Looking forward, looking back.
Amgen's retrospective sortie into personalized Vectibix treatment poses some difficult questions for regulators concerning the oversight of companion diagnostics.


Postnatal changes in enteric plexus axonal thickness.
Chronological age has not always been an accurate predictor of gut motility in newborns. We hypothesized that the enteric plexus is immature at birth. We studied whole-mount preparations of the myenteric plexus in pigs from mid-point of gestation to adulthood. Distal large bowel whole-mount preparations of the myenteric plexus were stained using ACHE histochemistry in five pigs from six different age groups (60 and 90 days gestation, newborn, 4 and 12 weeks old, and adult pigs). With the aid of light micrographs and Image J program the axonal diameter, distance between ganglia, neuronal size and neuronal nucleus size were measured. Statistical significance was measured using one-way ANOVA test. There was significant increase in axonal diameter and interganglionic distance, with increasing age in the myenteric plexus of rectum in pigs (P < 0.05). Neuronal cell size and nucleus size of the enteric neurons also increased with age, but was not statistically significant. This study shows for the first time that the axonal thickness in the enteric myenteric plexus undergoes striking changes during the first 12 weeks of life in piglets. Assessment of axonal thickness in rectal biopsies may be a valuable morphological feature in diagnosing functional intestinal obstruction in infants.


Regulation of cadmium tolerance and accumulation by miR156 in Arabidopsis.
Plants have evolved effective strategies to cope with heavy metals Cd toxicity, but the regulatory mechanism underlying Cd tolerance and accumulation are still poorly understood. miR156 has been shown to be the master regulator of development and stress response in plants. However, whether miR156 is also involved in plant Cd stress response remains unknown. Here, we show that plants overexpressing miR156 (miR156OE) accumulated significantly less Cd in the shoot, and conferred enhanced tolerance to Cd stress. Plants with a knocked-down level of miR156 (MIM156) were sensitive to Cd stress, and accumulated significantly higher Cd. Under Cd stress, miR156OE had significantly longer primary root length, higher biomass and chlorophyll content, increased activities of antioxidative enzymes and lower levels of endogenous reactive oxygen species (ROS), while MIM156 had the opposite phenotype. To investigate the underlying mechanism of miR156-mediated Cd stress response in Arabidopsis, we profiled the expression of several Cd transporter genes. The expression of Cd uptake transporter of AtZIP1、AtZIP2 and vacuole segregated transporter AtABCC1 was significantly elevated in miR156OE, whereas it was significantly reduced in MIM156. MIM156 also led to an elevated level of AtHMA4 responsible for transporting Cd from the root to the shoot. Our results indicate that miR156 acts as a positive regulator of plant tolerance to Cd stress by modulating ROS levels and Cd uptake/transport genes expression. Therefore, our study adds a new layer of regulatory mechanism for Cd transport and tolerance in plants, and provides a perspective to regulate Cd transport artificially by modulating plant vegetative growth and development using miR156.


CRISPR/Cas9 based gene editing of Frizzled class receptor 6 (FZD6) reveals its role in depressive symptoms through disrupting Wnt/β-catenin signaling pathway.
As one of the common psychiatric diseases, depression poses serious threats to human health. Although many genes have been nominated for depression, few of them were investigated in details at the molecular level. To demonstrate Frizzled class receptor 6 (FZD6) functions in depression through disrupting Wnt/β-catenin signal pathway. The FZD6 edited cell line and mouse model were generated by using CRISPR/Cas9 technique. The expression of key genes and proteins in Wnt/β-catenin pathway was determined by qRT-PCR and Western blotting, respectively. Animal behavioral tests, including open field test (OFT), elevated plus maze test (EPM), forced swimming test (FST), tail suspension test (TST), and sucrose preference test (SPT), were employed to determine anxiety- and depressive-like behaviors. Immunofluorescent staining was used to assess cell proliferation in the hippocampus of mouse brain. Among patients with depression, FZD6, one of the receptors of Wnt ligand, was significantly decreased. In CRISPR/Cas9-based FZD6 knockdown cells, we showed that FZD6 plays a significant role in regulating expression of genes involved in Wnt/β-catenin pathway. Subsequently behavioral studies on Fzd6 knockdown mice (with a 5-nucleotide deletion; Fzd6-Δ5) revealed significant changes in depressive symptoms, including increased immobility duration in FST, less preference of sucrose in SPT, reduction of distance traveled in OFT, and decreased time spent in open arms in EPM. Immunofluorescent staining showed decreased cell proliferation in the hippocampus of Fzd6-Δ5 mice with reduced number of Ki67+ and PCNA+ cells. Moreover, decreased Gsk3β mRNA expression, phosphorylated GSK3β, and cytoplasmic β-catenin in the hippocampus of Fzd6-Δ5 mice provided further evidence supporting the role of Fzd6 in depression. Together, above findings proved the significant role of FZD6 in depression through its effect on hippocampal cell proliferation and its ability to regulate canonical Wnt/β-catenin pathway.


Green tea flavonoid epigallocatechin-3-gallate (EGCG) inhibits cardiac hERG potassium channels.
The catechin EGCG is the main flavonoid compound of green tea and has received enormous pharmacological attention because of its putative beneficial health effects. This study investigated for the first time the effect of EGCG on hERG channels, the main pharmacological target of drugs that cause acquired long QT syndrome. Cloned hERG channels were expressed in Xenopus oocytes and in HEK293 cells. Heterologous hERG currents were inhibited by EGCG with an IC50 of 6.0 micromol/l in HEK293 cells and an IC50 of 20.5 micromol/l in Xenopus laevis oocytes. Onset of effect was slow and only little recovery from inhibition was observed upon washout. In X. laevis oocytes EGCG inhibited hERG channels in the open and inactivated states, but not in the closed states. The half-maximal activation voltage of hERG currents was shifted by EGCG towards more positive potentials. In conclusion, EGCG is a low-affinity inhibitor of hERG sharing major electrophysiological features with pharmaceutical hERG antagonists.


[Premature tracheoesophageal fistula as a complication after short- term intubation of the patient after craniocerebral trauma].
We have described a rare case of early tracheo-esophageal fistula after short-term intubation. 18-year old male patient was admitted to ICU after craniocerebral trauma. After 6 days of intubation the tracheo-esophageal fistula appeared. We suggest that tracheoesophageal fistula was caused by compression of the trachea by tracheostomies tube cuff, shock and poor general condition.


Characterization of hemoglobin variants. Prenatal diagnosis on a fetus at risk of having the hemoglobin variants S and/or C in combination with beta-thalassemia.
The determination of hemoglobin types in a fetus whose father and mother were heterozygous for Hb S and Hb C, respectively, is used as an example for demonstrating different techniques. The parents were furthermore suspected of being heterozygous for beta-thalassemia. Several of the possible combinations give rise to such serious conditions that abortus provocatus would be considered. The conclusion from the analyses was that the fetus was normal, having no variants nor thalassemia.


Development of a sociometric web application to study the relationship among secondary school learners.
This research aimed to develop a sociometric web application to study the relationship among Thai secondary school learners. The first phase studied conditions and needs for a sociometric web application by interviewing 8 teachers (100% females) who have teaching experiences between 3-38 years (Mean = 16.63, SD = 11.58). The second phase developed a sociometric web application which was reviewed by 5 experts and received the overall highest level of appropriateness. Then, the application was piloted with 34 teachers and learners. Overall, the sociometric web application and user manual are suitable for use. The third phase studied results for the sociometric web application usage. Samples included teachers and secondary school learners. The experiment was conducted in a large group of 6 teachers (100% females) having teaching experiences between 4-22 years (Mean = 8.67, SD = 7.03) and students in 5 classrooms, totaling 204 participants (88.73% of response rate, 60.2% females, 39.8% males, age range = 10-23 years old, Mean = 15.72, SD = 1.67) selected via a purposive sampling method. The research tools were the observation form, interview forms, and opinion questionnaire regarding sociometric web application usage. Data were analyzed by qualitative data and descriptive statistics, including frequency distributions, percentages, means, standard deviations, t-test, crosstabs, and chi-square. The teachers' and learners' opinions on web application usage showed an overall highest level of suitability. Furthermore, results concerning the consistency of the sociometric status analysis and the teachers' opinions showed overall average consistency at 87.21%. Finally, the students' sociometric status was divided into five student groups: (1) average (34.3%); (2) popular (24%); (3) neglected (19.1 %); (4) rejected (15.7 %); and (5) controversial (6.9%). Students' gender and academic performance were related to the sociometric status with a .05 level statistical significance (χ2 = 17.742, sig = .001, χ2 = 23.831, sig = .002), respectively. This signifies that students of different genders and academic performances had different sociometric statuses.


Acetoacetyl-CoA synthetase gene is abundant in rat adipose, and related with fatty acid synthesis in mature adipocytes.
Acetoacetyl-CoA synthetase (AACS, acetoacetate-CoA ligase, EC 126.96.36.199) is a novel cytosolic ketone body (acetoacetate)-specific ligase, the physiological role of which remains to be elucidated. We examined the expression profiles of AACS mRNA in adult rat tissues, finding that it was particularly abundant in male subcutaneous white adipose tissue after weaning. In white adipose tissue, AACS mRNA was preferentially detected in mature adipocytes but not in preadipocytes. The AACS mRNA expression in primary preadipocytes increased during the adipocyte differentiation. These expression profiles were similar to that of acetyl-CoA carboxylase-1, but not like to that of 3-hydroxy-3-methylglutaryl-CoA reductase. These results suggest that AACS in adipose tissue plays an important role in utilizing ketone body for the fatty acid-synthesis during adipose tissue development.


Re-emergence of fatal human influenza A subtype H5N1 disease.
Human disease associated with influenza A subtype H5N1 re-emerged in January, 2003, for the first time since an outbreak in Hong Kong in 1997. Patients with H5N1 disease had unusually high serum concentrations of chemokines (eg, interferon induced protein-10 [IP-10] and monokine induced by interferon gamma [MIG]). Taken together with a previous report that H5N1 influenza viruses induce large amounts of proinflammatory cytokines from macrophage cultures in vitro, our findings suggest that cytokine dysfunction contributes to the pathogenesis of H5N1 disease. Development of vaccines against influenza A (H5N1) virus should be made a priority.


[The Swiss approach for cardiac rehabilitation].
Structured cardiac rehabilitation goes back to the late 1960s also in Switzerland and in the beginning was only available in rehabilitation clinics. In 1972 the first ambulatory rehabilitation programs became available to patients in Zurich and Bern. In the following years, in addition to the increasing number of rehabilitation centers for inpatients, more and more ambulatory rehabilitation programs were developed, especially in the larger Midlands population area in German and French-speaking Switzerland. In 1985 the Swiss Working Group of Cardiac Rehabilitation (SAKR) was initiated as an official working group of the Swiss Society of Cardiology and one of its first tasks was to establish a list of the institutions for cardiac rehabilitation in Switzerland. At that time there were 42 rehabilitation programs for a population of approx. 6.5 million, 21 for inpatients and 21 ambulatory; however, 90% of the patients were in inpatient programs. In 1992 the SAKR group defined the quality criteria which were to be applied for official recognition of institutions for cardiac rehabilitation in Switzerland. Due to these criteria, plus the fact that an increasing number of rehabilitation clinics in the mountains had been closed down, the number of inpatient rehabilitation centers decreased from 21 to 11 between 1989 and 2011, whereas the number of ambulatory programs increased from 21 to 51. The ambulatory rehabilitation centers are partially organized by local medical groups; however, most have integrated their activities into the local hospitals. The trend shows a developing preference for ambulatory rehabilitation. More and more elderly, polymorbid patients, however, will still need care in inpatient programs.


Early onset pneumonia: a multicenter study in intensive care units.
A prospective multicenter study concerning the incidence, onset time, risk factors and mortality of pneumonia was carried out by the Intensive Care Units Collaborative Group for Infection Control in Lombardy, Northern Italy. Out of 1304 patients admitted over 3 months in 16 intensive care units (ICUs), 441 met the criteria for the protocol (no previous pulmonary infection or irreversible terminal illness, ICU stay greater than 48 h). The incidence of acquired pneumonia was 21.3% (94/441), with 54.2% of cases diagnosed within 4 days of admission (early onset pneumonia). Impairment of airway reflexes on admission and more than 24 h respiratory assistance were shown as significant risk factors (RR) for early onset pneumonia (respectively RR = 12.4, with 95% confidence interval (CI) = 5.3-28.9 and RR = 3.3, with 95% CI = 1.8-5.9). A suggested pathogenetic mechanism is aspiration of oropharyngeal contents at the onset of acute illness, due to depression of protective reflexes with delayed clearance of bacterial contamination. No protection was offered by routinely applied prophylactic antibiotic therapy.


The relative merits of therapies being developed to tackle inappropriate ('self'-directed) complement activation.
The complement system is an enzyme cascade that helps defend against infection. Many complement proteins occur in serum as inactive enzyme precursors or reside on cell surfaces. Complement components have many biologic functions and their activation can eventually damage the plasma membranes of cells and some bacteria. Although a direct link between complement activation and autoimmune diseases has not been found, there is increasing evidence that complement activation significantly contributes to the pathogenesis of a large number of inflammatory diseases that may have autoimmune linkage. The inhibition of complement may therefore be very important in a variety of autoimmune diseases since their activation may be detrimental to the individual involved. However, a complete and long-term inhibition of complement may have some contra side effects such as increased susceptibility to infection. The site of complement activation will, however, determine the type of inhibitor to be used, its route of application and dosage level. Compared with conventional drugs, complement inhibitors may be the best option for treatment of autoimmune diseases. The review takes a critical look at the relative merits of therapies being developed to tackle inappropriate complement activation that are likely to result in sporadic autoimmune diseases or worsen already existing one. It covers the complement system, general aspects of complement inhibition therapy, therapeutic strategies and examples of complement inhibitors. It concludes by highlighting on the possibility that a better inhibitor of complement activation when found will help provide a formidable treatment for autoimmune diseases as well as preventing one.


Revision surgery after failed surgical treatment of midshaft clavicle fractures is often associated with positive detection of bacteria.
Midshaft clavicle fractures are common, and the proportion of patients treated surgically has increased in recent years. With this increase in surgical treatments, the complication rate, for instance of infection, non-union, or implant failure, has also risen. This study evaluates the frequency of pathogen detection during revision surgeries occurring after a prior failed osteosynthesis of midshaft clavicle fractures. All patients treated in our hospital with a prior failed surgical therapy of a clavicle midshaft fracture between January 2013 and March 2022 were screened. Epidemiological data, intraoperative tissue samples, sonication, and the type of revision surgery were assessed. A postoperative follow-up at a minimum of 6 month was defined and osseous consolidation was verified. Twenty-one patients (twelve male and eight female) were included with a mean age of 40.4 ± 14.1 years. Eleven of the patients showed pathogen detection (Group I), and seven remained without (Group II). A significant difference in age existed between Groups I and II (36.1 ± 12.8 and 51.6 ± 11.5, p ≤ 0.05). The three most common pathogens were Cutibacterium acnes (n = 7), Staphylococcus epidermidis (n = 4), and Staphylococcus sacchorlyticus (n = 3), respectively. Thirteen patients presented for a follow-up. In nine patients (69%), bone healing was detectable. Four patients received a second revision surgery. Revision surgery frequently shows pathogen detection without signs of infection. Cutibacterium acnes is the most common pathogen. Despite pathogen detection, bone healing can be achieved with revision surgery, although the rate of repeat revision surgeries is high.


1α,25-dihydroxyvitamin D3 supplementation alleviates perfluorooctanesulfonate acid-induced reproductive injury in male mice: Modulation of Nrf2 mediated oxidative stress response.
Perfluorooctanesulfonate acid (PFOS) is a typical persistent organic pollutant that widely exists in the environment. To clarify the toxic effects and mechanisms of PFOS and to find effective intervention strategies have been attracted global attention. Here, we investigated the effects of PFOS on the male reproductive system and explored the potential protective role of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2 D3 ). Our results showed that 1α,25(OH)2 D3 intervention significantly improved PFOS-induced sperm quality decline and testicular damage. Moreover, 1α,25(OH)2 D3 aggrandized the total antioxidant capacity. Furthermore, after PFOS exposure, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1, NQO1, and SOD2. Meanwhile, 1α,25(OH)2 D3 ameliorated PFOS-induced augment of Nrf2 and target genes. These findings indicated that 1α,25(OH)2 D3 might attenuate PFOS-induced reproductive injury in male mice via Nrf2-mediated oxidative stress.


UV spectroscopy study on complexes of phosphonate ApA analogs with poly(U): promising step in prediction of oligonucleotide analog properties?
The isopolar nonisosteric phosphonate analogs of ApA differing in the position of extra methylene group introduced into the sugar-phosphate backbone, featuring both possible 2',5'- and 3',5'- pairs as well as their conformationally restricted congeners, were investigated for their ability to form complexes with polyU. The results may lead to the specification of candidates for synthesis of novel oligonucleotides.


Functional Genomic Analysis of the Impact of Camelina (Camelina sativa) Meal on Atlantic Salmon (Salmo salar) Distal Intestine Gene Expression and Physiology.
The inclusion of plant meals in diets of farmed Atlantic salmon can elicit inflammatory responses in the distal intestine (DI). For the present work, fish were fed a standard fish meal (FM) diet or a diet with partial replacement of FM with solvent-extracted camelina meal (CM) (8, 16, or 24 % CM inclusion) during a 16-week feeding trial. A significant decrease in growth performance was seen in fish fed all CM inclusion diets (Hixson et al. in Aquacult Nutr 22:615-630, 2016). A 4x44K oligonucleotide microarray experiment was carried out and significance analysis of microarrays (SAM) and rank products (RP) methods were used to identify differentially expressed genes between the DIs of fish fed the 24 % CM diet and those fed the FM diet. Twelve features representing six known transcripts and two unknowns were identified as CM responsive by both SAM and RP. The six known transcripts (including thioredoxin and ependymin), in addition to tgfb, mmp13, and GILT, were studied using qPCR with RNA templates from all four experimental diet groups. All six microarray-identified genes were confirmed to be CM responsive, as was tgfb and mmp13. Histopathological analyses identified signs of inflammation in the DI of salmon fed CM-containing diets, including lamina propria and sub-epithelial mucosa thickening, infiltration of eosinophilic granule cells, increased goblet cells and decreased enterocyte vacuolization. All of these were significantly altered in 24 % CM compared to all other diets, with the latter two also altered in 16 % CM compared with 8 % CM and control diet groups. Significant correlation was seen between histological parameters as well as between five of the qPCR analyzed genes and histological parameters. These molecular biomarkers of inflammation arising from long-term dietary CM exposure will be useful in the development of CM-containing diets that do not have deleterious effects on salmon growth or physiology.


α-Farnesene and ocimene induce metabolite changes by volatile signaling in neighboring tea (Camellia sinensis) plants.
Herbivore-induced plant volatiles (HIPVs) act as direct defenses against herbivores and as indirect defenses by attracting herbivore enemies. However, the involvement of HIPVs in within-plant or plant-to-plant signaling is not fully clarified. Furthermore, in contrast to model plants, HIPV signaling roles in crops have hardly been reported. Here, we investigated HIPVs emitted from tea (Camellia sinensis) plants, an important crop used for beverages, and their involvement in tea plant-to-plant signaling. To ensure uniform and sufficient exposure to HIPVs, jasmonic acid combined with mechanical damage (JAMD) was used to simulate herbivore attacks. Metabonomics techniques based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry and gas chromatography-mass spectrometry were employed to determine metabolite changes in undamaged tea plants exposed to JAMD-stimulated volatiles. JAMD-stimulated volatiles mainly enhanced the amounts of 1-O-galloyl-6-O-luteoyl-α-d-glucose, assamicain C, 2,3,4,5-tetrahydroxy-6-oxohexyl gallate, quercetagitrin, 2-(2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)-4,5-dihydroxy-6-(hydroxymethyl)-tetrahydro-2H-pyran-3-yl, 3,4-dimethoxybenzoate, 1,3,4,5,6,7-hexahydroxyheptan-2-one, and methyl gallate in neighboring undamaged tea leaves. Furthermore, α-farnesene and β-ocimene, which were produced after JAMD treatments, were identified as two main JAMD-stimulated volatiles altering metabolite profiles of the neighboring undamaged tea leaves. This research advances our understanding of the ecological functions of HIPVs and can be used to develop crop biological control agents against pest insects in the future.


Dietary NaCl supplementation prevents muscle necrosis in a mouse model of Duchenne muscular dystrophy.
The mdx mouse is an animal model for Duchenne muscular dystrophy. Mdx mice fed a 12% NaCl diet from birth up to 20 days of age (mdx-Na mice) had an approximately 50% reduction in serum creatine kinase (CK) activity compared with mdx mice fed a standard diet. Most notably, necrotic fibers in tibialis anterior (TA) muscle of mdx-Na mice were reduced by 99% and were similar in control mice. These mdx mice displayed significantly elevated blood Ca2+ and Na+ levels, while the total calcium content of their TA muscle was reduced to the level of control mice. In addition, mdx-Na mice had elevated zinc and magnesium contents in their TA muscle. These results suggest that elevated serum Na+ leads to Ca2+ extrusion from muscle via the Na+/Ca2+ exchanger causing a decrease in intracellular Ca2+ levels and an increase in blood Ca2+ levels. Extracellular Ca2+ and, in addition, Zn2+ and Mg2+ might also contribute to the stabilization of the cell membrane. Other possibilities explaining the surprisingly efficacious beneficial effect of dietary sodium exist and are discussed.


Late sigma factor of bacteriophage T4. Formation and properties of RNA polymerase-promoter complexes.
Bacteriophage T4 late gene promoters do not display sequence homology in the -35 region (Christensen, A. C., and Young, E. T. (1982) Nature 299, 369-371), suggesting an unusual geometry of RNA polymerase-promoter interaction. We have analyzed in vitro utilization of a late T4 promoter by RNA polymerase reconstituted from E. coli core enzyme (E) and bacteriophage T4 late sigma factor (sigma gp55). The E sigma gp55 holoenzyme forms a stable promoter complex which lacks protein-DNA contacts upstream from position -30 and is sensitive to direct attack by heparin. This complex is capable of reiterative oligonucleotide synthesis (abortive initiation). Kinetic analysis of complex formation reveals a rapidly forming inactive intermediate (closed complex) which is slowly isomerized into a catalytically active form (open complex). The results indicate that all components essential for promoter binding, open complex formation, and initiation of transcription are present in the "downstream" part of the RNA polymerase molecule, which is defined by the -30 to +20 footprint. On the basis of these observations and the results of others, we suggest that during transcription initiation at bipartite (Escherichia coli) promoters, an "upstream" DNA-binding domain of RNA polymerase which recognizes specific sequence elements in the -35 region plays an auxiliary role by regulating the rate of productive interactions in the downstream part of the molecule through an allosteric mechanism.


Water temperature and concomitant waterborne ethinylestradiol exposure affects the vitellogenin expression in juvenile brown trout (Salmo trutta).
Environmental estrogens have the potential to considerably affect the reproduction and development of aquatic vertebrates by interfering with the endocrine system. In addition to the potential risk of environmental estrogens, increasing water temperatures as a result of global warming have become a serious problem in many rivers and streams. To assess the degree of estrogenic exposure, the analysis of the estrogen-dependent protein vitellogenin (Vtg) is a frequently used biomarker in field studies. Little, however, is known regarding the potential interaction between ambient water temperature and the Vtg production induced by waterborne environmental estrogens. In order to test the influence of temperature on Vtg synthesis, we exposed juvenile brown trout to an environmentally relevant concentration of ethinylestradiol (EE(2)) and held them either at low or high temperatures (12 and 19 degrees C, respectively), but also at temperature cycles of 12-19 degrees C in order to simulate the field situation. The EE(2) exposure caused a 7-74-fold increase of hepatic Vtg mRNA. The synthesis of Vtg mRNA was clearly stimulated in fish held at higher water temperatures (12-19 degrees C and 19 degrees C, respectively). On the protein level, Vtg showed a similar pattern; the higher the temperature, the higher the concentration of Vtg in the plasma. The experiment further revealed a temperature-dependent increasing amount of hepatic estrogen receptor alpha mRNA (ERalpha) after exposure to waterborne EE(2). The gene expression of estrogen receptor beta-1 (ERbeta-1) and the glucocorticoid receptor (GR) in the liver of EE(2) exposed fish, however, showed no treatment-related alterations. In line with observed constant bile cortisol concentrations, our data do not indicate corresponding stress related effects on hepatic Vtg production. The present survey, however, clearly demonstrates that increased temperature significantly elevates the estrogen-induced expression of Vtg and therefore has to be considered when interpreting environmental monitoring studies.


Recent Advances in Foot and Ankle Surgery in Mainland China: Correction of Severe Foot and Ankle Deformities.
Foot and ankle physicians in China encounter quite a large amount of severe and complex deformities. The main cause of severe ankle and foot deformity is trauma, while the other causes may be neuromuscular diseases, improper reduction and fixation and so on. Staged procedure may sometimes be a safer way to correct deformities in the presence of severe soft tissue contracture. Periarticular osteotomy combined with soft tissue balancing can be used in treating severe varus ankle arthritis, including stage IIIb cases and patients with talar tilt of more than 10 degrees.


Ontogeny of QRFP and its receptor expression in mouse testis during post-natal development.
Pyroglutamylated RFamide peptide (QRFP), a neuropeptide, binds to its receptor GPR103 and influences various biological functions. In the present study, expression and localization of QRFP and GPR103 in mouse testis during post-natal development were investigated. The results showed that QRFP and GPR103 and also the isoforms of the receptor, viz. GPR103A and GPR103B were expressed in mouse testis during post-natal development. Expression of QRFP and its receptor was high during the early periods of post-natal development. Immunohistochemical study demonstrated the localization of QRFP and GPR103 in both interstitial and tubular compartments of the testis throughout post-natal development. A shift in the germ cell types expressing QRFP and its receptor along the course of testicular development and also a prominent immunoreactivity of QRFP in germ cells and of GPR103 in Sertoli cells was observed. Further, the immunoreactivity of QRFP and GPR103 appeared to be stage-specific in spermatogenetically active testis. Besides in intercellular spaces, localization of QRFP was also noticed in nuclei of germ cells. In conclusion, the present results suggest potential involvement of QRFP system in the development, proliferation and differentiation of testicular cells, possibly by regulating the energy requirement for these processes.


Evaluation of catch-up growth from orthodontic treatment and supplemental growth hormone therapy by using Z-scores.
Pituitary dwarfism causes short stature due to partial or complete inhibition of growth hormone (GH) secretion. Supplemental therapy with human GH (rhGH) accelerates the statural growth of patients, but there is limited information about its effects on craniofacial growth. This study describes the orthodontic treatment of 2 patients (a boy and a girl) diagnosed with pituitary dwarfism and treated with rhGH therapy. Growing children have different growth velocities depending on age and sex, and this complicates the assessment of treatment effects; therefore, we used the Z-score to evaluate changes in stature and craniofacial components. Growth in craniofacial structures and stature were both enhanced by rhGH therapy during orthodontic treatment.


Efficacy of a heparin based rota-flush solution in patients undergoing rotational atherectomy.
The efficacy of heparin based flush solutions in rotational atherectomy (RA) has not been validated. Recently, a single center study demonstrated the feasibility of an alternative flush solution with 10,000U of unfractionated heparin (UFH) in 1L of normal saline. We aimed to evaluate the safety and efficacy of an alternative flush solution intermittently utilized at our institution. We retrospectively identified 150 patients undergoing RA over a three year period. One hundred cases utilized an alternative flush solution containing 10,000U UFH, 400mcg nitroglycerin, and 10mg verapamil in 1L normal saline and fifty cases utilized RotaGlide Lubricant (Boston Scientific) in addition to heparin and vasodilators in the same dose. The primary end point was to compare rates of procedural success. Secondary endpoints were to report procedural characteristics including the incidence of major adverse cardiac events (MACE) and minor periprocedural complications. Procedural success was achieved in 98% (98/100) of cases utilizing the alternative Rota-Flush solution compared to 100% (50/50) in the Rota-Glide group (P=0.553). A total of 292 lesions (200 Rota-Flush vs 92 Rota-Glide) were targeted for intervention. MACE occurred in 13 (13%) and 4 (8%) cases in the Rota-Flush and Rota-Glide groups, respectively (P=0.425). Rotational atherectomy performed with the previously defined Rota-Flush or Rota-Glide solutions resulted in similar rates of procedural success. There were no significant disparities in incidence of MACE and minor periprocedural complications between the two groups. Heparin based rota-flush solutions can be effective alternatives to traditional solutions containing RotaGlide Lubricant.


The effect of band Jahn-Teller distortion on the magnetoresistivity of manganites: a model study.
We present a model study of magnetoresistance through the interplay of magnetisation, structural distortion and external magnetic field for the manganite systems. The manganite system is described by the Hamiltonian which consists of the s-d type double exchange interaction, Heisenberg spin-spin interaction among the core electrons, and the static and dynamic band Jahn-Teller (JT) interaction in the e(g) band. The relaxation time of the e(g) electron is found from the imaginary part of the Green's function using the total Hamiltonian consisting of the interactions due to the electron and phonon. The calculated resistivity exhibits a peak in the pure JT distorted insulating phase separating the low temperature metallic ferromagnetic phase and the high temperature paramagnetic phase. The resistivity is suppressed with the increase of the external magnetic field. The e(g) electron band splitting and its effect on magnetoresistivity is reported here.


Synthesis of glyceroyl beta-N-acetyllactosaminide and its derivatives through a condensation reaction by cellulase.
A condensation reaction between N-acetyllactosamine and glycerol was directly catalyzed by using a commercially available cellulase preparation from Trichoderma reesei. 1-O-beta-N-Acetyllactosaminyl-(R, S)-glycerols (1) were readily synthesized in a 5% yield based on the N-acetyllactosamine added and conveniently isolated by two-step column chromatographies. The use of a partially purified enzyme increased 2.3-fold the yield of 1, compared to that of the crude enzyme containing beta-D-galactosidase activity. When various alkanols (n:2-4) were used in the condensation reaction, the corresponding alkyl beta-N-acetyllactosaminides were obtained in yields of 0.3-1.1% of the desired compounds.


Patient and provider perspectives of the implementation of remote consultations for community-dwelling people with mental health conditions: A systematic mixed studies review.
Remote, or tele-, consultations became a necessary form of mental healthcare provision during the COVID-19 pandemic. As the prevalence of mental health problems rises, they may have a role in future mental health services. We aimed to review the literature on patient and provider perspectives on factors influencing the implementation of remote consultations for community-dwelling people with mental health conditions. We searched five electronic databases (PubMed, EMBASE, Web of Science, CINAHL, and PsycINFO) for empirical research up to July 13th, 2022. Only studies of synchronous, interactive remote consultations conducted via video, phone, or live-messaging between patients and providers were included. Two reviewers independently assessed the quality of included studies using the Mixed Methods Appraisal Tool. We integrated qualitative and quantitative data from 39 studies into a single mixed-methods synthesis. We mapped reported factors to the domains of the Consolidated Framework for Implementation Research (CFIR). Acceptability was generally high among participants, despite concerns about the quality of care and the perceived impeded therapeutic relationship. A prominent facilitator was the increased accessibility and convenience of remote consultations, while lack of appropriate infrastructure and low patient comfort and competence were among the most prevalent barriers. This review highlights the importance of patient preferences and provider buy-in to the future of remote consultations.


Spatiotemporal trends in global burden of rheumatic heart disease and associated risk factors from 1990 to 2019.
The aim of this study was to estimate the burden of rheumatic heart disease (RHD) and its trends in different countries, regions, genders and age groups globally. Data were obtained from the Global Burden of Disease 2019 study. Age-standardized rates (ASRs) and the estimated annual percentage changes (EAPCs) in the ASRs were used to describe the burden of disease and its trends. Pearson's correlation was used to evaluate the correlation between sociodemographic index (SDI) values and the observed trends. In 2019, the ASRs of the incidence, prevalence, mortality and disability-adjusted life years (DALYs) of RHD were 37.39/105 (95%UI, 28.59/105 to 46.74/105), 513.68/105 (95%UI, 405.01/105 to 636.25/105), 3.85/105 (95%UI, 4.29/105 to 3.29/105) and 132.88/105 (95%UI, 115.02/105 to 150.34/105), respectively. From 1990 to 2019, the incidence and prevalence of RHD showed upward trends and the mortality and DALYs showed downward trends. Countries or regions in Africa, South America and South Asia had a greater burden of RHD. The burden of RHD was greater in women, where as men showed more obvious increasing trends in the incidence and prevalence. The incidence of RHD was highest in adolescents, and the prevalence was highest in young and middle-aged. The mortality and DALYs rate associated with RHD increased with age. The EAPCs in the ASRs were negatively correlated with the SDI value. Although the ASRs of mortality and DALYs attributable to RHD are decreasing globally, RHD remains an important public health problem that needs to be addressed urgently, especially in certain low- and middle-income countries and regions.


Phosphorlyation of H1 and H5 histones by cyclic AMP-dependent protein kinase reduces DNA binding.
Phosphorylation of H1 histones by cyclic AMP-dependent protein kinase may be an important transcriptional control mechanism. We have used affinity chromatography to examine the effect of phosphorylation by this enzyme on the DNA-binding properties of calf thymus H1 histones and two highly basic H1 homologues from condensed and transcriptionally silent nuclei: duck erythrocyte H5 and Strongylocentrotus purpuratus sperm H1. Without in vitro phosphorylation, all three histones were eluted from native DNA-Sephadex G-25 columns at salt concentrations which closely resembled those required to extract these histones from nuclei or chromatin. When a small portion of radioactively phosphorylated histone was chromatographed with untreated carrier histone, the phosphorylated species was consistently eluted from the DNA column at slightly lower salt concentrations than the main histone peak. Rechromatography experiments showed that in vitro phosphorylation of H1 can shift its elution position to lower salt concentrations.


Current utilization and influencing factors of complementary and alternative medicine among children with neuropsychiatric disease: a cross-sectional survey in Korea.
Complementary and alternative medicine (CAM) is widespread but has various utilization rates according to country and the condition of patients. Generally, CAM is more frequently used in diseases that have no clear treatment method in conventional medicine. Therefore, a high utilization rate of CAM can be assumed in pediatric neurological diseases, but few studies have investigated the utilization of CAM in children with neuropsychiatric diseases. In particular, studies regarding the current use of CAM are scarce. We conducted a survey of the parents or caregivers of patients who visited the pediatric rehabilitation clinic, pediatric neurology clinic, or pediatric psychiatry clinic at one university hospital from April to July 2011. We analyzed the factors that affect the utilization of CAM and other rehabilitation therapies. Among the 578 patients recruited, 258 patients have ever received CAM (51.5%), and the current CAM utilization rate was 19.0% (110 patients). Two hundred patients (34.6%) were currently receiving only other rehabilitation therapies, and 268 patients (46.4%) were currently receiving no type of therapy. The rate of current CAM usage was significantly high in epilepsy patients. The ORs of 1-6-year-old and 7-12-year-old children compared with 13-19-year-old children were 3.14 (95 % CI 1.31-7.53) and 3.34 (95% CI 1.64-6.79), respectively, and the OR of the group with longer disease duration (≥48 months) compared with the group with shorter disease duration was 3.36 (95% CI 1.71-6.59). Only the age and disease duration showed statistically significant differences between the patients who were administered CAM and those who received other rehabilitation therapies (p < 0.0001). CAM is preferred by patients under 13 years of age compared with patients aged 13-19 years, whereas other rehabilitation therapies are preferred by patients aged 1-6 years, followed by those aged 6-12 years and then by those aged 13-19 years. The patient's age and disease duration are the major factors influencing CAM use. Future studies should specify particular diseases, rather than combining all types of neuropsychiatric diseases, and include the socio-economic status of the parents.


Estimating the prevalence of female genital mutilation in Portugal.
Due to globalized migratory processes, female genital mutilation/cutting (FGM/C) has spread to other countries, including countries in Europe, where, with a few exceptions, it remains a concealed problem. To the authors' knowledge, this is the first national extensive study to estimate the prevalence of FGM/C in Portugal. Prevalence estimation. Using extrapolation of country-of-origin prevalence data and the 2011 Census data, this study estimated: the prevalence of FGM/C in Portugal among women of reproductive age (15-49 years) and among all women aged ≥15 years; and the number of girls aged <15 years living in Portugal who have undergone or will probably undergo FGM/C. It is estimated that 6576 women aged ≥15 years living in Portugal have undergone FGM/C, with cases distributed unevenly throughout the national territory. In addition, it is estimated that 1830 girls aged <15 years living in Portugal have undergone or are likely to undergo FGM/C. This study estimated that more than 6000 women living in Portugal have undergone FGM/C, and many girls remain at risk. These two groups need different types of interventions. Awareness of the number and geographical dispersion of cases of FGM/C will enable more informed and targeted definition of public health policies for protection of females who have undergone or are at risk of undergoing FGM/C.


Age-dependent accumulation of dicarbonyls and advanced glycation endproducts (AGEs) associates with mitochondrial stress.
Aging is a strong risk factor for brain dementia and cognitive decline. Age-related accumulation of metabolites such as advanced glycation end products (AGEs) could serve as danger signals to initiate and accelerate disease process and neurodegeneration. The underlying causes and consequences of cerebral AGEs accumulation remain largely unknown. Here, we comprehensively investigate age-related accumulation of AGEs and dicarbonyls, including methylglyoxal (MG), glyoxal (GO), and 3-deoxyglucosone (3-DG), and the effects of mitochondrial reactive oxygen species (ROS) on cerebral AGEs accumulation, mitochondrial function, and oxidative stress in the aging human and mouse brain. We demonstrate that AGEs, including arginine and lysine derived N(6)-carboxymethyl lysine (CML), Nε-(1-Carboxyethyl)-l-lysine (CEL), and methylglyoxal-derived hydroimidazolone-1 (MG-H1), were significantly elevated in the cerebral cortex and hippocampus with advanced age in mice. Accordingly, aging mouse and human brains revealed decrease in activities of mitochondrial respiratory chain complexes I & IV and ATP levels, and increased ROS. Notably, administration of mitoTEMPO (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (mTEMPO), a scavenger of mitochondrial ROS, not only suppressed ROS production but also reduced aged-induced accumulation of AGEs and dicarbonyls. mTEMPO treatment improved mitochondrial respiratory function and restored ATP levels. Our findings provide evidence linking age-related accumulation of toxic metabolites (AGEs) to mitochondrial oxidative stress. This highlights a novel mechanism by which AGEs-dependent signaling promotes carbonyl stress and sustained mitochondrial dysfunction. Eliminating formation and accumulation of AGEs may represent a new therapeutic avenue for combating cognitive decline and mitochondrial degeneration relevant to aging and neurodegenerative diseases including Alzheimer's disease.


Hormone replacement and contraceptive therapy in autoimmune diseases.
Sex hormones, including estrogens, influence the immune system in a complex manner, playing an important role in the pathophysiology of autoimmune diseases. Estrogen receptors can be found in almost all cells, including those of the adaptive and innate immune systems. Depending on the relative preponderance and stimulation of different receptors in various tissues, estrogens may demonstrate pro-inflammatory or anti-inflammatory properties. Traditionally, exogenous estrogens were considered to have the potential of worsening the autoimmune processes and hence were avoided in patients with rheumatic diseases. Recent studies have demonstrated the efficacy of exogenous hormone therapies, either in the form of oral contraceptives or post-menopausal hormonal replacement therapy, in the majority of patients with rheumatic diseases. However, caution needs to be exercised as a higher incidence of mild to moderate flares of systemic lupus erythematosus was noted with hormonal replacement therapy in the large randomized controlled trial, HRT-SELENA. Exogenous estrogens can also increase the risk of thrombosis in patients with positive antiphospholipid antibodies and should be avoided in this subgroup. This review will discuss the current evidence on the efficacy, safety and impact of exogenous sex hormone therapies in patients with autoimmune rheumatic diseases.


Exploring the lived experience of homelessness from an occupational perspective.
Working in homelessness is a growing area of practice for occupational therapists, however, there is limited literature on the lived experiences of homelessness and occupational engagement Study aim: To explore the lived experience of homeless men in relation to how they engaged in day-to-day occupations when sleeping rough or hostel dwelling Methods: Data were gathered from five men residing in a homeless hostel in the UK. Data collection included semi-structured interviews and photographic diaries. Data were analyzed using Interpretative Phenomenological Analysis Results: Participants described their experiences of occupational engagement whilst sleeping on the streets which included engaging in survival occupations, the significance of apparently ordinary occupations and moving beyond survival occupations. The homeless hostel provided opportunities for occupational engagement that the men perceived in an idiosyncratic manner. The men described benefits of engaging in novel occupations and reengaging in known occupations. Occupational injustices were a common theme that occurred throughout participants experiences Conclusion: This study has highlighted the diversity of occupational engagement for 'roofless' or 'houseless' participants and how different individuals experience occupational adaption Significance: This study has furthered understandings of the concept of 'survival occupations' and the importance of community resources to facilitate occupational engagement whilst homeless.


The socioeconomic correlates of global complication prevalence in type 1 diabetes (T1D): a multinational comparison.
We sought to determine the extent to which the geographic variation in the complications of type 1 diabetes (T1D) may reflect the socioeconomic status (SES) conditions and health care performance (HCP) of countries around the world. The World Health Organization (WHO) DiaMond complications study (DiaComp) is a multinational, cross-sectional study of complications in T1D. Information on complications was identified for 892 subjects from 14 clinical centers in 12 countries. All participants were diagnosed with diabetes in childhood (<15 years of age) and had disease duration of 5-24 years. Complications were assessed by self-report, and by clinical exam, with microalbuminuria identified by Micral II dipstick, neuropathy by the Michigan Neuropathy Screening Instrument exam and hypertension using the HDFP protocol. These data were linked to center-specific information on the local social and economic landscape, health care access and diabetes management practices and health care costs. Country-specific indicators of social and economic development were also linked to the complications data. Both diabetes complications and economic and health care factors vary widely across the DiaComp centers. Health system performance, as measured by disability adjusted life expectancy (DALE), gross national investment (GNI) per capita and purchasing power all showed strong consistent correlations with complications, and significant independent associations with complication prevalence after controlling for HbA1c and hypertension. In conclusion, health system performance, social distribution of wealth and purchasing power may play important roles in explaining the geographic variation of diabetes complications.


Comparison of pregnancy rates between patients with and without local endometrial scratching before intrauterine insemination.
To determine the implantation success of local endometrial injury in patients undergoing intrauterine insemination following ovulation induction with gonadotropins as an infertility treatment. In this prospective randomized controlled trial, ovulation induction was performed with gonadotropins in 80 patients following intrauterine insemination. In 40 patients, local endometrial injury (scratch) was performed in the midluteal phase of the cycle preceding ovarian stimulation with a Novak curette to the posterior side of the endometrial cavity. Fifteen pregnancies (37.5%) and 11 clinical pregnancies (27.5%) occurred in the intervention group, whereas eight pregnancies (20%) and five clinical pregnancies (12.5%) occurred in the control group. Although the pregnancy rates and clinical pregnancy rates were increased in the intervention group, no statistically significant difference was found between the intervention and control groups (pregnancy rates: P=0.084; clinical pregnancy rates: P=0.094). Performing local endometrial injury (scratch) in the cycle preceding ovulation induction in patients with a diagnosis of infertility and indication for intrauterine insemination increased the pregnancy and clinical pregnancy rates. This increase was not, however, statistically significant. More randomized, controlled, prospective studies with larger patient numbers are required before the use of iatrogenic induction of local endometrial injury can be recommended in routine clinical practice.


Antidiuretic hormone secretion and urine flow in aged catheterized patients.
Repeated measurements of urine flow, every 10 min, and plasma ADH levels, every 20 min, were done in six aged, supine catheterized patients for seven hours. Orthogonal spectral analysis revealed 80 to 130 ultradian rhythms in urinary osmolality and in Na+ and K+ concentrations, but not in the flow of urine that fluctuated rapidly. Plasma ADH levels were constant, ranging from 0.5 pg/ml to 1.5 pg/ml, without evidence for pulsatile episodic secretion.


The contribution of Gaetano Perusini to the definition of Alzheimer's disease.
This paper seeks to examine Perusini's scientific contribution to Alzheimer's disease, on the basis of critical reading of the three fundamental papers he produced between 1906 and 1911, and published between 1909 and 1911. The examination of three publications clearly shows that, after Alzheimer's concise clinical report of 3 November 1906, Perusini was responsible for more clearly defining its clinical and histopathological characteristics without ever claiming be the discoverer of the new disease. The paper also describes Alzheimer's express wish to entrust the investigation of the disease to Perusini, and the brilliant manner in which this was achieved. The on-going debate on the difference between senile and pre-senile dementia, which was originally raised by Kraepelin's distinction of the two forms, is also discussed.


Account of Haly Abbas regarding the management of hydrocephalus in children: a text from medieval times.
To present the text on hydrocephalus from Haly Abbas's book Kitāb al-Malikī / Liber Regius (The Royal Book), which was accepted as a classical textbook in the Eastern and Western worlds for a long time. The Arabic (Süleymaniye Manuscript Library, Murad Molla Collection, Nr: 1482 and Būlāḳ, 1294 /1877) and the Latin (Venice, 1492) versions of the related chapter was translated and compared to create an English text. Additionally, relevant literature was reviewed in detail. The text on hydrocephalus in Haly Abbas's The Royal Book virtually resembles Paul of Aegina's work. For hydrocephalic cases where the fluid collects between skin and pericranium, and pericranium and bone, Haly Abbas had made little change in surgical intervention; for the third type, skin incision, he preferred a T-type incision instead of an H-type. Like Paul of Aegina, Haly Abbas also did not advise any surgical intervention for the cases of hydrocephalus, where fluid accumulation is between bone and the dura mater. Haly Abbas's approach to hydrocephalus was as brave as that of his predecessors Antyllus, Oribasius, and Paulus, although the cases they dealt with were almost all cephalic hematomas. Although his chapter on the treatment of water accumulation in the head contains surgical interventions in extracranial hydrocephalic conditions, his account on hydrocephalus is extremely precise and gives adequate detail as in other chapters in his book.


Duration of untreated psychosis: Impact of the definition of treatment onset on its predictive value over three years of treatment.
While reduction of DUP (Duration of Untreated Psychosis) is a key goal in early intervention strategies, the predictive value of DUP on outcome has been questioned. We planned this study in order to explore the impact of three different definition of "treatment initiation" on the predictive value of DUP on outcome in an early psychosis sample. 221 early psychosis patients aged 18-35 were followed-up prospectively over 36 months. DUP was measured using three definitions for treatment onset: Initiation of antipsychotic medication (DUP1); engagement in a specialized programme (DUP2) and combination of engagement in a specialized programme and adherence to medication (DUP3). 10% of patients never reached criteria for DUP3 and therefore were never adequately treated over the 36-month period of care. While DUP1 and DUP2 had a limited predictive value on outcome, DUP3, based on a more restrictive definition for treatment onset, was a better predictor of positive and negative symptoms, as well as functional outcome at 12, 24 and 36 months. Globally, DUP3 explained 2 to 5 times more of the variance than DUP1 and DUP2, with effect sizes falling in the medium range according to Cohen. The limited predictive value of DUP on outcome in previous studies may be linked to problems of definitions that do not take adherence to treatment into account. While they need replication, our results suggest effort to reduce DUP should continue and aim both at early detection and development of engagement strategies.


Flanking regions, amyloid cores, and polymorphism: the potential interplay underlying structural diversity.
The β-sheet-rich amyloid core is the defining feature of protein aggregates associated with neurodegenerative disorders. Recent investigations have revealed that there exist multiple examples of the same protein, with the same sequence, forming a variety of amyloid cores with distinct structural characteristics. These structural variants, termed as polymorphs, are hypothesized to influence the pathological profile and the progression of different neurodegenerative diseases, giving rise to unique phenotypic differences. Thus, identifying the origin and properties of these structural variants remain a focus of studies, as a preliminary step in the development of therapeutic strategies. Here, we review the potential role of the flanking regions of amyloid cores in inducing polymorphism. These regions, adjacent to the amyloid cores, show a preponderance for being structurally disordered, imbuing them with functional promiscuity. The dynamic nature of the flanking regions can then manifest in the form of conformational polymorphism of the aggregates. We take a closer look at the sequences flanking the amyloid cores, followed by a review of the polymorphic aggregates of the well-characterized proteins amyloid-β, α-synuclein, Tau, and TDP-43. We also consider different factors that can potentially influence aggregate structure and how these regions can be viewed as novel targets for therapeutic strategies by utilizing their unique structural properties.


Need to educate primary caregivers about the risk factor profile of smokeless tobacco users.
Many cancer risk factors are correlated with one another, and the presence of 1 risk factor may be a marker for other unhealthy behaviors. In this article, we focus on smokeless tobacco (ST), a known risk factor for oral leukoplakia and oral cancer, and the cancer risk factors associated with its use. We analyzed cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) I and the 1982-1984 NHANES I Epidemiologic Follow-up Study. Risk factor information was available on individuals 25-74 years of age, most of whom would be middle age or elderly today. Older subjects, Black males, and those living in the Southern Unite States had the highest prevalence of ST use. ST use was associated with current smoking (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.5), former smoking (OR, 1.6; 95% CI, 1.4-2.0), low fruit and vegetable intake, low SES, increased alcohol consumption (among nonsmoking ST users), and increased body mass index, all of which elevate cancer risk. CONCLUSION. Physicians and dentists should ask their patients about current or former ST use. Identification of ST users should prompt the physician or dentist to inquire about other chronic disease risk factors that the patient may have and to educate the ST using patient about ways to reduce their risk of cancer.


Four novel mutations in the β-galactosidase gene identified in infantile type of GM1 gangliosidosis.
The aim of this study is to find out mutations of Turkish GM1 gangliosidosis patients and to make genotype-phenotype correlations. β-galactosidase activities were measured by using fluorometric substrate. Mutation screening of 16 exons of β-galactosidase gene and mutation detection were done by PCR-SSCP and DNA sequencing, respectively. Four new mutations, c.188_189insT in exon 2, c.569_570insA in exon 6, p.K142Q in exon 4, p.G190D in exon 6, and one known mutation p.P549L in exon 15, were identified in the β-galactosidase gene in 5 Turkish patients. Mutations in exons 4 and 6 are in the active site and mutation in exon is in the galactose-binding domain of the β-galactosidase gene. This is the first mutational analysis performed in Turkish GM1 gangliosidosis patients and shows the molecular heterogeneity of the disease in Turkish population. All identified mutations result in severe enzyme deficiency and infantile phenotype.


Developmental effects of perinatal exposure to PBDE and PCB on gene expression in sexually dimorphic rat brain regions and female sexual behavior.
The developing nervous system is a potential target of environmental contaminants such as polybrominated diphenylethers (PBDE), which accumulate in the biosphere. We compared effects of 2,2',4,4',5-pentabromo-BDE (PBDE99), a PBDE congener present in environmental samples, and PCB on brain development. Time-pregnant rats were subcutaneously injected with PBDE99 (1 or 10mg/kg), the PCB mixture Aroclor 1254 (10mg/kg), or vehicle from gestational day 10-18. mRNA levels of genes involved in central control of reproductive functions and sexual behavior were analyzed by real time RT PCR in two sexually dimorphic brain regions, medial preoptic area (MPO) and ventromedial hypothalamus (VMH) of adult offspring of both sexes. Exposure to PBDE99 or the PCB mixture during pre- and postnatal development affected mRNA expression levels in a treatment-, region- and sex-specific manner, and changed the sensitivity of target genes to estradiol. The sex difference in progesterone receptor mRNA levels of VMH normally seen in untreated controls was abolished by both, PBDE99 and PCB. Estrous cycles were significantly affected, and preliminary experiments suggest an impairment of female sexual behavior. Our data indicate that developmental exposure to PBDE99 at doses below signs of general toxicity affects the regulation of estrogen target genes in rat brain. Since PBDE99 was detected in blood and adipose tissue of adult offspring, these effects may result from interactions with developmental processes, with adult functions, or a combination of both.


[Enhancement effect on fluorescence of Tm3+ mixed dysprosium perchlorate in phenyl-phenacyl sulfoxide].
Nine different proportional complexes of different nuclear rare earth perchlorate (Dy3+ and Tm3+ are mixed) with phenyl-phenacyl sulfoxide (L= C6H5COCH2SOC6H5) have been synthesized and characterized. Element analysis and coordination titration studies suggest that the complexes have the composition of (DyxTmy) L5 (ClO4)3 x 2H2O (x : y = 1.000 : 0.000, 0.999 : 0.001, 0.995 : 0.005, 0.990 : 0.010, 0.900 : 0.100, 0.800 : 0.200, 0.700 : 0.300, 0.600 : 0.400, 0.500 : 0.500). IR studies indicate that the ligand is bonded with RE (III) through one oxygen atom in sulfoxyl group, and the oxygen atom in carbonyl group did not bond. The molar conductivities measured in the DMF solution indicate that three inorganic anions ClO4(-) are non-coordinated. The fluorescence emission intensity of Dy3+ complexes would be enhanced strongly by mixing Tm3+. Tm3+ has the best sensitization to the fluorescence of Dy3+ in the ratio of 0.990 : 0.010. The fluorescence intensity can be increased to 246%.


Skin cancer signal associated with phosphodiesterase inhibitors: gaining insight through the FDA pharmacovigilance database.
Panoramic views of post-marketing safety profiles, such as cancer signal, of phosphodiesterase 5A (PDE5A) inhibitors have yet to be fully evaluated. Data from the FDA Adverse Event Reporting System (FAERS) concerning the timeframe between January 1st, 2004 to 30 June 2022 was analyzed through a disproportionality study to understand the association between sildenafil, tadalafil, and vardenafil and cancer. This association was identified using the Reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) approaches. Sildenafil associated ROR values and IC025 ranged from 9.19 (95% CI 7.72-10.94, IC025 2.77) for metastatic malignant melanoma to 132.23 (95% CI 95.49-183.11, IC025 4.69) for malignant melanoma stage II. Tadalafil associated ROR and IC025 ranged from 6.79 (95% CI 5.41-8.54, IC025 2.27) for metastatic malignant melanoma to 180.17 (95% CI 130.11-249.50, IC025 4.89) for malignant melanoma stage II. Vardenafil associated ROR and IC025 ranged from 23.38 (95% CI 15.20-35.96, IC025 2.63) for metastatic malignant melanoma to 245.77 (95% CI 154.42-391.16, IC025 2.10) for malignant melanoma stage III. This study supports the association between sildenafil, tadalafil, and vardenafil with skin cancer signal in erectile dysfunction (ED) patients.


Coping with dementia caregiving: a mixed-methods study on feasibility and benefits of a psycho-educative group program.
Persons with dementia experience a progressive decline associated with an increasing dependency. Most of the support they require to stay at home comes from their informal caregivers (IC). Dementia informal caregiving imposes high costs on IC's health and quality of life, related to long periods of chronic stress. Based on evidence that more adequate coping strategies can reduce chronic stress and its negative consequences, and that psycho-educative interventions have the broadest effects on IC quality of life, the program "Learning to feel better… and help better" was developed in French-speaking Canada. This group intervention focusing on coping with the daily stress of dementia caregiving showed efficacy in decreasing the behavior problems of the person with dementia and the associated stress reactions in their IC. The objectives of our study were to examine within a one group pre- and post-test design 1) the feasibility of implementing the program in two regions of French-speaking Switzerland, 2) the effects of the program, and 3) the participants' use of the trained strategies in daily life. A mixed-methods concurrent nested design was used to quantitatively evaluate the feasibility, the effects on five core outcomes, and strategy use in daily life. Additional qualitative data documented in depth the acceptability and impact of the intervention. We analyzed 18 complete data sets. Regarding feasibility, qualitative and quantitative results converged towards a very good acceptance of the program and a strong implication of the participants. Regarding effects, the program resulted in substantial and significant improvements in burden (d = 0.41, p < .05), psychological distress (d = 0.54, p < .05) and self-efficacy (d = 0.43, p < .05). The qualitative results emphasized the benefits of a group format: Participants felt understood by peers, could build new social bonds and experienced reduced social isolation. Data regularly collected in daily life showed that participants were using more and more over time the strategies they learned (β01 = 0.55, p < .001), particularly reframing. This study expands on the original one conducted by the developers of the program in French-speaking Canada, by showing the feasibility and the very promising effects of this intervention in two regions of French-speaking Switzerland.


Prognostic significance of vascular endothelial growth factor, basic fibroblastic growth factor, and microvessel density and their relation to cell proliferation in B-cell non-Hodgkin's lymphoma.
Vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (b-FGF) have been described as essential cytokines in the regulation of angiogenesis. Their elevation has been associated with an unfavorable outcome in different neoplasms. However, their role in angiogenesis and proliferation in B-cell non-Hodgkin's lymphoma (B-NHL) is unclear. Seventy cases of B-NHL besides 5 cases with reactive lymphadenitis were collected randomly and classified according to World Health Organization classification, Ann Arbor staging. They were subjected to immunostaining using VEGF, b-FGF, CD34, and Ki67 markers. There were a positive correlation between the proliferation and aggressiveness of the tumor as measured with Ki67 and both VEGF and b-FGF, and this was reflected on the stromal increase in microvessel density as measured by CD34. In conclusion, as the tumor becomes more aggressive, it also becomes independent of stromal paracrine factors by the establishment of an autocrine VEGF and b-FGF stimulation that can increase its angiogenesis and proliferation.


Sleep apnoea in babies born after in vitro fertilization.
Babies born after in vitro fertilisation (IVF) are increasing in number, and, although these babies are considered as very precious, no data are available regarding their risk for sudden infant death or apnoea. To evaluate the respiratory maturity of IVF babies, we evaluated the incidence of apnoea during an 8-h polysomnography in 50 consecutively presented IVF babies and in a group of 50 unselected naturally conceived babies. All infants were in good health and matched for term (born > 38 weeks of gestation), birth weight, sex and age at the time of investigation (6-11 weeks post term, median 8.0). There were 24 twins in the IVF and 6 twins in the control group. The incidence of obstructive and isolated central apnoea was comparable in the IVF and control group. However, IVF babies had significantly more periodic breathing episodes than control babies (median 2.30 (range 0-15.30) in IVF, and 1.02 (range 0-11.2) in control babies; P < 0.01). This difference was not related to the higher number of twins in the IVF group. Single IVF babies had significantly more short central apnoeas (5-10 s) than IVF twins (5-10 s) (mean 38.80 +/- 18.63 and 22.33 +/- 13.35; P < 0.001). This difference between single and twin babies was not found in the control group. IVF babies have more periodic breathing episodes indicating an immature respiratory pattern than normally conceived babies.


Advancing the science of nursing, improving the quality of care.
The director of the Magnet Recognition Program provides a comprehensive look at the Magnet model component new knowledge, innovation, and improvements. This article examines Magnet organizations' responsibility to advance evidence-based practice, improve quality, and develop new models of care. It includes exemplars of innovative contributions from Magnet organizations around the country.


Criminal justice involvement of crack cocaine users in the city of Rio de Janeiro and Greater Metropolitan Area: Implications for public health and the public security agenda.
The international literature has expressed different and sometimes contrasting perspectives when addressing criminal involvement by crack cocaine users, highlighting psychopharmacological aspects, the cycles of craving and pressing economic need, and the interplay with overall deprivation and structural violence. The current study aims to identify variables associated with the arrest and imprisonment of regular crack cocaine users. Interviewees were recruited from open drug scenes in the city of Rio de Janeiro and Greater Metropolitan Area from September 2011 to June 2013. Multilevel logistic regression models were fitted to the data. Most of the recruited crack cocaine users were male (78.2% [95%CI: 76.3-79.4]), 18-30 years old (64.7% [95%CI: 62.5-66.2]), non-white (92.9% [95%CI: 91.2-93.4]), single (68.9% [95%CI: 66.8-70.3]), and with 0-7 years of schooling (70.6% [95%CI: 68.5-71.9]). Factors independently associated with arrest were history of inpatient addiction treatment (adjOR 4.31 [95%CI: 1.70-11.32]); male gender (adjOR 2.05 [95%CI: 1.40-3.04); polydrug use (adjOR 1.82 [95%CI: 1.32-2.51]); and 0 to 7 years of schooling (adjOR 1.64 [95%CI: 1.17-2.32]). As for the outcome variable lifetime history of incarceration, the independently associated factors were: male gender (adjOR 2.47 [95%CI: 1.74-3.55]) and longer use of crack cocaine and related substances (e.g., free base and local varieties/denominations of coca products) (adjOR 1.05 [95%CI: 1.01-1.10]). The study's findings support the use of comprehensive multisector interventions, integrating health promotion and mental health rehabilitation, access to quality education, and management of combined/concomitant use of different substances to reduce and/or prevent criminal involvement by individuals that use crack cocaine and other substances, as well as to prevent/manage relapse.


Primary malignant tumours in the non-cirrhotic liver.
Intrahepatic chlangiocarcinomas (CCs), the second most common primary malignant liver tumours, usually occur in non-cirrhotic liver, and can be classified into three types based on gross morphology: mass-forming; periductal infiltrating; and intraductal growing. Among them, mass-forming intrahepatic CCs are the most common type and characterized by homogeneous mass with an irregular but well-defined margin with peripheral enhancement on late arterial phase and delayed enhancement in central portion of tumours corresponding to the fibrous stroma. Several imaging features such as enhancement pattern and degree of diffusion restriction have been suggested as prognostic markers for mass-forming CCs. Hepatocellular carcinomas (HCCs) are the most common primary malignant liver tumors, and usually arise from the cirrhotic liver. However, approximately 20% of HCCs involve the non-cirrhotic liver (hereafter, non-cirrhotic HCC), and non-cirrhotic HCCs are often detected at an advanced stage due to the lack of surveillance for patients with non-cirrhotic liver. Other primary malignant liver tumours other than CCs and HCCs including angiosarcoma, undifferentiated embryonal sarcoma are quite rare, and imaging diagnosis is often difficult. This review offers a brief overview of epidemiology, risk factors and imaging features of primary malignant tumours in non-cirrhotic liver. Understanding of radiologic appearance and predisposing clinical features as well as differentials of primary malignant tumour in non-cirrhotic liver can be helpful for radiologists to adequately assess these tumours, and subsequently to make optimal management plan.


Association between sexual abuse victimization during the life course and suicidal behaviors in male and female college students in China: Timing, duration, types and patterns.
A certain link between sexual abuse (SA) victimization and suicidal behaviors has been confirmed, but it remains unclear whether this association varies with regard to SA characteristics and gender. Participants were 4034 college students drawn from a cross-sectional study conducted in Hefei, China. Gender-stratified latent class analysis (LCA) and logistic regression models were used to examine the relationships between timing, duration, types and patterns of SA victimization and suicidal behaviors. For the males, SA in the elementary school or earlier period was associated with suicidal ideation (OR: 3.29, 95%CI: 2.20-5.38), plans (OR: 3.44, 95% CI: 1.54-7.77) and preparations (OR:3.05, 95% CI: 1.19-7.74). All types of SA were significantly associated with the four types of suicidal behaviors. Dose-response relationship and cumulative effect were found between duration, types of SA victimization and suicidal behaviors. Three latent classes of SA victimization were identified for males and females, respectively. For males, the "moderate SA" class and "persistent SA" class were associated with the four types of suicidal behaviors. For the females, SA during the university period was associated with suicidal ideation (OR: 2.47, 95% CI: 1.24-4.93). Only suicidal ideation was associated with the "moderate SA" class. The cross-sectional survey design did not allow to conclude any causality. The relationship between SA victimization and suicidal behaviors varies in terms of SA victimization characteristics and the relationships were stronger in males than in females.


Suprathreshold static perimetry in glaucoma and other optic nerve disease.
Comparisons between automated suprathreshold static perimetry and manual kinetic perimetry were performed for 226 eyes with glaucoma or ocular hypertension, and 147 eyes with other optic nerve disease. Both techniques produced similar high detection rates for glaucomatous visual field defects, whereas suprathreshold static perimetry performed significantly better than kinetic testing in optic nerve disease other than glaucoma. It is concluded that automated suprathreshold static perimetry is an excellent quantitative screening technique for detecting visual field defects.


Neck rejuvenation.
The neck has long been neglected when it comes to facial rejuvenation. More often than not the neck is left untreated, leaving the patient with a line of demarcation along the mandible separating a rejuvenated face from an aged neck. Neck rejuvenation involves targeting all of the layers of tissue that are affected by the aging process. Neck rejuvenation is usually performed in conjunction with facial rejuvenation, but can be an isolated procedure. Neck rejuvenation can be nonsurgical or surgical, with many options for combined approaches and modalities.


Assessment of Prediction Tasks and Time Window Selection in Temporal Modeling of Electronic Health Record Data: a Systematic Review.
Temporal electronic health record (EHR) data are often preferred for clinical prediction tasks because they offer more complete representations of a patient's pathophysiology than static data. A challenge when working with temporal EHR data is problem formulation, which includes defining the time windows of interest and the prediction task. Our objective was to conduct a systematic review that assessed the definition and reporting of concepts relevant to temporal clinical prediction tasks. We searched PubMed® and IEEE Xplore® databases for studies from January 1, 2010 applying machine learning models to EHR data for patient outcome prediction. Publications applying time-series methods were selected for further review. We identified 92 studies and summarized them by clinical context and definition and reporting of the prediction problem. For the time windows of interest, 12 studies did not discuss window lengths, 57 used a single set of window lengths, and 23 evaluated the relationship between window length and model performance. We also found that 72 studies had appropriate reporting of the prediction task. However, evaluation of prediction problem formulation for temporal EHR data was complicated by heterogeneity in assessing and reporting of these concepts. Even among studies modeling similar clinical outcomes, there were variations in terminology used to describe the prediction problem, rationale for window lengths, and determination of the outcome of interest. As temporal modeling using EHR data expands, minimal reporting standards should include time-series specific concerns to promote rigor and reproducibility in future studies and facilitate model implementation in clinical settings. The online version contains supplementary material available at 10.1007/s41666-023-00143-4.


Does freezing and dynamic flexing of frozen branches impact the cavitation resistance of Malus domestica and the Populus clone Walker?
Frost damage to the xylem conduits of trees is a phenomenon of eco-physiological importance. It is often documented in terms of the percentage loss of conductivity (PLC), an indicator of air filling of the conduits. However, trees that refill their conduits in spring could be impacted more by damage to the conduits that reduce cavitation resistance, making them more susceptible to future drought events. We investigated whether ice formation, dynamic flexing of frozen branches or freeze-thaw events could reduce the cavitation resistance (cause "frost fatigue") in first-year shoots of apple (Malus domestica) and clonal hybrid cottonwood (Walker). Frost fatigue was measured in terms of P50 (the negative xylem pressure required to cause a 50 % loss of conductivity). All treatment groups showed significant frost fatigue, with the exception of the pre-flushed, constantly frozen poplar branches. The P50 following freeze treatments was approximately 50 % of the pre-freeze values. The effect tended to be greater in freeze-thawed branches. Dynamic bending of the branches had no effect on either PLC or P50. In three out of four cases, there was a significant correlation between P50 and PLC. Frost fatigue occurred in both apple and poplar, two unrelated species with different drought and frost tolerances, suggesting that it may be a widespread phenomenon that could impact the ecophysiology of temperate forests.


The use of consumption data to assess exposure to biotechnology-derived foods and the feasibility of identifying effects on human health through post-market monitoring.
The pre-market safety assessment of foods derived through biotechnology provides a scientific basis for concluding reasonable certainty of no harm and ensuring safety. At a minimum, the outcome of such an assessment provides sufficient information to estimate the likelihood of adverse effects on consumers, generally precluding the need for post-market monitoring. Post-market monitoring (PMM) may be appropriate under certain conditions where a better estimate of dietary exposure and/or nutritional consequence of a biotechnology-derived food is required, when a potential safety issue, such as allergenicity, cannot be adequately addressed through pre-market studies, or to corroborate dietary intakes of a nutritionally improved food with beneficial effects on human health. Monitoring programs must be hypothesis-driven, and are dependent upon the availability of accurate consumption data. Exposure assessment methods include both deterministic and probabilistic estimates of intakes using food supply data, individual dietary surveys, household surveys, or total diet studies. In the development of a monitoring approach, resource allocation should be dependent upon both the desired level of conservatism and the endpoint of interest. However, the cost of monitoring varies substantially, and the potential to determine causation may be limited.


Spatial patterning of water quality in Biscayne Bay, Florida as a function of land use and water management.
An objective classification analysis was performed on a water quality data set from 25 sites collected monthly during 1994-2003. The water quality parameters measured included: TN, TON, DIN, NH4+, NO3-, NO2-, TP, SRP, TN:TP ratio, TOC, DO, CHL A, turbidity, salinity and temperature. Based on this spatial analysis, Biscayne Bay was divided into five zones having similar water quality characteristics. A robust nutrient gradient, driven mostly by dissolved inorganic nitrogen, from alongshore to offshore in the main Bay, was a large determinant in the spatial clustering. Two of these zones (Alongshore and Inshore) were heavily influenced by freshwater input from four canals which drain the South Dade agricultural area, Black Point Landfill, and sewage treatment plant. The North Bay zone, with high turbidity, phytoplankton biomass, total phosphorus, and low DO, was affected by runoff from five canals, the Munisport Landfill, and the urban landscape. The South Bay zone, an embayment surrounded by mangrove wetlands with little urban development, was high in dissolved organic constituents but low in inorganic nutrients. The Main Bay was the area most influenced by water exchange with the Atlantic Ocean and showed the lowest nutrient concentrations. The water quality in Biscayne Bay is therefore highly dependent of the land use and influence from the watershed.


Single low-dose rHuIL-12 safely triggers multilineage hematopoietic and immune-mediated effects.
Recombinant human interleukin 12 (rHuIL-12) regulates hematopoiesis and cell-mediated immunity. Based on these hematopoietic and immunomodulatory activities, a recombinant human IL-12 (rHuIL-12) is now under development to address the unmet need for a medical countermeasure against the hematopoietic syndrome of the acute radiation syndrome (HSARS) that occurs in individuals exposed to lethal radiation, and also to serve as adjuvant therapy that could provide dual hematopoietic and immunotherapeutic benefits in patients with cancer receiving chemotherapy. We sought to demonstrate in healthy subjects the safety of rHuIL-12 at single, low doses that are appropriate for use as a medical countermeasure for humans exposed to lethal radiation and as an immunomodulatory anti-cancer agent. Two placebo-controlled, double-blinded studies assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of rHuIL-12. The first-in-human (FIH) dose-escalation study randomized subjects to single subcutaneous injections of placebo or rHuIL-12 at 2, 5, 10, and 20 μg doses. Due to toxicity, dose was reduced to 15 μg and then to 12 μg. The phase 1b expansion study randomized subjects to the highest safe and well tolerated dose of 12 μg. Thirty-two subjects were enrolled in the FIH study: 4 active and 2 placebo at rHuIL-12 doses of 2, 5, 10, 12, and 15 μg; 1 active and 1 placebo at 20 μg. Sixty subjects were enrolled in the expansion study: 48 active and 12 placebo at 12 μg dose of rHuIL-12. In both studies, the most common adverse events (AEs) related to rHuIL-12 were headache, dizziness, and chills. No immunogenicity was observed. Elimination of rHuIL-12 was biphasic, suggesting significant distribution into extravascular spaces. rHuIL-12 triggered transient changes in neutrophils, platelets, reticulocytes, lymphocytes, natural killer cells, and CD34+ hematopoietic progenitor cells, and induced increases in interferon-γ and C-X-C motif chemokine 10. A single low dose of rHuIl-12 administered subcutaneously can elicit hematological and immune-mediated effects without undue toxicity. The safety and the potent multilineage hematopoietic/immunologic effects triggered by low-dose rHuIL-12 support the development of rHuIL-12 both as a radiation medical countermeasure and as adjuvant immunotherapy for cancer. ClinicalTrials.gov: NCT01742221.


Effects of Sodium Formate and Calcium Propionate Additives on the Fermentation Quality and Microbial Community of Wet Brewers Grains after Short-Term Storage.
The objective of this research was to examine the effect of sodium formate (SF) and calcium propionate (CAP) on the fermentation characteristics and microbial community of wet brewers grains (WBG) after short-term storage. In the laboratory environment, fresh WBG was ensiled with (1) no additive (CON), (2) sodium formate (SF, 3 g/kg fresh weight), and (3) calcium propionate (CAP, 3 g/kg fresh weight) for 20 days. After opening, fermentation characteristics, chemical composition, rumen effective degradability, and the microbial community of ensiled WBG were analyzed. The addition of CAP had no effect on pH and lactic acid concentration and increased the concentrations of propionic acid; the SF group had the lowest pH and acetic acid, butyric acid, and ammonia nitrogen contents and the highest lactic acid concentration. After fermentation, the SF group had the highest contents of dry matter (DM), water-soluble carbohydrates (WSCs), and neutral detergent fiber (NDF). The contents of the three nutrients in the CAP group were significantly higher than those in the CON group. The addition of the two additives had little influence on the crude protein (CP) and acid detergent fiber (ADF) contents of the ensiled WBG. Two additives elevated in situ effective degradability of DM and NDF compared with the parameters detected in the CON group; WBG ensiled with SF had higher effective in situ CP degradability than that in the CON and CAP groups. The results of the principal component analysis indicate that the SF group and two other groups had notable differences in bacterial composition. The analysis of the genus level of the bacterial flora showed that the content of Lactobacillus in the SF group was significantly higher than that in the two other treatment groups, while the content of Clostridium was significantly lower than that in the two other treatment groups. Therefore, the addition of sodium formate can suppress the undesirable microorganisms, improve the fermentation qualities, and ensure that WBG is well preserved after 20 days of ensiling.


Will jumping snails prevail? Influence of near-future CO₂, temperature and hypoxia on respiratory performance in the tropical conch Gibberulus gibberulus gibbosus.
Tropical coral reef organisms are predicted to be especially sensitive to ocean warming because many already live close to their upper thermal limit, and the expected rise in ocean CO2 is proposed to further reduce thermal tolerance. Little, however, is known about the thermal sensitivity of a diverse and abundant group of reef animals, the gastropods. The humpbacked conch (Gibberulus gibberulus gibbosus), inhabiting subtidal zones of the Great Barrier Reef, was chosen as a model because vigorous jumping, causing increased oxygen uptake (ṀO2 ), can be induced by exposure to odour from a predatory cone snail (Conus marmoreus). We investigated the effect of present-day ambient (417-454 µatm) and projected-future (955-987 µatm) PCO2 on resting (ṀO2 , rest) and maximum (ṀO2 , max) ṀO2 , as well as ṀO2 during hypoxia and critical oxygen tension (PO2 , crit), in snails kept at present-day ambient (28°C) or projected-future temperature (33°C). ṀO2 , rest and ṀO2 , max were measured both at the acclimation temperature and during an acute 5°C increase. Jumping caused a 4- to 6-fold increase in ṀO2 , and ṀO2 , max increased with temperature so that absolute aerobic scope was maintained even at 38°C, although factorial scope was reduced. The humpbacked conch has a high hypoxia tolerance with a PO2 , crit of 2.5 kPa at 28°C and 3.5 kPa at 33°C. There was no effect of elevated CO2 on respiratory performance at any temperature. Long-term temperature records and our field measurements suggest that habitat temperature rarely exceeds 32.6°C during the summer, indicating that these snails have aerobic capacity in excess of current and future needs.


Diabetic yoga protocol improves glycemic, anthropometric and lipid levels in high risk individuals for diabetes: a randomized controlled trial from Northern India.
To study the effectiveness of diabetic yoga protocol (DYP) against management of cardiovascular risk profile in a high-risk community for diabetes, from Chandigarh, India. The study was a randomized controlled trial, conducted as a sub study of the Pan India trial Niyantrita Madhumeha Bharath (NMB). The cohort was identified through the Indian Diabetes Risk Scoring (IDRS) (≥ 60) and a total of 184 individuals were randomized into intervention (n = 91) and control groups (n = 93). The DYP group underwent the specific DYP training whereas the control group followed their daily regimen. The study outcomes included changes in glycemic and lipid profile. Analysis was done under intent-to-treat principle. The 3 months DYP practice showed diverse results showing glycemic and lipid profile of the high risk individuals. Three months of DYP intervention was found to significantly reduce the levels of post-prandial glucose levels (p = 0.035) and LDL-c levels (p = 0.014) and waist circumference (P = 0.001). The findings indicate that the DYP intervention could improve the metabolic status of the high-diabetes-risk individuals with respect to their glucose tolerance and lipid levels, partially explained by the reduction in abdominal obesity. The study highlights the potential role of yoga intervention in real time improvement of cardiovascular profile in a high diabetes risk cohort. CTRI, CTRI/2018/03/012804. Registered 01 March 2018-Retrospectively registered, http://www.ctri.nic.in/ CTRI/2018/03/012804.


[Experimental principles of immunotherapy in malignant tumors using microbial substances. 2. Effect of streptococci on ascites-rethotelsarcoma of the mouse in vitro].
The antitumoral activity of specific strains of beta-hemolytic streptococci, group A, published by Okamoto and his group, could be confirmed also with an in vivo-method. An own strain (No. 1C) with good antitumoral effect was used in the ascites-retothelsarcoma of the mouse. This effect was strain-specific. A hypothetical anti-tumor-factor of the streptococci is assumed. First clinical results are described.


Simultaneous determination of L-cysteine and L-tyrosine using Au-nanoparticles/poly-eriochrome black T film modified glassy carbon electrode.
A novel Au-nanoparticles/poly-eriochrome black T film modified glassy carbon electrode (AuNPs/PEBT/GCE) was constructed for the simultaneous determination of l-cysteine (L-Cys) and l-tyrosine (L-Tyr) by differential pulse voltammetry. Fourier transform infrared spectra and electrochemical impedance spectroscopy indicate that the PEBT film was successfully polymerized on the surface of GCE and the film efficiently decreased the charge transfer resistance value of electrode and improved the electron transfer kinetic between analytes and electrode. The scanning electron microscope image shows that the immobilized AuNPs were spherical in shape and enhanced the electrical conductivity of PEBT film. In addition, PEBT film increased the oxidation currents of analytes four times when compared to bare GCE, and the AuNPs separated the oxidation potentials of L-Cys and L-Tyr by 488 mV while bare GCE failed to resolve them. The amperometry results exhibit that the electrocatalytic currents increased linearly with L-Cys concentrations in the range 0.05-100 μM (r=0.9981), and the detection limits of L-Cys and L-Tyr were 8 nM and 10 nM (S/N=3), respectively. With high sensitivity and selectivity, the proposed electrochemical sensor provides a simple method for simultaneous determination of L-Cys and L-Tyr.


Nitroreductase-based therapy of prostate cancer, enhanced by raising expression of heat shock protein 70, acts through increased anti-tumour immunity.
Gene-directed enzyme-prodrug therapy (GDEPT) using nitroreductase (NTR), with efficient adenoviral delivery, and CB1954 (CB), is an effective means of directly killing tumours. However, an immune-mediated bystander effect remains an important product of GDEPT since it is often critical to the elimination of untransduced tumour cells both locally and at distal metastatic sites through generation of tumour-specific immunity without the need for tumour antigen identification or the generation of a personalised vaccine. The mode of induced tumour cell death is thought to contribute to the immunisation process, together with the induction and release of stress proteins. Here, RM-9 murine prostate tumour cells were efficiently killed by adenovirally delivered NTR/CB treatment both in vitro and in vivo, and bystander effects were observed. Cells appeared to die by pathways that suggest necrosis more than that of classical apoptosis. NTR/CB-induced expression of a range of stress proteins was determined by proteomic analysis, revealing chiefly heat shock protein (HSP)25 and HSP70 upregulation, whilst immune responses in vivo were weak. In an attempt to enhance the anti-tumour effect, an adenoviral vector was constructed that co-expressed NTR and HSP70, the latter being a known immune stimulator and chaperone of antigen. This combination elicited significantly enhanced protection over NTR alone for both the treated tumour and a subsequent re-challenge. Protection was CD4+ and CD8+ T cell-dependent and was associated with tumour-specific CTL, IFNgamma and IL-5 responses. The use of such a cytotoxic and immunomodulatory gene combination in cancer therapy warrants further pursuit.


Predictors of nurses' perceptions of barriers to research utilization.
To identify predictors of nurses' self-reported barriers to using research findings in clinical practice. Several studies have shown that nurses perceive barriers to research utilization but to our knowledge predictors of nurses perceptions of barriers to research utilization have not been identified before. Three questionnaires were answered by 833 nurses: the Barriers Scale, the Quality Work Competence questionnaire and a questionnaire including questions on professional issues. Dissatisfaction with support from immediate superiors for participating in research and/or development projects, having no academic degree and unclear and unrealistic workplace goals were identified as factors increasing the risk of perceiving barriers to the use of research findings in clinical practice. The results imply that head nurses, nursing managers and other health care leaders should create strategies for supporting nurses' professional development and possibilities to implement research findings in clinical practice. To support research utilization and evidence-based care health care leaders, head nurses and nurse managers should create clear and realistic goals for the work place including demands on evidence-based care. It is also important for head nurses and nurse managers to create strategies for supporting nurses' professional development and possibilities to implement research findings in clinical practice.