Risk Factors for Delirium in Older Adults in the Emergency Department: A Systematic Review and Meta-Analysis.
We conducted a systematic review and meta-analysis to identify risk factors for delirium in geriatric patients in the emergency department and to identify emergency department (ED)-based modifiable risk factors for developing delirium during hospitalization. We searched evidence based medicine reviews, EMBASE, MEDLINE, Scopus, and Web of Science for observational studies from the time of their inception to July 2020. We included studies that evaluated potential risk factors for either prevalent or incident delirium among older adults (age ≥ 60 years) presenting to the ED. When appropriate, we meta-analyzed estimates for risk factors using a random-effects model. The certainty of evidence was evaluated using the grading of recommendations assessment, development and evaluation approach. The study's protocol was registered in PROSPERO (CDR42020175261). A total of 4,513 citations were reviewed, and 34 studies met the criteria for inclusion: 27 evaluating risk factors for ED delirium (13,412 patients) and 7 evaluating ED-based risk factors for developing delirium during hospitalization (2,238 patients). The prevalence of ED delirium ranged from 7% to 35%. Four factors had strong associations with ED delirium and were graded as high-certainty evidence, including nursing home residence (4 studies; odds ratio [OR], 3.45; 95% confidence interval [CI], 2.17 to 5.48), cognitive impairment (7 studies; OR, 4.46; 95% CI, 3.38 to 5.89), hearing impairment (3 studies, OR, 2.57; 95% CI, 1.03 to 6.41), and a history of stroke (3 studies; OR, 3.20; 95% CI, 1.17 to 8.75). The rate of developing delirium during hospitalization ranged from 11% to 27%. A length of stay of more than 10 hours in ED was associated with a higher risk of delirium (1 study; OR, 2.23; 95% CI, 1.13 to 4.41). One study reported that severe pain, rather than the use of opioids, was associated with the development of delirium. These findings can be used to prioritize delirium screening in the ED and develop novel ED delirium risk scores or prevention interventions.


Spatial and temporal patterns and their influence on fish community at Itupararanga Reservoir, Brazil.
The Itupararanga Reservoir is located at the Sorocaba River Basin, São Paulo State, Brazil. Five cities use the waters of this reservoir for human consumption. Despite this intensive use of the water resource, no study has been undertaken on the ichthyofauna of this reservoir. Collections were performed in nine sampling stations, where each three were located in the riverine, transitional and lacustrine zones. Fish specimens were collected using eight monofilament gillnets of 10 m length each, with varied mesh sizes, in the rainy and dry seasons, which corresponded to our spatial scale of analysis. Overall, 14 species of fish were identified, with the highest contribution from Characidae and Curimatidae. The most abundant species were: the "lambari", Astyanax fasciatus, the "saguiru", Cyphocharax modestus, the "lambari bocarra", Oligosarcus paranaensis, and the "mandi", Iheringichthys labrosus. Diversity tended to be higher during the dry season, although the difference was not statistically significant. Cluster analysis identified four season sampling groups differentiated by within-season distribution of species. Mantel's test showed that this distribution was little affected by environmental factors, suggesting that biotic factors were more important in determining the species distribution within the reservoir.


Wireless audio and burst communication link with directly modulated THz photoconductive antenna.
We demonstrate transmission of audio and burst signals through a prototype THz analog communication link employing laser-gated low-temperature-grown GaAs dipole antenna as THz emitter and receiver. The transmission distance is about 100 cm. By using a direct voltage modulation format, we successfully demodulated a burst signal with a rising time of 41 micros. The corresponding modulating bandwidth achieved was 23 kHz in this first experiment. Noise analysis reveals a 10% power fluctuation in the received signal with on-off extinction ratio of greater than 1000. The transmission of a six-channel analog and burst audio signal with least distortion is also demonstrated. We further demonstrate the fidelity of the transmission of a melody through the THz link with and without any amplification.


Male victims of domestic violence and their history of perpetrating violence.
To determine whether male victims of domestic violence have similar rates of violence perpetration compared with men evaluated in the ED with other causes of injury. Case-control retrospective ED record review with linkage to police department records. Cases were identified by ICD code N-code 995.81 (adult maltreatment syndrome) over a 4-year period (January 1, 1991, to December 31, 1994) at one urban trauma center. Medical records were reviewed to confirm that the assailant was an intimate female partner. Controls were identified by E-codes 880-888 (unintentional falls) and matched by age, race, and date of visit. All names were linked to police department record information regarding arrests for domestic violence perpetration, nonaggravated assaults, aggravated assaults, firearms violations, and driving under the influence of alcohol (DUI). This information was reported without patient identifiers. Comparisons between cases and controls were made with chi2 analysis. Forty-five cases and 45 controls were identified. The cases were injured by unarmed fights, E960 (31%); cuttings, E966 (33%); blunt objects, E968.2 (31%); and bites, E968.8 (5%). Median age (interquartile range) for cases was 32 (25.75, 38.25) years and for controls was 31 (25, 36.5) years. Median follow-up (interquartile range) of police records after ED visit was 45 (37, 50) months for cases and 45 (36.75, 51) months for controls. Fifty-one percent of the cases had arrests for domestic violence perpetration vs 22.2% of the controls (p=0.009). Forty-four percent of the cases had been arrested for nonaggravated assaults vs 20.0% of the controls (p=0.024). There was no statistical difference between the cases and controls in arrests for aggravated assaults (13.3% vs 4.4%), firearm violations (22.2% vs 17.8%), or DUIs (35.6% vs 20%). Men who present to the ED with injuries inflicted by their female partners have a high rate of domestic violence perpetration. This information calls into question whether many male "victims" of domestic violence are injured in self-defense by the female "victim." Also, injury by a female partner may be a useful indicator to identify batterers, so they can be referred by appropriate resources.


Potential risk of asymptomatic osteomyelitis around mandibular third molar tooth for aged people: a computed tomography and histopathologic study.
The purpose of this study was to explore the relationship between bone mineral density and histopathological features of mandibular alveolar bone evaluated quantitatively by Hounsfield units [HU] and by histopathology in human subjects. Fifty-six mandibular molars were extracted in 50 patients. Computed tomography was obtained preoperatively, and a cortical bone biopsy was obtained on the extracted sites for histopathological evaluation. The mean cortical and cancellous bone radiodensity was 1846 ± 118 HU and 926 ± 436 HU, respectively. There was no correlation between age and cortical bone HU (r = -0.004, P = 0.976); however, the correlation between age and cancellous bone HU was significant (r = 0.574, P<0.0000). Significant differences in the cancellous bone between young (0-30 years), middle (31-60 years) and old patient groups (61< years) were evident (P<0.05), whereas the cortical bone presented no significant differences. The histopathological evaluation showed that the young patient group had relatively few osteomyelitis, whereas the old patient group showed 100% focal sclerotic osteomyelitis regardless of the fact that the patients had no clinical symptoms. The mean osteocyte number/unit bone area was 170.7 ± 82.2. Negative correlation between age and osteocyte number was significant (r = -0.51, P<0.0001). Mean lacunae numbers/unit cortical bone area were 413.1 ± 130 with non-significant negative correlation (r = -0.257, P = 0.056). The mean empty lacunae numbers/cortical bone were 242.5±145, with no correlation (r = 0.081, P = 0.559). The young patients had high osteocyte number, whereas the old patients showed reduction of the osteocytes in the cortical bone (P < 0.05). Bone quality might correlate better to viable cell numbers, which influenced the osseous healing. It is suggested that the outermost layer of cortical bone may have lost its cellular activities over the years due to chronic infection, which may have provoked sclerotic changes in the cancellous bone around tooth.


The role of carbon monoxide in metabolic disease.
Metabolic disease is a complex disorder defined by various factors that increase the risk of cardiovascular disease and type 2 diabetes mellitus. In recent years, the incidence of chronic metabolic disease has dramatically increased throughout the world. These chronic metabolic diseases are associated with elevated inflammatory activities. In addition, endoplasmic reticulum (ER) stress leads to metabolic syndrome. Inflammation and ER stress are linked in the context of metabolic homeostasis and disease. Carbon monoxide (CO), a reaction product of heme oxygenase-1 (HO-1), reduces oxidative stress and inflammatory response and protects cells from ER stress. CO has anti-inflammatory effects via induction of HO-1 expression and prevents ER stress-induced apoptosis by inhibiting the C/EBP homologous protein expression. In addition to its anti-inflammatory effects and antiapoptotic effects, HO-1 plays an important role in insulin release and glucose metabolism. In our study, inhalation of CO gas or CO-releasing molecule injection ameliorates 30% fructose or methionine-deficient- and choline-deficient-diet-induced hepatic steatosis. Therefore, CO can be studied in the search for potential therapeutic targets for metabolic diseases via inhibition of inflammatory response and ER stress.


[Specific features of the clincal course of infectious endocarditis in a multi-field hospital].
The clinical course of infectious endocardities (IE) was followed in 112 patients admitted to the Botkin City Hospital in 2000-2007 with reference to the age and social structure of the pathology, its clinical symptoms, results of laboratory and instrumental analysis, strategy of antibacterial therapy, and outcome of the disease. The data were compared with those obtained in the previous period (1987-1955). He study demonstrated an increased number of men with IE (up to 65%) in the recent years and an almost two-fold rise in the incidence of primary endocardities. The frequency of thromboembolic complications also increased (from 34 to 69%) involving the pulmonary artery system (24%). The same refers to the number of patients with multivalvular lesions (2, 3 or 4 heart valves) and affected right cardiac chambers (28.4%). Shortcomings at various stages of the treatment of patients with endocarditis have been revealed.


Cytoprotection "gone astray": Nrf2 and its role in cancer.
Nrf2 has gained great attention with respect to its pivotal role in cell and tissue protection. Primarily defending cells against metabolic, xenobiotic and oxidative stress, Nrf2 is essential for maintaining tissue integrity. Owing to these functions, Nrf2 is regarded as a promising drug target in the chemoprevention of diseases, including cancer. However, much evidence has accumulated that the beneficial role of Nrf2 in cancer prevention essentially depends on the tight control of its activity. In fact, the deregulation of Nrf2 is a critical determinant in oncogenesis and found in many types of cancer. Therefore, amplified Nrf2 activity has profound effects on the phenotype of tumor cells, including radio/chemoresistance, apoptosis protection, invasiveness, antisenescence, autophagy deficiency, and angiogenicity. The deregulation of Nrf2 can result from various epigenetic and genetic alterations directly affecting Nrf2 control or from the complex interplay of Nrf2 with numerous oncogenic signaling pathways. Additionally, alterations of the cellular environment, eg, during inflammation, contribute to Nrf2 deregulation and its persistent activation. Therefore, the status of Nrf2 as anti- or protumorigenic is defined by many different modalities. A better understanding of these modalities is essential for the safe use of Nrf2 as an activation target for chemoprevention on the one hand and as an inhibition target in cancer therapy on the other. The present review mainly addresses the conditions that promote the oncogenic function of Nrf2 and the resulting consequences providing the rationale for using Nrf2 as a target structure in cancer therapy.


SliceIt: A genome-wide resource and visualization tool to design CRISPR/Cas9 screens for editing protein-RNA interaction sites in the human genome.
Several protein-RNA cross linking protocols have been established in recent years to delineate the molecular interaction of an RNA Binding Protein (RBP) and its target RNAs. However, functional dissection of the role of the RBP binding sites in modulating the post-transcriptional fate of the target RNA remains challenging. CRISPR/Cas9 genome editing system is being commonly employed to perturb both coding and noncoding regions in the genome. With the advancements in genome-scale CRISPR/Cas9 screens, it is now possible to not only perturb specific binding sites but also probe the global impact of protein-RNA interaction sites across cell types. Here, we present SliceIt (http://sliceit.soic.iupui.edu/), a database of in silico sgRNA (single guide RNA) library to facilitate conducting such high throughput screens. SliceIt comprises of ~4.8 million unique sgRNAs with an estimated range of 2-8 sgRNAs designed per RBP binding site, for eCLIP experiments of >100 RBPs in HepG2 and K562 cell lines from the ENCODE project. SliceIt provides a user friendly environment, developed using advanced search engine framework, Elasticsearch. It is available in both table and genome browser views facilitating the easy navigation of RBP binding sites, designed sgRNAs, exon expression levels across 53 human tissues along with prevalence of SNPs and GWAS hits on binding sites. Exon expression profiles enable examination of locus specific changes proximal to the binding sites. Users can also upload custom tracks of various file formats directly onto genome browser, to navigate additional genomic features in the genome and compare with other types of omics profiles. All the binding site-centric information is dynamically accessible via "search by gene", "search by coordinates" and "search by RBP" options and readily available to download. Validation of the sgRNA library in SliceIt was performed by selecting RBP binding sites in Lipt1 gene and designing sgRNAs. Effect of CRISPR/Cas9 perturbations on the selected binding sites in HepG2 cell line, was confirmed based on altered proximal exon expression levels using qPCR, further supporting the utility of the resource to design experiments for perturbing protein-RNA interaction networks. Thus, SliceIt provides a one-stop repertoire of guide RNA library to perturb RBP binding sites, along with several layers of functional information to design both low and high throughput CRISPR/Cas9 screens, for studying the phenotypes and diseases associated with RBP binding sites.


The vulnerabilities of lives: Zika, women and children in Alagoas State, Brazil.
Until 2015, Zika was mostly unknown in Brazil and in the world. Since then, the Zika virus has been found to be vertically transmitted and to cause congenital Zika syndrome (CZS). This study aims to describe and analyze the vulnerabilities of the women and children most affected by the Zika epidemic in Brazil. Alagoas has the lowest Human Development Index in Brazil and one of the highest rates of adolescent pregnancy. Between December 2016 and March 2017, interviews were conducted with 54 women with children affected by Zika. The interviews had two components: a narrative-oriented conversation and a semi-structured questionnaire. This comprehensive mixed methods case study represented 45% of the confirmed CZS cases and 20% of the cases under investigation in the state at that time. The women are predominantly Afro-Brazilian; most experienced their first pregnancy during adolescence, and had little education. Many were not covered by social protection programs and were not receiving adequate health care. The rights and needs of these women and children are impacted by a systemic lack of access to services and medications. There is inadequate transportation to services that many families depend on. Discrimination against their children with disabilities is a new and complex concept in their lives. The Zika epidemic has compounded rights violations in their lives and worsened their social and economic layers of vulnerability. There is an urgent need for a robust public response to guarantee the rights of these women and children and to implement mechanisms to prevent and eliminate their vulnerabilities.


Tissue biomarker development in a multicentre trial context: a feasibility study on the PETACC3 stage II and III colon cancer adjuvant treatment trial.
We evaluated the feasibility of biomarker development in the context of multicenter clinical trials. Formalin-fixed, paraffin-embedded (FFPE) tissue samples were collected from a prospective adjuvant colon cancer trial (PETACC3). DNA was isolated from tumor as well as normal tissue and used for analysis of microsatellite instability, KRAS and BRAF genotyping, UGT1A1 genotyping, and loss of heterozygosity of 18 q loci. Immunohistochemistry was used to test expression of TERT, SMAD4, p53, and TYMS. Messenger RNA was retrieved and tested for use in expression profiling experiments. Of the 3,278 patients entered in the study, FFPE blocks were obtained from 1,564 patients coming from 368 different centers in 31 countries. In over 95% of the samples, genomic DNA tests yielded a reliable result. Of the immmunohistochemical tests, p53 and SMAD4 staining did best with reliable results in over 85% of the cases. TERT was the most problematic test with 46% of failures, mostly due to insufficient tissue processing quality. Good quality mRNA was obtained, usable in expression profiling experiments. Prospective clinical trials can be used as framework for biomarker development using routinely processed FFPE tissues. Our results support the notion that as a rule, translational studies based on FFPE should be included in prospective clinical trials.


Extrinsic Muscle Forces Affect Ankle Loading Before and After Total Ankle Arthroplasty.
Joint loading conditions have an effect on the development and management of ankle osteoarthritis and on aseptic loosening after total ankle arthroplasty (TAA). Apart from body weight, compressive forces induced by muscle action may affect joint loading. However, few studies have evaluated the influence of individual muscles on the intraarticular pressure distribution in the ankle. The purpose of this study was to measure intraarticular pressure distribution and, in particular, (1) to quantify the effect of individual muscle action on peak-pressure magnitude; and (2) to identify the location of the center of pressure in the weightbearing native ankles and ankles that had TAA. Peak pressure and intraarticular center of pressure were quantified during force alterations of four muscle groups (peronei, tibialis anterior, tibialis posterior, and triceps surae) in 10 cadaveric feet. The pressure was measured with a pressure sensitive array before and after implantation of a three-component mobile-bearing TAA prosthesis. Linear mixed-effects models were calculated and the y-intercept (b0) and the slope (b1) of the regression were used to quantify the size of the effect. Mean maximum peak pressures of 2 MPa (± 2.6 MPa) and 6.2 MPa (± 3.6 MPa) were measured for the native and TAA joint respectively. The triceps surae greatly affect the magnitude of peak pressure in the native ankle (slope b1 = 0.174; p = 0.001) and TAA joint (slope b1 = 0.416; p = 0.001). Furthermore, the force of most muscles caused a posterior and lateral shift of the center of pressure in both conditions. Our results suggest that muscle force production has the potential to alter the pressure distribution in the native ankles and those with and TAA. Our study results help us to understand the effect of muscle forces on joint loading conditions which could be used in muscle training strategies and the design of better prosthetic components. Physical therapy or guided exercises may provide the potential to relieve areas in the joint that show signs of early osteoarthritis or reduce the contact stress on prosthetic components, potentially reducing the risk of TAA failure attributable to wear.


Quantitative magnetization transfer characteristics of the human cervical spinal cord in vivo: application to adrenomyeloneuropathy.
Magnetization transfer (MT) imaging has assessed myelin integrity in the brain and spinal cord; however, quantitative MT (qMT) has been confined to the brain or excised tissue. We characterized spinal cord tissue with qMT in vivo, and as a first application, qMT-derived metrics were examined in adults with the genetic disorder Adrenomyeloneuropathy (AMN). AMN is a progressive disease marked by demyelination of the white matter tracts of the cervical spinal cord, and a disease in which conventional MRI has been limited. MT data were acquired at 1.5 Tesla using 10 radiofrequency offsets at one power in the cervical cord at C2 in 6 healthy volunteers and 9 AMN patients. The data were fit to a two-pool MT model and the macromolecular fraction (M(ob)), macromolecular transverse relaxation time (T(2b)) and the rate of MT exchange (R) for lateral and dorsal column white matter and gray matter were calculated. M(ob) for healthy volunteers was: WM = 13.9 +/- 2.3%, GM = 7.9 +/- 1.5%. In AMN, dorsal column M(ob) was significantly decreased (P < 0.03). T(2b) for volunteers was: 9 +/- 2 micros and the rate of MT exchange (R) was: WM = 56 +/- 11 Hz, GM = 67 +/- 12 Hz. Neither T(2b) nor R showed significant differences between healthy and diseased cords. Comparisons are made between qMT, and conventional MT acquisitions.


Progressive reconfiguration of resting-state brain networks as psychosis develops: Preliminary results from the North American Prodrome Longitudinal Study (NAPLS) consortium.
Mounting evidence has shown disrupted brain network architecture across the psychosis spectrum. However, whether these changes relate to the development of psychosis is unclear. Here, we used graph theoretical analysis to investigate longitudinal changes in resting-state brain networks in samples of 72 subjects at clinical high risk (including 8 cases who converted to full psychosis) and 48 healthy controls drawn from the North American Prodrome Longitudinal Study (NAPLS) consortium. We observed progressive reduction in global efficiency (P = 0.006) and increase in network diversity (P = 0.001) in converters compared with non-converters and controls. More refined analysis separating nodes into nine key brain networks demonstrated that these alterations were primarily driven by progressively diminished local efficiency in the default-mode network (P = 0.004) and progressively enhanced node diversity across all networks (P < 0.05). The change rates of network efficiency and network diversity were significantly correlated (P = 0.003), suggesting these changes may reflect shared neural mechanisms. In addition, change rates of global efficiency and node diversity were significantly correlated with change rate of cortical thinning in the prefrontal cortex in converters (P < 0.03) and could be predicted by visuospatial memory scores at baseline (P < 0.04). These results provide preliminary evidence for longitudinal reconfiguration of resting-state brain networks during psychosis development and suggest that decreased network efficiency, reflecting an increase in path length between nodes, and increased network diversity, reflecting a decrease in the consistency of functional network organization, may be implicated in the progression to full psychosis.


Coronary sinus narrowing therapy: A "Reducer" for angina and beyond.
Refractory Angina (RA) is an increasingly common clinical diagnosis, in which patients unsuitable for further percutaneous or surgical procedures experience anginal symptoms, despite receiving optimal medical therapy. This clinical condition challenges the everyday activities and diminishes the quality of life of these patients. A wide variety of novel therapies for this type of angina are being investigated for clinical use. One of them is coronary sinus narrowing, which is performed as a percutaneous interventional procedure using catheter-delivered device, the Reducer. The device is implanted in the coronary sinus creating a physical narrowing and a pressure gradient in the sinus. This intervention improves the impaired blood flow in the ischemic regions of the heart leading to the relief of the anginal symptoms and, therefore, the overall clinical improvement of these patients. Several clinical trials have established both the safety and efficacy of the coronary sinus Reducer, while ongoing trials are aiming to further establish the procedure's safety and efficiency in both RA and other cardiovascular diseases, such as coronary microvascular dysfunction. This review aims to discuss the pathophysiology and the role of the coronary sinus Reducer in RA, the clinical trials documenting its safety and efficacy, as well as the future perspectives of this procedure among cardiovascular diseases.


Photoreceptor Cell Replacement Using Pluripotent Stem Cells: Current Knowledge and Remaining Questions.
Retinal degeneration is an increasing global burden without cure for the majority of patients. Once retinal cells have degenerated, vision is permanently lost. Different strategies have been developed in recent years to prevent retinal degeneration or to restore sight (e.g., gene therapy, cell therapy, and electronic implants). Herein, we present current treatment strategies with a focus on cell therapy for photoreceptor replacement using human pluripotent stem cells. We will describe the state of the art and discuss obstacles and limitations observed in preclinical animal models as well as future directions to improve graft integration and functionality.


Mood Disorders: The Gut Bacteriome and Beyond.
Knowledge of the microbiome-gut-brain axis has revolutionized the field of psychiatry. It is now well recognized that the gut bacteriome is associated with, and likely influences, the pathogenesis of mental disorders, including major depressive disorder and bipolar disorder. However, while substantial advances in the field of microbiome science have been made, we have likely only scratched the surface in our understanding of how these ecosystems might contribute to mental disorder pathophysiology. Beyond the gut bacteriome, research into lesser explored components of the gut microbiome, including the gut virome, mycobiome, archaeome, and parasitome, is increasingly suggesting relevance in psychiatry. The contribution of microbiomes beyond the gut, including the oral, lung, and small intestinal microbiomes, to human health and pathology should not be overlooked. Increasing both our awareness and understanding of these less traversed fields of research are critical to improving the therapeutic benefits of treatments targeting the gut microbiome, including fecal microbiome transplantation, postbiotics and biogenics, and dietary intervention. Interdisciplinary collaborations integrating systems biology approaches are required to fully elucidate how these different microbial components and distinct microbial niches interact with each other and their human hosts. Excitingly, we may be at the start of the next microbiome revolution and thus one step closer to informing the field of precision psychiatry to improve outcomes for those living with mental illness.


Elevated partial thromboplastin time as an indicator of hemorrhagic risk in postoperative patients on warfarin prophylaxis.
Warfarin provides effective prophylaxis against postoperative venous thromboembolic complications in adults undergoing elective hip surgery, but at the risk of increased bleeding complications. Although patients on this drug are routinely monitored by prothrombin time (PT), mild elevations of the partial thromboplastin time (PTT) have been reported with warfarin therapy. In a prospective study of 194 patients undergoing elective hip surgery, the authors assessed the incidence of elevation of the PTT above 50 seconds while the patient was receiving warfarin prophylaxis and the effect of this elevation on bleeding complications. The prophylactic warfarin was begun the night prior to surgery. Thirty-eight patients (19.6%) had a PTT greater than 50 seconds (group 1) and 156 had milder or no elevation of the PTT (group 2). The mean maximum PTT in group 1 was 61.2 ( +/- 12.9), versus 39.9 ( +/- 5.0) seconds in group 2. Major postoperative bleeding complications occurred in 26.3% of group 1 patients, versus 4.5% of group 2 (P less than .01). This subset of patients with an abnormal PTT elevation despite appropriate control of the PT is at a significantly increased risk of major postoperative bleeding. This observation may also prove valuable in reducing bleeding complications from warfarin use in nonsurgical patients.


Perceptions and Knowledge towards COVID-19 Vaccine Hesitancy among a Subpopulation of Adults in Kenya: An English Survey at Six Healthcare Facilities.
Background: Vaccine hesitancy, as defined by the WHO, is the reluctance or refusal to vaccinate despite the availability of vaccines and is one of the ten threats to global health in 2019. Vaccine hesitancy remains a complex matter influenced by multiple factors, especially in sub-Saharan Africa. Methods: We conducted a cross-sectional study between November 2021 and January 2022 among the general adult public seeking care at six different healthcare facilities in Kenya. The survey, in English, consisted of questions based on demographics, knowledge, and attitudes, including hesitancy towards the COVID-19 vaccine. Results: Of the 3996 surveys collected, 55.1% were from private, 19.5% from faith-based and 25.3% from government facilities., Approximately 81.0% of all the participants reported it was important to get a vaccine to protect other people from COVID-19, 79.9% reported they would take a vaccine to protect against COVID-19, yet 40.5% reported being hesitant to take the vaccine primarily due to side effects. Most of the variables were associated with receiving a vaccine. Only 52.1% of those seeking care from the government facility and 54.5% of those seeking care from the faith-based facility were vaccinated, compared to 81.5% seeking care from the private facilities (p < 0.001). More participants from private facilities felt that vaccines are safe as compared to those at the faith-based and government facilities (p < 0.001). Conclusion: Vaccine hesitancy in Kenya, even though much lower than reported in other countries, remains a dynamic problem. Mitigating strategies specific to Africa need to be developed to help address vaccine hesitancy in this part of the continent.


Incidence of Candidemia Is Higher in COVID-19 versus Non-COVID-19 Patients, but Not Driven by Intrahospital Transmission.
There is scarce information on the actual incidence of candidemia in COVID-19 patients. In addition, comparative studies of candidemia episodes in COVID-19 and non-COVID-19 patients are heterogeneous. Here, we assessed the real incidence, epidemiology, and etiology of candidemia in COVID-19 patients, and compared them with those without COVID-19 (2020 vs. 2019 and 2020, respectively). We also genotyped all C. albicans, C. parapsilosis, and C. tropicalis isolates (n = 88), causing candidemia in both groups, providing for the first time a genotypic characterization of isolates gathered in patients with either COVID-19 or non-COVID-19. Incidence of candidemia was higher in patients with COVID-19 than non-COVID-19 (4.73 vs. 0.85 per 1000 admissions; 3.22 vs. 1.14 per 10,000 days of stay). No substantial intergroup differences were found, including mortality. Genotyping proved the presence of a low number of patients involved in clusters, allowing us to rule out rampant patient-to-patient Candida transmission. The four patients, involved in two clusters, had catheter-related candidemia diagnosed in the first COVID-19 wave, which demonstrates breaches in catheter management policies occurring in such an overwhelming situation. In conclusion, the incidence of candidemia in patients with COVID-19 is significantly higher than in those without COVID-19. However, genotyping shows that this increase is not due to uncontrolled intrahospital transmission.


[Influence of methane and trichloroethylene domestication on bacterial community structure in landfill cover soil.]
The biological oxidation capacity and change of microbial community structure of typical landfill cover soil cultured in situ by methane and trichloroethylene (TCE) were studied. The rates of CH4 oxidation and TCE degradation were 0.20-0.87 Μmol·g-1 soil·h-1 and 0.009-0.013 mg·L-1·h-1 among these landfill cover soils, respectively. The activity of CH4 oxidation in Shandong landfill cover soil was higher than that in landfill cover soils sampled from Guangdong, Shanghai and Chongqing. The α-diversity and microbial community structure before and after co-metabolism degradation were then investigated in all landfill cover soils by Illumina MiSeq sequencing. The results indicated that bacterial Operational Taxonomic Units (OTUs) were assigned to 39 phyla, 85 classes and 562 genera in all the commented OTUs clustering. The dominant bacterial populations were Proteobacteria, Bacteroidetes, Chloroflexi and Acidobacteria and the sum of the proportion was over 77.4% in all landfill cover soils. In addition, total percent of γ-Protebacteria, β--Protebacteria, α-Proteobacteria, Actinobacteria and Acidobacteria was over 26.5%. Specifically, the relative abundances of Methylophilaceae_uncultured, Anaerolineaceae_uncultured, Arthrobacter and Pseudomonas increased obviously after acclimated by TCE. These results suggested that there were co-metabolism degradation with non-methane compounds and aerobic assimilation of TCE besides the widely-agreed co-metabolism degradation by methanotrophs.


Evaluating the genetic component of ischemic stroke subtypes: a family history study.
Twin and family history studies support a role for genetic factors in stroke risk. Because the etiology of ischemic stroke is heterogeneous, genetic factors may vary by etiologic subtype. We determined the familial aggregation of stroke risk in different stroke phenotypes and used the results to model estimated sample size requirements for case-control studies. One thousand consecutive white subjects with ischemic stroke and 800 white controls matched for age and sex were recruited. A first-degree family history of stroke and myocardial infarction was obtained by structured interview. Stroke subtype was determined with the use of modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. A family history of stroke at < or =65 years was a significant risk factor for large-vessel disease (odds ratio [OR], 2.24; 95% CI, 1.49 to 3.36; P<0.001) and for small-vessel disease (OR, 1.93; 95% CI, 1.25 to 2.97; P=0.003). When only cases aged <or =65 years were considered, these ORs increased to 2.93 (95% CI, 1.68 to 5.13) (P<0.001) and 3.15 (95% CI, 1.81 to 5.50) (P<0.001), respectively. No significant associations were seen for cardioembolic stroke or stroke of undetermined etiology. A family history of vascular disease is an independent risk factor for both large-vessel atherosclerosis and small-vessel disease, especially in cases presenting before age 65 years. The estimated sample sizes for case-control studies illustrate how candidate gene studies for ischemic stroke might be made more effective by focusing on these specific phenotypes, in which the genetic component of the disease appears to be strongest.


Adolescents' Reward-related Neural Activation: Links to Thoughts of Nonsuicidal Self-Injury.
Adolescence is a critical developmental period marked by an increase in risk behaviors, including nonsuicidal self-injury (NSSI). Heightened reward-related brain activation and relatively limited recruitment of prefrontal regions contribute to the initiation of risky behaviors in adolescence. However, neural reward processing has not been examined among adolescents who are at risk for future engagement for NSSI specifically, but who have yet to actually engage in this behavior. In the current fMRI study (N = 71), we hypothesized that altered reward processing would be associated with adolescents' thoughts of NSSI. Results showed that NSSI youth exhibited heightened activation in the bilateral putamen in response to a monetary reward. This pattern of findings suggests that heightened neural sensitivity to reward is associated with thoughts of NSSI in early adolescence. Implications for prevention are discussed.


A ZZ-ZW sex chromosome system in the finless eel Dalophis imberbis (Anguilliformes, Ophichtidae).
The karyotype of the finless eel Dalophis imberbis was investigated by conventional (C and replication banding, CMA(3) fluorescence) and molecular (FISH with 45S rDNA probe) techniques. The diploid chromosome number was 2n = 46 and the karyotype consisted of four pairs of meta-submetacentric and 18 pairs of subtelo-acrocentric autosomes and a pair of sex chromosomes heteromorphic in females, composed by a large subtelocentric Z, and a medium sized acrocentric W chromosome; in males this pair was composed by two large subtelocentric ZZ chromosomes. Multiple NORs have been localized by FISH and have been found to be CMA(3) positive; one of the NORs was located on the W chromosome and it was found transcriptionally active by silver staining. The Z chromosome contained distinct intercalar C-positive heterochromatin and W was almost completely heterochromatic. Our report contributes to the knowledge to the cytotaxonomy of Anguilliformes where differentiated sex chromosomes are reported in about a quarter of the species: both male and female heterogamety as well as a multiple chromosome system have been reported. Moreover, this is the first anguilliform species in which multiple NORs have been reported.


[Clinical and experimental studies on qumotang for bleeding after medical abortion in 214 cases].
To relieve the side-effect of heavy vaginal bleeding after medical abortion. Two hundred and fourteen clinical cases were enrolled, 111 of them were treated with Qumotang (QMT) and 103 cases were the control group. The average bleeding durations is 8.7 +/- 6.4 days and 13.6 +/- 7.1 days respectively. The percentages of the cases with bleeding amount less than normal menstruation in QMT group and the control were 18.44% and 30.63% respectively, the difference was significant (P < 0.05). QMT increased the intrauterine pressure and contraction frequency of rabbit uterus in vivo and it is the effective herbal recipe for bleeding after medical abortion. QMT presented its efficacy of removing blood stasis and stopping bleeding, increasing the contraction of uterine muscles and vessels.


'Selfish herds' of guppies follow complex movement rules, but not when information is limited.
Under the threat of predation, animals can decrease their level of risk by moving towards other individuals to form compact groups. A significant body of theoretical work has proposed multiple movement rules, varying in complexity, which might underlie this process of aggregation. However, if and how animals use these rules to form compact groups is still not well understood, and how environmental factors affect the use of these rules even less so. Here, we evaluate the success of different movement rules, by comparing their predictions with the movement seen when shoals of guppies (Poecilia reticulata) form under the threat of predation. We repeated the experiment in a turbid environment to assess how the use of the movement rules changed when visual information is reduced. During a simulated predator attack, guppies in clear water used complex rules that took multiple neighbours into account, forming compact groups. In turbid water, the difference between all rule predictions and fish movement paths increased, particularly for complex rules, and the resulting shoals were more fragmented than in clear water. We conclude that guppies are able to use complex rules to form dense aggregations, but that environmental factors can limit their ability to do so.


Comparison of two culture media on morphokinetics and ploidy status of sibling embryos.
To investigate the effects of culture media with different lactate concentrations on early embryonic development, data collected from our patients undergoing preimplantation genetic testing (PGT) were assessed using the EmbryoScope™ time-lapse culturing system. After intracytoplasmic sperm injection (ICSI), sibling oocytes were cultured in the same EmbryoScope (Vitrolife) slides including two different commercially available media. The patients with fewer than five mature oocytes were not included in the analyses. All embryos were hatched on day 3, and trophectoderm biopsies (n = 212) were performed accordingly. PGT for aneuploidy (PGT-A) on biopsied materials was carried out using next generation sequencing. Morphokinetic parameters, fertilization, irregular division, degeneration, blastulation, euploidy, and pregnancy rates of embryos cultured in LifeGlobal Global Total medium (LGGT) and Continuous Single Culture-NX Complete medium (CSCM-NXC) were compared. There were no differences observed in time to pronuclear fade, or in time spent as 2-cell (cc2) and 3-cell (s2), to 4-cell, 5-cell, morula and blastocyst stages (P > 0.05). Embryos reached the 2-cell (t2) and 3-cell (t3) stages significantly faster in LGGT (P < 0.05), whereas embryos grown in CSCM-NXC with lower lactate reached starting blastulation significantly sooner (P = 0.026). However, there were no statistical differences observed in fertilization, blastulation, degeneration, irregular division euploidy, and pregnancy rates between the two groups (P > 0.05). Even though pregnancy and fertilization rates did not indicate statistical differences, results are significant to provide better insight on potential roles of lactate in embryo development. These finding will advance the fundamental knowledge of human embryo development and assisted reproductive technologies.


The fast and the furious-An experimental investigation of the pace of life and risky speed choice in traffic.
Despite discernible improvements in the last decades, speeding is still a pertinent problem for road safety, fuel efficiency, and greenhouse gas mitigation. In order to understand individual speeding decisions, we need a better understanding of who speeds. In our paper, we test whether individuals' general pace of life is associated with speeding decisions. We use a novel speed-choice experiment that confronts participants with a scenario in which they repeatedly decide between driving fast or slow. This decision is associated with different accident risks. Before the experiment, each participant's pace of life was measured. Our results show that individuals with a slower pace of life are more likely to choose slow in the experiment and are also more likely to switch to slow, even when they had success by driving fast in the preliminary round. Therefore, individuals' pace of life may contribute to our understanding of speeding.


Changes in the Demographic Distribution of Chicago Gun-Homicide Decedents From 2015-2021: Violent Death Surveillance Cross-sectional Study.
Homicide is one of the 5 leading causes of death in the United States for persons aged 1 to 44 years. In 2019, 75% of US homicides were by gun. Chicago has a gun-homicide rate 4 times the national average, and 90% of all homicides are by gun. The public health approach to violence prevention calls for a 4-step process, beginning with defining and monitoring the problem. Insight into the characteristics of gun-homicide decedents can help frame next steps, including identifying risk and protective factors, developing prevention and intervention strategies, and scaling effective responses. Although much is known about gun homicide because it is a long-standing, entrenched public health problem, it is useful to monitor trends to update ongoing prevention efforts. This study aimed to use public health surveillance data and methods to describe changes in the race/ethnicity, sex, and age of Chicago gun-homicide decedents from 2015-2021, in the context of year-to-year variation and an overall increase in the city's gun-homicide rate. We calculated the distribution of gun-related homicide deaths by 6 race/ethnicity and sex groups (non-Hispanic Black female, non-Hispanic White female, Hispanic female, non-Hispanic Black male, non-Hispanic White male, and Hispanic male), age in years, and age by age group. We used counts, percentages, and rates per 100,000 persons to describe the distribution of deaths among these demographic groups. Comparisons of means and column proportions with tests of significance set at P≤.05 were used to describe changes in the distribution of gun-homicide decedents over time by race-ethnicity-sex and age groups. The comparison of mean age by race-ethnicity-sex group is done using 1-way ANOVA with significance set at P≤.05. The distribution of gun-homicide decedents in Chicago by race/ethnicity and sex groups had been relatively stable from 2015 to 2021 with 2 notable exceptions: a more than doubling of the proportion of gun-homicide decedents who were non-Hispanic Black female (3.6% in 2015 to 8.2% in 2021) and an increase of 3.27 years in the mean age of gun-homicide decedents. The increase in mean age coincided with a decrease in the proportion of non-Hispanic Black male gun-homicide decedents between the ages of 15-19 and 20-24 years and, conversely, an increase in the proportion of non-Hispanic Black male gun-homicide decedents aged 25-34 years. The annual gun-homicide rate in Chicago had been increasing since 2015 with year-to-year variation. Continued monitoring of trends in the demographic makeup of gun-homicide decedents is necessary to provide the most relevant and timely information to help shape violence prevention efforts. We detected several changes that suggest a need for increased outreach and engagement marketed toward non-Hispanic Black female and non-Hispanic Black male individuals between the ages of 25-34 years.


Polyethylenimine derivate conjugated with RGD-TAT-NLS as a novel gene vector.
To solve the contradiction between the cell toxicity and transfection efficiency of polyethylenimine (PEI) derivate in non-viral gene therapy, a novel gene vector, P123-PEI-R18 was synthesized by using biodegradable PEI derivate conjugated with trifunctional peptide RGD-TAT-NLS. The particle size of P123-PEI-R18/DNA was around 100-250 nm. The gene vector could condense DNA at the weight ratio of 2 and protect plasmid DNA from being dissolved in the blood circulation. Importantly, the complexes exhibited lower cell toxicity and higher transfection efficiency contrasted with PEI 25 kDa in vitro. P123-PEI-R18 holds high potential as a safe and efficient gene vector.


Patterns of angiotensin-converting enzyme inhibitor prescriptions, educational interventions, and outcomes among hospitalized patients with heart failure.
Among hospitalized patients with heart failure, we describe characteristics associated with prescription of angiotensin-converting enzyme (ACE) inhibitors in the doses recommended by clinical practice guidelines. We also describe the impact of ACE inhibitor prescriptions, increases in ACE inhibitor dose, and nonpharmacologic educational interventions on readmission-free survival rates. We hypothesize that care by a cardiologist physician and higher mean arterial blood pressure on admission are associated with receipt of optimal ACE inhibitor doses. We hypothesize that receipt of an ACE inhibitor at discharge and an increase in ACE inhibitor dose during hospitalization are associated with superior readmission-free survival. Between January 1, 1992, and December 31, 1993, medical records were reviewed for consecutively hospitalized patients with a principal diagnosis of heart failure at an academic medical center. Documented instructions and medications prescribed at discharge were abstracted. Deaths and readmissions through December 31, 1994, were identified with the National Death Index and the study institution's administrative data base, respectively. During 1992 and 1993, 387 patients were discharged alive from hospitalization for heart failure. Among patients discharged on enalapril or captopril, 18% received doses recommended by heart failure clinical practice guidelines. Patients discharged on a recommended ACE inhibitor dose were more likely to be African-American and had lower sodium levels and higher mean arterial pressures than patients discharged on lower ACE inhibitor doses. In survival analyses, an increase in ACE inhibitor dose was associated with improved readmission-free survival, independent of left ventricular systolic function type. Receipt of an ACE inhibitor at discharge was also associated with superior readmission-free survival, while nonpharmacologic educational instructions were not associated with improved outcomes. Interventions are needed to improve the frequency with which ACE inhibitors are prescribed at recommended doses to hospitalized patients with heart failure. We conclude that among these patients, receipt of an ACE inhibitor at discharge and an increase in ACE inhibitor dose during hospitalization are each associated with measurable effects on readmission-free survival, while provision of educational instructions as currently practiced is not associated with better outcomes.


The ubiquity of intraguild predation among predatory arthropods.
Intraguild predation (IGP) occurs when one predator species attacks another predator species with which it competes for a shared prey species. Despite the apparent omnipresence of intraguild interactions in natural and managed ecosystems, very few studies have quantified rates of IGP in various taxa under field conditions. We used molecular analyses of gut contents to assess the nature and incidence of IGP among four species of coccinellid predators in soybean fields. Over half of the 368 predator individuals collected in soybean contained the DNA of other coccinellid species indicating that IGP was very common at our field site. Furthermore, 13.2% of the sampled individuals contained two and even three other coccinellid species in their gut. The interaction was reciprocal, as each of the four coccinellid species has the capacity to feed on the others. To our knowledge, this study represents the most convincing field evidence of a high prevalence of IGP among predatory arthropods. The finding has important implications for conservation biology and biological control.


High-Resolution Longitudinal Dynamics of the Cystic Fibrosis Sputum Microbiome and Metabolome through Antibiotic Therapy.
Microbial diversity in the cystic fibrosis (CF) lung decreases over decades as pathogenic bacteria such as Pseudomonas aeruginosa take over. The dynamics of the CF microbiome and metabolome over shorter time frames, however, remain poorly studied. Here, we analyze paired microbiome and metabolome data from 594 sputum samples collected over 401 days from six adult CF subjects (subject mean = 179 days) through periods of clinical stability and 11 CF pulmonary exacerbations (CFPE). While microbiome profiles were personalized (permutational multivariate analysis of variance [PERMANOVA] r 2 = 0.79, P < 0.001), we observed significant intraindividual temporal variation that was highest during clinical stability (linear mixed-effects [LME] model, P = 0.002). This included periods where the microbiomes of different subjects became highly similar (UniFrac distance, <0.05). There was a linear increase in the microbiome alpha-diversity and in the log ratio of anaerobes to pathogens with time (n = 14 days) during the development of a CFPE (LME P = 0.0045 and P = 0.029, respectively). Collectively, comparing samples across disease states showed there was a reduction of these two measures during antibiotic treatment (LME P = 0.0096 and P = 0.014, respectively), but the stability data and CFPE data were not significantly different from each other. Metabolome alpha-diversity was higher during CFPE than during stability (LME P = 0.0085), but no consistent metabolite signatures of CFPE across subjects were identified. Virulence-associated metabolites from P. aeruginosa were temporally dynamic but were not associated with any disease state. One subject died during the collection period, enabling a detailed look at changes in the 194 days prior to death. This subject had over 90% Pseudomonas in the microbiome at the beginning of sampling, and that level gradually increased to over 99% prior to death. This study revealed that the CF microbiome and metabolome of some subjects are dynamic through time. Future work is needed to understand what drives these temporal dynamics and if reduction of anaerobes correlate to clinical response to CFPE therapy.IMPORTANCE Subjects with cystic fibrosis battle polymicrobial lung infections throughout their lifetime. Although antibiotic therapy is a principal treatment for CF lung disease, we have little understanding of how antibiotics affect the CF lung microbiome and metabolome and how much the community changes on daily timescales. By analyzing 594 longitudinal CF sputum samples from six adult subjects, we show that the sputum microbiome and metabolome are dynamic. Significant changes occur during times of stability and also through pulmonary exacerbations (CFPEs). Microbiome alpha-diversity increased as a CFPE developed and then decreased during treatment in a manner corresponding to the reduction in the log ratio of anaerobic bacteria to classic pathogens. Levels of metabolites from the pathogen P. aeruginosa were also highly variable through time and were negatively associated with anaerobes. The microbial dynamics observed in this study may have a significant impact on the outcome of antibiotic therapy for CFPEs and overall subject health.


Reducing extracellular Cl- suppresses dihydropyridine-sensitive Ca2+ currents and synaptic transmission in amphibian photoreceptors.
A reduction in extracellular chloride suppresses light-evoked currents of second-order retinal neurons (bipolar and horizontal cells) by reducing release of glutamate from photoreceptors. The underlying mechanisms responsible for this action of reduced extracellular Cl- were studied with a combination of electrophysiological recordings from single neurons in a retinal slice preparation and image analyses of intracellular Ca2+ (Fura-2) and pH [2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester] in dissociated photoreceptors. The results show that reducing extracellular Cl- suppresses a dihydropyridine (DHP)-sensitive Ca2+ current (I(Ca)) in photoreceptors. It is proposed that suppression of I(Ca) results in suppression of photoreceptor neurotransmission. The suppressive effect of low Cl- on I(Ca) is not due to antagonism by the substituting anion nor is it mediated by changes in extracellular or intracellular pH. We conclude that normal extracellular levels of Cl- are important for maintenance of the voltage-gated Ca2+ channels that support neurotransmission from photoreceptors. Several ideas are presented about the mechanisms by which Cl- supports photoreceptor neurotransmission and the possibility that modulations of Cl- might play a physiological role in the regulation of Ca2+ channels in photoreceptors and, hence, photoreceptor function.


Patient Derived Organoids Confirm That PI3K/AKT Signalling Is an Escape Pathway for Radioresistance and a Target for Therapy in Rectal Cancer.
Partial or total resistance to preoperative chemoradiotherapy occurs in more than half of locally advanced rectal cancer patients. Several novel or repurposed drugs have been trialled to improve cancer cell sensitivity to radiotherapy, with limited success. We aimed to understand the mechanisms of resistance to chemoradiotherapy in rectal cancer using patient derived organoid models. To understand the mechanisms underlying this resistance, we compared the pre-treatment transcriptomes of patient-derived organoids (PDO) with measured radiotherapy sensitivity to identify biological pathways involved in radiation resistance coupled with single cell sequencing, genome wide CRISPR-Cas9 and targeted drug screens. RNA sequencing enrichment analysis revealed upregulation of PI3K/AKT/mTOR and epithelial mesenchymal transition pathway genes in radioresistant PDOs. Single-cell sequencing of pre & post-irradiation PDOs showed mTORC1 and PI3K/AKT upregulation, which was confirmed by a genome-wide CRSIPR-Cas9 knockout screen using irradiated colorectal cancer (CRC) cell lines. We then tested the efficiency of dual PI3K/mTOR inhibitors in improving cancer cell sensitivity to radiotherapy. After irradiation, significant AKT phosphorylation was detected (p=0.027) which was abrogated with dual PI3K/mTOR inhibitors and lead to significant radiosensitisation of the HCT116 cell line and radiation resistant PDO lines. The PI3K/AKT/mTOR pathway upregulation contributes to radioresistance and its targeted pharmacological inhibition leads to significant radiosensitisation in CRC organoids, making it a potential target for clinical trials.


Polymerization of 5,6-dihydroxyindole-2-carboxylic acid to melanin by the pmel 17/silver locus protein.
Recent advances in melanogenesis have focused on the role of dihydroxyindole-2-carboxylic acid[(HO)2IndCOOH]. For example, it has been shown that formation of (HO)2IndCOOH from dopachrome is catalyzed by dopachrome tautomerase, that the melanogenic protein tyrosinase-related protein (TRP)-1 can oxidize (HO)2IndCOOH to its indole quinone, that (HO)2IndCOOH-melanins can be synthesized chemically, that mammalian melanins are naturally rich in (HO)2IndCOOH subunits, and that (HO)2IndCOOH is incorporated into melanins of melanomas in mice. The question thus emerges as to the mechanism(s) by which (HO)2IndCOOH and other precursors become incorporated into melanins in vivo. Accordingly, an activity was partially purified that catalyzed melanin formation with (HO)2IndCOOH as a substrate. Analyses of the (HO)2IndCOOH polymerization factor from Cloudman melanoma cells revealed the following: it was proteinaceous in that it was heat labile and destroyed by proteinase K; it was a glycoprotein in that it adhered to wheat germ agglutinin and was eluted with N-acetyl glucosamine; it was located predominantly in the melanosomal fraction of cell homogenates; the activity was reduced by exposure to the metal chelators EDTA and EGTA, but not by phenylthiourea, a tyrosinase inhibitor; the (HO)2IndCOOH polymerization reaction was inhibited by superoxide dismutase. In addition, the activity was found with the mouse pmel 17/silver locus protein immunopurified from human melanoma cells, and was significantly reduced in extracts of mouse melanocytes cultured from silver (si/si) mice compared to extracts from Si/Si melanocytes. In summary, an activity has been identified in human and mouse melanoma cells that catalyzes the superoxide-dependent polymerization of (HO)2IndCOOH to melanin in vitro, and appears to be a function of the pmel 17/silver protein of the human pmel 17 gene and the mouse silver locus.


Quantative MRI predicts tendon mechanical behavior, collagen composition, and organization.
Quantitative magnetic resonance imaging (qMRI) measures have provided insights into the composition, quality, and structure-function of musculoskeletal tissues. Low signal-to-noise ratio has limited application to tendon. Advances in scanning sequences and sample positioning have improved signal from tendon allowing for evaluation of structure and function. The purpose of this study was to elucidate relationships between tendon qMRI metrics (T1, T2, T1ρ and diffusion tensor imaging [DTI] metrics) with tendon tissue mechanics, collagen concentration and organization. Sixteen human Achilles tendon specimens were collected, imaged with qMRI, and subjected to mechanical testing with quantitative polarized light imaging. T2 values were related to tendon mechanics [peak stress (rsp = 0.51, p = 0.044), equilibrium stress (rsp = 0.54, p = 0.033), percent relaxation (rsp = -0.55, p = 0.027), hysteresis (rsp = -0.64, p = 0.007), linear modulus (rsp = 0.67, p = 0.009)]. T1ρ had a statistically significant relationship with percent relaxation (r = 0.50, p = 0.048). Collagen content was significantly related to DTI measures (range of r = 0.56-0.62). T2 values from a single slice of the midportion of human Achilles tendons were strongest predictors of tendon tensile mechanical metrics. DTI diffusivity indices (mean diffusivity, axial diffusivity, radial diffusivity) were strongly correlated with collagen content. These findings build on a growing body of literature supporting the feasibility of qMRI to characterize tendon tissue and noninvasively measure tendon structure and function. Statement of Clinical Significance: Quantitative MRI can be applied to characterize tendon tissue and is a noninvasive measure that relates to tendon composition and mechanical behavior.


Bidirectional effects between maternal mental health and adolescent internalizing problems across six years in Northern Ireland.
Emerging evidence indicates the existence of bidirectional relations between mothers' mental health and adolescent adjustment, but few studies have examined these relations in contexts of high environmental adversity, including economic deprivation and political violence. Given other empirical connections between political violence and adolescent adjustment problems, the impact of child adjustment problems on maternal mental health may be exacerbated in contexts of sectarian violence. Addressing this gap, latent change score modeling was used to examine interrelations between trajectories of maternal mental health and adolescent internalizing symptoms over time in communities afflicted by political conflict. Over six years, 999 adolescent-mother dyads participated in a longitudinal study in Belfast, Northern Ireland. Six-hundred ninety-five families were originally recruited in year 1, with 304 recruited to supplement the sample in year 3; the largest available sample for a given year was 760 dyads. Models including maternal mental health, adolescent internalizing symptomatology, and political violence (i.e., sectarian antisocial behavior) as a time-varying covariate were tested. Results demonstrated that for both mothers and adolescents in a dyadic pairing, higher rates of symptomology in one member of the dyad were related to symptoms observed in the other member. Results also suggest that political violence and factors related to social deprivation increased symptoms across the dyad. This study advances understanding of the bidirectional impact between maternal mental health and adolescent internalizing over time in contexts of political violence.


Co-expression and Transcriptome Analysis of Marchantia polymorpha Transcription Factors Supports Class C ARFs as Independent Actors of an Ancient Auxin Regulatory Module.
We performed differential gene expression (DGE) and co-expression analyses with genes encoding components of hormonal signaling pathways and the ∼400 annotated transcription factors (TFs) of M. polymorpha across multiple developmental stages of the life cycle. We identify a putative auxin-related co-expression module that has significant overlap with transcripts induced in auxin-treated tissues. Consistent with phylogenetic and functional studies, the class C ARF, MpARF3, is not part of the auxin-related co-expression module and instead is associated with transcripts enriched in gamete-producing gametangiophores. We analyze the Mparf3 and MpmiR160 mutant transcriptomes in the context of coexpression to suggest that MpARF3 may antagonize the reproductive transition via activating the MpMIR11671 and MpMIR529c precursors whose encoded microRNAs target SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) transcripts of MpSPL1 and MpSPL2. Both MpSPL genes are part of the MpARF3 co-expression group corroborating their functional significance. We provide evidence of the independence of MpARF3 from the auxin-signaling module and provide new testable hypotheses on the role of auxin-related genes in patterning meristems and differentiation events in liverworts.


Stochastic Constrained Extended System Dynamics for Solving Charge Equilibration Models.
We present a new stochastic extended Lagrangian molecular dynamics solution to charge equilibration that eliminates self-consistent field (SCF) calculations, thus eliminating the computational bottleneck in solving the charge distribution with standard SCF solvers. By formulating both charges and chemical potential as latent variables and introducing a holonomic constraint that satisfies charge conservation, the SC-XLMD method accurately reproduces thermodynamic, dynamic, and structural properties within the framework of ReaxFF for a bulk water system and highly reactive RDX molecules simulated at high temperature. The SC-XLMD method shows excellent computational performance and is available in the publicly available LAMMPS package.


Pancreatic cancer clusters and arsenic-contaminated drinking water wells in Florida.
We sought to identify high-risk areas of pancreatic cancer incidence, and determine if clusters of persons diagnosed with pancreatic cancer were more likely to be located near arsenic-contaminated drinking water wells. A total of 5,707 arsenic samples were collected from December 2000 to May 2008 by the Florida Department of Health, representing more than 5,000 individual privately owned wells. During that period, 0.010 ppm (10 ppb) or greater arsenic levels in private well water were considered as the threshold based on standard of United States Environmental Protection Agency (EPA). Spatial modeling was applied to pancreatic cancer cases diagnosed between 1998-2002 in Florida (n = 11,405). Multivariable logistic regression was used to determine if sociodemographic indicators, smoking history, and proximity to arsenic-contaminated well sites were associated with residence at the time of pancreatic cancer diagnosis occurring within versus outside a cluster. Spatial modeling identified 16 clusters in which 22.6% of all pancreatic cancer cases were located. Cases living within 1 mile of known arsenic-contaminated wells were significantly more likely to be diagnosed within a cluster of pancreatic cancers relative to cases living more than 3 miles from known sites (odds ratio = 2.1 [95% CI = 1.9, 2.4]). Exposure to arsenic-contaminated drinking water wells may be associated with an increased risk of pancreatic cancer. However, case-control studies are needed in order to confirm the findings of this ecological analysis. These cluster areas may be appropriate to evaluate pancreatic cancer risk factors, and to perform targeted screening and prevention studies.


[Persistence of Newcastle disease virus in mouse cells].
The course of persistent infection in Newcastle disease virus (NDV)-infected mouse L cells (LNDV) was analysed. The production of infectious intra- and extracellular virus was markedly reduced (less than 10(1) PFU/ml), 30% of the cells produced virus-specific antigen. Analysis of the synthesis of 3H-nucleocapsid RNA in the LNDV system revealed predominance of low molecular weight RNAs. Virus-specific sequences were shown to be present in fraction of DNA extracted by Hirt's method. Only the "supernatant" Hirt's fraction was infectious. The possibility of the presence of virus-specific sequences in free unintegrated form is discussed.


Inhibition of neuronal migration by JONES antibody is independent of 9-O-acetyl GD3 in GD3-synthase knockout mice.
It has been shown previously that the migration of granule neurons in neonatal cerebellum can be inhibited by a monoclonal antibody (Mab) JONES. Because the inhibition is presumed to be mediated through binding of the JONES antibody to 9-O-acetyl GD3, we used GD3-synthase knockout (GD3S-/-) mice that do not express 9-O-acetyl GD3 and also have no detectable defect in brain development, to examine the mechanism of the inhibitory effect. We found no difference between the migration of granule neurons in the neonatal cerebellar explant culture in GD3S-/- mice and in wild-type mice. Addition of the Mab JONES, but not Mab R24 or A2B5, in the culture medium blocked the neuronal migration in the explant culture of the wild-type mice. The inhibitory effect of Mab JONES was also observed, however, in the explant culture of GD3S-/- mice. Immuno-HPTLC analysis showed at least two JONES-positive glycolipids bands in the lipid extract of GD3S+/+ mice, and none was detected in that of GD3S-/- mice. Western blot analysis of the cerebellum homogenate of wild-type and GD3S-/- mice identified at least 3 JONES-positive protein bands, one of which is beta1-integrin. Because the JONES antibody also blocked neuronal migration in the cerebellar explant culture of GD3S-/- mice that do not express 9-O-acetyl-GD3, it suggested an alternative mechanism for the inhibitory effect of the antibody, at least in the GD3S knockout mice, and the inhibitory effect of the JONES antibody on neuronal migration could be mediated through its binding to beta1-integrin.


Isolated Tibial Component Failure in Total Knee Arthroplasty: A Case Series Evaluating Inflammatory Response versus Mechanical Failure.
Total knee prostheses are routinely redesigned to improve performance, longevity, and to closer mimic the native kinematics of the knee. Despite continued improvements, all knee implants, even those with proven design features, have failures. We identified a cohort of patients with isolated tibial component failures that occurred in a popular and successful knee system. Our purpose was to (1) characterize the observed radiographic failure pattern; (2) investigate the biologic response that may have contributed to the failure; and (3) to determine if the failure mechanism was of a biological or a mechanical nature. Twenty-one knees from 19 patients met the inclusion criteria of isolated tibial component failure in a single knee implant system. Radiographs from the primary and revision knee surgery were analyzed for implant positioning and the failure pattern. Inflammatory biomarkers interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were available in 16/21 knees and peripheral CD14+/16+ monocytes were measured in 14 of the aforementioned 16 knee revisions. Serum CD3, CD4, and CD19 were measured in 10 of the aforementioned 14 knees. Additionally, white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were measured to rule out infection as a cause of the cytokine upregulation. Radiographic findings demonstrated that all of the 21 tibial components were implanted in either neutral or 2 to 3 degrees varus in the coronal plane, and none of the revisions was implanted in valgus. All tibias showed obvious radiographic loosening and the implant failed into varus. The inflammatory biomarkers IL-1β, IL-6, and TNF-α were negative. WBC, ESR, and CRP were normal. Serum CD3, CD4, and CD19 flow cytometry analyses were found to be in the normal range. Peripheral CD14+/16+ and total CD16+ monocytes measurements were consistent with previous findings of patients with osteoarthritis, rather than particulate-induced inflammatory loosening. The findings support the implant failure observed in our study occurred by a different mechanism than the wear debris-induced aseptic loosening. We believe that a mechanical failure can occur based on our findings. The loosening, collapse, and debonding from the cement may have been related to the implantation technique, stresses due to favorable rotational freedoms of the implant, or patient characteristics/behavior. Continued exploration into implant failure mechanisms and particularly into the biologic response associated with failure is ongoing.


Engineered core-shell magnetic nanoparticle for MR dual-modal tracking and safe magnetic manipulation of ependymal cells in live rodents.
Tagging recognition group(s) on superparamagnetic iron oxide is known to aid localisation (imaging), stimulation and separation of biological entities using magnetic resonance imaging (MRI) and magnetic agitation/separation (MAS) techniques. Despite the wide applicability of iron oxide nanoparticles in T 2-weighted MRI and MAS, the quality of the images and safe manipulation of the exceptionally delicate neural cells in a live brain are currently the key challenges. Here, we demonstrate the engineered manganese oxide clusters-iron oxide core-shell nanoparticle as an MR dual-modal contrast agent for neural stem cells (NSCs) imaging and magnetic manipulation in live rodents. As a result, using this engineered nanoparticle and associated technologies, identification, stimulation and transportation of labelled potentially multipotent NSCs from a specific location of a live brain to another by magnetic means for self-healing therapy can therefore be made possible.


Variability in Zinc Concentration among Mueller-Hinton Broth Brands: Impact on Antimicrobial Susceptibility Testing of Metallo-β-Lactamase-Producing Enterobacteriaceae.
Zinc concentrations in cation-adjusted Mueller-Hinton broth (caMHB) from different manufacturers have been found to differ. Here, we evaluated the impact of utilizing different brands and lots of commercially available caMHB on the classification of the antimicrobial susceptibility of metallo-β-lactamase (MBL)-harboring Enterobacteriaceae We also evaluated the addition of EDTA to caMHB as a means of achieving zinc-limited media. Fifteen clinical Enterobacteriaceae isolates (harboring NDM [n = 7], VIM [n = 3], IMP [n = 2], or KPC [n = 3]) and nine different commercial lots from three caMHB manufacturers (Becton, Dickinson; Oxoid; and Sigma-Aldrich) were utilized. Zinc-limited media were prepared by the addition of EDTA at concentrations ranging from 3 to 300 μg/ml. Meropenem MICs were determined in triplicate for each lot of conventional caMHB and zinc-limited media by broth microdilution. The zinc concentration in each lot of conventional caMHB was determined by inductively coupled plasma mass spectrometry. Up to 8-fold differences in meropenem MICs were observed between the commercial lots, resulting in different classifications of susceptibility among MBL-harboring isolates. Mean zinc concentrations were highest among conventional Becton, Dickinson caMHB lots relative to those for Oxoid and Sigma-Aldrich broth. Among MBL-harboring isolates, the impact of EDTA on MICs was dependent on the lot, correlating with initial zinc availability (i.e., less MIC reduction with higher initial zinc concentrations), while MICs for KPC-harboring isolates were unchanged. In summary, zinc variability was observed among commercial lots of caMHB, resulting in different classifications of susceptibility among MBL-harboring Enterobacteriaceae The addition of EDTA at concentrations of ≥30 μg/ml was sufficient to provide a zinc-limited medium, resulting in MICs that reflect in vivo meropenem activity.


Herbal medicine--sets the heart racing!
The potential for pharmaceuticals to produce side effects and drug interactions is well known to medical practitioners and the lay public alike. However, the potential for alternative medicines to produce such effects is less widely known. We describe a potentially dangerous interaction between a herbal medicine and concomitant selective serotonin re-uptake inhibitor (SSRI) ingestion.


Farnesol blocks the L-type Ca2+ channel by targeting the alpha 1C subunit.
We recently demonstrated that farnesol, a 15-carbon isoprenoid, blocks L-type Ca2+ channels in vascular smooth muscle cells. To elucidate farnesol's mechanism of action, we performed whole-cell and perforated-patch clamp experiments in rat aortic A7r5 cells and in Chinese hamster ovary (CHO) C9 cells expressing smooth muscle Ca2+ channel alpha 1C subunits. Farnesol dose-dependently and voltage-independently inhibited Ba2+ currents in both A7r5 and CHOC9 cells, with similar half-maximal inhibitions at 2.6 and 4.3 micromol/L, [corrected] respectively (P=NS). In both cell lines, current inhibition by farnesol was prominent over the whole voltage range without changes in the current-voltage relationship peaks. Neither intracellular infusion of the stable GDP analogue guanosine-5'-O-(2-thiodiphosphate) (100 micromol/L) [corrected] via the patch pipette nor strong conditioning membrane depolarization prevented the inhibitory effect of farnesol, which indicates G protein-independent inhibition of Ca2+ channels. In an analysis of the steady-state inactivation curve for voltage dependence, farnesol induced a significant, negative shift ( approximately 10 mV) of the potential causing 50% channel inactivation in both cell lines (P<0. 001). In contrast, the steepness factor characterizing the voltage sensitivity of the channels was unaffected. Unlike pharmacological Ca2+ channel blockers, farnesol blocked Ca2+ currents in the resting state: initial block was 63+/-8% in A7r5 cells and 50+/-9% in CHOC9 cells at a holding potential of -80 mV. We then gave 500 mg/kg body weight farnesol by gavage to Sabra hypertensive and normotensive rats and found that farnesol reduced blood pressure significantly in the hypertensive strain for at least 48 hours. We conclude that farnesol may represent an endogenous smooth muscle L-type Ca2+ channel antagonist. Because farnesol is active in cells expressing only the pore-forming alpha1 subunit, the data further suggest that this subunit represents the molecular target for farnesol binding and principal action. Finally, farnesol has a blood pressure-lowering action that may be relevant in vivo.


Diverse functions of microRNAs in nervous system development.
MicroRNAs (miRNAs) are integral parts of the gene regulatory networks that control most developmental processes. Through their regulatory action, miRNAs introduce an additional layer of genetic complexity that can translate into increased cellular diversity, something that is extremely relevant to nervous system structure. In addition, miRNAs sharpen the spatial and temporal boundaries between different cellular states during development. Here, we illustrate these roles with a number of specific miRNAs that act during distinct steps of neural development. We further discuss specific aspects of miRNA function that make these regulators particularly suited to provide the robustness and complexity that are essential for the dynamic nature of both the development and activity of the nervous system.


Fluorodopa PET scanning in Parkinson's disease.
In summary, FD PET is a valid method for assessing the functional state of the nigrostriatal dopaminergic pathway. It is particularly useful for studies requiring repeated measures such as examinations of the course of a disease and the effect of treatment.


Inferring the evolutionary history of Indian Plasmodium vivax from population genetic analyses of multilocus nuclear DNA fragments.
The human malaria parasite Plasmodium vivax is globally widespread, causing high malaria morbidity. As P. vivax is highly endemic to India, and previous reports indicate genetic homogeneity in population samples, we tested the hypothesis of no genetic structuring in Indian P. vivax. Further, based on the reports of increasing incidence of Plasmodium falciparum infection in comparison with P. vivax in recent years in India, it was important to understand whether reduction in population size has resulted in decrease in P. vivax infection rate in India. For this, we utilized recently developed putatively neutral markers from chromosome 13 of P. vivax to score single nucleotide polymorphisms in 126 P. vivax isolates collected from 10 different places in India. The overall results indicated that Indian P. vivax bears high nucleotide diversity within population samples but moderate amount of genetic differentiation between population samples. STRUCTURE analysis grouped 10 population samples into three clusters based on the proportion of the genetic ancestries in each population. However, the pattern of clustering does not correlate with sampling locations in India. Furthermore, analyses of past demographic events indicated reduction in population size in majority of population samples, but when isolates from all the 10 samples were considered as a single population, the data fit to the demographic equilibrium model. All these observations clearly indicate that Indian P. vivax presents complex evolutionary history but possesses several features of being a part of ancestral distribution range of this species.


Localization of substance P-like immunoreactivity in neurons and nerve terminals in the neostriatum of the rat: a correlated light and electron microscopic study.
An antiserum, to substance P has been used to study the neostriatum of rats which has received intracerebral injections of colchicine. Both cell bodies and nerve fibres were found to display immunoreactivity. Some of the fibres were swollen and could be traced back to their parent cell body. Examination in the electron microscope of structures that had first been identified in the light microscope showed that there are two different types of substance P-immunoreactive cell body. The first kind (type I) of immunoreactive cell body was of medium size and had a smooth surfaced nucleus. It displayed the ultrastructural features typical of medium-size spiny neurons. Identified axons of type I neurons gave rise to immunoreactive axon collaterals within the neostriatum: boutons along these collaterals were found to form symmetrical synaptic contacts. The second kind (type II) of immunoreactive cell body was also of medium-size and had a round or oval shape, but the nucleus was deeply indented and was surrounded by a thin rim of cytoplasm. Synaptic input to this neuron was sparse and consisted of small boutons that made symmetrical contacts with the perikaryon and proximal dendrites. Many immunoreactive dot-like structures could be seen in the light microscope: upon examination in the electron microscope these were found to be boutons. All fifty-six synaptic boutons that were studied made symmetrical synaptic contacts. These boutons were indistinguishable from the boutons of axon collaterals of identified type I immunoreactive neurons. The most common postsynaptic structures were dendrites, including some dendritic spines, although synapses between immunoreactive boutons and several perikarya, and an axon initial segment were observed. The morphological features of the immunoreactive boutons in the neostriatum were very similar to one type of substance P-immunoreactive bouton in the substantia nigra and to a bouton type in the substantia nigra which is labelled following the anterograde transport of horseradish peroxidase from the striatum. It is suggested that there are two kinds of substance P-containing neurons in the striatum and that one of these is likely to belong to the medium-spiny class. The latter type of neuron is probably the source of the striatonigral substance P-containing projection and of the immunoreactive boutons within the striatum. The finding of substance P-immunoreactive synaptic boutons within the neostriatum provides a morphological basis for the view that substance P might serve as a neurotransmitter in the neostriatum.


Selective inhibition of CTCF binding by iAs directs TET-mediated reprogramming of 5-hydroxymethylation patterns in iAs-transformed cells.
Methylation at cytosine (5mC) is a fundamental epigenetic DNA modification recently associated with iAs-mediated carcinogenesis. In contrast, the role of 5-hydroxymethylcytosine (5hmC), the oxidation product of 5mC in iAs-mediated carcinogenesis is unknown. Here we assess the hydroxymethylome in iAs-transformed cells, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks. Moreover, this pathologic iAs-mediated carcinogenesis is characterized by a shift toward a higher hydroxymethylation pattern genome-wide. At specific promoters, hydroxymethylation correlated with increased gene expression. Furthermore, this increase in hydroxymethylation occurs concurrently with an upregulation of ten-eleven translocation (TET) enzymes that oxidize 5-methylcytosine (5mC) in DNA. To gain an understanding into how iAs might impact TET expression, we found that iAs inhibits the binding of CTCF at the proximal, weak CTCF binding sites of the TET1 and TET2 gene promoters and enhances CTCF binding at the stronger distal binding site. Further analyses suggest that this distal site acts as an enhancer, thus high CTCF occupancy at the enhancer region of TET1 and TET2 possibly drives their high expression in iAs-transformed cells. These results have major implications in understanding the impact of differential CTCF binding, genome architecture and its consequences in iAs-mediated pathogenesis.


Biofeedback and the electromyographic activity of pelvic floor muscles in pregnant women.
Maintaining continence is among the functions of the pelvic floor muscles (PFM) and their dysfunction can cause urinary incontinence (UI), which is a common occurrence during pregnancy and the puerperal period. Pelvic floor muscle training (PFMT), therefore, is important during pregnancy, although most women perform the muscle contractions unsatisfactorily. This study is an exploratory analysis of the results of three electromyographic (EMG) activity biofeedback sessions in pregnant women. The study sample included 19 nulliparous women with low risk pregnancies. The participants performed three sessions of EMG biofeedback consisting of slow and fast contractions. The average value of the normalized amplitudes of surface electromyography was used to evaluate the results. The linear regression model with mixed effects was used for statistical analysis, with the EMG data normalized by maximum voluntary contraction (MVC). A steady increase in EMG amplitude was observed during each contraction and by the end of the biofeedback sessions, although this difference was only significant when comparing the first tonic contraction of each session (p=0.03). The results indicate that three sessions of training with biofeedback improved PFM EMG activity during the second trimester in women with low-risk pregnancies. The effectiveness of this protocol should be further investigated in randomized controlled trials.


Interobserver Agreement of Usual Interstitial Pneumonia Diagnosis Correlated With Patient Outcome.
- The histopathologic criteria for idiopathic pulmonary fibrosis were revised in the American Thoracic Society/European Respiratory Society/Japan Respiratory Society/Latin American Thoracic Association guidelines in 2011. However, the evidence of diagnosis based on the guidelines needs further investigation. - To examine whether the revised histopathologic criteria for idiopathic pulmonary fibrosis improved interobserver agreement among pathologists and the predicted prognosis in patients with interstitial pneumonia. - Twenty, consecutive, surgical lung-biopsy specimens from cases of interstitial pneumonia were examined for histologic patterns by 11 pathologists without knowledge of clinical and radiologic data. Diagnosis was based on American Thoracic Society/European Respiratory Society guidelines of 2002 and 2011. Pathologists were grouped by cluster analysis, and interobserver agreement and association to the patient prognosis were compared with the diagnoses for each cluster. - The generalized κ coefficient of diagnosis for all pathologists was 0.23. If the diagnoses were divided into 2 groups: usual interstitial pneumonia (UIP)/probable UIP (the UIP group) or possible/not UIP (the non-UIP group), according to the 2011 guidelines, the κ improved to 0.37. The pathologists were subdivided into 2 clusters in which 1 showed an association between UIP group diagnosis and patient prognosis (P < .05). - Agreement about pathologic diagnosis of interstitial pneumonia is low; however, results after division into UIP and non-UIP groups provided favorable agreement. The cluster analysis revealed 1 of the 2 clusters providing high interobserver agreement and prediction of patient prognosis.


Recent Advances on Pt-Free Electro-Catalysts for Dye-Sensitized Solar Cells.
Since Prof. Grätzel and co-workers achieved breakthrough progress on dye-sensitized solar cells (DSSCs) in 1991, DSSCs have been extensively investigated and wildly developed as a potential renewable power source in the last two decades due to their low cost, low energy-intensive processing, and high roll-to-roll compatibility. During this period, the highest efficiency recorded for DSSC under ideal solar light (AM 1.5G, 100 mW cm-2) has increased from ~7% to ~14.3%. For the practical use of solar cells, the performance of photovoltaic devices in several conditions with weak light irradiation (e.g., indoor) or various light incident angles are also an important item. Accordingly, DSSCs exhibit high competitiveness in solar cell markets because their performances are less affected by the light intensity and are less sensitive to the light incident angle. However, the most used catalyst in the counter electrode (CE) of a typical DSSC is platinum (Pt), which is an expensive noble metal and is rare on earth. To further reduce the cost of the fabrication of DSSCs on the industrial scale, it is better to develop Pt-free electro-catalysts for the CEs of DSSCs, such as transition metallic compounds, conducting polymers, carbonaceous materials, and their composites. In this article, we will provide a short review on the Pt-free electro-catalyst CEs of DSSCs with superior cell compared to Pt CEs; additionally, those selected reports were published within the past 5 years.


Sildenafil reduces respiratory muscle weakness and fibrosis in the mdx mouse model of Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy caused by mutations in the dystrophin gene. Loss of dystrophin initiates a progressive decline in skeletal muscle integrity and contractile capacity which weakens respiratory muscles including the diaphragm, culminating in respiratory failure, the leading cause of morbidity and mortality in DMD patients. At present, corticosteroid treatment is the primary pharmacological intervention in DMD, but has limited efficacy and adverse side effects. Thus, there is an urgent need for new safe, cost-effective, and rapidly implementable treatments that slow disease progression. One promising new approach is the amplification of nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signalling pathways with phosphodiesterase 5 (PDE5) inhibitors. PDE5 inhibitors serve to amplify NO signalling that is attenuated in many neuromuscular diseases including DMD. We report here that a 14-week treatment of the mdx mouse model of DMD with the PDE5 inhibitor sildenafil (Viagra(®), Revatio(®)) significantly reduced mdx diaphragm muscle weakness without impacting fatigue resistance. In addition to enhancing respiratory muscle contractility, sildenafil also promoted normal extracellular matrix organization. PDE5 inhibition slowed the establishment of mdx diaphragm fibrosis and reduced matrix metalloproteinase-13 (MMP-13) expression. Sildenafil also normalized the expression of the pro-fibrotic (and pro-inflammatory) cytokine tumour necrosis factor α (TNFα). Sildenafil-treated mdx diaphragms accumulated significantly less Evans Blue tracer dye than untreated controls, which is also indicative of improved diaphragm muscle health. We conclude that sildenafil-mediated PDE5 inhibition significantly reduces diaphragm respiratory muscle dysfunction and pathology in the mdx mouse model of Duchenne muscular dystrophy. This study provides new insights into the therapeutic utility of targeting defects in NO-cGMP signalling with PDE5 inhibitors in dystrophin-deficient muscle.


Safety of minimally invasive radical prostatectomy in patients with prior abdominopelvic or inguinal surgery.
Despite the widespread use of minimally invasive radical prostatectomy (MIRP), there remain concerns regarding its safety in patients with a history of prior abdominopelvic or inguinal surgery. A prospective database of 1165 MIRP procedures performed by a single surgeon at a high-volume tertiary care center from 2001 to 2013 was analyzed. After an initial period of transperitoneal MIRP (TP), an extraperitoneal (EP) approach was used preferentially beginning in 2005 (for both laparoscopic and robotic cases), and robotics were used preferentially beginning in 2010. Overall perioperative complications, major complications (Clavien-Dindo III or IV), and abdominal complications (e.g., ileus, bowel/organ injury, or vascular injury) were compared for patients with and without a prior surgical history. Uni- and multivariate logistic regression were used to control the impact of robotics, approach, operative time, estimated blood loss, case number, prostate weight, and primary Gleason on complications. Three hundred patients undergoing MIRP had prior abdominopelvic or inguinal surgery (25.8%). Of these, 102 (34%) underwent TP and 198 (66%) EP MIRP. Robotics was used in 286 cases (24.6%) and pure laparoscopy in 879 (75.4%). Complications occurred in 111 patients (9.5%) from the total cohort, with major complications in 32 (2.75%) and abdominal complications in 19 (1.63%). Prior surgery was not associated with overall, major, or abdominal complications. Of the controlling factors, only increasing operative time was associated with postoperative abdominal complications (most of which were ileus) on multivariate analysis. In this large single-surgeon series where both EP and TP approaches to MIRP are utilized, prior abdominopelvic or inguinal surgery was not associated with an increased risk of perioperative complications.


Can you tell that I'm in a relationship? Attachment and relationship visibility on Facebook.
People often attempt to shape others' perceptions of them, but the role of romantic relationships in this process is unknown. The present set of studies investigates relationship visibility, the centrality of relationships in the self-images that people convey to others. We propose that attachment underlies relationship visibility and test this hypothesis across three studies in the context of Facebook. Avoidant individuals showed low desire for relationship visibility, whereas anxious individuals reported high desired visibility (Studies 1 and 2); however, similar motives drove both groups' actual relationship visibility (Study 1). Moreover, both avoidant individuals and their partners were less likely to make their relationships visible (Studies 1 and 3). On a daily basis, when people felt more insecure about their partner's feelings, they tended to make their relationships visible (Study 3). These studies highlight the role of relationships in how people portray themselves to others.


Requirement for Hsp90 and a CyP-40-type cyclophilin in negative regulation of the heat shock response.
The heat shock response is a highly conserved mechanism that allows cells to withstand a variety of stress conditions. Activation of this response is characterized by increased synthesis of heat shock proteins (HSPs), which protect cellular proteins from stress-induced denaturation. Heat shock transcription factors (HSFs) are required for increased expression of HSPs during stress conditions and can be found in complexes containing components of the Hsp90 molecular chaperone machinery, raising the possibility that Hsp90 is involved in regulation of the heat shock response. To test this, we have assessed the effects of mutations that impair activity of the Hsp90 machinery on heat shock related events in Saccharomyces cerevisiae. Mutations that either reduce the level of Hsp90 protein or eliminate Cpr7, a CyP-40-type cyclophilin required for full Hsp90 function, resulted in increased HSF-dependent activities. Genetic tests also revealed that Hsp90 and Cpr7 function synergistically to repress gene expression from HSF-dependent promoters. Conditional loss of Hsp90 activity resulted in both increased HSF-dependent gene expression and acquisition of a thermotolerant phenotype. Our results reveal that Hsp90 and Cpr7 are required for negative regulation of the heat shock response under both stress and nonstress conditions and establish a specific endogenous role for the Hsp90 machinery in S. cerevisiae.


Effect of heavy dynamic resistive exercise on acute upper-body power.
There is limited research to support the notion that heavy resistive exercise immediately before a power movement may acutely enhance performance. Upper-body acute power enhancement during a stretch-shorten cycle (SSC) movement has not been previously investigated. The aim of this project was to determine whether a set of 5 repetitions of 5 repetition maximum (RM) bench press preceding explosive push-ups would significantly influence indicators of power: impulse and maximum rate of force development. Subjects randomly performed either explosive push-ups only over a force platform or a set of 5RM bench press before the explosive push-ups. There were no significant differences for any of the force platform data when the explosive push-ups were preceded by a set of 5RM bench press. It appears that heavy dynamic resistive upper-body exercise on its own before an upper-body power activity is inadequate in augmenting short-term power.