Autophagy and vitamin D.
Vitamin D receptor represses basal autophagy in breast tissue, which is derepressed by vitamin D, slowing cancer progression.


Osteoblastic Wnts differentially regulate bone remodeling and the maintenance of bone marrow mesenchymal stem cells.
Wnt signaling has important roles in embryonic bone development and postnatal bone remodeling, but inconsistent impact on bone property is observed in different genetic alterations of Lrp5 and β-catenin. More importantly, it is still controversial whether Lrp5 regulate bone formation locally or globally through gut-derived serotonin. Here we explored the function of Wnt proteins in osteoblastic niche through inactivation of the Wntless (Wls) gene, which abrogates the secretion of Wnts. The depletion of Wls in osteoblast progenitor cells resulted in severe osteopenia with more profound defects in osteoblastogenesis, osteoclastogenesis and maintenance of bone marrow mesenchymal stem cells (BMSCs) compared to that observed in Lrp5 and β-catenin mutants. These findings support the point of view that Wnt/Lrp5 signaling locally regulates bone mass accrual through multiple effects of osteoblastic Wnts on osteoblastic bone formation and osteoclastic bone resorption. Moreover, osteoblastic Wnts confer a niche role for maintenance of BMSCs, providing novel cues for the definition of BMSCs niche in bone marrow.


Prospects of vaccination as a means of preventing mother-to-child transmission of HIV-I.
Although short-course antiretroviral therapy is efficient in reducing mother-to-child transmission (MTCT) of HIV-1, it does not prevent transmission during the breastfeeding period. There is therefore an urgent need to test various approaches, including HIV-1 vaccination, to try to prevent postnatal transmission of HIV-1 in breastfeeding populations in developing countries.


A discussion of the biology of testicular cancer and current concepts in the management of stage I and bilateral disease.
This case was the subject of a Grand Round Presentation at the Royal Marsden Hospital, Sutton, UK on 8 June 2004. A case of metachronous, bilateral testicular germ-cell tumours (TGCTs) arising in a patient with a family history of this disease was presented. The second primary was managed conservatively. The rationale and outcome of this approach was presented, along with a discussion of the management of early stage TGCTs and the genetics of familial and bilateral disease.


Depleted interstitial cells of Cajal and fibrosis in the pylorus: Novel features of gastroparesis.
Depletion and ultrastructural changes of interstitial cells of Cajal (ICC) in the gastric body and antrum have been observed in gastroparesis. This research was performed to investigate the ICC population in the muscularis propria and fibrosis of the muscular layer of the pylorus in gastroparesis. Full thickness pyloric and antral biopsies were obtained from 17 gastroparetic and 6 non-gastroparetic controls. Biopsies were stained with C-Kit for ICC and Trichrome for collagen fibrosis. Interstitial cells of Cajal depletion in the antrum was defined as mean ICC count <10 per 20 high power fields (HPF) based on established data. The average pyloric ICC count was ≥10/HPF in the control patients. Twelve (70.5%) gastroparetic patients had pyloric ICC loss. Only five patients (29.4%) had ICC loss in the antrum. Gastric emptying (GE) was not significantly different in patients with depleted vs normal pyloric ICC. However, GE at 2 h was slower in patients with antral ICC <10/HPF compared to those with normal antral ICC populations. Collagen fibrosis was observed in the pylorus of 14 (82.3%) patients. Inclusion bodies in the muscularis propria of the pylorus were identified in four patients, all with diabetic gastroparesis. In gastroparetic patients, ICC loss in the pylorus is twice as common as in the antrum and fibrosis in the pyloric smooth muscle is nearly three times more common than the antrum. These findings can provide one explanation for pyloric dysfunction which is a contributing factor to the pathophysiology of gastroparesis.


Peer-Reviewed Studies on the Effects of Anthropogenic Noise on Marine Invertebrates: From Scallop Larvae to Giant Squid.
Marine invertebrates at the base of oceanic trophic webs play important ecological and economical roles supporting worldwide fisheries worth millions. There is an increasing concern about the effects of anthropogenic noise on marine fauna but little is known about its effects on invertebrates. Here the current peer-reviewed literature on this subject is reviewed, dealing with different ontogenetic stages and taxa. These studies show that the noise effects on marine invertebrates range from apparently null to behavioral/physiological responses to mortalities. They emphasize the need to consider potential interactions of human activities using intense sound sources with the conservation and fisheries of local invertebrate stocks.


Oral administration of vanadate to diabetic rats restores liver 6-phosphofructo-2-kinase content and mRNA.
Vanadate and insulin were administered to diabetic (streptozotocin) rats to compare their effects on the activity and mRNA content of 6-phosphofructo-2-kinase and L-type pyruvate kinase in the liver. The activity of 6-phosphofructo-2-kinase in livers of diabetic rats was about 40% of that found in normal rats. A similar decrease was found for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase content, measured by immunoprecipitation, and for mRNA, measured by hybridization of Northern blots. Administration of vanadate to the diabetic rats led to a progressive recovery of 6-phosphofructo-2-kinase activity, and 6-phosphofructo-2-kinase/fructose- 2,6-bisphosphatase content and mRNA. This recovery, which was complete after 15 days of oral treatment, was also obtained after 60 h of insulin administration. L-type pyruvate kinase activity and mRNA were also decreased by about 70% in livers of diabetic rats. Both parameters normalized after 15 days of vanadate treatment, whereas insulin administration (60 h) raised L-pyruvate kinase mRNA three-fold above control values. Oral treatment for 15 days with vanadate can thus mimic the effect of insulin on both pyruvate kinase and 6-phosphofructo-2-kinase/fructose-2,6- bisphosphatase in livers of diabetic rats.


25-hydroxyvitamin D circulates in different fractions of calf plasma if the parent compound is vitamin D₂ or vitamin D₃, respectively.
Vitamin D has become one of the most discussed nutrients in human nutrition, which has led to an increased interest in milk as a vitamin D source. Problems related to fortifying milk with synthetic vitamin D can be avoided by securing a high content of natural vitamin D in the milk by supplying dairy cows with sufficient vitamin D. However, choosing the most efficient route and form of supplementation requires insight into how different vitamin D metabolites are transported in the body of cattle. There are two forms of vitamin D: vitamin D2 (D2) and vitamin D3 (D3). Vitamin D2 originates from fungi on roughage. Vitamin D3 originates either from endogenous synthesis in the skin or from feed supplements. Vitamin D2 is chemically different from, and less physiologically active than, D3. Endogenous and dietary D3 is chemically similar but dietary D3 is toxic, whereas endogenous D3 appears well regulated in the body.


[Tests for evaluating tobacco dependence].
The primary reason why there is such a heavy burden of tobacco smoking induced illness and death is dependence on nicotine which makes it difficult for smokers to quit. For clinical or research purposes, the degree of dependence, the intensity of the withdrawal syndrome and/or craving have been evaluated by different scales. This review provides a list of questionnaires that are used in smoking cessation. It pays particular attention to the validated and translated resources that are available in French. Research should be conducted in order to provide French speaking smoking cessation specialists with all the relevant scales allowing better evaluation of tobacco dependence.


Treatment of murine lupus with monoclonal antibody to L3T4. I. Effects on the distribution and function of lymphocyte subsets and on the histopathology of autoimmune disease.
Monoclonal antibodies (MoAb) to L3T4 have been used successfully to suppress autoimmunity in murine models for several human autoimmune diseases. To clarify the immunologic and clinical consequences of treatment with anti-L3T4, we examined the effects of chronic administration of anti-L3T4 on the composition of lymphoid organs, the function of lymphocytes, and the histopathology of autoimmune disease in lupus-prone NZB/NZW F1 (B/W) mice. Weekly treatment with anti-L3T4 (2 mg/mouse) from age 5 to 8 months depleted L3T4+ cells from the spleen and lymph nodes, and prevented the development of splenomegaly and lymphadenopathy. The MoAb bound to target cells in the thymus and modulated their expression of the L3T4 antigen but, in contrast to its effect in extrathymic sites, anti-L3T4 did not deplete the target population from the thymus. In fact, after 3 months of therapy, mice that had been treated with anti-L3T4 had much larger thymuses than control mice that had been treated with saline, suggesting that treatment with anti-L3T4 prevented the thymic atrophy that occurs spontaneously in murine lupus. Despite depleting L3T4+ cells from the spleen, treatment with anti-L3T4 did not diminish the response of splenic lymphocytes to T and B cell mitogens, and it augmented splenic natural killer (NK) cell activity. Finally, treatment with anti-L3T4 decreased the diverse histopathologic manifestations of murine lupus. It dramatically reduced glomerular immunoglobulin and complement deposition and diminished lymphocytic infiltration and vasculitis in the kidneys. Treatment also reduced extrarenal immunopathology, including focal hepatitis and salivary gland infiltration. These observations have implications regarding the use of CD4 MoAb in people with autoimmune diseases.


Notes from the field: Exposures to discarded sulfur mustard munitions - Mid-Atlantic and New England States 2004-2012.
Before the 1970s, the United States sometimes disposed of at sea excess, obsolete, or unserviceable munitions, including chemical munitions. Chemical munitions known to have been disposed of at sea included munitions filled with sulfur mustard, a vesicant (i.e., an agent that causes chemical burns or blisters of the skin and mucous membranes). Signs and symptoms of exposure to a mustard agent can include redness and blistering of the skin, eye irritation, rhinorrhea, hoarseness, shortness of breath, and (rarely) diarrhea and abdominal discomfort. Since 2004, CDC has received notification of three separate incidents of exposure to sulfur mustard munitions. In one incident, a munition was found with ocean-dredged marine shells used to pave a driveway. The other two incidents involved commercial clam fishing operations. This report highlights the importance of considering exposure to sulfur mustard in the differential diagnosis of signs and symptoms compatible with exposure to a vesicant agent, especially among persons involved with clam fishing or sea dredging operations.


Growth hormone-deficient adults are insulin-resistant.
Patients with growth hormone deficiency (GHD) have traditionally been described as having increased insulin sensitivity with a tendency toward fasting hypoglycemia, at least in children. In other studies, impaired glucose tolerance has been found. To evaluate basal insulin sensitivity, a hyperinsulinemic, normoglycemic clamp was performed with an insulin rate of 40 mU/m2/min after an overnight fast. Fifteen patients (four women and 11 men aged 20 to 62 years) with GHD for at least 1 year were compared with 15 healthy controls matched for sex, age, and body mass index (BMI). Thirteen patients had complete pituitary deficiency and were being treated with conventional hormone replacement therapy. Two men had isolated GHD since childhood. Four men were being treated with bromocriptin. There were no significant differences between fasting blood glucose (4.4 +/- 0.1 v 4.7 +/- 0.2 [mean +/- SEM] mmol/L) or fasting plasma insulin (9.5 +/- 1.4 v 8.8 +/- 1.1 mU/L) in patients and controls, respectively. Fasting free fatty acid (FFA) levels were lower in patients (444 +/- 35 v 796 +/- 94 mumol/L, P < .01). Blood glucose levels during the clamp were similar (4.6 +/- 0.1 v 4.9 +/- 0.1 mmol/L), as were insulin levels (81 +/- 4 v 93 +/- 4 mU/L). A decrease in glucose infusion rate (GIR) was seen during the clamp in GHD subjects (3.9 +/- 0.5 v 9.9 +/- 0.7 mg/kg body weight/min) as compared with controls (P = .001). Even if corrections were made for body fat, there was a significant difference (GIR corrected per lean body mass, 5.8 +/- 0.8 v 13.9 +/- 0.9 mg/kg lean body mass/min, P < .001). The results suggest that adults with GHD are insulin-resistant. Despite this finding, normal fasting plasma insulin levels were seen.


Complex signatures of locus-specific selective pressures and gene conversion on Human Growth Hormone/Chorionic Somatomammotropin genes.
Reduced birth weight and slow neonatal growth are risks correlated with the development of common diseases in adulthood. The Human Growth Hormone/Chorionic Somatomammotropin (hGH/CSH) gene cluster (48 kb) at 17q22-24, consisting of one pituitary-expressed postnatal (GH1) and four placental genes (GH2, CSH1, CSH2, and CSHL1) may contribute to common variation in intrauterine and infant growth, and also to the regulation of feto-maternal and adult glucose metabolism. In contrast to GH1, there are limited genetic data on the hGH/CSH genes expressed in utero. We report the first survey of sequence variation encompassing all five hGH/CSH genes. Resequencing identified 113 SNPs/indels (ss86217675-ss86217787 in dbSNP) including 66 novel variants, and revealed remarkable differences in diversity patterns among the homologous duplicated genes as well as between the study populations of European (Estonians), Asian (Han Chinese), and African (Mandenkalu) ancestries. A dominant feature of the hGH/CSH region is hyperactive gene conversion, with the rate exceeding tens to hundreds of times the rate of reciprocal crossing-over and resulting in near absence of linkage disequilibrium. The initiation of gene conversion seems to be uniformly distributed because the data do not predict any recombination hotspots. Signatures of different selective constraints acting on each gene indicate functional specification of the hGH/CSH genes. Most strikingly, the GH2 coding for placental growth hormone shows strong intercontinental diversification (F(ST)=0.41-0.91; p<10(-6)) indicative of balancing selection, whereas the flanking CSH1 exhibits low population differentiation (F(ST)=0.03-0.09), low diversity (non-Africans, pi=8-9 x 10(-5); Africans, pi=8.2 x 10(-4)), and one dominant haplotype worldwide, consistent with purifying selection. The results imply that the success of an association study targeted to duplicated genes may be enhanced by prior resequencing of the study population in order to determine polymorphism distribution and relevant tag-SNPs.


Clinical significance of late CMV disease in adult patients who underwent allogeneic stem cell transplant.
Late cytomegalovirus (CMV) disease, which was defined as CMV disease occurring >100 days post-transplant, remains an important complication among allogeneic stem cell transplant recipients, even now that the prophylactic strategy using ganciclovir preemptive therapy has been established. Due to the recent expansion of donor sources and conditioning regimens, it is therefore appropriate to reevaluate the incidence, risk factors, and clinical impacts of late CMV disease. This study included the 1295 adult patients, who underwent transplant for the first time from 2008 to 2015, without underlying disease relapse or CMV disease within 100 days post-transplant. There were no restrictions on underlying diseases or transplant procedures. During the median follow-up period of 48.4 months, 21 patients developed late CMV disease and the 5-year cumulative incidence of late CMV disease was 1.6%. By multivariate analysis, haploidentical related donor, adult T-cell leukemia lymphoma, and preemptive therapy before 100 days post-transplant were extracted as independent risk factors. Late CMV disease negatively affected transplant outcomes, and was identified as an independent risk factor for the non-relapse mortality rate (hazard ratio 3.83, p < 0.001) and overall survival rate (hazard ratio 4.01, p < 0.001). Although 17 of 21 patients with late CMV disease died, the main causes of death were not related to CMV, except in three patients with CMV pneumonia. Although the incidence of late CMV disease is low in transplant recipients, this complication negatively affects clinical courses. Therefore, transplant recipients with these risk factors should be more carefully managed.


Dollfusiella qeshmiensis n. sp. (Cestoda: Trypanorhyncha) from the cowtail stingray Pastinachus sephen (Forsskål) in the Persian Gulf, with a key to the species of Dollfusiella Campbell & Beveridge, 1994.
A new species of the genus Dollfusiella Campbell & Beveridge, 1994 is described from Pastinachus sephen (Forsskål) in the Persian Gulf. Dollfusiella qeshmiensis n. sp. is allocated to the genus Dollfusiella based on the possession of two bothria, prebulbar organs, a heteroacanthous typical armature with tightly spaced rows of hollow hooks, a basal swelling and a characteristic basal armature without prominent macrohooks. The presence of an enlarged external seminal vesicle in Dollfusiella qeshmiensis n. sp. distinguishes this species from D. michiae (Southwell, 1929), D. bareldsi (Beveridge, 1990), D. owensi (Beveridge, 1990), D. geraschmidti (Dollfus, 1974), D. angustiformis Schaeffner & Beveridge, 2013, D. hemispinosa Schaeffner & Beveridge, 2013, D. spinosa Schaeffner & Beveridge, 2013 and D. taminii Menoret & Ivanov, 2014. The new species is distinguished from the remaining species within the genus by a combination of the following morphological features: the number of testes per segment, the number of testis columns and the number of homeomorphous hooks per half spiral row in the metabasal region. In the most recent taxonomic key to the species of Dollfusiella, the presence or absence of enlarged, microscopically visible spinitriches on the scolex was used as the first distinguishing character dividing the congeners into two groups. Since the existence of visible microtriches on the scolex peduncle of D. vooremi (São Clemente & Gomes, 1989), a species so far grouped among the species lacking visible microtriches on the scolex, has been recently demonstrated, and given the fact that the presence of microscopically visible microtriches on the scolex is variable in some eutetrarhynchid species, a new key to the species of Dollfusiella is provided in which the spinitriches have been given less priority.


Static Facial Slings: Approaches to Rehabilitation of the Paralyzed Face.
Facial paralysis results from a variety of different causes. Patients with facial paralysis have cosmetic and functional defects that significantly affect quality of life. Surgical intervention has the potential to help improve cosmetic and functional outcomes. The 2 main categories of surgical rehabilitation are static and dynamic surgical procedures. Static rehabilitation of the midface is typically performed using autologous tissue grafts, allografts, synthetic grafts, permanent suspension sutures, and a novel technique using percutaneous suture-based slings.


Maternal Vitamin A deficiency during pregnancy and lactation induced damaged intestinal structure and intestinal flora homeostasis in offspring mice.
The small intestine serves as the first channel of dietary Vitamin A (VA) and the unique organ of VA absorption and metabolism. However, there have not been extensive investigations on the exact mechanisms within VA-related changes in intestinal metabolic disorders. This research is designed to analyze whether and how VA affects intestinal metabolic phenotypes. Male C57BL/6 mice after weaning were randomly fed a VA control diet (VAC) or a VA-deficient diet (VAD) during the entire pregnancy and lactation process. After a total of 11 weeks, cohorts of VA deprived were next fed to a VA control diet (VAD-C) for another 8 weeks. The concentration of retinol was measured by a high-performance liquid chromatography system. The 16S gene sequencing was used to evaluate the intestinal microbiota changes. Through the use of histological staining, western blots, quantitative PCR, and enzyme-linked immunosorbent assays, the intestinal morphology, inflammatory factors, and intestinal permeability were all evaluated. Following the decrease of the tissue VA levels, VAD mice show a decrease in tissue VA levels, community differences, and the richness and diversity of intestinal microbiota. VAD diet-driven changes occur in intestinal microbiota, accompanied by a higher mRNA expression of intestinal inflammatory cytokines and an increase in intestinal permeability. As dietary VA is reintroduced into VAD diet-fed mice, the tissue VA levels, inflammatory response, and intestinal homeostasis profiles are all restored, which are similar to those found after the occurrence of VA-controlled changes within intestinal microbiota. VA deficiency caused the imbalance of intestinal metabolic phenotypes through a mechanism involving changes in intestinal microbiota. It is thought that intestinal microbiota metabolic influences represent a new salient and additional mechanism, which can be used as a new method to achieve the onset and treatment of the effect of VAD on intestinal homeostasis impairment.


Physicochemical characteristics and pollen spectrum of monofloral honeys from Tenerife, Spain.
Physicochemical parameters, sugar composition and botanical origin were determined in four monofloral honeys, chestnut, fennel, tajinaste, and Teide broom honeys, abundantly produced in Tenerife Island. All the parameters were within the established intervals in Europe for each type of honey. Large differences between the four monofloral honeys were observed, being the chestnut honeys with most of differential characteristics. Linear discriminant analysis on the physicochemical parameters and sugar composition allows to distinguishing the four types of honeys analysed.


Antibodies to Toxoplasma gondii, Leishmania spp., and Leptospira spp. in Free-Ranging Six-Banded Armadillos (Euphractus sexcinctus) from Northeastern Brazil.
Antibodies to pathogens of public health importance were investigated in 33 free-ranging six-banded armadillos (Euphractus sexcinctus) from Brazil. The frequency of seropositive animals for Toxoplasma gondii, Leishmania spp., and Leptospira spp. were two, three, and two, respectively.


A multimeric quinacrine conjugate as a potential inhibitor of Alzheimer's beta-amyloid fibril formation.
Amyloid formation and accumulation of the amyloid beta-peptide (Abeta) in the brain is associated with Alzheimer's disease (AD) pathogenesis. Therefore, among the therapeutic approaches in development to fight the disease, the direct inhibition of the Abeta self-assembly process is currently widely investigated and is one of the most promising approaches. In this study we investigated the potential of a multimeric display of quinacrine derivatives, as compared to the monomer quinacrine, as a design principal for a novel class of inhibitors against Abeta fibril formation. The presented multimeric conjugate exhibits a cluster of four quinacrine derivatives on a rigid cyclopeptidic scaffold. Herein is reported the synthesis of the conjugate, together with the in vitro inhibitory evaluation of Abeta(1-40) fibrils using the thioflavin T fluorescence assay, and imaging with atomic force microscopy. Our data show that the multimeric compound inhibits Abeta(1-40) fibril formation with an IC(50) value of 20+/-10 microM, which contrasts with the nonactive monomeric analogue. This work suggests that assembling multiple copies of acridine moieties to a central scaffold, for multiple interactions, is a promising strategy for the engineering of inhibitors against Abeta fibril formation.


A prospective study of ¹⁸FDG-PET with CT coregistration for radiation treatment planning of lymphomas and other hematologic malignancies.
This prospective single-institution study examined the impact of positron emission tomography (PET) with the use of 2-[(18)F] fluoro-2-deoxyglucose and computed tomography (CT) scan radiation treatment planning (TP) on target volume definition in lymphoma. 118 patients underwent PET/CT TP during June 2007 to May 2009. Gross tumor volume (GTV) was contoured on CT-only and PET/CT studies by radiation oncologists (ROs) and nuclear medicine physicians (NMPs) for 95 patients with positive PET scans. Treatment plans and dose-volume histograms were generated for CT-only and PET/CT for 95 evaluable sites. Paired t test statistics and Pearson correlation coefficients were used for analysis. 70 (74%) patients had non-Hodgkin lymphoma, 10 (11%) had Hodgkin lymphoma, 12 (10%) had plasma-cell neoplasm, and 3 (3%) had other hematologic malignancies. Forty-three (45%) presented with relapsed/refractory disease. Forty-five (47%) received no prior chemotherapy. The addition of PET increased GTV as defined by ROs in 38 patients (median, 27%; range, 5%-70%) and decreased GTV in 41 (median, 39.5%; range, 5%-80%). The addition of PET increased GTV as defined by NMPs in 27 patients (median, 26.5%; range, 5%-95%) and decreased GTV in 52 (median, 70%; range, 5%-99%). The intraobserver correlation between CT-GTV and PET-GTV was higher for ROs than for NMPs (0.94, P<.01 vs 0.89, P<.01). On the basis of Bland-Altman plots, the PET-GTVs defined by ROs were larger than those defined by NMPs. On evaluation of clinical TPs, only 4 (4%) patients had inadequate target coverage (D95 <95%) of the PET-GTV defined by NMPs. Significant differences between the RO and NMP volumes were identified when PET was coregistered to CT for radiation planning. Despite this, the PET-GTV defined by ROs and NMPs received acceptable prescription dose in nearly all patients. However, given the potential for a marginal miss, consultation with an experienced PET reader is highly encouraged when PET/CT volumes are delineated, particularly for questionable lesions and to assure complete and accurate target volume coverage.


Gone with the fire: Market reaction to cryptocurrency exchange shutdown.
Disruption and shutdown of exchanges frequently happen in the cryptocurrency market, though its potential impacts are relatively under-investigated due to several empirical challenges. This study employs 20-h of service interruption on October 15th at Upbit, the dominant cryptocurrency exchange in Korea, as an exogenous shock to examine the effect of unexpected service interruption at the exchange on cryptocurrency market. Event study estimation using price data from Binance, the largest cryptocurrency exchange globally, shows the sharp and negative reactions to cryptocurrencies mostly traded at Upbit. Major currencies such as Bitcoin and Ethereum also presented limited reactions, implying that service interruption could be interpreted as vulnerability of overall cryptocurrencies.


Interpreters as Translation Machines: Telephone Interpreting Challenges as Awareness Problems.
Telehealth has been widely adopted during the COVID-19 pandemic, and this article examines challenges faced by telephone interpreters in working with healthcare providers in the context of the Australian healthcare system. Based on one-on-one interviews with 67 healthcare interpreters in Australia, it explores various elements which affect communication processes in telephone interpreting and interpreters' views on healthcare providers' abilities to collaborate with interpreters. Data analysis indicates that telephone interpreting is often affected by a lack of briefing, poor acoustics and the absence of visual cues. While these factors pose significant challenges to telephone interpreters, a provider's tendency to see interpreters as 'translation machines' was perceived as a deeper underlying problem by the interpreters. The mechanistic approaches to interpreting among healthcare providers pose barriers to interpreter-provider collaboration and exacerbate communication problems caused by the external elements in telephone-interpreted encounters. The article calls for urgent need to raise awareness of interpreting among healthcare providers as a key to ensuring desirable health outcomes for patients from minority backgrounds.


OsAAI1 Increases Rice Yield and Drought Tolerance Dependent on ABA-Mediated Regulatory and ROS Scavenging Pathway.
In this study, we investigated the function of OsAAI1 in yield and drought tolerance by constructing overexpression line OE-OsAAI1 and mutant line osaai1. Bioinformatics analysis showed that the AAI gene-OsAAI1- belongs to the HPS_like subfamily of the AAI_LTSS superfamily, and OsAAI1 was localized in the nucleus. The expression of OsAAI1 was significantly induced by ABA and drought stress. OsAAI1 overexpression (OE19) significantly increased, and gene mutant (osaai1-1) repressed plant height, primary root length, lateral root number, grain size and yield in rice. Moreover, physiological and biochemical analyses showed that osaai1 was sensitive to drought stress, while OE19 enhanced the drought tolerance in rice. DAB and NBT staining revealed that under drought treatment, osaai1 accumulated a large amount of ROS compared with the wild type, while OE19 accumulated the least, and CAT, APX, GPX, GR activities were higher in OE19 and lower in osaai1, suggesting that OE19 improves rice tolerance to drought stress by enhancing ROS scavenging ability. OE19 also induce the expression of ABA-mediated regulatory pathway genes and enhance accumulation of ABA content in rice seedling. Predictably, OE19 displayed enhanced sensitivity to ABA, and ROS accumulation was significantly higher than in wild type and osaai1 under 3 µM ABA treatment. Thus, these results suggest that OsAAI1 is a positive regulator of rice yield and drought tolerance dependent on the ABA-mediated regulatory and ROS scavenging pathway.


The organization of the efferent projections of the substantia nigra in the rat. A retrograde fluorescent double labeling study.
The organization of three of the efferent projections of substantia nigra has been investigated in rat by means of combined injections of two fluorescent retrograde tracers: red fluorescent Evans Blue and blue fluorescent DAPI-primuline mixture. First the distributions of the retrogradely labeled neurons in substantia nigra after injections of each of the two tracers in the striatum, thalamus and superior colliculus were compared with the distributions of the retrogradely labeled nigral neurons after HRP injections in these same structures. The findings in these sets of experiments were the same. This indicates that the two fluorescent retrograde tracers are as effective as HRP in tracing the efferent fiber connections of the substantia nigra. Subsequently the retrograde labeling of the substantia nigra neurons was studied after combined injections of the two fluorescent retrograde tracers in two of the above structures, in different combinations. In these experiments both single labeled neurons fluorescing either red or blue, as well as double labeled neurons fluorescing both red and blue were found. Double labeled neurons were present only in pars reticulata and occurred only after injections of the two tracers in thalamus and superior colliculus respectively. From this it has been concluded that in rat the various efferent projections from the substantia nigra are mainly derived from different neurons, but that at least part of the neurons which distribute fibers to superior colliculus also distributes collaterals to the thalamus.


Early identified risk factors and their predictive performance of brain death in out-of-hospital cardiac arrest survivors.
Early prediction of brain death (BD) after the return of spontaneous circulation (ROSC) in patients with cardiac arrest would be useful for the proper distribution of good quality transplantable organs and medical resources. We aimed to early identify independent risk factors of BD and their predictive performance in out-of-hospital cardiac arrest (OHCA) survivors. This retrospective observational study included adult OHCA survivors from May 2018 to February 2021. Independent risk factors for progression to BD were identified by performing multivariate logistic regression analysis, including clinical, laboratory, biological parameters and prognostic factors, obtained within 6 h after ROSC. Neuron-specific enolase (NSE) level were categorized into quartile. The primary outcome was BD occurrence. Overall, 108 patients were included in this analysis, 31 (29%) of whom had BD. In multivariate logistic regression analysis, initial serum NSE levels in the fourth quartile compared to the first quartile (odds ratio [OR], 88.5; 95% confidence interval [CI]: 7.0-1113.6) and absence of pupil light reflex (PLR) (OR, 40.3; 95% CI: 3.8-430.3) were independently associated with BD. According to the receiver operating characteristic curve analysis, initial serum NSE levels and PLR showed good-to-excellent and fair-to-good prognostic performance, respectively (area under the curve [AUC], 0.90; 95% CI: 0.83-0.95 vs. 0.81; 95% CI: 0.72-0.88). Additionally, the combination of both the risk factors (AUC, 0.96; 95% CI: 0.90-0.99) showed significantly higher predictive performance for BD than when using them individually (P = 0.04 and P < 0.01, respectively). High levels of initial serum NSE and PLR obtained within 6 h after ROSC may help early predict progression to BD in OHCA survivors. A large prospective multicenter study should be conducted to confirm these results.


Cautionary tales in the clinical interpretation of therapeutic trial reports.
Practising clinicians are assailed daily with reports of new therapeutic clinical trials. The evidence-based medicine movement has developed critical appraisal methods for assessing the validity and impact of such studies. However, challenges persist in regards to the appropriate interpretation and application of trial results within everyday clinical settings. Using selected examples from recently published literature, we illustrate 15 cautionary themes for translating research evidence from therapeutic trials into clinical practice.


Circular RNAs as biomarkers and therapeutic targets in environmental chemical exposure-related diseases.
Chemical contamination in the environment is known to cause abnormal circular RNA (circRNA) expression through multiple exposure routes; yet, the underlying molecular mechanisms remain unclear. Non-coding RNAs (ncRNAs), especially circRNAs, play important roles in epigenetic regulation and disease pathogenesis; however, few studies have examined the function of circRNAs in chemical contamination-induced diseases. CircRNAs are covalently closed continuous loops that do not possess 5' and 3' ends, increasing their structural stability and limiting degradation by exoribonucleases. In addition, environmental chemical exposure-related diseases are often accompanied by aberrant expression of specific circRNAs and those circRNAs are often detected in tissues and body fluids. Based on these characteristics, circRNAs may serve as candidate biomarkers for the diagnosis of diseases related to environmental chemical exposure. Here, we review the generation and function of circRNAs, and the possible molecular mechanisms underlying the regulation of environmental chemical exposure-related disorders by circRNAs. This is the first comprehensive review of the relationship between environmental chemical exposure and circRNAs in chemical exposure-induced diseases.


Human interferon-gamma mRNA autoregulates its translation through a pseudoknot that activates the interferon-inducible protein kinase PKR.
PKR, an interferon (IFN)-inducible protein kinase activated by double-stranded RNA, inhibits translation by phosphorylating the initiation factor eIF2alpha chain. We show that human IFN-gamma mRNA uses local activation of PKR in the cell to control its own translation yield. IFN-gamma mRNA activates PKR through a pseudoknot in its 5' untranslated region. Mutations that impair pseudoknot stability reduce the ability to activate PKR and strongly increase the translation efficiency of IFN-gamma mRNA. Nonphosphorylatable mutant eIF2alpha, knockout of PKR and PKR inhibitors 2-aminopurine, transdominant-negative PKR, or vaccinia E3L correspondingly enhances translation of IFN-gamma mRNA. The potential to form the pseudoknot is phylogenetically conserved. We propose that the RNA pseudoknot acts to adjust translation of IFN-gamma mRNA to the PKR level expressed in the cell.


The hyaluronan-binding protease upregulates ERK1/2 and PI3K/Akt signalling pathways in fibroblasts and stimulates cell proliferation and migration.
The hyaluronan-binding protease (HABP) is a serine protease in human plasma which is structurally related to plasminogen activators, coagulation factor XII and hepathocyte growth factor activator. It can in vitro activate the coagulation factor FVII, kininogen and plasminogen activators. The present study was initiated to gain a more complete picture of the cell-associated activities of this fibrinolysis-related protease. Treatment of lung fibroblasts with HABP lead to a rapid activation of signalling pathways, including the mitogen-activated protein kinase (MAPK) pathway with c-Raf, MEK and ERK1/2. Additionally the activation of the PI3K/Akt pathway and of several translation-related proteins was found. Proliferation assays confirmed the assumption of a strong growth-stimulating effect of HABP on human lung and skin fibroblasts. Intracellular signalling and growth stimulation were strongly dependent on the proteolytic activity of HABP. Stimulation of signalling and proliferation by HABP involved the fibroblast growth factor receptor 1 (FGFR-1). HABP-stimulated proliferation of lung fibroblasts MRC-5 was accompanied by a significant intracellular increase in basic fibroblast growth factor (bFGF), the major ligand of FGFR-1; bFGF could however not be identified in the supernatant of HABP-treated cells. Though, the conditioned medium from HABP-treated cells showed a strong growth-promoting activity on quiescent fibroblasts, indicating the release of a yet unknown growth factor amplifying the initial growth stimulus. In a two-dimensional wound model HABP stimulated the invasion of fibroblasts into a scratch area, adding a strong pro-migratory activity to this plasma protease. In summary, HABP exhibits a significant growth factor-like activity on quiescent human lung and dermal fibroblasts. Our findings suggest that this fibrinolysis-related plasma protease may participate in physiologic or pathologic processes where cell proliferation and migration are pivotal, like tissue repair, vascular remodelling, wound healing or tumor development.


Fine mapping of QTLs for rice grain yield under drought reveals sub-QTLs conferring a response to variable drought severities.
Fine-mapping studies on four QTLs, qDTY(2.1), qDTY(2.2), qDTY(9.1) and qDTY(12.1), for grain yield (GY) under drought were conducted using four different backcross-derived populations screened in 16 experiments from 2006 to 2010. Composite and bayesian interval mapping analyses resolved the originally identified qDTY(2.1) region of 42.3 cM into a segment of 1.6 cM, the qDTY(2.2) region of 31.0 cM into a segment of 6.7 cM, the qDTY(9.1) region of 32.1 cM into two segments of 9.4 and 2.4 cM and the qDTY(12.1) region of 10.6 cM into two segments of 3.1 and 0.4 cM. Two of the four QTLs (qDTY(9.1) and qDTY(12.1)) having effects under varying degrees of stress severity showed the presence of more than one region within the original QTL. The study found the presence of a donor allele at RM262 within qDTY(2.1) and RM24334 within qDTY(9.1) showing a negative effect on GY under drought, indicating the necessity of precise fine mapping of QTL regions before using them in marker-assisted selection (MAS). However, the presence of sub-QTLs together in close vicinity to each other provides a unique opportunity to breeders to introgress such regions together as a unit into high-yielding drought-susceptible varieties through MAS.


[I can hear you, but I don't understand you. Why is it so important to perceive high frequencies?].
The word personality is derived from the Latin word "persona" (mask, person); "per sona" means "by the sound or through the sound". In order to look through speech, to hear "behind the mask of a person", we have to be able to hear properly. Especially the frequencies between 2 kHz and 5 kHz and the overtones (the higher we can perceive them, the better) play a central role for decoding vowels, consonants and effects of emotions in voice and speech; beyond that they provide the perfect enjoyment of music and sound. Obviously they are also a vital physical necessity. High frequencies stimulate, they provoke attentiveness and concentration. The activity level of the reticular formation is affected by the influent of the sensory organs with a crucial role by the hearing sense. Hearing in high frequencies leads to higher metabolism, to better motility, to an activation of the gamma nervous system and to a better transfer of information.


Birthweights in Iceland 70 years apart.
Birthweights of 389 babies born in 1901-1910 and 6 303 born in 1972-1981 were compared. There had been a mean increase in birthweight of 85 g and the prevalence of low birthweight had fallen from 5.6% to 3.3%. It is unlikely that this apparent secular increase in birthweight is an artefact due to different methods of weighing. Probably an increase in maternal height accounts for much of the increase in birthweight rather than any other improvement in the quality of the intrauterine environment.


Mercury intoxication disrupts tonic signaling in B cells, and may promote autoimmunity due to abnormal phosphorylation of STIM-1 and other autoimmunity risk associated phosphoproteins involved in BCR signaling.
Epidemiological studies link exposure to mercury with autoimmune disease. Unfortunately, in spite of considerable effort, no generally accepted mechanistic understanding of how mercury functions with respect to the etiology of autoimmune disease is currently available. Nevertheless, autoimmune disease often arises because of defective B cell signaling. Because B cell signaling is dependent on phosphorylation cascades, in this report, we have focused on how mercury intoxication alters phosphorylation of B cell proteins in antigen-non stimulated (tonic) mouse (BALB/c) splenic B cells. Specifically, we utilized mass spectrometric techniques to conduct a comprehensive unbiased global analysis of the effect of inorganic mercury (Hg2+) on the entire B cell phosphoproteome. We found that the effects were pleotropic in the sense that large numbers of pathways were impacted. However, confirming our earlier work, we found that the B cell signaling pathway stood out from the rest, in that phosphoproteins which had sites which were affected by Hg2+, exhibited a much higher degree of connectivity, than components of other pathways. Further analysis showed that many of these BCR pathway proteins had been previously linked to autoimmune disease. Finally, dose response analysis of these BCR pathway proteins showed STIM1_S575, and NFAT2_S259 are the two most Hg2+ sensitive of these sites. Because STIM1_S575 controls the ability of STIM1 to regulate internal Ca2+, we speculate that STIM1 may be the initial point of disruption, where Hg2+ interferes with B cell signaling leading to systemic autoimmunity, with the molecular effects pleiotropically propagated throughout the cell by virtue of Ca2+ dysregulation.


Two immunoassay formats for fully automated CRP detection in human serum.
Immunoassays are a proven approach towards fast, sensitive, cost-effective and easy-to-use analytical systems which are able to measure a variety of interesting analytes, especially in medical diagnostics. Herein, we report two assay formats, binding inhibition and sandwich assay format, for detection of C-reactive protein (CRP) in human serum. Both assays were characterised and compared with respect to their suitability and adaption into a complete sensor system. An automated, optical biosensor system, based on evanescent field technology, was used to carry out a full threefold calibration in each case. Owing to the resulting working ranges, 0.044-2.9 mg L(-1) and 0.13-22.9 mg L(-1), respectively, the assays qualify for use in detecting high-sensitivity CRP (C-reactive protein).


Is there an association between socioeconomic status of General Practice population and postgraduate training practice accreditation? A cross-sectional analysis of Scottish General Practices.
Practice population socioeconomic status is associated with practice postgraduate training accreditation. General Practitioner recruitment to socioeconomically deprived areas is challenging, exposure during training may encourage recruitment. To determine the association of practice population socioeconomic deprivation score and training status, and if this has changed over time. Cross-sectional study looking at socioeconomic deprivation and training status for all General Practices in Scotland (n = 982). Data from Information Services Division, from 2015, were combined with the Scottish Index of Multiple Deprivation to calculate weighted socioeconomic deprivation scores for every practice in Scotland. Scottish training body database identified training practices (n = 330). Mean deprivation score for training and non-training practices was calculated. Logistic regression was used to quantify the odds ratio of training status based on deprivation score, adjusted for practice list size, and compared with a similar 2009 analysis. Socioeconomic deprivation score is associated with training status, but is not significant when adjusted for practice list size [OR (adjusted) 0.87, 95% CI: 0.74-1.04]. In contrast, in 2009, adjusted deprivation score remained significant. Mean deprivation score in training and non-training practices remained similar at both time points [2015: 2.98 (SD 0.88) versus 3.17 (SD 0.81); 2009: 2.95 versus 3.19), with a more deprived mean score in non-training practices. General practices in affluent areas remain more likely to train, although this association appears to be related to larger practice list sizes rather than socioeconomic factors. To ensure a variety of training environments training bodies should target, and support, smaller practices working in more socioeconomically deprived areas.


A naturalistic, 24-week, open-label, add-on study of vortioxetine in bipolar depression.
The efficacy of vortioxetine in major depressive disorder has been evaluated in many studies. However, there is a lack of studies assessing vortioxetine in bipolar depression. In 60 patients with bipolar depression, vortioxetine 10-20 mg daily was added to current mood stabilizing medication during 24-week, naturalistic, openlabel study. The most frequent mood stabilizers were lamotrigine, quetiapine, olanzapine, and valproates. The therapeutic efficacy was evaluated by the Clinical Global Impression - Improvement (CGI-I) and Clinical Global Impression - Severity (CGI-S) scales. Patients were classified as responding to vortioxetine when they achieved 1 or 2 points on the CGI-I scale at any stage of observation. The criterion of remission was defined as score 1 at the CGI-S. 73% of all patients (44/60) responded to vortioxetine and 52% (31/60) achieved clinical remission of depressive symptoms (in mean 8.97 ± 4.05 weeks). There were no significant associations between vortioxetine response/remission rates and: (1) the dose, (2) BD type, (3) clinical stage, (4) presence of rapid cycling, (5) history of psychotic symptoms, analyzed depressive symptoms, and (6) concomitantly used mood stabilizer. 4 patients (6.7%) stopped treatment due to adverse effects (nausea), and 7 patients (11.7%) discontinued treatment due to the phase switch. 14 patients (23%) experienced a loss of vortioxetine effectiveness after the initial response or remission. The results indicate relatively high rates of response and remission during 24-week treatment in depressed bipolar patients receiving vortioxetine concomitantly with a mood stabilizer. This may indicate that vortioxetine added to a mood stabilizer may constitute an efficient and well tolerated therapeutic option in bipolar depression.


Neurological and psychological development of low-risk preterm infants in the first year of life.
Twenty-four selected low-risk preterm and 10 full-term infants were followed in a prospective study of the evolution of neurological signs in the first year of life and to consider the prognostic value of transient neurological abnormalities in relation to learning disabilities at school age. We report the results of the assessments made during the first 12 months. The assessment at 3, 6, 9 and 12 months was made using the Amiel-Tison neurological schedule and the Griffiths developmental scale. A high percentage of our low-risk premature infants (69% of 37-34 weeks gestational age and 75% of 33-27 weeks gestational age group) showed transient neurological anomalies, whereas no major neurological sequelae, i.e., cerebral palsies or mental impairment, were found. Moreover, in our series, the syndrome of transient dystonia associated with low birth weight, already described by other authors in samples not selected for risk, was not observed. The psychological development of all our infants was within normal limits at every assessment. Nevertheless, a significantly decreased performance at the sixth month in both preterm groups, particularly in the group of low gestational age, was found, and its significance will be clarified by further follow-up studies of early school age.


Replacement of the descending thoracic aortic aneurysm with partial cardiopulmonary bypass in the era of endovascular repair.
Although the advent of thoracic endovascular aortic repair (TEVAR) has provided an alternative treatment option for descending thoracic aortic aneurysm (DTAA), open repair still plays a crucial role in DTAA repair. The purpose of this study was to re-evaluate the operative and long-term outcomes of open repair with partial cardiopulmonary bypass, compared to the results of TEVAR with a proximal landing zone of 3 or 4. Between 2007 and 2017, open repair was performed for 44 patients and TEVAR for 282 patients. Acute aortic dissection and open proximal anastomosis under circulatory arrest were excluded. Perioperative and long-term follow-up data were analyzed. In-hospital mortality rate (4.5% vs 3.2%, p = 0.42), and frequencies of spinal cord injury and neurological deficit showed no significant differences between the open repair and TEVAR groups (p = 0.41, 0.25, respectively). The propensity score-matched analysis showed similar cumulative survival (p = 0.23), but significantly higher reintervention rates for the repaired segment in the TEVAR group than in the open repair group (p = 0.0054). Twenty-two (7.8%) TEVAR patients required re-interventions for the repaired segment. Of those, 17 patients underwent additional TEVAR and 5 patients needed open conversion surgery with partial cardiopulmonary bypass. Reintervention rates for the repaired segment were significantly higher in the TEVAR group than in the open repair group (p = 0.012). Open repair DTAA using partial cardiopulmonary bypass showed operative outcomes comparable to TEVAR and lower reintervention rates, and thus remains an acceptable procedure for selected patients in this era of endovascular repair.


Critical issues in breast imaging by vibro-acoustography.
Clinically, there are two important issues in breast imaging: detection of microcalcifications and identification of mass lesions. X-ray mammography is the main imaging method used for detection of microcalcification, and ultrasound imaging is normally used for detection of mass lesions in breast. Both these methods have limitations that reduce their clinical usefulness. For this reasons, alternative breast imaging modalities are being sought. vibro-acoustography is an imaging modality that has emerged in recent years. This method is based on low-frequency harmonic vibrations induced in the object by the radiation force of ultrasound. This paper describes potential applications of vibro-acoustography for breast imaging and addresses the critical imaging issues such as detection of microcalcifications and mass lesions in breast. Recently, we have developed a vibro-acoustography system for in vivo breast imaging and have tested it on a number of volunteers. Resulting images show soft tissue structures and calcifications within breast with high contrast, high resolution, and no speckles. The results have been verified using X-ray mammography. The encouraging results from in vitro and in vivo experiments suggest that further development of vibro-acoustography technology may lead to a new clinical tool that can be used to detect microcalcifications as well as mass lesions in breast.


Synthesis and characterization of novel carboxymethylcellulose hydrogels and carboxymethylcellulolse-hydrogel-ZnO-nanocomposites.
New approach for preparation of CMC hydrogels was undertaken through reacting CMC with either malic, succinic or citric acid. Characteristics of the hydrogels, as monitored by the swelling behavior, FTIR, SEM, EDX, TEM and XRD were dependent on nature and concentration of the polycarboxylic acid, time and temperature of curing. The best practice achieved from these studies was harnessed to synthesize and characterize CMC hydrogel-ZnO-nanocomposites with additional study pertaining to the antibacterial activity of the nanocomposites. CMC hydrogel with excellent swelling behavior could be prepared by adding succinic acid (0.5%) to CMC solution then drying the obtained paste at 80 °C for 5 min followed by curing at 120 °C for 3 min. Similarly, addition of ZnNO3 solution to the CMC paste results in CMC hydrogel-ZnO-nanocomposites having biocidal activity to gram +ve and gram -ve bacteria.


Sequence and electron paramagnetic resonance analyses of nitrate reductase NarGH from a denitrifying halophilic euryarchaeote Haloarcula marismortui.
Genes encoding the NarG and NarH subunits of the molybdo-iron-sulfur enzyme, a nitrate reductase from a denitrifying halophilic euryarchaeota Haloarcula marismortui, were cloned and sequenced. An incomplete cysteine motif reminiscent of that for a [4Fe-4S] cluster binding was found in the NarG subunit, and complete cysteine arrangements for binding one [3Fe-4S] cluster and three [4Fe-4S] clusters were found in the NarH subunit. In conjunction with chemical, electron paramagnetic resonance, and subcellular localization analyses, we firmly establish that the H. marismortui enzyme is a new archaeal member of the known membrane-bound nitrate reductases whose homologs are found in the bacterial domain.


Synthesis of 15 N-labelled 3,5-dimethylpyridine.
15 N-labelled pyridines are liquid- and solid-state nuclear magnetic resonance (NMR) probes for chemical and biological environments because their 15 N chemical shifts are sensitive to hydrogen-bond and protonation states. By variation of the type and number of substituents, different target pyridines can be synthesized exhibiting different pKa values and molecular volumes. Various synthetic routes have been described in the literature, starting from different precursors or modification of other 15 N-labelled pyridines. In this work, we have explored the synthesis of 15 N 15 N-labelled pyridines using a two-step process via the synthesis of alkoxy-3,4-dihydro-2H-pyran as precursor exhibiting already the desired pyridine substitution pattern. As an example, we have synthesized 3,5-dimethylpyridine-15 N (lutidine-15 N) as demonstrated by 15 N-NMR spectroscopy. That synthesis starts from methacrolein, propenyl ether, and 15 N-labelled NH4 Cl as nitrogen source.


Organic halogen removal from chlorinated humic ground water and lake water by nitrifying fluidized-bed biomass characterised by electron microscopy and molecular methods.
The dechlorinating and genotoxicity-removing activities of nitrifying fluidized-bed reactor biomass towards chlorinated organic compounds in water were shown at level below 1 ppm. The removal rates of adsorbable organic halogens were 200 micrograms Cl (g VS day)-1 for chlorinated humic ground water and 50 micrograms Cl (g VS day)-1 for chlorinated lake water when studied in batch mode. In a sequenced batch mode the removal rates [micrograms Cl (g VS day)-1] were 2000 from chlorohumus, 1400-1800 from chlorophenols in chlorinated ground water, and 430-720 from chlorohumus in chlorinated lake water. Genotoxicity was removed to a large extent (60%-80%) from the chlorinated waters upon incubation with nitrifying reactor biomass. 2,6-Di-, 2,4,6-tri and 2,3,4,6-tetrachlorophenols competed with chlorinated water organohalogens for dechlorination. The dechlorination of chlorophenols and chlorohumus required no ammonia and was not prevented by inhibitors of ammonia oxidation, nitrapyrin, parathion, sodium diethyldithiocarbamate, or allylthiourea. Electron microscopical inspection of the biomass showed the dominance of clusters of bacteria resembling known nitrifying species, Nitrosomonas, Nitrobacter, and Nitrosospira. This was supported by polymerase chain reaction amplification of the biomass DNA with four different primers, revealing the presence of 16S rDNA sequences assignable to the same species. The most intensive band obtained with the Nitroso4E primer was shown to be closely related to Nitrosomonas europaea by restriction analysis.


Subtotal colectomy for toxic and fulminant colitis in the era of immunosuppressive therapy.
Prolonged use of immunosuppressive medication to avoid surgery is becoming more common in patients with inflammatory bowel disease, with severe or fulminant colitis. The effect of immunosuppression on postoperative outcomes was reviewed. Patients undergoing subtotal colectomy (STC) for fulminant or toxic colitis from 1992 to 2006 were studied to define the effect of immunosuppression (IS) on postoperative complications (POCs). Patient characteristics, diagnosis, operative indication, details of surgery, use of IS, and POC's were reviewed and univariate and multivariate analysis was performed. Eighty-nine patients were studied (55 males). Seventy-two (91%) patients had fulminant colitis and 17 (20%) had toxic colitis. The preoperative diagnosis was ulcerative colitis in 74, indeterminate in 10, and Crohn's disease in five patients. Eighty-two (92%) patients were on some form of immunosuppression, and 14 had a perforation at surgery. Thirty-nine (43.8%) patients experienced a POC. There was no operative mortality. Univariate analysis identified perforation (P = 0.048) and length of surgery (P = 0.002) as predictive of POCs, while multivariate analysis failed to identify a predictor of complications. There was no association between immunosuppression and postoperative complications. Complications in this setting are a result of the severity of the inflammatory bowel disease.


Nucleotide-dependent binding of the gene 4 protein of bacteriophage T7 to single-stranded DNA.
The gene 4 protein of bacteriophage T7 is a multifunctional enzyme that catalyzes (i) the hydrolysis of nucleoside 5'-triphosphates, (ii) the synthesis of tetraribonucleotide primers at specific recognition sequences on a DNA template, and (iii) the unwinding of duplex DNA. All three activities depend on binding of gene 4 protein to single-stranded DNA followed by unidirectional 5' to 3' translocation of the protein (Tabor, S., and Richardson, C. C. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 205-209). Binding of gene 4 protein to single-stranded DNA, assayed by retention of DNA-protein complexes on nitrocellulose filters, is random with regard to DNA sequence. Although gene 4 protein does not bind to duplex DNAs, the presence of a 240-nucleotide-long single-stranded tail on a 7200-base pair duplex DNA molecule is sufficient for gene 4 protein to cause retention of the DNA on a filter. The binding reaction requires, in addition to MgCl2, the presence of a nucleoside 5'-triphosphate, but binding is not dependent on hydrolysis; nucleoside 5'-diphosphate will substitute for nucleoside 5'-triphosphate. Of the eight common nucleoside triphosphates, dTTP promotes optimal binding. The half-life of the gene 4 protein-DNA complex depends on both the secondary structure of the DNA and on whether or not the nucleoside 5'-triphosphate cofactor can be hydrolyzed. Using the nonhydrolyzable nucleoside 5'-triphosphate analog, beta,gamma-methylene dTTP, the half-life of the gene 4 protein-DNA complex is greater than 80 min. In the presence of the hydrolyzable nucleoside 5'-triphosphate, dTTP, the half-life of the gene 4 protein-DNA complex using circular M13 DNA is at least 4 times longer than that observed using linear M13 DNA.


Epigenome-metabolome-microbiome axis in health and IBD.
Environmental triggers in the context of genetic susceptibility drive phenotypes of complex immune disorders such as Inflammatory bowel disease (IBD). One such trigger of IBD is perturbations in enteric commensal bacteria, fungi or viruses that shape both immune and neuronal state. The epigenome acts as an interface between microbiota and context-specific gene expression and is thus emerging as a third key contributor to IBD. Here we review evidence that the host epigenome plays a significant role in orchestrating the bidirectional crosstalk between mammals and their commensal microorganisms. We discuss disruption of chromatin regulatory regions and epigenetic enzyme mutants as a causative factor in IBD patients and mouse models of intestinal inflammation and consider the possible translation of this knowledge. Furthermore, we present emerging insights into the intricate connection between the microbiome and epigenetic enzyme activity via host or bacterial metabolites and how these interactions fine-tune the microorganism-host relationship.


Ethnic, gender, and acculturation influences on sexual behaviors.
Much research has been conducted on ethnic differences in sexuality, but few studies have systematically assessed the importance of acculturation in sexual behavior. The present study assessed general differences in normative sexual practices in healthy Euro-American, Asian, and Hispanic populations, using measures of acculturation to analyze the relative effects of heritage and mainstream cultures within each group. A total of 1,419 undergraduates (67% Euro-American, 17% Hispanic, 16% Asian; 33% men, 67% women) completed questionnaires which assessed sexual experience and causal sexual behaviors. In concordance with previous studies, Asians reported more conservative levels of sexual experience and frequency of sexual behaviors, fewer lifetime partners, and later ages of sexual debut than Euro-American or Hispanic counterparts. Hispanic reported sexual experiences similar to that of Euro-Americans. There was a significant interaction between mainstream and heritage acculturation in predicting number of lifetime sexual partners in Asian women such that the relationship between heritage acculturation and casual sexual behavior was stronger at lower levels of mainstream acculturation. On the other hand, in Hispanic men, higher levels of mainstream acculturation predicted more casual sexual behavior (one-time sexual encounters and number of lifetime sexual partners) when heritage acculturation was low but less casual sexual behavior when heritage acculturation was high. These results suggest that, for sexual behavior, Hispanic men follow an "ethnogenesis" model of acculturation while Asian women follow an "assimilation" model of acculturation.


Outer membrane protein A of Acinetobacter baumannii regulates pulmonary inflammation through the TLR2-NF-κB pathway.
Acinetobacter baumannii (A. baumannii) is characterized by a high prevalence of drug resistance; how to effectively treat it is still a major clinical challenge. Our previous experiments confirmed that ompA, which is one of the most well-characterized virulence factors, may be dependent on the caspase-1 pathway-stimulated expression of NLRP3 inflammasome to enhance inflammation. TLRs (i.e., TLR2, etc.) is the initiating signal for NLRP3 inflammasome activation; how it relates to ompA in its underlying pathogenic mechanism is not clear. In this study, we proofed that ompA promoted NLRP3 inflammasome activation while the TLR2-NF-κB pathway was also activated after A. baumannii infection. Additionally, the expression of NLRP3 inflammasome-associated proteins and genes was inhibited by silencing TLR2 and NLRP3. This indicated that ompA might depend on the TLR2-NF-κB pathway to assemble and activate the NLRP3 inflammasome. OmpA promoted the assembly of the NLRP3 inflammasome through the TLR2-NF-κB pathway and inhibited the degradation of caspase-1 by the proteasome so that a large number of mature IL-1β/IL-18 and other proinflammatory factors were released extracellularly to enhance the body's inflammatory response. Taken together, the results of the joint pre-study confirmed a novel TLR2-NF-κB/NLRP3/caspase-1-modulated mechanism underpinning ompA activity, the NLRP3 inflammasome pathway may be as a potential immunomodulatory target against A. baumannii infections.


Multi-level multi-leaf collimators: Optimization of layer thicknesses and a feasibility study.
The function of multi-leaf collimators (MLC) is to modulate and shape the intensity of a radiotherapy beam by either blocking or unblocking beamlets. A variation on this functionality is tested in this work wherein the MLC is split into layers, with each layer attenuating the beam by a different amount. In this design, full blocking of a beamlet occurs only if all layers are blocked. This work suggests that such a device, a multi-layer MLC (MLMLC), can deliver dose distributions like a single layer MLC can deliver while requiring less time and monitor units (MU) METHODS: Optimal fluences were made for prostate plans using the Eclipse v13.6. An algorithm was developed to create step-and-shoot MLMLC patterns to match these optimal fluences when using up to six layers of MLC. Twelve MLMLC plans were made in total. These patterns were imported back into Eclipse as equivalent tungsten compensators and doses were calculated. Dose-volume histogram (DVH) values, total monitor units (MU), and total time to deliver were compared between arc-style MLMLC plans and nine-field step and shoot IMRT plans created completely in Eclipse using a single layer MLC. When using three or more layers, specified DVH values between the two sets agreed to within 5% while requiring roughly half as much time to deliver and about 20% fewer MU. Demonstrated that having multi-layer MLC can deliver dose distributions like a single layer MLC with less time and monitor units.


Perioperative external ventricular drainage in obstructive hydrocephalus secondary to infratentorial brain tumours.
Of 148 patients with infratentorial brain tumours which were operated upon during a 5 year period, 59 patients had associated obstructive hydrocephalus, as evidenced by preoperative CT scan. External ventricular drainage was performed in these cases at time of surgery. CSF drainage was continued in the postoperative period for a mean of 2.3 (+/- 1.6) days. Only 6 of these 59 patients (10%) required a subsequent indwelling shunt. The infection rate was 10% and the total mortality was 8%. Perioperative ventricular drainage during and following the removal of posterior fossa tumours causing hydrocephalus provides an effective alternative to the preoperative placement of an indwelling shunt. Problems of shunt dysfunction, tumour seeding and upward herniation are thereby avoided. Postoperative ICP monitoring and drainage of blood and debris laden CSF is performed, increasing the safety of the postoperative period and possibly reducing the incidence of aseptic meningitis and postoperative shunt requirement.


Prospects for the control of AIDS by immunizing seropositive individuals.
The long incubation period between infection and the development of clinical AIDS may be due to an immune response to the initial infection which persists with health and wanes with disease. If this response can be boosted, it may be possible to reduce the viral burden, prevent the development of disease and reduce contagiousness.


Detection of remaining Plasmodium DNA and gametocytes during follow up after curative malaria treatment among returned travellers in Norway.
PCR can be positive weeks after effective malaria treatment, potentially leading to over diagnose of recrudescence and re-infections. The DNA detected by PCR post-treatment might stem from residuals of destroyed asexual parasites, or from live gametocytes. The objective of this clinical observational study was to describe the presence of positive PCR for Plasmodium falciparum and Plasmodium vivax in follow-up samples post-treatment from returned travellers, and the proportion of positive PCR due to gametocytes. Whole blood was collected during hospitalization and outpatient routine follow-up from 13 patients with imported malaria. DNA was extracted applying QIAamp DNA Blood Mini Kit, while mRNA was collected and extracted applying PAXgene Blood RNA Tubes and Kit. All DNA samples (N = 25) were analysed with a genus-specific cytb real-time SYBR PCR, and P. falciparum DNA samples (N = 22) were also analysed with a falciparum-specific varATS real-time TaqMan PCR. All the mRNA samples (N = 18) were analysed with both a genus-specific 18S rRNA RT-PCR and a gametocyte-specific Pfs25 (P. falciparum)/Pvs25 (P. vivax) RT-PCR. Latest samples were collected at day 1 (n = 2) and from day 11-54 (n = 11) after treatment. Genus DNA cytb PCR was positive up to 49 days after effective treatment, and 18S rRNA transcripts from active P. falciparum parasites were detectable for at least 11 days. Gametocyte-specific mRNA was detected at latest only two days after treatment. Among six patients with late positive PCR for P. falciparum, four had high parasitaemia at admittance (6-30%), while two had parasitaemia < 2%. Late detection of P. vivax was not found by any of the PCR methods. DNA-based PCR can be positive up to at least seven weeks after curative malaria treatment, potentially leading to over-diagnose of recrudescence and re-infections. Based on the observations in this study, it is unclear if the DNA origins from residuals of destroyed parasites or live gametocytes, warranting further investigations.


Use of the Gen-Probe PACE system for the detection of Neisseria gonorrhoeae in urogenital samples.
The Gen-Probe PACE (Probe Assay-Chemiluminescent Enhanced) system for Neisseria gonorrhoeae was compared to Martin-Lewis medium in JEMBEC plates for the direct detection of N. gonorrhoeae in urogenital samples. This 2-hr, nonisotopic chemiluminescent test is based on the use of an acridinium ester-labeled DNA probe that binds with gonococcal target rRNA in a clinical sample. Following the separation of the hybridized probe from the unhybridized probe through the use of magnetic microparticles, the acridinium ester is hydrolyzed from the hybridized probe by the addition of an alkaline hydrogen peroxide solution, resulting in the production of light, which is measured in a luminometer. The amount of light generated is directly proportional to the amount of gonococcal target rRNA present in the sample. A total of 209 urethral and 203 endocervical specimens were collected from a high-risk, clinic population with a gonococcal disease prevalence of 24% during the study period. Statistical analyses of the overall results showed that, compared to culture, the Gen-Probe PACE System had a sensitivity, specificity, and positive and negative predictive values of 90%, 99%, 98%, and 97%, respectively. The comparative results of this study showed that the Gen-Probe PACE System for N. gonorrhoeae is a reasonable, noncultural alternative for detecting gonococci directly in urogenital specimens.


Modern neurosurgical techniques for psychiatric disorders.
Psychosurgery refers to an ensemble of more or less invasive techniques designed to reduce the burden caused by psychiatric diseases in patients who have failed to respond to conventional therapy. While most surgeries are designed to correct apparent anatomical abnormalities, no discrete cerebral anatomical lesion is evident in most psychiatric diseases amenable to invasive interventions. Finding the optimal surgical targets in mental illness is troublesome. In general, contemporary psychosurgical procedures can be classified into one of two primary modalities: lesioning and stimulation procedures. The first group is divided into (a) thermocoagulation and (b) stereotactic radiosurgery or recently introduced transcranial magnetic resonance-guided focused ultrasound, whereas stimulation techniques mainly include deep brain stimulation (DBS), cortical stimulation, and the vagus nerve stimulation. The most studied psychiatric diseases amenable to psychosurgical interventions are severe treatment-resistant major depressive disorder, obsessive-compulsive disorder, Tourette syndrome, anorexia nervosa, schizophrenia, and substance use disorder. Furthermore, modern neuroimaging techniques spurred the interest of clinicians to identify cerebral regions amenable to be manipulated to control psychiatric symptoms. On this way, the concept of a multi-nodal network need to be embraced, enticing the collaboration of psychiatrists, psychologists, neurologists and neurosurgeons participating in multidisciplinary groups, conducting well-designed clinical trials.


New anti-inflammatory thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azoles with antioxidant properties as potential iNOS inhibitors.
The objective of this study was to investigate the anti-inflammatory and antioxidant activity of new thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azole derivatives as potential iNOS inhibitors. The in vivo anti-inflammatory effects of the new thiazole compounds were studied in a turpentine oil induced inflammation model. Their anti-inflammatory activity was assessed by evaluating the acute phase bone marrow response, phagocytes' activity, NO synthesis and antioxidant capacity. The new thiazole compounds have anti-inflammatory effects by lowering bone marrow acute phase response and oxidative stress. The best anti-inflammatory and antioxidant effect was found for thiazolyl-carbonyl-thiosemicarbazides Th-1-8, thiazolyl-1,3,4-oxadiazole Th-20 and thiazolyl-1,3,4-thiadiazole Th-21. Virtual screening of thiazole derivatives against the oxygenase domain of chain A from 2Y37 revealed that all twenty-two compounds bind the active site of inducible nitric oxide synthase (iNOS). Based on the virtual screening and on the results obtained above, the activity may be due to their capacity to reduce the NO synthesis by blocking the bind of L-Arg in the active site of iNOS, the compounds binding the synthase by hydrogen bonds between the NH (2 and/or 4) of thiosemicarbazide fragment (Th-2-8) or N2/N3 from azole cycles and by the thiol function (Th-9-22).


Addressing Postpandemic Clinician Mental Health : A Narrative Review and Conceptual Framework.
Previous pandemics have seen high psychiatric morbidity among health care workers. Protecting clinician mental health in the aftermath of coronavirus disease 2019 (COVID-19) requires an evidence-based approach to developing and deploying comprehensive clinician mental health support. In a narrative review of 96 articles addressing clinician mental health in COVID-19 and prior pandemics, 7 themes emerged: 1) the need for resilience and stress reduction training; 2) providing for clinicians' basic needs (food, drink, adequate rest, quarantine-appropriate housing, transportation, child care, personal protective equipment); 3) the importance of specialized training for pandemic-induced changes in job roles; 4) recognition and clear communication from leadership; 5) acknowledgment of and strategies for addressing moral injury; 6) the need for peer and social support interventions; and 7) normalization and provision of mental health support programs. In addition to the literature review, in collaboration with the Collaborative for Healing and Renewal in Medicine (CHARM) network, the authors gathered practice guidelines and resources from health care organizations and professional societies worldwide to synthesize a list of resources deemed high-yield by well-being leaders. Studies of previous pandemics demonstrate heightened distress in health care workers years after the event. The COVID-19 pandemic presents unique challenges that surpass those of previous pandemics, suggesting a significant mental health toll on clinicians. Long-term, proactive individual, organizational, and societal infrastructures for clinician mental health support are needed to mitigate the psychological costs of providing care during the COVID-19 pandemic.


Pre-existing diabetic retinopathy as a prognostic factor for COVID-19 outcomes amongst people with diabetes: A systematic review.
Certain patients with Diabetes Mellitus (DM) have high risk for complications from COVID-19. We aimed to test the hypothesis that pre-existing diabetic retinopathy (DR), a microvascular disease, is a prognostic indicator for poor COVID-19 outcome in this heterogeneous population. Seven databases (including MEDLINE) and grey literature were searched, identifying eligible studies using predetermined selection criteria. The Quality in Prognosis Studies (QUIPS) tool was used for quality assessment, followed by narrative synthesis of included studies. Eight cohort studies were identified. Three showed significant positive associations between DR and poor COVID-19 outcomes. The highest quality study, McGurnaghan, found increased risk of the combined outcome fatal or critical care unit (CCU)-treated COVID-19 with referable-grade DR (OR 1.672, 95% CI 1.38-2.03). Indirectly, four studies reported positive associations with microvascular disease and poorer prognosis. Variability between studies limited comparability. The current literature suggests an independent association between DR and poorer COVID-19 prognosis in patients with DM after controlling for key variables such as age. The use of standardised methodology in future studies would establish the predictive value of DR with greater confidence. Researchers should consider comparing the predictive value of DR and its severity, to other microvascular complications of DM.


Use of polymerase chain reaction for the identification of Leptospira sp. in urine of carriers.
The objectives of the present work were to detect Leptospira seropositive animals. The ELISA results report only IgG antibodies, which could be attributable to chronic infections or else, that they are healthy carriers. All polymerase chain reaction positive animals should be considered potential sources of infection.


Identification of a novel pathogen-induced gene encoding a leucine-rich repeat protein expressed in phloem cells of Capsicum annuum.
The CALRR1 gene, expressed in pepper leaves following infection by Xanthomonas campestris pv. vesicatoria, encodes a secreted leucine-rich repeat (LRR) with five tandem repeats of a 24-amino-acid LRR motif. Northern blot analyses revealed that CALRR1 is not constitutively expressed in pepper plants, but is strongly induced upon the infection by X. campestris pv. vesicatoria, Phytophthora capsici, Colletotrichum coccodes and Colletotrichum gloeosporioides on leaves. CALRR1 was not systemically induced in upper leaves by bacterial infection. The inoculation of bacterial live cells, and treatment with dead cells and culture filtrates of pathogenic or nonpathogenic bacteria triggered the accumulation of CALRR1 transcripts. Treatment with signaling molecules, including salicylic acid (SA), ethylene (ET), methyl jasmonate (MeJA), dl-beta-amino-n-butyric acid (BABA) and benzothiadiazole (BTH), did not activate the transcription of the CALRR1 gene, indicating that CALRR1 expression is not regulated by defense signaling pathways activated by these molecules. CALRR1 was induced by treatment with high salinity, abscisic acid (ABA) and wounding, but not by drought and cold stress. An in situ hybridization study showed that CALRR1 mRNA was localized in phloem tissues of leaves, stems, and green fruits of pepper plants during the pathogen infection and ABA exposure. The location characteristics and the spatio-temporal expression pattern of CALRR1 suggest that it may play a role in protecting phloem cells against biotic and abiotic stresses affecting phloem function.


Tacit knowledge in dyads of persons with profound intellectual and multiple disabilities and their caregivers: An interpretative literature study.
Caring for persons with profound intellectual and multiple disabilities (PIMD) demands specific expertise. Tacit knowledge seems to play an important role, but little is known about its nature, including what is necessary for its development and transfer. To gain understanding of the nature and development of tacit knowledge between persons with PIMD and their caregivers. We conducted an interpretative synthesis of literature on tacit knowledge in caregiving dyads with persons with PIMD, persons with dementia or infants. Twelve studies were included. Tacit knowledge is about caregivers and care-recipients becoming sensitive and responsive to each other's cues and together crafting care routines. Learning takes place in a constant process of action and response that transforms those involved. Building tacit knowledge together is necessary for persons with PIMD to learn to recognise and express their needs. Suggestions are made for ways to facilitate its development and transfer.


Antiphospholipid syndrome: a series of surgical emergencies and the current evidence for its management.
It is generally accepted that antiphospholipid syndrome remains a major medical problem characterised by hypercoagulability, arterial and venous thrombosis and thrombocytopenia. It is unclear how best to treat these patients should they require emergency surgery. If a lupus anticoagulant is present, hypercoagulability may occur de novo but surgical interventions along with sepsis are two important predisposing factors. We describe three patients with primary antiphospholipid syndrome and discuss the implications for surgery.


Mapping the spliced and unspliced late lytic SV40 RNAs.
The sizes and map positions of the major late lytic SV40 cytoplasmic mRNAs and the abundant nuclear RNA species have been determined by the technique of Berk and Sharp (1977, 1978). From these experiments, the coding sequences (bodies) of the 16S and 19S late cytoplasmic SV40 RNAs have been located at 0.935-0.17 and 0.765-0.17 map units, respectively. The cytoplasmic 16S RNA molecules contain a leader sequence of approximately 210 nucleotides, corresponding to SV40 map positions 0.72-0.76 units, spliced to the coding sequences. In a population of the late 19S RNA molecules, there are several different leader segments, each spliced to the same coding sequences. The size of these 19S leader RNA segments was estimated to be 50-70, 100-120 and 200-210 nucleotides in length. The 5' ends of the 19S leader RNA segments were located at 0.72, 0.71, 0.695 and 0.69 map units. An analysis of the nuclear viral RNAs has provided insight into the biogenesis of the cytoplasmic messages. Poly (A)-containing nuclear RNA has a number of species in addition to those found in the cytoplasm. The 3' ends of the poly (A)-containing RNAs map at 0.17 SV40 units. The 5' ends of the more abundant nuclear molecules map approximately at 0.72, 0.70, 0.67, 0.64 and 0.59 units. Since these nuclear SV40 RNA molecules are both colinear with the viral DNA and larger than the cytoplasmic nRNAs, they may represent intermediates in a stepwise processing system. Alternatively, the variation in 5' ends of nuclear SV40 transcripts may represent a number of separate initiation sites for transcription. The presence of the intervening RNA sequences (between the leader and the coding sequences of the mature mRNAs) in these nuclear RNA molecules suggests that the synthesis of "spliced" SV40 RNA involves the direct transcription of the DNA sequences and the subsequent splicing out of the intervening seqment of RNA. Evaluation of the more abundant nonpolyadenylated nuclear RNA molecules showed that they have the same 5' ends as the poly (A)-containing nuclear RNAs. The 3' ends of the nonpolyadenylated RNA molecules map heterogeneously in a broad region extending beyond 0.28 map units. The presence of these long nuclear viral transcripts suggests that transcription of late SV40 RNA does not terminate at 0.17 map units. The location of poly (A) in mature cytoplasmic viral RNA at 0.17 map units suggest that poly (A) addition to RNA molecules may occur by a specific cleavage of the longer transcripts. Based on these analyses, we propose that the longer nonpolyadenylated viral RNA molecules in the nuclei of SV40-infected cells may represent the primary transcripts. While their 5' termini are being processed, the specific addition of poly (A) at 0.17 map units takes place. The polyadenylation of RNA is followed by splicing events to generate the cytoplasmic forms of SV40 mRNA.


Advances in Data-Driven Responses to Preventing Spread of Antibiotic Resistance Across Health-Care Settings.
Among the most urgent and serious threats to public health are 7 antibiotic-resistant bacterial infections predominately acquired during health-care delivery. There is an emerging field of health-care epidemiology that is focused on preventing health care-associated infections with antibiotic-resistant bacteria and incorporates data from patient transfers or patient movements within and between facilities. This analytic field is being used to help public health professionals identify best opportunities for prevention. Different analytic approaches that draw on uses of big data are being explored to help target the use of limited public health resources, leverage expertise, and enact effective policy to maximize an impact on population-level health. Here, the following recent advances in data-driven responses to preventing spread of antibiotic resistance across health-care settings are summarized: leveraging big data for machine learning, integration or advances in tracking patient movement, and highlighting the value of coordinating response across institutions within a region.


Anxiety-like behavior in rats: a computational model.
This work describes a neural network model of the rat exploratory behavior in the elevated plus-maze, a test used to study anxiety. It involves three parameters: drive to explore; drive to avoid aversive stimuli; and spontaneous locomotor activity. Each network unit corresponds to a specific location in the maze and the connections, only between closest neighbors, represent the possible adjacent places to which a virtual rat can navigate. Competitive learning is used to generate a sequence of network states that correspond to the virtual rat successive locations in the maze. To evaluate the generality of the model it was also tested for two modifications of the elevated plus-maze: one with totally closed arms and the other with totally open arms. The results are compared with data obtained with rats. The simulations are consistent with experimental evidence and may provide an efficient way of describing the anxiety-like rat behavior in the elevated plus-maze. This could be useful for researching the emotional parameters involved in this anxiety animal model.


Modulation of phenotype in cultures of human milk epithelial cells and its relation to the expression of a membrane antigen.
Primary cultures of human milk epithelial cells, labelled with HMFG-1, a monoclonal antibody that recognises a differentiation antigen on the membranes of breast epithelia, were separated from unlabelled cells in a fluorescence-activated cell sorter (FACS). Cells not expressing the HMFG-1 antigen have a greater in vitro growth potential than the positive ones, and give rise to cultures containing both HMFG-1 antigen positive and negative cells. The cultures derived from negative cells usually contain colonies with 'open' cuboidal cells and these do not express the HMFG-1 antigen. However, when they differentiate into other phenotypes such as the 'closed' cuboidal cell type, expression of the differentiation antigen becomes evident and the cultures then show a reduced growth potential. When milk cells are subcultured several times, a new cell type emerges which does not express the HMFG-1 antigen or the intermediate filaments typical of epithelial cells but instead express high levels of fibronectin which is found in an extracellular matrix. Whether these cells emerge by selection of an existing phenotype or by phenotypic modulation is discussed.


Observation and Characterization of the Hg-O Diatomic Molecule: A Matrix-Isolation and Quantum-Chemical Investigation.
Mercuric oxide is a well-known and stable solid, but the diatomic molecule Hg-O is very fragile and does not survive detection in the gas phase. However, laser ablation of Hg atoms from a dental amalgam alloy target into argon or neon containing about 0.3 % of 16 O2 or of 18 O2 during their condensation into a cryogenic matrix at 4 K allows the formation of O atoms which react on annealing to make ozone and new IR absorptions in solid argon at 521.2 cm-1 for Hg-16 O or at 496.4 cm-1 for Hg-18 O with the oxygen isotopic frequency ratio 521.2/496.4=1.0499. Solid neon gives a 529.0 cm-1 absorption with a small 7.8 cm-1 blue shift. CCSD(T) calculations found 594 cm-1 for Hg16 O and 562 cm-1 for Hg18 O (frequency ratio=1.0569). Such calculations usually produce harmonic frequencies that are slightly higher than the anharmonic (observed) values, which supports their relationship. These observed frequencies have the isotopic shift predicted for Hg-O and are within the range of recent high-level frequency calculations for the Hg-O molecule. Spectra for the related mercury superoxide and ozonide species are also considered for the first time.


Understanding the mobile healthcare applications continuance: The regulatory focus perspective.
Although mobile healthcare (mHealth) applications have proliferated and offer new opportunities for personal health management, many users exhibit discontinuance behavior. Various factors in mHealth applications can strongly impact users' continuance behavior, but it is not yet fully understood how they interact with each other to yield maximized effects. This study highlights the importance of identifying the antecedents and moderators of continuance intention to broaden the demographic reach of mHealth applications and thus contribute to maintaining a sustainable healthcare system. This research explores three dimensions of perceived values (hedonic, utilitarian, and social) in mHealth platforms that lead to user satisfaction and, ultimately, continuance intention. It further investigates the moderating effects of personal traits defined by regulatory focus on the relationship between perceived value and user satisfaction. Data was collected from 259 respondents with experience using the Samsung Health application. The research tests the proposed model and hypotheses by implementing PLS-SEM and multi-group analyses. Each dimension of perceived values positively influences user satisfaction, with hedonic and utilitarian values exhibiting stronger relationships. Regarding moderating effects, promotion (versus prevention) focus has a stronger enhancing effect on the positive relationship between utilitarian value and user satisfaction. In contrast, prevention (versus promotion) focus more strongly enhances the positive relationship between hedonic value and user satisfaction. Regulatory focus does not yield a significant moderating effect on the relationship between social value and user satisfaction. User satisfaction exerts a strong positive influence on continuance intention in mHealth environments. The moderating effect of individuals' regulatory focus has been identified. Combined effects of antecedents and moderators on user satisfaction influence their continuance intention in mHealth ecologies. Considering individual users' characteristics may guide mHealth application developers to design personalized platforms and establish enforced marketing strategies.


Evidence that the prostaglandin E2 receptor and the anhydrolevuglandin E2 receptor in the rat uterus are the same receptor.
Anhydrolevuglandin E2 (AnLGE2) is closely related to prostaglandin E2 (PGE2) and has been found to inhibit the uterotonic activity of PGE2. The binding of PGE2 and its inhibition by AnLGE2 has been determined in rat uterine membrane fractions. AnLGE2 inhibited the binding of 3HPGE2 in a dose related fashion. 3HAnLGE2 also binds to rat uterine membrane fractions and its binding is inhibited by PGE2 in a dose related fashion. These data support previous physiological observations that AnLGE2 inhibits the actions of PGE2 by acting at the PGE2 receptor. Thus, AnLGE2 appears to be a specific inhibitor of PGE2 actions at its uterine receptors.


Effects of aldrin-transdiol on neuromuscular facilitation and depression.
The effects of aldrin-transdiol, one of the active metabolites of the insecticide dieldrin, on evoked transmitter release, neuromuscular facilitation and neuromuscular depression have been studied in frog sartorius nerve-muscle preparations. Conventional techniques of intracellular recordings were used. Aldrin-transdiol caused a marked increase in end-plate potential amplitude under conditions of low quantal content, i.e., in Mg2+-blocked junctions. The increase in end-plate potential amplitude was less pronounced in curarized junctions, in which the transmitter release was not impaired. Concomitant with the increase in end-plate potential size there was a marked enhancement of facilitation during short trains of stimuli applied to the motor nerve. The decay of facilitation was, however, not seriously affected by aldrin-transdiol. These effects may be explained in terms of the known 'calcium hypothesis' by assuring that aldrin-transdiol increases the amount of calcium which enters the nerve terminal during the nerve impulse. The increase in end-plate potential amplitude and in facilitation by aldrin-transdiol was transient. At later stages of poisoning, end-plate potential and facilitation decreased below control level and neuromuscular depression was significantly enhanced. This latter effect may be the result of a direct inhibitory effect of aldrin-transdiol on transmitter mobilization. As far as the fall in end-plate potential amplitude is concerned the known suppressive action of aldrin-transdiol on the chemical sensitivity of the postsynaptic membrane and on the nerve action potential probably plays a part as well. Finally, neuromuscular transmission was completely blocked by aldrin-transdiol.


Rib fracture as a predictor of future fractures in young and older postmenopausal women: National Osteoporosis Risk Assessment (NORA).
A rib fracture history after age 45 was associated with a 5.4-fold increase in new rib fracture risk and a 2.4-fold increase in risk of any new clinical fracture in 155,031 postmenopausal women. A rib fracture history suggests osteoporosis and should be considered when evaluating patients for interventions to prevent fractures. Until recently, little attention was paid to rib fracture as an osteoporosis marker. Emerging evidence suggests rib fracture may be an osteoporotic fracture in men and women. We report the 5-year independent association between baseline rib fracture histories and self-reported future fractures by age (decade) in the NORA cohort (155,031 postmenopausal women, 50-99 years). Participants reported fracture history and responded to follow-up surveys at years 1, 3, or 6. Women with a baseline rib fracture history without other fractures were compared with women with no fracture. At baseline, 4,758 (3.07%) women reported a rib fracture history without other fractures; 6,300 women reported 6,830 new clinical fractures, including wrist (2,271), rib (1,891), spine (1,136), hip (941), and forearm (591). Adjusted relative risk (ARR) values (95% confidence interval [CI]) for future fractures in women with rib fracture history versus women with no fracture history were 5.4 (4.8-6.1) at the rib, 2.1 (1.7-2.6) at the spine, and 1.4 (1.1-1.7) at the wrist, and not significant for forearm or hip fractures. Future fracture risk was at least doubled in women with a rib fracture history in all ages: ARR (95% CI) 3.4 (2.8-4.0) for ages 50-59, 2.5 (2.1-3.0) for ages 60-69, 2.0 (1.7-2.3) for ages 70-79, and 2.0 (1.6-2.6) for ages >80. Rib fracture, the second most common clinical fracture in women (after wrist fracture), predicted future fractures of the rib, wrist, and spine at all ages. Women presenting with rib fractures should be evaluated for appropriate management to prevent future fractures.


Schistosomiasis in northern Mozambique.
A survey of 12 schools in Cabo Delgado, northern Mozambique, was performed to assess the extent of schistosomiasis infection. Questionnaires validated by parasitological examination of stools and urine were used. Very high prevalences of Schistosoma haematobium infection were found in all schools (77.5% was the lowest recorded), so the questionnaires did not distinguish 'high risk' schools. However, they clearly indicated a good knowledge of the infection by students and teachers. The disease was recognized by teachers to be a public health problem in the area. S. mansoni infection was rare. It had not been reported in previous surveys, but its vector Biomphalaria was discovered in the area. Revised mapping of the disease is advisable in view of probable changes after many years of conflict.