Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review.
Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most important manifestations of SLE, and includes a variety of clinical manifestations, classified by the American College of Rheumatology in 19 different neuropsychiatric syndromes. To date, more than 116 antibodies have been reported in SLE and at least 20 of them, including 11 brain-specific and 9 systemic antibodies, have been controversially associated with NPSLE. To systematically review the available evidence, to define the association between the above antibodies and NPSLE as a whole and with the 19 neuropsychiatric syndromes associated with SLE, by strictly applying the American College Rheumatology case definitions. Medline reports published between 1999 and 2013 investigating the association between antibodies and NPSLE were included. Whenever possible, associations between antibodies and both NPSLE as a whole and with the 19 syndromes were analysed. This systematic review is based on available data from more than 8,000 patients and controls from 42 studies analysing antibodies and NPSLE. Nineteen studies analysed the role of antiphospholipid antibodies (aPL), 11 focused on anti-ribosomal-P protein antibodies and 5 on anti-N-Methyl-D-Aspartate receptor antibodies. Two studies analysed, respectively, antibodies to aquaporin-4 and VH4-34 encoded antibodies. Given the multitude of clinical manifestations related to NPSLE, a single biomarker failed to be reliably associated with all neuropsychiatric events. Our findings provide evidence that aPL, mainly the lupus anticoagulant, and anti-ribosomal P antibodies are significantly associated with specific manifestations of neuropsychiatric disease attributed to SLE, namely, cerebrovascular events and psychosis, respectively.


Nurses' beliefs and perceptions regarding family-centered care services in acute pediatric healthcare settings.
To describe pediatrics nurses' beliefs about family-centered services (FCS) as a model of providing healthcare to children in acute care settings in Jordan. This is a cross-sectional descriptive study. Nurses who provide direct acute care to children (n = 246) completed the 'Measure of Beliefs about Participation in Family-Centered Service' questionnaire. Descriptive statistics were used to describe nurses' beliefs about participation, practical feasibility, implementation self-efficacy, principles, and potential adverse outcomes of FCS. Many nurses feel confident (70%) about their ability to work with others in providing FCS and perceive having the ability to operate according to family-centered care (FCC) principles (68%). Many (75%) nurses believed parents should be encouraged to decide how much they want to be involved in the child's care. However, only 46% of the nurses valued attending to family priorities if the health decisions made by the family differed from the healthcare providers' priorities. Many nurses (70%) believed that healthcare professionals' competencies and capacities to work utilizing FCC are more important than their personal preferences and opinion. The findings of this study clearly indicate that nurses positively viewed providing children's care within a FCS. This supports the efforts to reasonably integrate FCC as an operating model in the pediatric healthcare settings in Jordan. FCS is a complex task requiring integrating multidisciplinary effort and healthcare providers' positive attitudes toward families as care partners. Steps should help maximize the organizational resources to facilitate family presence and create opportunities for professional-families partnerships for children's care.


Genetic analysis of coding SNPs in blood-brain barrier transporter MDR1 in European Parkinson's disease patients.
Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons and the presence of intracytoplasmic inclusions (Lewy bodies). Iron, which is elevated in the substantia nigra of PD patients, seems to be of pivotal importance, because of its capacity to enhance the amplification of reactive oxygen species. As iron enters and exits the brain via transport proteins in the blood-brain barrier (BBB), these proteins may represent candidates for a genetic susceptibility to PD. P-glycoprotein (P-gp) is one important efflux pump in the BBB. There is evidence that the function of P-gp is impaired in PD patients. In the current study we examined ten coding single nucleotide polymorphisms in the multidrug resistance gene 1 (MDR1) encoding P-gp to assess whether certain genotypes are associated with PD. However, genotyping of 300 PD patients and 302 healthy controls did not reveal a significant association between coding MDR1 gene polymorphisms and PD.


Procalcitonin, a high acute phase reactant in antiepileptic hypersentivity syndrome in pediatric age.
Antiepileptic hypersensitivity syndrome (AHS) is a potentially life-threatening syndrome in pediatric cases. It is associated with aromatic anticonvulsivant drugs and others antibiotics with or without associated reactivation of virus. The pathogenesis of the process is not clear. Clinical feature of this syndrome include cutaneous reactions, fever and lymphadenopathies, but different organs can be involved. In laboratory analyses we can find leucocytosis, eosinophilia, and increase in transaminase levels. Significant elevation of procalcitonin (PCT) has been described in two adults patients. This study we report two cases of a 14-year-old male and a 13-year-old female with a AHS and a high level of the PCT. These are the first cases described in pediatric age. Establishing a diagnosis of AHS is important to avoid the use of the involved drug. The treatment is based on the withdrawal of the drugs that are supposed and if there is no improvement or a deterioration of the patient, the use of systemic corticosteroids is often useful.


Postoperative adjuvant and salvage radiotherapy for prostate cancer: impact on freedom from biochemical relapse and survival.
To determine the therapeutic outcomes in patients with high-risk prostate cancer treated with adjuvant or salvage radiotherapy (RT) after radical prostatectomy. Between 1982 and 2000, 163 patients were treated with RT after radical prostatectomy. Adjuvant therapy was administered to 107 consecutive node-negative patients (T2-T4N0) referred to our institution less than 1 year after surgery for postoperative RT. Salvage treatment was delivered to 56 patients for a persistently elevated prostate-specific antigen level, biochemical relapse after surgery, or local recurrence. The median follow-up was 70 months (range 2 to 167) from the initiation of RT. Patients treated with adjuvant RT were less likely than those treated with salvage RT to experience biochemical relapse. At 5 and 10 years, the rate of freedom from biochemical relapse was 80% and 66% in the adjuvant cohort compared with 39% and 22% for patients treated with salvage intent, respectively (P <0.0001). This did not translate into a statistically significant improvement in absolute survival (72% versus 70%) or cause-specific survival (93% versus 86%) at 10 years. On multivariate analysis, neoadjuvant hormonal therapy (P = 0.0187), presence of seminal vesicle involvement (P = 0.0002), and referral indication for postoperative RT (salvage versus adjuvant RT; P <0.001) were predictors of biochemical relapse. In this single-institution experience, patients at high risk of disease recurrence after radical prostatectomy realized a greater biochemical relapse-free survival benefit when treated with adjuvant RT than with salvage RT. Neoadjuvant hormonal therapy and seminal vesicle involvement predicted for inferior treatment outcome.


[The significance of theramus palatinus to the development of the vomerine bar inSalamandra salamandra (L.)].
The influence of theramus palatinus (VII.) and the postion of the vomer on the vomerine bar, which develops during metamorphosis, was studied by various amputation procedures. Cutting off the nerve cord does not prevent the development of the vomerine bar, as the nerve soon regenerates, whereas cutting off and displacement as well as the removal of portions of theramus palatinus do prevent development. Removal of portions of the nerve cord during metamorphosis produces only parts of the vomerine bar. Obviously an intact ramus palatinus is necessary for the outgrowth of the novel osseous vomerine bar. The course of this outgrowth is independent of the position of the larval vomer.


Metal-associated human health risk assessment due to consumption of pelagic and benthic ichthyofaunal resources from the highly contaminated Cuddalore coast in Southern India.
We present seasonal variation of four metals (Cd, Cu, Pb, and Zn) in nine pelagic and three benthic fish species from the highly polluted Cuddalore coast in Tamil Nadu, India. Metals were assessed using atomic absorption spectrometry and detected in all fish species, in at least one season, except Iniistius cyanifrons where cadmium was not detected throughout. In both benthic and pelagic fish, order of metal concentration was Zn > Cu > Pb > Cd. Multivariate statistical analysis revealed that metals may have originated from both natural and anthropogenic sources. Health risk assessment revealed that consumption of fish from Cuddalore coast does not pose health risk for now; however, hazard index values (pelagic = 0.97; benthic = 0.90) are in borderline. Even a slight increase in metal concentration in fish can prove hazardous for human consumption. Sooner or later, eating fish from Cuddalore coast may pose a considerable health risk to humans if metal pollution is not held at Bay.


Aberrant glycosaminoglycan biosynthesis by tumor suppressor EXTL2 deficiency promotes liver inflammation and tumorigenesis through Toll-like 4 receptor signaling.
Certain proteoglycans, consisting of a core protein and glycosaminoglycan (GAG) chains, are among the many types of biomolecules that can function as damage-associated molecular pattern molecules (DAMPs). We, therefore, hypothesized that the expression level and structural alteration of GAGs affect inflammation. We have previously reported that the effects on GAG biosynthesis caused by loss of the tumor suppressor gene exostosin-like 2 (Extl2) influence liver injury and regeneration processes. To examine how altered GAG biosynthesis may underscore the relationship between inflammation and tumorigenesis, we assessed its role in non-alcoholic steatohepatitis and hepatocarcinoma (HCC) induced by dietary obesity and insulin-resistance. We demonstrated that GAGs produced in the absence of EXTL2 act as DAMPs and directly input signals into cells via the Toll-like 4 receptor. In addition, the subsequent transcriptional activation of inflammatory and tumor-promoting cytokines by NF-κB contributes to injury- and inflammation-driven tumor promotion. Thus, dysregulated biosynthesis of GAGs is considered to increase the risk of HCC in a background of obesity and diabetes.


Hygroscopic and hydrolytic effects in dental polymer networks.
The objective of this manuscript is to outline the factors associated with hygroscopic and hydrolytic effects in dental polymer networks, and to review the literature generated over the past thirty years or more in this area. Information was gathered from nearly 90 published articles or abstracts appearing in the dental and polymer literature. Studies were predominantly identified through a search of the PubMED database. Studies were included that provided direct evidence for the uptake of solvent by a polymer network and its subsequent physical or chemical effect, or the loss of molecular species into solvents. An attempt was made to select articles that spanned the timeframe from approximately 1970 to today to ensure that most of the classic literature as well as the latest information was included. Dental polymer networks have been shown to be susceptible to hygroscopic and hydrolytic effects to varying extents dependent upon their chemistry and structure. The importance of these effects on the clinical performance of polymer restoratives is largely unknown, though numerous investigators have alluded to the potential for reduced service lives. While the physical and mechanical properties of these materials may be significantly altered by the effects of solvent uptake and component elution, what may constitute the greatest concern is the short-term release of unreacted components and the long-term elution of degradation products in the oral cavity, both of which should be strongly considered during restorative material development.


A Systematic Review for Health Disparities and Inequities in Multiparametric Magnetic Resonance Imaging for Prostate Cancer Diagnosis.
Multi-parametric Magnetic Resonance Imaging (mpMRI) is a novel procedure recommended by the American Urological Association for Prostate Cancer (PCa) diagnosis. In radiology, differences in utilization of expensive screening techniques are described but never reviewed for mpMRI. Thus, our article aims at summarizing disparities relating to the expensive yet revolutionary mpMRI in United States men with PCa while highlighting needed research areas. Eligible articles were gathered via PubMed query, referred publications known to the authors or from the reference lists of the identified publications. We excluded studies that didn't specifically evaluate mpMRI technique, weren't conducted in the United States, or didn't directly assess the relationship between disparities and mpMRI. No date restrictions were applied, resulting articles were published through 2020. Out of 80 publications, 17 were selected. Two unique themes were identified: 1) disparities in mpMRI utilization, and 2) performance. While demographic factors such as race, age and socioeconomic status played a significant role in utilization, mpMRI demonstrated equal and sometimes superior performance in AAs. Our findings illustrate the importance of disparity awareness in PCa mpMRI and highlight the need to examine additional mpMRI disparities across other races and social determinants. A new area of inequity in PCa was theoretically illustrated, as lower utilization of mpMRI was detected in a group that could potentially benefit from it the most. Major limitation was the selected search terms. Our review is unique as disparities related to mpMRI were found to be multilayered, affecting utilization and performance. Continued research is needed to discover additional areas in efforts to reduce disparity gaps related to mpMRI and PCa.


An applied anatomical study of the superior laryngeal nerve loop.
The aim of this study was to provide some specific information about the morphology and topography of the superior laryngeal n., its branches, and its anastomoses with the cervical sympathetic chain, as well as its relations with the thyroid gland. Sixty adult cadavers, i.e. 120 superior laryngeal nn., were dissected and analysed. An anastomotic loop connecting the cervical sympathetic chain and the distal laryngeal n. was present in 111 of the 120 cases. The morphology of this loop made it possible to define 5 different groups. This study supplies information valuable in thyroid surgery.


Evaluation of a PCR based assay for specific detection of Campylobacter jejuni in chicken washes.
An assay for Campylobacter jejuni based on the polymerase chain reaction was developed in our laboratory and shown to be a sensitive and specific method to identify this bacterium in pure culture. This assay was evaluated as a method to rapidly detect C. jejuni attached to chicken carcasses. Chicken carcasses were sampled for PCR using three methods including pre-enrichment of the washes, direct plating of the washes and differential centrifugation of the washes prior to testing. It was found that plating the wash solutions on Campy Cefex plates prior to performing PCR was the most specific and reliable of the three treatment methods evaluated.


Biliary complications in 106 consecutive duct-to-duct biliary reconstruction in right-lobe living donor liver transplantation performed in 1 year in a single center: a new surgical technique.
Biliary complications remain a major source of morbidity after living donor liver transplantation (LDLT). Of 109 consecutive right lobe (RL)-LDLTs performed in 1 year in our institution, we present the biliary complications among 106 patients who underwent a new duct-to-duct anastomosis technique known as University of Inonu. Of 153 liver transplantations performed in 1 year from January to December of 2008, 128 were LDLTs including 109 RL-LDLTs. The others were left or left lateral grafts. All RL-LDLT patients were adults, all of whom except three included a duct-to-duct anastomosis. All, but three, biliary reconstructions were completed with a surgical technique, so called UI, in which 6-0 prolene sutures were used. Nine bile leaks were seen in 106 recipients (8.49%) performed in a duct-to-duct fashion in a time period of 1 to 4 weeks. Seventeen patients (16.03%) posed bile duct stricture (BDS). Five patients had both. Although endoscopic stent placement and percutaneous balloon dilatation, 4 patients continued to suffer from BDS on whom a permanent access hepatico-jejunostomy (PAHJ) procedures were performed. We recommend a duct-to-duct biliary reconstruction because of its de facto advantages over other types of anastomosis provided the native duct is not diseased. After almost 2 years, the bile tract complication rate was 22.64%.


[Microwave coagulation therapy with potassium titanyl phosphate (KTP) laser therapy for airway stenosis from a recurrent tracheocarinal tumor].
About 2 years after right lower lobectomy for anadenocarcinoma in the right lung, an 80-year-old man had a reccurent tumor in tracheocarinal lymph nodes. Although concurrent chemoradiotherapy was performed, there was no change (NC) and the tumor grew back slowly. He was admitted to our hospital with exertional dyspnea and stridor 2 years later. The bronchoscopic microwave coagulation therapy was performed in the right main bronchus. After potassium titanyl phosphate (KTP) laser therapy had been performed in the tracheocarinal lumen, an expandable metallic stent was performed. The postopertive course was uneventful.


Analysis of the RNA species isolated from defective particles of vesicular stomatitis virus.
Serial high multiplicity passage of a cloned stock of vesicular stomatitis virus was found to generate defective interfering particles containing three size classes of RNA, with sedimentaiton coefficients of 31 S, 23 S and 19 S. The 31 S and 23 S RNA species were found to be complementary to both the 12 to 18 S and 31 S size classes of VSV mRNAs. The 19 S class of RNA was found to be partially base-paired. All three RNA species were found to contain ppAp at their 5' termini.


Involvement of leukocytes in the oxygenation and chlorination reaction of phenylbutazone.
A center carbon atom of 1,3-diketone moiety of phenylbutazone was oxidized to give three metabolites--4-hydroxyphenylbutazone (metabolite I), 4-hydroperoxyphenylbutazone (metabolite II) and 4-chlorophenylbutazone (metabolite III)--by the action of enzymes present in leukocyte extract obtained from peritoneal exudate of rats. Both metabolites II and III were produced by peroxidases, while metabolite I was produced by enzymes other than the peroxidases.


Comparative study of lung ultrasound and chest computed tomography scan in the assessment of severity of confirmed COVID-19 pneumonia.
The relationship between lung ultrasound (LUS) and chest computed tomography (CT) scans in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia is not clearly defined. The primary objective of our study was to assess the performance of LUS in determining severity of SARS-CoV-2 pneumonia compared with chest CT scan. Secondary objectives were to test the association between LUS score and location of the patient, use of mechanical ventilation, and the pulse oximetry (SpO2)/fractional inspired oxygen (FiO2) ratio. A multicentre observational study was performed between 15 March and 20 April 2020. Patients in the Emergency Department (ED) or Intensive Care Unit (ICU) with acute dyspnoea who were PCR positive for SARS-CoV-2, and who had LUS and chest CT performed within a 24-h period, were included. One hundred patients were included. LUS score was significantly associated with pneumonia severity assessed by chest CT and clinical features. The AUC of the ROC curve of the relationship of LUS versus chest CT for the assessment of severe SARS-CoV-2 pneumonia was 0.78 (CI 95% 0.68-0.87; p < 0.0001). A high LUS score was associated with the use of mechanical ventilation, and with a SpO2/FiO2 ratio below 357. In known SARS-CoV-2 pneumonia patients, the LUS score was predictive of pneumonia severity as assessed by a chest CT scan and clinical features. Within the limitations inherent to our study design, LUS can be used to assess SARS-CoV-2 pneumonia severity.


alpha 7-type acetylcholine receptor localization and its modulation by nicotine and cholesterol in vascular endothelial cells.
The neuronal-type α7 nicotinic acetylcholine receptor (α7AChR) is also found in various non-neural tissues, including vascular endothelium, where its peculiar ionotropic properties (high Ca(2+) permeability) and its supervening Ca(2+) -mediated intracellular cascades may play important roles in physiology (angiogenesis) and pathology (inflammation and atherogenesis). Changes in molecular (up-regulation, affinity, and conformational states) and cellular (distribution, association with membranes) properties of the α7AChR related to angiogenesis (wound-repair cell migration) and atherogenesis (alterations in cholesterol content) were studied in living endothelial cells, with the aim of determining whether such changes constitute early markers of inflammatory response. The combination of pharmacological, biochemical, and fluorescence microscopy tools showed that α7AChRs in rat arterial endothelial (RAEC) and human venous endothelial (HUVEC) cells occur at extremely low expression levels (∼50 fmol/mg protein) but undergo agonist-induced up-regulation at relatively high nicotine concentrations (∼300-fold with 50 µM ligand), increasing their cell-surface exposure. When analyzed in terms of cold Triton X-100 solubility and subcellular distribution, α7AChRs occur in the "non-raft" subcellular membrane fractions. Acute cholesterol depletion reduced not only cholesterol levels but also the number of cell-surface α7AChRs. Nicotine exposure markedly stimulated cell migration and accelerated wound repair, which drastically diminished in cells deprived of the sterol. The angiogenic effect of nicotine appears to be synergistic with cholesterol content. Finally, the apparent K(D) of α7AChRs for the open-channel blocker crystal violet was found to be ∼600-fold lower in receptor-enriched membranes obtained from up-regulated HUVEC.


Moment-to-moment interaction between affectivity and coping behaviours in bipolar disorder and the role of cognitive appraisals.
Individuals with bipolar disorder respond to affective symptoms with a range of coping behaviours, which may further maintain the symptoms. To examine moment-to-moment dynamics between affective states and coping behaviours, and to evaluate the role of cognitive appraisals of internal states as moderators. Forty-six individuals with bipolar disorder completed a clinical interview and an experience sampling assessment over 6 days. Time-lagged analyses were conducted by multilevel regression modelling. A total of 1807 momentary entries were analysed. Negative affect predicted an increase in rumination at the subsequent time point (β = 0.21, s.e. = 0.08, P = 0.009, 95% CI 0.05-0.36), and vice versa (β = 0.03, s.e. = 0.01, P = 0.009, 95% CI 0.01-0.05). Positive affect predicted an increase in adaptive coping (β = 0.26, s.e. = 0.11, P = 0.018, 95% CI 0.04-0.47), and vice versa (β = 0.02, s.e. = 0.01, P = 0.019, 95% CI 0.00-0.03). Positive affect also predicted a decrease in rumination (β = -0.15, s.e. = 0.06, P = 0.014, 95% CI -0.26 to -0.03), and vice versa (β = -0.03, s.e. = 0.01, P = 0.016, 95% CI -0.06 to -0.01). Extreme cognitive appraisals predicted stronger associations between affective states and coping behaviours. Feedback loops between affective states and coping behaviours were revealed in the daily life of individuals with bipolar disorder, which were moderated by extreme cognitive appraisals. None.


Physiological and metabolomics responses of two wheat (Triticum aestivum L.) genotypes differing in grain cadmium accumulation.
To reduce cadmium (Cd) pollution of food chains, screening and breeding of low-Cd-accumulating genotypes have received increasing attention. However, the mechanisms involving Cd tolerance and accumulation are not fully understood. Here, we investigated the physiological responses and metabolomics profiling on two wheat (Triticum aestivum L.) genotypes, a low-Cd-accumulating genotype in grains (Aikang58, AK58) and a high-Cd-accumulating genotype in grains (Zhenmai10, ZM10), in hydroponic culture treated without/with Cd for 7 days. The results showed that AK58 was a Cd tolerant genotype with higher capacity of antioxidant systems in root. In addition, the concentrations of Cd bound to root cell walls were higher in AK58 than ZM10, of which pectin and hemicellulose played important roles in Cd binding. Moreover, subcellular distribution manifested that Cd sequestrated in the vacuoles was another tolerance mechanism in AK58. Simultaneously, metabolomics profiling showed that, in AK58, phenylalanine metabolism, alanine, aspartate and glutamate metabolism, isoquinoline alkaloid biosynthesis, arginine and proline metabolism, arginine biosynthesis and glyoxylate and dicarboxylate metabolism are highly related to antioxidant defense system, cell wall biosynthesis and metabolisms of phytochelatins together with other organic ligands, playing crucial roles in Cd tolerance and Cd fixation mechanisms in roots. These novel findings should be useful for molecular assisted screening and breeding of low Cd-accumulating genotypes for wheat crop.


Medicaid expansion and surgery for HPB/GI cancers: NCDB difference-in-difference analysis.
It is unclear if Medicaid expansion improved access to surgical resection for hepatopancreatobiliary (HPB) and gastrointestinal (GI) cancers. This was a quasi-experimental, cohort study using difference-in-difference analysis to evaluate differences in surgical resection for HPB/GI cancers in the post-Medicaid expansion era compared to the pre-Medicaid expansion era among patients residing in states that had Medicaid expansion versus not. During the pre- (2011-2013) and post-Medicaid expansion (2015-2017) eras, there were 49,954 patients between the ages of 40-64 who had liver cancer (n = 19,384; 38.8%), pancreatic cancer (n = 14,351; 28.7%), colorectal liver metastasis (n = 7566; 15.1%), or gastric cancer (n = 8653; 17.3%). 43.2% resided in expansion states (n = 21,577). There were no significant differences in the overall rates of surgical resection between expansion and non-expansion states before and after Medicaid expansion. Medicaid expansion did not impact surgical resection for HPB/GI cancers.


Selective naming (and comprehension) deficits in Alzheimer's disease?
The study addresses the issue of the selective preservation of verbs in Alzheimer's disease (AD). Twenty three AD patients and age-matched controls named pictures of objects and actions and took part in a word-picture verification task. The results for picture naming revealed that both patients and controls were faster and produced more target responses for objects than actions. In the comprehension task, accuracy levels were comparable for nouns and verbs, but response times were longer for verbs. Although patients were more error prone and had longer latencies in both tasks than controls, the only qualitative difference in performance between the groups was in response to trials with semantically related foils in the word-picture verification task. Patients were particularly error prone in this condition. We conclude that the results do not provide support for the notion that verbs are selectively preserved in AD. They also do not provide conclusive evidence for claims that depressed naming and comprehension is (always) due to loss of semantic knowledge or inadequate access to semantic knowledge. Finally, we discuss the findings in relation to comparable investigations in patients with semantic dementia.


Children's attitudes toward elderly individuals: a comparison of two ethnic groups.
The present study investigated the attitudes of Indian and American children toward elderly people. The "Children's Attitudes Toward the Elderly" questionnaire was used to measure how children perceived elderly people. Chi-square analyses indicated that children of Indian origin gave behavioral responses more often than affective or cognitive ones, while American children were more affective in their responses to questions about their interactions with elderly individuals. The results indicated that Indian children though born and raised in America were encouraged to follow the traditional values of their families' culture. Further research should include actual observations of children from different ethnic backgrounds interacting with elderly people.


The receptor for advanced glycation endproducts (RAGE) decreases survival of tumor-bearing mice by enhancing the generation of lung metastasis-associated myeloid-derived suppressor cells.
Metastatic cancer has a poor prognosis. Novel pharmacologic targets need to be identified. The receptor for advanced glycation endproducts (RAGE) is a pattern recognition receptor constitutively expressed in the lungs. Absence of overt disease in RAGE null mice suggests that RAGE is unnecessary or redundant in health. We report that RAGE null tumor-bearing mice have reduced lung metastasis and improved survival. Bone marrow chimera studies suggest that hematopoietic cell RAGE is an important contributor to these effects. Deletion of RAGE reduces both the quantity and suppressive activity of tumor-induced MDSC. Protein and mRNA studies suggest that RAGE contributes to the generation and function of MDSC including expression of the alarmins S100A8/A9 and activity of inducible nitric oxide synthase, arginase-1, and NF-κB. These findings demonstrate the important role of RAGE in determining the quantity and function of tumor-associated MDSC and suggest RAGE as a pharmacologic target for patients with metastatic disease.


Prevalence and clinical correlates of antinuclear antibody in patients with gastroparesis.
Autoimmunity may play a role in the pathogenesis of gastroparesis in a subset of patients. Antinuclear antibody (ANA) testing is often used to screen for autoimmune disorders. 1) Determine prevalence of a positive ANA in patients with gastroparesis; 2) Describe characteristics of idiopathic gastroparesis patients with positive ANA. Patients were assessed with gastric emptying scintigraphy (GES), symptom assessment via Patient Assessment of Upper GI Symptoms [PAGI-SYM], and blood tests-ANA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). Positive ANA was seen in 148 of 893 (17%) patients with gastroparesis, being similar in idiopathic (16% of 536 patients), T1DM (16% of 162), T2DM (18% of 147), and postfundoplication (19% of 48 patients) gastroparesis. Among 536 patients with idiopathic gastroparesis, ANA titer 1:40-1:80 was seen in 33 (6%) patients, 1:160-1:320 in 36 (7%) patients, and ≥1:640 in 17 (3%) patients. Increasing ANA titer was associated with female gender (p = 0.05), Hispanic ethnicity (p = 0.02), comorbid rheumatoid arthritis (p = 0.02), systemic sclerosis (p = 0.004), and elevated ESR (p = 0.007). ANA positivity was associated with lower total GCSI (p = 0.007) and lower nausea/vomiting subscale (p = 0.0005), but not related to gastric emptying. The prevalence of a positive ANA in patients with gastroparesis was high at ~17% and did not differ significantly based on etiology. In idiopathic patients, ANA positivity was associated with rheumatoid arthritis, systemic sclerosis, and elevated ESR. ANA-positive gastroparesis represents a subset who often have other autoimmune symptoms or disorders, but less severe nausea and vomiting.


Cortical plasticity following surgical extension of lower limbs.
Human cortical plasticity has been studied after peripheral sensory alterations due to amputations or grafts, while sudden 'quasi-physiological' changes in the dimension of body parts have not been investigated yet. We examined the cortical reorganization in achondroplastic dwarfs submitted to progressive elongation (PE) of lower limbs through the Ilizarov technique. This paradigm is ideal for studying cortical plasticity because it avoids the perturbation connected with deafferentation and re-afferentation. Somatosensory evoked-potentials (SEP) and fMRI studies were performed before and after PE during foot and knee stimulation, above and below the surgical fracture. A body schema test was also performed. Following PE, cortical modifications were observed in the primary somatosensory cortex for foot stimulation and in higher order somatosensory cortices for foot and knee. The former modifications tended to decrease 6 months after the elongation ending, whereas the latter tended to persist. Results are interpreted in terms of cortical adaptation mediated by temporary disorganization.


Smoke from regional wildfires alters lake ecology.
Wildfire smoke often covers areas larger than the burned area, yet the impacts of smoke on nearby aquatic ecosystems are understudied. In the summer of 2018, wildfire smoke covered Castle Lake (California, USA) for 55 days. We quantified the influence of smoke on the lake by comparing the physics, chemistry, productivity, and animal ecology in the prior four years (2014-2017) to the smoke year (2018). Smoke reduced incident ultraviolet-B (UV-B) radiation by 31% and photosynthetically active radiation (PAR) by 11%. Similarly, underwater UV-B and PAR decreased by 65 and 44%, respectively, and lake heat content decreased by 7%. While the nutrient limitation of primary production did not change, shallow production in the offshore habitat increased by 109%, likely due to a release from photoinhibition. In contrast, deep-water, primary production decreased and the deep-water peak in chlorophyll a did not develop, likely due to reduced PAR. Despite the structural changes in primary production, light, and temperature, we observed little significant change in zooplankton biomass, community composition, or migration pattern. Trout were absent from the littoral-benthic habitat during the smoke period. The duration and intensity of smoke influences light regimes, heat content, and productivity, with differing responses to consumers.


Regulation of neutrophil phagocytosis of Escherichia coli by antipsychotic drugs.
Antipsychotic drugs (APDs) have been used to ease the symptoms of schizophrenia. APDs have recently been reported to regulate the immune response. Our previous studies revealed that the atypical APDs risperidone and clozapine and the typical APD haloperidol can inhibit the phagocytic ability of macrophages. Our research next determined the effects of APDs on the phagocytic ability of neutrophils, which are the most abundant type of white blood cells in mammals. Here we provide evidence that clozapine and haloperidol can induce increased phagocytic uptake of Escherichia coli by differentiated HL-60 cells and by purified human neutrophils. Furthermore, clozapine and haloperidol can increase the myeloperoxidase activity and IL-8 production in neutrophils. Our results also show that clozapine can inhibit E. coli survival within differentiated HL-60 cells. Furthermore, clozapine and haloperidol are shown to enhance cell surface Mac-1 expression and the activated AKT signaling pathway in purified neutrophils exposed to E. coli. These results indicate that clozapine and haloperidol can increase the phagocytic ability of neutrophils by increasing AKT activation when cells are exposed to bacteria.


Findings in routine laboratory examination in progressive myoclonus epilepsy.
Thirty-one patients suffering from progressive myoclonus epilepsy, (also called Unverricht-Lundborg's disease) without Lafora bodies, were examined to check the findings reported in literature and to chart out the main abnormalities in routine laboratory findings. Many alterations could be pointed out, but a high proportion of them were due to factors which are secondary to the syndrome of progressive myoclonus epilepsy: continuous anticonvulsive medication; immobilization; frequent infections; and the patient's poor nutritional condition. The most remarkable finding, and the only one which supported the abnormality reported earlier, was the raised excretion of indican which could not be explained by fermentation in the bowels. The urinary 5-hydroxyindoleacetic acid excretion was a little low, but still within the normal range. The tryptophan and 5-hydroxytryptamine metabolism deserves further investigation in attempting to discover the aetiology of progressive myoclonus epilepsy.


Binding and agonist/antagonist actions of M35, galanin(1-13)-bradykinin(2-9)amide chimeric peptide, in Rin m 5F insulinoma cells.
The chimeric peptide M35 [galanin(1-13)-bradykinin(2-9) amide] is a high-affinity galanin receptor ligand acting as a galanin receptor antagonist in the rat spinal cord, rat hippocampus and isolated mouse pancreatic islets. We have radiolabelled M35 and performed equilibrium binding studies with [125I]M35 on the rat pancreatic beta-cell line Rin m 5F, whereby we show the existence of high-affinity binding site (KD = 0.9 +/- 0.1 nM) with a Bmax of 72 +/- 3 fmol/mg protein. Galanin displaces [125I]M35 with the same affinity (KD = 1 nM) as it displaces [125I]galanin. Displacement of [125I]galanin by M35 from Rin m 5F cell membranes shows the presence of two binding sites for M35 with KD-values of 0.3 +/- 0.1 nM and 0.52 +/- 0.03 microM, respectively. The GTP- and pertussis toxin-sensitivity of M35 binding to Rin m 5F membranes shows that binding of [125I]M35 is almost completely abolished by the presence of GTP or after pertussis toxin treatment of the cells, indicating an agonist-like binding of M35 to the galanin receptors. M35 has a dual effect on the galanin mediated inhibition of forskolin stimulated cyclic AMP production in Rin m 5F cells: at low concentrations M35 antagonises the effect of galanin, whereas at concentrations above 10 nM M35 acts as a galanin receptor agonist. These agonist-like effects of galanin and M35 are not additive, thus the mixed agonist/antagonist properties arise from the chimeric nature of M35[galanin(1-13)-bradykinin(2-9)amide] acting solely at galanin receptors.


Erratum to "Impact of satellite blood culture on early diagnosis of sepsis" [Journal of Intensive Medicine volume 2 (2022) 56-60].
[This corrects the article DOI: 10.1016/j.jointm.2021.11.003.].


Toxoplasma gondii: an evaluation of diagnostic value of recombinant antigens in a murine model.
Laboratory diagnostics of toxoplasmosis depends primarily on serological methods detecting specific antibodies. Since these methods do not always enable specific and sensitive recognition of the infection and phase of toxoplasmosis, the search for new diagnostic tools continues. Recombinant antigens promise a new alternative in diagnostics of Toxoplasma gondii infections. In this work the usefulness of six recombinant T. gondii antigens: GRA1, GRA6, GRA7, p35, SAG1, and SAG2 in the detection of primary murine toxoplasmosis was evaluated. Sera obtained from infected mice differing in their natural susceptibility to T. gondii infection, BALB/c (relatively resistant) and C57BL/6 (relatively susceptible), were tested using ELISA. During acute infection high response to GRA7, GRA6, and p35 antigens was noticed, whereas a strong reactivity with surface antigens SAG1 and SAG2 was characteristic for chronic toxoplasmosis. Our results show that the recombinant antigens are useful in distinguishing between acute and chronic toxoplasmosis regardless of the genetically determined susceptibility of the host.


Bone marrow mesenchymal stem cell treatment improves post-stroke cerebral function recovery by regulating gut microbiota in rats.
Early intervention with bone marrow mesenchymal stem cells to change the form and function of the gut microbiota may help rats regain neurological function after a stroke.


Pressure effect on the three-dimensional charge-transfer ferromagnet [{Ru₂(m-FPhCO₂)₄}₂(BTDA-TCNQ)].
The magnetic properties of a three-dimensional infinite network compound, [{Ru₂(m-FPhCO₂)₄}₂(BTDA-TCNQ)] (m-FPhCO₂⁻ = m-fluorobenzoate; BTDA-TCNQ = bis(1,2,5-thiadiazolo)tetracyanoquinodimethane), were investigated under hydrostatic pressures up to 12.9 kbar. The applied pressure caused the intralattice exchange couplings to weaken, inducing a decrease in the magnetic phase transition temperature from 107 K at ambient pressure to 57 K at 12.9 kbar.


[Spatial similarity between crystal cells of various agonists of amino acid receptors and the biological effects of these substances].
Space likeness of crystal cells of GABA, glycine, muscimol and taurine has been estimated by special calculation. The relation between the likeness degree of crystal cells and their biological effect on amino acid receptors is marked.


Spiritual well-being correlates with quality of life of both cancer and non-cancer patients in palliative care - further validation of EORTC QLQ-SWB32 in Finnish.
The European Organisation for Research and Treatment of Cancer (EORTC) has developed the Spiritual Well-being Questionnaire (EORTC QLQ-SWB32), a measure of spiritual well-being validated with people receiving palliative care for cancer, although its usefulness is not restricted to that population. We aimed to translate and validate this tool in Finnish and to study the relationship between spiritual well-being (SWB) and quality of life (QOL). A Finnish translation was produced according to the guidelines of EORTC and included forward- and back-translations. Face, content, construct and convergence/divergence validity and reliability were studied in a prospective manner. QOL was assessed with EORTC QLQ-C30 and 15D questionnaires. Sixteen individuals participated in the pilot testing. 101 cancer patients drawn from oncology units, and 89 patients with other chronic diseases drawn from religious communities in different parts of the country participated in the validation stage. Retest was obtained from 16 individuals (8 cancer and 8 non-cancer patients). Inclusion criteria included patients with either a well-defined palliative care plan, or who would benefit from palliative care, as well as the capacity to understand and communicate in Finnish. The translation appeared understandable and acceptable. Factorial analysis identified four scoring scales with high Cronbach alfa values: Relationship with Self (0.73), Relationship with Others (0.84), Relationship with Something Greater (0.82), Existential (0.81), and, additionally, a scale on Relationship with God (0.85). There was a significant correlation between SWB and QOL in all participants. The Finnish translation of EORTC QLQ-SWB32 is a valid and reliable measure both for research and clinical practice. SWB is correlated with QOL in cancer and non-cancer patients undergoing palliative care or who are eligible for it.


Double cone-unit laparoscopic hepatic resection using indocyanine green negative counterstaining (with video).
A hepatic cone-unit represents an anatomical unit dominated by a smaller Glissonean pedicle. Anatomical resection of a tumor located in an intersegmental plane is challenging, but could be achieved effectively by performing multiple cone-unit resection. We performed double cone-unit laparoscopic resection of hepatocellular carcinoma located on the intersegmental plane between segments 6a, b. The liver parenchyma covering the posterior Glissonean pedicle was divided along Rouviere's sulcus, the Glissonean branches of segments 6a, b were isolated and ligated, and indocyanine green (ICG) negative counterstaining was performed. The hepatic parenchyma was dissected along the demarcation line to identify the right hepatic vein and the double cone-unit resection was then completed with a negative surgical margin. Thus, double cone-unit laparoscopic hepatectomy with ICG negative counterstaining may be a feasible option for tumors located in an intersegmental plane.


Assessment accuracy of core needle biopsy for hormone receptors in breast cancer: a meta-analysis.
The concordance of hormone receptors (HR) status identified by core needle biopsy (CNB) compared with excisional biopsy (EB) has been widely reported, but results were extremely variable and underpowered. To derive a more precise estimation of assessment accuracy of CNB for HR in breast cancer, we conducted a meta-analysis of all eligible studies comparing concordance or disconcordance between CNB and EB for HR status. Eligible articles were identified by search of databases including PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature database for the period up to November 2011, and the reference lists of identified studies, relevant reviews, meta-analyses, and abstracts from recent conference proceedings were reviewed as a augmented searching. Finally, a total of 21 articles involving 2,450 patients for estrogen receptor (ER) and 2,448 patients for progesterone receptor (PR) were included and analyzed in this analysis. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies checklist. The overall aggrement between CNB and EB were 92.8 % for ER (κ = 0.78) and 85.2 % for PR (κ = 0.66), indicating a good agreement in PR and a better result in ER. The pooled sensitivity and specificity were 97.3 % (95 % CI 96.0-98.2) and 82.0 % (95 % CI 68.2-90.6) for ER, and the corresponding values for PR were 92.3 % (95 % CI 88.2-95.1) and 76.5 % (95 % CI 64.6-85.3), respectively. The pooled positive likelihood ratios was 5.39 % (95 % CI 2.92-9.97) and the negative likelihood ratios was 0.03 % (95 % CI 0.02-0.05) for ER, the corresponding values for PR were 3.93 % (95 % CI 2.53-6.11) and 0.10 % (95 % CI 0.07-0.16), respectively. In summary, although a good agreement was observed between CNB and EB for both ER and PR, we still suggest that negative HR testing results should be interpreted with caution or repeated on EB.


New Horizons in the Treatment of Neurological Disorders with Tailorable Gold Nanoparticles.
Neurological disorders, such as epilepsy, dementia, Parkinson's disease and Alzheimer's disease, occur due to disorganization of the neurons in the nervous system. Disturbances in the nervous system cause problems with the memory, senses and moods. In order to treat such disorders, scientists have been working extensively, utilizing different approaches. Nanoneurotechnology has emerged as a promising tool to manage these complicated disorders, where nanoparticles with their tunable properties such as size, shape, increased solubility, biodegradability, surface area and sharp penetration through the biological barriers, target the central nervous system. This technology targets damaged neurons without affecting healthy neurons and the Blood-Brain Barrier (BBB). In this review, we discuss neurological disorders and challenges in their diagnosis and treatment by emphasizing on the role of tailorable gold nanoparticles in therapeutic drug approaches.


Surgical technique: posterior deltoid-to-triceps transfer in tetraplegic patients.
Several surgical techniques exist for restoring triceps function in tetraplegic patients. The goal is to establish a more synchronized, better controlled arm that allows increased self-sufficiency and further reconstructive surgery on the hand. To obtain the most secure fixation, adjust the tension, and allow early mobilization, the technique we prefer uses the central tendon of the triceps muscle and bony block fixation reinforced by the palmaris longus.


Resource recovery of Eichhornia crassipes as oil superabsorbent.
The elastic cellulose-based aerogels (CBAs) with highly porous (99.56%) and low-density (0.0065gcm-1) were prepared using Eichhornia crassipes as cellulose source and polyvinyl alcohol directly as cross-linker via a facile and environment-friendly process. The prepared CBAs exhibited excellent oil/solvent sorption capacities (60.33-152.21gg-1), super-hydrophobicity (water contact angle of 156.7°) as well as remarkable reusability. More importantly, the absorbed oil could be quickly recovered by simple squeezing without significantly structure damage (at least 16 times). All these merits make CBAs very promising materials for oil spillage cleaning.


Synthesis and SAR investigations of novel 2-arylbenzimidazole derivatives as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists.
Compounds containing 2-arybenzimidazole ring systems linked to arylpiperidines were synthesized and evaluated as MCH-R1 antagonists. The results of structure-activity relationship studies led to the identification of compound 4c as a potent MCH-R1 antagonist (IC(50)=1 nM). This compound also has good metabolic stability, and favorable pharmacokinetic and brain penetration properties. However 4c was found to be potent inhibitor of the hERG potassium channel.


Droplet evaporation on porous fabric materials.
Droplet evaporation on porous materials is a complex dynamic that occurs with spontaneous liquid imbibition through pores by capillary action. Here, we explore water dynamics on a porous fabric substrate with in-situ observations of X-ray and optical imaging techniques. We show how spreading and wicking lead to water imbibition through a porous substrate, enhancing the wetted surface area and consequently promoting evaporation. These sequential dynamics offer a framework to understand the alterations in the evaporation due to porosity for the particular case of fabric materials and a clue of how face masks interact with respiratory droplets.


The changes in kynurenine metabolites induced by rTMS in treatment-resistant depression: A pilot study.
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that is considered a valuable and promising technique for improving depressive symptoms in treatment-resistant depression (TRD). However, the exact mechanism by which rTMS ameliorates depressive symptoms remains to be clarified. The aim of the present study was to analyzed the changes in metabolites of patients with TRD in the rTMS treatment, especially focusing on the kynurenine (KYN) pathway. Thirteen participants with TRD were enrolled in a high-frequency (10 Hz) rTMS study. Cognitive function, depressive symptoms and the concentration of plasma tryptophan (TRP) metabolites were measured at baseline and at the endpoint of rTMS treatment. rTMS treatment significantly improved depressive symptom scores and some subscales of cognitive dysfunction. The present study has demonstrated that rTMS treatment significantly increased plasma TRP levels and significantly decreased plasma serotonin levels, while plasma KYN and kynurenic acid level as well as KYN/TRP ratio remained unchanged. This is the first metabolomic study of patients with TRD undergoing rTMS treatment. To validate the present results, it is necessary to increase the number of cases including controls, use a sample of cerebrospinal fluid, and measure blood concentration over time in the course of rTMS treatment.


Adipose-derived stem cells and obesity: The spear and shield relationship.
With the transformation of modern lifestyles and population ageing, obesity has become a global epidemic, as one of the important threat to human health of chronic non-communicable diseases (NCD). Stem cell therapy seems promising as an alternative strategy for managing obesity and related metabolic problems. Adipose tissue-derived stem cells (ADSCs) have received widespread attention, which provides new ideas for the treatment of obesity and various metabolic-related diseases, due to their abundant reserves, easy acquisition, rapid expansion, and multi-directional differentiation potential, low immunogenicity and many other advantages. Accordingly, there seems to be a "shield and spear paradox" in the relationship between ADSCs and obesity. In this review, we emphatically summarized the role of ADSCs in the occurrence and development of obesity and related metabolic disease processes, in order to pave the way for clinical practice.


Direct and indirect fluorescent-antibody staining techniques using commercial monoclonal antibodies for detection of respiratory syncytial virus.
A comparison was made between direct and indirect fluorescent-antibody staining techniques using commercial monoclonal antibodies for detection of respiratory syncytial virus in respiratory secretions. Overall agreement between the two tests was 94%. Using virus isolation as the reference method, the indirect test had a higher sensitivity but a similar specificity when compared with the direct test. The slight delay in reporting using the indirect technique is not clinically significant and is offset by the possibility of convenient combination of the technique with indirect fluorescent-antibodies for detection of other respiratory viruses in respiratory secretions.


Presence of CTAK/CCL27, MCP-3/CCL7 and LIF in human colostrum and breast milk.
Human colostrum and breast milk are known to contain high levels of cytokines and chemokines, which are thought to contribute to the development of the newborn. The aim of this study was to investigate the difference in the presence and levels of 21 soluble cytokines and chemokines in paired samples of human colostrum (day 2 after delivery) and breast milk (day 4-5 after delivery) by using the multiplex technology. Of the 21 cytokine investigated in 10 pairs of samples, only β-NGF was absent in both colostrum and milk, while INF-α2, SCF and TNF-β were present in colostrum but not in human milk. As a general rule, colostrum contained higher concentrations of cytokines and chemokines with respect to breast milk. The majority of cytokines, detected in colostrum alone or in colostrum and human milk (IL-1α, IL-2Rα, IL-3, IL-16, IL-18, GRO-α, HGF, IFN-α2, M-CSF, MIF, MIG, TNF-β, SDF-1α, TRAIL) have been described in previous studies, while for the first time we describe the presence of additional cytokines either in colostrum alone (SCF) or in both colostrum and breast milk (CTAK/CCL27, MCP-3/CCL7, LIF). Our data confirm and expand previous studies showing that some cytokines/chemokines, which might contribute to the development of the gastro-intestinal and nervous systems, are overexpressed in human colostrum and breast milk, and might contribute to the development of these systems.


Herbivory changes soil microbial communities and greenhouse gas fluxes in a high-latitude wetland.
Herbivory can have strong impacts on greenhouse gas fluxes in high-latitude ecosystems. For example, in the Yukon-Kuskokwim (Y-K) Delta in western Alaska, migratory goose grazing affects the magnitude of soil carbon dioxide (CO2) and methane (CH4) fluxes. However, the underlying drivers of this relationship are unclear, as few studies systematically tease apart the processes by which herbivores influences soil biogeochemistry. To examine these mechanisms in detail, we conducted a laboratory incubation experiment to quantify changes in greenhouse gas fluxes in response to three parameters altered by herbivores in situ: temperature, soil moisture content, and nutrient inputs. These treatments were applied to soils collected in grazing lawns and nearby ungrazed habitat, allowing us to assess how variation in microbial community structure influenced observed responses. We found pronounced differences in both fungal and prokaryotic community composition between grazed and ungrazed areas. In the laboratory incubation experiment, CO2 and CH4 fluxes increased with temperature, soil moisture, and goose fecal addition, suggesting that grazing-related changes in the soil abiotic environment may enhance soil C losses. Yet, these abiotic drivers were insufficient to explain variation in fluxes between soils with and without prior grazing. Differences in trace gas fluxes between grazed and ungrazed areas may result both from herbivore-induced shifts in abiotic parameters and grazing-related alterations in microbial community structure. Our findings suggest that relationships among herbivores and soil microbial communities could mediate carbon-climate feedbacks in rapidly changing high-latitude ecosystems.


Disulfide bond based cascade reduction-responsive Pt(IV) nanoassemblies for improved anti-tumor efficiency and biosafety.
The platinum-based drugs prevail in the therapy of malignant tumors treatment. However, their clinical outcomes have been heavily restricted by severe systemic toxicities. To ensure biosafety and efficiency, herein, we constructed a disulfide bond inserted Pt(IV) self-assembled nanoplatform that is selectively activated by rich glutathione (GSH) in tumor site. Disulfide bond was introduced into the conjugates of oxaliplatin (IV) and oleic acid (OA) which conferred cascade reduction-responsiveness to nanoassemblies. Disulfide bond cleavage and reduction of Pt(IV) center occur sequentially as a cascade process. In comparison to oxaliplatin solution, Pt(IV) nanoparticles (NPs) achieved prolonged blood circulation and higher maximum tolerated doses. Furthermore, Oxa(IV)-SS-OA prodrug NPs exhibited potent anti-tumor efficiency against 4T1 cells and low toxicities in other normal tissues, which offers a promising nano-platform for potential clinical application.


The heart's content-renewable resources.
Heart regeneration is a huge, complex area involving numerous lines of research ranging from the stem cell therapy to xenografts and bioengineering. This review will focus on two avenues of regenerative research, cardiac progenitor cells and adult cardiomyocyte proliferation, both of which offer great promise for the field of heart regeneration. However, the principles behind how this could be achieved by either technique are very different. Cardiac progenitor cells represent a population of somatic stem cells which reside within the adult heart. These cells appear to have the capacity to proliferate and differentiate into the different cell types found within the adult heart and thus have the potential, if the correct stimuli can be found, to effectively regenerate a heart damaged by ischemia/infarction. Inducing adult cardiomyocytes to proliferate offers a different approach to achieving the same goal. In this case, the cardiomyocytes that remain after the damage has occurred would need to be stimulated into effecting a regenerative response. In this review, we will discuss the current understanding of how heart regeneration could be achieved by either of these very different approaches.


Predictor variables for half marathon race time in recreational female runners.
The relationship between skin-fold thickness and running performance has been investigated from 100 m to the marathon distance, except the half marathon distance. To investigate whether anthropometry characteristics or training practices were related to race time in 42 recreational female half marathoners to determine the predictor variables of half-marathon race time and to inform future novice female half marathoners. Observational field study at the 'Half Marathon Basel' in Switzerland. In the bivariate analysis, body mass (r = 0.60), body mass index (r = 0.48), body fat (r = 0.56), skin-fold at pectoral (r = 0.61), mid-axilla (r = 0.69), triceps (r = 0.49), subscapular (r = 0.61), abdominal (r = 0.59), suprailiac (r = 0.55) medial calf (r = 0.53) site, and speed of the training sessions (r = -0.68) correlated to race time. Mid-axilla skin-fold (p = 0.04) and speed of the training sessions (p = 0.0001) remained significant after multi-variate analysis. Race time in a half marathon might be predicted by the following equation (r² = 0.71): Race time (min) = 166.7 + 1.7x (mid-axilla skin-fold, mm) - 6.4x (speed in training, km/h). Running speed during training was related to skinfold thickness at mid-axilla (r = -0.31), subscapular (r = -0.38), abdominal (r = -0.44), suprailiacal (r = -0.41), the sum of eight skin-folds (r = -0.36) and percent body fat (r = -0.31). Anthropometric and training variables were related to half-marathon race time in recreational female runners. Skin-fold thicknesses at various upper body locations were related to training intensity. High running speed in training appears to be important for fast half-marathon race times and may reduce upper body skin-fold thicknesses in recreational female half marathoners.


Radioimmunoassay of methionine(5)-enkephalin sulphoxide: phylogenetic and anatomical distribution.
A sensitive and specific radioimmunoassay (RIA) for the oxidised form of methionine(5)-enkephalin (Met(5)-Enk), Met(5)-Enk sulphoxide (Met(5)-Enk-S), has been developed. Antisera were raised in rabbits against Met(5)-Enk coupled to carrier proteins with glutaraldehyde or carbodiimide. Displacement of (125I) Met(5)-Enk bound to antiserum by Met(5)-Enk was poor, but Met(5)-Enk-S displayed good displacement suggesting that the Met(5)-Enk immunogen was oxidised to Met(5)-Enk-S and that the antisera were formed against this compound. The sensitivity of the RIA for Met(5)-Enk-S was 0.02 pmole/tube using the most sensitive antiserum. The antisera showed negligible cross-reactivity with leucine(5)-enkephalin and with both native and oxidised endorphins. Cross-reactivity was between 15% and 28% with the fragment Met(5)-Enk (2--5) sulphoxide and between 9% and 25% with D-Ala(2)-Met(5)-Enk sulphoxide. The antisera showed less than 0.01% cross-reactivity with other Met(5)-Enk fragments and naturally occurring neuropeptides. Tissue extracts were oxidised with hydrogen peroxide prior to assay. Met(5)-Enk-S immunoreactivity (IMR) was detected in brain, pituitary gland, pancreas, and intestine extracts of the rat, chicken, toad and teleost, and in cerebral-suboesophageal ganglion extracts of the snail. All tissue extracts showed parallelism in serial dilution to synthetic mammalian Met(5)-Enk-S, suggesting possible immunological identity. The results indicate that spontaneous oxidation of Met(5)-Enk immunogen occurs such that antisera are produced against the sulphoxide analogue of Met(5)-Enk, and may account for the relative insensitivity of some published RIAs using Met(5)-Enk standard. Our findings demonstrate a wide phylogenetic and anatomical distribution of Met(5)-Enk IMR.


Ethanol-induced delta-opioid receptor modulation of glutamate synaptic transmission and conditioned place preference in central amygdala.
Alcoholism involves compulsive behaviors of alcohol drinking, which is thought to be related at least initially to the rewarding effect of alcohol. It has been shown that mu-opioid receptors play an essential role in drug reward and dependence for many drugs of abuse including alcohol, but the function of delta-opioid receptors (DOR) in drug reward remains largely unknown at present. Previous animal studies using systemic approaches with DOR antagonists or DOR knockout animals have yielded inconsistent results, showing a decrease, an increase or no change in alcohol consumption and behaviors of alcohol reward after DOR inhibition or deletion. In the present study, we used ethanol-conditioned rats to investigate adaptive DOR function in neurons of the central nucleus of the amygdala (CeA), a key brain site for alcohol reward and addiction. We found that functional DOR was absent in glutamate synapses of CeA neurons from control rats, but it emerged and inhibited glutamate synaptic currents in CeA neurons from rats displaying ethanol-induced behavior of conditioned place preference (CPP). Analysis of paired-pulse ratios and miniature glutamate synaptic currents revealed that the recruited DOR was present on glutamatergic presynaptic terminals. Similar induction of functional DOR was also found on GABA synapses. Furthermore, microinjection of a DOR antagonist into the CeA reversed ethanol-induced CPP behavior in rats in vivo. These results suggest that repeated alcohol exposure recruits new functional DOR on CeA glutamate and GABA synapses, which may be involved in the expression or maintenance of ethanol-induced CPP behavior.


Population prevalence of individuals meeting criteria for hereditary breast and ovarian cancer testing.
Personal cancer diagnosis and family cancer history factor into which individuals should undergo genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome. Family history is often determined in the research setting through kindreds with disease clusters, or clinically from self-report. The population prevalence of individuals with diagnostic characteristics and/or family cancer history meeting criteria for HBOC testing is unknown. Utilizing Surveillance, Epidemiology, and End Results (SEER) cancer registry data and a research resource linking registry records to genealogies, the Utah Population Database, the population-based prevalence of diagnostic and family history characteristics meeting National Comprehensive Cancer Network (NCCN) criteria for HBOC testing was objectively assessed. Among Utah residents with an incident breast cancer diagnosis 2010-2015 and evaluable for family history, 21.6% met criteria for testing based on diagnostic characteristics, but the proportion increased to 62.9% when family history was evaluated. The proportion of cases meeting testing criteria at diagnosis was 94% for ovarian cancer, 23% for prostate cancer, and 51.1% for pancreatic cancer. Among an unaffected Utah population of approximately 1.7 million evaluable for family history, 197,601 or 11.6% met testing criteria based on family history. This study quantifies the population-based prevalence of HBOC criteria using objectively determined genealogy and cancer incidence data. Sporadic breast cancer likely represents a portion of the high prevalence of family cancer history seen in this study. These results underline the importance of establishing presence of a deleterious mutation in an affected family member, per NCCN guidelines, before testing unaffected relatives.


Injection laryngoplasty under ultrasonographic control.
Cervical ultrasound allows real-time visualization of the laryngeal structures. We describe its application for injection laryngoplasty in the voice clinic. Hyaluronic acid infiltration of the vocal fold under ultrasonographic control. With this technique, the position of the needle in the depth of the vocal fold and its spatial relations with nearby structures can be assessed. This allows for an accurate infiltration of the material in contrast to other techniques and avoids discomfort related to the gag reflex with nasofibrolaryngoscopy. No specific complications have been observed so far, however, this technique may be difficult in cases with calcified cartilages or uncooperative patients.


Prevalence of different parasomnias in the general population.
To estimate lifetime and current prevalence (defined as having experienced the specific parasomnia at least once during the last 3 months) of different parasomnias in the general population. In addition, to study the relationship between the different parasomnias and gender, depressive mood, and symptoms of sleep apnea, insomnia and restless legs, as well as estimating the prevalence of having multiple parasomnias. Population based cross-sectional study. One thousand randomly selected adults (51% female), 18years and above, participated in a telephone interview in Norway. Lifetime prevalence of the different parasomnias varied from about 4% to 67%. For sleep walking lifetime prevalence was 22.4% and current prevalence 1.7%. For the other parasomnias, lifetime and current prevalence were as follows: sleep talking 66.8% and 17.7%, confusional arousal 18.5% and 6.9%, sleep terror 10.4% and 2.7%, injured yourself during sleep 4.3% and 0.9%, injured somebody else during sleep 3.8% and 0.4%, sexual acts during sleep 7.1% and 2.7%, nightmare 66.2% and 19.4%, dream enactment 15.0% and 5.0%, sleep related groaning 31.3% and 13.5%, and sleep-related eating 4.5% and 2.2%. Depressive mood was associated with confusional arousal, sleep terror, sleep-related injury, and nightmare. There were few associations between the parasomnias and gender and symptoms of sleep apnea, insomnia, and restless legs, respectively. About 12% reported having five or more parasomnias. This is one of few population based studies investigating the prevalence of parasomnias. Several parasomnias were highly prevalent in the general population. The data need to be interpreted with caution due to methodological issues, i.e., low response rate and single questions.


Correlates of insomnia in patients with social phobia: role of depression and anxiety.
The severity of insomnia and the relationships between social fear, anxiety, depression and insomnia were examined in 179 patients with social phobia. Two-thirds of our sample had insomnia. Depression, anxiety, social anxiety, and insomnia were positively correlated. General and social anxiety contributed to insomnia when accounting for depression.


Overview on the target population and methods used in care pathway projects: A narrative review.
There is evidence that the efficiency and effectiveness of care processes can be improved in all countries. Care pathways (CPs) are proposed as a method to improve the quality of care by reducing variation. During the last decades, CPs have been intensively used in practice. The objective of this study is to examine the study designs for investigating CPs, for which pathologies CPs are used and what the reported indicators to measure the impact of CPs are. A narrative review of the literature published from 2015 to 2019 was performed. We identified 286 studies, of which 207 evaluated the impact of CPs, 33 were review articles, 29 studies described the development of a CP, 12 were study protocols and 5 opinion papers. The most frequently reported study design for studying the impact of a CP is pre-posttest (n = 82), followed by cross-sectional studies (n = 50). Oncology, cardiovascular disease and abdominal surgery are the domains with the highest numbers of studies evaluating the impact of CPs. Financial (n = 86), process (n = 76) and clinical indicators (n = 74) are the most frequently reported indicators while service (n = 12) and team indicators (n = 6) are less reported. Based on the relative low number of identified studies compared with the number of CP projects in organisations, we conclude that the CP knowledge is not only found in the literature. We, therefore, argue that (inter)national scientific societies should not only focus on searching and spreading evidence on the content of care but also enhance their knowledge sharing initiatives on the organisation of care processes.


Necessity of sentinel lymph node biopsy in ductal carcinoma in situ patients: a retrospective analysis.
Sentinel lymph node biopsy (SLNB) is unnecessarily performed too often, owing to the high upstaging rates of ductal carcinoma in situ (DCIS). This study aimed to evaluate the upstaging rates of DCIS to invasive cancer, determine the prevalence of axillary lymph node metastasis, and identify the clinicopathological factors associated with upstaging and lymph node metastasis. We also examined surgical patterns among DCIS patients and determined whether SLNB guidelines were followed. We retrospectively analysed 307 consecutive DCIS patients diagnosed by preoperative biopsy in a single centre between 2014 and 2018. Data from clinical records, including imaging studies, axillary and breast surgery types, and pathology results from preoperative and postoperative biopsies, were extracted. Univariate analyses using Chi-square tests and multiple logistic regression analyses were used to analyse the data. The rate of upstaging to invasive cancer was 19.2% (59/307). DCIS diagnosed by core-needle biopsy (odds ratio [OR]: 6.861, 95% confidence interval [CI]: 2.429-19.379), the presence of ultrasonic mass-forming lesions (OR: 2.782, 95% CI: 1.224-6.320), and progesterone receptor-negative status (OR: 3.156, 95% CI: 1.197-8.323) were found to be associated with upstaging. The rate of sentinel lymph node metastasis was only 1.9% (4/202), and all were total mastectomy patients diagnosed by core-needle biopsy. SLNB was performed in 37.2% of 145 breast-conserving surgery patients and 91.4% of 162 total mastectomy patients. Among the 202 patients who underwent SLNB, 145 (71.7%) without invasive cancer on final pathology had redundant SLNB. Two of 59 patients (3.4%) with disease upstaged to invasive cancer had inadequate primary staging of the axilla, as the rate seemed sufficiently small. In patients with a preoperative diagnosis of DCIS, although an unavoidable possibility of upstaging to invasive cancer exists, axillary metastasis is unlikely. Only 2.7% of patients with DCIS undergoing total mastectomy were found to have sentinel lymph node metastases. SLNB should not be performed in breast-conserving surgery patients and should be reserved only for total mastectomy patients diagnosed by core-needle biopsy.


Structure of the O-specific polysaccharide of Proteus penneri strain 25 containing N-(L-alanyl) and multiple O-acetyl groups in a tetrasaccharide repeating unit.
Based on sugar and methylation analyses, O-deacetylation, Smith degradation, and 1H and 13C NMR spectroscopy, including 2D COSY, 1H-detected 1H, 13C heteronuclear single-quantum coherence (HSQC), and 1H-detected 1H, 13C heteronuclear multiple-bond connectivity (HMBC) experiments, the following structure of the O-specific polysaccharide of Proteus penneri strain 25 was established: [formula: see text] where D-GlcN(L-Ala) is 2-(L-alanylamido)-2-deoxy-D-glucose.


FX1, a BCL6 inhibitor, reactivates BCL6 target genes and suppresses HTLV-1-infected T cells.
Human T cell leukemia virus type 1 (HTLV-1) is responsible for adult T cell leukemia (ATL); however, molecular and cellular mechanisms underlying HTLV-1-induced leukemogenesis are unclear. BCL6 oncogene is involved in cancer progression and a preferred target of anti-cancer treatments. Here, we aimed to evaluate BCL6 expression and the effects of BCL6 inhibitor (FX1) on HTLV-1-infected T cell lines. BCL6 expression was higher in HTLV-1-infected T cell lines than that in uninfected T cell lines. BCL6 was localized mostly in the nucleus. The virus oncoprotein Tax induced BCL6 mRNA expression in T cells, whereas BCL6 knockdown reduced HTLV-1-infected T cell proliferation; thus, confirmed the association of BCL6 with cancer progression. Further, FX1 efficiently inhibited the cell growth and survival of HTLV-1-infected T cell lines in a dose- and time-dependent manner. The decreased levels of cell cycle regulatory proteins (phosphorylated retinoblastoma protein, cyclin-dependent kinase 4, cyclin D2 and c-Myc) and the increased levels of BCL6 target proteins (p21, p27 and p53) showed that FX1 arrested cell cycle at the G1 phase. Apoptosis was induced concomitantly with Bak upregulation and downregulation of survivin, Bcl-xL and Mcl-1, as well as with the activation of caspase-3, -8, -9 and poly(ADP-ribose) polymerase. FX1 also inhibited NF-κB and Akt signaling pathways. These events were because of the induction of the activity of cell cycle checkpoint proteins and relief of direct repression of the targets of cell cycle checkpoint proteins. Thus, BCL6 might be considered a novel target for ATL treatment.


Studying pathogens degrades BLAST-based pathogen identification.
As synthetic biology becomes increasingly capable and accessible, it is likewise increasingly critical to be able to make accurate biosecurity determinations regarding the pathogenicity or toxicity of particular nucleic acid or amino acid sequences. At present, this is typically done using the BLAST algorithm to determine the best match with sequences in the NCBI nucleic acid and protein databases. Neither BLAST nor any of the NCBI databases, however, are actually designed for biosafety determination. Critically, taxonomic errors or ambiguities in the NCBI nucleic acid and protein databases can also cause errors in BLAST-based taxonomic categorization. With heavily studied taxa and frequently used biotechnology tools, even low frequency taxonomic categorization issues can lead to high rates of errors in biosecurity decision-making. Here we focus on the implications for false positives, finding that BLAST against NCBI's protein database will now incorrectly categorize a number of commonly used biotechnology tool sequences as the pathogens or toxins with which they have been used. Paradoxically, this implies that problems are expected to be most acute for the pathogens and toxins of highest interest and for the most widely used biotechnology tools. We thus conclude that biosecurity tools should shift away from BLAST against general purpose databases and towards new methods that are specifically tailored for biosafety purposes.


Esophageal and Small Intestinal Mucosal Integrity in Eosinophilic Esophagitis and Response to an Elemental Diet.
The esophageal mucosal integrity is impaired in eosinophilic esophagitis (EoE) and it has been suggested that the duodenal permeability is increased. The absence of food allergens may restore the integrity. The aims of this study were to assess duodenal permeability in EoE and to evaluate the effect of an elemental diet on the esophageal and duodenal integrity. In this prospective study 17 adult EoE patients and 8 healthy controls (HC) were included. Esophageal biopsy specimens were sampled before and after 4 weeks of elemental diet to measure eosinophil counts and gene expression of tight junction and barrier integrity proteins. Esophageal and duodenal impedance were measured by electrical tissue impedance spectroscopy and Ussing chambers were used to measure transepithelial resistance (TER) and transepithelial molecule flux. Small intestinal permeability was measured using a test, measuring lactulose/mannitol (L/M) ratios. In EoE patients, the esophageal but not the duodenal integrity was impaired, compared with HC. We observed no significant difference between L/M ratios of HC and EoE patients. After diet, eosinophil counts decreased significantly, which was paralleled by normalization of esophageal impedance and transepithelial molecule flux. The esophageal TER improved significantly, but did not reach values seen in HC. Esophageal expression of genes encoding for barrier integrity proteins filaggrin and desmoglein-1 was impaired at baseline and restored after diet. An elemental diet restores esophageal integrity, suggesting that it is at least partly secondary to allergen exposure. Duodenal integrity seems not to be affected in EoE, and possibly plays a minor role in its pathophysiology.


Fixed- versus mobile-bearing UKA: a systematic review and meta-analysis.
Two design concepts are currently used for unicondylar knee arthroplasty (UKA) prostheses: fixed bearing (FB) and mobile bearing (MB). While MB prostheses have theoretical advantages over their FB counterparts, it is not clear whether they are associated with better outcomes. A systematic review was conducted to examine survivorship differences and differences in failure modes of between FB and MB designs. PubMed, Scirus and Cochrane library databases were searched for medial UKA outcome studies. A total of 44 papers, involving 9,463 knees, were eligible. Outcomes examined included knee function, survivorship and the reasons for, and incidence of, revision for FB and MB prostheses. Random effects meta-analysis was employed to obtain pooled revision rate estimates. Where available, cause-specific time to revision was extracted. Mean follow-up was 8.7 years for FB and 5.9 years for MB prostheses. There were no other relevant baseline differences. The overall crude revision rate for FB and for MB prostheses was 0.90 (95 % confidence interval (CI) 0.65-1.21) and 1.51 (95 % CI 1.11-1.93) per 100 component years, respectively. After stratification on follow-up time and age, the revision rates were not substantially different, aside for younger patients in short term from studies with short-term follow-up. No essential differences between the two designs were observed. MB and FB UKA designs have comparable revision rates. As our study is based on predominantly observational data, with large variations in reporting standards, inferences should be drawn with caution. IV.


Increased risk for non-autoimmune hypothyroidism in young patients with congenital heart defects.
Newborns with congenital hypothyroidism (CH) have an increased risk for congenital heart defects (CHD) due to a common embryonic developmental program between thyroid gland and heart and great vessels. Our objective was to investigate the prevalence and origin of thyroid disorders in young patients with CHD. We conducted a prospective observational study between January 2007 and January 2009 in academic Pediatric Cardiosurgery and Endocrinology. Patients included 324 children (164 males, 160 females, aged 0.2-15.4 yrs) with CHD. Subjects underwent hormonal and genetic screening. Serum TSH and thyroid hormone levels were assessed. Two CHD patients were diagnosed with CH at the neonatal screening (1:162). Mild hypothyroidism (serum TSH > 4.0 μU/ml) was diagnosed and confirmed 6 months later [TSH = 5.4 ± 1.5 μU/ml; free T(4) = 1.3 ± 0.2 ng/dl (normal values 0.8-1.9)] in 37 children (11.5%) who were negative at neonatal screening. Hypothyroidism was not related to type of CHD, whereas TSH levels positively correlated with serum N-terminal pro-type B natriuretic peptide levels. Biochemical and ultrasound findings consistent with thyroid autoimmunity were present in three of 37 hypothyroid children (8.1%). One patient had hemiagenesis (2.7%). Variations in candidate genes were screened in CHD patients. NKX2.5 coding sequence was normal in all samples. A 3-Mb microdeletion in 22q11.2 was detected in three patients (8.3%), whereas only known polymorphisms were identified in TBX1 coding sequence. CHD patients have an increased risk for both CH (10-fold higher) and acquired mild hypothyroidism (3-fold higher). Unrecognized mild hypothyroidism may negatively affect the outcome of CHD children, suggesting that thyroid function should be repeatedly checked. Thyroid autoimmunity and 22q11.2 microdeletions account for small percentages of these cases, and still unknown mechanisms underline such a strong association.


Ghrelin levels in patients with juvenile idiopathic arthritis: relation to anti-tumor necrosis factor treatment and disease activity.
Studies in adults with rheumatoid arthritis reported low serum ghrelin that increased following anti-tumor necrosis factor (TNF) infusion. Data on juvenile idiopathic arthritis (JIA) are lacking. The aim of this pilot study was to explore serum ghrelin levels in patients with JIA and the possible association with anti-TNF treatment, disease activity, and nutritional status. Fifty-two patients with JIA (14/52 on anti-TNF treatment) were studied. Juvenile idiopathic arthritis was inactive in 3 of 14 anti-TNF-treated patients and in 11 of 38 non-anti-TNF-treated patients. The nutritional status, energy intake/requirements, appetite, and fasting serum ghrelin levels were assessed. Ghrelin control values were obtained from 50 individuals with minor illness matched for age, sex, and body mass index. Ghrelin levels in patients with JIA were significantly lower than in controls (P < .001, confidence interval [CI] = -101 to -331). Analysis according to anti-TNF treatment and disease activity showed that ghrelin levels were comparable to control values only in 3 patients with anti-TNF-induced remission. Ghrelin in non-anti-TNF-treated patients in remission was low. Multiple regression analysis showed that disease activity (P = .002, CI = -84.16 to -20.01) and anti-TNF treatment (P = .003, CI = -82.51 to -18.33) were significant independent predictors of ghrelin after adjusting for other potential confounders. Ghrelin did not correlate with nutritional status, energy balance, and appetite. Serum ghrelin is low in patients with JIA and is restored to values similar to those in controls following anti-TNF-induced remission. Our study provides evidence that TNF blockade is independently associated with serum ghrelin, which possibly contributes to anti-TNF-induced remission. These preliminary results could form the basis for future research.


Custom-Molded Offloading Footwear Effectively Prevents Recurrence and Amputation, and Lowers Mortality Rates in High-Risk Diabetic Foot Patients: A Multicenter, Prospective Observational Study.
Recurrence of high-risk diabetic feet, after wound, healing is a common challenge among diabetic patients. Continuous use of an offloading device significantly prevents recurrence of high-risk diabetic feet, although patient adherence is imperative to ensuring this therapy's clinical efficacy. In this study, we explored clinical outcomes of patients with a high-risk diabetic foot who had been prescribed with custom-molded offloading footwear under different adherence conditions. A total of 48 patients (17 females and 31 males) with high-risk diabetic feet, who had been with prescribed offloading footwear in 13 medical centers across 4 cities, were enrolled in the current study. The patients were assigned into either continuous offloading therapy (COT, n = 31) or interrupted offloading therapy (IOT, n = 17) groups, according to their adherence to the therapy. All patients were followed up monthly, and differences in recurrence, amputation, and deaths between the groups were analyzed at 4 months after therapy. Forty-eight patients met our inclusion criteria and were therefore included in the final analysis. Among them, 31 were stratified into the COT group and adhered to offloading therapy throughout the study period, whereas 17 were grouped as IOT and exhibited interrupted adherence to offloading therapy. We found statistically significant differences in recurrence rates (0 vs 38.46%, p < 0.01), amputation (0 vs 11.76%, p < 0.01), and deaths (0% vs 5.88%, p < 0.01) between the groups during follow-up. Patients' adherence is imperative to efficacy of custom-molded offloading footwear during treatment of high-risk diabetic foot. Further studies are needed to elucidate the role of improved design of the offloading device and the need for enhanced patient education for improved adherence.


Farm worker injuries associated with cows. New York State 1991-1996.
1. The size of cows and their unpredictable behavior constitute a hazard for workers who handle them. 2. When cows are startled by sudden movements and unfamiliar situations, they may kick, push, knock down, fall, or step on workers. 3. Cows in heat or those with calves are particularly excitable. Working in confining situations, such as milking stalls, exacerbates the danger of injury to handlers. 4. Knowledge of effective animal handling techniques and well designed handling facilities can reduce the incidence of injury.


Synthesis and biological evaluation of norcantharidin analogues: towards PP1 selectivity.
Simple modifications to the anhydride moiety of norcantharidin have lead to the development of a series of analogues displaying modest PP1 inhibition (low muM IC(50)s) comparable to that of norcantharidin (PP1 IC(50)=10.3+/-1.37 microM). However, unlike norcantharidin, which is a potent inhibitor of PP2A (IC(50)=2.69+/-1.37 microM), these analogues show reduced PP2A inhibitory action resulting in the development of selective PP1 inhibitory compounds. Data indicates that the introduction of two ortho-disposed substituents on an aromatic ring, or para-substituent favours PP1 inhibition over PP2A inhibition. Introduction of a p-morphilinoaniline substituent, 35, affords an inhibitor displaying PP1 IC(50)=6.5+/-2.3 microM; and PP2A IC(50)=7.9+/-0.82 microM (PP1/PP2A=0.82); and a 2,4,6-trimethylaniline, 23, displaying PP1 IC(50)=48+/-9; and PP2A IC(5) 85+/-3 microM (PP1/PP2A=0.56). The latter shows a 7-fold improvement in PP1 versus PP2A selectivity when compared with norcantharidin. Subsequent analysis of 23 and 35 as potential PP2B inhibitors revealed modest inhibition with IC(50)s of 89+/-6 and 42+/-3 microM, respectively, and returned with PP1/PP2B selectivities of 0.54 and 0.15. Thus, these analogues are the simplest and most selective PP1 inhibitors retaining potency reported to date.


Coeruleotrigeminal suppression of nociceptive sensorimotor function during inflammation in the craniofacial region of the rat.
Descending action from the locus coeruleus (LC) on the trigeminal sensorimotor function was evaluated in a rat model of oral-facial inflammation. For the induction of oral-facial inflammation, mustard oil (20% solution in 20microl mineral oil) was injected into the region of the temporomandibular joint (TMJ). One week before testing, rats received bilateral lesions of the LC using a cathodal current. The electromyogram (EMG) threshold, which is the threshold intensity for the onset of EMG activity of the masseter muscle evoked by pressure on the TMJ region, was used in the present study as an indicator of the trigeminal sensorimotor function. Following mustard oil injection, in the LC-lesioned rats, EMG thresholds significantly decreased at 30min, which lasted up to 240min. In contrast, EMG thresholds in the LC-intact rats returned to the level before injection after 180min. Systemic naloxone (1.3mg/kg, i.v.) produced a further decrease of EMG thresholds in both the LC-intact and LC-lesioned rats. Under the existence of naloxone, EMG thresholds in the LC-lesioned rats were significantly lower than those of the LC-intact rats. These results suggest that oral-facial inflammation activates the coeruleotrigeminal modulating system and that an action of this system is independent of the opioid depressive mechanism.


Early postnatal exposure to traffic-related air pollution and asthma in adolescents: vulnerability factors in the PARIS birth cohort.
Associations between early traffic-related air pollution (TRAP) exposure and respiratory and allergic morbidity in adolescents are inconsistent. However, sub-groups might be more vulnerable to the health effects of this exposure. We investigated associations between early exposure to TRAP and respiratory and allergic morbidity at age 13 years in the PARIS birth cohort, and potential modifying effects of sex, parental allergy, stressful family event and lower respiratory tract infections (LRTI). This study deals with data from 732 children of the PARIS birth cohort followed up using repeated questionnaires until 13 years of age. Prenatal TRAP exposure was assessed by measuring daily concentrations of nitrogen dioxide at the nearest station to mother's home. Early postnatal TRAP exposure was calculated for each child during the first year of life by a nitrogen oxides (NOx) air dispersion model taking into account both residence and daycare. Associations between TRAP exposures and asthma, rhinitis and related symptoms were assessed using multivariable logistic regression models adjusted for potential confounding factors. Effect modification was explored by testing multiplicative interactions. An increase in interquartile range (17.0 μg/m3) of early postnatal NOx exposure was positively related to current asthma (adjusted odds ratio aOR = 1.21; 95% confidence interval CI: 1.02, 1.43), severe wheeze (aOR = 1.23; 95% CI: 1.02, 1.47) and persistent asthma at 13 years old (aOR = 1.26; 95% CI: 1.03, 1.55) and tended to be associated with asthma ever. Parental history of allergy, asthma, early stressful family event and LRTI modified these associations with TRAP exposure. No relationship with rhinitis was found. Prenatal TRAP exposure did not show any association with respiratory and allergic morbidity. This study is one of the first to show several modifiers of the association between early postnatal TRAP exposure and asthma at adolescence. Not all adolescents seem equally affected by early postnatal TRAP exposure: those presenting parental history of allergy, especially asthma, those with early stressful family event or LRTI appear to be more vulnerable.


GPs' perceptions of their relationship with the pharmaceutical industry: a qualitative study.
The pharmaceutical industry invests heavily in promoting medications to physicians. This promotion may influence physicians' prescribing behaviour and lead to inappropriately increased prescribing rates. To understand GPs' experience of interacting with the pharmaceutical industry, and explore their views and perceptions of the impact of this interaction in general practice in Ireland. A qualitative design was used, and GPs practicing in Ireland were eligible. A combination of purposive and snowball sampling techniques was applied and semi-structured interviews were conducted. Thematic analysis was used to develop themes from the data. Twenty-one GPs and one GP trainee participated. Five themes were developed: 1) GP and pharmaceutical industry interface; 2) the industry's methods of influence; 3) the uncomfortable relationship between GPs and industry; 4) GPs' perceptions of being unconsciously influenced; and 5) GPs' lack of knowledge of relevant regulations.Participants interacted with pharmaceutical representatives in their surgery and through continuing professional development (CPD). Reported methods of influence included biased information and the offer of gifts. Most participants felt their prescribing was unconsciously influenced. A minority felt that they were only influenced in a way that improved their prescribing. The study shows that there can be a lack of clarity among GPs about relevant regulations and about the potential impact on prescribing of interactions with the pharmaceutical industry. Education of trainees and GPs has the potential to address this. Restrictions on interactions with the pharmaceutical industry may also play a role, although alternative CPD funding sources would need to be established.


BCG treatment of malignant pleural effusions in the rat.
Intrapleurally injected cells of an ascitic rat tumour produced intrapleural effusions and solid pleural deposits. BCG, or its methanol extraction residue (MER) injected into the pleural space, suppressed tumour development and prolonged survival. Treatment was effective if given a few days before or after tumour injection. In contrast, active specific immunotherapy by repeated s.c. injection of viable or radiation-attenuated tumour cells in admixture with BCG was unsuccessful, and did not improve the response to intrapleural BCG treatment.


Natural remedies for Alzheimer's disease: A systematic review of randomized controlled trials.
Alzheimer's disease (AD) is the common type of dementia and is currently incurable. Existing FDA-approved AD drugs may not be effective for everyone, they cannot cure the disease nor stop its progression and their effects diminish over time. Therefore, the present review aimed to explore the role of natural alternatives in the treatment of AD. A systematic search was conducted using Ovid MEDLINE, CINAHL, Cochrane and PubMed databases and reference lists up to November 30, 2021. Only randomized control trials were included and appraised using the National Institute of Health framework. Data analysis showed that herbs like Gingko Biloba, Melissa Officinalis, Salvia officinalis, Ginseng and saffron alone or in combination with curcumin, low-fat diet, NuAD-Trail, and soy lecithin showed significant positive effects on AD. Moreover, combination of natural and pharmaceuticals has far better effects than only allopathic treatment. Thus, different herbal remedies in combination with FDA approved drugs are effective and more promising in treatment of AD.


Factors promoting shared decision-making in renal replacement therapy for patients with end-stage kidney disease: systematic review and qualitative meta-synthesis.
Shared decision-making (SDM) about the type of renal replacement therapy to use is a matter of great importance involving patients, their families, and health treatment teams. This review aims to synthesize the volume of qualitative work explaining the factors influencing SDM regarding renal replacement therapy. A systematic review and qualitative meta-synthesis approach recommended by JBI was used, six databases were searched. Studies were qualitative or mixed research published since 2000, with a primary focus on patient experiences, perceptions and practices regarding which method to choose for renal replacement therapy in End-Stage Kidney Disease (ESKD) patients. All themes were analyzed and compared to the established connectedness. A total of 1313 patients were enrolled in 32 studies focusing on factors associated with SDM regarding renal replacement therapy were included. All quality evaluations of the literature were medium to high. Four common themes were identified in our synthesis: (1) patient personal reasons, (2) family-related factors, (3) health care professional-related factors, and (4) social factors influence. The model proposes pathways that could be explored further in future qualitative and quantitative studies and suggests that patients' beliefs, emotions, and awareness should be targeted alongside patients' decision-making practices to increase the efficacy of interventions. The majority of studies included in this review focus on older patients, and all report patients' perspectives. Further research is required to understand the family member perspectives on SMD of renal replacement therapy.