Combination of synthetic acaricides with (E)-cinnamaldehyde to control Rhipicephalus microplus.
This work had the objectives to (1) evaluate the susceptibility of various Rhipicephalus microplus populations to commercial acaricides, and (2) select commercial acaricides (50-80% effective) and evaluate the effects of binary combinations of the phenylpropanoid (E)-cinnamaldehyde with selected commercial acaricides to control R. microplus under laboratory and field conditions. Using adult immersion tests with 116 populations and 14 commercial acaricides, products showing 50-80% effectiveness (percent control) with the lowest number of active ingredients were selected. Acaricides containing amitraz or chlorfenvinphos were tested in combination with (E)-cinnamaldehyde on a field population (strain CM). We found that (E)-cinnamaldehyde enhanced the activity of both commercial acaricides against R. microplus larvae; however, the enhancement was more accentuated when using amitraz. Experiments combining (E)-cinnamaldehyde + amitraz on unfed larvae and engorged females from another population (strain Gyn) were performed, verifying (E)-cinnamaldehyde enhanced the activity of amitraz. In the field experiment, the application of (E)-cinnamaldehyde appeared toxic to the tick hosts (cattle). We concluded that (E)-cinnamaldehyde enhanced the activity of amitraz against unfed larvae and engorged females of R. microplus; however, in the field test this phenylpropanoid caused intoxication in the cattle. Studies searching for new combinations of compounds from essential oils with amitraz deserve attention, as well as studies to develop formulations using amitraz + (E)-cinnamaldehyde that will be efficient and will not have toxic effects in cattle.


Edible fungus degrade bisphenol A with no harmful effect on its fatty acid composition.
Bisphenol A (BPA) is an endocrine-disrupting chemical that is ubiquitous in the environment because of its broad industrial use. The authors report that the most widely cultivated mushroom in the world (i.e., white-rot fungus, Pleurotus ostreatus) efficiently degraded 10mg/L of BPA in 7 days. Extracellular laccase was identified as the enzyme responsible for this activity. LC-MS analysis of the metabolites revealed the presence of both low- and high-molecular-weight products obtained via oxidative cleavage and coupling reactions, respectively. In particular, an analysis of the fatty acid composition and chemical structure of the fungal mycelium demonstrated that exposure to BPA resulted in no harmful effects on this edible fungus. The results provide a better understanding of the environmental fate of BPA and its potential impact on food crops.


The effect of melatonin on spinal cord after ischemia in rats.
Experimental animal model to assess ischemic spinal cord injury (SCI) following occlusion of the thoraco-abdominal aorta. In the present study, we aimed to investigate the role of melatonin on SCI induced by ischemia and following reperfusion. Animal Research Laboratory, Inonu University, Malatya, Turkey. We evaluated oxidative damage and caspase-3 activity. In total, 32 adult Wistar albino rats were divided into four groups: Group 1, control (n=8); Group 2 (n=8), those subjected to ischemia/reperfusion (IR) by clamping the thoraco-abdominal aorta; Group 3 (n=8), melatonin (50 mg kg(-1)) treated; and Group 4 (n=8), melatonin (50 mg kg(-1)) followed by ischemia. All animals were kept alive for 48 h, and then spinal cord samples were removed. We assayed oxidative damage by measuring malondialdehyde (MDA), apoptosis by measuring activated caspase-3 (using immunoblots) and intrinsic antioxidative capacity by measuring reduced glutathione (GSH) levels in the spinal cord. The results indicated a significant decrease in activity of caspase-3 in SCI animals after treatment with melatonin, as it significantly decreased the formation of MDA and decelerated the loss of GSH. This study suggested that melatonin could be an effective neuroprotective agent for treatment of SCI.


Basics of compounding: basics of compounding with organic salts.
The purity and form of all ingredients used in compounding, especially of active pharmaceutical ingredients, must be known and considered during formulation. When a prescription is received, it is the responsibility of the pharmacist, and should be routine procedure, to correctly determine whether or not the salt or base/acid form of a drug is to be used as the basis for the dose. This is important information because the bulk substance, or active pharmaceutical ingredient, in a salt form is not 100% active drug. The purpose of the salt form is usually to enhance the solubility of the drug, but it may also enhance and change other attributes of the drug that make it easier to handle and manipulate for producing dosage forms. Resources for the purpose of determining this information include the United States Pharmacopeia, product package insert, and a call to the manufacturer or physician as appropriate. This article discusses compounding with salts and the factors that may affect a final compounded preparation.


Studies on dopamine turnover in ovariectomized or hypophysectomized female rats. Effects of 17 beta-estradiol benzoate, ethynodioldiacetate and ovine prolactin.
The effects of 17 beta-estradiol benzoate (EB), ethynodioldiacetate and ovine prolactin on dopamine (DA) turnover have been studied. As an index for a change in turnover, differences in DA depletion following tyrosine hydroxylase inhibition with alpha-methyl-tyrosine methylester were observed. DA was measured by means of mass fragmentographical analysis in the rat median eminence, the olfactory tubercle and the striatum. The actions of ethynodioldiacetate and ovine prolactin on DA turnover in various subregions of the rat median eminence were analysed by quantitative microfluorimetry. Repeated injections of EB to ovariectomized rats resulted in a significant increase of DA turnover in the median eminence. Administration of ethynodioldiacetate to ovariectomized rats almost significantly increased DA turnover in the olfactory tubercle. In the median eminence DA turnover was significantly increased only in the lateral palisade zone. In male hypophysectomized rats ovine prolactin increased DA turnover in both the lateral and the medial palisade zone of the median eminence. The results support the involvement of DA neurons in the control of prolactin and luteinizing hormone secretion. It is suggested that the tubero-infundibular DA neurons are involved in mediating the central inhibitory feedback actions of prolactin and gonadal steroids on prolactin and LH secretion, respectively.


Express Sequence Tag Analysis - Identification of Anseriformes Trypsin Genes from Full-Length cDNA Library of the Duck (Anas platyrhynchos) and Characterization of Their Structure and Function.
Trypsins are key proteins important in animal protein digestion by breaking down the peptide bonds on the carboxyl side of lysine and arginine residues, hence it has been used widely in various biotechnological processes. In the current study, a full-length cDNA library with capacity of 5·10(5) CFU/ml from the duck (Anas platyrhynchos) was constructed. Using express sequence tag (EST) sequencing, genes coding two trypsins were identified and two full-length trypsin cDNAs were then obtained by rapid-amplification of cDNA end (RACE)-PCR. Using Blast, they were classified into the trypsin I and II subfamilies, but both encoded a signal peptide, an activation peptide, and a 223-a.a. mature protein located in the C-terminus. The two deduced mature proteins were designated as trypsin-IAP and trypsin-IIAP, and their theoretical isoelectric points (pI) and molecular weights (MW) were 7.99/23466.4 Da and 4.65/24066.0 Da, respectively. Molecular characterizations of genes were further performed by detailed bioinformatics analysis. Phylogenetic analysis revealed that trypsin-IIAP has an evolution pattern distinct from trypsin-IAP, suggesting its evolutionary advantage. Then the duck trypsin-IIAP was expressed in an Escherichia coli system, and its kinetic parameters were measured. The three dimensional structures of trypsin-IAP and trypsin-IIAP were predicted by homology modeling, and the conserved residues required for functionality were identified. Two loops controlling the specificity of the trypsin and the substrate-binding pocket represented in the model are almost identical in primary sequences and backbone tertiary structures of the trypsin families.


The levels and distribution of organochlorine pesticides (OCPs) in sediments from the Haihe River, China.
The levels and distribution patterns of the selected organochlorine pesticides (OCPs=p,p'-DDT, o,p'-DDT, p,p'-DDE, p,p'-DDD, alpha-, beta-, gamma- and delta-HCH) in surficial sediments from the Haihe River and Dagu Drainage River of Tianjin were investigated by means of gas chromatography coupled with micro-electronic capture detector (GC-microECD). Concentrations of OCPs in the sediments from the Haihe River ranged from 1.88 to 18.76ng g(-1) (mean 7.33ng g(-1)) for sum HCH, 0.32-80.18ng g(-1) (mean 15.94ng g(-1)) for sum DDT. Compared with the Haihe River, the Dagu Drainage River was much more contaminated by HCHs and DDTs, wherein sum HCH ranged from 33.24 to 141.03ng g(-1) (mean 87.74ng g(-1)) and sum DDT ranged from 3.60 to 83.49ng g(-1) with a mean value of 35.52ng g(-1). The concentration distribution of sum DDT and sum HCH was different indicated their different contamination sources. Composition analyses indicated that a recent usage or discharge of HCH and DDT into the Dagu Drainage River.


Editorial Commentary: Off-Track Hill-Sachs Lesions in Adolescents With Multiple Anterior Dislocations: The Case for Stabilizing Adolescent First-Time Dislocators.
Recurrent anterior dislocations in adolescents reveal a high rate of off-track Hill-Sachs lesions, much higher than in adults. This new information makes a strong case in favor of arthroscopic Bankart repair for adolescents with a first-time anterior dislocation of the shoulder.


In vivo testing of an infection-resistant annuloplasty ring.
An infection-resistant surface incorporated into a prosthetic cardiac valve has great potential clinical applications. A sewing ring construct was created using ciprofloxacin-treated polyester. Then ciprofloxacin-treated and untreated constructs were implanted subcutaneously on the dorsum of rats and inoculated with Staphylococcus aureus. At 7, 14, and 30 days animals were sacrificed and the implants were retrieved. Each implant was assessed for frank purulence and gross tissue incorporation by a blinded observer. The implants were processed for conventional histology and examined by a blinded Pathologist. Ciprofloxacin-treated rings were also implanted in the absence of a bacterial challenge. At explantation, a maximal zone of inhibition, if present, was measured. Finally, ciprofloxacin was eluted with methanol from the explanted segments and the concentration of ciprofloxacin eluted was determined. Ciprofloxacin-treated sewing rings had greater gross tissue incorporation than untreated rings in the presence of a bacterial challenge (P=0.005). Ciprofloxacin-treated rings also had a lower incidence of frank purulence, but this did not reach statistical significance. After 14 days of implantation, ciprofloxacin treated rings had fewer neutrophils (P=0.018) and greater histological tissue incorporation (P=0.017) than untreated rings. The explanted ciprofloxacin-treated rings maintained a zone of inhibition of 3.0+/-1.0 mm after 1 day of implantation and 1.3+/-0.6 mm after 2 days. Ciprofloxacin could be eluted in significant quantities from the explanted rings after 7 days of implantation. Ciprofloxacin treated polyester can be incorporated into an annuloplasty ring construct that demonstrates excellent tissue incorporation and infection resistance. This study supports the use of this construct in the mitral position in a large animal model.


Influencing the national policy process: the role of health consumer groups.
Whilst recent research has focused on consumer involvement at local level in the UK, there have been few studies of the representation of user, carer and patients' interests nationally. This paper concentrates on the role of health consumer groups in representing the collective interests of patients, users and carers in the national policy process. The research consisted of (a) a semi-structured postal questionnaire survey of 123 health consumer groups; (b) semi-structured interviews with key informants from 39 health consumer groups; and (c) semi-structured interviews with 31 policy actors. Health consumer groups were diverse in their origins, scope and structure, and undertook a wide range of activities relating to policy and service provision. Whilst around half the groups described their primary purpose as service provision, over four-fifths identified influencing policy at national level as 'very important' or 'important'. Health consumer groups had developed relationships with civil servants, ministers, MPs and peers to widen their policy objectives. Key facilitators in the policy process included experiential knowledge, relationships with policy makers and working in alliances with other health consumer groups or other stakeholders. Key barriers included problems relating to the political agenda, problems with the consultation process, lack of resources and working within a context of unequal power relationships. Health consumer groups are becoming increasingly involved in the health policy process and collectively are becoming an increasingly influential stakeholder. They have a key role to play in ensuring that the patient, user and carer voice is heard in the policy process.


Acupuncture in the treatment of fatigue in Parkinson's disease: A protocol for systematic review and meta-analysis.
Fatigue is a commonly occurring nonmotor symptom among individuals of Parkinson's disease (PD). Little is known about how to measure fatigue in PD. This study is aiming to investigate the safety and efficacy of acupuncture for PD-related fatigue. RCTs of acupuncture for PD-related fatigue will be retrieved from inception to July 2020 in 9 different databases such as Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and so on. Search words will be used for the BC and acupuncture. The analysis would include randomised, controlled, clinical trials of PD patients with fatigue that were published in either Chinese or English. The primary outcome is the fatigue condition. Two or three reviewers should be in charge of study selection, data extraction and evaluating the risk of bias. RevMan software (V.5.3) will be used to perform the assessment of the risk of bias and data synthesis. To provide evidence for the efficacy and safety of acupuncture treating PD-related fatigue. This study will be helpful for understanding the effect and safety of acupuncture for PD-related fatigue. CRD42020160823.


Phytate-iron molar ratio and bioavailability of iron in Bangladesh.
Phytate, an important component of plant origin foods, works as a chelator for mineral nutrients such as iron. Estimating the phytate-iron molar ratio is a traditional method to assess the bioavailability of dietary iron, and a ratio >1 is suggestive of poor absorption of iron through the intestinal mucosa. In Bangladesh, the ratio is considerably higher; nonetheless, the haemoglobin and ferritin status are satisfactory. Hence, we appraised phytate-iron molar ratios and concomitant haemoglobin and ferritin status. Dietary intake of iron and phytate was estimated in non-pregnant non-lactating women and school-age children from a nationally representative survey. The phytate-iron molar ratios were estimated. Linear regressions on haemoglobin for the phytate-iron molar ratios and on molar ratios predicting inflammation-adjusted ferritin were performed. The median ratios were 6.12 in women and 5.47 in children, with corresponding haemoglobin concentrations of 12.6 and 12.5 g/dl. Hypothetical lowering of the ratios by ~50% revealed a nominal increment of haemoglobin and ferritin. The standard cut-off phytate-iron molar ratio of >1 is inconsistent with the iron and haemoglobin status of the Bangladeshi population. One plausible explanation for the inconsistency is a non-dietary environmental factor-groundwater iron. Isotope studies incorporating the iron from dietary and the drinking groundwater sources are needed to establish a ratio which might better explain iron bioavailability.


PI3K/PTEN signaling in tumorigenesis and angiogenesis.
The phosphatidyl inositol 3-kinase (PI3K) can be activated by a variety of extracellular signals and involved in a number of cellular processes including cell proliferation, survival, protein synthesis, and tumor growth. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is an antagonist of PI3K. The alterations of PI3K pathway such as activation of oncogenes, gene amplification, and inactivation of tumor suppressors, commonly occur in many human cancers. Angiogenesis is required for tumor growth and metastasis when the tumor reaches more than 1 mm in diameter. Recent studies have shown that PI3K and Akt play an important role in regulating tumor growth and angiogenesis through VEGF and HIF-1 expression. PI3K regulates the expression of these two proteins through HDM2 and p70S6K1 in human cancer cells. The frequent dysregulation of the PI3K/PTEN pathway in human cancer demonstrates that this pathway is an appropriate target for cancer therapeutics. In this review, we describe the recent advances in understanding the PI3K/PTEN pathway, the role and mechanism of PI3K in regulating tumor growth and angiogenesis, and the potential therapeutic opportunities for targeting this pathway for cancer treatment.


Pitfalls in liver imaging.
Localized, abnormal attenuation/intensity areas on unenhanced and/or enhanced study of CT/MR imaging do not necessarily correspond to tumors themselves or real tumor size. Pitfalls in the diagnosis of liver tumor are described dividing into enhanced study (vascular variants, vascular abnormalities, hyperplastic nodules, around the tumor, and miscellaneous) and unenhanced study (fatty change, focal spared area of diffuse fatty liver, and miscellaneous).


Heteroduplex analysis of the nonhomology region between Moloney MuLV and the dual host range derivative HIX virus.
The dual host range virus HIX has been previously characterized as an envelope gene recombinant between Moloney murine leukemia virus (Mo-MuLV) and an unidentified xenotropic murine leukemia virus. Using long reverse transcripts of Mo-MuLV, a region of nonhomology has been mapped by electron microscopic analysis of heteroduplexes formed with HIX 35S virion RNA. In this nonhomology region, the Mo-MuLV cDNA strand measured approximately 900 nucleotides, mapping between 1.6 and 2.5 kilobases from the 3' end. In a previous study, hybridization of Mo-MuLV 21S RNA with Mo-MuLV cDNA resulted in the formation of different heteroduplex structures diagnostic of a noncontiguously coded leader sequence at the 5' end of the 21S RNA. Following hybridization of poly(A)+ HIX 21S RAN with 8.2 kb Mo-MuLV cDNA, analogous heteroduplex structures were observed exhibiting the Mo-MuLV:HIX substitution loop in the DNA:RNA segment of the molecules. This analysis permitted more precise mapping of the nonhomology region with respect to the splice point in the 21S presumptive glycoprotein mRNA. The mapping of this nonhomology region in HIX virus provides an internal visual marker for the 3' end of the genome which may prove useful in future analyses of other deletion or substitution derivatives of Mo-MuLV.


Orbital metastasis from cutaneous malignant melanoma.
Orbital metastasis is a rare presenting sign of a cutaneous malignant melanoma. Fewer than 30 cases of orbital metastases have been published so far. A 69-year-old man was remitted to our clinic for removal of an orbital tumour verified with CT. Fine-needle aspiration biopsy revealed the tumour to be a metastasis from a cutaneous malignant melanoma diagnosed 4 years earlier. The patient died 3 months after detection of the orbital metastatic tumour. This case illustrates the value of simple fine-needle aspiration biopsy in the diagnosis of orbital tumours.


Molecular cloning and characterization of the inositol 1,4,5-trisphosphate receptor in Drosophila melanogaster.
We isolated a cDNA encoding an inositol 1,4,5-trisphosphate receptor (InsP3R) of Drosophila melanogaster. The predicted Drosophila InsP3R (2,833 amino acids) has extensive sequence similarity to the mouse InsP3R. The polypeptide encoded by the cDNA was functionally expressed and showed characteristic InsP3-binding activity. The Drosophila InsP3R gene is located at the region 83A5-9 on the third chromosome and expresses throughout development but predominantly in the adult. Localization of the InsP3R mRNA in adult tissues suggests strong expression in the retina and antenna, indicating the involvement of the InsP3R in visual and olfactory transduction. In addition, the InsP3R mRNA is abundant in the legs and thorax, which are enriched with a muscular system. Such localization is apparently consistent with the quantitatively predominant sites for [3H]InsP3 binding in Drosophila and the fleshfly (Boettcherisca peregrina). The present study points to the likely functional importance of the InsP3/Ca2+ signaling system in Drosophila.


A monoclonal antibody demonstrating specificity for drug-resistance cells.
We have described a monoclonal antibody with specificity for permeability-altered drug-resistant cells. This gamma G2b antibody was characterized by antibody-mediated complement-dependent cytotoxicity and by immunofluorescence analysis using a flow cytometer-cell sorter. Further experiments with the flow cytometer showed that vinblastine=resistant cells exposed to that drug had a wider range of fluorescence intensity and had a modal channel 4 times as bright as the same cells cultured in growth medium. We believe that this monoclonal antibody recognizes part of the "P' glycoprotein found on drug-resistant Chinese hamster ovary cells.


Prediction of cerebral hyperperfusion syndrome after carotid artery stenting by CT perfusion imaging with acetazolamide challenge.
Cerebral hyperperfusion syndrome (HPS) is an uncommon but serious complication of carotid artery stenting (CAS). The purpose of this study was to investigate the efficacy of CT perfusion imaging (CTP) with acetazolamide challenge to identify patients at risk for HPS after CAS. We retrospectively analyzed 113 patients who underwent CTP with rest and acetazolamide challenge before CAS. CTP maps were assessed for absolute and relative cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and change of each parameter before and after acetazolamide challenge. Patients were divided into two groups according to the HPS after the CAS. Receiver-operating characteristic (ROC) curve analysis was performed to determine the most accurate CTP parameter for the prediction of HPS. Nine of 113 patients had HPS. There were significant differences for absolute and relative values of resting CBF (p = 0.001 and p = 0.026), resting MTT (p < 0.001 and p = 0.004), post-acetazolamide CBF (p < 0.001 and p = 0.001), post-acetazolamide MTT (p < 0.001 and p = 0.002), and % changes of CBF (p = 0.009) between the HPS and non-HPS groups. ROC curve analysis showed that the CTP parameters with the maximal area under the receiver-operating characteristic curve (AUC) for HPS was the absolute value of post-acetazolamide MTT (AUC 0.909) and the absolute value of resting MTT (AUC 0.896). Pretreatment CTP with acetazolamide challenge could identify patients at risk for HPS after CAS. Although the CTP parameter that most accurately identified patients at risk for HPS was the absolute value of post-acetazolamide MTT, resting MTT was sufficiently accurate.


Neurotrophic action of Alzheimer's disease brain extract is due to the loss of inhibitory factors for survival and neurite formation of cerebral cortical neurons.
Cell cultures of neonatal rat cerebral cortex in a serum-free medium were used to investigate whether specific neurotrophic factors are accumulated or inhibitory factors for neuronal survival and neurite formation decrease in AD brain extract. Neurotrophic activity in brain extract was quantified by using the ELISA for microtubule-associated protein 2 (MAP2). Inhibitory factors, which blocked neurotrophic activity, were present in normal brain extract. In AD brain extract, loss of the inhibitory factors resulted in a relative increase in neurotrophic activity. The inhibitory factors in normal brain extract were retained on the ultrafiltration membrane with molecular weight cutoff of 10 kDa.


Mandibular reconstruction in adults: a review.
Mandibular defects may result from trauma, inflammatory disease and benign or malignant tumours. Mastication, speech and facial aesthetics are often severely compromised without reconstruction. The goal of mandibular reconstruction is to restore facial form and function, implying repair of mandibular continuity and muscle attachments. There should also be room for implant insertion so as to allow for rehabilitation of occlusion and articulation, whereas the function of the inferior alveolar nerve should be restored to assure adequate sensitivity of the lips. Mandibular reconstruction principles and techniques have evolved dramatically over the years. Refinements in techniques continue to improve patient quality of life. This paper reviews current techniques of mandibular reconstruction in adults and discusses the strengths and weaknesses of each.


Ergonomics for the inclusion of older workers in the knowledge workforce and a guidance tool for designers.
The ageing of the population and the inverted population pyramid is bringing important changes to society as a whole. These changes are associated with the inclusion of an older workforce in knowledge work and the challenge they represent in adapting the work environment accordingly. In order to approach a more universal design of the work environment, industrial designers need support from user-sensitive inclusive design studies. While there are plenty of guidelines and tools containing relevant information, there is a need to develop more appropriate tools for Industrial Designers that cover the initial phase of the design process. This study provides a review of the available tools and guidelines and proposes a theoretical framework intended for developing a design guidance tool for inclusive workstation design.


Follow-up study in eyes with choroidal neovascularization caused by presumed ocular histoplasmosis.
Sixty-four eyes of 60 patients with ocular histoplasmosis, and choroidal neovascularization documented by fluorescein angiography, and not treated with photocoagulation, were followed for an average of 29 months. The primary determinant of visual outcome was the proximity of the neovascular membrane to the fovea. Sixty-four percent of eyes with membranes 0.25 disk diameter or greater from the fovea had a final visual acuity of 6/12 (20/40) or better, and 71% of such eyes maintained or improved initial visual acuity. All eyes with subfoveal neovascularization had a poor visual result. Other factors related to visual prognosis included initial visual acuity, size of the neovascular membrane, size of sensory retinal detachment, and presence of hemorrhage.


Next-generation sequencing-based 5' rapid amplification of cDNA ends for alternative promoters.
Mammalian genomes contain many unknown alternative first exons and promoters. Thus, we have modified the existing 5'RACE (5' rapid amplification of cDNA ends) approach into a next-generation sequencing (NGS)-based new protocol that can identify these alternative promoters. This protocol has incorporated two main ideas: (i) 5'RACE starting from the known second exons of genes and (ii) NGS-based sequencing of the subsequent cDNA products. This protocol also provides a bioinformatics strategy that processes the sequence reads from NGS runs. This protocol has successfully identified several alternative promoters for an imprinted gene, PEG3. Overall, this NGS-based 5'RACE protocol is a sensitive and reliable method for detecting low-abundant transcripts and promoters.


The reliability of prayer-based self-efficacy scale to assess self-confidence of Muslims with low back pain.
Low back pain (LBP) may challenge an individual's self-confidence to perform usual daily activities such as Islamic daily prayer. Existing self-efficacy scales may not be appropriate to assess individual's self-confidence to perform Islamic prayers. This study aimed to develop a scale to assess self-confidence to prepare and perform Islamic prayer in the presence of LBP, the Islamic Prayer-based Self-efficacy Scale (IpbSeS), and to determine its consistency. The IpbSeS consists of three parts: pre-prayer preparation, getting to and from the mosque, and positions and movements during prayer. On a scale of 0 to 6, 0 indicates 'not at all confident' and 6 'fully confident'. Sixty individuals with LBP gave their responses on two different visits. Pain intensity was assessed by the Visual Analogue Scale (VAS), and the pain intensity changes were assessed using a seven-point global patient rating scale. Descriptive statistics, Pearson's correlation coefficient, Wilcoxon test and t-test were used in the analysis (alpha set at 0.05). VAS scores did not differ significantly between visits. No association was found between VAS and age (r = 0.039, p = 0.77) and between VAS and body mass index (BMI; r = 0.06, p = 0. 67). All 28 questions have consistent responses on two visits (0.75 ≤ r ≤ 0.99, p < 0.001 for all) indicating a very high reliability. IpbSeS appears to be a reliable instrument to assess the self-confidence of Muslims in the presence of LBP to pray.


Changes in cancer diagnoses and stage distribution during the first year of the COVID-19 pandemic in the USA: a cross-sectional nationwide assessment.
The emergence of COVID-19 disrupted health care, with consequences for cancer diagnoses and outcomes, especially for early stage diagnoses, which generally have favourable prognoses. We aimed to examine nationwide changes in adult cancer diagnoses and stage distribution during the first year of the COVID-19 pandemic by cancer type and key sociodemographic factors in the USA. In this cross-sectional study, adults (aged ≥18 years) newly diagnosed with a first primary malignant cancer between Jan 1, 2018, and Dec 31, 2020, were identified from the US National Cancer Database. We included individuals across 50 US states and the District of Columbia who were treated in hospitals that were Commission on Cancer-accredited during the study period. Individuals whose cancer stage was 0 (except for bladder cancer), occult, or without an applicable American Joint Committee on Cancer staging scheme were excluded. Our primary outcomes were the change in the number and the change in the stage distribution of new cancer diagnoses between 2019 (Jan 1 to Dec 31) and 2020 (Jan 1 to Dec 31). Monthly counts and stage distributions were calculated for all cancers combined and for major cancer types. We also calculated annual change in stage distribution from 2019 to 2020 and adjusted odds ratios (aORs) using multivariable logistic regression, adjusted for age group, sex, race and ethnicity, health insurance status, comorbidity score, US state, zip code-level social deprivation index, and county-level age-adjusted COVID-19 mortality in 2020. Separate models were stratified by sociodemographic and clinical factors. We identified 2 404 050 adults who were newly diagnosed with cancer during the study period (830 528 in 2018, 849 290 in 2019, and 724 232 in 2020). Mean age was 63·5 years (SD 13·5) and 1 287 049 (53·5%) individuals were women, 1 117 001 (46·5%) were men, and 1 814 082 (75·5%) were non-Hispanic White. The monthly number of new cancer diagnoses (all stages) decreased substantially after the start of the COVID-19 pandemic in March, 2020, although monthly counts returned to near pre-pandemic levels by the end of 2020. The decrease in diagnoses was largest for stage I disease, leading to lower odds of being diagnosed with stage I disease in 2020 than in 2019 (aOR 0·946 [95% CI 0·939-0·952] for stage I vs stage II-IV); whereas, the odds of being diagnosed with stage IV disease were higher in 2020 than in 2019 (1·074 [1·066-1·083] for stage IV vs stage I-III). This pattern was observed in most cancer types and sociodemographic groups, although was most prominent among Hispanic individuals (0·922 [0·899-0·946] for stage I; 1·110 [1·077-1·144] for stage IV), Asian American and Pacific Islander individuals (0·924 [0·892-0·956] for stage I; 1·096 [1·052-1·142] for stage IV), uninsured individuals (0·917 [0·875-0·961] for stage I; 1·102 [1·055-1·152] for stage IV), Medicare-insured adults younger than 65 years (0·909 [0·882-0·937] for stage I; 1·105 [1·068-1·144] for stage IV), and individuals living in the most socioeconomically deprived areas (0·931 [0·917-0·946] for stage I; 1·106 [1·087-1·125] for stage IV). Substantial cancer underdiagnosis and decreases in the proportion of early stage diagnoses occurred during 2020 in the USA, particularly among medically underserved individuals. Monitoring the long-term effects of the pandemic on morbidity, survival, and mortality is warranted. None.


Comparative studies of cardiovascular effects of a new dopamine agonist (SK&F 38393A) and dopamine.
SK&F 38393A (DAA) dose-dependently decreased the contractility of isolated frog hearts with an ED50 of 6.60 +/- 0.28 X 10(-5) M, while, dopamine (DA) elicited a dose-dependent increase in the contractility of the preparation with an ED50 of 5.13 +/- 0.36 X 10(-5) M. The results of in situ investigation, using cardiac output as the index of cardiac contractility, were in agreement with the in vitro results. Haloperidol (10(-6) M), a dopaminergic receptor blocker, did not block the cardiovascular effects of DAA and DA. However, propranolol (10(-8) M), a beta-adrenergic receptor blocker, prevented the positive inotropic effects of DA but had no effects on the negative inotropic effects of DAA. The results suggest that DAA might be acting on this preparation through a mechanism which is probably not associated with beta-adrenergic and/or dopaminergic receptors.


Contemporary Surgical Management of Pancreatic Necrosis.
For decades, infected or symptomatic pancreatic necrosis was managed by open surgical necrosectomy, an approach that has now been largely supplanted by an array of techniques referred to as the step-up approach. This review describes the evidence base behind the step-up approach, when to use the different techniques, and their technical basics. The most common treatment strategies are included: percutaneous drainage, video-assisted retroperitoneal debridement, sinus tract endoscopy, endoscopic transgastric necrosectomy, and surgical transgastric necrosectomy. Also included is the evidence base around management of common complications that can occur during step-up management, such as hemorrhage, intestinal fistula, and thrombosis, in addition to associated issues that can arise during step-up management, such as the need for cholecystectomy and disconnected pancreatic duct syndrome. The treatment strategies highlighted in this review are those most commonly used during step-up management, and this review is designed as a guide to the evidence base underlying these strategies, as surgeons tailor their therapeutic approach to individual patients.


[Mixed linear regression model for longitudinal data: application to an unbalanced anthropometric data set].
A longitudinal data set is characterized by a time sequence of two or more observations from each individual. In cohort studies, these data are usually not balanced. A data set related to longitudinal height measurements in children of HIV-infected mothers was recorded at the university hospital of the Federal University in Minas Gerais, Brazil. The objective was to assess the application of the mixed effect model to this unbalanced data set. At six months of age, on average boys were 1.8 cm taller than girls, and seroreverter infants were 2.9 cm taller than their HIV+ peers. At 12 months of age, on average boys were 2.4 cm taller than girls and seroreverter children were 3.5 cm taller than HIV+ ones. In addition to describing longitudinal height behavior, this model also includes the growth rate estimation for this infant population by gender and group.


A general approach to categorizing a continuous scale according to an ordinal outcome.
In practice, disease outcomes are often measured in a continuous scale, and classification of subjects into meaningful disease categories is of substantive interest. To address this problem, we propose a general analytic framework for determining cut-points of the continuous scale. We develop a unified approach to assessing optimal cut-points based on various criteria, including common agreement and association measures. We study the nonparametric estimation of optimal cut-points. Our investigation reveals that the proposed estimator, though it has been ad-hocly used in practice, pertains to nonstandard asymptotic theory and warrants modifications to traditional inferential procedures. The techniques developed in this work are generally adaptable to study other estimators that are maximizers of nonsmooth objective functions while not belonging to the paradigm of M-estimation. We conduct extensive simulations to evaluate the proposed method and confirm the derived theoretical results. The new method is illustrated by an application to a mental health study.


Antioxidant-restricted diet reduces plasma nonesterified fatty acids in trained athletes.
Nonesterified FA (NEFA) are a major fuel source for humans at rest and during moderate exercise. The effect of dietary antioxidant restriction on plasma NEFA levels and exercise performance in trained athletes was examined. Seventeen athletes followed a 2-wk restricted-antioxidant (R-AO) diet, which resulted in a threefold reduction in antioxidant intake (ascorbic acid, 139 to 49 mg; beta-carotene, 5093 to 1142 microg) and a significant (P = 0.001) reduction in the plasma NEFA. The amount and types of fat consumed were not different between the R-AO and habitual diets. Exercise time to exhaustion was not affected by the R-AO diet, but rating of perceived exertion (RPE) was significantly (P = 0.03) elevated. The increase in RPE may have occurred as a result of the R-AO diet and subsequent reduction in plasma NEFA; however, further research is required to confirm this conclusion.


Separation, detection, and identification of peptides by ion-pair reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry at high and low pH.
Bioactive peptides and tryptic digests of various proteins were separated under acidic and alkaline conditions by ion-pair-reversed-phase high-performance liquid chromatography (RP-HPIPC) in 200 microm I.D. monolithic, poly(styrene-divinylbenzene)-based capillary columns using gradients of acetonitrile in 0.050% aqueous trifluoroacetic acid, pH 2.1, or 1.0% triethylamine-acetic acid, pH 10.6. Chromatographic performances with mobile phases of low and high-pH were practically equivalent and facilitated the separation of more than 50 tryptic peptides of bovine serum albumin within 15-20 min with peak widths at half height between 4 and 10 s. Neither a significant change in retentivity nor efficiency of the monolithic column was observed during 17-day operation at pH 10.6 and 50 degrees C. Upon separation by RP-HPIPC at high-pH, peptide detectabilities in full-scan negative-ion electrospray ionization mass spectrometry (negESI-MS) were about two to three times lower as compared to RP-HPIPC at low-pH with posESI-MS detection. Tandem mass spectra obtained by fragmentation of deprotonated peptide ions in negative ion mode yielded interpretable sequence information only in a few cases of relatively short peptides. However, in order to obtain sequence information for peptides separated with alkaline mobile phases, tandem mass spectrometry (MS/MS) could be performed in positive ion mode. The chromatographic selectivities were significantly different in separations performed with acidic and alkaline eluents, which facilitated the fractionation of a complex peptide mixture obtained by the tryptic digestion of 10 proteins utilizing off-line, two-dimensional RP-HPIPC at high pH x RP-HPIPC at low pH and subsequent on-line identification by posESI-MS/MS.


Enhanced electrorheological activity of polyaniline coated mesoporous silica with high aspect ratio.
Polyaniline-coated mesoporous silica (PANI/mSiO2) materials with different aspect ratios (L/D=1, 5, and 10) were fabricated by a vapor deposition polymerization (VDP) method to investigate the geometric effect on electrorheological (ER) activity. The PANI/mSiO2 materials were dedoped by a facile NH4OH treatment to reduce the conductivity to a level appropriate for ER applications. Notably, the PANI/mSiO2-based ER fluids exhibited enhanced ER performance with increasing aspect ratio. In particular, the PANI/mSiO2 material with the highest aspect ratio manifested the highest ER activity, which was attributed to geometric effects on flow resistance and mechanical stability. Moreover, the ER materials with higher aspect ratios showed improved dielectric properties of large achievable polarizability and short relaxation time. Hence, the synergistic contribution of geometric effects and dielectric properties resulted in enhanced ER activity. Consequently, this study provides insight into an effective method to improve ER performance by simple manipulation of the particle geometry.


Fermentation of Chlorella sp. for anaerobic bio-hydrogen production: influences of inoculum-substrate ratio, volatile fatty acids and NADH.
This study evaluated the influences of inoculum-substrate ratio (ISR), volatile fatty acids (VFAs) and nicotinamide adenine dinucleotide, the reduced form (NADH) on hydrogen production during the anaerobic fermentation of Chlorella sp. in batch tests at 35 °C. The results indicated that the hydrogen concentration and lag time increased when ISR decreased, and the maximum hydrogen production and hydrogen content, 7.13 mL/g VS and 45.3%, respectively, were obtained when ISR was equal to 0.3. On the other hand, VFAs concentrations increased with the increase of hydrogen. The NADH increased while the daily output of hydrogen decreased as the fermentation carried on. The results suggested that ISR, VFAs, and NADH were important parameters for effective anaerobic hydrogen production using Chlorella sp. as substrate.


A novel kynurenic acid analog (SZR104) inhibits pentylenetetrazole-induced epileptiform seizures. An electrophysiological study : special issue related to kynurenine.
The concentration of kynurenic acid (KYNA) in the cerebrospinal fluid, which is in the nanomolar range, is known to decrease in epilepsy. The experimental data suggest that treatment with L: -KYN dose dependently increases the concentration of the neuroprotective KYNA in the brain, which itself hardly crosses the blood-brain barrier. However, it is suggested that new synthetic KYNA analogs may readily cross the blood-brain barrier. In this study, we tested the hypothesis that a new KYNA analog administered systemically in a sufficient dose results in a decreased population spike activity recorded from the pyramidal layer of area CA1 of the hippocampus, and also provides protection against pentylenetetrazole-induced epileptiform seizures.


Super-high procoagulant activity of gecko thrombin: A gift from sky dragon.
Gecko, the "sky dragon" named by Traditional Chinese Medicine, undergoes rapid coagulation and scarless regeneration following tail amputation in the natural ecology, providing a perfect opportunity to develop the efficient and safe drug for blood clotting. Here, gecko thrombin (gthrombin) was recombinantly prepared and comparatively studied on its procoagulant activity. The 3D structure of gthrombin was constructed using the homology modeling method of I-TASSER. The active gthrombin was prepared by the expression of gecko prethrombin-2 in 293 T cells, followed by purification with Ni2+ -chelating column chromatography prior to activation by snake venom-derived Ecarin. The enzymatic activities of gthrombin were assayed by hydrolysis of synthetic substrate S-2238 and the fibrinogen clotting. The vulnerable nerve cells were used to evaluate the toxicity of gthrombin at molecular and cellular levels. The active recombinant gthrombin showed super-high catalytic and fibrinogenolytic efficiency than those of human under different temperatures and pH conditions. In addition, gthrombin made nontoxic effects on the central nerve cells including neurons, contrary to those of mammalian counterparts, which contribute to neuronal damage, astrogliosis, and demyelination. A super-high activity but safe procoagulant candidate drug was identified from reptiles, which provided a promising perspective for clinical application in rapid blood clotting.


A post-marketing acceptability study in 11,685 patients of the efficacy of timolol/bendrofluazide in the management of hypertension in general practice.
A post-marketing acceptability study was performed in 11,685 patients to assess the efficacy and acceptability of 10 mg timolol/2.5 mg bendrofluazide in patients with mild to moderate hypertension in general practice. The initial dose was 1 tablet/day. This was adjusted at weekly intervals up to a maximum of 4 tablets/day or until blood pressures of less than or equal to 95 mmHg diastolic or, in patients of greater than or equal to 60 years, less than or equal to 100 mmHg plus the patient's age (in years) systolic, were achieved. Stabilized patients were followed-up after 12, 24 and 48 weeks. Of the patients enrolled, 69% (8039) were successfully treated for at least 8 weeks, 26% (3033) were withdrawn and 5% (613) defaulted. One tablet/day was required by 61% of patients and 29% required 2 tablets/day to achieve stabilization. The mean reductions in systolic and diastolic blood pressures and pulse rate were 31 and 19 mmHg, and 11 beats/min, respectively. Over 60% of the patients enrolled were still taking timolol/bendrofluazide after 12 months' continuous therapy. The most frequently reported reason for withdrawal was an 'adverse event' which occurred in 15.4% (1805) of patients. Only 1.9% (217) failed to achieve target blood pressure on 4 tablets/day. This large study has shown timolol/bendrofluazide to be a highly effective and acceptable once daily therapy for mild to moderate hypertension in general practice.


Cortical reorganization during adolescence: What the rat can tell us about the cellular basis.
The human cortex, particularly the prefrontal cortex, decreases in volume during adolescence which indicates considerable pruning. There is consistent evidence from human, monkey and rat tissue that synapses, dendritic spines and dendrites are pruned during this time. However, our work with a rat model of adolescence shows that other cellular components are remodeling at this time as well. Neurons are also pruned and we have found that in female rats, puberty is a key signal for this process. Other critical developmental events occur that are not detectable in gross size changes including the growth of dopaminergic inputs. The changes in the inhibitory GABAergic system, especially the parvalbumin-expressing neuronal subtype, are an essential part of the maturation of the prefrontal cortex. This involves the formation of perineuronal nets around parvalbumin interneurons that allow mature fast spiking. We have found a large increase in perineuronal nets from early adolescence to adulthood in both sexes. We also have seen a temporary pause in this increase at the time of puberty in females. These complicated events cannot be deduced from MRI. The cellular reorganization that is indicated by size changes in the human cortex during adolescence can be informed by work from rodent models.


[Hellp syndrome may precede the appearance of arterial hypertension in pregnancy toxemia].
The "Hellp syndrome" describes the association of three biological abnormalities (hemolysis, liver abnormalities and thrombocytopenia) establishing the severity of arterial hypertension during pregnancy and requiring the interruption of pregnancy as much for the child as for the mother. This article reports a case of "Hellp syndrome" which was special in that the biological abnormalities preceded the occurrence of pre-eclampsia. The signs, diagnosis, prognosis and treatment of the "Hellp syndrome" are studied in this article.


Aromatase in atherosclerotic lesions of human aorta.
It is well documented that estrogens have atheroprotective effects in humans. Peripheral aromatization of circulating androgens has been demonstrated to exert estrogenic actions in many human tissues, especially in men and post-menopausal women. Recently, production of estrogens mediated by aromatase was detected in cultured smooth muscle cells and aortic endothelial cells and it has been proposed that this in situ produced estrogen may influence the development of atherosclerosis. In this study, we first examined aromatase expression by immunohistochemistry in human aortic tissues obtained from 85 autopsy cases (50 males, 35 females, 49.6 +/- 2.9-year-old) and by mRNA in situ hybridization in 10 cases. We then semi-quantified the level of aromatase mRNA in aortic tissues of 12 men and 12 post-menopausal women by reverse transcriptase-polymerase chain reaction (RT-PCR) to examine whether or not and in which cell types aromatase was expressed. We also studied alternative use of multiple exon 1 of its gene and immunolocalization of 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD I), which converts estrone produced by aromatase to estradiol, a biologically active estrogen. Aromatase immunoreactivity and mRNA hybridization signals and 17beta-HSD I immunoreactivity were all detected in smooth muscle cell (SMC) of the media and thickened intima, especially in SMC adjacent to an atheromatous plaque. The levels of aromatase mRNA were significantly higher in female cases than in male cases (P<0.05). The amount of aromatase mRNA was significantly higher in the specimens with fibroatheroma (P<0.05) than other lesions, and was also significantly higher in the cases utilizing 1c (I.3) or 1d (PII) of exon 1, i.e. gonadal types than those utilizing 1b (I.4), i.e. fibroblasts type as the promoter (P<0.01). These results suggest that estrone and estradiol are produced in SMC of the human aortic wall and that their production is mediated by aromatase and 17beta-HSD I, respectively. Moreover, it was suggested that aromatase overexpression, possibly as a result of alternative splicing, may play some roles in the development of atherosclerosis.


Long-term effects on cortical glutamate release induced by prenatal exposure to the cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone: an in vivo microdialysis study in the awake rat.
The aim of the present in vivo microdialysis study was to investigate whether prenatal exposure to the CB(1) receptor agonist WIN55,212-2 mesylate (WIN; (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone), at a dose of 0.5 mg/kg (s.c. from the fifth to the 20th day of gestation), that causes neither malformations nor overt signs of toxicity, influences cortical glutamate extracellular levels in adult (90-day old) rats. Dam weight gain, pregnancy length and litter size at birth were not significantly affected by prenatal treatment with WIN. Basal and K(+)-evoked dialysate glutamate levels were lower in the cerebral cortex of adult rats exposed to WIN during gestation than in those born from vehicle-treated mothers. In both group of animals WIN (0.1 mg/kg, i.p.) increased dialysate glutamate levels. However, while the blockade of the CB1 receptors with the selective receptor antagonist SR141716A completely counteracted the WIN-induced increase in those rats exposed to vehicle during gestation, it failed to antagonise the increase in those born from WIN-treated dams. These findings suggest that prenatal exposure to the CB1 receptor agonist WIN, at a concentration which is not associated with gross malformations and/or overt signs of toxicity, induces permanent alterations in cortical glutamatergic function. The possibility that these effects might underlie, at least in part, some of the cognitive deficits affecting the offspring of marijuana users is discussed.


The ETT2 transcriptional regulator EivF affects the serum resistance and pathogenicity of avian pathogenic Escherichia coli.
Avian pathogenic Escherichia coli (APEC), a pathotype of extraintestinal pathogenic Escherichia coli (ExPEC), can cause serious systemic infectious diseases in poultry. Escherichia coli type III secretion system 2 (ETT2) is widely distributed in E. coli strains, including ExPEC and Enterohemorrhagic Escherichia coli (EHEC). The transcriptional regulator EivF, which is located at the ETT2 cluster, affects the secretion of LEE-encoded proteins and increases bacterial adhesion to human intestinal epithelial cells in EHEC O157:H7. In a previous study, we demonstrated the transcriptional regulator can affect APEC's motility and biofilm formation. Here, we evaluated whether EivF is involved in the pathogenicity of APEC, and we found that inactivation of eivF significantly enhanced resistance to the serum, adherence to chicken embryo fibroblast (DF-1) cells, and the colonization ability of APEC in chicks. To further clarify the regulation mechanism of transcriptional regulator EivF, we performed transcriptome sequencing to analyze the differentially expressed genes and pathways, showing that EivF regulates membrane, adhesion, environmental stress, and secretion protein genes, and EivF is involved in the localization, biological adhesion, biological regulation, membrane, and toxin activity. These findings indicated that the ETT2 transcriptional regulator EivF plays a crucial role in the pathogenicity of APEC as a negative repressor.


Biological robustness and the role of microRNAs: a network perspective.
Over the past decade, microRNA molecules have emerged as critical regulators in the expression and function of animal genomes. This review discusses the relationship between microRNA-mediated regulation and the robustness of biochemical networks that contain microRNAs. Most biochemical networks are robust; they are relatively insensitive to the precise values of reaction constants and concentrations of molecules acting within the network. MicroRNAs involved in network robustness may appear to be nonessential under favourable uniform conditions used in conventional laboratory experiments. However, the function of these molecules can be revealed under environmental and genetic perturbations. Recent advances have revealed unexpected features of microRNA organization in networks that help explain their promotion of robustness.


[Supplementary innervation of lower teeth. Review of the literature].
When pain persists after a successful injection of the inferior alveolar nerve, the professional must think on the possibility of supplementary nerve supply of the region. This review updates the current knowledge of this supplementary innervation. Not every patient will require this kind of anesthesia, however, the dentist must be aware of its existence.


Scanning electron microscopic study of the human auditory ossicles.
The human mallei, incudes and stapedes from 34 cadavers were examined using scanning electron microscope (SEM) to compare the bone surface type among different regions of auditory ossicles for males and females. On the malleus of both males and females, almost all of the surfaces showed a smooth fibrous appearance, characteristic of resting surface. Limited bone-forming or resorbing surfaces were identified on the malleus. As compared with the malleus, the percentage area of the resorbing surface and the vascular canal openings were higher on the incus and stapes, especially on the long process (Crus longum) of the incus and the neck of the stapes for both males and females. The percentage area occupied by the resorbing surface of the long process of the incus and the neck of the stapes correlated with that of the vascular canal openings. We consider that the malleus maintained the stable condition, while the long process of the incus and the neck of the stapes demonstrated marked bone resorption. We suppose that the bone erosion may be related to the vascularization in these regions. Though the percentage area of the resorbing surface and the vascular canal openings had the tendency to be high in females, we did not find any significant differences between the males and females. There was no significant correlation between the age and the area of resorbing surface or vascular canal openings.


Evidence-based recommendations for gastrointestinal cancers during the COVID-19 pandemic by the Brazilian Gastrointestinal Tumours Group.
As of 2020, the world is facing the great challenge of the COVID-19 (Coronavirus disease 2019) pandemic, caused by the SARS-CoV-2 virus. While the overall mortality is low, the virus is highly virulent and may infect millions of people worldwide. This will consequently burden health systems, particularly by those individuals considered to be at high risk of severe complications from COVID-19. Such risk factors include advanced age, cardiovascular and pulmonary diseases, diabetes and cancer. However, few data on the outcomes of cancer patients infected by SARS CoV-2 exist. Therefore, there is a lack of guidance on how to manage cancer patients during the pandemic. We sought to propose specific recommendations about the management of patients with gastrointestinal malignancies. The Brazilian Gastrointestinal Tumours Group board of directors and members sought up-to-date scientific literature on each tumour type and discussed all recommendations by virtual meetings to provide evidence-based-and sometimes, expert opinion-recommendation statements. Our objectives were to recommend evidence-based approaches to both treat and minimise the risk of COVID-19 for cancer patients, and simultaneously propose how to decrease the use of hospital resources at a time these resources need to be available to treat COVID-19 patients. Overall and tumour-specific recommendations were made by stage (including surgical, locoregional, radiotherapy, systemic treatments and follow-up strategies) for the most common gastrointestinal malignancies: esophagus, gastric, pancreas, bile duct, hepatocellular, colorectal, anal cancer and neuroendocrine tumours. Our recommendations emphasise the importance of treating cancer patients, using the best evidence available, while simultaneously taking into consideration the world-wide health resource hyperutilisation to treat non-cancer COVID-19 patients.


Perceived quality of health care services among people with osteoarthritis - results from a nationwide survey.
To assess the perceived quality of care received by people with osteoarthritis (OA) in Norway and explore factors associated with the quality of care. A national survey in which members of the Norwegian Rheumatism Association with OA registered as their main diagnosis completed a questionnaire. The perceived quality of care was reported on a 17-item OsteoArthritis Quality Indicator questionnaire, covering both pharmacological and non-pharmacological aspects of OA care. In addition, the four-page questionnaire covered areas related to demographic characteristics, the location and impact of the OA, and utilization and satisfaction with health care services. The quality of care is calculated as pass rates, where the numerator represents the number of indicators passed and the denominator represents the number of eligible persons. In total, 1,247 participants (response rate 57%) completed the questionnaire. Mean age was 68 years (standard deviation 32) and 1,142 (92%) were women. Respondents reported OA in hand only (12.4%), hip only (7.3%), knee only (10.4%), in two locations (42%) or all three locations (27%). The overall OsteoArthritis Quality Indicator pass rate was 47% (95% confidence interval [CI] 46%-48%), and it was higher for pharmacological aspects (53% [51%-54%]) than for non-pharmacological aspects of care (44% [43%-46%]). The pass rate for the individual quality indicators ranged from 8% for "referral for weight reduction" to 81% for "receiving advice about exercises". Satisfaction with care was strongly associated with perceived quality. The pass rate for those who were "very satisfied" was 33% (25%-40%) higher than those who were "very unsatisfied" with care. While the OA patient seems to be rather satisfied with the perceived OA care, there is still room for improvement in the quality of care. Although the quality of care in the present study is somewhat higher than in other studies, less than 50% of the recommended care has been provided.


[Bilateral scapulohumeral luxation, a complication of aldrin poisoning].
The present paper reports on a case of bilateral scapulohumeral luxation caused by convulsions brought about by intoxication with Aldrin, an organochlorate insecticide.


Adsorption and desorption of CO on Ni decorated stepped Rh(553).
Vicinal surfaces are important in surface science, as they show interesting electronic structures and reactivities due to the steps. In this paper the adsorption and desorption of carbon monoxide on the stepped Rh(553) surface decorated with Ni is reported. With 0.1 to 0.3 monolayer Ni on Rh(553) one and two atoms broad Ni wires along the Rh steps are formed. The adsorption and desorption of carbon monoxide on these surfaces is investigated using thermal desorption spectroscopy (TDS) and reflection absorption infra red spectroscopy (RAIRS). TDS shows a marked change from just one broad TDS peak on pure Rh(553) to 4 distinct peaks with increasing Ni decoration. RAIRS shows that already at 0.1 monolayer Ni the CO adsorption states on bridge sites on the Rh step atoms are completely quenched. In addition it is shown that with Ni films up to 3 monolayer the on top adsorption sites for CO on Ni are preferred over the bridge and hollow adsorption sites in contrast to what is known from the Ni(111) surface.


Adherence of urease-induced crystals to rat bladder epithelium.
Apart from urine supersaturation with respect to struvite and calcium phosphate caused by urease-producing microorganisms, retention of formed crystals in the urinary tract is necessary for the formation of infection stones. This study was performed to investigate the role of the mucous coat lining the urothelium in the adhesion of urease-induced crystals. Removal of this glycosaminoglycan-containing layer from rat bladders increased the adherence of struvite and calcium phosphate crystals 5-6 times compared to that in intact rat bladders. Heparin completely restored the antiadherence capacity while chondroitin sulphate had a very weak restorative effect and human urine had no restorative effect. These findings support the view that the mucous coat is of importance in preventing retention of urease-induced crystals.


Chemiluminescence detection of superoxide anion release and superoxide dismutase activity: modulation effect of Pulsatilla chinensis.
A novel flow-injection chemiluminescence-based method has been developed for determination of superoxide dismutase (SOD) activity. An in-vitro superoxide anion generation xanthine/xanthine oxidase stable source was established on line with FIA/CL-detection apparatus, for measuring SOD activity. This method can detect SOD in the linear range of 0.002-2.00 U mL(-1) with a detection limit of 0.001 U mL(-1). Another method for detection of superoxide anion is based on the luminol-FeCl(3) chemiluminescence (CL) reaction. This method was used to evaluate superoxide release and SOD activity in rats treated with the traditional Chinese herb Pulsatilla chinensis, which resulted in high clearance of hepatitis B virus (HBV) after treatment of a hepatitis B patient. Interestingly, we found that treatment with Pulsatilla chinensis can specifically increase superoxide release by liver tissues and, at the same time, slightly increase extracellular SOD (ECSOD) activity in plasma; in particular it can markedly increase MnSOD activity in mitochondria in liver tissue. This work revealed a possible mechanism whereby Pulsatilla chinensis prevents possible infection (for example HBV) by specifically increasing superoxide release in the liver and increasing MnSOD activity to minimize superoxide-mediated toxicity.


A universal biosensing platform based on optical micro-ring resonators.
The use of optical micro-ring resonators as a platform for quantitative and qualitative biosensing applications was explored. Vertically coupled, high refractive index micro-ring resonators, used as sensing elements, were fabricated on silicon chips by photolithographic techniques. An optical reader system consisting of a near-infrared broad band light source and an optical spectrum analyzer were employed for data acquisition. Micro-ring resonator surfaces were modified with specific target receptors, including antibodies and single-stranded DNA oligonucleotides. The system was successfully used for label-free, specific, and rapid detection of whole bacterial cells, proteins and nucleic acids.


Relationships between putative G-quadruplex-forming sequences, RecQ helicases, and transcription.
Putative G-quadruplex-forming sequences (PQS) have long been implicated in regulation of transcription, though the actual mechanisms are not well understood. One proposed mechanism involves the activity of PQS-specific helicases belonging to the RecQ helicase family. However, patterns of PQS that correlate with transcriptional sensitivity to RecQ helicases are not well studied, and no adequate transcriptional model exists to account for PQS effects. To better understand PQS transcriptional effects, we analyze PQS motifs in genes differentially-transcribed in Bloom Syndrome (BS) and Werner Syndrome (WS), two disorders resulting in loss of PQS-interacting RecQ helicases. We also correlate PQS genome-wide with transcription in multiple human cells lines while controlling for epigenetic status. Finally, we perform neural network clustering of PQS motifs to assess whether certain motifs are over-represented in genes sensitive to RecQ helicase loss. By analyzing PQS motifs in promoters of genes differentially-transcribed in BS and WS, we demonstrate that abundance of promoter PQS is generally higher in down-regulated genes and lower in up-regulated genes, and show that these effects are position-dependent. To interpret these correlations we determined genome-wide PQS correlations with transcription while controlling for epigenetic status. Our results identify multiple discrete transcription start site-proximal positions where PQS are correlated with either increased or decreased transcription. Finally, we report neural network clustering analysis of PQS motifs demonstrating that genes differentially-expressed in BS and WS are significantly biased in PQS motif composition. Our findings unveil unappreciated detail in the relationship between PQS, RecQ helicases, and transcription. We show that promoter PQS are generally correlated with reduced gene expression, and that this effect is relieved by RecQ helicases. We also show that PQS at certain positions on the downstream sense strand are correlated with increased transcription. We therefore propose a new transcriptional model in which promoter PQS have at least two distinct types of transcriptional regulatory effects.


"Keeping our mission, changing our system": translation and organizational change in natural foods co-ops.
Institutional theory has played a central role in the study of organizations for over half a century, but it often overlooks the actions of the people who bring organizations to life. This article advances an inhabited approach to institutional analysis that foregrounds the creativity of organizational members. It argues that people use local cultures to translate and respond to institutional pressures. The article analyzes qualitative data from countercultural co-op stores that have been pushed to conform to mainstream forms of business organization by a competitive market and demonstrates that translation explains why outcomes that institutional theory would not predict have come to pass.


Developmental needs of infants and toddlers who require lengthy hospitalization.
To describe demographic and medical characteristics of a sample of children younger than age 3 years who required lengthy hospitalization in a tertiary care hospital. To determine the proportion of children in the sample with biologic handicaps, developmental delays, or risk factors for developmental disorders who met eligibility criteria for early intervention services based on federal law PL 99-457 and state regulations. Survey of medical records. Large, urban, tertiary care children's hospital. All 135 children younger than age 3 years hospitalized for more than 30 days during 1990 and 1991. None. The most prevalent cause of lengthy hospitalization was congenital anomaly followed by chronic and perinatal conditions; 38 patients (28%) required technology assistance at the time of discharge. Seventy-three children (54%) were eligible for early intervention services based on the presence of a biologic handicap or developmental delay. An additional 48 patients (36%) were eligible for developmental screening and periodic developmental monitoring on the basis of medical and social risk factors. Because of the high prevalence of developmental disorders and risk factors in infants and toddlers requiring lengthy hospitalizations, hospital-wide systems for identification, developmental assessment, and early intervention services should be designed and implemented.


The effects of Losartan on abdominal wall fascial healing.
Losartan, a commonly used angiotensin II receptor blocker (ARB) for blood pressure control, also impairs cutaneous wound healing. Our current study will analyze how Losartan affects wound healing in the muscle and fascia from both biomechanical and histological aspects. A total of 26 Sprague-Dawley rats were separated into one control group (NS, N = 13) and one experimental group (LG, N = 13) to receive normal saline and 40 mg/kg of Losartan by way of gastric lavage, respectively. 7 days later, all animals were subjected to a 5 cm midline laparotomy. The fascia and skin were then closed with 4-0 prolene and 5-0 vicryl. 15 days postoperatively, the animals were sacrificed and the abdominal wall harvested for wound tensiometric test and histological analysis. All 26 rats survived to the time of necropsy. Tensiometry detected significantly higher wound tensile strength in the NS group (1.6 ± 0.31 N/mm) than in the LG (1.3 ± 0.28 N/mm) group (p = 0.016). Transection histology with trichrome staining demonstrated higher degree of immature fibroplasia inside the wound in the LG group than in the NS group (p = <0.0001). The LG group also had larger incisional gaps than the NG group. The antihypertensive drug, Losartan, retards wound healing in the abdominal fascia and reduces wound tensile strength in our rat model. Attention should be paid to the potential effects of various medications on fascial wound healing to guarantee optimal surgical outcomes.


Transpupillary thermotherapy (TTT) in circumscribed choroidal hemangioma.
Choroidal hemangioma presents a therapeutic dilemma. Although it is a benign tumor, it may lead to massive exudation of subretinal fluid and a loss of visual function. Argon laser photo-coagulation in a grid pattern may be followed by initial absorption of subretinal fluid, but recurrence is common. Trans-scleral cryotherapy is difficult to apply at the posterior pole of the eye. External beam irradiation may bear a risk of maculopathy and papillopathy. Brachytherapy does not allow placement of radiation to the hemangioma sparing other retinal or choroidal structures. We sought to determine whether transpupillary thermotherapy (TTT) is suitable for treatment of choroidal hemangioma at the posterior pole. We present ten patients with choroidal hemangioma. All of these received TTT. The mean follow-up period was 13.3 months (3-21 months). TTT was delivered via a slitlamp microscope with a diode laser at 810 nm. After TTT, reduction in tumor prominence was observed in eight patients at 3 months after treatment by A scan sonography. Visual acuity improved by more than three lines in four patients, and remained unchanged in all other patients. Two patients were retreated to achieve complete absorption of fluid. Serous retinal detachment persisted in three patients because the hemangioma could not be treated completely because of proximity to the fovea. Our preliminary results suggest that TTT may be used effectively to treat some choroidal hemangiomas in the first instance and prevent fluid leakage provided the lesion does not involve the fovea. However, long-term follow-up and more cases are needed to evaluate the long-term visual outcome and potential risks.


Efficiency of host utilisation by coleopteran parasitoid.
In insect larvae, optimising food utilisation with respect to available meals and time is essential for achieving maximum adult body size, which is a relevant proxy of fitness. We studied the efficiency of food conversion, body size, mortality, and development time in a solitary idiobiont ectoparasitoid, Brachinus explodens (Coleoptera: Carabidae), reared in the laboratory on the pupae of another carabid genus, Amara. The efficiency of conversion index (ECI - ratio of ingested to assimilated food) was, on average, 54.1±1.1% (n=76), with a minimum of 26.9% and a maximum of 81.6%. The rate of increase in biomass gained (W(gained)) with biomass of the host was constant in females, but it decreased in males over the range of host body mass. Females, therefore, grew heavier from hosts of the same mass compared to males. Body length increased with the host mass and was correlated with W(gained) identically for both sexes. Mortality was unaffected by the host mass, but it significantly increased below 20°C. In contrast, the development time of the feeding phase of the larva increased with the host mass at 20.3 and 23.7°C, but it remained unaffected at 26.9°C and in all three temperatures considering pupal development. W(gained) increased with development time up to ca. 8 days of larval feeding at 23.7°C. To our knowledge, our data are the first on food utilisation in solitary idiobiont coleopteran ectoparasitoids, and they present the highest values of ECI in insects.


For avid glucose tumors, the SUV peak is the most reliable parameter for [(18)F]FDG-PET/CT quantification, regardless of acquisition time.
This study is an assessment of the impact of acquisition times on SUV with [(18)F]FDG-PET/CT on healthy livers (reference organ with stable uptake over time) and on tumors. One hundred six [(18)F]FDG-PET/CT were acquired in list mode over a single-bed position (livers (n = 48) or on tumors (n = 58)). Six independent datasets of different durations were reconstructed (from 1.5 to 10 min). SUVmax (hottest voxel), SUVpeak (maximum average SUV within a 1-cm(3) spherical volume), and SUVaverage were measured within a 3-cm-diameter volume of interest (VOI) in the right lobe of the liver. For [(18)F]FDG avid tumors (SUVmax ≥ 5), the SUVmax, SUVpeak, and SUV41% (isocontour threshold method) were computed. For tumors, SUVpeak values did not vary with acquisition time. SUVmax displayed significant differences between 1.5- and 5-10-min reconstruction times. SUV41% was the most time-dependent parameter. For the liver, the SUVaverage was the sole parameter that did not vary over time. For [(18)F]FDG avid tumors, with short acquisition times, i.e., with new generations of PET systems, the SUVpeak may be more robust than the SUVmax. The SUVaverage over a 3-cm-diameter VOI in the right lobe of the liver appears to be a good method for a robust and reproducible assessment of the hepatic metabolism.


The Role of Renin Angiotensin Aldosterone System Genes in Diabetic Nephropathy.
The role of the renin angiotensin aldosterone system (RAAS) and the gene variants of its components in susceptibility to diabetic nephropathy (DN) have been investigated in numerous studies. The effects of some RAAS gene variants, including angiotensin converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R), on the risk for DN have been studied more extensively, but there has been controversy. The reasons for controversy in this field could be attributed to the effect of ethnicity, gender, stage of diabetes complications, the presence of intrarenal RAAS, methodologic limitations of the association studies in multifactorial diseases, inadequate sample size, genetic heterogeneity, and the lack of studies that involved all RAAS genes and their interactions. This review looks at the current available information about the role of all RAAS gene variants in the pathogenesis of DN. Further, the concomitant study of both systemic and local RAAS, counter-regulators of ACE and ACE2, and also AT1R and angiotensin II type 2 receptor (AT2R) genes could help to elucidate the role of the genes of this system in the pathogenesis of DN.


Brain gene expression, metabolism, and bioenergetics: interrelationships in murine models of cerebral and noncerebral malaria.
Malaria infection can cause cerebral symptoms without parasite invasion of brain tissue. We examined the relationships between brain biochemistry, bioenergetics, and gene expression in murine models of cerebral (Plasmodium berghei ANKA) and noncerebral (P. berghei K173) malaria using multinuclear NMR spectroscopy, neuropharmacological approaches, and real-time RT-PCR. In cerebral malaria caused by P. berghei ANKA infection, we found biochemical changes consistent with increased glutamatergic activity and decreased flux through the Krebs cycle, followed by increased production of the hypoxia markers lactate and alanine. This was accompanied by compromised brain bioenergetics. There were few significant changes in expression of mRNA for metabolic enzymes or transporters or in the rate of transport of glutamate or glucose. However, in keeping with a role for endogenous cytokines in malaria cerebral pathology, there was significant up-regulation of mRNAs for TNF-alpha, interferon-gamma, and lymphotoxin. These changes are consistent with a state of cytopathic hypoxia. By contrast, in P. berghei K173 infection the brain showed increased metabolic rate, with no deleterious effect on bioenergetics. This was accompanied by mild up-regulation of expression of metabolic enzymes. These changes are consistent with benign hypermetabolism whose cause remains a subject of speculation.


Experience in the management of 50 consecutive penetrating wounds of the heart.
Fifty patients with penetrating wounds of the heart were grouped into three categories, based on the clinical severity of the injuries. Gunshot wounds consistently resulted in a higher mortality than knife wounds. Central venous pressure (CVP) was the single most important means of determining cardiac tamponade. The survival rates in the respective groups were 6, 79 and 100 per cent. The improved survival in our series was due to a rapid transportation system, increased awareness of the significance of cardiac injuries and an aggressive surgical approach.


Prognostic significance of PCR-based molecular staging in patients with diffuse large B-cell lymphoma treated with R-CHOP immunochemotherapy.
The prognostic role of detecting clonal immunoglobulin gene rearrangement (IgR) from bone marrow (BM) aspirates was evaluated by BIOMED-2 PCR in 97 patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-CHOP immunochemotherapy. Sixteen (16.5%) patients had BM involvement (BMI) defined by BM biopsy (MOR+) and 39 (40.2%) had positive IgR (PCR+). Patients with MOR + BMI showed inferior event-free survival (EFS) compared to those with MOR-/PCR- (p < 0.001) or those with MOR-/PCR + BMI (p = 0.002), while no significant difference in EFS was observed between patients with MOR-/PCR + and those with MOR-/PCR - BMI (p = 0.497). Use of the BIOMED-2 for PCR resulted in significant increase in detection of BMI. However, the increased sensitivity by PCR did not translate into improved prediction of prognosis, emphasizing the essential role of histopathological review of trephine biopsy for the detection of BMI.


Inflammation Drives MicroRNAs to Limit Hepatocyte Bile Acid Transport in Murine Biliary Atresia.
Biliary atresia (BA) is an inflammatory pediatric cholangiopathy with only surgical means for treatment. Many contributors to bile acid synthesis and transport have previously been reported to be downregulated in patients with BA; yet, the driving factors of the abnormal bile acid synthesis and transport in regard to BA have not been previously studied. Wild type or Ig-α-/- mice were injected with salt solution (control) or rotavirus on day of life 0, and analyses were performed on day of life 14. The mRNA levels of bile acid transporters/nuclear receptors and liver microRNAs (miRNAs) were compared between groups. A mouse hepatocyte cell line was used to examine the effects of innate cytokines on miRNA levels and bile acid transporter/nuclear receptor expression and miRNAs on bile acid transporter/nuclear receptor expression. BA mice had significantly increased mRNA expression of innate cytokines and miRNAs known to bind bile acid transporters/nuclear receptors (miRNAs -22-5p, -34a-5p, and -222-3p) and decreased mRNA expression of bile acid transporters and nuclear receptors. In vitro, TNF-α and IL-1β decreased BSEP and CYP7A1 while increasing miRNA-34a-5p and miRNA 222-3p. LXR, SHP, CYP7A1, NTCP, and MRP2 were decreased by miRNA-34a-5p, whereas miRNA-222-3p decreased NTCP and MRP4. TNF-α and IL-1β increased expression of miRNAs 34a-5p and 222-3p and these miRNAs then decrease expression of multiple bile acid transporters and nuclear receptors. Loss of bile acid transporters increases hepatotoxicity via bile acid retention. Therapeutic agents that increase bile acid transport or nuclear receptor functioning should be investigated in BA.


Sympathetic influence on biomechanical skin properties after spinal cord injury.
Case-control study. To investigate changes of biomechanical skin properties and their relationship with paralysis following spinal cord injury (SCI). South Korea. A total of 48 male subjects with chronic SCI and 48 age-matched healthy controls were enrolled into this study. The C4 shoulder group and L2 thigh group were prescribed by two measured anatomical regions that represented the C4 and L2 American Spinal Injury Association sensory dermatomes. Each anatomical group was comprised of one control subgroup and three SCI subgroups determined by sympathetic paralysis at the measured region and somatic completeness. The following biomechanical skin properties were compared between the subgroups in each anatomical group by using Cutometer, a non-invasive suction device: distensibility (Uf), elasticity (Ua/Uf and Ur/Uf) and viscoelasticity (Uv/Ue and H). The impact of sympathetic and somatic sensory paralysis, somatic completeness, age, smoking, body mass index and duration of injury on the indices of skin properties were analyzed. In each anatomical group, sympathetic paralyzed subgroups regardless of somatic sensory completeness showed lower value of skin distensibility (Uf), and higher values of elasticity (Ua/Uf and Ur/Uf) and viscoelasticity (Uv/Ue and H), compared with other subgroups. Age and duration of injury had significant impact on biomechanical skin properties. The non-invasive suction method is useful for quantitative evaluation of skin affected by SCI. In chronic SCI patients, biomechanical skin properties are significantly altered in the skin with sympathetic paralysis rather than somatic sensory paralysis.


The feasibility of amide proton transfer imaging at 3 T for bladder cancer: a preliminary study.
To investigate the optimal amide proton transfer (APT) imaging parameters for bladder cancer (BCa), the influence of different protein concentrations and pH values on APT imaging, and to establish the reliability of APT imaging in healthy volunteers and patients with BCa. The optimal APT imaging parameters for BCa were experimentally optimised using cross-linked bovine serum albumin (BSA) phantoms. BSA phantoms were scanned with different values for the saturation power, saturation duration and number of excitations. Meanwhile, BSA phantoms containing different protein concentrations and solutions of different pH levels were scanned. The interobserver agreement of the asymmetric magnetisation transfer ratio (MTRasym) was assessed in 11 healthy volunteers and 18 patients with BCa. The optimal scanning scheme consisted of 1 excitation, a saturation power of 2 μT, and a saturation time of 2 s. The APT signal intensity increased as the protein concentration increased and as the pH decreased. The MTRasym showed good concordance for all subjects. The MTRasym of BCa tissue was significantly higher (1.81 ± 0.71) than that of bladder wall in healthy volunteers (0.34 ± 0.12) and normal bladder wall in patients with BCa (0.31 ± 0.11; p<0.001). There was no significant difference between the bladder wall of healthy volunteers and the normal bladder wall of patients with BCa. APT imaging showed potential value for application in BCa.


Follow up study: The influence of rTMS with high and low frequency stimulation on motor and executive function in Parkinson's disease.
rTMS may influence on both cognitive and motor function in PD but the daily routine and the predictors of responders to rTMS are not known. We hypothesized that the frequency and intensity of stimulation somehow relate to each other. Our goal was to select the optimal frequency with low intensity for PD. We clarified the importance of age in the effect of rTMS. A total sixty-six patients with PD were included in the study. In an open investigation, randomly selected patients were divided into three groups. The effects of 1Hz (N=28), 5Hz (N=13) and 5+1Hz (N=25) frequency at low intensity over each DLPFC and the brain stem for 7days were compared. Patients were followed for six months. UPDRS, the Trail Making Test, and dual tasks were applied. Patients ≤65years >65yrs were compared. Data were analyzed by repeated measure ANOVA. Only 1Hz had an effect on motor scores. Before the trial patients≤65 yrs had UPDRS total scores of 30.3±16.9, after 1 month: 17.8±8.9 p<0.001, after 6 months 18.3±8.8 p<0.001. Improvement of patients >65yrs was observed after one month (p<0.01). Executive function >65yrs (N=16) was significantly worse compared with C (N=15) and it was improved temporarily by 1Hz. Five Hertz and 5+1Hz did not cause improvement. One Hertz with proper intensity has a good outcome in PD. Patients >65yrs show deterioration in their executive function and they have shorter duration in their therapeutic effect of rTMS. This study draws attention to the importance of stimulation intensity and age as a predictor of the effect of rTMS.


Fibre-fluorescence in situ hybridization unravels apparently seven DAZ genes or pseudogenes clustered within a Y-chromosome region frequently deleted in azoospermic males.
Using the technique of 'fibre-FISH' (fluorescence in situ hybridization), we describe the direct visualization of seven longer DAZ signal stretches and in addition a maximum of four isolated single DAZ signals on Y-chromatin fibres of four different individuals. These seven longer DAZ signal stretches may represent seven DAZ genes or pseudogenes, whereas the single DAZ signals may represent truncated DAZ genes.


An Exploration of Social Cognition in Children with Different Degrees of Genetic Deletion in Williams Syndrome.
An explanation for the social dysfunction observed in Williams syndrome may be deficits in social cognition. This study explored aspects of social cognition in children with Williams syndrome with different genotypes. The 12 participants included one with a 1.1 Mb deletion that retained the GTF2IRD1, GTF2I, and GTF2IRD2 genes, seven with a 1.5 Mb deletion that preserved the GTF2IRD2 gene, and four with a 1.8 Mb deletion with loss of all three genes. The participant retaining all three genes was found to have better performance on social judgment and first-order theory of mind tasks than the group with loss of all three genes. These results may reflect the influence of the GTF2I gene family on social cognition in Williams syndrome.


Home-based tDCS for apathy in Alzheimer's disease: a protocol for a randomized double-blinded controlled pilot study.
Apathy is among the most common behavioral symptoms in dementia and is consistently associated with negative outcomes in Alzheimer's disease (AD). Despite its prevalence and clinical relevance, available pharmacological and non-pharmacological strategies to treat apathy in AD have been marked, respectively, by potentially severe side effects and/or limited efficacy. Transcranial direct current stimulation (tDCS) is a relatively novel non-pharmacological method of neuromodulation with promising results. Compared to previous tDCS formats, recent technological advances have increased the portability of tDCS, which creates the potential for caregiver-administered, home use. Our study aims to evaluate the feasibility, safety, and efficacy of home-based tDCS for the treatment of apathy in AD. This is an experimenter- and participant-blinded, randomized, sham-controlled, parallel-group (1:1 for two groups) pilot clinical trial, involving 40 subjects with AD. After a brief training, caregivers will administer tDCS for participants at home under remote televideo supervision by research staff to ensure the use of proper technique. Participants will be assessed at baseline, during treatment (week 2, week 4, and week 6), and 6 weeks post-treatment. Dependent measures will cover cognitive performance, apathy, and other behavioral symptoms. Data about side effects and acceptability will also be collected. Our study will address apathy, an overlooked clinical problem in AD. Our findings will advance the field of non-pharmacological strategies for neuropsychiatric symptoms, presenting a great potential for clinical translation. ClinicalTrials.gov, NCT04855643.


The influence of adjacent level disc disease on discectomy outcomes.
The state of adjacent level discs and its impact on surgical outcomes following single-level lumbar discectomy have not been previously investigated. The purpose of the present study was to determine if a significant relationship exists between the degree of preoperative adjacent level disc degeneration and post-operative clinical outcomes following lumbar discectomy. This study retrospectively used preoperative magnetic resonance imaging (MRI) and prospectively collected data from a randomized clinical trial at two tertiary-care academic hospitals. Patients who underwent a primary, single-level lumbar discectomy were included. Exclusion criteria included prior lumbar surgery. Outcome measures were the Modified Oswestry Disability Index (ODI) score and Visual Analog Scale (VAS) scores for back and leg pain. These were recorded at baseline and at 3 months, 1, and 2 years postoperatively. An independent reviewer graded adjacent level disc degeneration on all preoperative MRIs using the Pfirrmann grading scale. These data were then analyzed for correlation with each outcome measure. Forty-seven patients were included in the study. No statistically significant correlations were found when comparing preoperative 3-month or 1-year postoperative scores or change from baseline of any outcome measure between Pfirrmann grades. Only about half the patients had 2-year follow-up, but at that time point a statistically significant difference in back VAS scores was observed between Pfirrmann groups. No other significant differences were observed at that point. The degree of preoperative adjacent level degeneration does not significantly affect functional or pain relief outcomes following lumbar discectomy up to 1 year after surgery.


Clonotype patterns of antibodies released by single lymph nodes.
Experimental primary, secondary and tertiary stimulation with streptococcal vaccine of isolated lymph nodes in vivo in the sheep model induces largely persistence of anti-group polysaccharide antibody clonotype patterns with the rare occurrence of additional clonotypes demonstrable after secondary stimulation persisting during the tertiary stimulus. It is not clear whether these additional clonotypes are the products of mutants or whether they pre-existed and were demonstrable only after a secondary stimulus, because of threshold concentrations required for identification. Further, isolated contralateral popliteal and prescapular lymph nodes of individual sheep share completely overlapping clonotype patterns during experimental primary anti-polysaccharide antibody responses indicating an identical repertoire of specific clonotypes under this condition of responsiveness.


Clinicopathological and embryological considerations of single ectopic ureters opening into Gartner's duct cyst: a unique subtype of single vaginal ectopia.
We report 6 cases of single ectopic ureters opening into a Gartner's duct cyst. All but 1 patient were children. The presenting symptoms were urinary incontinence, urinary tract infection, a vaginal mass or weight loss. All but 1 patient had a mass protruding into the vagina. In 5 cases nephroureterectomy was performed successfully. The cyst wall was left untouched to allow for its spontaneous collapse. Although 2 cysts were found to communicate with the vagina, 4 presented as a closed space. All resected kidneys were more dysplastic than those with vaginal ectopia without cyst formation. The etiology and pathogenesis of the anomaly are unknown but some speculations are made.


Development of liposomal immunosensor for the measurement of insulin with femtomole detection.
The monitoring of insulin is of great relevance for the management of diabetes, the detection of pancreatic islet-cell malfunction, the definition of hypoglycemia, and the diagnosis of insulinoma. A liposomal immunosensing system for the determination of insulin was developed in this study. The insulin sensor was constructed by the immobilization of anti-insulin antibodies on the inner wall of the microcapillary immunoseparator. Liposomes tagged with anti-insulin and encapsulating a fluorescent dye were used as the detectable label. In the presence of insulin, sandwich immunocomplexes were formed between the immobilized antibodies in the column, the sample of insulin, and the antibody-tagged sulforhodamine B-dye-loaded liposomes. Signals generated by lysing the bound liposomes with 30 mM n-octyl-beta-D-glucopyranoside were measured by a fluorescence detector. The detected signal was directly proportional to the amount of insulin in the test sample. The liposomal immunosensing system successfully detected as low as 136 attomole. MeOH (30%) was used for the regeneration of antibody-binding sites in the microcapillary after each measurement, which allowed the immunoseparator to be used for at least 70 repeated assays. The antibody activity in this proposed microcapillary immunoseparator could be well maintained for at least 1 week. The calibration curve for insulin in Tris-buffered saline had a linear dynamic range of 10 pM-10 nM, and the total assay time was less than 30 min. The coefficient of variation for triplicate measurements was <5.00%, which indicated that well-reproducible results can be obtained by this newly developed method.


Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy.
In 8 brains of patients with various combinations of striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome, inclusion bodies were demonstrated in the cytoplasm and nucleus of both neuronal and oligodendroglial cells and in neuronal processes by means of silver staining, immunocytochemistry and electron microscopy. Differing from oligodendroglial cytoplasmic inclusions recognized by anti-ubiquitin, anti-alpha- and anti-beta-tubulin, and anti-tau antibodies, neuronal cytoplasmic inclusions were stained only by anti-ubiquitin antibody but not with those raised against cytoskeletal proteins. Tubular structures forming the inclusion bodies irrespective of their glial or neuronal location, have fuzzy cover and side extensions which make them similar to the linear structures described in motor neuron diseases. Our study proves that the accumulation of abnormal tubular structures in both oligodendrocytes and neurons is the basic pathological alteration in multiple system atrophy and defines multiple system atrophy as a group of diseases with similar cellular pathology or as a nosological entity.