Mesolimbic dopaminergic neurons are not spared by MPTP neurotoxicity in mice.
In C57 black mice, MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) (30 mg/kg X 2, 20 mg/kg X 15, 30 mg/kg X 15, or 35 mg/kg X 1) depleted DA in both striatum and accumbens but not in frontal cortex, hypothalamus and retina. DA decreases were more pronounced in striatum than in accumbens, were maximal at 2 days, partially reversed later but persisted up to 30 days after treatment. DA depletions in nigra were smaller earlier and maximal later. The study suggests that, in mice, MPTP damages nigrostriatal and mesolimbic projections but spares other DA neurons.


Glucocerebrosidase, a lysosomal enzyme that does not undergo oligosaccharide phosphorylation.
Labelling of cultured human skin fibroblasts from either control subjects or patients with mucolipidosis II (I-cell disease) with [32P]phosphate resulted in tight association of phosphate with immunoprecipitated glucocerebrosidase, a membrane-associated lysosomal enzyme. Endoglycosidase F digestion of the immunoprecipitated glucocerebrosidase did not release labelled phosphate, suggesting that the phosphate was not associated with the oligosaccharide moiety of this glycoprotein. Purification of the enzyme from cells labelled with [32P]phosphate and [35S]methionine by an immunoaffinity chromatography procedure, which included a washing step with detergent, resulted in complete separation of the phosphate label from the peak of glucocerebrosidase activity and methionine labelling. We conclude that oligosaccharide phosphorylation, which is essential for transport of soluble lysosomal enzymes to the lysosomes in fibroblasts, does not occur in glucocerebrosidase.


Recombinant PBP2a/autolysin conjugate as PLGA-based nanovaccine induced humoral responses with opsonophagocytosis activity, and protection versus methicillin-resistant Staphylococcus aureus infection.
Methicillin-resistant Staphylococcus aureus (MRSA) reasons extreme infections, can resist various conventional antimicrobial agents, and cause morbidity and mortality worldwide. Vaccination seems to help modulate MRSA infections. Nanovaccine is considered a novel strategy in vaccine technology. The primary purpose of the present study was to develop a conjugate vaccine based on recombinant PBP2a and MRSA autolysin formulated in PLGA as a nanoparticle capable of enhancing protective responses against MRSA in the murine model. Recombinant PBP2a and autolysin have been expressed and purified by nickel-nitrilotriacetic acid (Ni-NTA) affinity column and characterized by SDS-PAGE and western blot. PLGA was bound to recombinant proteins by using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) and adipic acid dihydrazide (ADH) as a linker and spacer, respectively. Conjugation of recombinant proteins to PLGA was confirmed by the AFM assay, zeta potential, and size distribution, and its efficacy was evaluated in mice. Total IgG, IgG1, IgG2a, IgG2b, and IgM titers were analyzed to assess immune responses. Lastly, the bioactivity of antibodies was tested by using the opsonophagocytosis assay. Mice immunized with the r-PBP2a-r-autolysin-PLGA nanovaccine led to increased levels of opsonic antibodies and IgG1, IgG2a, IgG2b, and IgM when compared with other experimental groups. Our results confirmed that vaccination with nanovaccine could reduce the mortality rate against the sub-lethal dose of MRSA challenge. Furthermore, the nanovaccine could eliminate MRSA from the kidney of infected mice. This study may provide valuable insights into the protective power of the r-PBP2a-r-autolysin-PLGA conjugate vaccine against MRSA infection.


Detection and identification of coronaviruses in human tissues using electron microscopy.
The identification of viral particles within a tissue specimen requires specific knowledge of viral ultrastructure and replication, as well as a thorough familiarity with normal subcellular organelles. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has underscored how challenging the task of identifying coronavirus by electron microscopy (EM) can be. Numerous articles have been published mischaracterizing common subcellular structures, including clathrin- or coatomer- coated vesicles, multivesicular bodies, and rough endoplasmic reticulum, as coronavirus particles in SARS-CoV-2 positive patient tissue specimens. To counter these misinterpretations, we describe the morphological features of coronaviruses that should be used to differentiate coronavirus particles from subcellular structures. Further, as many of the misidentifications of coronavirus particles have stemmed from attempts to attribute tissue damage to direct infection by SARS-CoV-2, we review articles describing ultrastructural changes observed in specimens from SARS-CoV-2-infected individuals that do not necessarily provide EM evidence of direct viral infection. Ultrastructural changes have been observed in respiratory, cardiac, kidney, and intestinal tissues, highlighting the widespread effects that SARS-CoV-2 infection may have on the body, whether through direct viral infection or mediated by SARS-CoV-2 infection-induced inflammatory and immune processes. HIGHLIGHTS: The identification of coronavirus particles in SARS-CoV-2 positive tissues continues to be a challenging task. This review provides examples of coronavirus ultrastructure to aid in the differentiation of the virus from common cellular structures.


Aspergillus nidulans in the post-genomic era: a top-model filamentous fungus for the study of signaling and homeostasis mechanisms.
The accessibility to next-generation sequencing (NGS) techniques has enabled the sequencing of hundreds of genomes of species representing all kingdoms. In the case of fungi, genomes of more than a thousand of species are publicly available. This is far from covering the number of 2.2-3.8 million fungal species estimated to populate the world but has significantly improved the resolution of the fungal tree of life. Furthermore, it has boosted systematic evolutionary analyses, the development of faster and more accurate diagnostic analyses of pathogenic strains or the improvement of several biotechnological processes. Nevertheless, the diversification of the nature of fungal species used as model has also weakened research in other species that were traditionally used as reference in the pre-genomic era. In this context, and after more than 65 years since the first works published by Pontecorvo, Aspergillus nidulans remains as one of the most referential model filamentous fungus in research fields such as hyphal morphogenesis, intracellular transport, developmental programs, secondary metabolism, or stress response. This mini-review summarizes how A. nidulans has contributed to the progress in these fields during the last years, and discusses how it could contribute in the future, assisted by NGS and new-generation molecular, microscopy, or cellular tools.


Binding of LPS and LPS--LDL complexes to rat hepatocytes.
We studied binding of 3H-LPS toxin and LPS complexes with serum 125I-LDL to primary culture of rat hepatocytes. Receptor binding of LPS and LDL--LPS complex was 50 and 77% of the total, respectively. Scatchard plot was linear in both cases. LDL and LDL--LPS complexes were inessential for LPS binding, while LDL--LPS binding was appreciably suppressed by LPS (-30%) and LDL (-65%).


Mediating role of resilience in relationship between negative life events and depression among Chinese adolescents.
To explore whether resilience acted as a protective factor between negative life events and depression among Chinese adolescents. Using convenient sampling, students (N = 278) in two junior and senior high schools in Wuhan, China were investigated, and structural equation model was used to examine the mediating effect of resilience in the relationship between negative life events and depression. Resilience was negatively correlated with negative life events and depression, and negative life events were positively correlated with depression. Resilience partially mediated the effects of negative life events on depression in Chinese adolescents. It is important for educators to improve adolescents' resilience to mitigate the effects of negative life events on depression.


Effect of cysteamine on suckling-induced prolactin secretion in the rat.
We have examined the effects of the thiol agent cysteamine on physiological prolactin secretion in the female rat. Administration of cysteamine completely abolishes suckling-induced prolactin secretion in a dose-dependent manner. Cysteamine treatment does not alter nursing behavior of the mothers. Further, we have found that the prolactin-depleting ability of cysteamine is not altered by a prior suckling stimulus. These results indicate that cysteamine administration inhibits physiologically-induced prolactin secretion with similar potency and efficacy as previously reported for cysteamine effects on basal and pharmacologically-induced prolactin secretion. Furthermore, the effect of cysteamine is not compromised by a previous suckling stimulus, suggesting that "depletion-transformation" of pituitary prolactin stores does not protect against the effect of cysteamine.


Management of Bronchial Stumps in Anatomic Lung Segmentectomy.
Stapling or suturing techniques are commonly used to close bronchial stumps in lung lobectomy, although with the segmentectomy procedure, various types of closure are likely to be performed. We investigated the safety of various types of bronchial closure methods used in anatomic lung segmentectomy. Between 2005 and 2013, we performed anatomic lung segmentectomies including segmentectomies through open thoracotomy for 41 patients and thoracoscopy for 167 patients. Bronchial closures were performed through open and thoracoscopy methods for 66 and 231 stumps, respectively. Data were collected regarding segmental bronchus type, stump closure methods, and closure-related complications. Since 2006, bronchial caliber was measured from preoperative 1 mm(3) computed tomography. In the open group, 17 stumps (26%) were closed by stapling, 48 (73%) by thread ligation, and 1 (1%) by suturing. In the thoracoscopy group, 116 stumps (50%) were closed by stapling, 76 (33%) by thread ligation, and 39 (17%) by polymer clip ligation (p < 0.001). Staplers were used for all bronchial trunks that supplied more than a single segment; the mean diameter was 8.1 mm. For single segmental bronchi, ligation was used for 80% in the open group and stapling for 75% in the thoracoscopy group; the mean diameter was 6.6 mm. For subsegmental bronchi, ligation or clipping were applied for 95% in both groups; the mean diameter was 4.6 mm. One bronchopleural fistula was observed at 6 months postoperatively in upper division segmentectomy of the left upper lobe using a stapler in the open group. Ligation can be used safely for small-diameter segmental bronchial stump closures in anatomic lung segmentectomies or subsegmentectomies. The use of a polymer clip can be an alternative method to close the bronchial stump of subsegmentectomies.


Fat talk and its relationship with body image disturbance.
Although past studies have highlighted fat talk as relevant to body image disturbance, the majority of these have only investigated the link between fat talk and body esteem, to the exclusion of other body image constructs. One hundred and ninety-nine women completed an online survey measuring levels of appearance-based comparisons, body surveillance, thin ideal internalization, body esteem, and fat talk (FT-body concerns and FT-body comparisons). Results showed that fat talk made a significant contribution in explaining additional variance in body esteem above the other three body image factors, with FT-body concerns in particular making the highest unique contribution. Hierarchical regression analyses suggest that fat talk should be viewed as an independent psychosocial predictor of body esteem in both theoretical and therapeutic contexts. Future research should explore these relationships from a longitudinal perspective, and also clarify the nuances in the relationships by investigating the nature of women's everyday body image experiences.


Breast Cytology and Pathology in Pregnancy and Lactation.
Breast tissue reveals some physiologic changes during pregnancy and lactation due to hormonal alterations. Whole range of breast diseases including inflammatory, benign and malignant neoplasms can be seen in pregnancy but due to concurrent physiologic changes, may lead to diagnostic challenges. This chapter reviews sampling methods and histologic features of common benign breast lesions in pregnancy and lactation periods.


Ovarian mucinous cystadenocarcinoma of low malignant potential associated with a mature cystic teratoma.
A 54-year-old female underwent exploratory laparotomy for evaluation of a large abdominopelvic mass. She was found to have a 29-pound multicystic tumor arising from the right ovary. There were no other gross intraabdominal abnormalities. Histologic examination of the mass revealed a mucinous cystadenocarcinoma of low malignant potential and a mature cystic teratoma. To our knowledge, this is the first case report of an ovarian epithelial adenocarcinoma of low malignant potential associated with a mature cystic teratoma.


The two-factorial symptom structure of post-traumatic stress disorder: depression-avoidance and arousal-anxiety.
The first part of this study showed that the DSM-III-R symptom structure of post-traumatic stress disorder (PTSD), i.e. criteria B (reexperience), C (avoidance-numbing), and D (arousal), and, consequently the diagnosis of PTSD, could not be validated in fire and car-accident victims. The aims of this study were to: (i) determine the factors as well as their structure in the symptoms of PTSD; and (ii) develop a new classification or typology of PTSD. Exploratory and confirmatory factor analyses and cluster analyses were employed to: (i) examine the factors in PTSD symptomatology; and (ii) find and validate adequate diagnostic criteria for PTSD. The Composite International Diagnostic Interview (CIDI), PTSD Module, was used between 7 and 9 months after the traumatic event in a study group of 185 victims of two different traumatic events, i.e. 130 fire and 55 car-accident victims. Our findings support the existence of two factors, i.e. a first labeled 'depression-avoidance (DAV) dimension', as it contains items reminiscent of depression and avoidance, and a second labeled 'the anxiety-arousal (AA) dimension', as it contains symptoms reminiscent of anxiety and increased arousal. Cluster analysis yielded two clusters, i.e. a cluster of subjects with PTSD cases and another with non-cases. Our PTSD algorithm was significantly less restrictive than the DSM-III-R diagnosis of PTSD. There are only quantitative, but no qualitative, differences between the cluster analytically derived classes. PTSD is not a well-delineated clinical entity, as there is a clinical continuum from PTSD non-cases to cases with less and more severe DAV and AA symptoms. It is more appropriate to express PTSD in terms of general severity of PTSD and severity of the DAV and AA dimensions.


Risk factors and indication for dissection of right paraesophageal lymph node metastasis in papillary thyroid carcinoma.
Right paraesophageal lymph nodes (RPELNs) are located behind right recurrent laryngeal nerve which often ignored in central compartment lymph nodes (LNs) dissection of papillary thyroid carcinoma (PTC) patients. The aim of this study was to identify the risk factors for RPELN metastasis and indications for RPELN dissection. Medical record of 246 consecutive PTC patients (194 female, 52 male), who underwent total thyroidectomy (244 patients) or right lobectomy (2 patients) with central compartment LN dissection (13 ipsilateral and 233 bilateral), were reviewed. The RPELNs were kept separately during the operation. The clinical pathology data was collected and analyzed. RPELN metastasis was confirmed in 33 patients (13.4%) and were discovered in 18.5% (31/168) of right lesion, 34.4% (31/90) of right central group LN (rCLN) metastasis, 33.3% (18/54) of lateral compartment LN (LLN) metastasis, 25.7% (9/35) of local recurrent patients respectively. The ultrasound suspected metastatic LNs, tumor diameter, tumor number, tumor location, and numbers of metastatic Delphian LNs, central group LNs (CLNs), rCLNs, and LLNs between patients with and without RPELN metastasis showed significant differences in univariate analysis (P < 0.05). In multivariate analysis, number of metastatic rCLNs (1-2: OR 13.6, 95% CI, 2.7-67.5; ≧3: OR39.4, 95% CI, 7.7-200.9), right side tumor (OR 6.4, 95% CI, 1.1-35.6), and three or more metastatic LLNs (OR 3.5, 95% CI, 1.2-10.2) were independent risk factors for RPELN metastasis. PTC patients with right lobe lesions, especially with potential rCLN metastasis, are at considerable risk of RPELN metastasis. RPELN dissection should be considered in these patients.


Applying an equity lens to liver health and research in Europe.
Liver disease is a major cause of premature death and disability in Europe. However, morbidity and mortality are not equally distributed in the population. In spite of this, there are few studies addressing the issue of health inequalities in Europe. In this Public Health Corner article, we compare the research conducted on health inequalities in Europe to other settings and highlight the main differences based upon an extensive review of the literature. We report that only 10.2% of studies were led by European institutions or conducted in European populations and that certain topics such as alcohol-related liver disease are largely overlooked. In addition, we discuss the relevance of including a health equity lens when conducting clinical, epidemiological and health systems' research in liver disease and set out the basic requirements to tackle health inequalities in liver disease in Europe.


Deaths from copper toxicity of sheep at pasture and the use of fresh seaweed.
A number of sheep of the Orkney breed died of suspected copper poisoning while at pasture under circumstances which left sheep of other breeds apparently unaffected. Fresh seaweed offered to sheep with symptoms of copper toxicity appeared to be therapeutic and to lead to a reduction in plasma Cu level.


Development of context-sensitive pronunciation in reading: The case of ‹c› and ‹g›.
Writing systems sometimes deviate from one-to-one associations between letters and phonemes, but the deviations are often predictable from sublexical context. For initial ‹c› and ‹g› in English, deviations from the typical /k/ and /g/ pronunciations are influenced by adjacent context (the following vowel, as in center vs. canter) and nonadjacent context (the presence of a Latinate vs. basic suffix, as in gigantic vs. giggling). We conducted two experiments with participants ranging in reading level from early elementary school to university to study the development of context use. Experiment 1 focused on adjacent context, and Experiment 2 also examined nonadjacent context. Use of context developed slowly, and readers at all levels were not as influenced by it as would be expected given the contextual effects in the English vocabulary. We discuss possible reasons for these phenomena and the need to teach children to use context more effectively.


The measurement of body-mind-spirit well-being toward multidimensionality and transcultural applicability.
The Body-Mind-Spirit model of health promotion (Chan, Ho&Chow, 2002) guided the construction of a multidimensional inventory for assessing holistic health. Named Body-Mind-Spirit Well-Being Inventory (BMSWBI), it comprises four scales: Physical Distress, Daily Functioning, Affect, and Spirituality (differentiated from religiosity and conceived as ecumenical). Respondents (674 Chinese adults from Hong Kong) completed the BMSWBI via the Internet. Results indicate that all four scales have high reliability, with alpha coefficients ranging from .87 to .92, and concurrent validity. Factor analysis indicates that (a) positive and negative affect form two distinct factors; and (b) spirituality comprises three distinct aspects, tranquility, resistance to disorientation, and resilience. Spirituality is positively associated with mental well-being, positive affect, satisfaction with life, and hope; but negatively associated with negative affect and perceived stress. These results suggest that the inventory may be used to assess different dimensions of health satisfactorily.


Effect of Surface Functionalization on the Cellular Uptake and Toxicity of Nanozeolite A.
Extensive use of zeolite nanoparticles in many areas, including medicine, has led to the concern about an impact and possible risk of their use for human health and the environment.In our studies, we investigated an uptake, retention, and cytotoxicity of nanozeolite A (BaA) functionalized with aminopropyl or poly(ethylene glycol) (PEG) of different chain lengths using human cervical carcinoma cell line. For internalization studies, nanozeolite was labeled with (133)Ba radionuclide.The results show that in the case of PEG modification, toxicity and uptake depend on the PEG chain length. The highest toxicity has been observed for nanozeolites coated with short-length chain (Ba-silane-PEGm(MW350). Also, amine-modified nanozeolites exhibited high toxicity, while nanozeolites coated with long PEG molecules, BaA-silane-PEGm(MW1000), and BaA-silane-PEGm(MW2000), as well as unmodified nanozeolite, seem to be nontoxic.In conclusion, this study shows that uptake, retention, and toxicity of nanozeolites coated with various length PEG molecules groups depend on the molecular weight of PEG.


A randomised controlled trial of the costs of hospital as compared with hospital in the home for acute medical patients.
To test the cost effectiveness of Hospital in the Home compared to hospital admission for acute medical conditions. Randomised controlled trial at the Prince of Wales Hospital, Sydney, from October 1995 to February, 1997; 100 patients with acute medical conditions admitted through the Emergency Department. The Hospital in the Home (HITH) group costs per separation ($1,764, CI 95% $1,416-$2,111, n = 50) were significantly lower (p < 0.0001, Mann-Whitney U-Wilcoxon Rank Sum) than the control group hospital separation ($3,614, CI 95% $2,881.37-$4,347.27, n = 47) with no significant difference in clinical outcomes, and comparable or better user satisfaction. Given the favourable clinical outcomes the HITH model produces at a lower cost, the cost-effectiveness of the care mode is high, and the allocative efficiency favourable. As a care model and critical pathway, HITH offers hospitals real bed day savings that can either be used to rationalise resource usage for a given level of activity, or increase throughput.


Outcomes of a Latino community-based intervention for the prevention of diabetes: the Lawrence Latino Diabetes Prevention Project.
We tested the effectiveness of a community-based, literacy-sensitive, and culturally tailored lifestyle intervention on weight loss and diabetes risk reduction among low-income, Spanish-speaking Latinos at increased diabetes risk. Three hundred twelve participants from Lawrence, Massachusetts, were randomly assigned to lifestyle intervention care (IC) or usual care (UC) between 2004 and 2007. The intervention was implemented by trained Spanish-speaking individuals from the community. Each participant was followed for 1 year. The participants' mean age was 52 years; 59% had less than a high school education. The 1-year retention rate was 94%. Compared with the UC group, the IC group had a modest but significant weight reduction (-2.5 vs 0.63 lb; P = .04) and a clinically meaningful reduction in hemoglobin A1c (-0.10% vs -0.04%; P = .009). Likewise, insulin resistance improved significantly in the IC compared with the UC group. The IC group also had greater reductions in percentage of calories from total and saturated fat. We developed an inexpensive, culturally sensitive diabetes prevention program that resulted in weight loss, improved HbA1c, and improved insulin resistance in a high-risk Latino population.


The effect of vitamin D auxiliary rehabilitation therapy in children with cerebral palsy and language dysfunction.
The aim of the present study was to observe the clinical efficacy of vitamin D auxiliary rehabilitation therapy in children with cerebral palsy and language dysfunction. Eighty-two cases of children with cerebral palsy and language dysfunction in our hospital from March 2011 to June 2014 were selected for this study. They were divided into two groups: the rehabilitation treatment group (simple group, N.=39) and the vitamin D auxiliary rehabilitation therapy group (combination group, N.=43). After three months of treatment, language development, Gesell Child Development Scale, Bayley Infant Development Scale score and vitamin D and calcium levels were compared. The language development, Gesell Child Development Scale, Bayley Infant Development Scale score and vitamin D and calcium levels for two of the groups, after treatment, are improved compared to before treatment. The difference was statistically significant (P<0.05). The total efficiency of the language development in the combination group was obviously higher than the simple group. The difference was significant (95.3% vs. 74.4%, χ2=2.486, P=0.032). The Gesell Child Development Scale improved in the combination group compared to the simple group. The difference was statistically significant (70.4±11.3 vs. 53.3±10.5, t=3.127, P=0.026). The proportion of normal children was significantly higher than the rehabilitation treatment group, and the difference was statistically significant (30.2% vs. 20.5%, χ2=3.016, P=0.029). In the combination group, the vitamin D and calcium levels were statistically increased compared to the rehabilitation treatment group. It had statistical differences between the two groups (P<0.05). Vitamin D auxiliary rehabilitation therapy could improve the language function and the language development status in children with cerebral palsy and language dysfunction.


Chemical speciation of carbon in municipal solid waste incinerator residues.
Incinerators do not achieve a complete mineralization of organic constituents of municipal solid waste. The solid residues (bottom ash, boiler ash and air pollution control residues) contain carbon which can be determined as total organic carbon (TOC). This work focuses on the TOC composition and its significance to the genesis and diagenesis of the solid residues. An analytical procedure is presented to characterize carbon species by different chemical and microscopic analytical methods. The procedure is based on two steps. In the first step a quantitative classification of TOC into four different carbon species (elemental carbon, water extractable organic carbon, dichloromethane extractable organic carbon and non extractable organic carbon) is performed to obtain a first survey of the TOC composition. Based on this survey a further characterization of individual carbon species is performed. The results of the qualitative and quantitative characterization of carbon species allow to postulate hypotheses on the influence of organic carbon on the long-term behavior of the solid residues.


Enhanced acetyl-CoA production is associated with increased triglyceride accumulation in the green alga Chlorella desiccata.
Triglycerides (TAGs) from microalgae can be utilized as food supplements and for biodiesel production, but little is known about the regulation of their biosynthesis. This work aimed to test the relationship between acetyl-CoA (Ac-CoA) levels and TAG biosynthesis in green algae under nitrogen deprivation. A novel, highly sensitive liquid chromatography mass spectrometry (LC-MS/MS) technique enabled us to determine the levels of Ac-CoA, malonyl-CoA, and unacetylated (free) CoA in green microalgae. A comparative study of three algal species that differ in TAG accumulation levels shows that during N starvation, Ac-CoA levels rapidly rise, preceding TAG accumulation in all tested species. The levels of Ac-CoA in the high TAG accumulator Chlorella desiccata exceed the levels in the moderate TAG accumulators Dunaliella tertiolecta and Chlamydomonas reinhardtii. Similarly, malonyl-CoA and free CoA levels also increase, but to lower extents. Calculated cellular concentrations of Ac-CoA are far lower than reported K mAc-CoA values of plastidic Ac-CoA carboxylase (ptACCase) in plants. Transcript level analysis of plastidic pyruvate dehydrogenase (ptPDH), the major chloroplastic Ac-CoA producer, revealed rapid induction in parallel with Ac-CoA accumulation in C. desiccata, but not in D. tertiolecta or C. reinhardtii. It is proposed that the capacity to accumulate high TAG levels in green algae critically depends on their ability to divert carbon flow towards Ac-CoA. This requires elevation of the chloroplastic CoA pool level and enhancement of Ac-CoA biosynthesis. These conclusions may have important implications for future genetic manipulation to enhance TAG biosynthesis in green algae.


[Effect of temperature and the active acidity of the medium on the metabolism of reserve carbohydrates and the survivability of baker's yeast].
The effect of the cultivation temperature and active acidity of the medium on the contrent of trehalose and glycogen in baker's yeast was investigated. With the temperature growth from 20 to 40 degrees C the trehalose content in the cells increased, thus enhancing survivability of yeast during storage. The same results were observed upon temperature rise at the end of cultivation. pH of 4.5-5.0 intensified the synthesis of both reserve carbohydrates in baker's yeast.


[Pathogenesis of the cytopenia syndrome in patients with cirrhosis of the liver complicated by portal hypertension].
One of the main causes of cytopenia and cellular immunodeficiency in patients with cirrhosis of the liver and portal hypertension is increased portal pressure, which, in turn, induces increased storage of formed elements in the spleen. Shunting operations producing a stable decompressive effect correct cytopenia similar to splenectomy but at the same time are devoid of the menacing postoperative complications characteristic of splenectomy.


Experimental data from the simulation of on-chip communication architectures using RedScarf simulation environment.
This article presents data from an extensive set of simulation-based experiments to compare the performance of on-chip communication architectures. These experiments were performed using the RedScarf simulation environment [1], which is described in the article entitled 'RedScarf: an open-source multi-platform simulation environment for performance evaluation of Networks-on-Chip' [2]. In the experiments presented here, several intra-chip communication architectures were compared under different traffic patterns. Latency, jitter, and throughput metrics were collected. Data is useful for researchers investigating on-chip communication architectures who need baseline data for comparison.


Editorial: Are Group-Based Interventions Effective for Treating Trauma-Related Psychopathology in Children and Young People?
Trauma-exposed young people are about twice as likely as their unexposed peers to develop mental health problems, which, if left untreated, can have long-term negative consequences.1 There is robust evidence for the effectiveness of individual trauma-focused psychological therapies to improve trauma-related psychopathology, particularly posttraumatic stress disorder (PTSD), in young people.2 However, there are minimal services that provide such specialist treatments in low/middle-income countries where most young people live,3 and services may be severely disrupted at times of extreme stressors, such as war, natural disasters, and other humanitarian crises, when need is greatest.4 Moreover, even in high-income stable regions where child mental health services are established and treatments are available, these health care resources are limited, and can only be accessed by a minority of affected trauma-exposed young people.5 There is therefore a need for research to indicate effective interventions that are more accessible and can be delivered on a greater scale to treat more young people with trauma-related psychopathology.6 The recent meta-analysis by Davis et al.7 focused on the more accessible intervention of group-based psychological treatment for child PTSD symptoms, and found evidence of effectiveness compared with control conditions. The study provides an important advancement in this field, and also highlights the need for further research to better understand how group interventions can be most usefully implemented.


[Dental professionals in the future: flexible team players. The vision of dental professionals on future professional structure and occupation].
The project 'From care-demand for care to a social dental occupational and educational structure' was carried out to reach an agreement about the organization of the future social occupational and educational structure and the future performance of one's profession. A descriptive analysis of data, obtained by literature search and consensus-meetings was used. All relevant professional associations participated in this project. The project resulted in profiles for the future dental professionals and for the future dental team. In this project the dental professionals come to an agreement about the future professional performance. However, the discussion has not yet been finished. Further collaboration between the professional associations is recommended.


Impact of Adolescent Gender Dysphoria on Treatment Uptake in an Obesity Management Program.
A 13-year-old biological female patient presented with gender dysphoria while receiving treatment for obesity. Body distress and a desired masculine phenotype motivated his engagement with various therapies. We describe body image concerns in an obese adolescent with gender dysphoria to highlight the importance of assessing gender in adolescents.


A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts.
The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET) biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo. We assess changes in RhoA activity during mechanosensing of osteocytes within the bone and during neutrophil migration. We also demonstrate spatiotemporal order of RhoA activity within crypt cells of the small intestine and during different stages of mammary gestation. Subsequently, we reveal co-option of RhoA activity in both invasive breast and pancreatic cancers, and we assess drug targeting in these disease settings, illustrating the potential for utilizing this mouse to study RhoA activity in vivo in real time.


Association between chronic kidney disease and periodontitis. A systematic review and metanalysis.
Aims of this SR were to assess the association of Periodontitis (PD) with Chronic Kidney Disease (CKD) and with different CKD stages. MEDLINE, Cochrane Central Register of Trials and EMBASE, up to April 4, 2021 were searched. RCTs, prospective and retrospective cohort studies, case-control studies and cross-sectional studies were considered. JBI's Critical Appraisal Tool for risk of bias assessment was used. The risk of PD was calculated using the Mantel-Haenszel odds ratios (MH-OR); weighted mean difference for clinical attachment level (CAL) and periodontal probing depth (PPD) were also evaluated. Out of 1949 titles screened, 142 full texts were evaluated and 17 studies were included. CKD was associated to higher risk of PD (MH-OR = 2.36, [95% C.I. 1.25, 4.44]; p = 0.008), higher mean CAL (WMD = 0.41 mm [95% C.I. 0.22, 0.60]; p < 0.0001) and mean PPD (WMD = 0.25 mm [95% C.I. 0.03, 0.47]; p = 0.02) compared to healthy individuals. Severe CKD (stages 4-5 vs 2-3) resulted at higher risk of PD (MH-OR = 2.21, [95% C.I. 1.07, 4.54]; p = 0.03). Heterogeneity and risk of bias were high. An association between PD and CKD was found. It could be appropriate to consider PD a frequent CKD comorbidity.


Expression of epidermal growth factor receptor in the goat cumulus-oocyte complex.
It has been previously reported that epidermal growth factor (EGF) influences meiotic maturation and development competence of oocytes in various mammalian species. The present study was undertaken to analyze the expression of the gene encoding the EGF-receptor (EGF-R) in the goat cumulus-oocyte complex during meiotic competence acquisition. Expression of EGF-R mRNA was evaluated by PCR on reverse transcribed mRNA from follicular cells and oocytes, using EGF-R specific primers designed from human cDNA. The presence of the EGF-R transcript was evidenced in follicular cells as well as in meiotically competent and incompetent oocytes. Western blot analysis performed with specific anti EGF-R antibody revealed in meiotically competent and incompetent oocytes and in follicular cells a 170 kD polypeptide corresponding to the goat EGF-R protein. In oocytes the amount of EGF-R increased with meiotic competence acquisition. EGF-R distribution was examined by indirect immunofluorescence on frozen sections of cumulus-oocyte complexes (COCs). EGF-R immunoreactivity was observed in cumulus cells and in oocytes. Staining appeared to be confined to the periphery of the cells for both oocytes and cumulus cells. In this study, we identified the main component required for signaling via EGF-R in the goat oocyte and in follicular cells. These results suggest a possible involvement of EGF in the regulation of follicular growth and oocyte maturation in goat.


Immunologic defense mechanisms of the ocular surface.
The ocular surface represents an immunologic microcosm in which certain local immunologic and paraimmunologic defense systems analogous or identical to those of other mucosal surfaces are operative. These defenses include a resident normal flora; intrinsic anatomic barriers; secretion of mucous and certain chemical bacteriostatics and bacteriolytics; local humoral (slgA) antibody secretion; and local T-lymphocyte cellular responses. A series of sophisticated mechanisms has evolved to defend the ocular surface against diverse environmental pathogens. Often, the activation of one system leads to the subsequent activation of another, providing a highly integrated, series of mechanisms for host defense. And, it is clear that close integration of these various mechanisms provides a highly efficient amplification system for host defense, so that when one mechanism fails to deal with the invading pathogen the next mechanism is then efficiently initiated. Only in those situations where the pathogen overwhelms these defense systems, or is of such a persistent nature that it becomes resistant to removal by these various mechanisms, or alternatively is able to subvert its identity and, therefore, evade these mechanisms do organisms infect and cause disease. It is undoubtedly the complex interaction of all of these defense systems, both paraimmunologic and immunologic, which finally determines the integrity of the ocular surface.


Rutaecarpine may improve neuronal injury, inhibits apoptosis, inflammation and oxidative stress by regulating the expression of ERK1/2 and Nrf2/HO-1 pathway in rats with cerebral ischemia-reperfusion injury.
Cerebral ischemia-reperfusion (CI/R) injury is a more serious brain injury caused by the recovery of blood supply after cerebral ischemia for a certain period of time. Rutaecarpine (Rut) is an alkaloid isolated from Evodia officinalis with various biological activities. Previous studies have shown that Rut has a certain protective effect on ischemic brain injury, but the specific molecular mechanism is still unknown. In this study, a rat model of CI/R was established to explore the effects and potential molecular mechanisms of Rut on CI/R injury in rats. The results showed that Rut alleviated neuronal injury induced by CI/R in a dose-dependent manner. Besides, Rut inhibited neuronal apoptosis by inhibiting the activation of caspase 3 and the expression of Bax. In addition, Rut alleviated the inflammatory response and oxidative stress caused by CI/R through inhibiting the production of pro-inflammatory factors (IL-6 and IL-1β), lactate dehydrogenase (LDH), malondialdehyde (MDA) and ROS, and increased the levels of anti-inflammatory factors (IL-4 and IL-10) and superoxide dismutase (SOD). Biochemically, Western blot analyses showed that Rut inhibited the phosphorylation of ERK1/2 and promoted the expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway-related proteins (Nrf2, heme oxygenase 1 (HO-1) and NAD (P) H-quinone oxidoreductase 1) in a dose-dependent manner. These results show that Rut may alleviate brain injury induced by CI/R by regulating the expression of ERK1/2 and the activation of Nrf2/HO-1 pathway. In conclusion, these results suggest that Rut may be used as an effective therapeutic agent for damage caused by CI/R.


Characterization of axonally transported glycoproteins in regenerating garfish olfactory nerve.
This study examined changes in composition and concanavalin A (Con A) binding of axonally transported glycoproteins and their pronase-generated glycopeptides in regenerating garfish olfactory nerve. A previous study had demonstrated a regeneration-related increase in the proportion of [3H]glucosamine label in lower-molecular-weight Con A-binding glycopeptides derived from transported glycoproteins. Further analysis of carbohydrate composition shows that these molecules resemble mannose-rich oligosaccharides in composition and are increased in absolute amount in regenerating nerve. Subcellular analysis shows that the Con A-binding glycopeptides are enriched in membrane subfractions, particularly in a high-density fraction that morphologically resembles isolated cell surface coat. Regeneration-related changes in intact axonally transported glycoproteins were also detected. Sodium dodecyl sulfate gel electrophoresis of transport-labeled glycoproteins disclosed growth-correlated increases in radioactivity associated with 180-200K, 105-115K, and 80-90K components, while a 150-160K molecular weight class of glycoproteins was diminished in relative labeling. Intact glycoproteins displaying an affinity for Con A were also augmented in regenerating nerve, the increases occurring primarily in molecules in the 50-140K range.


Crystal structure of (μ-1,4-di-carb-oxy-butane-1,4-di-carboxyl-ato)bis-[bis-(tri-phenyl-phosphane)silver(I)] di-chloro-methane tris-olvate.
The mol-ecular structure of the tetra-kis(tri-phenyl-phosphan-yl)disilver salt of butane-1,1,4,4-tetra-carb-oxy-lic acid, [Ag2(C8H8O8)(C18H15P)4]·3CH2Cl2, crystallizes with one and a half mol-ecules of di-chloro-methane in the asymmetric unit. The coordination complex exhibits an inversion centre through the central CH2-CH2 bond. The Ag(I) atom has a distorted trigonal-planar P2O coordination environment. The packing is characterized by inter-molecular T-shaped π-π inter-actions between the phenyl rings of the PPh3 substituents in neighbouring mol-ecules, forming a ladder-type superstructure parallel to [010]. These ladders are arranged in layers parallel to (101). Intra-molecular hydrogen bonds between the OH group and one O atom of the Ag-bonded carboxyl-ate group results in an asymmetric bidendate coordination of the carboxyl-ate moiety to the Ag(I) ion.


Prospective randomised comparative study of pulse spray and conventional local thrombolysis.
To compare the time required to achieve lysis with the pulse spray technique and the conventional slow continuous infusion technique. Prospective randomised open Study. Eighteen patients suitable for intra-arterial thrombolytic therapy with conventional and pulse spray technique were randomised 1:1 to receive either pulse spray thrombolysis with 0.33 mg/ml rt-PA injected as a bolus of 0.2 ml or conventional thrombolysis with 0.05 mg/ml rt-PA infused at a rate of 10 ml/h. The age, duration of symptoms, length of occlusion and prethrombolysis ankle brachial pressure index were comparable in the two groups. The median duration of thrombolytic therapy in the pulse spray group was 195 min (range 90-1260) compared to 1390 min (range 300-2400) in the Conventional group. The difference between the two groups was significant, p < 0.002 (Mann-Whitney test). Significantly shorter time is required to achieve local thrombolysis with pulse spray compared to the conventional infusion method.


Close-to-native bone repair via tissue-engineered endochondral ossification approaches.
In order to solve the clinical challenges related to bone grafting, several tissue engineering (TE) strategies have been proposed to repair critical-sized defects. Generally, the classical TE approaches are designed to promote bone repair via intramembranous ossification. Although promising, strategies that direct the osteogenic differentiation of mesenchymal stem/stromal cells are usually characterized by a lack of functional vascular supply, often resulting in necrotic cores. A less explored alternative is engineering bone constructs through a cartilage-mediated approach, resembling the embryological process of endochondral ossification. The remodeling of an intermediary hypertrophic cartilaginous template triggers vascular invasion and bone tissue deposition. Thus, employing this knowledge can be a promising direction for the next generation of bone TE constructs. This review highlights the most recent biomimetic strategies for applying endochondral ossification in bone TE while discussing the plethora of cell types, culture conditions, and biomaterials essential to promote a successful bone regeneration process.


The impact of climatic conditions on the dynamics of tick-borne encephalitis in Slovakia in 2012-2016.
The main aim of our work was to analyse the development of the dynamics of tick-borne encephalitis (TBE) in connection with climatic conditions in Slovakia in 2012-2016. We performed the analysis based on the data provided by the Epidemiological Information System and the Slovak Hydrometeorological Institute. The study group consisted of 639 patients with confirmed diagnosis. The highest incidence of TBE was recorded in 2016. The highest standardized incidence rate of TBE was in the districts of the Trenčín, Žilina and Banská Bystrica regions. The relation of TBE to air temperature showed that most cases of TBE were recorded at an air temperature of 10-20 °C during the months of May to October in 2012-2016. The relationship between air temperature and number of days with snow cover and the number of TBE cases proved to be statistically significant (p-value < 0.001). There is a statistically significant difference in the average number of disease cases according to the air temperature category (p-value = 0.03). This disease occurs mainly in districts with an altitude of 200-400 m a. s. l. The dynamics of TBE in Slovakia is two-peaked with a decline in August. The main season of the disease lasts from May to October, peaking during the summer months of June and July. The results of the study point to a prognosis of the development of the disease in connection with air temperature. Based on the findings that in recent years we have observed a slightly increasing trend of TBE in Slovakia due to climate change, this disease is considered a persistent public health problem.


MCM2 mutation causes autosomal dominant nonsyndromic hearing loss (DFNA70): novel variant in the second family.
Pathogenic variants in MCM2 could result in mild to severe sensorineural hearing loss in the affected individuals (deafness, autosomal dominant 70; DFNA70; OMIM: 616968), an extremely rare autosomal dominant progressive disorder. Here, we report a novel missense variant (NM_004526:c.388C>T, p.R130C; Clinvar: SCV002072508) in MCM2 in an Iranian family identified by whole-exome sequencing and confirmed by Sanger sequencing. The heterozygous variant (NM_004526:c.388C>T, p.R130C) in MCM2 was identified in the proband and his mother. The proband is a nine-year-old male born to nonconsanguineous parents. The proband was characterized by nonsyndromic hearing loss, while his mother showed a mild form of the disorder. This study reports the second disease-causing variant in MCM2 in the world and confirms that hearing loss arising from variants in MCM2 is nonsyndromic. Nevertheless, as was reported in the previous family, phenotype could vary among the patients with the same variant.


Identification of G protein-coupled receptors required for vitellogenin uptake into the oocytes of the red flour beetle, Tribolium castaneum.
Previous studies suggested that a membrane receptor might be involved in mediating vitellogenin (Vg) uptake and juvenile hormone (JH)-regulated remodeling of follicular epithelium (also called 'patency'). G protein-coupled receptor (GPCR) family is one of the largest membrane receptor protein families and controls many key physiological processes. To investigate the role of GPCRs in insect reproduction and juvenile hormone-regulated Vg uptake, we performed a comprehensive RNA interference (RNAi) screen targeting GPCRs in the red flour beetle, Tribolium castaneum. Out of 112 GPCRs tested, knockdown of 41 GPCRs resulted in a reduction in fecundity. Interestingly, RNAi against two GPCRs (a Rhodopsin-like receptor and a Dopamine D2-like receptor) led to a significant reduction in Vg accumulation in developing oocytes. Functional assays of these two GPCRs showed that JH triggers a dose-dependent inhibition of intracellular cAMP levels in HEK293 cells expressing Tribolium Dopamine D2-like receptor. These data suggest that Dopamine D2-like receptor plays crucial roles in regulating Vg uptake and is a promising candidate membrane receptor mediating JH regulation of patency in the red flour beetle.


Diagnosis of Mycoplasma pneumoniae infection by microparticle agglutination and antibody-capture enzyme-immunoassay.
The performance of two new commercial assays for the serological diagnosis of Mycoplasma pneumoniae infection (microparticle agglutination and antibody-capture enzyme-immunoassay) was studied using a panel of 169 serum samples from patients with Mycoplasma pneumoniae pneumonia and a control group. Both assays were shown to be sensitive and specific for diagnosis. The performance of the capture immunoassay, however, decreased in older patients, probably due to its inability to detect cases of reinfection without IgM antibody response.


Arterial aging: a review of the pathophysiology and potential for pharmacological intervention.
This review begins with a perspective on the effects of arterial aging on society and world events over the past century. Until recently, the use of just one technique to measure blood pressure non-invasively limited progress in understanding the mechanisms involved and the potential of antihypertensive drug therapies. New methods for extracting information from the arterial waveform have followed the (re)introduction of arterial tonometry into clinical practice, together with mathematical analysis in the frequency and time domains. These new methods have exposed the phenomenon of aortic stiffening with age, and early wave reflection arising therefrom, and identified it as the major cause of cardiovascular degeneration. Such findings point to arterial aging as a logical target for the treatment and prevention not only of cardiac, aortic and large artery disease, but also of damage to microvessels in the brain and kidney, which in turn leads insidiously to dementia and renal failure, respectively.


Effects of oxygen supplementation on acute mountain sickness symptoms and functional capacity during a 2-kilometer walk test on Chajnantor plateau (5050 meters, Northern Chile).
The aim of this study was to test the hypothesis that administration of low-flow oxygen will improve physical performance in subjects unacclimatized to altitude. We evaluated the effects of oxygen supplementation on functional capacity and acute mountain sickness (AMS) symptoms in young, healthy male and female subjects who performed a 2-km fast walk test following rapid ascent to the Chajnantor plateau (5050 m above sea level) in Northern Chile. The participants were randomly distributed into 2 groups according to oxygen supplementation levels: 1 or 3 L O(2) · min(-1). Within each group, males and females were evaluated separately. A preliminary walk test was carried out at sea level on a 100-m long, flat track with 10 U-turns. For the first walk at altitude, subjects carried the supplementary oxygen system but did not breathe the oxygen. Subjects received oxygen through a facemask the following day during the second test. The nights prior to altitude tests were spent at 2400 m in San Pedro de Atacama. Supplementary oxygen administration during a 2-km walk test significantly improved walking times at 5050 m. We also observed a significant improvement in AMS symptoms. As expected, however, performance was poorer at altitude compared to test values at sea level, despite supplementary oxygen administration. Our findings demonstrate the beneficial effects of supplementary oxygen administration on physical capacity, reducing the incidence of AMS and, thus, improving health and safety conditions for high altitude workers following rapid ascent, when adequate acclimatization is not possible.


Correlates of prior HIV testing and schistosomiasis treatment: Baseline survey findings from the "creating demand for fishermen's schistosomiasis HIV services" (FISH) cluster-randomized trial in Mangochi, Malawi.
Fishing exposes fishermen to schistosomiasis-infested fresh water and concurrently through precarious livelihoods to risky sexual behaviour, rendering these two infections occupational hazards for fishermen. This study aimed to characterize the knowledge of the two conditions to obtain necessary data for a subsequent cluster randomized trial designed to investigate demand creation strategies for joint HIV-schistosomiasis service provision in fishing villages on the shores of southern Lake Malawi. Enumeration of all resident fishermen in 45 clusters (fishing communities) was carried out between November 2019 and February 2020. In a baseline survey, fishermen reported their knowledge, attitudes and practices in the uptake of HIV and schistosomiasis services. Knowledge of HIV status and previous receipt of praziquantel were modelled using random effects binomial regression, accounting for clustering. Prevalence of willingness to attend a beach clinic was computed. A total of 6,297 fishermen were surveyed from the 45 clusters with harmonic mean number of fishermen per cluster of 112 (95% CI: 97; 134). The mean age was 31.7y (SD: 11.9) and nearly 40% (2,474/6,297) could not read or write. Overall, 1,334/6,293 (21.2%) had never tested for HIV, with 64.4% (3,191/4,956) having tested in the last 12 months, and 5.9% (373/6290) taking antiretroviral therapy (ART). In adjusted analyses, being able to read and write (adjusted risk ratio [aRR: 1.91, 95% CI: 1.59-2.29, p<0.001); previous use of praziquantel (aRR: 2.00,95% CI: 1.73-2.30, p<0.001); knowing a relative or friend who died of HIV (aRR: 1.54,95% CI: 1.33-1.79, p<0.001); and being on ART (aRR: 12.93, 95% CI: 6.25-32.93, p<0.001) were associated with increased likelihood of ever testing for HIV. Only 40% (1,733/4,465) had received praziquantel in the last 12 months. Every additional year of age was associated with 1% decreased likelihood of having taken praziquantel in the last 12 months (aRR: 0.99, 95% CI: 0.98-0.99, p<0.001). However, recent HIV testing increased the likelihood of taking praziquantel by over 2-fold (aRR 2.24, 95% CI: 1.93-2.62, p<0.001). Willingness to attend a mobile beach clinic offering integrated HIV and schistosomiasis services was extremely high at 99.0% (6,224/6,284). In a setting with an underlying high prevalence of both HIV and schistosomiasis, we found low knowledge of HIV status and low utilization of free schistosomiasis treatment. Among fishermen who accessed HIV services, there was a very high likelihood of taking praziquantel suggesting that integrated service delivery may lead to good coverage. This trial is registered in the ISRCTN registry: ISRCTN14354324; date of registration: 05 October 2020.


The suppression of experimental allergic encephalomyelitis in Lewis rats by treatment with myelin basic protein-cell conjugates.
Pretreatment of Lewis rats with guinea pig (GP) myelin basic protein (MBP) coupled to syngeneic spleen leukocytes (SL) suppressed the subsequent induction of experimental allegic encephalomyelitis (EAE) with GP-MBP in Freund's complete adjuvant. The degree of suppression correlated positively with the amount of antigen coupled to the SL. GP-MBP coupled to syngeneic red blood cells (RBC) also resulted in suppression of EAE and the extent of the suppression was related to the dose of cells. These regimens of pretreatment also resulted in a decrease in the in vitro lymphocyte proliferative response to GP-MBP and in the extent of perivascular cuffing in the spinal cord. No decrease in the anti-MBP antibody response was detected in rats pretreated with either GP-MBP-SL or GP-MBP-RBC conjugates. Transfer of lymph node cells from rats pretreated with GP-MBP-RBC resulted in a decrease in disease severity in recipients. It is concluded that prior administration of MBP-cell conjugates is an effective way of suppressing the symptoms of EAE.


Implications of fungal infections and mycotoxins in camel diseases in Saudi Arabia.
Natural feed ingredients (corn, barley and wheat bran) and compound feed (manufactured pellet) are two types of fodder used for animal feeding, especially camel in Saudi Arabia. Twenty samples of each type of fodder were collected from seven different regions and screened for the presence of fungi, aflatoxins, ochratoxin and zearalenone. Fungal isolation of natural feed ingredients yielded 10 genera and 38 species of different fungi. Compound fodder samples were contaminated with 16 genera and 32 species of fungi. Total counts of Aspergillus, Penicillium and Fusarium in the animal feed samples were ranged from 54 to 223 × 10(3), 31.9 to 60 × 10(3) and 18 to 29 × 10(3) CFU/g, respectively. These isolates when tested for aflatoxin, ochratoxin and zearalenone producing ability, revealed this property in only four isolate, identified as Aspergillus flavus, A. parasiticus, A. ochraceus and Fusarium graminaerum. The percentage of toxigenic fungi was ranged from 5.5% to 30% for natural feed ingredients and from 4.5% to 20% for compound feed. The incidence of aflatoxins (AFT) in samples of natural feed ingredients was found to be ranged from 1 to 24.8 ppb, ochratoxin A (OTA) ranged from 1 to 44 ppb and zearalenone (ZON) ranged from 1 to 23 ppb. Contamination of compound feed with aflatoxin and ochratoxin A was ranged from 1 to 6.4 ppb and 1 to 4.7 ppb, respectively. All samples collected were found contaminated with fungi or their toxins and natural feed samples were more contaminated compared to compound feed samples. The concentrations detected were in the allowed limit (<20 ppb) except four samples of natural feed ingredients which were above the allowed limit of the tested mycotoxins. In conclusion, feed samples were contaminated with fungi and some toxigenic isolates which were responsible about mycotoxin production. Some samples had exceeded amount of AFT, OTA and ZON and may be contaminated with other mycotoxins which mean implication of fungi in camel health problems and death in Saudi Arabia.


Patients admitted to the new central hospital in Bhutan.
A new 100-bedded hospital was opened in Thimphu, the capital of Bhutan, in 1974. The hospital serves a large district, and also acts as a referral hospital for the rest of the country. This study analyses the first complete year of running the hospital with a full medical staff.


The Ideal Cortical Button Location on the Lateral Femur for Anterior Cruciate Ligament Suspensory Fixation is 30 mm Proximal to the Lateral Epicondyle.
To determine the ideal location for anterior cruciate ligament (ACL) suspensory cortical button placement on the lateral femur with the highest failure load and to establish the relationship of tunnel diameter and cortical thickness on load to failure. Computed tomography (CT) data were obtained from 45 cadaveric distal femurs. A Cartesian coordinate system was established along the lateral femur with the lateral epicondyle (LE) as a reference point. Locations 0, 20 and 30 mm from the LE along lines 0°, 25°, 50°, and 75° posterioproximal from the axial plane were created. Tunnels connecting from each location to the center of the ACL footprint were simulated. Cortical thickness and long axis diameter of the oval cortical holes were determined for each location. Based on the CT data, custom drill guides were created and used to drill 4.5 mm tunnels at each lateral femur location to the ACL footprint on the cadaver femurs. Cortical buttons were placed at each location and pulled using a servohydraulic testing system. The correlation of tunnel diameter and cortical thickness to button failure load were analyzed using a regression analysis. Significant differences were found for failure load (P<.0001) and cortical thickness between the locations tested (P<.0001). The location 30 mm proximal from the LE and 75⁰ from the axial plane had the highest failure load of 573 N. A regression analysis (R2 = .15) indicated that the cortical thickness was significantly correlated with load to failure (P <.0001), whereas the long-axis diameter was not (P = .33). The ideal cortical button location on the lateral femur for ACL suspensory fixation was located 30 mm proximal from the lateral epicondyle, based on this area's high failure load. Oblique tunnel drilling of this proximal location may cause a larger long-axis diameter cortical hole, but the cortex is also thicker, which is more closely correlated with failure load. Different ACL suspensory cortical button locations on the lateral femur have different failure loads based on the cortical thickness of the bone supporting the button. It is important for surgeons to understand which drilling techniques place the button in a proximal and posterior location, especially if the bone quality of the patient is of concern.


Salbutamol increases tristetraprolin expression in macrophages.
Tristetraprolin (TTP) is a tandem zinc finger protein that can bind to AU-rich elements (AREs) in the 3'-untranslated regions (3'-UTR) in mRNAs of transiently expressed genes, e.g. tumor necrosis factor-alpha (TNF-alpha) and granulocyte macrophage colony-stimulating factor (GM-CSF). TTP increases the turnover rate of the target mRNAs, thereby reducing, for example, the expression of TNF-alpha and GM-CSF. We examined the role of beta(2)-agonists, cAMP analogs, and forskolin (an activator of adenylate cyclase) on TTP mRNA and protein expression by quantitative real-time RT-PCR and Western blotting in J774 murine macrophages and THP-1 human macrophages. All of these agents increased TTP expression. A nonspecific inhibitor of phosphodiesterases (PDEs) 3-isobutyl-1-methylxanthine (IBMX) and type IV PDE-inhibitor rolipram further enhanced the increase in TTP expression levels, suggesting a cAMP-mediated effect. A possible mediator of these effects is transcription factor activator protein 2 (AP-2), whereas nuclear factor kappaB (NF-kappaB) seemed not to play any role. This mechanism may, at least in part, explain the anti-inflammatory effects which beta(2)-agonists have been reported to have in macrophages.


Combined treatment with a traditional Chinese medicine, Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) and alendronate improves bone microstructure in ovariectomized rats.
Hachimi-jio-gan is one of the most common recipes in traditional Chinese, Japanese and Korean medicines and has been used for preventing and treating various diseases associated with aging, including osteoporosis. The present study was performed to examine the combined effects of a traditional Chinese medicine, Hachimi-jio-gan (HJG) and antiresorptive agent, alendronate (ALN) on ovariectomy-induced bone loss in rats. Six-month-old female Sprague-Dawley rats were underwent ovariectomy (OVX) or sham operation. Eight weeks later, the OVX rats were treated either with HJG or ALN alone or in combination of both. The skeletal response was evaluated using micro-computed tomography (micro-CT), image analysis software, and biochemical markers. This study demonstrated that treatment with HJG or ALN alone increased trabecular bone volume and bone mineral density (BMD), and partially improved bone microstructure of the proximal tibia and vertebra in OVX rats. Treatment with ALN to OVX rats resulted in significant reduction in both bone resorption and bone formation. Treatment with HJG to OVX rats inhibited bone resorption, with no marked effects on bone formation. Combined treatment of HJG and ALN significantly improved trabecular bone mass and bone microstructure, compared with either agent alone. We conclude that the combined treatment with HJG and ALN has beneficial effects on trabecular bone mass, improving the structural properties of both tibia and vertebra in OVX rats.


Gallbladder stones and gallbladder polyps associated with increased risk of colorectal adenoma in men.
Most cases of colorectal cancer develop via an adenoma to carcinoma sequence. Gallbladder polyps share some risk factors with colorectal polyps. Little is known about the relationship between gallbladder diseases and different status of colorectal polyps by gender. This study was to investigate the association of gallbladder stones and polyps with colorectal adenomas by gender in a Taiwanese population. A total of 7066 eligible subjects who underwent a total colonoscopy as a part of health check-up between January 2001 and August 2009 were recruited. Colonoscopic findings were classified into polyp-free, non-neoplastic polyps and colorectal adenomas. Gallbladder stones and gallbladder polyps were diagnosed based on ultrasonographic findings. There was a significant difference in the status of colon polyps between subjects with and without gallbladder polyps. However, the status of colon polyps was not significantly different between subjects with or without gallbladder stones. After adjusting obesity, fasting plasma glucose, and other variables, there was a positive relationship between gallbladder polyps and colorectal adenomas (odds ratio [OR]: 1.396, 95% confidence interval [CI]: 1.115-1.747) but not non-neoplastic polyps in all subjects. In men, gallbladder polyps (OR: 1.560, 95% CI: 1.204-2.019) and gallbladder stones (OR: 1.465, 95% CI 1.081-1.984) were positively associated with colorectal adenomas. In women, neither gallbladder polyps nor gallbladder stones were significantly related to colon polyps. Both gallbladder polyps and gallbladder stones were associated with an increased risk of colorectal adenomas in men but not in women. Gender difference was significant for the association between gallbladder lesions and colorectal polyps.


Oncoplastic reduction mammoplasty for breast cancer in women with macromastia: Oncological long-term outcomes.
To evaluate the long-term results of tumorectomy and concomitant bilateral oncoplastic reduction mammoplasty (ORM) for early stage breast cancer patients with macromastia in terms of local disease control and long-term oncological results. Data of 82 patients with macromastia undergoing ORM for breast cancer between 1996 and 2011 were retrospectively examined and evaluated with regard to oncological results. The median age was 50 years. The median follow-up was 121 months (range 28-212 months). The median breast volume was 1402 cm3 and the median weight of excised breast material was 679 g. The median surgical margin was 16 mm. Ten-year local recurrence rate was 8.7%. The 10-year overall survival rate was 82.2% and the disease-free survival rate was 73.2%. Early and late complication rates were 12.2% and 14.6%, respectively. From the standpoint of local disease control and long-term observation, ORM can be considered a very safe and acceptable treatment for early stage breast cancer in women with macromastia.


Magnetic resonance imaging diagnosis and new classification of the osteoporotic vertebral fracture.
The purpose of this study was to investigate the usefulness of magnetic resonance imaging (MRI) in the diagnosis of, and when deciding on treatment policies for, vertebral fractures in patients with osteoporosis by comparing the diagnostic success rates for such fractures using MRI and plain radiographs. We also devised a new classification of vertebral fractures in osteoporotic patients based on MRI findings. The subjects were 34 patients with a total of 316 osteoporosis-related vertebral fractures treated in our department during the past 2 years. They consisted of 30 women and 4 men with an average age of 82 years (range 61-95 years). The site diagnostic rates of plain radiographs and MRI for the vertebral fractures were compared, and changes in signal intensity of the fractured vertebrae in MRI were examined. The areas of change in signal intensity in T1-weighted sagittal images were classified into six types: total, anterior, posterior, superior, inferior, central. The site diagnostic rate for vertebral fractures was 98% for MRI, which was better than the 87% obtained with plain radiographs. Changes in signal intensity in the vertebrae showed no intraspinal protrusion in the inferior and superior types, and neurological stability was achieved; but there was a high frequency of intraspinal protrusion in the total and posterior types.


The influence of the decompressive operation on the intracranial pressure and the pressure-volume relation in patients with severe head injuries.
Measurements of intracranial pressure by ventricular catheter were performed in 47 patients with severe head injuries. Thirty-three patients with decompressive operations such as osteoclastic craniotomy and dilatation by means of duraplastic have been compared with 14 patients with closed heads with regard to volume pressure response (intracranial elasticity). This was determined either by intraventricular injection of 2ml saline or by drainage of cerebrospinal fluid. The examination clearly shows that patients with closed heads have a much higher intracranial elasticity than patients who have decompressive operations, so that in the first group minor differences of the intracranial volume cause extreme deviations of the intracranial pressure. Therefore, the decompressive operation has been advised in severe head injuries with increased intracranial pressure as a measure additional to high dose dexamethasone therapy and hyperventilation.


Tuning inflammation response via adjusting microstructure of hydroxyapatite and biomolecules modification.
Excellent biocompatibility and inflammatory regulation ability are essential to bone repair materials. Herein, Rod-like HAP with a diameter of 0.1 μm and Flake-like HAP with a width of 0.5-1 μm were synthesized by hydrothermal method, and then combined with two kinds of biomolecules, Icariin and Kaempferol. Two kinds of HAPs have similar crystal structure, but different zeta potentials and specific surface area. Rod-like HAP possesses stronger loading capacity and internalization efficiency than Flake-like one. in vitro inflammation assay reveals that HAP particles up-regulate the expression of IL-1β, TNF-α, IL-6, IL-10, IFN-γ and IL-2 cytokines. HAP particles loaded with Icariin or Kaempferol biomolecules up-regulate anti-inflammatory cytokines and down-regulate the expression of inflammatory cytokines.


Hepathic, biochemical, hematological, and histological effects of the ultracavitation in rabbits livers.
To collect data capable of pointing out the effects of the ultracavitation treatment on the liver of rabbits after adipose tissue application, by means of histological analyses of the liver and hematological and biochemical exams. This is an experimental study with 12 albino rabbits as sample, which were divided into 3 groups and submitted to a hypercaloric diet for one month. Subsequently, subjects underwent UCV treatment: 3 minutes, 30 W, continuous mode at 100%, every 2 ERAS = 441.02 J/cm2, intensity of 10w/cm2. They were then euthanized and underwent biopsy after 24 hours. After 48 hours from the ultracavitation treatment, the animals' livers presented greater amount of fat infiltration if compared to the amount presented 96 hours after the treatment. However, laboratory tests showed no alterations. Values were maintained within normal parameters of cholesterol, triglycerides, liver enzymes, hemoglobin and hematocrit levels. This study has identified that infiltrates may appear on livers after the treatment, despite high hematological and biochemical tests results. The fat infiltrates reduction 96 h after treatment suggests lower risks to animal health, if the period between applications is respected.


Immunoception: Defining brain-regulated immunity.
The emerging understanding of homeostatic neuroimmune interactions requires developing relevant terminology. In this NeuroView, Koren and Rolls define "immunoception" as the brain's bidirectional monitoring and control of immunity. They propose that the physiological trace storing immune-related information, the "immunengram," is distributed between the brain and memory cells residing in peripheral tissues.


Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab.
BCD-022 is a trastuzumab biosimilar which was shown to be equivalent to reference trastuzumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to comparatively assess efficacy and safety of BCD-022 and reference trastuzumab in combination with paclitaxel used as the therapy of metastatic HER2(+) breast cancer. Pharmacokinetics and immunogenicity were also studied. Patients with no previous treatment for metastatic HER2(+) breast cancer were randomly assigned 1:1 to BCD-022 or reference trastuzumab and were treated with trastuzumab + paclitaxel. Therapy continued for 6 cycles of therapy (every 3 weeks), until progression of the disease or unbearable toxicity. Primary study endpoint was overall response rate. Study goal was to prove equivalent efficacy of BCD-022 and reference trastuzumab. Equivalence margins for 95% CI for difference in overall response rates were set at [- 20%; 20%]. In total 225 patients were enrolled into the study, 115 in BCD-022 arm and 110 in reference trastuzumab arm. Overall response rate was 49.6% in BCD-022 arm and 43.6% in reference trastuzumab arm. Limits of 95% CI for difference of overall response rates between arms were [(- 8.05)-19.89%], thus, they lied within predetermined equivalence margins [- 20%; 20%]. Profile of adverse events was similar between groups (any AEs were reported in 93.81% of patients in BCD-022 arm and 94.55% of patients in reference arm). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding antibody occurrence rate (either BAb or NAb) was found between BCD-022 (n = 3; 2.65%) and comparator (n = 4; 3.64%). Both drug products are characterized with low occurrence rate and short life of anti-trastuzumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures: AUC0-504, Сmах, Тmax, T1/2. Analysis of Ctrough did not reveal any significant inter-group differences as well. Thus, results of this study have demonstrated therapeutic equivalence of trastuzumab biosimilar BCD-022 and referent trastuzumab drug. The trial was registered with ClinicalTrials.gov (Study Number NCT01764022 ). The date of registration was January 9, 2013.


What happened to harmonization of the PTSD diagnosis? The divergence of ICD11 and DSM5.
The development of ICD11 and DSM5 was seen as an opportunity to harmonize the two major classification systems for mental disorders. The proposed ICD11 and DSM5 diagnostic criteria for PTSD are markedly different. The implications of this remain to be seen, but have the potential to cause confusion to PTSD sufferers, clinicians, researchers and others impacted on by the condition.


Absorption of polycyclic aromatic hydrocarbons to cellulose.
Polycyclic aromatic hydrocarbons (PAHs) are widespread toxic chemicals. The environmental fate of these chemicals is in part controlled by sorption to (organic matter in) sediments and soils. One of the most abundant organic matter compounds on earth is cellulose. Remarkably, sorption of PAHs to cellulose has hardly been studied; only two reports on the binding of some low-molecular-weight PAHs exist in the literature. In this study, sorption of PAHs to cellulose was investigated in more detail, by measuring isotherms for a series of 13 PAHs, covering a wide hydrophobicity range. The results indicated that sorption of PAHs to cellulose is a linear partition process for all PAHs investigated (phenanthrene-indeno[1,2,3-cd]pyrene). The affinity of PAHs for cellulose appeared to be about 400 times lower than for octanol and even up to 300000 times lower than for black carbon or coal. Linked to the estimated yearly production of cellulose and black carbon, these results suggest that cellulose is probably not a major environmental sorption domain for PAHs.


Effect of horticultural waste composting on infected plant residues with pathogenic bacteria and fungi: integrated and localized sanitation.
The aim of this work was to study the effect of composting on the viability of plant pathogenic fungi and bacteria. The research consisted of pilot-scale composting of horticultural waste in compost windrows. Studies were carried out on vegetable residues infected with plant pathogenic microorganisms included by either integrated or localized infection. In the first case, the plant pathogen viability was investigated when infected material was mixed throughout compost, while the localized infection was used to study the effect of the composting process on plant waste spot-inoculated with pathogenic microorganisms. Results for localized sanitation showed the total elimination of all tested phytopathogens between 48 and 120 h after composting began. In this case significant differences were observed in relation to 9 different zones in the pile. The disappearance of these microorganisms was similar when all plant waste included in the windrow was infected (integrated infection). Additionally, the results obtained confirmed that the bacteria showed a greater capacity to persist during composting than the fungi. Composting is therefore considered a useful method for recycling horticultural waste and eliminating phytopathogenic bacteria and fungi that inhabit this kind of residue.


[Massive reconstruction of acetabulum and proximal femur].
In revision hip surgery, allografts are useful for restoring the bone stock and allow the muscle fixation avoiding the use of massive metallic prothesis. We have reviewed 51 hip reconstructions with a follow up of 4 years and half (1982 - 1991). Indications were: - revision arthroplasties with destroyed acetabulum, - bone tumors (mainly chondrosarcoma). The results are good for pain, articular movement and the consolidation of the allograft host bone junction. Some complications were encountered: - Post-operative death (early or late for tumoral extension) in case of major surgery for tumor (4 cases). - Deep infections (2 cases). - Weakness of the gluteus medius with hip dislocation needing anti-dislocation device. - Aseptic serous fluid leak meaning immunobiologic reaction of bone grafts (3 cases). This surgery has to be compared to massive reconstruction prostheses, arthrodesis with limb shortening, femoral head and neck resection and in some cases inter ilio-abdominal amputation which gives also major post-operative complication.


Cytokinin signaling and transcriptional networks.
The cytokinin signaling pathway consists of a phosphorelay mechanism that is initiated by binding of cytokinin to histidine kinase receptors and culminates with the transcription of cytokinin-responsive genes in the nucleus. Type-B response regulators (ARR) encode transcription factors that act as major players in the transcriptional activation of cytokinin-responsive genes, among which are many transcription factors. In this review, we highlight the transcriptional networks regulated by cytokinin that have been identified and their roles in the regulation of a subset of the many developmental and physiological processes regulated by this plant hormone.


A case of moclobemide-induced hyperorgasmia.
Moclobemide-induced sexual hyperarousal of a female patient is presented. Remarkable similarities with a previously reported case and implications of the phenomenon are discussed.


Bulk Organic-Inorganic Methylammonium Lead Halide Perovskite Single Crystals for Indirect Gamma Ray Detection.
Scintillators that convert ionization radiation photons to UV-visible photons have attracted extraordinary attention. Traditional scintillators are associated with a vacuum photomultiplier tube that faces strict constraints of fragility, magnetic fields, and operated voltage, or coupled to a silicon photomultiplier (SiPM) with optical silicone grease. Here, we report a high-performance radiation detector with an indirect photon-to-photon conversion radiation detection model based on perovskite single crystals (SCs), where perovskite SCs have been directly integrated into the window of SiPM by using the solution growth method at low temperature. Tunable X (γ)-ray excited light emission in the range of 414 to 600 nm is obtained with different concentrations of Br doping, which greatly matches the response wavelength of SiPM. Small Br-doped CH3NH3PbBr0.05Cl2.95 SCs exhibit high transmittance and weak self-absorption, resulting in improved scintillation light emissions. Moreover, we have successfully collected a 137Cs source gamma-ray pulse height spectrum with the SiPM readout. The MAPbBr0.05Cl2.95 scintillator exhibits a decay time of 0.14 ± 0.02 ns and a light yield of 18 000 photons/MeV with an energy resolution of 10.5 ± 0.4% at 662 keV. The results indicate that the CH3NH3PbBrxCl3-x perovskite SCs could enable the next generation of low-cost, fast, and fine-energy resolution scintillators.


An odyssey in search of a cure: the evolution of treatment of childhood acute lymphoblastic leukemia in the United Kingdom.
This review charts the evolution of therapy for childhood acute lymphoblastic leukaemia (ALL) in the United Kingdom. The present chemotherapeutic regimen is the result of experience gained from carefully planned randomised cooperative studies carried out during the last two decades. In common with the experience of the West German and American groups, the best results have been in those treated with post remission intensification blocks. With current chemotherapy protocols, almost 70% of children with ALL in U.K. can be cured but there may be a medical cost of such a cure, in terms of both acute and long term toxicity. This was especially true when central nervous system (CNS) therapy with cranial irradiation was used. Therefore present regimens are examining chemotherapeutic options for CNS disease control and the efficacy of additional post remission intensification. Failure of chemotherapy is most often seen in those children with a presenting white cell count of more than 50 x 10(9)/l, very young children and/or the presence of certain chromosomal rearrangements (e.g. t4: 11, t9: 22). At present the optimum therapeutic option for such high risk patients and for the majority of those in second remission, is an allogenic bone marrow transplant if an HLA-matched sibling is available. Modern day therapy is both complicated and costly and will be beyond the resources available for most children with ALL in developing countries. A significant decrease in worldwide mortality due to ALL will only occur if either the disease can be prevented or a simpler cure devised.


Natural occurrence of ustiloxins in rice from five provinces in China and the removal efficiencies of different milling steps.
The widespread incidence of "false smut" disease in rice has caused extensive ustiloxin contamination around the world. Until now there has been a lack of knowledge regarding the natural occurrence of ustiloxins in paddy. The development of efficient removal methods is also still a challenge that remains unexplored. In the current study, three main ustiloxins - ustiloxin A (UA), ustiloxin B (UB), and ustiloxin G (UG) - were determined simultaneously by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in 206 paddy samples collected in 2021 from five rice-producing provinces in China. The predominant ustiloxin was UA with an occurrence of 46.1% and an average concentration of 49.71 μg kg-1 . This was followed by UB (31.1%, 13.31 μg kg-1 ) and UG (18.4%, 9.19 μg kg-1 ). No targeted ustiloxins were detected in white rice samples randomly collected from supermarkets in Shanghai. To reveal the causes, two approaches were tested for the removal of the ustiloxins: most of the targeted ustiloxins (>93%) were removed in brown rice by husking and, subsequently, all targeted ustiloxins (100%) were removed by whitening. A wide distribution of ustiloxins was discovered in paddy samples in this study. The UA contaminations were significantly different depending on their origin, with the highest occurrence in paddy from Shanghai and Jiangsu, southeast coast provinces in China. Contamination by UG was also found in paddy for the first time and was strongly correlated with those of UA and UB. A combination of husking and whitening has been verified to be a practicable and promising way to ensure efficient removal and food safety. © 2023 Society of Chemical Industry.


Real-time assessment of tissue oxygen saturation during endovascular therapy for chronic limb threatening ischemia using a novel oximeter.
In the present study, we have introduced a novel real-time, near-infrared spectroscopy oximeter, the TOE-20 (Astem, Co, Ltd, Kawasaki, Japan), which can simultaneously measure the regional tissue oxygen saturation (rSO2) in the skin and subcutaneous tissue at three angiosomes of the foot. Seven patients with chronic limb threatening ischemia who had undergone successful revascularization of the superficial femoral artery were included. The analysis revealed a significant correlation between the rSO2 and skin perfusion pressure. After revascularization, the rSO2 and skin perfusion pressure had both increased at the three regions, although the increase at the plantar foot was insignificant. These results indicate that the TOE-20 can be successfully used to monitor the rSO2 during endovascular treatment.


Nonsteroidal anti-inflammatory drug use and the risk of cognitive impairment and Alzheimer's disease.
Some observational studies have established an association between exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and a decreased risk of subsequently developing Alzheimer's disease (AD). Mild cognitive impairment or cognitive impairment, not dementia (CIND) is more likely to convert to AD, and no specific preventive method is currently available. The objective of this study was to determine the association of NSAID use in 5276 cognitively normal subjects of the Canadian Study of Health and Aging, a 10-year population-based cohort study, with the incidence of CIND, AD, and all-cause dementia. Hazard ratios were calculated from Cox proportional hazards models with age as the time scale according to three study samples including 824 cases of dementia (563 cases of AD), 630 cases of dementia (435 cases of AD), and 883 cases of CIND, respectively. Adjustments were made for gender, education, lifestyle factors, comorbid diseases, and vascular risk factors. Lower risks for AD and all-cause dementia were significantly associated with the use of any NSAIDs and the salicylates without barbiturates subgroup in the study sample including subjects with CIND at baseline. There was a weak association between any NSAIDs and the risk of CIND (hazard ratio, 0.87; 95% confidence interval, 0.76-1.00). These results suggest that there is an association between NSAID use and a lower incidence of AD and, to a lesser extent, of CIND.


Pharmacokinetics of single-dose cefuroxime in porcine intervertebral disc and vertebral cancellous bone determined by microdialysis.
Pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates. Nevertheless, tissue pharmacokinetic studies of relevant antimicrobials in both prophylactic and therapeutic situations are still sparse. Previous approaches based on bone biopsy and discectomy exhibit important methodological limitations. The objective of this study was to assess the C3-C4 intervertebral disc (IVD), C3 vertebral body cancellous bone, and subcutaneous adipose tissue (SCT) pharmacokinetics of cefuroxime by use of microdialysis in a large animal model. This was a single-dose, dense sampling large animal study of cefuroxime spine penetration. Ten female pigs were assigned to receive 1,500 mg of cefuroxime intravenously over 15 minutes. Measurements of cefuroxime were obtained from plasma, SCT, vertebral cancellous bone, and IVD for 8 hours thereafter. Microdialysis was applied for sampling in solid tissues. For both IVD and vertebral cancellous bone, the area under the concentration curve from zero to the last measured value (AUC(0-last)) was significantly lower than that of free plasma. As estimated by the ratio of tissue AUC(0-last) to plasma AUC(0-last), tissue penetration (95% confidence interval) of cefuroxime was significantly incomplete for the IVD 0.78 (0.57; 0.99), whereas for vertebral cancellous bone 0.78 (0.51; 1.04) and SCT 0.94 (0.73; 1.15) it was not. The penetration of cefuroxime from plasma to the IVD was delayed, and the maximal concentration and the elimination of cefuroxime were also reduced compared with both SCT and vertebral cancellous bone. Because of this delay in elimination of cefuroxime, the time with concentrations above the minimal inhibitory concentration (T(>MIC)) was significantly longer in the IVD compared with the remaining compartments up to MICs of 6 µg/mL. Microdialysis was successfully applied for serial assessment of the concentration of cefuroxime in the IVD and the vertebral cancellous bone. Penetration of cefuroxime from plasma to IVD was found to be incomplete and delayed, but because of a prolonged elimination, superior T(>MIC) was found in the IVD up to MICs of 6 µg/mL.


MicroRNA-mediated epigenetic silencing of sirtuin1 contributes to impaired angiogenic responses.
Transforming growth factor (TGF)-β was linked to abnormal vessel function and can mediate impairment of endothelial angiogenic responses. Its effect on microRNAs and downstream targets in this context is not known. To study the role of microRNAs in TGF-β-mediated angiogenic activity. MicroRNA profiling after TGF-β treatment of endothelial cells identified miR-30a-3p, along with other members of the miR-30 family, to be strongly silenced. Supplementation of miR-30a-3p restored function in TGF-β-treated endothelial cells. We identified the epigenetic factor methyl-CpG-binding protein 2 (MeCP2) to be a direct and functional target of miR-30a-3p. Viral overexpression of MeCP2 mimicked the effects of TGF-β, suggesting that derepression of MeCP2 after TGF-β treatment may be responsible for impaired angiogenic responses. Silencing of MeCP2 rescued detrimental TGF-β effects on endothelial cells. Microarray transcriptome analysis of MeCP2-overexpressing endothelial cells identified several deregulated genes important for endothelial cell function including sirtuin1 (Sirt1). In vivo experiments using endothelial cell-specific MeCP2 null or Sirt1 transgenic mice confirmed the involvement of MeCP2/Sirt1 in the regulation of angiogenic functions of endothelial cells. Additional experiments identified that MeCP2 inhibited endothelial angiogenic characteristics partly by epigenetic silencing of Sirt1. TGF-β impairs endothelial angiogenic responses partly by downregulating miR-30a-3p and subsequent derepression of MeCP2-mediated epigenetic silencing of Sirt1.


Mass concentration coupled with mass loading rate for evaluating PM(2.5) pollution status in the atmosphere: A case study based on dairy barns.
This study investigated particulate matter (PM) loading rates and concentrations in ambient air from naturally ventilated dairy barns and also the influences of pertinent meteorological factors, traffic, and animal activities on mass loading rates and mass concentrations. Generally, relationships between PM2.5 concentration and these parameters were significantly poorer than those between the PM loading rate and the same parameters. Although ambient air PM2.5 loading rates correlated well with PM2.5 emission rates, ambient air PM2.5 concentrations correlated poorly with PM2.5 concentrations in the barns. A comprehensive assessment of PM2.5 pollution in ambient air, therefore, requires both mass concentrations and mass loading rates. Emissions of PM2.5 correlated strongly and positively with wind speed, temperature, and solar radiation (R(2) = 0.84 to 0.99) and strongly but negatively with relative humidity (R(2) = 0.93). Animal activity exhibited only moderate effect on PM2.5 emissions, while traffic activity did not significantly affect PM2.5 emissions.


Corrigendum: Impact of body composition on prognosis and dose-limiting toxicities on metastatic colorectal cancer.
[This corrects the article DOI: 10.3389/fnut.2021.671547.].


[Carpal Malalignment in Malunited Fractures of the Distal Radius].
To evaluate and classify carpal alignment in malunited fractures of the distal radius. On standardized lateral radiographs of the involved wrist of 72 patients with a symptomatic extra-articular malunion of the distal radius, 43 with a dorsal and 29 with a palmar angulation, radius tilt (RT), radiolunate (RL) and lunocapitate angle were measured. Malposition of the radius was defined as RT plus 11° in dorsal malunion and RT minus 11° in palmar malunion. A palmar tilt of the radius was marked with a minus sign. At the time of corrective osteotomy 9 dorsal malunions underwent for different reasons evaluation of the scapholunate ligament with 4 having a complete scapholunate ligament disruption. With respect to the RL-angle, carpal malalignment was categorized as follows: type P with a RL-angle less than -12°, type K with a RL-angle between -12 and 10°, type A with a RL-angle more than 10°, but less than the malposition of the radius, type D with a RL-angle greater than the malposition of the radius. All types of carpal malalignment were found in both, dorsally and palmarly tilted malunion. Type A carpal alignment was identified as the leading type in dorsal malunion (25 out of 43 patients), whilst in palmar malunion colinear subluxation of the carpus (type C) was the dominant type (12 out of 29 patients). To return the hand to a neutral position the rotation of the lunate was compensated by a contrarotation of the capitate in the dorsal malunion. In the palmar malunion a dorsal extension of the capitate returned the hand to a neutral position. In 4 of the 5 patients with type D carpal alignment, who had scapholunate ligament evaluation, a complete ligament tear was found. In this study four different types of carpal alignment in malunited extra-articular fractures of the distal radius were identified. Based on this data we suspect that type D carpal alignment in dorsal malunion may be associated with a scapholunate ligament tear. Therefore, we recommend wrist arthroscopy for this group of patients.


Understanding Treatment Response in Individual Profiles of Men with Prostatic Enlargement at Risk of Progression.
It is unclear how cumulative multivariable effects of clinically relevant covariates impact response to pharmacological treatments for lower urinary tract symptoms (LUTS)/benign prostatic enlargement (BPE). To develop models to predict treatment response in terms of International Prostate Symptom Score (IPSS) and the risk of acute urinary retention (AUR) or BPE-related surgery, based on large data sets and using as predictors baseline characteristics that commonly define the risk of disease progression. A total of 9167 patients with LUTS/BPE at risk of progression in three placebo-controlled dutasteride trials and one comparing dutasteride, tamsulosin, and dutasteride + tamsulosin combination therapy (CT) were included in the analysis to predict response to placebo up to 24 mo and active treatment up to 48 mo. Predictors included age, IPSS, total prostate volume (PV), maximum urinary flow rate (Qmax), prostate-specific antigen, postvoid residual urine (PVR), α-blocker usage within 12 mo, and randomised treatment. A generalised least-squares model was developed for longitudinal IPSS and a Cox proportional-hazards model for time to first AUR/surgery. The vast majority of patients benefit from dutasteride or CT when compared with tamsulosin alone. The predicted IPSS improvement with dutasteride or CT increased with greater PV and severity of symptoms at baseline. The tamsulosin effect was lower with greater baseline PV and tended to decrease over time. Predicted AUR/surgery risk was greater with tamsulosin versus CT or dutasteride; this risk increased with larger PV, higher PVR, and lower Qmax (all at baseline). An educational interactive web-based tool facilitates visualisation of the results (www.bphtool.com). Limitations include: the placebo and active-treatment predictions are from different studies, the lack of similar studies for external validation, and the focus on a population at risk of progression from the 4-yr CombAT study. Predictive modelling based on large data sets and visualisation of the risk for individual profiles can improve our understanding of how risk factors for disease progression interact and affect response to different treatments, reinforcing the importance of an individualised approach for LUTS/BPE management. We used data from previous studies to develop statistical models for predicting how men with lower urinary tract symptoms or benign prostate enlargement and at risk of disease complications respond to certain treatments according to their individual characteristics.