Azorella compacta Infusion Activates Human Immune Cells and Scavenges Free Radicals In vitro.
Azorella compacta is traditionally used in the form of tea (infusion), in the Andean region of South America, to treat various chronic diseases. However, the health-promoting properties of this herbal tea have not yet been extensively explored. The free radical scavenging activity of A. compacta infusion (ACI) was evaluated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and superoxide anion radical assays. The activation of immune cells by ACI, as determined by cell surface cluster of differentiation 69 expression, was measured by flow cytometry. The qualitative polyphenolic composition of ACI was investigated by HPLC/PDA/ESI-MS, (High-performance liquid chromatography coupled with photodiode array detection and electrospray ionization - mass spectrometry) and the total content of polyphenols was estimated by spectrophotometric methods. Eight polyphenols including chlorogenic acid, 6,8-di-C-hexosyl apigenin, isoorientin, orientin, dicaffeoylquinic acid, biochanin A-O-glucoside, biochanin A-O-(malonyl)-glucoside, and licoisoflavone A were tentatively identified in ACI. The total contents of phenols, flavonoids, and tannins in lyophilized ACI were 5.40 mg/100 mg ACI, 1.79 mg/100 mg ACI, and 1.76 mg/100 mg ACI, respectively. ACI, within the range of 25-400 μg/mL, scavenged DPPH and O2.- by 15-90% and 20-88%, respectively. The human natural killer (NK) cells were substantially activated by ACI, whereas T cells and granulocytes were slightly stimulated. Overall, the results demonstrate the free radical scavenging and immune-stimulating properties of ACI, and support, at least in part, its potential utilization as a functional herbal tea. for preventing chronic diseases and as a nonspecific immune stimulator during human immunosenescence. The total contents of phenols, flavonoids, and tannins in Azorella compacta infusion (ACI) were 5.40 mg/100 mg ACI, 1.79 mg/100 mg ACI, and 1.76 mg/100 mg ACI, respectively.Eight polyphenols including chlorogenic acid, 6,8-di-C-hexosyl apigenin, isoorientin, orientin, dicaffeoylquinic acid, biochanin A-O-glucoside, biochanin A-O-(malonyl)-glucoside, and licoisoflavone A were tentatively identified in ACI by HPLC/PDA/ESI-MS.ACI, within the range of 25-400 μg/ml, scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) and O2. by 15-90% and 20-88%, respectively.The human natural killer (NK) cells were substantially activated by ACI, whereas T cells and granulocytes were slightly stimulated. Abbreviations used: ESI: electrospray ionization, HPLC: high performance liquid chromatography, PDA: photodiode array detector, MS: mass spectrometry, MS/MS: tandem mass spectrometry, MW: molecular weight, m/z: mass-to-charge ratio, FITC: fluorescent isothiocyanate, PE: phycoerythrin.


Toxicology. Mercury report backs strict rules.
The debate, finally, seemed to be settled. After an 18-month review, a panel of the National Academy of Sciences last week weighed in on the health risks of mercury, endorsing strict safety levels proposed by the Environmental Protection Agency in 1995. But already some scientists are contesting the panel's conclusions, and federal agencies are grappling with how to reconcile competing regulations.


Oxidized low-density lipoprotein and 15-deoxy-delta 12,14-PGJ2 increase mitochondrial complex I activity in endothelial cells.
Oxidized lipids are capable of initiating diverse cellular responses through both receptor-mediated mechanisms and direct posttranslational modification of proteins. Typically, exposure of cells to low concentrations of oxidized lipids induces cytoprotective pathways, whereas high concentrations result in apoptosis. Interestingly, mitochondria can contribute to processes that result in either cytoprotection or cell death. The role of antioxidant defenses such as glutathione in adaptation to stress has been established, but the potential interaction with mitochondrial function is unknown and is examined in this article. Human umbilical vein endothelial cells (HUVEC) were exposed to oxidized LDL (oxLDL) or the electrophilic cyclopentenone 15-deoxy-Delta 12,14-PGJ2 (15d-PGJ2). We demonstrate that complex I activity, but not citrate synthase or cytochrome-c oxidase, is significantly induced by oxLDL and 15d-PGJ2. The mechanism is not clear at present but is independent of the induction of GSH, peroxisome proliferator-activated receptor (PPAR)-gamma, and PPAR-alpha. This response is dependent on the induction of oxidative stress in the cells because it can be prevented by nitric oxide, probucol, and the SOD mimetic manganese(III) tetrakis(4-benzoic acid) porphyrin chloride. This increased complex I activity appears to contribute to protection against apoptosis induced by 4-hydroxynonenal.


Dehydro-alpha-lapachone isolated from Catalpa ovata stems: activity against plant pathogenic fungi.
The methanol extract of stems of Catalpa ovata G Don exhibits potent in vivo antifungal activity against Magnaporthe grisea (Hebert) Barr (rice blast) on rice plants, Botrytis cinerea Pers ex Fr (tomato grey mould) and Phytophthora infestans (Mont) de Bary (tomato late blight) on tomato plants, Puccinia recondita Rob ex Desm (wheat leaf rust) on wheat plants and Blumeria graminis (DC) Speer f. sp. hordei Marchal (barley powdery mildew) on barley plants. An antifungal substance was isolated and identified as dehydro-alpha-lapachone from mass and nuclear magnetic resonance spectral data. It completely inhibited the mycelial growth of B. cinerea, Colletotrichum acutatum Simmonds, Colletotrichum gloeosporioides Simmonds, M. grisea and Pythium ultimum Trow over a range of 0.4-33.3 mg litre(-1). It also controlled the development of rice blast, tomato late blight, wheat leaf rust, barley powdery mildew and red pepper anthracnose (Colletotrichum coccodes (Wallr) S Hughes). The chemical was particularly effective in suppressing red pepper anthracnose by 95% at a concentration of 125 mg litre(-1).


Zinc overload mediated by zinc oxide nanoparticles as innovative anti-tumor agent.
The predicted global cancer burden is expected to surpass 20 million new cancer cases by 2025. Despite recent advancement in tumor therapy, a successful cancer treatment remains challenging. The emerging field of nanotechnology offers great opportunities for diagnosis, imaging, as well as treatment of cancer. Zinc oxide nanoparticles (ZnO NP) were shown to exert selective cytotoxicity against tumor cells via a yet unknown mechanism, most likely involving the generation of reactive oxygen species (ROS). These nanoparticles are a promising therapeutic opportunity as zinc is a nontoxic trace element and its application in medically-related products is considered to be safe. We could show that ZnO NP can exert cytotoxic effects on several human tumor cell lines. There can be found ZnO NP concentrations which selectively damage tumor cells while human fibroblasts do not sustain lasting damage. Cytotoxicity is attributable to the release of zinc ions from the nanoparticles outside the cells as well as to a direct cell-nanoparticle interaction. This involves uptake of the particles into the tumor cells. With a silica shell the cytotoxicity can be delayed which can help in the future for a safe transport in the blood stream. Cellular damage finally cumulates in apoptotic cell death via zinc overload within 48 h after treatment with ZnO NP. A therapeutical perspective could be the targeted accumulation of ZnO NP at the tumor side to induce local zinc overload that substantially damages the tumor cells with no or low side effects. We suggest further studies to explore the potential of ZnO NP as an innovative anti-tumor agent.


Transitioning the eating experience in survivors of head and neck cancer.
Applying the Social Cognitive Transition (SCT) Model of Adjustment as an interpretive framework, this mixed-methods case series explored how head and neck cancer (HNC) survivors participate in the dimensions of the eating experience (described as physiological, psychological, social, cultural). This was a sub-study of a primary study, "The Natural History and Impact of Taste Change in Oncology Care." Qualitative interviews and quantitative data (questionnaires and exams) were intersected to examine and describe the complexities of transitioning the eating experience after treatment for HNC. Triangulation of qualitative and quantitative data within and across cases was examined to produce rich descriptions of the changes and transitions in the eating experience. Four case studies were detailed. All reported some taste and/or smell changes. Each case described worry about weight loss and the decreased ability to engage and finding meaning in the eating experience. Each expressed coping strategies that drew upon the social and cultural dimensions of their prior eating experience that brought meaning and purpose to the post-treatment eating experience. This case series explored the impact of taste and oral function and the participant's pre- and post-treatment mental model of the eating experience. Application of the SCT Model of Adjustment to the eating experience in adults with HNC provided a deeper insight into how cognitive adaptation and coping strategies supported transition in identity related to the eating experience following cancer therapy.


Gastrocnemius recession: A cadaveric study of surgical safety and effectiveness.
Background and purpose - Many methods of gastrocnemius lengthening have been described, with different surgical challenges, outcomes, and risks to the sural nerve. Our aims were (1) to locate the gastrocnemius muscular-tendinous junction in relation to the mid-length of the fibula (from here on designated the mid-fibula), (2) to compare the dorsiflexion achieved with dorsal recession or ventral recession, and (3) to determine the risk of injury to the sural nerve during gastrocnemius recession. Methods - In 10 pairs of fresh-frozen adult cadaveric lower extremities transected above the knee, we measured dorsiflexion, performed dorsal or ventral gastrocnemius recession at the mid-fibula, and then measured the increase in dorsiflexion and fasciotomy gap. We noted the course of the sural nerve and whether the gastrocnemius muscle provided it with enough muscular coverage to protect it during recession. Results - Dorsal and ventral recession produced statistically (p < 0.05) and clinically significant mean increases in dorsiflexion with extended knee from 12° to 19°, but they were not statistically significantly different from each other in this measure or in fasciotomy gap size. At the mid-fibula, the sural nerve coursed superficially between both heads of the gastrocnemius muscle in 14 of 20 specimens. Sufficient gastrocnemius muscle coverage to protect the sural nerve was provided by the medial head in 18 of 20 specimens and by the lateral head in only 5 of 20 specimens. Interpretation - A ventral gastrocnemius recession proximal to the mid-fibula level poses less risk to the sural nerve than a recession at the mid-fibula. This procedure provides adequate lengthening (1-3 cm) and increased dorsiflexion (compared with baseline), with less risk to the sural nerve than is incurred with recession at the mid-fibular reference line.


Isolation of cationic and neutral (allenylidene)(carbene) and bis(allenylidene)gold complexes.
The one-electron reduction of a cationic (allenylidene)[cyclic(alkyl) (amino)carbene]gold(i) complex leads to the corresponding neutral, paramagnetic, formally gold(0) complex. DFT calculations reveal that the spin density of this highly robust coinage metal complex is mainly located on the allenylidene fragment, with only 1.8 and 3.1% on the gold center and the CAAC ligand, respectively. In addition, the first homoleptic bis(allenylidene)gold(i) complex has been prepared and fully characterized.


Pulsatile secretion of gonadotropins and prolactin in male marathon runners. Relation to the endogenous opiate system.
We tested the hypothesis that sustained, strenuous physical training alters the neuroendocrine regulation of pulsatile gonadotropin and/or prolactin secretion in men. Blood was sampled at 20-minute intervals over 8 hours in five endurance-trained men after a 10-15 mile run in the middle of the active training season, and in 11 nonendurance trained normal controls. In these two groups, basal patterns of physiologically pulsatile secretion of LH, FSH, and prolactin (PRL) were not significantly different in relation to the following parameters: mean serum concentration of each of the three hormones (N = 25 samples); areas under the hormone concentration vs. time curves; fractional, incremental, and absolute pulse amplitudes; and pulse frequency, or periodicity. To test for enhanced suppressive effects of endogenous opiates in trained male marathon runners, subjects were administered the potent opiate-receptor antagonist, naltrexone (1 mg/kg). This antagonist significantly stimulated pulsatile LH secretion by increasing mean serum LH values from 10.94 to 13.58 mIU/ml (P = 0.007); area under the LH concentration vs. time curve increased from 5370 to 6510 mIU/ml X 8 hours (P = 0.05) and, pulse frequency rose from 2.8 to 4.9 pulses/8 hours (P = 0.006). Naltrexone also enhanced pulse frequency of FSH secretion from 3.4 to 5.4 pulses/8 hours (P = 0.009), but did not alter serum prolactin concentrations. None of these responses differed significantly from those in normal sedentary controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Osteoma of the promontory mimicking a congenital cholesteatoma.
Osteoma of the temporal bone most commonly occurs in the external ear. Osteomas in the middle ear are not common, and only 25 relevant cases (18 papers) have been reported in the English literature. With only 5 cases reported to date, osteoma of the promontory in the middle ear is rare. This study reports a case of asymptomatic osteoma of the promontory in the middle ear mimicking a congenital cholesteatoma in a 4-year-old girl.


Ultrasmall calcium-enriched Prussian blue nanozymes promote chronic wound healing by remodeling the wound microenvironment.
Chronic wound healing remains challenging due to the oxidative microenvironment. Prussian blue (PB) nanoparticles exhibiting multiple antioxidant enzyme-like activities have attracted widespread attention, while their antioxidant efficacy remains unsatisfied. Herein, ultrasmall calcium-enriched Prussian blue nanoparticles (CaPB NPs) are simply constructed with high yields for the wound repair application. Owing to the ultrasmall size and synergistic effect of the generated dual active sites, the CaPB NPs exhibit prominent antioxidase-like activities, protecting cells from oxidative stress-induced damage. In addition to the effect of Ca on regulating keratinocyte and fibroblast growth, it has been demonstrated that the administration of CaPB NPs obviously promoted wound closure as well as collagen deposition and neovascularization in the full-thickness wound defect model in mice. Importantly, the CaPB NP treatment can effectively up-regulate the expression levels of anti-inflammatory cytokines and vascular endothelial growth factors to remodel the wound microenvironment, thereby accelerating the wound healing process. Overall, this work reveals that metal atom substitution is an effective strategy to construct ultrasmall and high-catalytic-performance PB-based nanozymes and further potentiate their effectiveness for chronic wound management.


Fixational eye movements following concussion.
The purpose of this study was to evaluate fixational eye movements (FEMs) with high spatial and temporal resolution following concussion, where oculomotor symptoms and impairments are common. Concussion diagnosis was determined using current consensus guidelines. A retinal eye-tracking device, the tracking scanning laser ophthalmoscope (TSLO), was used to measure FEMs in adolescents and young adults following a concussion and in an unaffected control population. FEMs were quantified in two fixational paradigms: (1) when fixating on the center, or (2) when fixating on the corner of the TSLO imaging raster. Fixational saccade amplitude in recent concussion patients (≤ 21 days) was significantly greater, on average, in the concussion group (mean = 1.03°; SD = 0.36°) compared with the controls (mean = 0.82°; SD = 0.31°), when fixating on the center of the imaging raster (t = 2.87, df = 82, p = 0.005). These fixational saccades followed the main sequence and therefore also had greater peak velocity (t = 2.86, df = 82, p = 0.006) and peak acceleration (t = 2.80, df = 82, p = 0.006). These metrics significantly differentiated concussed from controls (AUC = 0.67-0.68, minimum p = 0.005). No group differences were seen for the drift metrics in either task or for any of the FEMs metrics in the corner-of-raster fixation task. Fixational saccade amplitudes were significantly different in the concussion group, but only when fixating on the center of the raster. This task specificity suggests that task optimization may improve differentiation and warrants further study. FEMs measured in the acute-to-subacute period of concussion recovery may provide a quick (<3 minutes), objective, sensitive, and accurate ocular dysfunction assessment. Future work should assess the impact of age, mechanism of injury, and post-concussion recovery on FEM alterations following concussion.


Tooth brushing behaviour in twelve year old children and dental enamel.
This paper examines the association between the use of fluoride toothpastes by 12-year-old children and enamel opacities. Some problems inherent in measuring the effect of fluoride toothpaste on developing enamel are discussed. Data are shown that consider the association between tooth brushing behaviour and dental enamel defects in 1,934 children from areas in North Wales with low levels of fluoride in the drinking water (< 0.1 ppm F). Children who brushed more frequently were at greater risk of having diffuse types of enamel opacity present. No associations were identified between the amount of toothpaste used by the 12 year old subjects or the rinsing method used when brushing and enamel opacities.


No relationship is indicated between FHIT expression and clinicopathologic prognostic parameters in early stage cervical carcinoma.
In this study we investigated FHIT (Fragile Histidine Triad) protein alterations in cervical carcinomas to assess the relation of this gene with cervical cancer. Eighty-eight patients with surgically treated FIGO (International Federation of Gynecology and Obstetrics) stage IB carcinomas of the cervix were included in this study. Clinicopathologic prognostic factors were compared with FHIT expression status. Disease-free and overall survival was evaluated according to prognostic factors and FHIT expression. The FHIT gene was found to be depressed in 53% (47/88) of the tumors. None of the clinicopathologic prognostic parameters showed a correlation with FHIT expression. Univariate survival analysis with the Kaplan-Meier method showed that only the age of the patient is significantly correlated with disease-free survival. Interestingly, when the same analysis was done for 5-year overall survival; diameter of the primary tumor, depth of invasion, occurrence of lymph node involvement, and number of metastatic lymph nodes were found to be statistically significant. Furthermore, multivariate analysis with Cox regression revealed that lymph node involvement was the only independent variable for 5-year overall survival. In the present study there was no statistical correlation between FHIT expression and clinicopathologic prognostic factors or survival figures of the patients. These findings may be explained with the carcinogenic role of FHIT in tumoral progression but not in the tumoral development that takes place after the carcinogenetic period.


Detection and preliminary characterization of a new rabbit calicivirus related to rabbit hemorrhagic disease virus but nonpathogenic.
A new rabbit calicivirus related to the rabbit hemorrhagic disease virus (RHDV) was identified. The new virus contains significant differences from the previously characterized RHDV isolates in terms of pathogenicity, viral titer, tropism, and primary sequence of the structural protein. Cross-protection experiments, antigenic data, and sequence comparisons demonstrate that the new virus is more closely related to RHDV than to the European brown hare syndrome virus, another member of the caliciviruses of the lagomorph group. The existence of a nonpathogenic calicivirus, which we propose to name rabbit calicivirus (RCV), provides an explanation for the early discrepancies found in the course of serological surveys of the rabbit population in European countries.


Conserved synthetic peptides from the hemagglutinin of influenza viruses induce broad humoral and T-cell responses in a pig model.
Outbreaks involving either H5N1 or H1N1 influenza viruses (IV) have recently become an increasing threat to cause potential pandemics. Pigs have an important role in this aspect. As reflected in the 2009 human H1N1 pandemia, they may act as a vehicle for mixing and generating new assortments of viruses potentially pathogenic to animals and humans. Lack of universal vaccines against the highly variable influenza virus forces scientists to continuously design vaccines à la carte, which is an expensive and risky practice overall when dealing with virulent strains. Therefore, we focused our efforts on developing a broadly protective influenza vaccine based on the Informational Spectrum Method (ISM). This theoretical prediction allows the selection of highly conserved peptide sequences from within the hemagglutinin subunit 1 protein (HA1) from either H5 or H1 viruses which are located in the flanking region of the HA binding site and with the potential to elicit broader immune responses than conventional vaccines. Confirming the theoretical predictions, immunization of conventional farm pigs with the synthetic peptides induced humoral responses in every single pig. The fact that the induced antibodies were able to recognize in vitro heterologous influenza viruses such as the pandemic H1N1 virus (pH1N1), two swine influenza field isolates (SwH1N1 and SwH3N2) and a H5N1 highly pathogenic avian virus, confirm the broad recognition of the antibodies induced. Unexpectedly, all pigs also showed T-cell responses that not only recognized the specific peptides, but also the pH1N1 virus. Finally, a partial effect on the kinetics of virus clearance was observed after the intranasal infection with the pH1N1 virus, setting forth the groundwork for the design of peptide-based vaccines against influenza viruses. Further insights into the understanding of the mechanisms involved in the protection afforded will be necessary to optimize future vaccine formulations.


Helicobacter pylori infection in Xinjiang Uyghur Autonomous Region: Prevalence and analysis of related factors.
14C urea breath test (14C UBT) and immunohistochemical staining (IHC) are widely used for detection Helicobacter pylori (H. pylori) infection with different sensitivity, and there is a difference in H. pylori infection rate in Uyghur and Han ethnic groups. Both need large cohort studies to evaluate the differences more accurately. To analyze the difference between 14C UBT and IHC for H. pylori detection in Xinjiang Uyghur Autonomous Region and the difference between Uyghur and Han populations. There were 3944 cases of H. pylori infection detected by both IHC and 14C UBT at the same time (interval < 1 wk, with sampling site including gastric antrum, selected from 5747 patients). We compared the sensitivity of 14C UBT and IHC. We also compared 555 pairs of Han/Uyghur cases (completely matched for gender and age) for their H. pylori infection rates. The overall H. pylori infection rate of all 5747 cases and the correlation with other clinicopathological data were also further analyzed. SPSS V23.0 software was used for statistical analysis. The sensitivity was 94.9% for 14C UBT and 65.1% for IHC, which was a significant difference (n = 3944, P < 0.001). However, among those cases negative for H. pylori by 14C UBT (detection value ≤ 100), 4.8% were positive by IHC. Combining both methods, the overall H. pylori infection rate was 48.6% (n = 5747), and differences in gender, age group, ethnicity and region of residence significantly affected the H. pylori positive rates. According to age group (Han/Uyghur), the positive rates were ≤ 30 years (62.2%/100.0%), 31-40 years (45.2%/85.7%), 41-50 years (47.2%/79.2%), 51-60 years (44.6%/76.1%), 61-70 years (40.9%/68.2%), 71-80 years (41.7%/54.1%) and ≥ 81 years (42.9%/NA). The H. pylori infection rates of Han/Uyghur paired cases were 41.4% and 73.3%, which was a significant difference (P < 0.001) (555 pairs). H. pylori positivity was significantly related to moderate-severe grade 2-3 chronic/active gastritis and intestinal metaplasia (all P < 0.05). The sensitivity of 14C UBT was significantly higher, but combined application can still increase the accuracy. The prevention H. pylori should be emphasized for Uygur and young people.


Comparison of specimen collection and laboratory techniques for isolation of Haemophilus ducreyi.
Sixteen patients with clinical chancroid were studied prospectively; different culture media and sampling techniques from genital lesions were evaluated. Technique A was aspiration of a saline wash from the ulcer which was pooled and inoculated into rabbit blood, rabbit blood + vancomycin (5 microgram/ml), and semisolid chocolate agar + vancomycin (3 microgram/ml). Each primary culture medium was subcultured to chocolate agar with 1% IsoVitaleX (CA), CA with vancomycin (3 microgram/ml) plus polymyxin (7.5 microgram/ml; CA + vp). Technique B was the use of a cotton swab, plated directly on CA, CA + v, and CA + vp. Nine strains of Haemophilus ducreyi were obtained. Technique A yielded seven strains, whereas technique B yielded eight strains; with each technique, five strains were isolated only after use of selective antibiotic media. CA + v medium yielded the largest number of isolates. Direct inoculation by swab to CA + v from chancroidal ulcers is effective as an isolation technique for growth of H. ducreyi.


Enhanced engraftment of HTLV-I-infected human T cells in severe combined immunodeficiency mice by anti-asialo GM-1 antibody treatment.
The effects of anti-asialo GM-1 antibody (AAGM) treatment on the engraftment of human T-cell leukemia virus type I (HTLV-I)-infected human T cells in severe combined immunodeficiency (SCID) mice were studied. The frequency of tumor formation in an HTLV-I-transformed human T-cell line, MT-2 cells, at the site of inoculation was significantly higher in AAGM-treated than untreated mice (P<0.05): 16/18 (89%) and 16/26 (62%), respectively. The promotive effect of AAGM treatment on tumor development was marked in the early stage (less than 3 weeks), suggesting that the immediate reaction of natural killers to the inoculated cells may be important for the prevention of tumor development. The surface phenotypes and clonality of the tumor cells were the same as the MT-2 cells inoculated. Inoculation of peripheral blood mononuclear cells (PBMC) from one of the 4 adult T-cell leukemia/lymphoma (ATL) patients resulted in the development of tumors in AAGM-treated SCID mice. However, the surface phenotypes of the cells from these tumors were a mixture of B cells and T cells, suggesting that these tumors consisted of Epstein-Barr virus-transformed B cells and HTLV-I-transformed T cells. In addition, HTLV-I was detected by polymerase chain reaction in various organs of the mice inoculated with PBMC from the ATL patient and the asymptomatic carrier examined. These results suggest that elimination of natural killer function by AAGM treatment is important, although such treatment is not always necessary for the engraftment of HTLV-I-infected cells in SCID mice.


Mechanisms and Functions of Chemerin in Cancer: Potential Roles in Therapeutic Intervention.
Chemerin [RARRES2 [retinoic acid receptor responder 2], TIG2 [tazarotene induced gene 2 (TIG2)]] is a multifunctional cytokine initially described in skin cultures upon exposure to the synthetic retinoid tazarotene. Its secreted pro-form, prochemerin, is widely expressed, found systemically, and is readily converted into active chemerin by various proteases. Subsequent studies elucidated major roles of chemerin as both a leukocyte chemoattractant as well as an adipokine. Chemerin's main chemotactic receptor, the G-protein coupled receptor CMKLR1, is expressed on macrophages, dendritic, and NK cells. With respect to its role in immunology, chemerin mediates trafficking of these cells to sites of inflammation along its concentration gradient, and likely helps coordinate early responses, as it has been shown to have antimicrobial and angiogenic properties, as well. Recently, there has been mounting evidence that chemerin is an important factor in various cancers. As with its role in immune responses-where it can act as both a pro- and anti-inflammatory mediator-the potential functions or correlations chemerin has in or with cancer appears to be context dependent. Most studies, however, suggest a downregulation or loss of chemerin/RARRES2 in malignancies compared to the normal tissue counterparts. Here, we perform a comprehensive review of the literature to date and summarize relevant findings in order to better define the roles of chemerin in the setting of the tumor microenvironment and tumor immune responses, with an ultimate focus on the potential for therapeutic intervention.


Longitudinal data resource from the Wellbeing of Older People cohort of people aged >50 years in Uganda and South Africa from 2009 to 2019.
The population of people aged ≥60 years continues to increase globally, and has been projected by the United Nations Population Division to increase to 21% of the total population by 2050. In addition, the number of older people living with HIV has continued to increase owing to the introduction of antiretroviral therapy as a treatment for HIV-infected people. Most of the older people living with HIV are in sub-Saharan Africa, an area that faces the biggest burden of HIV globally. Despite the high burden, there are limited reliable data on how HIV directly and indirectly affects the health and wellbeing of older people within this region. To showcase the availability of data on how HIV directly and indirectly affects the health and wellbeing of older people in Uganda and South Africa (SA). The World Health Organization Study on global AGEing and adult health (SAGE), in collaboration with Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit and the Africa Health Research Institute (AHRI) in SA, started the SAGE Wellbeing of Older People Study (WOPS) in Uganda and SA in 2009. Since initiation, respondents have been surveyed every 2 years, with four waves of surveys conducted in Uganda and three waves in South Africa. The available datasets consist of two cohorts of people, aged >50 years, who were surveyed every 2 years between 2009 and 2018. The prevalence of HIV positivity over this period increased from 39% to 54% in Uganda and 48% to 62% in SA. The datasets provide comparisons of variables at a household level and at an individual level. At the individual level, the following measures can be compared longitudinally for a 10-year period for the following variables: sociodemographic characteristics; work history and benefits; health states and descriptions; anthropometrics performance tests and biomarkers; risk factors and preventive health behaviours; chronic conditions and health services coverage; healthcare utilisation; social cohesion; subjective wellbeing and quality of life; and impact of caregiving. This article describes the WOPS in Uganda and SA, the population coverage of this study, and the survey frequency of WOPS, survey measures, data resources available, the data resource access and the strengths and weaknesses of the study. The article invites interested researchers to further analyse the data and answer research questions of interest to enhance the impact of these data.


Ethnic differences: word descriptors used by African-American and white asthma patients during induced bronchoconstriction.
To determine if African-American and white patients with asthma (1) differ in the words they use to describe their breathlessness, and (2) differ in their perception of breathlessness. Descriptive cross-sectional design. The study setting was located in Northern California, an ethnically and economically diverse area. A total of 32 subjects, 16 per group, completed the study. All had a provocation concentration of methacholine chloride causing a 30% fall in FEV(1) (PC(30)) of </= 8 mg/mL. Serial pulmonary function testing was performed. Breathlessness was measured using the Borg scale and the visual analog scale. Word descriptors were measured by an open-ended word descriptor questionnaire. Significant ethnic differences in the words used to describe the sensation of breathlessness were present at PC(30). African Americans used upper airway word descriptors: tight throat (p < 0. 0004), scared-agitated (p < 0.006), voice tight (p < 0.04), itchy throat (p < 0.03), and tough breath (p < 0.04). Whites used lower airway or chest-wall symptom descriptors: deep breath (p < 0.03), light-headed (p < 0.03), out of air (p < 0.01), aware of breathing (p < 0.03), and hurts to breathe (p < 0.06). In addition, African Americans required a significantly smaller, 44.3% (mean), dose of methacholine to achieve PC(30) (p < 0.02). This study provides valuable new information about ethnicity and the words used to describe breathlessness during airflow obstruction. Asthmatic African Americans used primarily upper airway word descriptors; whites used lower airway or chest-wall word descriptors. Effective symptom monitoring requires asking the correct question and awareness that ethnic differences in the words used to describe breathlessness may exist.


Vitamin D deficiency in pregnancy - still a public health issue.
The objectives of this study were to quantify the prevalence of vitamin D insufficiency and deficiency in pregnancy, explore associated risk factors and discuss the public health implications. The study used retrospective analysis of randomly selected data. This is the first report on serum vitamin D levels in an unselected multi-ethnic population of pregnant women collected between April 2008 and March 2009. Women with sufficient stored serum were randomly selected from among all women who delivered between April 2008 and March 2009. Serum vitamin D levels were determined using liquid chromatography coupled to tandem mass spectrometry. Vitamin D levels were analysed with respect to ethnicity (marking skin tone), calendar quartile, body mass index (BMI), trimester and parity. Deficiency was defined as <25 nmol L(-1) , insufficiency 25-75 nmol L(-1) and adequacy >75 nmol L(-1) . Three hundred and forty-six women were included and represented the total population regarding skin tone, quartile, BMI, gestation and parity. Overall, 18% [95% confidence interval (CI): 15-23%] of sample women had adequate vitamin D levels; 36% were deficient, 45% insufficient. Among women with dark skin, only 8% (95% CI: 5-12%) had adequate levels compared with 43% (95% CI: 33-53%) of those with light skin. Obese women were found have significantly lower vitamin D levels than non-obese women. Vitamin D deficiency and insufficiency are prevalent year-round among pregnant women in North West London, especially those with darker skin. Existing supplementation guidelines should be supported; however, other measures are required to improve status among all women.


Double-blind 18-month trial of lithium versus divalproex maintenance treatment in pediatric bipolar disorder.
To determine whether divalproex sodium (DVPX) was superior to lithium carbonate (Li+) in the maintenance monotherapy treatment of youths diagnosed with bipolar disorder who had been previously stabilized on combination Li+ and DVPX (Li+/DVPX) pharmacotherapy. Youths ages 5-17 years with bipolar I or II disorder were initially treated with Li /DVPX. Patients meeting remission criteria for four consecutive weeks were then randomized in a double-blind fashion to treatment with either Li+ or DVPX for up to 76 weeks. Study participation ended if the subject required additional clinical intervention or if the subject did not adhere to study procedures. Patients were recruited between July 1998 and May 2002. One hundred thirty-nine youths with a mean (SD) age of 10.8 (3.5) years were initially treated with Li+/DVPX for a mean (SD) duration of 10.7 (5.4) weeks. Sixty youths were then randomized to receive monotherapy with Li+ (n = 30) or DVPX (n = 30). The Li+ and DVPX treatment groups did not differ in survival time until emerging symptoms of relapse (p = .55) or survival time until discontinuation for any reason (p = .72). DVPX was not found to be superior to Li+ as maintenance treatment in youths who stabilized on combination Li+/DVPX pharmacotherapy.


Acculturation, partner violence, and psychological distress in refugee women from Somalia.
This study examined the relations among acculturation, domestic violence, and mental health in 62 married refugee women from Somalia. Refugees from Somalia constituted the largest group of refugees entering the United States in 2005, and little is known about the presence of domestic violence in this group. The results showed that women who reported greater ability to speak English also reported more experiences of partner psychological abuse and physical aggression. Experiences of more psychological abuse and physical aggressions also predicted more psychological distress. Implications for future research and psychological services are addressed.


Energy balance in the newborn baby: use of a manikin to estimate radiant and convective heat loss.
Convective and radiant heat loss from a baby in an incubator were studied using a heated manikin. The mean radiant temperature of surrounding surfaces other than those vertically below the manikin was measured. The coefficients Af and hr were calculated as though this was the mean radiant temperature of the whole environment. The fraction (Af) of the body surface area which exchanged radiant energy with the surroundings increased from 0.48 for a foetal posture to 0.76 for a spreadeagle posture due to a decrease in radiant exchange between opposing body surfaces. The corresponding increase in the coefficient for heat exchange by radiation (hr) was from 3.1 to 4.9 Wm-2 K-1. The coefficient for convection (hc) increased from 4.0 to 5.4 WM-2 K-1 due to a decrease in effective body diameter as the limbs moved away from the trunk. These changes in Af, hr and hc show that posture is important in regulating heat loss from a baby. As the radiant temperature of the incubator canopy was between 2 and 4K below incubator air temperature, a baby loses more heat by radiation than by convection.


[The specific features of relations of the fleas Xenopsylla cheopis L. to the plague microbe of the Altai subspecies, its L-forms and revertant].
The rate and changes in the formation of bacterial lumps and blocks of the proventriculus in Xenopsylla cheopis fleas in their contamination with the plague microbe of the Altai subspecies, its L-form and revertant were studied to clarify the specific features of relations with the vector, including its transmission ability. The plague microbe of the Altai subspecies, which was exposed to L-transformation in the resistant organism of a warm-blooded host (a guinea pig), as well as L-form revertants obtained on nutrient media substantially lost their ability to get acclimatized in the vector and to form a proventricular block. The capacity to form lumps did not greatly differ in L- and original form of the microbe. At the same time, the ratio of the formed blocks and lumps was much lower, which points to the instability of the formed masses. This is supported by the detection of specimens with partial blocks only among the fleas infected with L-forms. The reversed bacterial form was exceeded in the rate of formation of lumps by the original and L-forms. This may be associated with the reversion of L-forms on the nutrient medium rather than in the vector. At the same time, the revertant formed stable blocks in shorter periods than did L-forms and caused a generalization of the infection in plague-infected mice, which may be important for further transmission of the microbe.


Cannabis use in Cape York Indigenous communities: high prevalence, mental health impacts and the desire to quit.
Anecdotal reports suggest that high rates of cannabis use and dependence are significant issues in Indigenous communities in north Queensland; however, there is little scientific evidence to support or refute this. The Cape York Cannabis Project seeks to investigate cannabis use rates, cannabis dependence and mental health impacts for the first time in three Cape York Indigenous communities. The current study reports preliminary findings, resulting from interviews with 133 Indigenous participants aged 14-47 years from one Cape York community. Quantitative data were gathered on rates of cannabis use, cannabis dependence as measured by a score of ≥ 3 the Severity of Dependence Scale. Qualitative self-report data were gathered concerning mental health impacts of cannabis and reasons for quitting. Very high rates of cannabis use were identified, with 66.2% of males and 30.5% of females interviewed being current users. An additional 12.2% of males and 30.5% of females were former users, and 21.6% of males and 39% of females had never used cannabis. High rates of cannabis dependence were also observed. Of those current users who used cannabis at least weekly, 67.7% reported cannabis dependence. A range of mental health impacts due to cannabis were reported. In total, 76.1% of current users were considering quitting or cutting down. Rates of use and dependence were much higher than national rates, and indicate significant mental health harms due to cannabis. Further investigation of mental health impacts of cannabis is required, as is intervention to reduce these impacts.


Polymyxin Monotherapy vs. Combination Therapy for the Treatment of Multidrug-resistant Infections: A Systematic Review and Meta-analysis.
The objective of this review was to compare the effectiveness of Colistin monotherapy and combination therapy for the treatment of multidrug-resistant gram-negative bacterial infections. PubMed, Cochrane Library. In this systematic review, we included all retrospective and prospective studies and randomized controlled trials (RCTs) that compared intravenous polymyxin monotherapy and combination therapy with any other antibiotic for treating multidrug-resistant infections. Studies using inhaled polymyxins with 5 or less than 5 patients were excluded. The primary outcome was 30-day all-cause mortality and if not reported at day 30 we extracted and documented the closest time point. Both crude outcome rates and adjusted effect estimates were extracted for mortality. Search string used was "(Colistin OR polymyxin) AND (Enterobacteriaceae OR Klebsiella OR Acinetobacter OR Escherichia coli OR Pseudomonas) AND (random OR prospective OR retrospective OR cohort OR observational OR blind)." Thirty-nine studies were included in our analysis; out of which 6 RCTs were included and 9 studies used carbapenem as the adjunctive antibiotic. Each study was screened and reviewed for eligibility independently by two authors and data extrapolated on an Excel sheet. The meta-analysis of polymyxin monotherapy vs. combination therapy in multidrug-resistant infections yielded an odds ratio (OR) of 0.81 (95% confidence interval [CI]: 0.65-1.01) with minimal heterogeneity (I 2 = 40%), whereas pooled analysis of this comparison in studies that included carbapenem as combination therapy yielded an OR of 0.64 (CI: 0.40-1.03; I 2 = 62%). Likewise, the pooled analysis of the RCTs yielded an OR of 0.82 (95% CI: 0.58-1.16, I 2 = 22%). All these showed no statistical significance. However, it was seen that polymyxin combination therapy was more effective in multidrug-resistant infections compared to polymyxin monotherapy. The effectiveness was more glaring when carbapenems were used as the combination drug instead of any other antibiotic and more so in many in vitro studies that used polymyxin combination therapy. Although statistically insignificant, it would be prudent to use polymyxin combination therapy to treat multidrug-resistant gram-negative bacilli (GNB) infection over monotherapy with preference to use carbapenem as the adjunct alongside polymyxins. Samal S, Mishra SB, Patra SK, Rath A, Dash A, Nayak B, et al. Polymyxin Monotherapy vs. Combination Therapy for the Treatment of Multidrug-resistant Infections: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2021;25(2):199-206.


Disability and poverty - Reflections on research experiences in Africa and beyond.
Whilst broadly agreed in the literature that disability and poverty are closely interlinked, the empirical basis for this knowledge is relatively weak. To describe and discuss the current state of knowledge and to suggest the need for further generation of knowledge on disability and poverty. Two recent attempts at statistically analysing the situation for disabled people and a series of qualitative studies on disability and poverty are applied in a discussion on the state of current knowledge. Firstly, the surveys confirm substantial gaps in access to services, and a systematic pattern of lower levels of living amongst individuals with disability as compared to non-disabled. Existing surveys are however not originally set up to study the disability - poverty relationship and thus have some important limitations. Secondly, the qualitative studies have shown the relevance of cultural, political and structural phenomena in relation to poverty and disability, but also the complexity and the contextual character of these forces that may sometimes provide or create opportunities either at the individual or the collective level. Whilst not establishing evidence as such, the qualitative studies contribute to illustrating some of the mechanisms that bring individuals with disability into poverty and keep them there. A longitudinal design including both quantitative and qualitative methods and based on the current conceptual understanding of both disability and poverty is suggested to pursue further knowledge generation on the relationship between disability and poverty.


PrivaTree: Collaborative Privacy-Preserving Training of Decision Trees on Biomedical Data.
Biomedical data generation and collection have become faster and more ubiquitous. Consequently, datasets are increasingly spread across hospitals, research institutions, or other entities. Exploiting such distributed datasets simultaneously can be beneficial; in particular, classification using machine learning models such as decision trees is becoming increasingly common and important. However, given that biomedical data is highly sensitive, sharing data records across entities or centralizing them in one location are often prohibited due to privacy concerns or regulations. We design PrivaTree, an efficient and privacy-preserving protocol for collaborative training of decision tree models on distributed, horizontally partitioned, biomedical datasets. Although decision tree models may not always be as accurate as neural networks, they have better interpretability and are helpful in decision-making processes, which are crucial for biomedical applications. PrivaTree follows a federated learning approach, where raw data is not shared, and where every data provider computes updates to a global decision tree model being trained, on their private dataset. This is followed by privacy-preserving aggregation of these updates using additive secret-sharing, in order to collaboratively update the model. We implement PrivaTree, and evaluate its computational and communication efficiency on three different biomedical datasets, as well as the accuracy of the resulting models. Compared to the model centrally trained on all data records, the obtained collaborative model presents a modest loss of accuracy, while consistently outperforming the accuracy of the local models, trained separately by each data provider. Moreover, PrivaTree is more efficient than existing solutions, which makes it usable for training decision trees with numerous nodes, on large complex datasets, with both continuous and categorical attributes, as often found in the biomedical field.


miRNA-122 Protects Mice and Human Hepatocytes from Acetaminophen Toxicity by Regulating Cytochrome P450 Family 1 Subfamily A Member 2 and Family 2 Subfamily E Member 1 Expression.
Acetaminophen toxicity is a leading cause of acute liver failure (ALF). We found that miRNA-122 (miR-122) is down-regulated in liver biopsy specimens of patients with ALF and in acetaminophen-treated mice. A marked decrease in the primary miR-122 expression occurs in mice on acetaminophen overdose because of suppression of its key transactivators, hepatocyte nuclear factor (HNF)-4α and HNF6. More importantly, the mortality rates of male and female liver-specific miR-122 knockout (LKO) mice were significantly higher than control mice when injected i.p. with an acetaminophen dose not lethal to the control. LKO livers exhibited higher basal expression of cytochrome P450 family 2 subfamily E member 1 (CYP2E1) and cytochrome P450 family 1 subfamily A member 2 (CYP1A2) that convert acetaminophen to highly reactive N-acetyl-p-benzoquinone imine. Upregulation of Cyp1a2 primary transcript and mRNA in LKO mice correlated with the elevation of aryl hydrocarbon receptor (AHR) and mediator 1 (MED1), two transactivators of Cyp1a2. Analysis of ChIP-seq data in the ENCODE (Encyclopedia of DNA Element) database identified association of CCCTC-binding factor (CTCF) with Ahr promoter in mouse livers. Both MED1 and CTCF are validated conserved miR-122 targets. Furthermore, depletion of Ahr, Med1, or Ctcf in Mir122-/- hepatocytes reduced Cyp1a2 expression. Pulse-chase studies found that CYP2E1 protein level is upregulated in LKO hepatocytes. Notably, miR-122 depletion sensitized differentiated human HepaRG cells to acetaminophen toxicity that correlated with upregulation of AHR, MED1, and CYP1A2 expression. Collectively, these results reveal a critical role of miR-122 in acetaminophen detoxification and implicate its therapeutic potential in patients with ALF.


Effects of shRNA Targeting Maspin on the Invasion of Extravillous Trophoblast Cell.
Objective Hypomethylation of the maspin gene results in increased expression of maspin in preeclamptic placentas. However, maspin gene function and the molecular aspects in placentation remain largely unclear. The study was designed to investigate the effects of maspin on the invasion of extravillous trophoblast cell line (TEV-1) and the molecular mechanism. Study Design We cloned short hairpin RNA (shRNA) targeting maspin gene into plasmid pGenesil-1.1 eukaryotic expression vector and then transfected it using adenovirus. The methylation rates in the maspin gene were detected by bisulfite sequencing polymerase chain reaction; the invasive ability of trophoblast cells was examined by Transwell chamber assay; the mRNA and protein expression of maspin and some invasive related gene was detected by reverse transcription-polymerase chain reaction and Western blot analysis. Results After the maspin expression was successfully knocked down, the methylation rates in the maspin gene were significantly increased, and the number of cells invading through Matrigel (Corning Life Sciences and BD Biosciences) was obviously increased. The mRNA levels of vascular endothelial growth factor-A (VEGF-A), vascular endothelial growth factor-C (VEGF-C), and matrix metalloproteinase-2 (MMP2) were increased significantly. Conclusion Using shRNA technology, this study further verified that maspin gene methylation could decrease maspin expression and inhibit the invasion of TEV-1 cells through VEGF-A, VEGF-C, and MMP2.


Differentiation of human embryonic stem cells and induced pluripotent stem cells to cardiomyocytes: a methods overview.
Since human embryonic stem cells were first differentiated to beating cardiomyocytes a decade ago, interest in their potential applications has increased exponentially. This has been further enhanced over recent years by the discovery of methods to induce pluripotency in somatic cells, including those derived from patients with hereditary cardiac diseases. Human pluripotent stem cells have been among the most challenging cell types to grow stably in culture, but advances in reagent development now mean that most laboratories can expand both embryonic and induced pluripotent stem cells robustly using commercially available products. However, differentiation protocols have lagged behind and in many cases only produce the cell types required with low efficiency. Cardiomyocyte differentiation techniques were also initially inefficient and not readily transferable across cell lines, but there are now a number of more robust protocols available. Here, we review the basic biology underlying the differentiation of pluripotent cells to cardiac lineages and describe current state-of-the-art protocols, as well as ongoing refinements. This should provide a useful entry for laboratories new to this area to start their research. Ultimately, efficient and reliable differentiation methodologies are essential to generate desired cardiac lineages to realize the full promise of human pluripotent stem cells for biomedical research, drug development, and clinical applications.


Adverse childhood experiences and lifetime suicide ideation: a cross-sectional study in a non-psychiatric hospital setting.
We have assessed the effect of adverse childhood experiences on the lifetime prevalence of suicide ideation in a cross-sectional study involving 182 patients aged 18 to 44 years, consecutive attenders at an A&E review clinic. All participants were interviewed by a psychologist using standardised questionnaire instruments addressing participants' demographic characteristics, drug use, depressed mood, eight major categories of adverse childhood experiences (including physical, emotional and sexual abuse) and suicide ideation. The response rate was 73%. In multivariate logistic regression analyses, those with a history of two or more forms of childhood adversity relative to those with none were at increased risk of depressed mood (OR = 5.5, 95% CI = 2.3-13.3) and suicide ideation (OR = 3.5, 95% CI = 1.5-8.3). The findings emphasise the need to set suicide prevention within the broader context of society's obligation to protect children from physical, emotional and sexual abuse.


The mutagenicity of cigarette smokers' urine.
Using the methods of Yamasaki and Ames (1977), we have studied the mutagenicity of urine samples from 29 cigarette smokers and 14 nonsmokers. Duplicate plates at each dose yield reproducible dose-response curves, evening and 24-hour samples of smokers' urine have similar levels of mutagenic activity, as do evening samples from the same smoker from different days. Smokers' daily cigarette tar intake is correlated with urinary mutagen concentration, but the correlation achieves statistical significance only in the sub-sample of smokers over 25 years old. Mutagenic activity is also detectable in some nonsmokers, but as a group, their urinary mutagenic activity is far lower than that of smokers.


[Exploratory analysis of risk factors of acute inner ear dysfunctions].
Aside from the clinical picture, the frequent occurrence of vascular risk factors favors a vascular pathogenesis of acute sensorineural hearing loss. However, the data on the association of vascular risk factors with sensorineural hearing loss are controversial. Achieving a sufficient number of patients and establishing a suitable control group is difficult. We analyzed the data of 393 patients suffering from acute sensorineural hearing loss. Risk factors, general, audiological, and laboratory parameters were investigated. Mean hearing loss and remission during 10 days of hospital treatment were calculated. The patient group was divided into patients with a certain risk factor and those without this risk factor, and mean remission and hearing loss were compared. Patients suffering from hyperlipidemia or hypotension had substantial and significantly higher mean hearing losses than patients not suffering from these diseases. Thrombosis, embolism, and hypertension were associated with a significantly worse remission of hearing loss. Repeated episodes of sensorineural hearing loss showed a significant worse remission, but less mean hearing loss before therapy. Smoking, diabetes mellitus, infections of the upper airways, and allergies had no influence on remission and mean hearing loss.


Programmatic management of patients with pre-extensively drug-resistant tuberculosis in Peru, 2011-2014.
In Peru, a treatment approach for extensively drug-resistant tuberculosis (XDR-TB) incorporating World Health Organization Group 5 drugs and patient-centred care has achieved 65% success. To extend this approach to pre-XDR-TB patients, we evaluated this population separately. To assess programmatic management of pre-XDR-TB. Retrospective study using the official national registry from 2011 to 2014. Cases were separately evaluated according to resistance to fluoroquinolones (FQs) (pre-XDR-F) or to second-line injectables (SLIs) (pre-XDR-I). Of 610 pre-XDR-TB patients, 120 (20%) had pre-XDR-F and 490 (80%) had pre-XDR-I. Pre-XDR-F cases were older (34 years vs. 28 years, P < 0.001) and a higher proportion had previously received two or more regimens (70% vs. 38%, P < 0.001). Among the 452 patients who started treatment in 2011-2013, treatment success was 43.3%, 26.5% were lost to follow-up, 12.1% died and 13.7% failed treatment. Success was higher in pre-XDR-I (48.5%) than pre-XDR-F (21.4%) patients. History of previous treatment (OR 2.23, 95%CI 1.52-3.38) and pre-XDR-F (OR 2.39, CI 1.18-4.83) were associated with unsuccessful outcomes. Programmatic management of pre-XDR-TB has not been successful, particularly in pre-XDR-F patients, with lower rates of success than those achieved in the same setting for XDR-TB. The strategy used for XDR-TB should be extended to pre-XDR-TB patients in Peru.


Flooding and Clostridium difficile Infection: A Case-Crossover Analysis.
Clostridium difficile is a bacterium that can spread by water. It often causes acute gastrointestinal illness in older adults who are hospitalized and/or receiving antibiotics; however, community-associated infections affecting otherwise healthy individuals have become more commonly reported. A case-crossover study was used to assess emergency room (ER) and outpatient visits for C. difficile infection following flood events in Massachusetts from 2003 through 2007. Exposure status was based on whether or not a flood occurred prior to the case/control date during the following risk periods: 0-6 days, 7-13 days, 14-20 days, and 21-27 days. Fixed-effects logistic regression was used to estimate the risk of diagnosis with C. difficile infection following a flood. There were 129 flood events and 1575 diagnoses of C. difficile infection. Among working age adults (19-64 years), ER and outpatient visits for C. difficile infection were elevated during the 7-13 days following a flood (Odds Ratio, OR = 1.69; 95% Confidence Interval, CI: 0.84, 3.37). This association was more substantial among males (OR = 3.21; 95% CI: 1.01-10.19). Associations during other risk periods were not observed (p < 0.05). Although we were unable to differentiate community-associated versus nosocomial infections, a potential increase in C. difficile infections should be considered as more flooding is projected due to climate change.


Jamshidi bone marrow needle modification.
A modification of the Jamshidi bone marrow biopsy needle is described. Modification includes designing a removable handle and changes to the obturator. These modifications allow for more precise use, prevention of instrument breakage, and greater convenience for the operator.


Protease-based cross-linked enzyme aggregates with improved catalytic stability, silver removal, and dehairing potentials.
Proteases have gained special research place due to their broader activity spectrum and applied perspectives for different industrial sectors. The present research focused on three aims, i.e., (1) to identify the best protease producer strain among three different Aspergillus strains, (2) the development of protease-based cross-linked enzyme aggregates (CLEAs) and (3) silver removal and dehairing potentialities of developed CLEAs. A. flavus gave optimum activity (98.50 U/mL) with the culture conditions (pH -7.5, 35 °C, inoculum 2.5 mL and fermentation time 48 h) by applying RSM under CCD. The protease-CLEAs were developed with recovery activity (37.45%) by optimizing conditions through RSM under CCD (80% ammonium sulfate, 65 mM glutaraldehyde, and 0.15 mM BSA). The adequacy of the model was checked by ANOVA, and the interactions among different variables were plotted using 3-D graphs. The characterization profile revealed high pH and thermal stability at pH -9 and 60 °C, respectively. The kinetic study revealed lower KM and higher Vmax values (31.02 μM and 91.16 U/mL, respectively) after CLEAs formation, as compared to the free protease (61.42 μM and 84.45 U/mL, respectively). By applying on X-ray film and animal hides, protease-CLEAs showed the best activity with minimum time as compared to free protease.


"I Would Do It All Over Again": Cherishing Time and the Absence of Regret in Continuing a Pregnancy after a Life-Limiting Diagnosis.
Parents, after learning of a life-limiting fetal condition (LLFC), experience emotional distress and must consider options that impact the remainder of the pregnancy, their future lives, and family members. For those who continue, little is known about their long-term presence or absence of regret about their choice, the reasons for this feeling, or its impact on their life. The aim of this research was to examine the concept of decision regret in parents who opted to continue a pregnancy affected by an LLFC. The contextual factors, conditions, and consequences surrounding the presence or absence of regret were analyzed. Data were retrieved from a cross-sectional study using the Quality of Perinatal Palliative Care and Parental Satisfaction Instrument. Participants were parents (N = 405) who experienced a life-limiting prenatal diagnosis and opted to continue their pregnancy. Secondary data analysis examined qualitative responses (121/402) to an item addressing regret. Dimensional analysis was used to examine data, identifying context, conditions, and consequences associated with the presence or absence of regret. Absence of regret was articulated in 97.5 percent of participants. Parents valued the baby as a part of their family and had opportunities to love, hold, meet, and cherish their child. Participants treasured the time together before and after the birth. Although emotionally difficult, parents articulated an empowering, transformative experience that lingers over time.


Phosphorylation-dephosphorylation cycle of HP1α governs accurate mitotic progression.
Heterochromatin protein 1α (HP1α), a bona fide factor of silent chromatin, is required for establishing as well as maintaining the higher-order chromatin structure in eukaryotes. HP1α is decorated with several post-translational modifications, and many of these are critical for its cellular functions. HP1α is heavily phosphorylated; however, its physiological relevance had remained to be completely understood. We have recently demonstrated that human HP1α is a mitotic target for NDR kinase, and the phosphorylation at the hinge region of HP1α at the G 2/M phase of the cell cycle is crucial for mitotic progression and Sgo1 loading at mitotic centromeres (Chakraborty et al., 2014). We now demonstrate that the dephosphorylation of HP1α within its hinge domain occurs during mitosis, specifically soon after prometaphase. In the absence of the hinge-specific HP1α phosphorylation, either as a consequence of depleting NDR1 or in cells expressing a non-phosphorylatable HP1α mutant, the cells arrest in prometaphase with several mitotic defects. In this study we show that NDR1-depleted cells expressing hinge-specific phosphomimetic HP1α mutant rescues the prometaphase arrest but displays defects in mitotic exit, suggesting that the dephosphorylation of HP1α is required for the completion of cytokinesis. Taken together, our results reveal that the phosphorylation-dephosphorylation cycle of HP1α orchestrates accurate progression of cells through mitosis.


Ratio of Simple versus Comminuted Lateral Wall Fractures of the Orbit.
Reduction of a fracture may be relatively easy with a simple, noncomminuted fracture along the zygomaticofrontal suture, zygomaticomaxillary buttress, or the inferior rim of the orbit. When one or more of these key landmarks is comminuted, it becomes more important to confirm that the fracture commonly seen between the greater wing of the sphenoid and the zygoma is properly repositioned. The zygomaticosphenoidal suture is an excellent landmark with a simple lateral orbital wall fracture (LOWF), but it may not be reliable in patients with a comminuted fracture. The purpose of this study is to determine the frequency that the lateral orbital wall (LOW) is a reliable landmark in the reduction of a zygoma fracture by determining the ratio between simple versus comminuted LOWF. To identify 100 patients with a LOWF, the authors reviewed consecutive midface computed tomography images of 877 patients performed over a 25-month period from one of our city's primary Level I trauma and teaching hospitals. A total of 121 LOWF were identified in 100 patients. In 60.3% of cases the facture was a simple, noncomminuted LOWF. In 39.7% of cases the fracture was comminuted (p = 0.023). Simple LOWF are significantly more common than comminuted fractures. In 39.7% of fractures the LOW is comminuted. This suggests that there are many fractures in which other modalities may be much more important to use to confirm the proper reduction of the zygoma.


Comparison of Direct Repair Versus Anatomic Graft Reconstruction of the Anterior Talofibular Ligament: A Biomechanical Cadaveric Study.
The goal of our study is to compare the stability of the anatomic reconstruction of the anterior talofibular ligament (ATFL) with direct repair of the ATFL, in a cadaver model. We performed the following techniques in 18 cadaveric ankles: the intact ATFL was cut, after which a direct repair using 2 anchors was performed. The repair was sectioned, and anatomic reconstruction was then performed with a tendon autograft. We measured angular displacement in 3 anatomic planes (axial, coronal, sagittal) for each situation in response to the anterior drawer test (ADT), talar tilt test (TTT) and pivot test (PT), using a specifically constructed arthrometer. The sectioned ATFL was inferior to the intact ATFL in the axial plane with the ADT (p = .012), in the axial plane with the PT (p = .001) and in the axial and coronal planes with the TTT (p = .013 and p = .016, respectively). Direct anatomic repair was inferior to the intact ATFL in the axial plane upon the PT (p = .009). No differences could be found between anatomic graft reconstructions and the intact ATFL with any manoeuver, nor when comparing anatomic graft reconstruction and direct repair with 2 anchors. We were able to conclude that anatomic graft reconstruction of the ATFL reproduces angular stability of the native ligament in a cadaver model. While we could not detect if anatomic graft reconstruction was superior to direct repair, the latter proved to be less stable in the axial plane upon internal rotation (pivot test) versus the intact ATFL.


The pyruvate-tricarboxylic acid cycle node: a focal point of virulence control in the enteric pathogen Yersinia pseudotuberculosis.
Despite our increasing knowledge of the specific pathogenicity factors in bacteria, the contribution of metabolic processes to virulence is largely unknown. Here, we elucidate a tight connection between pathogenicity and core metabolism in the enteric pathogen Yersinia pseudotuberculosis by integrated transcriptome and [(13)C]fluxome analysis of the wild type and virulence-regulator mutants. During aerobic growth on glucose, Y. pseudotuberculosis reveals an unusual flux distribution with a high level of secreted pyruvate. The absence of the transcriptional and post-transcriptional regulators RovA, CsrA, and Crp strongly perturbs the fluxes of carbon core metabolism at the level of pyruvate metabolism and the tricarboxylic acid (TCA) cycle, and these perturbations are accompanied by transcriptional changes in the corresponding enzymes. Knock-outs of regulators of this metabolic branch point and of its central enzyme, pyruvate kinase (ΔpykF), result in mutants with significantly reduced virulence in an oral mouse infection model. In summary, our work identifies the pyruvate-TCA cycle node as a focal point for controlling the host colonization and virulence of Yersinia.


Role of nitric oxide dependence on nitric oxide synthase-like activity in the water stress signaling of maize seedling.
Nitric oxide (NO) has been known as an important signal in plant antioxidative defense but its production and roles in water stress are less known. The present study investigated whether NO dependence on a NO synthase-like (NOS) activity is involved in the signaling of drought-induced protective responses in maize seedlings.NOS activity, rate of NO release and drought responses were analyzed when NO donor sodium nitroprusside (SNP), NO scavenger c-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) and NOS inhibitor L-NAME (NG-nitro-L-arginine methyl ester) were applied to both detached maize leaves and whole plants. Both NOS activity and the rate of NO release increased substantially under dehydration stress. The high NOS activity induced by c-PTIO as NO scavenger and NO accumulation inhibited by NOS inhibitor L-NAME in dehydration-treated maize seedlings indicated that most NO production under water deficit stress may be generated from NOS-like activity. After dehydration stress for 3 h, detached maize leaves pretreated with NO donor SNP maintained more water content than that of control leaves pretreated with water. This result was consistent with the decrease in the transpiration rate of SNP-treated leaves subjected to drought treatment for 3 h. Membrane permeability, a cell injury index, was lower in SNP-treated maize leaves under dehydration stress for 4 h when compared with the control leaves. Also, superoxide dismutase (SOD) activity of SNP combined drought treatment maize leaves was higher than that of drought treatment alone, indicating that exogenous NO treatment alleviated the water loss and oxidative damage of maize leaves under water deficit stress. When c-PTIO as a specific NO scavenger was applied, the effects of applied SNP were overridden. Treatment with L-NAME on leaves also led to higher membrane permeability, higher transpiration rate and lower SOD activities than those of control leaves, indicating that NOS-like activity was involved in the antioxidative defense under water stress. These results suggested that NO dependence on NOS-like activity serves as a signaling component in the induction of protective responses and is associated with drought tolerance in maize seedlings.


Vasopressor and Inotrope Therapy in Cardiac Critical Care.
Patients admitted to the cardiac intensive care unit (CICU) are often in shock and require hemodynamic support. Identifying and addressing the pathophysiology mechanisms operating in an individual patient is crucial to achieving a successful outcome, while initiating circulatory support therapy to restore adequate tissue perfusion. Vasopressors and inotropes are the cornerstone of supportive medical therapy for shock, in addition to fluid resuscitation when indicated. Timely initiation of optimal vasopressor and inotrope therapy is essential for patients with shock, with the ultimate goals of restoring effective tissue perfusion in order to normalize cellular metabolism. Use of vasoactive agents for hemodynamic support of patients with shock should take both arterial pressure and tissue perfusion into account when choosing therapeutic interventions. For most patients with shock, including cardiogenic or septic shock, norepinephrine (NE) is an appropriate choice as a first-line vasopressor titrated to achieve an adequate arterial pressure due to a lower risk of adverse events than other catecholamine vasopressors. If tissue and organ perfusion remain inadequate, an inotrope such as dobutamine may be added to increase cardiac output to a sufficient level that meets tissue demand. Low doses of epinephrine or dopamine may be used for inotropic support, but high doses of these drugs carry an excessive risk of adverse events when used for vasopressor support and should be avoided. When NE alone is inadequate to achieve an adequate arterial pressure, addition of a noncatecholamine vasopressor such as vasopressin or angiotensin-II is reasonable, in addition to rescue therapies that may improve vasopressor responsiveness. In this review, we discuss the pharmacology and evidence-based use of vasopressor and inotrope drugs in critically ill patients, with a focus on the CICU population.


A comparative study of functional assays for tissue factor pathway inhibitor using normal plasma and clinical samples.
Tissue factor pathway inhibitor (TFPI) is a Kunitz-type inhibitor that regulates the initiation of tissue factor-mediated coagulation. Recent reports in the literature have described variable results using different methodologies for TFPI measurement. In this study, we used one clotting and two amidolytic methodologies to assess TFPI functional levels. The study groups included normal healthy donors as well as patients with acute hepatitis, diabetes, coronary artery bypass graft operations, deep vein thrombosis, and prior to and during heparin therapy. The aims were to compare the results obtained in normal plasma using different assay systems, to compare TFPI levels in a range of clinical samples, including those previously not determined using a clotting methodology, and to report TFPI levels in patient groups previously not investigated. The results clearly demonstrate poor correlation between functional TFPI values using the different methodologies, highlighting the requirement for standardization.


Anaesthetic Approach for Patient with Hereditary Angioedema.
Hereditary Angioedema (HEA), a disease caused by a mutation in the gene that encodes for the production of the fraction C1 in the complement (C1-INH), is a rare pathology (1/50.000) that causes swelling of the skin and submucosa in various organs, either naturally triggered or provoked by physical and psychological traumas, infections, or by the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme inhibitors (ACEIs). Surgical trauma may spur the HEA crisis, leading to complications such as the swelling of the respiratory tracts and hemodynamic instability. Thus, the pre-surgical approach to HEA patients requires a specific plan that ensures short term prophylaxis, careful intra-operative management, rescue therapy and intensive post-surgery care. We present a report on a video-laparoscopic cholecystectomy approach for a 28-year-old woman diagnosed with asthma and HEA with symptomatic choledocholithiasis. We opted for short-term prophylaxis and immunology with the intravenous application of C1-INH. Ultrasonography imaging showed arterial wall oedema, which could correspond to a manifestation of C1-INH deficiency in the wall of the manipulated arteries during ultrasonography-guided puncture. Once the patient recovered consciousness, she was transferred to the intensive care unit and was discharged on the 6th day of hospitalisation.


Cyclic neutropenia (CN): a clue to the control of granulopoiesis.
A simple quantitative feedback model of granulopoiesis is presented and discussed within the framework of existing data on granulopoiesis in both normals and patients with cyclic neutropenia (CN). The model assumes that the controlled compartment is the bone marrow pool of mature neutrophils (PMNs), which sends a negative feedback signal to the mitotic pool of early granulocyte precursors (i.e., CFU-C, myeloblasts, etc.) thus controlling the granulocyte production rate. Three parameters are found to play important roles in determining the response of the system to perturbations. These are: TM, the granulocyte maturation time; a, a parameter reflecting the strength of the negative feedback exerted by mature PMNs on the granulocyte production rate; and b, a parameter describing the leakiness of the bone marrow for PMN egress. It is shown that depending on the relative magnitudes of a and b, the system will either respond to perturbations with a damped oscillation (a less than b: the normal state) or with a sustained oscillation (a greater than b: the CN state). In both cases, the oscillation period is found to approximately equal 2TM. Deductions of the values of a, b, and TM from experimental data are consistent with the predictions of the model and show an increased value of a in CN relative to the normal state. This suggests an overly active feedback mechanism as the pathophysiologic basis of CN. In addition, the model can explain how various therapeutic agent correct CN and also provides insight into why other hematologic cell lines and CSA oscillate in CN.


Molecular Signatures Integral to Natural Reprogramming in the Pigment Epithelium Cells after Retinal Detachment in Pleurodeles waltl.
The reprogramming of retinal pigment epithelium (RPE) cells into retinal cells (transdifferentiation) lies in the bases of retinal regeneration in several Urodela. The identification of the key genes involved in this process helps with looking for approaches to the prevention and treatment of RPE-related degenerative diseases of the human retina. The purpose of our study was to examine the transcriptome changes at initial stages of RPE cell reprogramming in adult newt Pleurodeles waltl. RPE was isolated from the eye samples of day 0, 4, and 7 after experimental surgical detachment of the neural retina and was used for a de novo transcriptome assembly through the RNA-Seq method. A total of 1019 transcripts corresponding to the differently expressed genes have been revealed in silico: the 83 increased the expression at an early stage, and 168 increased the expression at a late stage of RPE reprogramming. We have identified up-regulation of classical early response genes, chaperones and co-chaperones, genes involved in the regulation of protein biosynthesis, suppressors of oncogenes, and EMT-related genes. We revealed the growth in the proportion of down-regulated ribosomal and translation-associated genes. Our findings contribute to revealing the molecular mechanism of RPE reprogramming in Urodela.


Erbb4 Deletion From Inhibitory Interneurons Causes Psychosis-Relevant Neuroimaging Phenotypes.
Converging lines of evidence suggest that dysfunction of cortical GABAergic inhibitory interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and glutamatergic metabolite levels, and decreases in ligand binding to GABAA α5 receptors and to the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between inhibitory interneuron dysfunction and these neuroimaging readouts are yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal inhibitory interneurons leads to synaptic defects, and behavioral and cognitive phenotypes relevant to psychosis in mice. Here, we investigated how this inhibitory interneuron disruption affects hippocampal in vivo neuroimaging readouts. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F/F, n = 12) and their wild-type littermates (Erbb4F/F, n = 12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography. Erbb4 mutant mice showed significantly elevated ventral hippccampus CBF and glutamine levels, and decreased SV2A density across hippocampus sub-regions compared to wild-type littermates. No significant GABAA receptor density differences were identified. These findings demonstrate that specific disruption of cortical inhibitory interneurons in mice recapitulate some of the key neuroimaging findings in patients with psychosis, and link inhibitory interneuron deficits to non-invasive measures of brain function and neurochemistry that can be used across species.


Streptococcus bovimastitidis sp. nov., isolated from a dairy cow with mastitis.
Here we describe a new species of the genus Streptococcus that was isolated from a dairy cow with mastitis in New Zealand. Strain NZ1587T was Gram-positive, coccus-shaped and arranged as chains, catalase and coagulase negative, γ-haemolytic and negative for Lancefield carbohydrates (A-D, F and G). The 16S rRNA sequence did not match sequences in the NCBI 16S rRNA or GreenGenes databases. Taxonomic classification of strain NZ1587T was investigated using 16S rRNA and core genome phylogeny, genome-wide average nucleotide identity (ANI) and predicted DNA-DNA hybridisation (DDH) analyses. Phylogeny based on 16S rRNA was unable to resolve the taxonomic position of strain NZ1587T, however NZ1587T shared 99.4 % identity at the 16S rRNA level with a distinct branch of S. pseudoporcinus. Importantly, core genome phylogeny demonstrated that NZ1587T grouped amongst the 'pyogenic' streptococcal species and formed a distinct branch supported by a 100 % bootstrap value. In addition, average nucleotide identity and inferred DNA-DNA hybridisation analyses showed that NZ1587T represents a novel species. Biochemical profiling using the rapid ID 32 strep identification test enabled differentiation of strain NZ1587T from closely related streptococcal species. In conclusion, strain NZ1587T can be classified as a novel species, and we propose a novel taxon named Streptococcus bovimastitidis sp. nov.; the type strain is NZ1587T. NZ1587T has been deposited in the Culture Collection University of Gothenburg (CCUG 69277T) and the Belgian Co-ordinated Collections of Micro-organisms/LMG (LMG 29747).


Role of secondary sensory cortices in emotional memory storage and retrieval in rats.
Visual, acoustic, and olfactory stimuli associated with a highly charged emotional situation take on the affective qualities of that situation. Where the emotional meaning of a given sensory experience is stored is a matter of debate. We found that excitotoxic lesions of auditory, visual, or olfactory secondary sensory cortices impaired remote, but not recent, fear memories in rats. Amnesia was modality-specific and not due to an interference with sensory or emotional processes. In these sites, memory persistence was dependent on ongoing protein kinase Mzeta activity and was associated with an increased activity of layers II-IV, thus suggesting a synaptic strengthening of corticocortical connections. Lesions of the same areas left intact the memory of sensory stimuli not associated with any emotional charge. We propose that secondary sensory cortices support memory storage and retrieval of sensory stimuli that have acquired a behavioral salience with the experience.


Cambridge-Miami score for intestinal transplantation preoperative risk assessment: initial development and validation.
Preoperative quantification of survival after transplantation would assist in assessing patients. We have developed a preliminary preoperative scoring system, called the Cambridge-Miami (CaMi) score, for transplantation of the small intestine either alone or as a composite graft. The score combines putative risk factors for early-, medium-, and long-term survival. Factors included were loss of venous access and impairment of organs or systems not corrected by transplantation. Each factor was scored 0-3. A score of 3 indicated comorbidity approaching a contraindication for transplantation, that which might lead to but was not currently an adverse risk factor scored 1, and that presenting a definite but moderate increase in risk scored 2. The preoperative scores of 20 patients who had received intestinal transplants either isolated or as part of a cluster graft, who had either been followed up postoperatively for at least 10 years, or died within 10 years were compared with their survivals. Postoperative survival and CaMi score inversely correlated when analysed using Spearman test (r(s) = -0.82; P = .0001). A score of <3 associated with survival > or =3 years (12/12 patients) and >3 with survival of <6 months (4/4). Patient Kaplan-Meier (KM) survival curves for patients grouped according to CaMi score became significantly different from group 0 to group 3. Using this as a threshold score patients grouped as either >2 or <3 had significantly different survival rates (log-rank; P = .0001), KM median survival hazard ratio (HR) = 6, and rate of death KM HR = 5. Receiver-operator characteristics indicate a high degree of accuracy for prediction of death with an area under the curve (C statistic) at 3 years of 0.98, at 5 years of 0.82, and at 10 years of 0.65. This initial validation suggested that the preoperative CaMi score predicted postoperative survival.


Electrophysiologic Features of Inherited Demyelinating Neuropathies: A Reappraisal.
The observation that inherited demyelinating neuropathies tend to have uniform conduction slowing and acquired disorders (CIDP and variants) have nonuniform or multifocal slowing was made before the identification of genetic defects of specific myelin constituents that cause the different forms of Charcot-Marie-Tooth and other inherited disorders involving peripheral nerve myelin. It is becoming clear that the electrophysiologic aspects of these disorders are more complex than previously realized. We review the current information available on the electrophysiologic features of the inherited demyelinating neuropathies in hopes of clarifying the clinical electrodiagnostic features of these disorders as well as to shed light on the physiologic consequences of the different genetic mutations.


A neural marker of the start-gun in interval timing: Onset N1P2.
Although the neural markers of interval timing have been widely studied, the events that determine the onset and offset of an interval have only recently started to gain attention. In the present study, I compare the predictions of the perceptual (preonset and start-gun) and decisional bias hypotheses with respect to onset N1P2 amplitude, the point of subjective equality (PSE) and delta/theta activity. The onsets of the comparison intervals (CIs) were manipulated to begin earlier, later, or on-time with regard to a standard interval (SI). Results supported the start-gun account by demonstrating an increase in the N1P2 amplitude and delta power in the "early" and "late" onset conditions due to temporal mismatch. Delayed or premature initiation of timing with respect to the predicted temporal point were associated with rightward and leftward shifts in the PSEs of the "early" and "late" onset conditions, respectively. In addition to the observed increase in temporal prediction-related delta activity in the "early" and "late" onset conditions, higher theta power in the "early" onset suggested an additional neural response for unexpected events that might be linked to response caution. Moreover, the ramping activity during the CIs, namely the contingent negative variation (CNV), showed a decision-related attenuation toward the end of an interval in the "late" onset. The latter finding was supported by the changes in offset N1P2 amplitude. The present study contributes to the interval-timing literature by presenting support in favor of the hypothesis that the onset N1P2 is a neural marker for the initiation of timing. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Another's pain in my brain: No evidence that placebo analgesia affects the sensory-discriminative component in empathy for pain.
The shared representations account of empathy suggests that sharing other people's emotions relies on neural processes similar to those engaged when directly experiencing such emotions. Recent research corroborated this by showing that placebo analgesia induced for first-hand pain resulted in reduced pain empathy and decreased activation in shared neural networks. However, those studies did not report any placebo-related variation of somatosensory engagement during pain empathy. The experimental paradigms used in these studies did not direct attention towards a specific body part in pain, which may explain the absence of effects for somatosensation. The main objective of this preregistered study was to implement a paradigm overcoming this limitation, and to investigate whether placebo analgesia may also modulate the sensory-discriminative component of empathy for pain. We induced a localized, first-hand placebo analgesia effect in the right hand of 45 participants by means of a placebo gel and conditioning techniques, and compared this to the left hand as a control condition. Participants underwent a pain task in the MRI scanner, receiving painful or non-painful electrical stimulation on their left or right hand, or witnessing another person receiving such stimulation. In contrast to a robust localized placebo analgesia effect for self-experienced pain, the empathy condition showed no differences between the two hands, neither for behavioral nor neural responses. We thus report no evidence for somatosensory sharing in empathy, while replicating previous studies showing overlapping brain activity in the affective-motivational component for first-hand and empathy for pain. Hence, in a more rigorous test aiming to overcome limitations of previous work, we again find no causal evidence for the engagement of somatosensory sharing in empathy. Our study refines the understanding of the neural underpinnings of empathy for pain, and the use of placebo analgesia in investigating such models.


The prevalence of overweight/obesity in high school adolescents in Jeddah and the association of obesity association with dental caries.
The prevalence of overweight/obesity in children in Saudi Arabia is among the highest in the world. The prevalence of dental caries is also high in Saudi children. Studies on the relationship between caries and obesity in Saudi adolescents are lacking. To study the prevalence of overweight/obesity in adolescents, and determine any association between obesity and caries. An analytical cross-sectional study. Private and public schools in Jeddah. The study sample comprised high school children from public and private schools selected by multistage stratified random sampling. Height, weight, waist circumference (WC), and body mass index (BMI) were measured for all children, who were then classified as underweight/normal, overweight, or obese according to their BMI values, and nonobese or obese according to their WC values. The presence of caries was assessed using the Association of State and Territorial Dental Directors criteria. The prevalence of overweight/obesity and the association of obesity with the number of decayed permanent teeth. 801 high school children (48% boys, 49% from public schools) with a mean (SD) age of 16.5 (0.9) years. When the BMI classification was used, 24%, 16%, and 60% adolescents were obese, overweight, and underweight/normal, respectively. When the WC classification was used, 19% and 81% were obese and nonobese, respectively. Obesity was more prevalent in boys and in students attending private schools (P < .05). The number of decayed permanent teeth showed a very weak and insignificant correlation with BMI and WC. One in every four adolescents residing in Jeddah was obese, with a high obesity prevalence in boys and in children attending private schools. The prevalence of caries in the permanent dentition was not associated with BMI or WC. It was difficult to establish temporality in this cross-sectional study. Data on common risk factors were not adjusted for in the analyses.


Leveraging Google Earth Engine platform to characterize and map small seasonal wetlands in the semi-arid environments of South Africa.
Although significant scientific research strides have been made in mapping the spatial extents and ecohydrological dynamics of wetlands in semi-arid environments, the focus on small wetlands remains a challenge. This is due to the sensing characteristics of remote sensing platforms and lack of robust data processing techniques. Advancements in data analytic tools, such as the introduction of Google Earth Engine (GEE) platform provides unique opportunities for improved assessment of small and scattered wetlands. This study thus assessed the capabilities of GEE cloud-computing platform in characterising small seasonal flooded wetlands, using the new generation Sentinel 2 data from 2016 to 2020. Specifically, the study assessed the spectral separability of different land cover classes for two different wetlands detected, using Sentinel-2 multi-year composite water and vegetation indices and to identify the most suitable GEE machine learning algorithm for accurately detecting and mapping semi-arid seasonal wetlands. This was achieved using the object based Random Forest (RF), Support Vector Machine (SVM), Classification and Regression Tree (CART) and Naïve Bayes (NB) advanced algorithms in GEE. The results demonstrated the capabilities of using the GEE platform to characterize wetlands with acceptable accuracy. All algorithms showed superiority, in mapping the two wetlands except for the NB method, which had lowest overall classification accuracy. These findings underscore the relevance of the GEE platform, Sentinel-2 data and advanced algorithms in characterizing small and seasonal semi-arid wetlands.


The Effect of Tranexamic Acid on Functional Outcomes: An Exploratory Analysis of the CRASH-2 Randomized Controlled Trial.
Tranexamic acid improves survival in severely injured adults. However, its effectiveness on overall functional outcome is unknown. We hypothesized that tranexamic acid improves overall functional outcome compared with placebo in severely injured adults and conduct an exploratory analysis of the Clinical Randomization of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) data to investigate this hypothesis. We included injured adults from the CRASH-2 trial who were randomized 3 hours or less from injury. The primary outcome measure was functional status at hospital discharge or on day 28 if the subject was still in the hospital. Functional status was measured with the modified Oxford Handicap Scale, a 6-category ordinal functional outcome scale. We conducted 3 separate analyses using 3 different outcome measures to evaluate the effectiveness of tranexamic acid versus placebo on functional outcomes, including the mean utility-weighted modified Oxford Handicap Scale score (overall functional outcome), the area under the curve (based on functional outcome and rate of recovery), and a sliding dichotomy analysis (favorable versus unfavorable functional outcome) stratified by baseline mortality risk (stratified analysis). There were 13,432 patients (6,679 randomized to placebo and 6,753 to tranexamic acid) included in the study cohort. The mean utility-weighted modified Oxford Handicap Scale score was 0.66 (SD 0.33) for patients randomized to tranexamic acid compared with a mean of 0.64 (SD 0.34) for those randomized to placebo (mean difference 0.02; 95% confidence interval [CI] 0.01 to 0.03). The area under the curve analysis demonstrated that patients randomized to tranexamic acid had a higher 28-day mean utility-weighted modified Oxford Handicap Scale score compared with those randomized to placebo (mean score 0.55 [SD 0.30] versus 0.53 [SD 0.31]; mean difference 0.02 [95% CI 0.01 to 0.03]). The sliding dichotomy analysis demonstrated heterogeneity of treatment effects across risk groups. The overall proportion of patients with favorable functional outcomes was higher in the tranexamic acid group (5,360/6,753 [79.4%]; 95% CI 78.4% to 80.3%) compared with the placebo group (5,174/6,679 [77.5%]; 95% CI 76.5% to 78.5%; difference 1.9% [95% CI 0.5% to 3.3%]; number needed to treat=52). When each risk group was tested separately, only the lowest-risk group (<6% baseline mortality risk) demonstrated a statistically significant effect of tranexamic acid toward favorable functional outcomes (tranexamic acid versus placebo adjusted odds ratio 0.78; 95% CI 0.67 to 0.90). There were no differences between tranexamic acid and placebo in the other risk groups. Across 3 exploratory analyses, severely injured adult patients randomized within 3 hours from injury demonstrated better functional outcomes with tranexamic acid compared with placebo. When heterogeneity of treatment effects across risk groups was evaluated, only the lowest-risk group demonstrated a significant effect of tranexamic acid toward favorable outcomes. Given the overall safety and cost-effectiveness of tranexamic acid use in injured adults, our results further support the use of tranexamic acid for this population. Future trauma trials that evaluate tranexamic acid use should also consider functional status as an important outcome.