test (SKAT) and genome-wide complex trait analysis (GCTA), were used with 142 unrelated individuals in the sample. Both set-based and variance-component-based tests had high power and an adequate type I error rate. Of the various FBATs, FBAT-l demonstrated superior performance, indicating the potential for it to be used in rare-variant analysis. The updated FBAT package is available at: http://www.hsph.harvard.edu/fbat/.


Acyclo-retinoic acid induces apoptosis in human prostate cancer cells.
Acyclo-retinoic acid, a novel acyclic analogue of all-trans-retinoic acid, has been previously isolated as one of the in vitro oxidation products of lycopene. The effect of acyclo-retinoic acid on the growth of human prostate cancer cells was compared with those of the four retinoids: all-trans-retinoic acid, geranylgeranoic acid, 9-cis-retinoic acid and N-(4-hydroxyphenyl)retinamide. When prostate cancer cells, PC-3, DU 145 and LNCaP, were cultured in a retinoid-supplemented medium, acyclo-retinoic acid remarkably reduced the viability of the cells except for LNCaP. This effect was significantly higher than that of geranylgeranoic acid, all-trans-retinoic acid and 9-cis-retinoic acid, but was comparable to that of N-(4-hydroxyphenyl)retinamide. DNA fragmentations of nuclei in PC-3 and DU 145 cells treated with acyclo-retinoic acid were detected by in situ TUNEL assay. Furthermore, an apoptotic DNA ladder was observed in PC-3 cells. These results showed that acyclo-retinoic acid reduced cell viability by inducing apoptosis in human prostate cancer cells.


Refugee health and medical student training.
Cultural awareness training is an increasingly important priority within medical curricula. This article describes an academic family practice-community partnership focusing on health care needs of refugees that became the model for a medical school selective on cultural sensitivity training. The monthly Refugee Health Night program featured dinner with preceptors and patients, international sessions on special medical needs of refugees, and actual clinical encounters with patients. Students were not expected to become culturally competent experts but, rather, health care providers sensitive to and appreciative of cultural context, experience, and expectations. We worked with students to develop sensitive methods of inquiry about mental health, especially around issues of war and torture. We used problem-based cases to emphasize primary care continuity and the benefit of establishing trust over time. Over 2 years, 50 students and nearly 300 refugees (more than 73 families) participated. Students reported that their interactions with the refugees provided positive learning experiences, including expanded knowledge of diverse cultures and enhanced skills for overcoming communication barriers. Patients of refugee status were able to have emergent health care needs met in a timely fashion. Providing health care for refugee individuals and families presents many challenges as well as extraordinary opportunities for patients and practitioners to learn from one another.


The AMPK-like protein kinases Sik2 and Sik3 interact with Hipk and induce synergistic tumorigenesis in a Drosophila cancer model.
Homeodomain-interacting protein kinases (Hipks) regulate cell proliferation, apoptosis, and tissue development. Overexpression of Hipk in Drosophila causes tumorigenic phenotypes in larval imaginal discs. We find that depletion of Salt-inducible kinases Sik2 or Sik3 can suppress Hipk-induced overgrowth. Furthermore, co-expression of constitutively active forms of Sik2 or Sik3 with Hipk caused significant tissue hyperplasia and tissue distortion, indicating that both Sik2 and Sik3 can synergize with Hipk to promote tumorous phenotypes, accompanied by elevated dMyc, Armadillo/β-catenin, and the Yorkie target gene expanded. Larvae expressing these hyperplastic growths also display an extended larval phase, characteristic of other Drosophila tumour models. Examination of total protein levels from fly tissues showed that Hipk proteins were reduced when Siks were depleted through RNAi, suggesting that Siks may regulate Hipk protein stability and/or activity. Conversely, expression of constitutively active Siks with Hipk leads to increased Hipk protein levels. Furthermore, Hipk can interact with Sik2 and Sik3 by co-immunoprecipitation. Co-expression of both proteins leads to a mobility shift of Hipk protein, suggesting it is post-translationally modified. In summary, our research demonstrates a novel function of Siks in synergizing with Hipk to promote tumour growth.


Exogenous testosterone differentially affects myelination and neurone soma sizes in the brain of canaries.
We assessed the temporal and functional relationship of myelin maturation and of neuronal development in the telencephalic song motor centres of the canary at different developmental stages. Brain differentiation was modulated by exogenous testosterone, its effects on song quality were also monitored. Myelin maturation was studied by using computer aided analysis of silver impregnated brain sections, whereas the differentiation of neurones was determined by measuring neuronal soma sizes. At an early developmental stage, testosterone triggers growth of neurones but does not affect myelination. At a later developmental stage, both neurone soma sizes and myelination are enhanced by testosterone.


Balancing accuracy, delay and battery autonomy for pervasive seizure detection.
A promising alternative for treating absence seizures has emerged through closed-loop neurostimulation, which utilizes a wearable or implantable device to detect and subsequently suppress epileptic seizures. Such devices should detect seizures fast and with high accuracy, while respecting the strict energy budget on which they operate. Previous work has overlooked one or more of these requirements, resulting in solutions which are not suitable for continuous closed-loop stimulation. In this paper, we perform an in-depth design space exploration of a novel seizure-detection algorithm, which uses a complex Morlet wavelet filter and a static thresholding mechanism to detect absence seizures. We consider both the accuracy and speed of our detection algorithm, as well as various trade-offs with device autonomy when executed on a low-power processor. For example, we demonstrate that a minimal decrease in average detection rate of only 1.83% (from 92.72% to 90.89%) allows for a substantial increase in device autonomy (of 3.7x) while also facilitating faster detection (from 710 ms to 540 ms).


Exploration of the use of novel SiO2 nanocomposites doped with fluorescent Eu3+/sensitizer complex for latent fingerprint detection.
Silicon dioxide-based nanocomposites have shown great potential in novel chemical and biological sensor development due to their large loading capacity and high surface area to volume ratio for trapping molecular complexes of various sizes. However, their potential applications in forensic science, latent fingerprint detection in particular, were still unclear. In this study, we have succeeded in trapping the highly fluorescent and photo-stable Eu3+ metal ions/sensitizer complex in silicon dioxide-based nanocomposites, doped xerogels, using the sol-gel method. We have tested the spectroscopic properties of Eu3+ in several combinations of rare earth sensitizers and different derivatives of silicon dioxide nanoporous templates. Our results indicated that the use of 1,10-phenanthroline (OP) sensitizer in tetraethoxysilane (TEOS) template provides the best fluorescently doped xerogels applicable for latent fingerprint detections on various forensic relevant materials, including metal foil, glass, plastic, colored paper, and a green tree leaf. The fabrication procedure, UV/vis and fluorescence characterizations, and fingerprint labeling results of these new Eu3+/OP/TEOS nanocomposites are presented in this exploratory study.


Controlling Taenia solium in Nepal using the PRECEDE-PROCEED model.
Taenia solium is a predominant food-borne parasitic zoonosis (FBPZ) in Nepal. Using the PRECEDE framework, as defined by Green and Kreuter, we can identify the factors behind the high incidence of this disease. Armed with this information, we can define the actions necessary to control T. solium. In accordance with the first step of PRECEDE, social assessment, we set the goal of decreasing the potential for T. solium transmission in Nepal by the year 2003. This goal has yet to be endorsed by policy makers. However, an epidemiological assessment based on hospital data alone showed that T. solium is an endemic problem in urban Nepal that must be addressed. Based on behavioral and environmental assessments (Steps 1 and 2 of PRECEDE-PROCEED), we defined the following action objectives to be achieved by 2003: 1) Train meat producers and sellers to detect contaminated pork and avoid selling it, 2) Improve pig husbandry to limit the animals' access to human feces, 3) Construct hygienic model slaughterhouses. These improvements could control the meat-producing environment, thus limiting the potential for cross-carcass contamination and other hygiene deficiencies associated with the spread of T. solium. An educational and ecological assessment shows all predisposing, reinforcing and enabling factors are present in Nepal, consistent with PRECEDE requirements. While T. solium is clearly defined as a health problem according to PRECEDE, there remain significant hurdles to controlling it. These hurdles lie in administration and policy, where standardized law-enforcement and meat inspection practices are needed. Finally, the government of Nepal must assign high priority to T. solium control, as it is a preventable, yet prevalent disease.


[Acute esophageal necrosis: an unusual entity].
Acute esophageal necrosis (AEN), also designated black esophagus, is a rare disorder that is poorly described in the medical literature. We present the case of an 80 years old man, with upper gastrointestinal bleeding who developed a black esophagus after hypotensive episodes. Necrosis was confirmed histologically. Hematemesis and melena are present in more than 70% of the cases. Endoscopic findings show black discoloration of the distal esophagus with proximal extension ending sharply at the gastroesophageal junction. Diagnosis is reached endoscopically with histological support. Mortality is high (up to 50%) even though related to the patient's underlying condition. Finally, we may say that to keep in mind the possibility of AEN is a key factor in its diagnosis, particularly in older patients with associated morbidity and evidence of upper gastrointestinal bleeding. In the present report we describe the clinical, endoscopic and histophatological characteristics of a patient with a diagnosis of AEN.


Assessing interprofessional teamwork in a videoconference-based telerehabilitation setting.
We studied the workings of a rehabilitation team in a videoconference setting to note the pros and cons of videoconferencing in the development of interprofessional care plans (ICPs). We recorded every videoconference held by the teams of the specialized centre and the regional centre for clients with traumatic brain injuries over an 18-month period. Thirteen recorded videoconferences, lasting for 30-98 min, were analysed through an observation grid. On the whole, efficient teamwork was observed: the mean productivity level was 96%, while the percentage of time dedicated to the resolution of technical issues was 2%. During the videoconferences, the clinical coordinator and the client addressed the group most often. One of the most commonly mentioned advantages was the good visual contact provided by videoconferencing. The most often quoted disadvantage was the poor sound quality. The findings from the study support the adoption of videoconferencing and suggest a few guidelines for the development of ICPs.


Pectus deformities: a review of open surgery in the modern era.
Pectus deformities represent a spectrum of relatively common congenital chest malformations. The adoption of less invasive techniques has renewed interest in surgical repair by both patients and clinicians. The aim of this review is to identify current management, outcomes, and controversy in the treatment of pectus excavatum and pectus carinatum.


Effective information transfer from the alpha 1b-adrenoceptor to Galpha 11 requires both beta/gamma interactions and an aromatic group four amino acids from the C terminus of the G protein.
Co-expression of the alpha(1b)-adrenoreceptor and Galpha(11) in cells derived from a Galpha(q)/Galpha(11) knock-out mouse allows agonist-mediated elevation of intracellular Ca(2+) levels that is transduced by beta/gamma released from the G protein alpha subunit. Mutation of Tyr(356) of Galpha(11) to Phe, within a receptor contact domain, had little effect on function but this was reduced greatly by alteration to Ser and virtually eliminated by conversion to Asp. This pattern was replicated following incorporation of each form of Galpha(11) into fusion proteins with the alpha(1b)-adrenoreceptor. Following a [(35)S]guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) binding assay, immunoprecipitation of the wild type alpha(1b)-adrenoreceptor-Galpha(11) fusion protein indicated that the agonist phenylephrine stimulated guanine nucleotide exchange on Galpha(11) more than 30-fold. Information transfer by agonist was controlled in residue 356 Galpha(11) mutants with rank order Tyr > Phe > Trp > Ile > Ala = Gln = Arg > Ser > Asp, although these alterations did not alter the binding affinity of either phenylephrine or an antagonist ligand. Mutation of a beta/gamma contact interface in the alpha(1b)-adrenoreceptor-Tyr(356) Galpha(11) fusion protein did not alter ligand binding affinity but did reduce greatly beta/gamma binding and phenylephrine stimulation of [(35)S]GTPgammaS binding. It also prevented agonist elevation of intracellular Ca(2+) levels, as did a mutation in Galpha(11) that prevents G protein subunit dissociation. These results indicate that a bulky aromatic group is required four amino acids from the C terminus of Galpha(11) to maximize information transfer from an agonist-occupied receptor and disprove the hypothesis that tyrosine phosphorylation of this residue is required for G protein activation (Umemori, H., Inoue, T., Kume, S., Sekiyama, N., Nagao, M., Itoh, H., Nakanishi, S., Mikoshiba, K., and Yamamoto, T. (1997) Science 276, 1878-1881). This is distinct from Galpha(i1), where hydrophobicity of the amino acid is the key determinant at this location. They also further demonstrate a key role for the beta/gamma complex in enhancing receptor to G protein alpha subunit information transfer.


Ferrioxalate-polyoxometalate system as a new chemical actinometer.
A chemical actinometer that employs an aqueous solution of ferrioxalate and polyoxometalate (POM: SiW120404-) is proposed as a simple and fast method that quantifies the light intensity of UV radiation in the 300-390 nm range. As a modified ferrioxalate actinometer, illuminated ferrioxalate solution in the presence of POM generates C02 radical anions that lead to the production of blue-colored POM (SiW12O40(5-)) whose concentration can be easily determined spectrophotometrically (by monitoring absorbance at 730 nm). Photoproduction rate of POM- is linearly correlated with the light intensity. The measured quantum yields, phi(POM-), range 0.11-0.21 in the 300-390 nm region and is fairly constant around 0.18 in the 335-380 nm range, which makes this actinometry ideally suited for the rapid measurement of the light intensity in the UVA region such as in common black light sources. This alternative actinometry eliminates the postirradiation analytical procedure (which needs phenanthroline as a complexation reagent for Fe2+ and the subsequent color development) that is required in the standard ferrioxalate actinometry, and it enables the in-situ quantification of the light intensity in a simpler way by monitoring the formation of POM- as a proxy indicator.


Septic arthritis following Staphylococcus aureus infection in mice lacking inducible nitric oxide synthase.
Nitric oxide (NO), produced in large amounts by inducible NO synthase (iNOS), has emerged recently as an important microbicidal and immunomodulatory mediator. We have investigated its role in bacterial septic arthritis caused by Staphylococcus aureus infection using iNOS-deficient mice. The incidence, rate of development, and severity of arthritis were greater in iNOS-deficient than in heterozygous or wild-type control mice. Similarly, the incidence and severity of septicemia and mortality were significantly higher in iNOS-deficient mice compared with controls. Increased TNF-alpha synthesis in vivo and in vitro and enhanced IFN-gamma compared with IL-4 production in vitro in iNOS-mutant mice demonstrated exaggerated Th1 polarization of the host response. These data indicate that high output NO production is not a prerequisite for severe articular destruction and imply that NO is of importance in synovial defense against staphylococcal infection.


Robotic vs open radical cystectomy: prospective comparison of perioperative outcomes and pathological measures of early oncological efficacy.
To prospectively compare perioperative and pathological outcomes in a consecutive series of patients undergoing radical cystectomy (RC) and urinary diversion by the open or the robotic approach. From February 2006 to April 2007, 54 consecutive patients underwent RC by one surgeon at our institution. Twenty-one were open, while 33 utilized the da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA, USA). Data was collected prospectively, including patient demographics, operative and postoperative variables, and pathological outcomes. The robotic cohort had decreased blood loss (400 vs 750 mL, P = 0.002) and transfusion requirement (2.0 vs 0.5 units, P = 0.007), but increased operative duration (390 vs 300 min, P = 0.03). The time to resumption of a regular diet (4 vs 5 days, P = 0.002) and the hospital stay (5 vs 8 days, P = 0.007) were decreased in the robotic group. Overall the complication rates were similar (24% open, 21% robotic, P = 0.3). The open cohort had more patients with extravesical disease (57 vs 28%, P = 0.03) and nodal metastasis (34 vs 19%, P = 0.04). There were three patients in the open group and two in the robotic with positive margins (P = 0.2). The median number of lymph nodes removed was similar in the open and robotic cohorts (20 vs 17, P = 0.6). Robotic-assisted RC appears to offer some operative and perioperative benefits compared with the open approach without compromising pathological measures of early oncological efficacy, such as lymph node yield and margin status. Larger, randomized studies with long-term follow-up are required to confirm these findings and establish oncological equivalence.


The biochemistry and biology of the atypical chemokine receptors.
A subset of chemokine receptors, initially called "silent" on the basis of their apparent failure to activate conventional signalling events, has recently attracted growing interest due to their ability to internalize, degrade, or transport ligands and thus modify gradients and create functional chemokine patterns in tissues. These receptors recognize distinct and complementary sets of ligands with high affinity, are strategically expressed in different cellular contexts, and lack structural determinants supporting Gα(i) activation, a key signalling event in cell migration. This is in keeping with the hypothesis that they have evolved to fulfil fundamentally different functions to the classical signalling chemokine receptors. Based on these considerations, these receptors (D6, Duffy antigen receptor for chemokines (DARC), CCX-CKR1 and CXCR7) are now collectively considered as an emerging class of 'atypical' chemokine receptors. In this article, we review the biochemistry and biology of this emerging chemokine receptor subfamily.


Molecular and cellular effects of Auger emitters: 2008-2011.
To review recent Auger emitter research with an emphasis on a review of findings on targeting and accumulation of Auger emitters in tumor cells. Significant progress can be reported for targeting methods and improvements in methods to accumulate Auger emitters in the target cells, as well as advances in dose calculations. These studies further our understanding of how Auger emitters induce cell death at a cellular and molecular level, supporting the targeted radiomedical applications of Auger emitters.


Nonpeptide bradykinin B2 receptor antagonists: conversion of rodent-selective bradyzide analogues into potent, orally-active human bradykinin B2 receptor antagonists.
The 1-(2-nitrophenyl)thiosemicarbazide (TSC) derivative, (S)-1-[4-(4-benzhydrylthiosemicarbazido)-3-nitrobenzenesulfonyl]pyrrolidine-2-carboxylic acid [2-[(2-dimethylaminoethyl)methylamino]ethyl]amide (bradyzide; (S)-4), was recently disclosed as a novel, potent, orally active nonpeptide bradykinin (BK) B2 receptor antagonist. The compound inhibited the specific binding of [3H]BK to NG108-15 cell membrane preparations (rodent neuroblastoma-glioma) expressing B2 receptors with a K(i) of 0.5 +/- 0.2 nM. Compound (S)-4 also demonstrated oral efficacy against Freund's complete adjuvant (FCA)-induced mechanical hyperalgesia in rats with an ED50 value of 0.84 micromol/kg. After we optimized the terminal binding determinants projecting from the TSC framework, we found that it was possible to replace the potentially toxicophoric nitro and divalent sulfur moieties with only a 15-fold loss in binding affinity ((S)-14a). However, bradyzide and its congeners were found to have much lower affinities for cloned human B2 receptors, expressed in Cos-7 cells. The hitherto synthesized TSC series was screened against the human B2 receptor, and the dibenzosuberane (DBS) pharmacophore emerged as the key structural requirement for potency. Incorporation of this group resulted in a series of derivatives ((S)-14d,e and 19b-d) with K(i) ranges of 10.7-176 nM in NG108-15 cells (expressing the rodent B2 receptor) and 0.79-253 nM in Cos-7 cells (expressing the human B2 receptor). There was no evidence of agonist activity with any of the nonpeptides in any of the cell lines tested. In vivo, oral administration of compound 19c reversed FCA-induced and turpentine-induced mechanical hyperalgesia in rodents with ED50 values of 0.027 and 0.32 micromol/kg, respectively. The selectivity profiles of compounds (S)-14f and (S)-14g were also assessed to determine the conformational and/or steric preferences of the double-ring arrangement. The affinity of (S)-14 g for the human B2 receptor suggested that it may be a hydrophobic interaction with the ethane bridge of the DBS moiety that accounts for the increased potency of compounds (S)-14d,e and 19b,c at this receptor, by favoring a binding mode inaccessible to the unsubstituted diphenylmethyl derivative, (S)-4.


The long-term effect of calcium hydroxide application on dentin fracture strength of endodontically treated teeth.
The aim of this in vitro study was to evaluate the long-term effect of calcium hydroxide (CH) on the microtensile fracture strength (MTFS) of endodontically treated human teeth. A total of 105 caries-free extracted human mandibular incisors were used. The teeth were divided into seven experimental groups of 15 teeth each. The root canals of all the teeth were rotary instrumented. The teeth in the control group were immediately obturated and tested for MTFS. The rest of the teeth were vertically compacted with CH and a sterile saline solution mixture and sealed with temporary filling. The teeth were stored in a moist environment for 30, 90, 180, 270, 360, and 540 days. On scheduled dates, the root canals were obturated and then the teeth were tested for MTFS with an Instron testing machine. The Kruscal-Wallis test and a post hoc Dunn's multiple comparison test was utilized. The statistical significance level was established at P < 0.05. The introduction of CH into the root canals seems to decrease the MTFS of teeth statistically significantly through the 180th, 270th, 360th, and 540th days, respectively, compared with the control group. The results clearly indicated that there are statistically significant differences between group 2 and group 7 (P < 0.001) and between group 3 and group 7 (P < 0.05). There were no statistically significant differences between the rest of the groups (P > 0.05). The results indicate that long-term CH treatments can significantly reduce the strength of the teeth, causing an increase in fracture risk.


Evaluation of the Dissemination, Implementation, and Sustainability of the "Partnership for Health" Intervention.
Partnership for Health (PfH) is an evidence-based, clinician-delivered HIV prevention program conducted in the United States for HIV-positive patients. This intervention strives to reduce risky sexual behaviors through provider-patient discussions on safer sex and HIV status disclosure. A cross-sectional, mixed-methods design was used to evaluate the dissemination and implementation of PfH, including training evaluations, an online trainee survey, and interviews with national trainers for PfH. Descriptive statistics were calculated with the categorical data, whereas thematic analysis was completed with the qualitative data. Between 2007 and 2013, PfH was disseminated to 776 individuals from 104 different organizations in 21 states/territories. The smallest proportion of trainees was physicians (6.9%). More than three-fourths of survey respondents (78.6%) reported using PfH, but less than one-third (31.8%) used the intervention with every patient. The PfH training supports the implementation of the intervention; however, challenges were experienced in clinician engagement. Tailored strategies to recruit and train clinicians providing care to HIV-positive patients are required.


[Psychosomatic study of inhalation therapy in patients with bronchial asthma. I. Evaluation by questionnaire].
We investigated the use of metered-dose beta agonist inhalers (MDIs) by means of 17-item questionnaires from the standpoint of psychosomatic medicine in 56 subjects with bronchial asthma. The results can be summarized as follows: 1) Many asthmatics with neurotic characters used MDIs frequently; Thirteen percent of them suffered adverse effects. The number of times the inhalers were used increased in proportion to the severity and the duration of illness. Fifteen percent of the subjects used MDIs frequently because of anxiety. 2) Fifty percent of the subjects, most of them had neurotic or alexithymic characters, used MDIs without suffering from dyspnea or wheezes; the subjects who used MDIs because of anxiety increased in proportion to the duration of illness. 3) Seventy eight percent of the subjects were anxious about asthmatic attack when they did not carry any MDI; sixty two percent of the subjects, most of them had neurotic or alexithymic characters, actually experienced asthmatic attack. 4) Seventy three percent of the subjects used MDIs secretly; sixty percent of the subjects did not like to inhale in the presence of others. 5) There were some subjects who acted incorrectly on or after asthmatic attack when MDIs were not effective.


Determination of endocrine disrupting chemicals and antiretroviral compounds in surface water: A disposable sorptive sampler with comprehensive gas chromatography - Time-of-flight mass spectrometry and large volume injection with ultra-high performance liquid chromatography-tandem mass spectrometry.
Many rural dwellers and inhabitants of informal settlements in South Africa are without access to treated water and collect untreated water from rivers and dams for personal use. Endocrine disrupting chemicals (EDCs) have been detected in surface water and wildlife of South Africa. EDCs are often present in complex environmental matrices at ultra-trace levels complicating detection thereof. We report a simplified multi-residue approach for the detection and quantification of EDCs, emerging EDCs, and antiretroviral drugs in surface water. A low cost (less than one US dollar), disposable, sorptive extraction sampler was prepared in-house. The disposable samplers consisted of polydimethylsiloxane (PDMS) tubing fashioned into a loop which was then placed in water samples to concentrate EDCs and emerging pollutants. The PDMS samplers were thermally desorbed directly in the inlet of a GC, thereby eliminating the need for expensive consumable cryogenics. Comprehensive gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS) was used for compound separation and identification. Linear retention indices of EDCs and emerging pollutants were determined on a proprietary Crossbond® phase Rtx®-CLPesticides II GC capillary column. In addition, large volume injection of surface water into an ultra-performance liquid chromatograph tandem mass spectrometer (UPLC-MS/MS) was used as complementary methodology for the detection of less volatile compounds. Large volume injection reduced tedious and costly sample preparation steps. Limits of detection for the GC method ranged from 1 to 98pg/l and for the LC method from 2 to 135ng/l. Known and emerging EDCs such as pharmaceuticals, personal care products and pesticides, as well as the antiretroviral compounds, efavirenz and nevirapine, were detected in surface water from South Africa at concentration levels ranging from 0.16ng/l to 227ng/l.


What to Say When Seeking Support Online: A Comparison Among Different Levels of Self-Disclosure.
The current study examined the effect of exposure to online support-seeking posts containing different levels of depth self-disclosure (baseline, peripheral, core) affecting the quality (person-centeredness and politeness) of participants' support-provision messages. Participants of the study were assigned to the role of a support-provider. Compared to participants who read support-seeking posts with baseline and core self-disclosure, participants who read support-seeking posts with peripheral self-disclosure rated the support-seekers as less anonymous. Compared to participants who read support-seeking posts in the baseline condition, participants who read the support-seeking posts with peripheral self-disclosure wrote support-provision messages with higher level of person-centeredness and politeness. Participants' perceived anonymity of the support-seekers mediated the effect of the depth of self-disclosure on the politeness of the response messages.


Anticancer Activity of Periplanetasin-5, an Antimicrobial Peptide from the Cockroach Periplaneta americana.
Cockroaches live in places where various pathogens exist and thus are more likely to use antimicrobial compounds to defend against pathogen intrusions. We previously performed an in silico analysis of the Periplaneta americana transcriptome and detected periplanetasin-5 using an in silico antimicrobial peptide prediction method. In this study, we investigated whether periplanetasin-5 has anticancer activity against the human leukemia cell line K562. Cell growth and survival of K562 cells treated with periplanetasin-5 were decreased in a dose-dependent manner. By using flow cytometric analysis, acridine orange/ethidium bromide (AO/EB) staining and DNA fragmentation, we found that periplanetasin-5 induced apoptotic and necrotic cell death in leukemia cells. In addition, these events were associated with increased levels of the pro-apoptotic proteins Fas and cytochrome c and reduced levels of the anti-apoptotic protein Bcl-2. Periplanetasin-5 induces the cleavage of pro-caspase-9, pro-caspase-8, pro-caspase-3, and poly (ADP-ribose) polymerase (PARP). The above data suggest that periplanetasin-5 induces apoptosis via both the intrinsic and extrinsic pathways. Moreover, caspase-related apoptosis was further confirmed by using the caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (Z-VAD-FMK), which reversed the periplanetasin-5-induced reduction in cell viability. In conclusion, periplanetasin-5 caused apoptosis in leukemia cells, suggesting its potential utility as an anticancer therapeutic agent.


Captopril alleviates lung inflammation in SARS-CoV-2-infected hypertensive mice.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent responsible for the global coronavirus disease 2019 (COVID-19) pandemic. Numerous studies have demonstrated that cardiovascular disease may affect COVID-19 progression. In the present study, we investigated the effect of hypertension on viral replication and COVID-19 progression using a hypertensive mouse model infected with SARS-CoV-2. Results revealed that SARS-CoV-2 replication was delayed in hypertensive mouse lungs. In contrast, SARS-CoV-2 replication in hypertensive mice treated with the antihypertensive drug captopril demonstrated similar virus replication as SARS-CoV-2-infected normotensive mice. Furthermore, antihypertensive treatment alleviated lung inflammation induced by SARS-CoV-2 replication (interleukin (IL)-1β up-regulation and increased immune cell infiltration). No differences in lung inflammation were observed between the SARS-CoV-2-infected normotensive mice and hypertensive mice. Our findings suggest that captopril treatment may alleviate COVID-19 progression but not affect viral replication.


Preventing health problems that disrupt community living: A health promotion needs assessment.
People with physical disabilities experience health disparities and poor health outcomes that endanger community living and participation, and sometimes contribute to institutionalization. Centers for Independent Living (CILs) provide vital services to assist consumers with disabilities in achieving and maintaining community living; these organizations could be trusted sources in providing targeted health information. As first steps in devising a Health Promotion Assistance Tool for CIL staff to use with consumers, this project conducted a Needs Assessment study to collect feedback on what information would be most useful. First, researchers interviewed key informants from a sample of CIL staff members to gain input for a survey on the content of the proposed tool. Then, they disseminated the survey by e-mail to 426 CILs listed in a national data bank, and received responses from one or more staff members from 93 CILs. CIL staff reported that their consumers experienced a variety of chronic conditions (e.g., diabetes, high blood pressure) in addition to their physical disability, and that they also experienced secondary health conditions such as chronic pain and depression. CIL staff also reported that they believed their consumers were in need of supports to enable them to engage in preventive health care. We discuss implications for these findings to our further research.


Semisynthesis of autophagy protein LC3 conjugates.
Autophagy is a conserved catabolic process involved in the elimination of proteins, organelles and pathogens. Autophagosome formation is the key process in autophagy. Lipidated Atg8/LC3 proteins that are conjugated to phosphatidylethanolamine (PE) play a key role in autophagosome biogenesis. To understand the function of Atg8/LC3-PE in autophagosome formation and host-pathogen interaction requires preparation and structural manipulation of lipidated Atg8/LC3 proteins. Herein, we report the semisynthesis of LC3 proteins and mutants with modifications of different PE fragments or lipids using native chemical ligation and aminolysis approaches.


Attitudes That Might Impact upon Donation after Brain Death in Intensive Care Unit Settings: A Systematic Review.
Organ donation and transplantation can save or improve the quality of life of people worldwide. However, there are many challenges associated with organ donation, as the demand for organs greatly outstrips supply. Additionally, there are brain-dead patients who could be potential organ donors. It is thus important to determine the attitudes affecting organ donation and transplantation in intensive care unit settings. this study aimed to identify attitudes that might affect organ donation and transplantation in intensive care unit settings. Five electronic databases (CINAHL, Medline, PsycINFO, Scopus, and EMBASE) were searched systematically. A systematic search strategy was formulated. The quality of each study was assessed using the MMAT quality appraisal tool. A total of seven studies were included. The findings of this systematic review demonstrate that education, policy, and continuing professional development could help to address barriers to donation. therefore, to influence organ donation and transplantation positively, the main themes evaluated in this systematic review provide an opportunity to influence organ donation and transplantation attitudes in intensive care unit settings.


Physiological factors associated with falls in older community-dwelling women.
To determine the prevalence of impaired vision, peripheral sensation, lower limb muscle strength, reaction time, and balance in a large community-dwelling population of women aged 65 years and over, and to determine whether impaired performances in these tests are associated with falls. One-year prospective study. Conducted as part of the Randwick Falls and Fractures Study, in Sydney, Australia. Four hundred fourteen women aged 65 to 99 years (mean age 73.7 years, SD = 6.3) were randomly selected from the community; 341 of these women were included in the 1-year prospective study. The prevalence of impairment in all tests increased with age. In the year following assessment, 207 subjects (60.7%) experienced no falls, 63 subjects (18.5%) fell one time only, and 71 subjects (20.8%) fell on two or more occasions. After controlling for age, multiple falling was associated with low contrast visual acuity and contrast sensitivity, poor vibration sense and proprioception, reduced lower limb strength, slow reaction time, and impaired balance, as indicated by four sway tests and two clinical stability measures. Discriminant function analysis identified visual contrast sensitivity, proprioception in the lower limbs, quadriceps strength, reaction time, and sway on a compliant (foam rubber) surface with the eyes open as the variables that significantly discriminated between subjects who experienced multiple falls and subjects who experienced no falls or one fall only (Wilks' lambda = 0.73 (P < 0.001), canonical correlation = 0.52). This procedure correctly classified 75% of subjects into multiple faller or nonmultiple faller groups. These findings support previous results conducted in retirement village and institutional setting and indicate that the test procedure aids in the identification of older community-dwelling women at risk of falls.


[Change in diagnosis and therapy of extrauterine pregnancy in the last 4 decades].
2 groups of patients with ectopic pregnancy (376 cases from 1947 to 1966 and 81 from 1982 to 1988) are compared. The importance of evaluation of HCG, sonography and pelviscopy, which was only available in the 2nd group, is pointed out. The morbidity by collapse of circulation could be improved. Sonography and beta-HCG serum levels each are quite sensitive but not very specific. Together they give good information. The highest specificity shows the pelviscopy, but it is an invasive method and requires anesthesia. By early diagnosis of the ectopic pregnancy in the 2nd group 50% of the patients could be treated by an operation with conservative of the fallopian tube.


Robot-assisted vs laparoscopic adrenalectomy: a prospective randomized controlled trial.
The aim of this study was to assess the benefits and disadvantages of robot-assisted laparoscopic surgery for disorders of the adrenal gland in terms of feasibility, safety, and length of hospitalization. Twenty consecutive patients with benign lesions of adrenal gland were randomized into two groups: Patients in the laparoscopic group underwent traditional laparoscopic adrenalectomy (LAP), whereas those in the robotic group underwent robot-assisted adrenalectomy (ROBOT) using the da Vinci robotic system. There was no significant difference between the groups in terms of age, sex, body mass index, and size or locations of lesions. Operative times were significant longer in the ROBOT group (total operative time, 169.2 min [range, 136-215] vs 115.3 min (range, 95-155) p < 0.001. Skin-to-skin time was 107 m (range, 77-154) vs 82.1 min (range, 55-120) (p < 0.001). There were no conversions to open surgery. However, conversion to standard laparoscopic surgery was necessary in four of 10 ROBOT patients (40%; left, one right). Perioperative morbidity was higher in the ROBOT group (20% vs 0%). There was no difference in length of hospital stay. In the following ROBOT group, hospital stay was 5.7 days (range, 4-9) vs 5.4 days (range, 4-8) in the LAP group (p = NS). The total cost of the ROBOT procedure ($3,467) was significantly higher than that for LAP ($2,737) (p < 0.01). Laparoscopic adrenalectomy is superior to robot-assisted adrenalectomy in terms of feasibility, morbidity, and cost.


Kinetics of the NCN + NO reaction over a broad temperature and pressure range.
Rate coefficients for the reaction (3)NCN + NO → products (R3) were measured in the temperature range 251-487 K at pressures from 10 mbar up to 50 bar with helium as the bath gas. The experiments were carried out in slow-flow reactors by using pulsed excimer laser photolysis of NCN(3) at 193 or 248 nm for the production of NCN. Pseudo-first-order conditions ([NCN](0) ≪ NO) were applied, and NCN was detected time-resolved by resonant laser-induced fluorescence excited near 329 nm. The measurements at the highest pressures yielded values of k(3) ∼ 8 × 10(-12) cm(3) s(-1) virtually independent of temperature and pressure, which indicates a substantially smaller high-pressure limiting value of k(3) than predicted in earlier works. Our experiments at pressures below 1 bar confirm the negative temperature and positive pressure dependence of the rate coefficient k(3) found in previous investigations. The falloff behavior of k(3) was rationalized by a master equation analysis based on a barrierless association step (3)NCN + NO ↔ NCNNO((2)A″) followed by a fast internal conversion NCNNO((2)A″) ↔ NCNNO((2)A'). From 251-487 K and above 30 mbar, the rate coefficient k(3) is well represented by a Troe parametrization for a recombination/dissociation reaction, k(3)(T,P) = k(4)(∞)k(4)(0)[M]F(k(4)(0)[M] + k(4)(∞))(-1), where k(4) represents the rate coefficient for the recombination reaction (3)NCN + NO. The following parameters were determined (30% estimated error of the absolute value of k(3)): k(4)(0)[M=He] = 1.91 × 10(-30)(T/300 K)(-3.3) cm(6) s(-1)[He], k(4)(∞) = 1.12 × 10(-11) exp(-23 K/T) cm(3) s(-1), and F(C) = 0.28 exp(173 K/T).


New method for delineation of the intersegmental line in a deflated lung.
Preoperative three-dimensional (3D) computed tomography (CT) images have been widely used as surgical guides in lung surgery; however, the lungs tend to be deflated during surgery. Discrepancies between the preoperatively constructed 3D image and the intraoperative view of the deflated lungs often require preoperative and/or intraoperative marking methods for sublobar pulmonary resection. We have developed a lung deflation simulation algorithm in which 3D CT images of the deflated lungs can be predicted only based on the preoperative CT taken in an inflated phase of respiration. Using this system, we conducted a preliminary study to retrospectively compare the intersegmental line predicted by our lung deflation simulation algorithm with the intersegmental line delineated by the intravenous administration of indocyanine green. Sixteen patients who underwent unilateral segmentectomy between January 1, 2020, and June 30, 2022, were included in the study. The identified intersegmental lines were confirmed intraoperatively using indocyanine green. These actual intersegmental lines were compared with those delineated on 3D images using the lung deflation simulation algorithm. Of the 16 patients who underwent pulmonary segmentectomy, the consistency of these intersegmental lines was in complete agreement in twelve patients, partial agreement in three patients, and disagreement in one patient. The concordance rate of the intersegmental lines was 75%. The lung deflation simulation algorithm provides a new surgical guide in addition to the currently utilized ones. Continuous innovation might lead to a less invasive surgical technique for delineating the intersegmental line.


Distribution of polychlorinated biphenyls in effluent from a large municipal wastewater treatment plant: Potential for bioremediation?
This study involved an evaluation of the potential for bioremediation of polychlorinated biphenyls (PCBs) in the effluent from a large municipal wastewater treatment plant. It was focused on the presence of PCBs in two types of effluents: the continuous effluent present during dry weather conditions and the intermittently present effluent that was present during wet weather due to incoming stormwater. The annual discharge of PCBs for both types of effluent was calculated based on a five-year dataset (2011-2015). In addition, the toxicity and bioremediation potential of the PCBs in the effluent were also assessed. It was found that the continuous effluent was responsible for the majority of the discharged PCB into the receiving river (1821 g for five years), while the intermittent effluent contributed 260 g over the five years. The average number of chlorine per biphenyl for the detected PCB congeners showed a 19% difference between the two types of effluent, which indicated a potential for organohalide respiration of PCBs during the continuous treatment. This was further supported by a high level of tri-, tetra- and penta-chlorinated congeners accounting for 75% of the anaerobically respired PCBs. Potential for aerobic degradation and thus biomineralization of PCBs was identified for both effluents. Furthermore, toxicity of 12 dioxin-like PCBs showed that normal operation of the wastewater reduced the toxicity throughout the wastewater treatment plant.


HCV Drug Resistance Challenges in Japan: The Role of Pre-Existing Variants and Emerging Resistant Strains in Direct Acting Antiviral Therapy.
Sustained virological response (SVR) rates have increased dramatically following the approval of direct acting antiviral (DAA) therapies. While individual DAAs have a low barrier to resistance, most patients can be successfully treated using DAA combination therapy. However, DAAs are vulnerable to drug resistance, and resistance-associated variants (RAVs) may occur naturally prior to DAA therapy or may emerge following drug exposure. While most RAVs are quickly lost in the absence of DAAs, compensatory mutations may reinforce fitness. However, the presence of RAVs does not necessarily preclude successful treatment. Although developments in hepatitis C virus (HCV) therapy in Asia have largely paralleled those in the United States, Japan's July 2014 approval of asunaprevir plus daclatasvir combination therapy as the first all-oral interferon-free therapy was not repeated in the United States. Instead, two different combination therapies were approved: sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir/dasabuvir. This divergence in treatment approaches may lead to differences in resistance challenges faced by Japan and the US. However, the recent approval of sofosbuvir plus ledipasvir in Japan and the recent submissions of petitions for approval of paritaprevir/ritonavir plus ombitasvir suggest a trend towards a new consensus on emerging DAA regimens.


Nanosurface Texturing for Enhancing the Antibacterial Effect of Biodegradable Metal Zinc: Surface Modifications.
Zinc (Zn) as a biodegradable metal has attracted research interest for bone reconstruction, with the aim of eliminating the need for a second removal surgery and minimizing the implant-to-bone transfer of stress-shielding to maintain bone regeneration. In addition, Zn has been shown to have antibacterial properties, particularly against Gram-negative bacteria, and is often used as a surface coating to inhibit bacterial growth and biofilm formation. However, the antibacterial property of Zn is still suboptimal in part due to low Zn ion release during degradation that has to be further improved in order to meet clinical requirements. This work aims to perform an innovative one-step surface modification using a nitric acid treatment to accelerate Zn ion release by increasing surface roughness, thereby endowing an effective antimicrobial property and biofilm formation inhibition. The antibacterial performance against Staphylococci aureus was evaluated by assessing biofilm formation and adhesion using quantitative assays. The surface roughness of acid-treated Zn (Ra ~ 30 nm) was significantly higher than polished Zn (Ra ~ 3 nm) and corresponded with the marked inhibition of bacterial biofilm, and this is likely due to the increased surface contact area and Zn ion accumulation. Overall, surface modification due to nitric acid etching appears to be an effective technique that can produce unique morphological surface structures and enhance the antibacterial properties of biodegradable Zn-based materials, thus increasing the translation potential toward multiple biomedical applications.