"Being Married Doesn't Mean You Have to Reach the End of the World": Safety Planning With Intimate Partner Violence Survivors and Service Providers in Three Urban Informal Settlements in Nairobi, Kenya.
Intimate partner violence (IPV) harms women physically, sexually, and psychologically. Safety strategies, or harm reduction techniques implemented by women undergoing recurrent violence, may help mitigate the negative health, economic, and social consequences of IPV. This study aimed to understand recommended and utilized safety strategies among three urban informal settlements in Nairobi, Kenya. Semi-structured key informant discussions (KIDs; n = 18) with community-based service providers and focus group discussions (FGDs; n = 49) with IPV survivors were conducted. All interviews were audio-recorded, transcribed, and translated verbatim from Swahili to English. Inductive thematic analysis was used to structure codes. Convergence matrices were used to analyze emergent strategies by data source (service providers vs. IPV survivors). Women preferred safety strategies that they could implement unassisted as first line of harm reduction. Strategies included removing stressors, proactive communication, avoidance behaviors, sexual and reproductive health (SRH), economic, leaving partner for safety, child safety, and securing personal property. Strategies recommended by service providers and utilized by IPV survivors differed, with clear divergence indicated for leaving the abusive relationship, SRH, and personal property strategies. Innovative strategies emerged from IPV survivors for safeguarding property. Similar to upper-income and other low and middle-income contexts, women experiencing IPV in urban informal settlements of Nairobi actively engage in behaviors to maximize safety and reduce harm to themselves and their families. Integration of strategies known to be helpful to women in these communities into community-based prevention and response is strongly encouraged. Increased synergy between recommended and implemented safety strategies can enhance programming and response efforts.


Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2.
To investigate the clinical and imaging characteristics of computed tomography (CT) in novel coronavirus pneumonia (NCP) caused by SARS-CoV-2. A retrospective analysis was performed on the imaging findings of patients confirmed with COVID-19 pneumonia who had chest CT scanning and treatment after disease onset. The clinical and imaging data were analyzed. Fifty patients were enrolled, including mild type in nine, common in 28, severe in 10 and critically severe in the rest three. Mild patients (29 years) were significantly (P<0.03) younger than either common (44.5 years) or severe (54.7) and critically severe (65.7 years) patients, and common patients were also significantly (P<0.03) younger than severe and critically severe patients. Mild patients had low to moderate fever (<39.1 °C), 49 (98%) patients had normal or slightly reduced leukocyte count, 14 (28%) had decreased counts of lymphocytes, and 26 (52%) patients had increased C-reactive protein. Nine mild patients were negative in CT imaging. For all the other types of NCP, the lesion was in the right upper lobe in 30 cases, right middle lobe in 22, right lower lobe in 39, left upper lobe in 33 and left lower lobe in 36. The lesion was primarily located in the peripheral area under the pleura with possible extension towards the pulmonary hilum. Symmetrical lesions were seen in 26 cases and asymmetrical in 15. The density of lesion was mostly uneven with ground glass opacity as the primary presentation accompanied by partial consolidation and fibrosis. CT imaging presentations of NCP are mostly patchy ground glass opacities in the peripheral areas under the pleura with partial consolidation which will be absorbed with formation of fibrotic stripes if improved. CT scanning provides important bases for early diagnosis and treatment of NCP.


The transformation of the Plasmodium gallinaceum oocyst in Aedes aegypti mosquitoes.
Sporoblast and sporozoite formation from oocysts of the avian malarial parasite, Plasmodium gallinaceum, after the seventh day of infection in Aedes aegypti mosquitoes offers an interesting example of differentiation involving the appearance and modification of several cellular components. Sporoblast formation is preceded by (a) invaginations of the oocyst capsule into the oocyst cytoplasm, (b) subcapsular vacuolization and cleft formation, (c) the appearance of small tufts of capsule material on the previously noted invaginations, and (d) linear dense areas located just below the oocyst plasma membrane which predetermine the site of emerging sporozoites from the sporoblast. The subcapsular clefts subdivide the once-solid oocyst into sporoblast peninsulae. Within the sporoblast, nuclei migrate from the random distribution seen in the solid oocyst and come to lie at the periphery of the sporoblast just below the linear dense areas noted in the earlier stage. A typical nuclear fiber apparatus occurs in most of the nuclei seen in random sections at this stage although such a fiber apparatus may occasionally be seen in the solid oocyst stage. The nucleus, its associated fiber apparatus, and the overlying dense area appear to induce the onset of sporozoite budding from the sporoblast as well as the formation of the sporozoite pellicular complex and the paired organelle precursor. Several mitochondria are present in each sporozoite, in contrast to the single mitochondrion seen in the merozoites of the erythrocytic and exoerythrocytic stages of avian malaria infection. The paired organelles and associated dense inclusion bodies are formed by condensation of an irregular meshwork of membrane-bound, coarse, dense material. The nature of small, particulate cytoplasmic inclusions is described.


Mammalian X ray sensitive mutants: a tool for the elucidation of the cellular response to ionizing radiation.
The complexity of the cellular response to ionizing radiation is indicated by many complementation groups identified among mammalian cells sensitive to ionizing radiation. Genetic complementation analysis of these mutants has been based on cell fusion and complementation of cell killing by X ray, whereas complementation of RDS after gamma rays has led to false results among AT cell lines and could not also be used in rodent cells. Studies on the relationship between cell killing and RDS following gamma irradiation have indicated that (a) RDS is not responsible for cell killing and (b) DNA replication in response to gamma rays is controlled by several genes. Complementation groups established in rodent cell mutants have led to the identification of the gene function in several mutants, and remarkable progress has been made in the understanding of DSB repair and its involvement in V(D)J recombination. The remaining complementation groups of X ray sensitive mutants await the determination of the role of the defective genes in the pathways operating in mammalian cells against ionizing radiation. One group of rodent mutants seems to be defective in the gene homologous to the ATM gene, and so far no more human counterparts have been found among rodent mutants. Newly characterized mutants, V-C8 and UV40, showed combined features of several human disorders, suggesting that their defective gene products could be involved in several pathways handling the response to DNA damage.


Permanent Pacemaker Implantation Following Valve-in-Valve Transcatheter Aortic Valve Replacement: VIVID Registry.
Permanent pacemaker implantation (PPI) remains one of the main drawbacks of transcatheter aortic valve replacement (TAVR), but scarce data exist on PPI after valve-in-valve (ViV) TAVR, particularly with the use of newer-generation transcatheter heart valves (THVs). The goal of this study was to determine the incidence, factors associated with, and clinical impact of PPI in a large series of ViV-TAVR procedures. Data were obtained from the multicenter VIVID Registry and included the main baseline and procedural characteristics, in-hospital and late (median follow-up: 13 months [interquartile range: 3 to 41 months]) outcomes analyzed according to the need of periprocedural PPI. All THVs except CoreValve, Cribier-Edwards, Sapien, and Sapien XT were considered to be new-generation THVs. A total of 1,987 patients without prior PPI undergoing ViV-TAVR from 2007 to 2020 were included. Of these, 128 patients (6.4%) had PPI after TAVR, with a significant decrease in the incidence of PPI with the use of new-generation THVs (4.7% vs. 7.4%; p = 0.017), mainly related to a reduced PPI rate with the Evolut R/Pro versus CoreValve (3.7% vs. 9.0%; p = 0.002). There were no significant differences in PPI rates between newer-generation balloon- and self-expanding THVs (6.1% vs. 3.9%; p = 0.18). In the multivariable analysis, older age (odds ratio [OR]: 1.05 for each increase of 1 year; 95% confidence interval [CI]: 1.02 to 1.07; p = 0.001), larger THV size (OR: 1.10; 95% CI: 1.01 to 1.20; p = 0.02), and previous right bundle branch block (OR: 2.04; 95% CI: 1.00 to 4.17; p = 0.05) were associated with an increased risk of PPI. There were no differences in 30-day mortality between the PPI (4.7%) and no-PPI (2.7%) groups (p = 0.19), but PPI patients exhibited a trend toward higher mortality risk at follow-up (hazard ratio: 1.39; 95% CI: 1.02 to 1.91; p = 0.04; p = 0.08 after adjusting for age differences between groups). In a contemporary large series of ViV-TAVR patients, the rate of periprocedural PPI was relatively low, and its incidence decreased with the use of new-generation THV systems. PPI following ViV-TAVR was associated with a trend toward increased mortality at follow-up.


Assessment of autonomic nervous system functions in patients with vitamin B12 deficiency by power spectral analysis of heart rate variability.
The purpose of this study was to test the autonomic nervous system function of patients with vitamin B12 deficiency (megaloblastic anemia) by measuring heart rate variability (HRV). The study population consisted of 17 vitamin B12 deficient patients and 15 age- and sex-matched normal volunteers. HRV was measured by power spectral analysis from which power of the low frequency (LF) peak (0.04-0.15 Hz), normalized units of the LF peak (LFNU), power of the high frequency (HF) peak (0.15-0.4 Hz), normalized units of the HF (HFNU), and ratio of power of LF to power of HF (LF:HF) were calculated. Vitamin B12 deficient patients had lower LF, LFNU, HF, HFNU, and LF:HF ratio than normal volunteers (P < 0.05). Decreases in sympathetic indices (LF and LFNU) were greater than those measured in parasympathetic indices (HF and HFNU). All HRV parameters correlated positively with the level of vitamin B12 (P < 0.001) and negatively with the duration of disease (P < 0.001). After vitamin B12 replacement the HRV parameters of patients and controls became comparable (P > 0.05). Our data suggest that autonomic sympathetic and parasympathetic nervous activities are decreased in patients with vitamin B12 deficiency, an abnormality that can be corrected by vitamin B12 replacement therapy.


Central neurocytoma of the fourth ventricle. Case report.
The authors report on a 17-year-old boy who suffered from slowly progressive and long-standing symptoms of ataxia, neck pain, and headache. Computerized tomography (CT) and magnetic resonance (MR) imaging revealed a tumor arising from the floor of the fourth ventricle that resulted in a moderate hydrocephalus. A partial resection was performed. Histological and immunohistological findings led to the diagnosis of an atypical central neurocytoma of the fourth ventricle. The imaging features on CT scanning, MR imaging, and proton MR spectroscopy studies, the clinical picture, and the prognosis of this very unusual tumor are discussed. Three cases of neurocytomas in the posterior fossa have been described to date; however, in all three cases some atypical aspects were present. In the present case, with the exception of the very unusual location, both imaging findings and clinical history perfectly met the definition of this rare tumor.


Differences in the effects of Hg(II) on DNA repair induced in Chinese hamster ovary cells by ultraviolet or X-rays.
The effect of relatively nontoxic levels of HgCl2 on semiconservative DNA synthesis and on DNA repair induced following treatment of intact cells with X-ray or ultraviolet (UV) light has been studied in cultured Chinese hamster ovary cells. In the presence of 1 microM HgCl2 the repair of DNA strand breaks induced by 450 rads of X-rays was reduced by 37%. If a treatment of 2.5 microM HgCl2 was given to cells for only 15 min prior to a 450-rad irradiation, the rate of repair was reduced even further with only 25% of the breaks being repaired in the first hour following irradiation. When comparable treatments of HgCl2 were given to Chinese hamster ovary cells in conjunction with UV irradiation there was no significant effect on either the number of initial strand scission events or the return to high molecular weight DNA following completion of repair. Only after exposure of cells to toxic levels of Hg(II) (higher concentrations or longer treatments) was there measurable inhibition of UV-induced repair as evidenced by a reduced rate of ligation of DNA to a high molecular weight form. Inhibition of the endonuclease step of UV repair was not observed since Hg(II)-treated cells exhibited the same level of strand scission immediately following UV as cells not treated with Hg(II). The observed differences in the effects of Hg(II) on two pathways for DNA repair indicate that the potential for synergistic action between Hg(II) and other DNA damaging agents will be determined in part by the repair pathways induced by each agent. Additionally, it was found that inhibition of semiconservative synthesis also occurs at low concentrations of HgCl2 similar to those affecting X-ray-induced repair. The presence of Hg-DNA adducts in the DNA at these concentrations may cause a reduction in normal replication to facilitate DNA repair.


p53 protein expression in malignant, pre-malignant and non-malignant lesions of the lip.
To elucidate the role of the p53 tumour suppressor gene in the pathogenesis of lip cancer. Expression of p53 was evaluated immunocytochemically in a retrospective study of formalin fixed, paraffin wax embedded tissue. Five cases each of four types of lip lesions were studied; these comprised squamous cell carcinoma (SCC), solar keratosis (SK), chronic hyperplastic candidosis (CHC), and lichen planus (LP). Five cases each of normal lip mucosa, SCC, and SK from sun exposed facial skin as well as LP, CHC, and SCC from buccal mucosa were also analysed. Immunolocalisation of p53 was scored semiquantitatively. The degree of apoptosis was also assessed in selected lesions by determining cell nuclear fragmentation. All SCCs from lip lesions were immunopositive for p53. All cases of SK and two of five CHC lip lesions were also p53 positive. Normal lip mucosa samples were p53 negative. Sun exposed skin lesions of SCC and SK were all positive for p53, but only three of five cases of SCC from the buccal mucosa had detectable levels of p53. p53 expression was not detected in CHC and LP lesions of the buccal mucosa. The aberrant expression of p53 is likely to occur early in the pathogenesis of lip cancer and may be related to exposure to the sun. The immunopositive p53 cells identified in the benign LP lesions do not necessarily correlate with commitment of cells within the lesion to programmed cell death. In light of the prior reports which indicate that p53 positive cells may progress to form malignant tumours, it is suggested that patients with p53 positive but otherwise benign lesions should be followed more closely.


Remote cognitive behaviour therapy for social anxiety disorder: A meta-analysis.
Remote cognitive behaviour therapy (CBT) for social anxiety disorder (SAD) has the potential to improve access to treatment by reducing economic, geographic, and psychological barriers. The aim of this study was to use a meta-analytic approach to examine the efficacy of the different remote CBT methods for treating SAD. A systematic electronic database search was used to identify 31 studies (n = 2905; mean age range: 24.73-41.65 years; mean female representation = 60.2 %). Pooled within-group analyses indicated large effect sizes from pre-treatment to post-treatment (Hedges' g = 1.06; 95 % CI: 0.96-1.16) and pre-treatment to follow up (g = 1.18; 95 % CI: 1.03-1.33) for remote CBT. Internet-delivered CBT (g = 1.08; 95 % CI: 0.98-1.19) and application-delivered CBT (g = 1.19; 95 % CI: 0.75-1.64) produced large within-group effect sizes. Bibliotherapy-delivered CBT (g = 0.79; 95 % CI: 0.45-1.13) produced medium within-group effect sizes. Pooled between-group findings indicate that remote CBT treatments were more effective than passive control (g = 0.87; 95 % CI: 0.70-1.03) and non-CBT remote treatments (g = 0.41; 95 % CI: 0.17-0.66), and were at least as effective, or slightly more effective, than face-to-face CBT treatments (g = 0.34; 95 % CI: 0.14-0.54). These findings have important implications for the dissemination of remote and stepped-care treatments for SAD.


Potential Uses of Blockchain Technology for Outcomes Research on Opioids.
The scale and severity of the opioid epidemic call for innovative, multipronged solutions. Research and development is key to accelerate the discovery and evaluation of interventions that support pain and substance use disorder management. In parallel, the use and integration of blockchain technology within research networks holds the potential to address some of the unique challenges facing opioid research. This paper discusses the applications of blockchain technology and illustrates potential ways in which it could be applied to strengthen the validity of outcomes research on the opioid epidemic. We reviewed published and gray literature to identify useful applications of blockchain, specifically those that address the challenges faced by opioid research networks and programs. We then convened a panel of experts to discuss the strengths, limitations, and feasibility of each application. Blockchain has the potential to address some of the issues surrounding health data management, including data availability, data sharing and interoperability, and privacy and security. We identified five primary applications of blockchain to opioids: clinical trials and pharmaceutical research, incentivizing data donation and behavior change, secure exchange and management of e-prescriptions, supply chain management, and secondary use of clinical data for research and public health surveillance. The published literature was limited, leading us to rely on gray literature, which was also limited in its discussion of the technical aspects of implementation. The technical expert panel provided additional context and an assessment of feasibility that was lacking in the literature. Research on opioid use and misuse is challenging because of disparate data stored across different systems, data and system interoperability issues, and legal requirements. These areas must be navigated to make data accessible, timely, and useful to researchers. Blockchain technologies have the potential to act as a facilitator in this process, offering a more efficient, secure, and privacy-preserving solution for data exchange. Among the 5 primary applications, we found that clinical trial research, supply chain management, and secondary use of data had the most examples in practice and the potential effectiveness of blockchain. More discussions and studies should focus on addressing technical questions concerning scalability and tackling practical concerns such as cost, standards, and governance around the implementation of blockchain in health care. Policy concerns related to balancing the need for data accessibility that also protects patient privacy and autonomy in revoking consent should also be examined.


Opioid-related overdose deaths among people experiencing homelessness, 2017 to 2021: A population-based analysis using coroner and health administrative data from Ontario, Canada.
To measure the change in proportion of opioid-related overdose deaths attributed to people experiencing homelessness and to compare the opioid-related fatalities between individuals experiencing homelessness and not experiencing homelessness at time of death. Population-based, time-trend analysis using coroner and health administrative databases from Ontario, Canada from 1 July 2017 and 30 June 2021. Quarterly proportion of opioid-related overdose deaths attributed to people experiencing homelessness. We also obtained socio-demographic and health characteristics of decedents, health-care encounters preceding death, substances directly contributing to death and circumstances surrounding deaths. A total of 6644 individuals (median age = 40 years, interquartile range = 31-51; 74.1% male) experienced an accidental opioid-related overdose death, among whom 884 (13.3%) were identified as experiencing homelessness at the time of death. The quarterly proportion of opioid-related overdose deaths attributed to people experiencing homelessness increased from 7.2% (26/359) in July-September 2017 to 16.8% (97/578) by April-June 2021 (trend test P < 0.01). Compared with housed decedents, those experiencing homelessness were younger (61.3 versus 53.1% aged 25-44), had higher prevalence of mental health or substance use disorders (77.1 versus 67.1%) and more often visited hospitals (32.1 versus 24.5%) and emergency departments (82.6 versus 68.5%) in the year prior to death. Fentanyl and its analogues more often directly contributed to death among people experiencing homelessness (94.0 versus 81.4%), as did stimulants (67.4 versus 51.6%); in contrast, methadone was less often present (7.8 versus 12.4%). Individuals experiencing homelessness were more often in the presence of a bystander during the acute toxicity event that led to death (55.8 versus 49.7%); and where another individual was present, more often had a resuscitation attempted (61.7 versus 55.1%) or naloxone administered (41.2 versus 28.9%). People experiencing homelessness account for an increasing proportion of fatal opioid-related overdoses in Ontario, Canada, reaching nearly one in six such deaths in 2021.


Hallmarks of epithelial to mesenchymal transition are detectable in Crohn's disease associated intestinal fibrosis.
Intestinal fibrosis and subsequent stricture formation represent frequent complications of Crohn's disease (CD). In many organs, fibrosis develops as a result of epithelial to mesenchymal transition (EMT). Recent studies suggested that EMT could be involved in intestinal fibrosis as a result of chronic inflammation. Here, we investigated whether EMT might be involved in stricture formation in CD patients. Human colonic tissue specimens from fibrotic areas of 18 CD and 10 non-IBD control patients were studied. Immunohistochemical staining of CD68 (marker for monocytes/macrophages), transforming growth factor-β1 (TGFβ1), β-catenin, SLUG, E-.cadherin, α-smooth muscle actin and fibroblast activation protein (FAP) were performed using standard techniques. In fibrotic areas in the intestine of CD patients, a large number of CD68-positive mononuclear cells was detectable suggesting an inflammatory character of the fibrosis. We found stronger expression of TGFβ1, the most powerful driving force for EMT, in and around the fibrotic lesions of CD patients than in non-IBD control patients. In CD patients membrane staining of β-catenin was generally weaker than in control patients and more cells featured nuclear staining indicating transcriptionally active β-catenin, in fibrotic areas. In these regions we also detected nuclear localisation of the transcription factor, SLUG, which has also been implicated in EMT pathogenesis. Adjacent to the fibrotic tissue regions, we observed high levels of FAP, a marker of reactive fibroblasts. We demonstrate the presence of EMT-associated molecules in fibrotic lesions of CD patients. These findings support the hypothesis that EMT might play a role for the development of CD-associated intestinal fibrosis.


Effects of creative expression therapy on Chinese elderly patients with dementia: an exploratory randomized controlled trial.
Purpose: This study aimed to evaluate the effect of creative expression (CE) therapy on cognition, communication, emotion, and quality-of-life in people with dementia. Methods: One hundred individuals were included in this study, of whom 91 completed the study (mean age=84.33). The participants were randomly assigned to an intervention group (n=43) and a control group (n=48), and received the CE program or standard cognitive (SC) training twice a week for 6 weeks, respectively. Both groups were submitted to extensive neuropsychological tests, as follows - Mini-Mental State Examination (MMSE), Quality of Life-Alzheimer's Disease (QOL-AD), Cornell Scale for Depression in Dementia (CSDD), Functional Assessment of Communication Skills (FACS) at baseline, 1-, and 4 -weeks post-intervention, and the Observed Emotion Rating Scale (OERS) was measured during the intervention period at weeks 3 and 6. Results: The participants demonstrated significant improvements in cognitive function, quality-of-life, depression degree, communication ability, and emotion status (P<0.05) at post-intervention, which were maintained at 1-month follow-up. Conclusion: This study provides preliminary evidence that CE therapy developed in the study benefits elderly Chinese with dementia. The findings indicated that non-pharmacological intervention programs - CE therapy - can be applied in the management of neuropsychiatric symptoms of dementia.


Sacroiliac joint arthrodesis for chronic sacroiliac joint pain: an anterior approach and clinical outcomes with a minimum 5-year follow-up.
OBJECTIVE The authors evaluated the outcomes of sacroiliac joint (SIJ) arthrodesis via an original anterior approach to the upper anterior surface of the SIJ in patients with a minimum of 5 years' follow-up. METHODS The authors performed anterior SIJ arthrodesis in 45 patients between 2001 and 2015. Of these patients, 27 (11 men and 16 women; mean age at surgery 49 [24-86] years) were followed up for a minimum of 5 years (average 113 months, range 61-157 months). In the 14 patients in the earlier period of this study, the authors used an anterior approach to expose the SIJ by separating the iliac muscle from the iliac bone and performed internal fixation. In the 13 patients later in the study, the authors changed to a pararectal approach, which involved an incision along the lateral border of the rectus abdominal muscle. Then, extraperitoneally, the upper anterior surface of the SIJ was exposed between the psoas major muscle and the iliac muscle. RESULTS Among the 27 patients, 21 had unilateral anterior arthrodesis alone, 4 required additional posterior arthrodesis, and 2 required pelvic ring arthrodesis because of later pain on the opposite side. In the 21 patients with a unilateral anterior arthrodesis, outcome according to the modified Macnab criteria was excellent in 7, good in 11, and fair in 3. Outcomes were excellent, good, fair, and poor in 1 patient each among the 4 with additional posterior fusion. Outcomes were good and poor for 1 patient each among those with pelvic ring arthrodesis. All 27 patients demonstrated bone union of the SIJ on CT. Lateral femoral cutaneous neuralgia developed in 7 of the 27 patients; 6 patients had undergone the initial anterior method and 1 the later method. CONCLUSIONS Anterior SIJ arthrodesis was effective in most patients with severe SIJ pain resistant to conservative therapy. This approach has the advantage of direct curettage and bone graft into the wide area of the SIJ, which result in good bone union. In particular, the authors' current pararectal approach could decrease the potential risk of lateral cutaneous injury.


Histopathologic and immunohistochemical findings in two white-tailed deer fawns persistently infected with Bovine viral diarrhea virus.
Bovine viral diarrhea virus (BVDV) is an important pathogen of domestic cattle. Serologic, experimental, and individual case studies explored the presence and pathogenesis of the virus in wild ungulates; however, there remain large gaps in knowledge regarding BVDV infection in nonbovine species. Live twins were born from a white-tailed deer (Odocoileus virginianus) doe infected with noncytopathic BVDV during its first trimester of pregnancy. The twins died at 1 day of age from trauma unrelated to the infection, and tissues were collected for histologic and immunohistochemical examination. The most significant histologic abnormality was diffuse depletion of B-lymphocytes in both fawns. The BVDV antigen was distributed widely throughout many tissues and cell types, most notably epithelium and vascular endothelium, consistent with that reported in cattle. In contrast to cattle, lymphocytes exhibited only very rare positive staining.


[Renal form of dissecting aortic aneurysm].
The clinical data have been compared with the biopsy results of 24 patients who died of dissecting aneurysm of the aorta. The clinico-anatomical data permit the authors to conclude that if dissection of the walls of the abdominal aorta takes place at the level of emerging renal arteries the dissecting aneurysm assumes the character of the renal disease with the typical pain syndrome resembling "renal colic". A number of symptoms are described typical for the dissecting aneurysm distinguishing it from the true kidney disease.


Case of infiltrative optic neuropathy with hypertrophic pachymeningitis as a manifestation of en plaque meningioma.
We describe a case of infiltrative optic neuropathy with hypertrophic pachymeningitis noted on MRI of the brain, presenting a diagnostic dilemma with a wide variety of differential diagnoses to consider. Our patient is a middle-aged woman with a 20-year history of migranous-sounding headaches who was incidentally found to have worsening vision in her left eye during a routine driving test visual acuity check. Neurological examination revealed a left grade III relative afferent pupillary defect and a central scotoma with red desaturation. Subsequent MRI of her brain and anterior visual pathway revealed features suggestive of an infiltrative left optic neuropathy with hypertrophic pachymeningitis. An extended workup including diagnostic lumbar puncture and blood tests for possible autoimmune, infective and neoplastic causes proved unyielding. Eventually, an endoscopic transsphenoidal biopsy helped to clinch the diagnosis of a (meningothelial subtype) WHO grade 1 meningioma as the cause of her clinical and radiological presentation.


Light caustics of hydrodynamic solitons illuminated by a laser beam.
Properties of caustics of plane curves are used for interpretation of optical experiments with hydrodynamic solitons in a one-dimensional water channel. The water-free surface acts as a curvilinear plane mirror for incoming light beams. Experiments with single solitons and with couples of colliding solitons are presented and discussed within the framework of geometrical optics.


Association of Postoperative Clinical Outcomes With Sarcopenia, Frailty, and Nutritional Status in Older Patients With Colorectal Cancer: Protocol for a Prospective Cohort Study.
Older patients account for a significant proportion of patients undergoing colorectal cancer surgery and are vulnerable to a number of preoperative risk factors that are not often present in younger patients. Further, three preoperative risk factors that are more prevalent in older adults include frailty, sarcopenia, and malnutrition. Although each of these has been studied in isolation, there is little information on the interplay between them in older surgical patients. A particular area of increasing interest is the use of urine metabolomics for the objective evaluation of dietary profiles and malnutrition. Herein, we describe the design, cohort, and standard operating procedures of a planned prospective study of older surgical patients undergoing colorectal cancer resection across multiple institutions in the United Kingdom. The objectives are to determine the association between clinical outcomes and frailty, nutritional status, and sarcopenia. The procedures will include serial frailty evaluations (Clinical Frailty Scale and Groningen Frailty Indicator), functional assessments (hand grip strength and 4-meter walk test), muscle mass evaluations via computerized tomography morphometric analysis, and the evaluation of nutritional status via the analysis of urinary dietary biomarkers. The primary feasibility outcome is the estimation of the incidence rate of postoperative complications, and the primary clinical outcome is the association between the presence of postoperative complications and frailty, sarcopenia, and nutritional status. The secondary outcome measures are the length of hospital stay, 30-day hospital readmission rate, and mortality rate at days 30 and 90. Our study was approved by the National Health Service Research Ethics Committee (reference number: 19/WA/0190) via the Integrated Research Application System (project ID: 231694) prior to subject recruitment. Cardiff University is acting as the study sponsor. Our study is financially supported through an external, peer-reviewed grant from the British Geriatrics Society and internal funding resources from Cardiff University. The results will be disseminated through peer-review publications, social media, and conference proceedings. As frailty, sarcopenia, and malnutrition are all areas of common derangement in the older surgical population, prospectively studying these risk factors in concert will allow for the analysis of their interplay as well as the development of predictive models for those at risk of commonly tracked surgical complications and outcomes. PRR1-10.2196/16846.


The in vitro Analysis of Quality of Ovarian Follicle Culture Systems Using Time-Lapse Microscopy and Quantitative Real-Time PCR.
The aim of ovarian follicle in vitro culture is to obtain mature oocytes. To evaluate the efficiency of in vitro culture system, the status of the cultured oocyte can be analyzed. The preantral ovarian follicles retrieved from 14-day-old C57Bl/6J mice were cultured in 3D alginate hydrogel. The status of oocytes obtained from mature (3 months old, group A) and immature (3 weeks old, group B) mice was compared to the status of oocytes retrieved from ovarian follicles cultured in vitro (Group C) using qRT-PCR analysis and time-lapse microscopy. In the qRT-PCR analysis, 8 samples for group A (80 oocytes), 8 samples for group B (80 oocytes), and 6 samples for group C (60 oocytes) were included. Time-lapse analysis was performed in group A (oocytes n=31), group B (n=45), and group C (n=21). Statistical analysis was done by Kruskal-Wallis and chi-square tests and differences were considered statistically significant if p<0,05. The diameter of group C oocytes is lower in comparison to group A oocytes (67 μm vs. 75 μm, correspondingly). Groups B and C oocytes exhibited delayed meiosis in comparison to group A oocytes. Expression levels of six oocyte maturation genes (Ccnb, CDK1, Ccnh, Wee2, Mos and Epab) were evaluated using qRT-PCR analysis. Expression levels of Ccnh and Epab are lowered in group C oocytes compared to the expression levels of these genes in groups A and B oocytes (p< 0.05). Oocytes obtained after ovarian follicles in vitro culture have reduced development competence, future fundamental changes of in vitro culture systems can be expected.


Colorectal cancer in young patients: characteristics and outcome.
Colorectal cancer is predominantly a disease of the elderly population, but this disease is unusual in patients 40 years of age or under, and controversy persists as to prognosis in this subset of patients. The aim of this study was to determine the clinicopathologic features and their impact on patients survival of colorectal cancer in patients aged 40 years or younger, and to compare them with those of older patients. The records of 466 patients with non-metastatic colorectal adenocarcinoma who were referred between 1991 and 1999 to the University of Istanbul, Institute of Oncology, following curative surgery were retrospectively analysed. The clinicopathologic features of 84 (18%) colorectal cancers (group A; male:female ratio 48:36) which occurred in patients aged 40 years or younger were compared with 382 colorectal cancers in older patients (group B; male:female ratio 194:188). Patient gender, performance status, T stage, N stage, TNM stage, histologic grade, location of tumor, lymphatic invasion, serum levels of LDH and CEA, and survival rates were compared as prognostic factors. There was no statistically significant difference between group A and group B with respect to patient gender, performance status, T stage, N stage, TNM stage, histologic grade, location of tumor, serum levels of LDH and CEA, and survival rates of colorectal cancers. The proportion of lymphatic invasion was present in 27% of patients in group A vs. 12% in group B. With median follow-up of 69 months, the overall 5-year survival rate was 61% in group A and 56% in group B. In the univariate survival analysis according to age groups (group A and B), advanced TNM stage, location of rectal tumor, presence of lymphatic invasion, and presence of high serum LDH and CEA levels are predictors of poorer survival in young patients with colorectal cancer. In the Cox-Regression analysis, location of tumor and TNM stage were determined as independent prognostic factors for survival. This study revealed no difference in clinicopathologic characteristics in patients with colorectal cancer aged 40 years or younger compared with those aged above 40 years. However, in patients aged 40 years or younger, distal location of tumor and advanced stage should be considered as poor prognostic factors for overall survival.


Macrophage migration inhibitory factor levels correlate with an infection in trauma patients.
The role of migration inhibitory factor (MIF) is best understood in septic shock and septic disease; however, the role of MIF in a secondary infection after trauma has not yet been completely studied. This study aimed to evaluate the role of MIF in trauma patients. The patients in the study population were divided into two groups according to the results of their MIF levels. The initial MIF levels, trauma mechanism, revised trauma score, survival rate, length of stay (LOS) in the intensive care unit (ICU), level of leukocytes, and level of C-reactive protein (CRP) were compared between the groups. Overall, 116 patients were enrolled from August 1, 2014 to July 31, 2015. LOS in ICU in the elevated MIF group was 5.67±7.54 days compared with 2.09±2.26 days in the normal MIF group. Further, CRP level in the elevated MIF group was higher than that in the normal MIF group. In a place such as the department of emergency medicine, it is critical and important for emergency physicians to make a proper judgment and to prepare for the worst scenario. Therefore, the utilization of MIF level in trauma patients has a possibility for assisting emergency physicians.


Vascularized Cardiac Spheroids as Novel 3D in vitro Models to Study Cardiac Fibrosis.
Spheroid cultures are among the most explored cellular biomaterials used in cardiovascular research, due to their improved integration of biochemical and physiological features of the heart in a defined architectural three-dimensional microenvironment when compared to monolayer cultures. To further explore the potential use of spheroid cultures for research, we engineered a novel in vitro model of the heart with vascularized cardiac spheroids (VCSs), by coculturing cardiac myocytes, endothelial cells, and fibroblasts isolated from dissociated rat neonatal hearts (aged 1-3 days) in hanging drop cultures. To evaluate the validity of VCSs in recapitulating pathophysiological processes typical of the in vivo heart, such as cardiac fibrosis, we then treated VCSs with transforming growth factor beta 1 (TGFβ1), a known profibrotic agent. Our mRNA analysis demonstrated that TGFβ1-treated VCSs present elevated levels of expression of connective tissue growth factor, fibronectin, and TGFβ1 when compared to control cultures. We demonstrated a dramatic increase in collagen deposition following TGFβ1 treatment in VCSs in the PicroSirius Red-stained sections. Doxorubicin, a renowned cardiotoxic and profibrotic agent, triggered apoptosis and disrupted vascular networks in VCSs. Taken together, our findings demonstrate that VCSs are a valid model for the study of the mechanisms involved in cardiac fibrosis, with the potential to be used to investigate novel mechanisms and therapeutics for treating and preventing cardiac fibrosis in vitro.


A general framework for frequency domain multi-channel signal processing.
The authors provide a general framework for performing processing of stationary multichannel (MC) signals that is linear shift-invariant within channel and shift varying across channels. Emphasis is given to the restoration of degraded signals. It is shown that, by utilizing the special structure of semiblock circulant and block diagonal matrices, MC signal processing can be easily carried out in the frequency domain. The generalization of many frequency-domain single-channel (SC) signal processing techniques to the MC case is presented. It is shown that in MC signal processing each frequency component of a signal and system is presented, respectively, by a small vector and a matrix (of size equal to the number of channels), while in SC signal processing each frequency component in both cases is a scalar.


Genome-Wide Screen for Genes Involved in Caenorhabditis elegans Developmentally Timed Sleep.
In Caenorhabditis elegans, Notch signaling regulates developmentally timed sleep during the transition from L4 larval stage to adulthood (L4/A) . To identify core sleep pathways and to find genes acting downstream of Notch signaling, we undertook the first genome-wide, classical genetic screen focused on C. elegans developmentally timed sleep. To increase screen efficiency, we first looked for mutations that suppressed inappropriate anachronistic sleep in adult hsp::osm-11 animals overexpressing the Notch coligand OSM-11 after heat shock. We retained suppressor lines that also had defects in L4/A developmentally timed sleep, without heat shock overexpression of the Notch coligand. Sixteen suppressor lines with defects in developmentally timed sleep were identified. One line carried a new allele of goa-1; loss of GOA-1 Gαo decreased C. elegans sleep. Another line carried a new allele of gpb-2, encoding a Gβ5 protein; Gβ5 proteins have not been previously implicated in sleep. In other scenarios, Gβ5 GPB-2 acts with regulators of G protein signaling (RGS proteins) EAT-16 and EGL-10 to terminate either EGL-30 Gαq signaling or GOA-1 Gαo signaling, respectively. We found that loss of Gβ5 GPB-2 or RGS EAT-16 decreased L4/A sleep. By contrast, EGL-10 loss had no impact. Instead, loss of RGS-1 and RGS-2 increased sleep. Combined, our results suggest that, in the context of L4/A sleep, GPB-2 predominantly acts with EAT-16 RGS to inhibit EGL-30 Gαq signaling. These results confirm the importance of G protein signaling in sleep and demonstrate that these core sleep pathways function genetically downstream of the Notch signaling events promoting sleep.


[S.A.PH.O. syndrome: a still little known clinical syndrome].
S.A.P.H.O. syndrome is characterized by the association, even not simultaneous, of osteoarticular and cutaneous manifestations. This review has the purpose to clear up some features of clinical manifestations and the osteo-articular involvement. Articular mainly feature is the involvement of anterior chest wall, that begins with slow evolving pain. Skin involvement is characterized by acne conglobata and pustolosis palmaris-plantaris. Instrumental investigations that fit better for studying the anterior chest wall, complex region, are bone scintigraphy, computed tomography and nuclear magnetic resonance, with their domain pattern. Symptomatic therapy are mostly represented by NSAIDs, but still opiate drugs can be prescribed; corticosteroids have variable and unforeseeable efficacy. Bisphosfonates are usually utilized due to their anti-osteoclastic effects. Finally, because of documented incremented production of TNFalpha, TNFalpha blocking agents should be effectively utilized.


Incidence of Vibrio cholerae and related vibrios in a coastal lagoon and seawater influenced by lake discharges along an annual cycle.
Most probable numbers of Vibrio cholerae and related vibrios were determined in Albufera Lake, Valencia, Spain, and in coastal waters under the influence of the lake discharges over the course of an annual cycle. The influence of temperature, kind of water, and characteristics of the different sampling sites on the numbers of vibrios recovered was evaluated. Maximum recovery of vibrios reached 10(3)/ml in both types of waters analyzed. V. cholerae numbers reached 10(3)/ml in the lake and 10(2) in one of the coastal sites. Frequently during the warm season, all vibrios isolated were identified as V. cholerae. Occasionally, no V. cholerae was recovered. The recovery of vibrios was significantly influenced by the temperature of the water and the type of water analyzed. Most of the V. cholerae isolates were included in Heiberg groups I and II, and nearly 50% of the strains used chitin as sole carbon source. Indole was not produced by 100% of the strains. All strains tested were non-O1 serovars.


Beta-lactamase-producing nontypeable Haemophilus influenzae fails to protect Streptococcus pneumoniae from amoxicillin during experimental acute otitis media.
Acute otitis media (AOM) is the most common reason for outpatient antimicrobial therapy. Mixed infections pose a potential problem, since the first-line drug used for the treatment of AOM, amoxicillin, can be neutralized by beta-lactamase-producing pathogens of the upper respiratory tract. To study the effects of a 5-day course of amoxicillin on a mixed middle ear infection, rats were challenged with Streptococcus pneumoniae alone or in combination with beta-lactamase-producing nontypeable Haemophilus influenzae. Amoxicillin was introduced at the clinical peak of the infection. Local and systemic changes were monitored by otomicroscopy, bacterial culture, and analysis of histological changes and the expression of the transforming growth factor beta (TGF-beta) gene. beta-Lactamase-producing H. influenzae did not demonstrate an ability to protect S. pneumoniae. Amoxicillin eradicated the pneumococci in all treated animals but increased to some degree the ability of H. influenzae to persist at the site of infection. Thus, only an insignificant acceleration of the resolution of the AOM caused by a mixture of pathogens was observed during treatment. Moderate to major morphological changes could not be avoided by treatment of the mixed infections, but a slight downregulation of TGF-beta expression was observed. In contrast to infections caused by a single pathogen, the mixed infections induced white plaques in the tympanic membrane at a remarkably high frequency independent of treatment. These experimental findings constitute support for further studies of antimicrobial drugs and AOM caused by bacteria with and without mechanisms of antibiotic resistance.


Preterm birth: Transition to adulthood.
Preterm birth is associated with greater difficulty with transitions from childhood to adolescence to adulthood. Adolescents and young adults born preterm have higher rates of cerebral palsy, intellectual disability, cognitive impairment, learning disability, executive dysfunction, attention deficit disorder, and social-emotional difficulties than their peers born fullterm. Compared to individuals born fullterm, more preterm survivors have major neurodevelopmental or psychiatric disability and need financial supports and societal resources. Neuroimaging studies of adolescents and adults born preterm report higher rates of brain injury, differences in regional brain structure, and different brain circuits than in those born fullterm. Making the transition to adulthood is more difficult for young adults who were born preterm than their peers born fullterm, in that fewer complete high school and higher education, find and keep meaningful employment, and live independently from their parents. As a group, they do not tend to be risk-takers, and they have lower rates of alcohol abuse, use of illicit drugs, and criminal offenses than do their peers. Despite their many challenges, the majority of adults born preterm function well, form personal relationships, integrate well into their community, and are as satisfied with their quality of life as are their peers. Concerns regarding current preterm infants, with more extremely preterm survivors, overwhelming our medical, educational, and societal resources should serve as an impetus for research on prevention of preterm births and brain injury, as well as how to support and promote their ongoing neuromaturation and recovery from injury.


Local VEGF inhibition prevents ovarian alterations associated with ovarian hyperstimulation syndrome.
The relationship between human chorionic gonadotropin and ovarian hyperstimulation syndrome (OHSS) is partially mediated by vascular endothelial growth factor A (VEGF). The aim of this study was to investigate the effects of VEGF inhibition on the development of corpora lutea (CL) and cystic structures, steroidogenesis, apoptosis, cell proliferation, endothelial cell area, VEGF receptors (KDR and Flt-1), claudin-5 and occludin levels in ovaries from an OHSS rat model. The VEGF inhibitor used (VEGF receptor-1 (FLT-1)/Fc chimera, TRAP) decreased the concentrations of progesterone and estradiol as well as the percentage of CL and cystic structures in OHSS rats, and increased apoptosis in CL. Endothelial cell area in CL and KDR expression and its phosphorylation were increased, whereas claudin-5 and occludin levels were decreased in the OHSS compared to the control TRAP reversed these parameters. Our findings indicate that VEGF inhibition prevents the early onset of OHSS and decreases its severity in rats.


The duration of protection of school-aged BCG vaccination in England: a population-based case-control study.
Evidence of protection from childhood Bacillus Calmette-Guerin (BCG) against tuberculosis (TB) in adulthood, when most transmission occurs, is important for TB control and resource allocation. We conducted a population-based case-control study of protection by BCG given to children aged 12-13 years against tuberculosis occurring 10-29 years later. We recruited UK-born White subjects with tuberculosis and randomly sampled White community controls. Hazard ratios and 95% confidence intervals (CIs) were estimated using case-cohort Cox regression, adjusting for potential confounding factors, including socio-economic status, smoking, drug use, prison and homelessness. Vaccine effectiveness (VE = 1 - hazard ratio) was assessed at successive intervals more than 10 years following vaccination. We obtained 677 cases and 1170 controls after a 65% response rate in both groups. Confounding by deprivation, education and lifestyle factors was slight 10-20 years after vaccination, and more evident after 20 years. VE 10-15 years after vaccination was 51% (95% CI 21, 69%) and 57% (CI 33, 72%) at 15-20 years. Subsequently, BCG protection appeared to wane; 20-25 years VE = 25% (CI -14%, 51%) and 25-29 years VE = 1% (CI -84%, 47%). Based on multiple imputation of missing data (in 17% subjects), VE estimated in the same intervals after vaccination were similar [56% (CI 33, 72%), 57% (CI 36, 71%), 25% (-10, 48%), 21% (-39, 55%)]. School-aged BCG vaccination offered moderate protection against tuberculosis for at least 20 years, which is longer than previously thought. This has implications for assessing the cost-effectiveness of BCG vaccination and when evaluating new TB vaccines.


The Confluence of Accelerated Regulatory and Health Technology Assessment Access Pathways.
There is a growing interest in aligning accelerated regulatory pathways with flexible access and reimbursement pathways to expedite the equitable availability of high-quality, safe, and effective medicines that provide a value-based approach to meeting society's most important healthcare needs. The Centre for Innovation in Regulatory Science (CIRS) identified key issues regarding the confluence of regulatory and health technology assessment processes from discussions and presentations given by international regulators, health technology assessment bodies, payers, patient representatives, and multinational pharmaceutical company representatives on this topic at CIRS workshops held in 2014 and 2017 that focused on the commonalties and differences across these pathways. Recent publications have also been highlighted. The barriers to and opportunities for aligning stakeholder expectations and needs were investigated and recommendations provided. Early dialogue among the stakeholders is the process that will likely provide the greatest return on investment of time and effort to identify, develop, review, and recommend important new medicines, especially those that address an unmet medical need.


Sedation and general anaesthesia in children undergoing MRI and CT: adverse events and outcomes.
Quality assurance data were collected prospectively for children who were sedated (n = 922) or given general anaesthesia (n = 140) for magnetic resonance imaging (MRI) or computerized tomography (CT). The data included patient characteristics, concurrent medication, adequacy of sedation, adverse events and requirement for escalated care. The quality of scans was evaluated. Reasons for preselection of general anaesthesia included previously failed sedation (28%), potential for failed sedation (32%) and perceived medical risk (14%). Hypoxaemia occurred in 2.9% of sedated children, and was more common in children classified as ASA III or IV. Sedation was inadequate for 16% of children and failed in 7%. Failed sedation was associated with greater age (P = 0.009), higher ASA status (P = 0.04) and use of benzodiazepines as sole sedatives (P < 0.03). More of the children who underwent general anaesthesia were ASA III or IV than sedated children, yet the procedure was successful in all the children who underwent general anaesthesia, with one incident of laryngospasm. Excessive motion was noted in 12% of scans of sedated children and 0.7% of those completed with general anaesthesia. We conclude that sedation of children for MRI and CT is associated with risks of hypoxaemia and of inadequate or failed sedation. These adverse events were more likely to occur in older children, those with a higher ASA status and those in whom benzodiazepines had been used as sole sedatives. For a preselected high-risk group of children, general anaesthesia may make MRI and CT scans more successful with minimal adverse events.


Erosive pustular dermatosis of the scalp secondary to Erlotinib: A rare occurrence with trichoscopic perspective.
Epidermal growth factor receptor inhibitors are anti-tumour agents that are frequently used for the treatment of neoplastic disorders. In addition to their cutaneous adverse effects, these drugs can rarely lead to erosive pustular dermatosis of the scalp. We report a case of a 67-year-old female who developed erosive pustular dermatosis of the scalp after being started on erlotinib from a trichoscopic perspective, which has been described in literature only once till now.


Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies.
Lennox-Gastaut syndrome (LGS), a childhood-onset severe developmental and epileptic encephalopathy (DEE), is an entity that encompasses a heterogenous group of aetiologies, with no single genetic cause. It is characterised by multiple seizure types, an abnormal EEG with generalised slow spike and wave discharges and cognitive impairment, associated with high morbidity and profound effects on the quality of life of patients and their families. Drug-refractory seizures are a hallmark and treatment is further complicated by its multiple morbidities, which evolve over the patient's lifetime. This review provides a comprehensive overview of the current and future options for the treatment of seizures associated with LGS. Six treatments are specifically indicated as adjunct therapies for the treatment of seizures associated with LGS in the US: lamotrigine, clobazam, rufinamide, topiramate, felbamate and most recently cannabidiol. These therapies have demonstrated reductions in drop seizures in 15%-68% of patients across trials, with responder rates (≥ 50% reduction in drop seizures) of 37%-78%. Valproate is still the preferred first-line treatment, generally in combination with lamotrigine or clobazam. Other treatments frequently used off-label include the broad spectrum anti-epileptic drugs (AED) levetiracetam, zonisamide and perampanel, while recent evidence from observational studies has indicated that a newer AED, the levetiracetam analogue brivaracetam, may be effective and well tolerated in LGS patients. Other treatments in clinical development include fenfluramine in late phase III, perampanel, soticlestat-OV953/TAK-953, carisbamate and ganaxolone. Non-pharmacologic interventions include the ketogenic diet, vagus nerve stimulation and surgical interventions; these are also expanding, with the potential for less invasive techniques for corpus callosotomy that have promise for reducing complications. However, despite these advancements, patients continue to experience a significant burden. Because LGS is not a single entity, tailoring of treatment is needed as opposed to a 'one size fits all' approach. Further research is needed into the underlying aetiologies and pathophysiology of LGS, together with advancements in treatments that encompass the spectrum of seizures associated with this complex syndrome.


An Analysis of the Epidemic of Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae: Convergence of Two Evolutionary Mechanisms Creates the "Perfect Storm".
Carbapenem resistance is a critical healthcare challenge worldwide. Particularly concerning is the widespread dissemination of Klebsiella pneumoniae carbapenemase (KPC). Klebsiella pneumoniae harboring blaKPC (KPC-Kpn) is endemic in many areas including the United States, where the epidemic was primarily mediated by the clonal dissemination of Kpn ST258. We postulated that the spread of blaKPC in other regions occurs by different and more complex mechanisms. To test this, we investigated the evolution and dynamics of spread of KPC-Kpn in Colombia, where KPC became rapidly endemic after emerging in 2005. We sequenced the genomes of 133 clinical isolates recovered from 24 tertiary care hospitals located in 10 cities throughout Colombia, between 2002 (before the emergence of KPC-Kpn) and 2014. Phylogenetic reconstructions and evolutionary mapping were performed to determine temporal and genetic associations between the isolates. Our results indicate that the start of the epidemic was driven by horizontal dissemination of mobile genetic elements carrying blaKPC-2, followed by the introduction and subsequent spread of clonal group 258 (CG258) isolates containing blaKPC-3. The combination of 2 evolutionary mechanisms of KPC-Kpn within a challenged health system of a developing country created the "perfect storm" for sustained endemicity of these multidrug-resistant organisms in Colombia.


Statistical modeling of human liver incorporating the variations in shape, size, and material properties.
The liver is one of the most frequently injured abdominal organs during motor vehicle crashes. Realistic numerical assessments of liver injury risk for the entire occupant population require incorporating inter-subject variations into numerical models. The main objective of this study was to quantify the shape variations of human liver in a seated posture and the statistical distributions of its material properties. Statistical shape analysis was applied to construct shape models of the livers of 15 adult human subjects, recorded in a typical seated (occupant) posture. The principal component analysis was then utilized to obtain the modes of variation, the mean model, and 95% statistical boundary shape models. In addition, a total of 52 tensile tests were performed on the parenchyma of three fresh human livers at four loading rates (0.01, 0.1, 1, and 10 s^-1) to characterize the rate-dependent and failure properties of the human liver. A FE-based optimization approach was employed to identify the material parameters of an Ogden material model for each specimen. The mean material parameters were then determined for each loading rate from the characteristic averages of the stress-strain curves, and a stochastic optimization approach was utilized to determine the standard deviations of the material parameters. Results showed that the first five modes of the human liver shape models account for more than 60% of the overall anatomical variations. The distributions of the material parameters combined with the mean and statistical boundary shape models could be used to develop probabilistic finite element (FE) models, which may help to better understand the variability in biomechanical responses and injuries to the abdominal organs under impact loading.


Quantifying economic-social-environmental trade-offs and synergies of water-supply constraints: An application to the capital region of China.
Sustainable water management is one of the sustainable development goals (SDGs) and is characterized by a high level of interdependencies with other SDGs from regional to global scales. Many water assessment studies are restricted to silo thinking, mostly focusing on water-related consequences, while lacking a quantification of trade-offs and synergies of economic, social, and environmental dimensions. To fill this knowledge gap, we propose a "nexus" approach that integrates a water supply constrained multi-regional input-output (mixed MRIO) model, scenario analysis, and multi-criteria decision analysis (MCDA) to quantify the trade-offs and synergies at the sectoral level for the capital region of China, i.e. the Beijing-Tianjin-Hebei urban agglomeration. A total of 120 industrial transition scenarios including nine major industries with high water-intensities and water consumption under current development pathways were developed to facilitate the trade-off and synergy analysis between economic loss, social goals (here, the number of jobs) and environmental protection (with grey water footprint representing water pollution) triggered by water conservation measures. Our simulation results show that an imposition of a tolerable water constraint (a necessary water consumption reduction for regional water stress level to move from severe to moderate) in the region would result in an average economic loss of 68.4 (± 16.0) billion Yuan (1 yuan ≈ 0.158 USD$ in 2012), or 1.3 % of regional GDP, a loss of 1.94 (± 0.18) million jobs (i.e. 3.5 % of the work force) and a reduction of 1.27 (± 0.40) billion m3 or about 2.2% of the regional grey water footprint. A tolerable water rationing in water-intensive sectors such as Agriculture, Food and tobacco processing, Electricity and heating power production and Chemicals would result in the lowest economic and job losses and the largest environmental benefits. Based on MCDA, we selected the 10 best scenarios with regard to their economic, social and environmental performances as references for guiding future water management and suggested industrial transition policies. This integrated approach could be a powerful policy support tool for 1) assessing trade-offs and synergies among multiple criteria and across multiple region-sectors under resource constraints; 2) quantifying the short-term supply-chain effects of different containment measures, and 3) facilitating more insightful evaluation of SDGs at the regional level so as to determine priorities for local governments and practitioners to achieve SDGs.


Health-Related Quality of Life Among Caregivers of Individuals With Spinal Cord Injury.
The consequences of spinal cord injury (SCI) not only affect patients' health-related quality of life (HRQoL) but also extend to the entire family. The health condition the injury imposes requires the participation of a family caregiver, who will be responsible for taking care of the individual in a disabling condition. This is an observational, exploratory study using a cross-sectional design that aimed to study the association between HRQoL and gender, age, presence of comorbidities, and characteristics of the care among caregivers of individuals with SCI with the purpose of identifying potential factors that are associated with HRQoL in this population. Participants were 59 caregivers of individuals with traumatic SCI. The data were collected by consulting the patient histories and applying questionnaires. To assess the caregivers' HRQoL, the Short Form-36 was used. For analysis, exploratory and inferential statistics were used. Most of the caregivers of the individuals with SCI were female, with a mean age of 44.8 years. The domains that most contributed to a worse HRQoL were physical aspects, pain, vitality, and emotional aspects. No statistically significant associations were found between HRQoL and the variables gender, hours per day spent on care, and length of activity as caregiver. The associations between HRQoL and self-reported diseases and age were statistically significant. The results support the planning of nursing interventions from the perspective of aspects of the care demands, which can affect the caregiver's HRQoL. Interventions to prepare the individuals with SCI and their caregivers are a strategy aimed at improving the HRQoL of both.


Detection of high concentrations of organic acids in fish emulsion and their role in pathogen or disease suppression.
Fish emulsion (FE) added to a sandy-loam soil at 1 and 2% rates reduced the viability of Verticillium dahliae microsclerotia by 39 and 74% in 1 day, 87 and 98% in 3 days, and 95 and 99% in 6 days, respectively. The immediate kill of microsclerotia indicated that FE contains toxic substances. We found in FE high concentrations (400 mmol/liter) of organic acids, including some known toxicants. Glycolic, acetic, formic, n-butyric, and propionic acids were the major organic acids detected in FE at the proportions of 52.5, 26.9, 7.9, 7.2, and 4.7%, respectively. In solution assays, the viability of V. dahliae microsclerotia treated for 24 h in 1, 2, 5, and 10% FE (pH 3.6 to 3.0) or a mixture of organic acids (pH 4.1 to 3.9) equivalent to the proportions in FE was reduced by 74, 94, 97, and 99% or 81, 91, 98, and 99%, respectively. The viability of microsclerotia was increased when the treatment solutions were buffered to pH 6.0. The organic acids mixtures and formic (0.025%) and acetic (0.1%) acids were toxic to Pythium ultimum. A mixture of organic acids (1, 2, and 4%) provided immediate protection of cucumber seedlings from damping-off in P. ultimum-infested muck and sandy-loam soils but not in peat-based mix. FE (1 and 2%) provided immediate protection of cucumber seedlings from damping-off in an infested muck soil, and disease protection was consistent when planting was delayed for 7, 14, and 28 days after adding FE. FE (1, 2, and 4%) did not provide immediate protection of cucumber seedlings from damping-off in a P. ultimum-infested peat-based mix; however, disease suppression was evident when planting was delayed for 7, 14, and 21 days after adding FE. Real-time polymerase chain reaction analyses of the peat-based mix indicated that the P. ultimum populations in the FE-amended mix declined over time. This study suggests that these organic acids in FE played a major role in pathogen or disease suppression, depending on the soil and substrate.


Isolation of an unidentified agent from the respiratory tract of chickens.
A relatively stable filterable virus, not previously described, which hemagglutinated red blood cells of chickens, was isolated from the tracheae of birds suffering from an unusually severe outbreak of infectious laryngotracheitis. The latter disease concealed the infection caused by the new hemagglutinating agent, which was shown to cause, by itself, a mild and transient illness in susceptible chickens. Preliminary studies indicate that the new agent may be a new entity of the myxovirus group.


The roles of fused-ring organic semiconductor treatment on SnO2 in enhancing perovskite solar cell performance.
It took only 11 years for the power conversion efficiency (PCE) of perovskite solar cells (PSCs) to increase from 3.8% to 25.2%. It is worth noting that, as a new thin-film solar cell technique, defect passivation at the interface is crucial for the PSCs. Decorating and passivating the interface between the perovskite and electron transport layer (ETL) is an effective way to suppress the recombination of carriers at the interface and improve the PCE of the device. In this work, several acceptor-donor-acceptor (A-D-A) type fused-ring organic semiconductors (FROS) with indacenodithiophene (IDT) or indacenodithienothiophene (IDDT) as the bridging donor moiety and 1,3-diethyl-2-thiobarbituric or 1,1-dicyromethylene-3-indanone as the strong electron-withdrawing units, were deposited on the SnO2 ETL to prepare efficient planar junction PSCs. The PCEs of the PSCs increased from 18.63% for the control device to 19.37%, 19.75%, and 19.32% after modification at the interface by three FROSs. Furthermore, impedance spectroscopy, steady-state and time-resolved photoluminescence spectra elucidated that the interface decorated by FROSs enhance not only the extraction of electrons but also the charge transportation at the interface between the perovskite and ETL. These results can provide significant insights in improving the perovskite/ETL interface and the photovoltaic performance of PSCs.


Complete Genome Sequence of a Paenalcaligenes hominis Strain Isolated from a Paraplegic Patient with Neurogenic Bladder Using Single-Molecule Real-Time Sequencing Technology.
The genome of Paenalcaligenes hominis, isolated from a paraplegic patient with neurogenic bladder, was sequenced with the Pacific Biosciences RSII platform. The genome size is 2.68 Mb and includes 3,096 annotated coding sequences, including genes associated with quinone cofactors, which play crucial roles in the virulence of Gram-negative bacteria.


Sirolimus encapsulated liposomes for cancer therapy: physicochemical and mechanical characterization of sirolimus distribution within liposome bilayers.
Sirolimus has recently been introduced as a therapeutic agent for breast and prostate cancer. In the current study, conventional and Stealth liposomes were used as carriers for the encapsulation of sirolimus. The physicochemical characteristics of the sirolimus liposome nanoparticles were investigated including the particle size, zeta potential, stability and membrane integrity. In addition atomic force microscopy was used to study the morphology, surface roughness and mechanical properties such as elastic modulus deformation and deformation. Sirolimus encapsulation in Stealth liposomes showed a high degree of deformation and lower packing density especially for dipalmitoyl-phosphatidylcholine (DPPC) Stealth liposomes compared to unloaded. Similar results were obtained by differential scanning calorimetry (DSC) studies; sirolimus loaded liposomes were found to result in a distorted state of the bilayer. X-ray photon electron (XPS) analysis revealed a uniform distribution of sirolimus in multilamellar DPPC Stealth liposomes compared to a nonuniform, greater outer layer lamellar distribution in distearoylphosphatidylcholine (DSPC) Stealth liposomes.


Cardiomyocytes bind and activate native human prorenin : role of soluble mannose 6-phosphate receptors.
Cardiomyocytes bind, internalize, and activate recombinant human prorenin through mannose 6-phosphate/insulin-like growth factor II (M6P/IGFII) receptors. To investigate whether this also applies to native human prorenin, neonatal rat myocytes were incubated for 4 hours at 37 degrees C with various prorenin-containing human body fluids. Uptake and activation by M6P/IGFII receptors were observed for plasma prorenin from subjects with renal artery stenosis and/or hypertension and for follicular fluid prorenin. The total amount of cellular renin and prorenin (expressed as percentage of the levels of renin and prorenin in the medium) after 4 hours of incubation was 4 to 10 times lower than after incubation with recombinant human prorenin. Although plasma contains alkaline phosphatases capable of inactivating the M6P label as well as soluble M6P/IGFII receptors that block prorenin binding in a competitive manner and proteins (eg, insulin, IGFII) that increase the number of cell-surface M6P/IGFII receptors, these factors were not responsible for the modest uptake of native human prorenin. Uptake did not occur during incubation of myocytes with plasma prorenin from anephric subjects or with amniotic fluid prorenin, and this was not due to the presence of excessively high levels of M6P/IGFII receptors and/or phosphatase activity in these fluids. In conclusion, myocytes are capable of binding, internalizing, and activating native human prorenin of renal and ovarian origin through M6P/IGFII receptors. Differences in prorenin glycosylation and/or phosphorylation as well as the concentration of soluble M6P/IGFII receptors and growth factors affecting cell-surface M6P/IGFII receptor density determine the amount of prorenin entering the heart and thus cardiac angiotensin II production.


Sphingolipids signal heat stress-induced ubiquitin-dependent proteolysis.
Sphingolipids are essential eukaryotic membrane lipids that are structurally and metabolically conserved through evolution. Sphingolipids have also been proposed to regulate eukaryotic stress responses as novel second messengers. Here we show that, in Saccharomyces cerevisiae, phytosphingosine, a putative sphingolipid second messenger, mediates heat stress signaling and activates ubiquitin-dependent proteolysis via the endocytosis vacuolar degradation and 26 S proteasome pathways. Inactivation of serine palmitoyltransferase, a key enzyme in generating endogenous phytosphingosine, prevents proteolysis during heat stress. Addition of phytosphingosine bypasses the requirement for serine palmitoyltransferase and restores proteolysis. Phytosphingosine-induced proteolysis requires multiubiquitin chain formation through the stress-responsive lysine 63 residue of ubiquitin. We propose that heat stress increases phytosphingosine and activates ubiquitin-dependent proteolysis.


Theatre over-shoes do not reduce operating theatre floor bacterial counts.
Occasional staff or visitors to operating theatres are usually requested to don over-shoes as this is perceived to reduce bacterial floor colony counts. However, this entails some expense and considerable inconvenience. Using disposable surface contact plates floor bacterial counts were measured four times a day at five different sites during the 5 normal working days of one 2-week period in a general operating theatre when over-shoes were worn and one 2-week period when over-shoes were not worn. There was no significant difference in the mean bacterial floor colony counts between the two periods according to sampling times or sites. As in Intensive Therapy units, over-shoes should no longer be used in general operating theatres.


Medical Specialty Classification Based on Semiadversarial Data Augmentation.
Rapidly increasing adoption of electronic health record (EHR) systems has caused automated medical specialty classification to become an important research field. Medical specialty classification not only improves EHR system retrieval efficiency and helps general practitioners identify urgent patient issues but also is useful in studying the practice and validity of clinical referral patterns. However, currently available medical note data are imbalanced and insufficient. In addition, medical specialty classification is a multicategory problem, and it is not easy to remove sensitive information from numerous medical notes and tag them. To solve those problems, we propose a data augmentation method based on adversarial attacks. The semiadversarial examples generated during the dynamic process of adversarial attacking are added to the training set as augmented examples, which can effectively expand the coverage of the training data on the decision space. Besides, as nouns in medical notes are critical information, we design a classification framework incorporating probabilistic information of nouns, with confidence recalculation after the softmax layer. We validate our proposed method on an 18-class dataset with extremely unbalanced data, and comparison experiments with four benchmarks show that our method improves accuracy and F1 score to the optimal level, by an average of 14.9%.


Flow cytometry and karyotype analysis of D.melanogaster eye disc cells.
The developing Drosophila eye-antennal disc is a particularly suited system for the genetic and cellular studies of complex biological processes. Methods to analyze Drosophila eye discs by flow cytometry are mainly based on the dissociation of tissues with trypsin. Dissociation operated by trypsin is very effective, though it causes a lot of stress to live cells often compromising the use of treated cells for further analyses. Here, we report a method to produce dissociated eye-disc cells that retain cell-membrane markers and that can be used for flow cytometry and cytological analysis of mitotic chromosomes. The method described is a great complementing tool for the cellular characterization of phenotypes resulting from classic clonal and miss-expression approaches in the Drosophila eye.


Medial Auditory Thalamus Is Necessary for Expression of Auditory Trace Eyelid Conditioning.
Transforming a brief sensory event into a persistent neural response represents a mechanism for linking temporally disparate stimuli together to support learning. The cerebellum requires this type of persistent input during trace conditioning to engage associative plasticity and acquire adaptively timed conditioned responses (CRs). An initial step toward identifying the sites and mechanisms generating and transmitting persistent signals to the cerebellum is to identify the input pathway. The medial auditory thalamic nuclei (MATN) are the necessary and sufficient source of auditory input to the cerebellum for delay conditioning in rodents and a possible input to forebrain sites generating persistent signals. Using pharmacological and computational approaches, we test (1) whether the necessity of MATN during auditory eyelid conditioning is conserved across species, (2) whether the MATN are necessary for the expression of trace eyelid CRs, and if so, (3)whether this relates to the generation of persistent signals. We find that contralateral inactivation of MATN with muscimol largely abolished trace and delay CRs in male rabbits. Residual CRs were decreased in amplitude, but CR timing was unaffected. Results from large-scale cerebellar simulations are consistent with previous experimental demonstrations that silencing only CS-duration inputs does not abolish trace CRs, and instead affects their timing. Together, these results suggest that the MATN are a necessary component of both the direct auditory stimulus pathway to the cerebellum and the pathway generating task-essential persistent signals.SIGNIFICANCE STATEMENT Persistent activity is required for working memory-dependent tasks, such as trace conditioning, and represents a mechanism by which sensory information can be used over time for learning and cognition. This neuronal response entails the transformation of a discrete sensory-evoked response into a signal that extends beyond the stimulus event. Understanding the generation and transmission of this stimulus transformation requires identifying the input sources necessary for task-essential persistent signals. We report that the medial auditory thalamic nuclei are required for the expression of auditory trace conditioning and suggest that these nuclei are a component of the pathway-generating persistent signals. Our study provides a foundation for testing circuit-level mechanisms underlying persistent activity in a cerebellar learning model with identified inputs and well defined behavioral outputs.


[Parasitic carriage of the causative agents of tropical malaria].
In 1993 to 1999, a total of 1020 Russians temporarily living in the Republic of Guinea were examined; of them 26 (2.5%) persons were found to be asymptomatic carriers of P. falciparum. Single studies of cellular and humoral immunity were first conducted in 15 asymptomatic parasitic carriers of P. falciparum. Asymptomatic parasitic carriage of P. falciparum was established in nonimmune persons who developed immunopathological reactions. The nature of immune disorders gives grounds to regard parasitic carriage as a subclinical form of tropical malaria for the first time. By taking into account asymptomatic carriage of P. falciparum, a parasitological blood study should be made in all non-immune persons when they are leaving an endemic focus for Russia.


[An analysis of the quality of the clinical diagnosis based on autopsy data].
The findings from 4359 autopsies made in 4 Moscow hospitals during 1986 were analyzed with two proposed tables. The primary materials were processes with a computer. Table 1 includes data on the total number of unrecognized cases by the main disease, major complications, concomitant and underlying diseases in terms of their category and cause of diagnosis discrepancy. The rate of the discrepancy between clinical and postmortem diagnoses averaged 21.6 +/- 4.7% by the main disease, that of unrecognized fatal complications and major concomitant and underlying diseases was found to be 7.6 and some 2%, respectively. By the categories, the analysis of diagnosis discrepancy indicated 35, 58.6, and 6.4% in Categories I, II, and III, respectively. Table 2 (combined correlational one) makes it possible to study the range of diagnostic errors in various diseases and to find typical mistakes made by clinicians. Analyzing the quality of clinical diagnosis according to the given pattern is of advantage in routine practice to obtain comparable consistent data, to make a thorough examination, and to generalized discrepancy cases of clinical and postmortem diagnoses.


Detection of telomerase activity in exfoliated cancer cells obtained from bile.
Telomerase is detected by the telomeric repeat amplification protocol (TRAP) assay in more than 85% of primary cancers. In the present study, we determined telomerase activity using exfoliated bile cells obtained from biliary tract neoplasia specimens. The aim of this study was to provide additional information regarding minimally invasive approaches to the detection of biliary tract cancer in combination with routine cytologic examination. We analyzed for telomerase activity bile juice from patients with gallbladder carcinoma, cholangiocarcinoma, cholecystitis and cholangitis. Semiquantitative determination of telomerase activity was performed using both a fluorescence-based TRAP assay on cell extracts and at the cellular level by an in situ TRAP assay. The fluorescence-based TRAP assay detected bile telomerase activity in samples from 4 of 10 patients with biliary tract cancer. In contrast, the in situ TRAP assay detected telomerase positive cells in samples from 6 of 10 patients with biliary tract cancer. However, only one of these samples showed class V cytology. A combination of semiquantitative analysis and an in situ TRAP assay to detect telomerase positive cells may improve the diagnosis of biliary tract cancers with the combination of routine cytologic examination.


[Metabolic imaging--PET, PET/CT--in oncologic surgery].
The availability of PET/CT examinations in Hungary has significantly improved in the past few years. In the three Hungarian centres approximately 10,000 examinations can be performed yearly, which are financed by the national healthcare system. The PET/CT technique using FDG has become an efficient tumour diagnostic method due to its outstanding sensitivity and specificity. Similarly to other medical imaging techniques, PET/CT is a useful and cost-beneficial diagnostic modality in the hand of those clinicians, who clearly know its advantages and limitations. In the present paper the most frequent indications of PET/CT examinations are reviewed, with special attention to cases relevant to the everyday surgical practice. The applicability of this technique is also considered.


Indirect costs associated with premature mortality among those with veno-occlusive disease/sinusoidal obstruction syndrome with multiorgan dysfunction post-hematopoietic stem-cell-transplant.
The study objective was to develop an economic model to assess projected costs of lost productivity associated with premature deaths due to veno-occlusive disease (VOD)/ sinusoidal obstruction syndrome (SOS) with multiorgan dysfunction (MOD) among patients in the US who underwent hematopoietic stem-cell transplant (HSCT) in 2013. Data sources included the US Census Bureau and Department of Health, epidemiologic research organizations, and medical research literature. The model considered only lost productivity associated with premature death, with lifetime salary assumed to reflect productivity. Average annual salary was assumed to be the same for HSCT survivors and the general population, with a working age range between 18 and 65 years. Key data inputs included number of HSCTs by graft type (allogeneic and autologous) performed in the US in 2013, HSCT-related mortality, mortality associated with VOD/SOS with MOD, and life-expectancy reduction for HSCT survivors vs the general population. Excess mortality equaled total deaths among patients with VOD/SOS and MOD minus deaths in these patients due to causes other than VOD/SOS with MOD. Among 18,284 patients who underwent HSCT in the US in 2013, the model estimated that 361 excess deaths due to VOD/SOS with MOD occurred (158 following allogeneic and 203 after autologous transplants). These deaths accounted for total lost work productivity of 5,990 years and $124,212,173 in lost wages, averaging 17 years and $343,791 per patient. A sensitivity analysis incorporating adjustment factors for epidemiologic and economic inputs calculated total financial loss of $84 million to $194 million. Estimates of post-HSCT VOD/SOS with MOD incidence and mortality were approximated, due to changing HSCT practices. Premature death due to VOD/SOS with MOD imposes a substantial economic burden in this population in terms of lost productivity. Additional studies of this economic burden are warranted.


Nurses' Perceptions Towards Resuscitated Patients: A Qualitative Study.
Nurses' perceptions of resuscitated patients may affect their care, and this has not been investigated in previous literature. The aim of this study was to explore nurses' perceptions towards resuscitated patients. In this descriptive-qualitative study seventeen clinical nurses participated using purposive sampling. In-depth, semi-structured interviews were conducted and data were analyzed by conventional content analysis. Four main categories emerged: Injured, undervalued, problematic, and destroyer of resources. Participants considered resuscitated patients to have multiple physical injuries, which are an important source of legal problems and workplace violence, and they believed that these patients will eventually die. Resuscitated patients are considered forgotten and educational cases. Iranian nurses have a strong negative perception towards resuscitated patients. Improving the quality of cardiopulmonary resuscitation, improving the knowledge and skills of personnel in performing resuscitation, and supporting managers and doctors to nurses in the post-resuscitation period can change the attitude of nurses and improve post-resuscitation care.


Association between three functional polymorphisms of the dopamine D2 receptor gene and polydipsia in schizophrenia.
The underlying pathophysiology of polydipsia in schizophrenia is poorly understood. However, several studies suggest there may be a genetic predisposition to polydipsia, including our previous study demonstrating familial concordance of polydipsia among first-degree relatives with schizophrenia. Antipsychotic medications may contribute to the development of polydipsia and studies show that dopamine D2 receptors are involved in drinking behaviour pathophysiology. Our hypothesis is that polymorphisms in the dopamine D2 receptor gene (DRD2) may confer susceptibility to polydipsia in schizophrenia. We tested for an association between polydipsia in schizophrenia and three functional polymorphisms of DRD2. The three polymorphisms, -141C Ins/Del, Ser311Cys, and TaqIA, were genotyped in patients with polydipsia (n = 64) and in those without polydipsia (n = 91). Of the three polymorphisms, TaqIA was significantly associated with polydipsia [genotype: chi2 = 6.59, df = 2, p = 0.037; allele: chi2 = 6.52, df = 1, p = 0.011, OR 1.81, 95% CI 1.15-2.86]. Haplotype analysis of the three markers found increased significance of the association (global, p = 0.00091). Although based on a relatively small portion of the sample, individual comparison of the common haplotypes showed that haplotype Ins-Cys-A1 was significantly less frequent in patients with polydipsia (p = 0.00082). The present data suggests polymorphisms in DRD2 may confer susceptibility to polydipsia in schizophrenia. To confirm our findings, further studies are warranted on larger samples using more extensive biological measures for diagnosing the polydipsia phenotype.


Extended-spectrum beta-lactamases-producing gram-negative bacteria in companion animals: action is clearly warranted!
Extended-spectrum beta-lactamases (ESBL)-producing Gram-negative bacteria pose a serious threat to Public Health in human medicine as well as increasingly in the veterinary context worldwide. Several studies reported the transmission of zoonotic multidrug resistant bacteria between food-producing animals and humans, whilst the contribution of companion animals to this scenario is rather unknown. Within the last decades a change in the social role of companion animals has taken place, resulting in a very close contact between owners and their pets. As a consequence, humans may obtain antimicrobial resistant bacteria or the corresponding resistance genes not only from food-producing animals but also via close contact to their pets.This may give rise to bacterial infections with limited therapeutic options and an increased risk of treatment failure. As beta-lactams constitute one of the most important groups of antimicrobial agents in veterinary medicine, retaliatory actions in small animal and equine practices are urgently needed. This review addresses the increasing burden of extended-spectrum beta-lactam resistance among Enterobacteriaceae isolated from companion animals. It should emphasize the urgent need for the implementation of antibiotic stewardship as well as surveillance and monitoring programs of multi resistant bacteria in particular in view of new putative infection cycles between humans and their pets.


A controllable molecular sieve for Na+ and K+ ions.
The selective rate of specific ion transport across nanoporous material is critical to biological and nanofluidic systems. Molecular sieves for ions can be achieved by steric and electrical effects. However, the radii of Na(+) and K(+) are quite similar; they both carry a positive charge, making them difficult to separate. Biological ionic channels contain precisely arranged arrays of amino acids that can efficiently recognize and guide the passage of K(+) or Na(+) across the cell membrane. However, the design of inorganic channels with novel recognition mechanisms that control the ionic selectivity remains a challenge. We present here a design for a controllable ion-selective nanopore (molecular sieve) based on a single-walled carbon nanotube with specially arranged carbonyl oxygen atoms modified inside the nanopore, which was inspired by the structure of potassium channels in membrane spanning proteins (e.g., KcsA). Our molecular dynamics simulations show that the remarkable selectivity is attributed to the hydration structure of Na(+) or K(+) confined in the nanochannels, which can be precisely tuned by different patterns of the carbonyl oxygen atoms. The results also suggest that a confined environment plays a dominant role in the selectivity process. These studies provide a better understanding of the mechanism of ionic selectivity in the KcsA channel and possible technical applications in nanotechnology and biotechnology, including serving as a laboratory-in-nanotube for special chemical interactions and as a high-efficiency nanodevice for purification or desalination of sea and brackish water.


Trunk fat and leg fat in relation to free triiodothyronine in euthyroid postmenopausal women.
A high level of free triiodothyronine (FT3) within the reference range may be a potential metabolic risk marker. However, the relationship between different fat depots and FT3 has remained unclear. We aimed to explore the relationships between segmental fat distribution and FT3 in euthyroid middle-aged and elderly men and postmenopausal women. A total of 891 subjects (394 men and 497 women) were enrolled. A bioelectrical impedance analyzer was used to measure total, trunk, arm and leg fat mass (FM) and fat percentage (fat%). The leg fat mass to trunk fat mass ratio (LTR) was calculated to evaluate the relative distribution of leg fat compared with that of trunk fat. Thyroid hormones were measured by electrochemical luminescence immunoassay. FT3 in men did not change significantly with increases in LTR quartiles, while FT3 in women decreased significantly (P for trend = 0.004). In multivariate linear regression analysis, multiple metabolic and cardiovascular risk factors were adjusted. The LTR was negatively related to FT3 in women (P < 0.05). After further mutual adjustment for trunk fat and leg fat parameters, trunk FM and fat% were positively related to FT3, while leg FM and fat% were negatively related to FT3 in women (all P < 0.05). In euthyroid postmenopausal women, trunk fat was positively correlated with FT3, whereas leg fat was negatively correlated with FT3. Our findings supported that a high level of FT3 within the reference range was related to adverse fat distribution.


Association Between Home Blood Pressure and Body Composition by Bioimpedance Monitoring in Patients Undergoing Peritoneal Dialysis.
Home blood pressure (HBP) is an independent predictor of cardiovascular and renal function. However, no particular guidelines have been established for optimal HBP in peritoneal dialysis (PD) patients. Bioelectrical impedance analysis (BIA) is a beneficial tool for determining body composition. In the present study, we used BIA to determine body composition parameters that might play a role in the regulation of HBP in PD patients, and we compared HBP with office blood pressure (BP). Our study enrolled 15 patients (11 men, 4 women) receiving PD at Tohoku University Hospital, who, for 1 year, agreed to monitor HBP and to undergo body composition analysis. Patients were requested to measure HBP twice daily (morning, night) using a home BP device. A bioimpedance monitor was used to monitor body composition each month. Blood and urine samples were also analyzed each month. The relationships of average morning systolic HBP (sMHBP) with parameters of body composition and of blood and urine analyses were evaluated. The enrolledpatients were 66.3 ± 7.7 years of age and had a PD vintage of 28.3 ± 6.4 months. Overall, their sMHBP was 128 ± 13 mmHg and their office systolic BP was 126 ± 15 mmHg. Although office systolic BP and sMHBP both correlated with body fluid parameters [total body water (TBW)/height2], renal function (renal Kt/V serum creatinine), and heart function (left ventricular mass index), the correlation coefficient for sMHBP and TBW/height2 was highest, with sMHBP being the only independent predictor. Sodium intake was associated only with sMHBP. Our results suggest that body fluid status determined by BIA, heart and renal function, and sodium intake show better associations with sMHBP than with office systolic BP. Monitoring HBP and body composition by BIA are beneficial for the maintenance of volume status in PD patients.


[Nephrotic syndrome. What is new since the 1988 study?].
The authors make a retrospective review of 53 new cases of Nephrotic Syndrome followed up in the Nephrology Unit from November 1988 to March 1994, bearing in mind the evaluation of casual changes of the disease standard regarding a previous study of 1988. Epidemiological, clinical, therapeutical and evolutional aspects were studied. Forty-four cases of primary Nephrotic Syndrome (83%) were identified, 61.4% of which behaved as cortico-sensitive, 25% as cortico-dependent, and 13.6% as cortico-resistant; 8 cases (15%) of Nephrotic Syndrome secondary to infection, Systemic Lupus Erythematosus and Amyloidosis, and 1 case of congenital Nephrotic Syndrome (2%). The theory that the high number of cortico-dependent is, probably, related with a higher severity in the relapse diagnosis and/or changes in the children's standard of living is admissible. It was also observed that at present there is a lower number of hospital discharges, related to more careful attitudes adopted regarding the evolution of the disease.


Epinephrine in resuscitation: curse or cure?
The use of epinephrine during cardiac arrest has been advocated for decades and forms an integral part of the published guidelines. Its efficacy is supported by animal data, but human trial evidence is lacking. This is partly attributable to disparities in trial methodology. Epinephrine's pharmacologic and physiologic effects include an increase in coronary perfusion pressure that is key to successful resuscitation. One possible explanation for the lack of epinephrine's demonstrated efficacy in human trials of out-of-hospital cardiac arrest is the delay in its administration. A potential solution may be intraosseus epinephrine, which can be administered quicker. More importantly, it is the quality of the basic life support, early and uninterrupted chest compressions, early defibrillation and postresuscitation care that will provide the best chance of neurologically intact survival.