Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis.
Statins may improve outcomes in patients with chronic liver disease (CLD). We conducted a systematic review and meta-analysis to evaluate the impact of statins in the setting of CLD. We searched several databases from inception to 17 October 2016 to identify comparative studies evaluating the role of statins in CLD. Outcomes of interest were the associations between statin use and progression of fibrosis, development of hepatic decompensation in cirrhosis, and mortality in CLD. Adjusted hazard ratios (HRs) were pooled and analyzed using a random effects model. Subgroup analyses were performed based on the method of detection for progression of hepatic fibrosis and quality of studies. We included 10 studies (1 randomized controlled trial and 9 observational) with 259,453 patients (54,441 statin users and 205,012 nonusers). For progression of hepatic fibrosis, pooled HR (95% confidence interval) was 0.49 (0.39-0.62). On subgroup analysis of studies using ICD-9 (The International Classification of Diseases, Ninth Revision) coding and a second method to detect cirrhosis, pooled HR was 0.58 (0.51-0.65); pooled HR for studies using ICD-9 coding only was 0.36 (0.29-0.44). For progression of fibrosis in patients with hepatitis C virus (HCV) infection, pooled HR was 0.52 (0.37-0.73). For hepatic decompensation in cirrhosis, pooled HR was 0.54 (0.46-0.65). For mortality, pooled HR based on observational studies was 0.67 (0.46-0.98); in the randomized controlled trial, HR was 0.39 (0.15-0.99). However, the quality of evidence for these associations is low as most included studies were retrospective in nature and limited by residual confounding. Statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis, and may reduce all-cause mortality in patients with CLD. As the quality (certainty) of evidence is low, further studies are needed before statins can be routinely recommended.


Neuropsychiatric Manifestations of Colloid Cysts: a review of the literature.
Colloid cysts account for approximately 2% of primary brain tumours and the majority of cases are identified in the fourth and fifth decade. They are small, gelatinous neoplasms lined by a single layer of mucin-secreting columnar epithelium that are thought to arise from errors in folding of the primitive neuroepithelium. They develop in the rostral aspect of the third ventricle in the foramen of Monro in 99% of cases and despite their benign histology carry a poor prognosis, with a mortality greater than 10% in symptomatic cases. The location of colloid cysts within the ventricular system results in obstruction of the foramen of Monro as the cyst grows, disrupting the circulation of cerebrospinal fluid (CSF) and causing hydrocephalus. This is the mechanism behind the most common presenting symptoms of postural headache, nausea and vomiting - a clinical picture synonymous with hydrocephalus and intracranial pathology. In addition to these classical neurological symptoms, there is a high prevalence of psychiatric symptoms in the patient population, with symptoms ranging from anterograde amnesia to gustatory hallucination. These symptoms can occur with or without the presence of hydrocephalus, and are thought to be secondary to compression of connecting pathways between the mesocortices and subcortical limbic regions. These symptoms have been shown to be comparative in frequency to the classical symptoms, yet are rarely the reason for referral to a neurological or neurosurgical service for investigation.


A simple-time-series approach for evaluating an ocular plethysmograph.
A simple-time-series approach for testing the efficacy of an ocular plethysmograph has been developed. This statistical methodology is used to demonstrate the clinical potential of the Buffington ocular plethysmograph for the noninvasive detection of cerebral ischemia. This is done by correlating intraocular pulse amplitude to systemic blood pressure changes during controlled hypotension induced by the intravenous administration of sodium pentobarbital (25 mg/kg) in five dogs.


Two functionally distinct NADP+-dependent ferredoxin oxidoreductases maintain the primary redox balance of Pyrococcus furiosus.
Electron bifurcation has recently gained acceptance as the third mechanism of energy conservation in which energy is conserved through the coupling of exergonic and endergonic reactions. A structure-based mechanism of bifurcation has been elucidated recently for the flavin-based enzyme NADH-dependent ferredoxin NADP+ oxidoreductase I (NfnI) from the hyperthermophillic archaeon Pyrococcus furiosus. NfnI is thought to be involved in maintaining the cellular redox balance, producing NADPH for biosynthesis by recycling the two other primary redox carriers, NADH and ferredoxin. The P. furiosus genome encodes an NfnI paralog termed NfnII, and the two are differentially expressed, depending on the growth conditions. In this study, we show that deletion of the genes encoding either NfnI or NfnII affects the cellular concentrations of NAD(P)H and particularly NADPH. This results in a moderate to severe growth phenotype in deletion mutants, demonstrating a key role for each enzyme in maintaining redox homeostasis. Despite their similarity in primary sequence and cofactor content, crystallographic, kinetic, and mass spectrometry analyses reveal that there are fundamental structural differences between the two enzymes, and NfnII does not catalyze the NfnI bifurcating reaction. Instead, it exhibits non-bifurcating ferredoxin NADP oxidoreductase-type activity. NfnII is therefore proposed to be a bifunctional enzyme and also to catalyze a bifurcating reaction, although its third substrate, in addition to ferredoxin and NADP(H), is as yet unknown.


Effects of oral administration of purified micronized flavonoid fraction on increased microvascular permeability induced by various agents and on ischemia/reperfusion in the hamster cheek pouch.
The effects of a clinically used purified micronized flavonoid fraction (S 5682) containing 90% diosmin and 10% hesperidin on increased microvascular permeability induced by histamine, bradykinin, and leukotriene B4 (LTB4) were investigated by intravital microscopy in the hamster cheek pouch preparation. The authors also investigated the effects of S 5682 on macromolecular permeability increase and leukocyte adhesion during ischemia-reperfusion by using the same preparation. S 5682, suspended in 10% lactose solution, or vehicle (10% lactose) was administered orally to male hamsters for ten days at 20 mg/kg/day (10 mg/kg twice a day). Fluorescein isothiocyanate (FITC)-labeled dextran (mol wt 150,000) was given intravenously, thirty minutes after completion of the cheek pouch preparation. The leukocytes were stained by continuous IV infusion of acridine orange (0.5 mg/kg/minute). Histamine (2 microM), bradykinin (1 microM), and LTB4 (0.01 microM), applied topically for five minutes, increased the number of fluorescent vascular leakage sites in postcapillary venules. A temporary ischemia with total circulatory arrest of the cheek pouch was obtained by clamping the neck of the everted pouch. The maximum number of leaky sites (per cm2 in the prepared area) that occurred either at five minutes after the beginning of each topical application or ten minutes after the onset of reperfusion was quantified in ultraviolet light microscopy. The results from 60 animals divided into 10 groups of 6 animals each are presented as means +/- SEM. In comparison with vehicle, S 5682 significantly inhibited the macromolecular permeability increasing effect of histamine (343.5 +/- 22.3 versus 207.5 +/- 32.0 leaks/cm2; P < 0.01), bradykinin (345.2 +/- 19.0 versus 206.2 +/- 21.6 leaks/cm2; P < 0.01), and LTB4 (353.3 +/- 27.5 versus 242.7 +/- 33.6 leaks/cm2; P < 0.05). At reperfusion, after thirty minutes of ischemia, S 5682 significantly decreased the observed macromolecular permeability (103.6 +/- 15.4 versus 42.6 +/- 9.3 leaks/cm2; P < 0.01). Flavonoid-treated animals also displayed a statistically significant lower number of adhering leukocytes to the venular endothelium (83.5 +/- 9.5 versus 48.4 +/- 12.3 per 6 mm2; P < 0.05). These results demonstrate that oral administration of S 5682 for ten days at 20 mg/kg body weight/day had a protective effect against leakage of macromolecules after application of permeability-increasing substances and during ischemia-reperfusion in the cheek pouch microvasculature. Since firm leukocyte attachment to the endothelial wall and subsequent emigration of leukocytes into the interstitium is a mechanism for tissue damage during inflammation, attenuation of this phenomenon during conditions of ischemia-reperfusion can in part explain previous observations that this purified micronized flavonoid fraction decreases edema formation. The present data illustrating the inhibitory effect of a clinically relevant dose of S 5682 on the inflammatory processes induced in this in vivo model of microcirculation may serve as a rational basis to explain its clinical efficacy.


Factors associated with dual and polytobacco use among people in residential substance use disorder treatment.
Little is known about whether people in substance use disorder (SUD) treatment are at risk for multiple-tobacco use. We examined the factors associated with dual- and polytobacco use among clients in SUD treatment. A cross-sectional survey was conducted in 2019 among 562 clients (Mage = 39, 74% male) in 20 residential SUD treatment programs in California, USA. The outcomes included single-, dual- (use of two products), and polytobacco use (use of three of more products). Independent variables were nicotine dependence, quitting-related factors, blunt/spliff use, and health-related factors. A multinomial model examined associations between the independent variables and the outcome, controlling for demographics, and time in treatment. Overall, 32.6%, 18.9%, and 14.0% of the sample were single-, dual-, and polytobacco users, respectively. Factors associated with increased odds of polytobacco use included greater nicotine dependence (adjusted odds ratio [AOR] = 1.60; 95% CI = 1.19, 2.16), ever using e-cigarettes for quitting (AOR = 4.56; 95% CI = 2.23, 9.34), and past 30-day use of blunt/spliff (AOR = 2.96; 95% CI = 1.48, 5.89). Factors associated with increased odds of dual use were ever using e-cigarettes for quitting (AOR = 3.19; 95% CI = 1.79, 5.66) and reporting more mentally unhealthy days (AOR = 1.05; 95% CI = 1.02, 1.07). This study extends the literature on tobacco use among people in SUD treatment by revealing the high prevalence of dual- and polytobacco use and the unique characteristics of users. The findings have implications for interventions reducing all types of tobacco use in this understudied population.


Dust from cotton manufacture: changing from static to personal sampling.
Several designs of personal samplers were tested for use to collect cotton dust. The IOM personal inhalable-dust sampler was selected because: (1) collection of the whole inhalable fraction was preferred, since all inhaled sizes are under suspicion as contributing to respiratory symptoms in cotton exposure; (2) this sampler is well characterized; and (3) it was found to be practicable in the environments examined. Gauze shields to exclude 'fly' from the personal sampler were tried, but were rejected mainly because measurement of the whole inhalable fraction by a validated sampler was felt to be more appropriate. A range of processes at a representative selection of mills was assessed by a hygiene team, and classified as 'clean' or 'dirty' in terms of present standards of control. This classification agreed well with subsequent measurements using the present method, which uses a large static sampler. A personal sampling survey then showed that in about two-thirds of 'clean' processes personal exposure of at least 80% of those employed was less than about 2-2.5 mg m-3. Only one-tenth of 'dirty' processes met this standard. Personal exposure correlates poorly with the present static method, as expected, but comparison of the results suggested that a mean background level of 0.5 mg m-3 would correspond to a median personal exposure of about 2.2 mg m-3. Side-by-side measurements by the background method differed by less than 0.15 mg m-3 on about 95% of occasions. Niven et al. (to be published) have compared the IOM head used in this study with the Manchester University sampler previously used by Cinkotai et al. [Ann. occup. Hyg. 32, 103-113 (1988)] to derive a relationship between personal exposure and prevalence of byssinotic symptoms in spinners. According to Cinkotai et al.'s results the concentrations of 2-2.5 mg m-3 discussed would correspond to a prevalence of 3-5%. However, this prevalence probably reflects higher exposures in the past.


T cells cooperating in the induction of delayed-type hypersensitivity act via the linked recognition of antigenic determinants.
Culture conditions have been established that allow the induction of delayed-type hypersensitivity (DTH) precursor cells present in a cell population derived from unsensitized spleen cells only when antigen-specific, radioresistant, Thy-1-bearing helper cells are added. This specific cellular cooperation acts via the linked recognition of two determinants on the antigen; thus, cells primed to the protein antigen fowl gamma globulin (FGG) will only allow the induction of DTH reactivity against the second antigen, burro erythrocyte (BRBC), when the conjugate FGG-BRBC is present in the cultures. The requirement for physical linkage between the two antigens has been demonstrated by the observation that DTH to BRBC is induced when the conjugate FGG-BRBC is present and not when BRBC and FGG are given an uncoupled molecules.


[Determination of chlorzoxazone and its metabolite 6-hydroxychlorzoxazone in plasma by HPLC and their pharmacokinetics].
A rapid and sensitive HPLC assay was developed for the quantitation of chlorzoxazone and its metabolite 6-hydroxychlorzoxazone in plasma. These compounds, as well as internal standard 5-fluorobenzoxazolone, were extracted with ethyl acetate, then were analyzed on Alltima C18 column with a mobile phase of acetonitrile-0.5% acetic acid, and detected at 287 nm. The retention times of 6-hydroxychlorzoxazone, internal standard and chlorzoxazone were 6.12 min, 10.47 min and 18.65 min, respectively. The linearity of the method was tested in the concentration range 0.5-20 micrograms.ml-1, and the limits of detection of 6-hydroxychlorzoxazone and chlorzoxazone were found to be 0.2 and 0.5 microgram.ml-1, respectively. Inter-day and intra-day relative standard deviations (RSD) were below 8% and 11%. The recoveries of these two compounds were between 82.80%-100.76%. The pharmacokinetic profile of chlorzoxazone in human following an oral dose of 400 mg was studied. Both absorption and elimination of chlorzoxazone were found to be rapid in human. There seemed to be an obvious interindividual difference and perhaps an interracial difference as well, when compared with other races.


A 6-year follow-up of alcoholics after long-term outpatient treatment.
The predictors of the long-term outcome in alcoholics (n = 50) who had been treated in a 2-year outpatient treatment program were investigated. Previously, the sample had been followed up personally 2 years after the termination of treatment. This study is a repeated, independent follow-up of the same sample over a 4-year period, 3-6 years after termination of treatment. Outcome could be categorized in 38 subjects. Patients with a favorable outcome during at least 2 years of the 4-year follow-up period (n = 21), who were categorized as a positive outcome group, were compared with the other patients (n = 17). There was no significant correlation between initial patient characteristics and outcome 3-6 years after treatment. Drinking outcome during the 1st half-year of treatment had no correlation to positive drinking outcome in years 3-6, whereas there was a positive correlation for later phases of treatment and outcome reaching a significant level during the 2nd and 4th half-year of treatment. A favorable drinking outcome during years 1-2 after treatment had a positive significant correlation to outcome in years 3-6 after treatment [i.e., 80% of the patients with a favorable outcome during the 1st follow-up period also had a positive outcome during the 2nd follow-up period, and 72% of those who had an unfavorable outcome during the 1st follow-up period had an unfavorable outcome also during the 2nd follow-up period (chi 2 test = 10.4, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Differential behavior of human bronchial carcinoma cells in culture.
A feeder layer culture system suited to grow carcinoma cells derived from solid human lung tumors was developed. This report deals with culturing of the four main histological types of lung carcinomas observed in 37 patients: 19 squamous cell, 6 adenocarcinomas, 7 small cell, and 5 large cell carcinomas. The cultures were initiated from 24 fresh human surgical specimens and from 14 human lung tumors grown as xenografts in nude mice. Three different patterns of behavior in culture were found to be characteristic for squamous cell, adenocarcinomas, and small cell carcinomas, respectively. The culture pattern presented by the primary cultures did not appreciably change after passaging in vitro for periods of up to 2 years, even after infinite cell lines were established. Cultures of large cell carcinoma showed one or more of these patterns. From these patterns cells could be cloned and subsequently cultured as separate stable lines. The system described facilitates the identification of specific types of human lung carcinomas almost immediately (within 1 h) after plating (Phase I) as well as during culture.


Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies.
Sorafenib, an oral multikinase inhibitor, significantly prolonged overall survival (OS) vs. placebo in patients with unresectable hepatocellular carcinoma (HCC) in two phase III studies, SHARP (Sorafenib HCC Assessment Randomized Protocol) and Asia Pacific (AP). To assess prognostic factors for HCC and predictive factors of sorafenib benefit, we conducted a pooled exploratory analysis from these placebo-controlled phase III studies. To identify potential prognostic factors for OS, univariate and multivariate (MV) analyses were performed for baseline variables by Cox proportional hazards model. Hazard ratios (HRs) and median OS were evaluated across pooled subgroups. To assess factors predictive of sorafenib benefit, the interaction term between treatment for each subgroup was evaluated by Cox proportional hazard model. In 827 patients (448 sorafenib; 379 placebo) analyzed, strong prognostic factors for poorer OS identified from MV analysis in both treatment arms were presence of macroscopic vascular invasion (MVI), high alpha-fetoprotein (AFP), and high neutrophil-to-lymphocyte ratio (NLR; ⩽ vs. >median [3.1]). Sorafenib OS benefit was consistently observed across all subgroups. Significantly greater OS sorafenib benefit vs. placebo was observed in patients without extrahepatic spread (EHS; HR, 0.55 vs. 0.84), with hepatitis C virus (HCV) (HR, 0.47 vs. 0.81), and a low NLR (HR, 0.59 vs. 0.84). In this exploratory analysis, presence of MVI, high AFP, and high NLR were prognostic factors of poorer OS. Sorafenib benefit was consistently observed irrespective of prognostic factors. Lack of EHS, HCV, and lower NLR were predictive of a greater OS benefit with sorafenib. This exploratory pooled analysis showed that treatment with sorafenib provides a survival benefit in all subgroups of patients with HCC; however, the magnitude of benefit is greater in patients with disease confined to the liver (without extrahepatic spread), or in those with hepatitis C virus, or a lower neutrophil-to-lymphocyte ratio, an indicator of inflammation status. These results help inform the prognosis of patients receiving sorafenib therapy and provide further refinements for the design of trials testing new agents vs. sorafenib. Clinical Trial Numbers: NCT00105443 and NCT00492752.


Blunt bowel and mesenteric injuries in children: Do nonspecific computed tomography findings reliably identify these injuries?
Abdominal computed tomography has proven accurate for the detection of pediatric solid organ injuries following blunt abdominal trauma but is less reliable in detecting blunt bowel and mesenteric injuries (BBMI). The purpose of this study was to determine the significance of nonspecific findings on abdominal computed tomography (CT) scan in children at risk for BBMI. Retrospective chart review. Regional pediatric trauma center. All patients who received an abdominal CT scan as part of their evaluation following blunt abdominal trauma over a 10-yr period (September 1991 to September 2001). None. Individual records were reviewed by one of the authors and analyzed for age, gender, mechanism of injury, diagnostic studies and procedures, results of initial CT scan, treatment, surgical procedures, complications, and outcome. Patients were excluded if they suffered penetrating trauma, had an abdominal CT scan performed at another institution, had a surgical procedure before CT scan, or had incomplete records. A total of 2,114 patients met inclusion criteria. Sixty-five percent were male and ages ranged from 3 wks to 18 yrs. There were 178 patients who had at least one nonspecific finding on abdominal CT scan suggestive of BBMI; 151 patients had one finding, 24 patients had two findings, and three had three findings. The risk of BBMI increased with the number of nonspecific findings (positive predictive value = 11% with at least one finding and 44% with two or more findings). This increase in positive predictive value, however, was accompanied by a reduction in sensitivity (62% and 37%, respectively). A total of 32 patients had surgically proven BBMI. Of these, eight had a single nonspecific finding on CT scan, ten had two findings, and two had three findings (12 patients had no CT findings suggestive of BBMI). There were complications in four of the 32 patients with BBMI and one death (due to laceration of the superior mesenteric artery). The complications appeared to occur independent of the time to surgical intervention. The presence of multiple nonspecific findings on abdominal CT scan does not reliably predict BBMI in children. Children also appear to suffer complications from BBMI less frequently than adults, regardless of the time to surgery. Therefore, nonspecific findings alone do not warrant surgical exploration. The decision to operate should instead be based on clinical data that include serial physical examinations.


Establishing of a minimal set of tests (minimal standards) to identify species included in the genus Mycobacterium.
Mycobacterium genus includes over 100 species and subspecies; new species are discovered every year. Minimal standard criteria are represented by the resistance to acid-alcohol (e.g. in the Ziehl - Neelsen staining), the presence of some mycolic acids containing 60-90 carbon atoms that can be cleaved by pyrolysis in fatty acids with 22 - 26 carbon atoms and a guanine + cytosine content of the DNA of 61 to 71 mol %. The species with the highest rate of involvement are those from Mycobacterium tuberculosis complex, and tuberculosis is still one of the most widespread world diseases. The most important for a laboratory is to be able to identify the species from M. tuberculosis complex. We have done a series of experiments, their goal being to evaluate and establish a minimal set of useful tests for identification of mycobacterial species. We used strains from "Cantacuzino" Institute collection and applied a series of classical and modern methods. We appreciate that the minimal set of tests could be represented by the microscopic examination for acid-fast bacilli (AFB), the examination for the preferred growth temperature, the growth rate, the colonies morphology, pigmentation and photo reactivity, the niacin accumulation test, the test of nitrate reduction, the catalase test (in both variants), plus the susceptibility to Para-Amino Salicylic Acid, Para-Nitro-Benzoic Acid andto Tiophene-2-Carboxylic Acid Hydrazide.


Assessing the Performance of a Novel Stool-Based Microbiome Test That Predicts Response to First Line Immune Checkpoint Inhibitors in Multiple Cancer Types.
The intestinal microbiome is by now an undebatable key player in the clinical outcome of ICI therapies. However, no microbiome profiling method to aid therapy decision is yet validated. We conducted a multi-centric study in patients with stage III/IV melanoma, NSCLC, or RCC receiving ICI treatment. The stool microbiome profile of 63 patients was analyzed with BiomeOne®, a microbiome-based algorithm that anticipates whether a patient will achieve clinical benefit with ICIs prior to therapy initiation. Classification of patient samples as Rs and NRs was achieved with a sensitivity of 81% and a specificity of 50% in this validation cohort. An ICI-favorable response was characterized by an intestinal microbiome rich in bacteria such as Oscillospira sp., Clostridia UCG-014, Lachnospiraceae UCG-010 sp., Prevotella copri, and a decrease in Sutterella sp., Lactobacillales, and Streptococcus sp. Patients who developed immune-related adverse events (irAEs) had an overall increased microbial diversity and richness, and a stool microbiome depleted in Agathobacter. When compared with the programmed death-ligand 1 (PD-L1) expression test in the subcohort of NSCLC patients (n = 38), BiomeOne® exhibited a numerically higher sensitivity (78.6%) in identifying responders when compared with the PD-L1 test (67.9%). This study provides an evaluation of BiomeOne®, the first microbiome-based test for prediction of ICI response, to achieve market authorization. Validation with further indications and expansion to other microbiome-based interventions will be essential to bring microbiome-based diagnostics into standard clinical practice.


Cocaine and cardiovascular complications.
Thirty-six million Americans older than 12 years of age have used cocaine in their lifetime. Cocaine abuse is on the rise and it brings the challenges to treat the complication associated with it, particularly cardiovascular complications. As the understanding of pathophysiology of cocaine-associated cardiovascular complications is advancing, the treatment modalities are also modifying. In this article, common cardiovascular complications associated with acute or chronic cocaine use and their treatment are reviewed.


Epistemological frameworks, homosexuality, and religion: how people of faith understand the intersection between homosexuality and religion.
Some gay men, lesbians, and other progressives view orthodox religious believers as perpetrators of oppression. Conversely, many orthodox believers, or as they might self-identity, people of faith, believe that gay men, lesbians, and other progressives wish to marginalize people of faith. Using Hunter's epistemologically based distinction between progressive and orthodox worldviews to understand the differences in perceptions, this article explores how numerous people of faith understand reality as it intersects the issue of homosexuality, both in the wider culture and in social work. The author suggests that to provide effective services to an increasingly diverse society and to remain grounded in the Code of Ethics, social work must work toward a more inclusive profession that accepts both progressives and people of faith.


Usefulness of soluble CD163 as a biomarker for macrophage activation syndrome associated with systemic lupus erythematosus.
We aimed to study the usefulness of serum soluble CD163 (sCD163) as a biomarker for macrophage activation syndrome (MAS) associated with systemic lupus erythematosus (SLE). Serum sCD163 levels were retrospectively measured by enzyme-linked immunosorbent assay for SLE patients associated with MAS (SLE-MAS), lupus nephritis (LN), or autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenia (ITP) and healthy controls (HCs). Posttreatment samples were also evaluated in the available SLE-MAS patients. The associations between serum sCD163 levels and clinical information were statistically analyzed. The serum sCD163 levels in SLE-MAS, LN and SLE-AIHA/ITP groups were significantly higher than those in HCs (n = 17, 29, 13, and 68, respectively; p < 0.01 for all comparisons). In addition, the serum sCD163 levels in the SLE-MAS group were even higher than those in the LN and SLE-AIHA/ITP groups (p < 0.01 for both comparisons). Serum sCD163 levels were correlated with the SLE Disease Activity Index 2000 scores (r = 0.53), whereas they were not correlated with the serum ferritin levels. With the determined cut-off value, the sensitivity and specificity of serum sCD163 for the diagnosis of SLE-MAS were 59% and 86%, respectively. Retesting showed that the serum sCD163 levels decreased significantly following treatment in parallel with disease amelioration in the SLE-MAS group (p < 0.01). The present study suggests the usefulness of serum sCD163 as a diagnostic and disease-activity biomarker for SLE-associated MAS. Serum sCD163 might also have a different role as a biomarker for SLE-associated MAS than serum ferritin does.


Parenteral nutrition supplemented with short-chain fatty acids: effect on the small-bowel mucosa in normal rats.
When enteral nutrition is excluded from animals maintained solely with total parenteral nutrition (TPN), atrophy of the intestinal mucosa is observed. Short-chain fatty acids (SCFAs) are produced in the colon by the fermentation of dietary carbohydrates and fiber polysaccharides and have been shown to stimulate mucosal-cell mitotic activity in the intestine. This study compared the effects of an intravenous and an intracecal infusion of SCFAs on the small-bowel mucosa. Rats received standard TPN, TPN with SCFAs (sodium acetate, propionate, and butyrate), TPN with an intracecal infusion of SCFAs, or rat food. After 7 d jejunal and ileal mucosal weights, DNA, RNA, and protein were determined. Standard TPN produced significant atrophy of the jejunal and ileal mucosa. Both the intracecal and intravenous infusion of SCFAs significantly reduced the mucosal atrophy associated with TPN. The intravenous and intracolonic infusion of SCFAs were equally effective in inhibiting small-bowel mucosal atrophy.


Portable and Error-Free DNA-Based Data Storage.
DNA-based data storage is an emerging nonvolatile memory technology of potentially unprecedented density, durability, and replication efficiency. The basic system implementation steps include synthesizing DNA strings that contain user information and subsequently retrieving them via high-throughput sequencing technologies. Existing architectures enable reading and writing but do not offer random-access and error-free data recovery from low-cost, portable devices, which is crucial for making the storage technology competitive with classical recorders. Here we show for the first time that a portable, random-access platform may be implemented in practice using nanopore sequencers. The novelty of our approach is to design an integrated processing pipeline that encodes data to avoid costly synthesis and sequencing errors, enables random access through addressing, and leverages efficient portable sequencing via new iterative alignment and deletion error-correcting codes. Our work represents the only known random access DNA-based data storage system that uses error-prone nanopore sequencers, while still producing error-free readouts with the highest reported information rate/density. As such, it represents a crucial step towards practical employment of DNA molecules as storage media.


Alternative metals for homogeneous catalyzed hydroformylation reactions.
Transition-metal-catalyzed hydroformylation reactions constitute one of the most powerful tools for C-C bond formation in organic synthesis and represent an outstanding example of the application of homogeneous catalysis on an industrial scale. This process allows for the straightforward conversion of inexpensive chemical feedstock into broadly applicable aldehydes, which serve as major building blocks for numerous chemical products. These products are highly valuable for the chemical industry and used as plasticizers, detergents, and surfactants on a million ton scale. Moreover, aldehydes serve as versatile chemical intermediates for the production of fine chemicals and pharmaceuticals. Currently, most of the bulk hydroformylation processes rely on rhodium-based catalysts. The increasing demand and resulting high cost of this precious metal has resulted in alternative transition-metal catalysts becoming highly desirable. The following Review summarizes the progress achieved utilizing Ru, Ir, Pd, Pt, and Fe catalysts in hydroformylation reactions.


Bacterial topoisomerase I as a target for discovery of antibacterial compounds.
Bacterial topoisomerase I is a potential target for discovery of new antibacterial compounds. Mutant topoisomerases identified by SOS induction screening demonstrated that accumulation of the DNA cleavage complex formed by type IA topoisomerases is bactericidal. Characterization of these mutants of Yersinia pestis and Escherichia coli topoisomerase I showed that DNA religation can be inhibited while maintaining DNA cleavage activity by decreasing the binding affinity of Mg(II) ions. This can be accomplished either by mutation of the TOPRIM motif involved directly in Mg(II) binding or by altering the charge distribution of the active site region. Besides being used to elucidate the key elements for the control of the cleavage-religation equilibrium, the SOS-inducing mutants of Y. pestis and E. coli topoisomerase I have also been utilized as models to study the cellular response following the accumulation of bacterial topoisomerase I cleavage complex. Bacterial topoisomerase I is required for preventing hypernegative supercoiling of DNA during transcription. It plays an important role in transcription of stress genes during bacterial stress response. Topoisomerase I targeting poisons may be particularly effective when the bacterial pathogen is responding to host defense, or in the presence of other antibiotics that induce the bacterial stress response.


In-vitro antileishmanial potential of peptide drug hirudin.
Hirudin is clinically an important drug used for the treatment of cardiac diseases, but has never been elucidated for antileishmanial potential. This study was designed to determine the therapeutic utility of hirudin against leishmaniasis. Binding affinities of 28 potent proteinase inhibitors were screened computationally against leishmanolysin (GP63), out of which hirudin exhibited higher binding affinity with GP63 and good expected IC50 values. Experimentally, hirudin showed most promising activity against promastigote and axenic amastigote forms of leishmanial parasites with IC50 values of 0.60 ± 0.36 μg/mL and 0.43 ± 0.23 μg/mL, respectively, in a dose- and time-dependent assay. The cytotoxicity assay revealed no adverse effects on human macrophages with LD50 value of 860.11 ± 53.44 μg/mL. Hirudin caused leishmanial cell death mainly by apoptosis and membrane permeability. In spite of the basic knowledge obtained, hirudin mechanism is considerably less prone to the induction of resistance than classical drugs. Collectively, this study fosters further studies for the hirudin as new antileishmania lead with a new mode of action.


The association between non-alcoholic fatty liver disease and atopic dermatitis: a population-based cohort study.
In previous studies, it was reported that non-alcoholic fatty liver disease (NAFLD) incidence and prevalence increased in children with atopic dermatitis. Nevertheless, the actual association between the two diseases has not been fully proven in large-scale studies, and real-world evidence is missing. The objective of this nationwide, longitudinal cohort study was to evaluate the association between NAFLD and atopic dermatitis. The National Health Insurance Research Database in Taiwan was utilized in this study. Patients with records of NAFLD diagnosis were recruited as the experimental group, and patients having less than three outpatient visits or one inpatient visiting record due to NAFLD were excluded from the study design. Non-NAFLD controls were matched based on a 1:4 propensity score matching. Potential confounders including age, gender, comorbidity, and medical utilization status were considered as covariates. The risk of future atopic dermatitis would be evaluated based on multivariate Cox proportional hazard regression. Compared with people without NAFLD, a decreased risk of atopic dermatitis in NALFD patients had been observed (aHR = 0.93, 95% CI 0.87-0.98). The trend was especially presented in young NAFLD patients. In patients younger than 40 years old, a 20% decreased risk of atopic dermatitis was reported (aHR = 0.80, 95% CI 0.70-0.92). People with NAFLD were not associated with an increased risk of atopic dermatitis. Conversely, a 0.93-fold risk was noted in NAFLD patients, compared with NAFLD-free controls. Future studies are warranted to evaluate further the mechanism regarding the interplay between the inflammatory mechanisms of NAFLD and atopic dermatitis.


Understanding history, and not repeating it. Neuroprotection for acute ischemic stroke: from review to preview.
Neuroprotection for ischemic stroke is a growing field, built upon the elucidation of the biochemical pathways of ischemia first studied in the 1970s. Beginning in the early 1990s, means by which to pharmacologically intervene and counteract these pathways have been sought, though with little clinical success. Through a comprehensive review of translations from laboratory to clinic, we aim to evaluate individual mechanisms of action, while highlighting potential barriers to success that will guide future research. The MEDLINE database and The Internet Stroke Center clinical trials registry were queried for trials involving the use of neuroprotective agents in acute ischemic stroke in human subjects. For the purpose of the review, neuroprotective agents refer to medications used to preserve or protect the potentially ischemic tissue after an acute stroke, excluding treatments designed to re-establish perfusion. This excludes mechanical or pharmacological thrombolytics, anti-thrombic medications, or anti-platelet therapies. This review summarizes previously trialed neuroprotective agents, including but not limited to glutamate neurotransmission blockers, anti-oxidants, GABA agonists, leukocyte migration blockers, various small cation channel modulators, narcotic antagonists, and phospholipid membrane stabilizers. We outline key biochemical steps in ischemic injury that are the proposed areas of intervention. The agents, time to administration of therapeutic agent, follow-up, and trial results are reported. Stroke trials in humans are burdened with a marked heterogeneity of the patient population that is not seen in animal studies. Also, trials to date have included patients that are likely treated at a time outside of the window of efficacy for neuroprotective drugs, and have not effectively combined thrombolysis with neuroprotection. Through an evaluation of the accomplishments and failures in neuroprotection research, we propose new methodologies, agents, and techniques that may provide new routes for success.


Alarmins, inflammasomes and immunity.
The elaboration of an effective immune response against pathogenic microbes such as viruses, intracellular bacteria or protozoan parasites relies on the recognition of microbial products called pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs). Ligation of the PRRs leads to synthesis and secretion of pro-inflammatory cytokines and chemokines. Infected cells and other stressed cells also release host-cell derived molecules, called damage-associated molecular patterns (DAMPs, danger signals, or alarmins), which are generic markers for damage. DAMPs are recognized by specific receptors on both immune and nonimmune cells, which, depending on the target cell and the cellular context, can lead to cell differentiation or cell death, and either inflammation or inhibition of inflammation. Recent research has revealed that DAMPs and PAMPs synergize to permit secretion of pro-inflammatory cytokines such as interleukin-1β (IL-1β): PAMPs stimulate synthesis of pro-IL-1β, but not its secretion; while DAMPs can stimulate assembly of an inflammasome containing, usually, a Nod-like receptor (NLR) member, and activation of the protease caspase-1, which cleaves pro-IL-1β into IL-1β, allowing its secretion. Other NLR members do not participate in formation of inflammasomes but play other essential roles in regulation of the innate immune response.


Clinical Evidence Supporting the Role of Lonidamine for the Treatment of BPH.
Glandular prostate epithelial cells of the peripheral zone are unique among normal cells in their dependence on glycolysis for energy production, due to a zinc-mediated enzymatic block in the citric acid cycle. Lonidamine (LND), a derivative of indazole-3-carboxylic acid, is thought to disrupt energy metabolism by interfering with glycolysis and to cause cell apoptosis. We evaluated the efficacy of oral LND treatment in subjects with symptomatic benign prostatic hyperplasia (BPH). The following reports the findings of an open-label study of orally administered LND. Thirty subjects with symptomatic BPH received oral LND (150 mg/day) once daily for 28 days. Subjects were assessed at baseline, at active-therapy assessment visits (days 14, 28), and 1, 2, 3, and 6 months post-therapy, for prostate volume (PV) by transrectal ultrasound (TRUS), maximum flow rate (Q(max)) on uroflowmetry, postvoid residual urine volume (PVR), International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, serum chemistry, and adverse events.


Influence of conserved amino acids on the structure and environment of the heme of cytochrome c2. A resonance Raman study.
Resonance Raman spectra using Soret excitations of oxidized and reduced Rhodobacter capsulatus cytochrome c2 at pH 7.5 were studied. The spectra of oxidized cytochrome c2 show three components for the v10 mode at 1638, 1633, and 1629 cm(-1). The intensities of these components are sensitive to the excitation wavelength. This effect is explained in the context of a conformational equilibrium of the ferriheme between a nearly planar structure and two ruffled structures. In the case of reduced cytochrome c2, the absolute frequencies as well as the excitation-dependent frequency dispersion of the v10 mode (1618-1621 cm(-1)) indicate a displacement of the conformational equilibrium of heme toward the more planar structures. To measure the influence of some key amino acid residues on the heme-protein interaction of cytochrome c2, four site-directed mutants of Rb. capsulatus cytochrome c2 have been studied by resonance Raman spectroscopy and their spectra compared with the spectra obtained for the wild type cytochrome. The mutants studied are K14E/K32E, P35A, W67Y, and Y75F. The spectral changes induced by the mutations are interpreted in terms of alterations in the structure and/or environment of the cytochrome c2 heme in the framework of the expected role of the different amino acid residues in the stability and redox potential.


Young children infer psychological ownership from stewardship.
Although people take care of their own possessions, they also engage in stewardship and take care of things they do not own. Here, we examined what young children infer when they observe stewardship behavior of an object. Through four experiments on predominantly middle-class Canadian children (total N = 350, 168 girls and 182 boys from a predominantly White and middle-class region), we found that children as young as 4 or 5 infer feelings of ownership from stewardship behaviors and distinguish between psychological and legal ownership. They also understand that psychological and legal ownership are independent as one can exist without the other, and children as young as 3 may link stewardship with welfare concerns. We also suggest that while stewardship has been shown to be a consequence of psychological ownership, it is also likely to be an antecedent. As future stewards of our resources, young children's understanding of the link between psychological ownership and stewardship links directly to sustainability concerns. We contribute theoretically both to the child development and psychological ownership literatures. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Colocalized granular cell tumor and infiltrating ductal carcinoma of the breast.
A 57-year-old woman presented with a 2-year history of a palpable mass in the upper inner quadrant of the right breast. A 1.1-cm, poorly circumscribed, firm tumor nodule was noted, consisting of 2 histologically distinct lesions in the same location, with some areas showing purely well-differentiated invasive ductal carcinoma and others composed of granular cell tumor. In 1 area, the 2 tumors collided and infiltrated each other. The invasive ductal carcinoma was admixed with ductal carcinoma in situ of solid and cribriform types. To our knowledge, this is the first case report demonstrating colocalization of these 2 neoplasms, which raises questions regarding causal relationship. We also review the literature on granular cell tumor of the breast.


Long-Term Monitoring of Amphibian Populations of a National Park in Northern Spain Reveals Negative Persisting Effects of Ranavirus, but Not Batrachochytrium dendrobatidis.
Amphibians are the most highly threatened vertebrates, and emerging pathogens are a serious threat to their conservation. Amphibian chytrid fungi and the viruses of the Ranavirus genus are causing disease outbreaks worldwide, including in protected areas such as National Parks. However, we lack information about their effect over amphibian populations in the long-term, and sometimes these mortality episodes are considered as transient events without serious consequences over longer time-spans. Here, we relate the occurrence of both pathogens with the population trends of 24 amphibian populations at 15 sites across a national Park in northern Spain over a 14-year period. Just one out 24 populations presents a positive population trend being free of both pathogens, while seven populations exposed to one or two pathogens experienced strong declines during the study period. The rest of the study populations (16) remain stable, and these tend to be of species that are not susceptible to the pathogen present or are free of pathogens. Our study is consistent with infectious diseases playing an important role in dictating amphibian population trends and emphasizes the need to adopt measures to control these pathogens in nature. We highlight that sites housing species carrying Ranavirus seems to have experienced more severe population-level effects compared to those with the amphibian chytrid fungus, and that ranaviruses could be just as, or more important, other more high-profile amphibian emerging pathogens.


What does imaging add to the management of Alzheimer's disease?
The prevalence of Alzheimer's disease (AD) and dementia continues to rise. However, a significant number of patients are undiagnosed or untreated. Given the complexities of detecting cognitive impairment and the early signs of AD, this review discusses how advances in brain imaging can help assist in improving overall management. Imaging techniques and surrogate markers may provide unique opportunities to diagnose accurately AD in presymptomatic stages with practical consequences for patients, caregivers, and physicians. The possible outcomes for using imaging and surrogate markers as adjuncts to clinical examination and as screening tools for AD, as well as tangible and intangible advantages to early diagnosis and treatment, will be discussed. The specific value of using advanced serial imaging in patients with a genetic disposition to AD will be evaluated. If neurons can be protected from neurodegenerative damage in early stages, this may preserve patient cognition, function, and quality of life, and may confer considerable societal healthcare benefits.


Inhaled carbenoxolone prevents allergic airway inflammation and airway hyperreactivity in a mouse model of asthma.
Asthma is a chronic respiratory disease, which needs a safer medication preferably in inhalation form. In view of this, we have evaluated the effect of inhaled carbenoxolone (CBX), a herbal-derived compound, on asthma in a mouse model. Mice were sensitized and challenged with ovalbumin (OVA) to develop certain characteristic features of asthma such as airway hyperreactivity (AHR), airway eosinophilia, lung inflammation and mucus hypersecretion. To evaluate the effect of CBX on the above asthmatic features, CBX (2.5, 5 and 10 mg/ml, 3 ml) or vehicle (water) was given by inhalation. AHR was determined using whole-body plethysmography. Infiltration of eosinophils was estimated by microscopy. Lung inflammation and mucus hypersecretion were assessed using hematoxylin and eosin, and periodic acid-Schiff staining, respectively. Th-2 cytokines, IL-4 and IL-5 were measured in bronchoalveolar lavage (BAL) fluid and IgE in sera. To identify the possible mode of CBX action, we measured corticosterone levels in the BAL fluid and 5-lipoxygenase (5-LO) expression in the lungs. CBX (5 mg/ml) inhalation markedly alleviated AHR (p = 0.0032) and reduced lung inflammation and mucus hypersecretion. Also, it prevented the increase in IL-4 (p = 0.0192), IL-5 (p = 0.0116) and eosinophils (p < 0.0005) in the BAL fluid, and OVA-specific IgE levels (p = 0.00061) in sera. 5-LO expression was also markedly reduced. However, corticosterone levels were not affected. Inhaled CBX alleviates the asthmatic features in mice and could be a potent nebulized therapy in clinical asthma.


Second Harmonic Generation Mediated by Aligned Water in Starch Granules.
The origin of second harmonic generation (SHG) in starch granules was investigated using ab initio quantum mechanical modeling and experimentally examined using polarization-in, polarization-out (PIPO) second harmonic generation microscopy. Ab initio calculations revealed that the largest contribution to the SHG signal from A- and B-type allomorphs of starch originates from the anisotropic organization of hydroxide and hydrogen bonds mediated by aligned water found in the polymers. The hypothesis was experimentally tested by imaging maize starch granules under various hydration and heat treatment conditions that alter the hydrogen bond network. The highest SHG intensity was found in fully hydrated starch granules, and heat treatment diminished the SHG intensity. The PIPO SHG imaging showed that dried starch granules have a much higher nonlinear optical susceptibility component ratio than fully hydrated granules. In contrast, deuterated starch granules showed a smaller susceptibility component ratio demonstrating that SHG is highly sensitive to the organization of the hydroxyl and hydrogen bond network. The polarization SHG imaging results of potato starch granules, representing starch allomorph B, were compared to those of maize starch granules representing allomorph A. The results showed that the amount of aligned water was higher in the maize granules. Nonlinear microscopy of starch granules provides evidence that varying hydration conditions leads to significant changes in the nonlinear susceptibility ratio as well as the SHG intensity, supporting the hypothesis from ab initio calculations that the dominant contribution to SHG is due to the ordered hydroxide and hydrogen bond network.


LIMITS TO THE SOUTHERN BORDER OF DROSOPHILA SERRATA: COLD RESISTANCE, HERITABLE VARIATION, AND TRADE-OFFS.
There are a number of evolutionary hypotheses about why species distributions are limited, but very little empirical information to test them. We present data examining whether the southern distribution of Drosophila serrata is limited by cold responses. Species comparisons were undertaken for cold resistance, development time, and viability at 15°C and 25°C for D. serrata and other species with a more southerly distribution (D. melanogaster, D. simulans, and D. immigrans). Relative to the other species, D. serrata had a long development time at both temperatures and a low level of cold resistance. Using isofemale lines collected in different seasons, central and marginal populations were compared for cold resistance, as well as development time and viability at 14°C. The border population had a relatively higher resistance to cold shock in postwinter collections, but there was no population differentiation for prewinter collections or for the other traits. The presence of variation among isofemale lines within the border populations suggests that genetic variation as measured in the laboratory is unlikely to limit range expansion. Population cages were used in the field to determine if D. serrata persisted over winter at borders. Although all cages yielded adult offspring at northern sites, only a few produced offspring at or just south of the border. In contrast, all cages with D. simulans produced adult offspring, suggesting that climatic factors limited D. serrata numbers. Offspring from surviving adults showed a phenotypic trade-off between fecundity and cold resistance. Comparisons of the cold resistance of field males and females with their laboratory-reared offspring provided evidence for heritable variation in field-reared flies. Overall, the results suggest that cold stress is important in limiting the southern distribution of D. serrata, but it seems unlikely that a lack of genetic variation restricts range expansion.


Enhanced expression of interleukin-18 receptor alpha chain by CD4+ T cells in sarcoidosis.
To investigate the expression of interleukin-18 receptor alpha chain (IL-18Ralpha) in BAL and peripheral blood (PB) T cells in patients with sarcoidosis compared with control subjects, to evaluate the relationship between the expression and clinical manifestations, and to clarify the mechanisms of altered expression. The study subjects consisted of 21 patients with sarcoidosis and 8 normal control subjects. The expression of IL-18Ralpha was examined by flow cytometry. The proportions of BAL CD4+ and PB CD4+ T cells expressing IL-18Ralpha were significantly increased in patients with sarcoidosis compared to control subjects. BAL CD4+ T cells expressed IL-18Ralpha in a higher proportion than did paired CD8+ T cells in patients with sarcoidosis but not in control subjects. Greater proportions of BAL CD4+ T cells and BAL CD8+ T cells than of their PB counterparts expressed IL-18Ralpha in both patients and control subjects. CD4+ T cells were more sensitive to the induction of IL-18Ralpha by cytokines in vitro, such as interleukin (IL)-2, IL-12, and tumor necrosis factor-alpha than were CD8+ T cells. Increased expression of IL-18Ralpha by BAL T cells commonly observed in patients and control subjects was associated with the expansion of CD45RO+ cells in BAL T cells. However, there were no significant correlations between the expression of IL-18Ralpha by any cell populations and BAL findings, serum angiotensin-converting enzyme activities, radiograph stages, or clinical courses. The overexpression of IL-18Ralpha predominantly by CD4+ T cells in sarcoidosis emphasizes crucial roles played by T-helper type 1 cells in the IL-18/IL-18Ralpha system in sarcoidosis.


Complications of abdominal contouring surgery in obese patients: current status.
Medical records of 122 patients who underwent an abdominoplasty or panniculectomy from 2003 to 2008 were reviewed to determine current rates of wound complications associated with these procedures in the presence of obesity. An additional aim was to determine current rates of complications as compared with those found 10 years ago at our institution to determine if the finding of obesity alone continues to adversely affect wound outcomes. Sixty-three of 122 patients (51.6%) experienced 1 or more wound-related complications. Major complications occurred in 13 patients (10.7%). A striking finding was that the lowest major complication rate 4.5%, was found in patients with extreme obesity (BMI >40). Comparisons between the 1999 and current studies found that the difference in major complications in those classified as obese, with 2 (9%) in the current study and 8 (40%) in the 1999 study, was significant (P = 0.039). Our findings suggest that high rates of major complications found in those with obesity in the 1999 study are not found today. Extreme obesity is not an absolute contraindication to operation and may be performed safely.


Self-assembled multivalency: dynamic ligand arrays for high-affinity binding.
Multivalency is a powerful strategy for achieving high-affinity molecular recognition in biological systems. Recently, attention has begun to focus on using self-assembly rather than covalent scaffold synthesis to organize multiple ligands. This approach has a number of advantages, including ease of synthesis/assembly, tunability of nanostructure morphology and ligands, potential to incorporate multiple active units, and the responsive nature of self-assembly. We suggest that self-assembled multivalency is a strategy of fundamental importance in the design of synthetic nanosystems to intervene in biological pathways and has potential applications in nanomedicine.


Intra individual variation in the number of B chromosomes in the yellow-necked mouse, Apodemus flavicollis (Mammalia, Rodentia).
The yellow-necked mouse, Apodemus flavicollis, is characterized by a frequent occurrence of B chromosomes. The frequency of intra individual mosaicism of Bs was studied in 995 animals collected at six localities in Serbia. It was found that 329 (33.06%) possessed B chromosomes. Among these, 87 animals (26.44%) were mosaics. A total of 32 mosaic animals with more than one B chromosome were analyzed for distribution of Bs which was found to be quite different between groups of animals with different numbers of Bs and increases with their number. The frequency of mosaics differs between localities and ranges from 0.22 to 0.55.


Immunodepression in Giardia muris and Spironucleus muris infections in mice.
Infections with the intestinal flagellates Giardia muris and Spironucleus muris are accompanied by a depression in the ability of mice to mount an immune response to a thymus-dependent antigen (sheep red blood cells) but not to a thymus-independent antigen (TNP-lipopolysaccharide). The number of splenic IgM plaque-forming cells and haemagglutination titres, of both IgM and IgG, to sheep red blood cells decreased between days 10 and 21, which correlated with the time of maximal trophozoite levels in the small intestine. The number of background IgM plaque-forming cells to sheep red blood cells or DNP was not significantly different from controls in either infection. No evidence for systemic macrophage activation was associated with these infections. In fact, adherent peritoneal exudate cells (PEC) from infected mice were slightly less cytostatic against target tumour cells than adherent PEC from normal mice, at a time when the parasites were being eliminated from the small intestine.


Bacterial capture by peptide-mimetic oligoacyllysine surfaces.
Most procedures for detecting pathogens in liquid media require an initial concentration step. However, poor recovery efficiencies of conventional methods, such as filtration, often lead to low sensitivity. Here, we describe a strategy for concentrating bacteria using their binding affinity for an oligoacyllysine (OAK), a novel peptide-mimetic antimicrobial compound. We show that the resin-linked OAK (ROAK) efficiently captures a variety of pathogens in different media, upon brief incubation with ROAK beads or after continuous flow through a ROAK-packed column. Using Escherichia coli expressing green fluorescent protein, we show that binding occurs rapidly during incubation and persists after filtration as visualized by confocal microscopy. The high binding affinity of bacteria was confirmed by surface plasmon resonance technology using an OAK-linked chip. ROAK-bound bacteria remained viable and were readily identifiable by real-time PCR after ethanol elution. A single ROAK bead is estimated to capture about 3,000 bacterial cells in culture medium, in contaminated saline or tap water. ROAK beads can be regenerated for multiple uses after brief ethanol treatment. Collectively, the data support the notion that OAK-based coating of polymeric surfaces might represent a useful means for medium filtration as well as for concentration of bacteria.


Spectroscopic studies on the protective effect of a specific sugar on concanavalin A at acidic, neutral and alkaline pH.
A Systematic investigation of the effect of pH on concanavalin A in the presence of specific and non-specific sugars is made using CD (circular dichroism) and fluorescence. The specific and non-specific sugars for concanavalin A were methyl alpha-D-glucopyranoside and methyl alpha-D-galactopyranoside respectively. Far-UV CD showed changes in the MRE value at 217 nm in the presence of the above-mentioned sugars. At pH 7, the CD and fluorescence spectra obtained in the presence of methyl alpha-D-glucopyranoside were slightly different from those for the native state and a significant difference was obtained in the presence of methyl alpha-D-galactopyranoside. Near-UV CD spectra showed the retention of a native-like tertiary structure in the presence of the specific sugar upon pH denaturation. Tryptophan fluorescence studies indicated a change in the tryptophan enviornment. The results obtained from our CD data are consistent with those obtained from fluorescence studies. Upon pH exposure of concanavalin A in the presence of methyl alpha-D-glucopyranoside and methyl alpha-D-galactopyranoside, the former acted as a protector preventing conformational alteration at different pH while the presence of latter induced a different stable conformational state and this state persists over the pH range from 2 to 10.


Prediction of RBP binding sites on circRNAs using an LSTM-based deep sequence learning architecture.
Circular RNAs (circRNAs) are widely expressed in highly diverged eukaryotes. Although circRNAs have been known for many years, their function remains unclear. Interaction with RNA-binding protein (RBP) to influence post-transcriptional regulation is considered to be an important pathway for circRNA function, such as acting as an oncogenic RBP sponge to inhibit cancer. In this study, we design a deep learning framework, CRPBsites, to predict the binding sites of RBPs on circRNAs. In this model, the sequences of variable-length binding sites are transformed into embedding vectors by word2vec model. Bidirectional LSTM is used to encode the embedding vectors of binding sites, and then they are fed into another LSTM decoder for decoding and classification tasks. To train and test the model, we construct four datasets that contain sequences of variable-length binding sites on circRNAs, and each set corresponds to an RBP, which is overexpressed in bladder cancer tissues. Experimental results on four datasets and comparison with other existing models show that CRPBsites has superior performance. Afterwards, we found that there were highly similar binding motifs in the four binding site datasets. Finally, we applied well-trained CRPBsites to identify the binding sites of IGF2BP1 on circCDYL, and the results proved the effectiveness of this method. In conclusion, CRPBsites is an effective prediction model for circRNA-RBP interaction site identification. We hope that CRPBsites can provide valuable guidance for experimental studies on the influence of circRNA on post-transcriptional regulation.


EWSR1-SMAD3-Positive Fibroblastic Tumor.
EWSR1-SMAD3-positive fibroblastic tumor is a recently characterized neoplasm with distinct clinicopathologic features and recurrent EWSR1-SMAD3 gene fusion. ESFT typically presents as a small, painless tumor in extremity subcutaneous tissues. Their behavior is benign, although they are prone to local recurrence. They typically comprise two components: intersecting fascicles of overlapping, uniform plump spindle cells, and less cellular hyalinized areas containing stippled calcifications. Immunohistochemically, the cells consistently show diffuse ERG nuclear expression, while other markers are negative. The morphology of this neoplasm can lead to histologic confusion with both benign and malignant soft tissue tumors, including monophasic synovial sarcoma, malignant peripheral nerve sheath tumor, and spindle cell sarcoma, not otherwise specified. Correct identification of ESFT is critical, most importantly to avoid unnecessary overtreatment as sarcoma.


Possible TRALI is a real entity.
After the consensus definition of transfusion-related acute lung injury (TRALI), studies have shown that the incidence of TRALI is high in critically ill and injured patients. When another risk factor for lung injury is present in these patients, the term "possible TRALI" is used. In the past years, both animal and clinical studies have taught us that a predisposing inflammatory risk factor is frequently present in TRALI, if not mandatory. The decline in the incidence of TRALI after implementation of the use of male-only plasma as observed in general hospital patients is also seen in the critically ill and injured, suggesting that antibodies play a role in possible TRALI. Thereby, introduction of the term "possible TRALI" has helped us in estimating incidence rates as well as to understand risk factors for TRALI in patient populations with a high exposure to transfusion.


Ultrastructural and Photosynthetic Responses of Pod Walls in Alfalfa to Drought Stress.
Increasing photosynthetic ability as a whole is essential for acquiring higher crop yields. Nonleaf green organs (NLGOs) make important contributions to photosynthate formation, especially under stress conditions. However, there is little information on the pod wall in legume forage related to seed development and yield. This experiment is designed for alfalfa (Medicago sativa) under drought stress to explore the photosynthetic responses of pod walls after 5, 10, 15, and 20 days of pollination (DAP5, DAP10, DAP15, and DAP20) based on ultrastructural, physiological and proteomic analyses. Stomata were evidently observed on the outer epidermis of the pod wall. Chloroplasts had intact structures arranged alongside the cell wall, which on DAP5 were already capable of producing photosynthate. The pod wall at the late stage (DAP20) still had photosynthetic ability under well-watered (WW) treatments, while under water-stress (WS), the structure of the chloroplast membrane was damaged and the grana lamella of thylakoids were blurry. The chlorophyll a and chlorophyll b concentrations both decreased with the development of pod walls, and drought stress impeded the synthesis of photosynthetic pigments. Although the activity of ribulose-1,5-bisphosphate carboxylase (RuBisCo) decreased in the pod wall under drought stress, the activity of phosphoenolpyruvate carboxylase (PEPC) increased higher than that of RuBisCo. The proteomic analysis showed that the absorption of light is limited due to the suppression of the synthesis of chlorophyll a/b binding proteins by drought stress. Moreover, proteins involved in photosystem I and photosystem II were downregulated under WW compared with WS. Although the expression of some proteins participating in the regeneration period of RuBisCo was suppressed in the pod wall subjected to drought stress, the synthesis of PEPC was induced. In addition, some proteins, which were involved in the reduction period of RuBisCo, carbohydrate metabolism, and energy metabolism, and related to resistance, including chitinase, heat shock protein 81-2 (Hsp81-2), and lipoxygenases (LOXs), were highly expressed for the protective response to drought stress. It could be suggested that the pod wall in alfalfa is capable of operating photosynthesis and reducing the photosynthetic loss from drought stress through the promotion of the C4 pathway, ATP synthesis, and resistance ability.


Effect of synthetic atrial natriuretic polypeptide on hemorrhage-induced adrenocorticotropin secretion of the rat.
The effect of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) on the in vivo and in vitro release of ACTH and corticosterone was examined. In the in vivo study ACTH and corticosterone responses to rapid 2-ml/rat hemorrhage were measured in sixteen conscious rats after alpha-hANP administration. The hemorrhage increased plasma ACTH and corticosterone concentrations in the control group of rats (p greater than 0.01). ANP inhibited hemorrhage-induced ACTH secretion (p less than 0.05), but the plasma corticosterone response was not affected. In the in vitro study a high concentration of ANP (1 microM) reduced basal corticosterone secretion from the isolated rat adrenal gland (p less than 0.05), but the response to ACTH (10 ng/ml) and dibutyryl cyclic AMP (0.5 mM, 5.0 mM) was not affected. Our data suggest that ANP inhibits hemorrhage-induced ACTH secretion from the anterior pituitary but inhibits corticosterone secretion from the adrenal gland very weakly.


Autoantibodies and HLA susceptibility markers in Canadian first-degree relatives of patients with type 1 diabetes.
We examined the frequencies of autoantibodies to glutamate decarboxylase, GAD65, protein tyrosine phosphatase, IA-2/ICA512, and insulin, and of HLA class II markers in ICA-positive first-degree relatives of patients with type 1 diabetes. Our results indicate that while the presence of HLA susceptibility markers is associated with anti-islet autoantibodies, protective DQB1 markers do not absolutely prevent development of autoantibodies or progression to autoimmune diabetes.


Influence of lipopolysaccharide chemotype on the interaction between Klebsiella pneumoniae and human polymorphonuclear leucocytes.
A series of isogenic mutants lacking either the O1 (O-:K66) or K66 (O1:K-) antigens or both (O-:K-), some of which had additional defects in their LPS core polysaccharide was used to examine the interaction between polymorphonuclear leucocytes (PMNLs) and K. pneumoniae serotype O1:K66. In the absence of serum complement, only a O-:K- strain with a deep rough LPS chemotype elicited a PMNL-dependent chemiluminescent (CL) response. However, following opsonization of the non-capsulated strains by complement, the largest CL response was to the O1:K- mutant. This mutant also activated and bound more complement C3 than any of the other encapsulated or non-capsulated strains examined. Despite the surface exposure of smooth and rough LPS in the encapsulated parent and mutant strains, the K66 antigen reduced the binding of C3 and prevented PMNL activation. Both anti-LPS and anti-K66 antibodies, however, stimulated a PMNL-dependent CL response to the K66 bearing strains.


Absence of hepatic cytochrome P450bufI causes genetically deficient debrisoquine oxidation in man.
The common genetic deficiency of drug oxidation known as debrisoquine/sparteine-type polymorphism was investigated with bufuralol as prototype substrate. In human liver microsomes the 1'-hydroxylation of bufuralol is catalyzed by two functionally distinct P-450 isozymes, the high-affinity/highly stereoselective P450bufI and the low-affinity/nonstereoselective P450bufII. We demonstrate that P450bufI is unique in hydroxylating bufuralol in a cumene hydroperoxide (CuOOH) mediated reaction whereas P450bufII is active only in the classical NADPH- and O2-supported monooxygenation. In microsomes of liver biopsies of in vivo phenotyped poor metabolizers of debrisoquine or sparteine, the CuOOH-mediated activity was drastically reduced. Rabbit antibodies against a rat P-450 isozyme with high bufuralol 1'-hydroxylase activity (P450db1) precipitated exclusively P450bufI-type activity from solubilized microsomes. Western blotting of microsomes with these antibodies revealed a close correlation between the immunoreactive protein and CuOOH-mediated (+)-bufuralol 1'-hydroxylation. No immunoreactive protein was detected in liver microsomes of in vivo phenotyped poor metabolizers. These data provide evidence for a specific deficiency of P450bufI and are consistent with the complete or almost complete absence of this protein in the liver of poor metabolizers.


Letter from the Editor-in-Chief.
It was in the mid-nineties when a senior colleague of mine, Dr. Bojan Biocina, introduced me to something called "OpenHeart-L" on The Heart Surgery Forum website. Suddenly, a whole new world appeared in front of me! The possibility to communicate with colleagues from all around the globe was amazing. And not only that-one could ask anything, and there was always someone who had an answer, gave a piece of advice…what to do, what to avoid...it was magic! The person responsible for this whole idea of sharing information and interactive communication was Mark Levinson. At that time I was more a lurker than a poster, eagerly waiting for discussions to develop and learning from other people's posts.


Intraosseous synovial sarcoma of the proximal femur: Case report.
Synovial sarcoma is primarily a soft tissue malignancy that most often affects adolescents and young adults. It very rarely presents as a primary bone tumour and has only been reported in nine other cases to date. We report a case of primary synovial sarcoma arising from the proximal femur in a 57-year-old man. Synovial sarcoma, primary bone tumour.


Highly efficient refractive Gaussian-to-tophat beam shaper for compact terahertz imager.
We describe an efficient and compact terahertz (THz) illumination system as part of an active THz imager. The design and fabrication methods are verified by comparing measurements with wave optical simulations that form a basis for the design of a Gaussian-to-tophat beam shaper. Introducing realistic alignment tolerances in the simulations led to an improved agreement with the experimental data. Furthermore, we propose a method to reduce the alignment effort for THz beam shaping elements by correlating measured results with simulated data of a misaligned system.


Design of a modular and compliant wrist module for upper limb prosthetics.
In the last decades, there have been great efforts in the development of advanced polyarticulated prosthetic hands; in contrast, prosthetic wrists have drawn less interest. Nevertheless, increasing the dexterity of the wrist improves handling skills because the wrist allows the prepositioning of the hand before carrying out a task, avoiding the onset of unwanted trunk or shoulders compensatory movements and potential onset or exacerbation of articular injuries. This study presents a novel 2-degree-of-freedom prosthetic wrist module with active pronation/supination and passive elastic flexion/extension. This system is suitable to be included in hand prostheses to improve anthropomorphism and produce a more physiological motion. The first submodule within the socket is able to rotate a prosthetic hand and an external load of 3 kg at 2.6 rad/s. The second one can guarantee a range of motion of ±75° with a centering elastic torque (compliant mode) or it can keep firms grasps (fixed mode). Compliant mode is based on a Scotch-Yoke mechanism converting wrist flexion/extension into the linear motion of a crossbeam acting on compression springs, while fixed mode is achieved by means of a piston that can be engaged/disengaged. The whole module fits with anthropometry and the modular design ensures the proposed system can be used in a stand-alone way and adapted to different hand prostheses. This device is expected to favor a more physiological dexterity with respect to simpler fixed prostheses that can potentially induce harmful motion of body districts not naturally involved in the reaching and grasping tasks.


Multiple transitions in an infinite range p-spin random crystal field Blume-Capel model.
We study a p-spin model with ferromagnetic coupling and quenched random crystal fields for p≥3 for spin-1 systems. We find that the model has lines of first-order transitions at finite temperature (T) for all p≥3. For bimodal distribution of the random crystal field these lines meet at a triple point for weak strength of the crystal field (Δ). Beyond a critical strength of Δ, they do not meet and one of the lines ends at a critical point (T_{c}). Interestingly, we find that on increasing T from T_{c}, keeping other parameters fixed, the system undergoes one more transition which is first order in its character. The system thus exhibits a Gardner-like transition for a range of parameters for all finite p≥3. For p→∞ the model behaves differently and there is only one random first-order transition at T=0.


Is pre-freeze sperm preparation more advantageous than post-freeze?
Human sperm cryopreservation is characterised to this day by sub-optimal success rates. Interestingly, a traditional approach to improving post-thaw outcome has been to integrate standard sperm preparation techniques into freezing protocols as a means of selecting sperm with the highest fertilisation potential prior to insemination. However, no consensus has been reached yet regarding the optimal timing (before or after freezing) of this selection step. Following analysis of a total of 20 human semen samples, which were divided into two aliquots prepared by density gradient centrifugation either before or after freezing, this study demonstrated higher post-thaw total (P < 0.0001), progressively motile (P = 0.005) and vital (P < 0.0001) sperm counts for frozen-prepared semen samples. The present study suggests that direct insemination with frozen-prepared sperm with minimal intervening post-thaw processing might be a more advantageous approach to current clinical practices, particularly for donor and patient intrauterine insemination programmes. Further research into cryopreservation-induced coiled sperm tail morphology is also warranted. Freezing and storing of sperm in liquid nitrogen ('sperm cryopreservation') is the current method of choice for preserving the fertility of a wide scope of men. Nevertheless, sub-optimal sperm survival is still associated with traditional cryopreservation methods, namely 'slow freezing', and may affect fertility treatment success rates. Interestingly, a widely applied approach for selecting high-quality sperm before treatment has been to incorporate 'sperm preparation' techniques, such as density gradient centrifugation, in slow freezing protocols. There is, however, an ongoing debate regarding which is the optimal timing of this selection step: before or after freezing. In this study, we collected 20 human semen samples which were divided into two portions and subjected to density gradient centrifugation either before or after freezing. Post-thaw semen analyses demonstrated significantly improved sperm counts (P < 0.05) when density gradient centrifugation was performed before freezing, thus suggesting this approach to be more advantageous for current clinical practices.


Photobiomodulation of human dermal fibroblasts in vitro: decisive role of cell culture conditions and treatment protocols on experimental outcome.
Photobiomodulation-based (LLLT) therapies show tantalizing promise for treatment of skin diseases. Confidence in this approach is blighted however by lamentable inconsistency in published experimental designs, and so complicates interpretation. Here we interrogate the appropriateness of a range of previously-reported treatment parameters, including light wavelength, irradiance and radiant exposure, as well as cell culture conditions (e.g., serum concentration, cell confluency, medium refreshment, direct/indirect treatment, oxygen concentration, etc.), in primary cultures of normal human dermal fibroblasts exposed to visible and near infra-red (NIR) light. Apart from irradiance, all study parameters impacted significantly on fibroblast metabolic activity. Moreover, when cells were grown at atmospheric O2 levels (i.e. 20%) short wavelength light inhibited cell metabolism, while negligible effects were seen with long visible and NIR wavelength. By contrast, NIR stimulated cells when exposed to dermal tissue oxygen levels (approx. 2%). The impact of culture conditions was further seen when inhibitory effects of short wavelength light were reduced with increasing serum concentration and cell confluency. We conclude that a significant source of problematic interpretations in photobiomodulation reports derives from poor optimization of study design. Further development of this field using in vitro/ex vivo models should embrace significant standardization of study design, ideally within a design-of-experiment setting.


Biology of BCG response in non-muscle invasive bladder cancer - 2021 IBCN Updates Part III.
Bacillus Calmette-Guerin (BCG) remains the only FDA-approved first-line therapy in patients with high-risk non-muscle invasive bladder cancer. Recurrences, even after adequate BCG therapy, are common and the efficacy of second-line therapies remains modest. Therefore, early identification of patients likely to recur and treatment after recurrence remain critical unmet needs in the clinical care of bladder cancer patients. To address these deficits, a better understanding of the mechanisms of resistance to BCG-therapy is needed. The virtual update of the International Bladder Cancer Network (IBCN) on the biology of response to BCG focused on potential mechanisms and markers of resistance to intravesical BCG therapy. The insights from this meeting will be highlighted and put into context of previously reported mechanisms of resistance to BCG in this review.


Inhibitory effect of Huangqi Zhechong decoction on liver fibrosis in rat.
To assess the inhibitory effect of Huangqi Zhechong decoction on hepatic fibrosis in rats induced by CCl(4) plus alcohol and high fat low protein diet. Male SD rats were randomly divided into hepatic fibrosis model group, control group and 3 treatment groups consisting of 12 rats in each group. Except for the normal control group, all the rats were subcutaneously injected with CCl(4) at a dosage of 3 mL/kg. In 3 treated groups, either high-dose group (9 mL/kg), or medium-dose group (6 mL/kg), or low-dose group (3 mL/kg) was daily gavaged with Huangqi Zhechong decoction, and saline vehicle was given to model and normal control rats. Enzyme-linked immunosorbent assay (ELISA) and biochemical examinations were used to determine the changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN), type-III-procollagen-N-peptide (PIIIP), and type IV collagen content in serum, and hydroxyproline (Hyp) content in liver after sacrificing the rats. Pathologic changes, particularly fibrosis were examined by hematoxylin and eosin (HE) and Van Gieson staining. Compared with the model control group, serum ALT, AST, HA, LN, PIIIP and type IV collagen levels dropped markedly in Huangqi Zhechong decoction groups, especially in the medium-dose Huangqi Zhechong decoction group (1 954+/-576 U/L vs 759+/-380 U/L, 2 735+/-786 U/L vs 1 259+/-829 U/L, 42.74+/-7.04 ng/mL vs 20.68+/-5.85 ng/mL, 31.62+/-5.84 ng/mL vs 14.87+/-1.45 ng/mL, 3.26+/-0.69 ng/mL vs 1.47+/-0.46 ng/mL, 77.68+/-20.23 ng/mL vs 25.64+/-4.68 ng/mL, respectively) (P<0.05). The Hyp content in liver tissue was also markedly decreased (26.47+/-11.24 mg/mgprot vs 9.89+/-3.74 mg/mgprot) (P<0.01). Moreover, the stage of the rat liver fibrosis in Huangqi Zhechong decoction groups was lower than that in model group, and more dramatic drop was observed in medium-dose Huangqi Zhechong decoction group (P<0.01). Huangqi Zhechong decoction can inhibit hepatic fibrosis resulted from chronic liver injure, retard the development of cirrhosis, and notably ameliorate the liver function. It may be a safe and effective therapeutic drug for patients with fibrosis.


Botulinum toxin type a injection for lateral canthal rhytids : effect on tear film stability and tear production.
Botulinum toxin injection for lateral canthal rhytids has been reported to result in dry eye, but its effect on tear film stability and tear production has not been studied thoroughly. To investigate the effect of botulinum toxin type A on tear film stability and tear production after treatment of lateral canthal rhytids. We performed a clinical intervention study at a regional hospital in Taiwan of 58 women 30 to 60 years of age with lateral canthal rhytids from January 1 through December 31, 2011. Botulinum toxin type A at 2 different preparations and doses (dose A: 3 injections of 2 U in 0.05 mL of normal saline per injection; dose B: 3 injections of 4 U in 0.05 mL of normal saline per injection) was injected at the lateral canthal areas. One eye of each study participant was randomly chosen for dose A, and the other eye received dose B. Baseline tear film break-up time (TBUT) and Schirmer tests without and with anesthesia were measured before and at 1 week, 1 month, 3 months, and 6 months after botulinum toxin injection. The TBUT and Schirmer test results were compared between different periods and doses. The TBUT decreased significantly at 1 week after botulinum toxin type A injection (P = .003), and the effect persisted at 1 month and 3 months after treatment (P = .01 and .02, respectively). In younger participants, the TBUT recovered faster than in older patients. The results of the Schirmer tests without and with anesthesia decreased gradually, with significant reduction at 1 month after treatment (P = .05 and .02, respectively) and then recovered gradually. Both the TBUT and Schirmer test results decreased more in eyes that received dose B than in those that received dose A; however, none of the differences were statistically significant. Tear film stability decreased as early as 1 week after botulinum toxin type A treatment for lateral canthal rhytids, and the effect persisted for more than 3 months. Tear production decreased to the trough at 1 month after treatment and then recovered gradually.


Hyperosmotic oral replacement fluid for diarrheic calves.
Twenty-five diarrheic neonatal calves, none of which was recumbent, were used to determine oral efficacy of a commercial product for fluid replacement, either by suckle or intubation. Changes in plasma protein, glucose, sodium, potassium, and osmolality as well as blood lactate and PCV were measured. Core body temperature and surface temperature at the hock and fetlock were monitored. Data were analyzed for interaction with time and response according to clinical condition. Significant differences (P less than 0.05) following therapy were restricted to glucose and potassium changes. Beneficial posttreatment trends were observed in cutaneous temperature, blood lactate, plasma protein, and PCV values.


A scoping review on climate change and tuberculosis.
Climate change is a global public health challenge. The changes in climatic factors affect the pattern and burden of tuberculosis, which is a worldwide public health problem affecting low and middle-income countries. However, the evidence related to the impact of climate change on tuberculosis is few and far between. This study is a scoping review following a five-stage version of Arksey and O'Malley's method. We searched the literature using the keywords and their combination in Google scholar, and PubMed. Climate change affects tuberculosis through diverse pathways: changes in climatic factors like temperature, humidity, and precipitation influence host response through alterations in vitamin D distribution, ultraviolet radiation, malnutrition, and other risk factors. The rise in extreme climatic events induces population displacement resulting in a greater number of vulnerable and risk populations of tuberculosis. It creates a conducive environment of tuberculosis transmission and development of active tuberculosis and disrupts tuberculosis diagnosis and treatment services. Therefore, it stands to reasons that climate change affects tuberculosis, particularly in highly vulnerable countries and areas. However, further studies and novel methodologies are required to address such a complex relationship and better understand the occurrence of tuberculosis attributable to climate change.


[Papillary carcinoma of the thyroid: development of the histological criteria for diagnosis. Study of 29 cases and review of the literature].
Papillary carcinoma (PAP) is the most frequent malignant tumour of the thyroid. PAP and follicular carcinoma of the thyroid are two biologically different tumours, without any intermediate or mixed form. Therefore the differentiation between PAP and follicular carcinoma is essential. The histological diagnosis of PAP is based upon several criteria, the most important being the papillae, the "ground glass" nuclei, and the psammoma bodies. The value of the "ground glass" nuclei in the diagnosis of PAP has been particularly emphasized in the last 10 years. The need to take into account all the diagnostic histological criteria of PAP is necessary in the definition of the different variants of PAP, particularly its follicular variant. We report 28 cases of PAP and one case of insular carcinoma, the latter probably originating from a PAP. "Ground glass" nuclei often associated with "grooved nuclei", were identified in the paraffin sections of 7 PAP. One case was classified as a follicular variant of PAP. Psammoma-bodies were seen in 6 PAP. Eleven PAP were less than 1 cm in diameter (microPAP). One microPAP presented with important lymph node metastases and blood vessels' involvement; 2 others microPAP arose in a vesicular adenoma. Six PAP were entirely encapsulated, without any lymph node metastasis or vessel invasion. Six PAP presented with lymph node metastases associated with lymphatic and/or blood vessels invasion. Lymphatic and blood vessel invasion was seen more often in association with PAP extending to the thyroid capsule. The histological classification and prognostic criteria are discussed and compared with those previously described in the literature.


Development of a social dependency scale.
Social dependence was defined in terms of three capacities identified as necessary for the performance of an adult role. The three capacities are everyday self-care competence, mobility competence, and social competence. Measurement of these concepts was facilitated through the use of 12 6-point scales (4 for each capacity). Scores were then computed for each capacity (range 4-24) and for all three capacities together (range 12-72). Operationally, social dependence was defined as the sum of the individual's scores in the three areas: everyday self-care competence, mobility competence, and social competence. The revised instrument was tested on 60 subjects with advanced diseases to determine its reliability. The reliability coefficient alpha was .90, and the standardized-item alpha was .91.


Are retrospective peer-review transfusion monitoring systems effective in reducing red blood cell utilization?
This research used a study-control group design and examined data collected from five hospitals to evaluate the effectiveness of retrospective peer-review systems on reducing utilization of red blood cells (RBCs). The effects of retrospective peer-review systems were studied in three parts: (1) trends of RBC utilization were compared by the slopes of linear regression lines that assessed the effect of time on RBC utilization among four study hospitals and one control hospital, (2) diagnosis-specific RBC utilization was compared between the control hospital and one matched study hospital, and (3) the effect of the retrospective review system of one study hospital was assessed by linear regression using data accumulated 1 year before and 2 years after implementation of the program. Three study hospitals showed no significant changes in RBC utilization during the 10-month study period. One study hospital and the control hospital demonstrated trends of reduced RBC use with negative slopes of regression lines; however, there was no difference in the degree of the two slopes, and the diagnosis-specific RBC utilization was not lower at the study hospital than at the control hospital. Furthermore, implementation of the retrospective peer-review system at one study hospital demonstrated no effect on RBC utilization. We conclude that the retrospective peer-review systems implemented at these four hospitals had no effect on reducing red blood cell utilization.


Inhibitory and Agonistic Autoantibodies Directed Against the β2-Adrenergic Receptor in Pseudoexfoliation Syndrome and Glaucoma.
Pseudoexfoliation syndrome (PEXS) and glaucoma (PEXG) are assumed to be caused by a generalized elastosis leading to the accumulation of PEX material in ocular as well as in extraocular tissues. The exact pathophysiology of PEXS is still elusive. PEXG, the most common type of secondary open-angle glaucoma (OAG), is characterized by large peaks of intraocular pressure (IOP) with a progressive loss of the visual field. Agonistic autoantibodies (agAAbs) against the β2-adrenergic receptor (AR) have been shown to be present in sera of patients with primary and secondary OAG and ocular hypertension and are seemingly linked to IOP. In the present study, we investigated the autoantibodies directed against the β2-AR in sera of patients with PEXS and PEXG. We recruited 15, 10, and 15 patients with PEXG, PEXS, and primary OAG, respectively. Ten healthy individuals served as controls. All patients underwent standard ophthalmological examination with Octopus G1 perimetry. agAAbs prepared from serum samples were analyzed in a rat cardiomyocyte-based bioassay for the presence of agAAbs. We identified the interacting loop of the β2-AR and the immunoglobulin G (IgG) subclasses using synthetic peptides corresponding to the extracellular loops of the receptors and enzyme-linked immunosorbent assay, respectively. None of the controls were β2-agAAb-positive (0.2 ± 0.5 U). No β2-agAAbs (0.2 ± 0.4 U), but inhibitory β2-AAbs were observed in 80% of the patients that partially blocked the drug-induced β2-adrenergic stimulation; 5.8 ± 1.7 U vs. 11.1 ± 0.9 U for clenbuterol in the absence and the presence of sera from patients with PEXS, respectively. Epitope analyses identified the third extracellular loop of the β2-AR as the target of the inhibitory β2-AAbs, being of IgG3 subtype in PEXS patients. In contrast, patients with PEXG showed β2-agAAbs (5.6 ± 0.9 U), but no inhibitory ones. The β2-agAAbs levels of patients with PEXG and primary OAG patients (3.9 ± 2.8 U; p > 0.05) were at a similar level. In two cases of PEXG, the β2-agAAbs exert synergistic effects with clenbuterol. The activity increased from 11.5 ± 0.3 (clenbuterol only) to 16.3 ± 0.9 U. As autoimmune mechanisms were reportedly involved in the pathogenesis of glaucoma, agonistic and inhibitory β2-AAbs seem to be a part of this multifactorial interplay.


Culture of bovine articular chondrocytes in funnel-like collagen-PLGA hybrid sponges.
Three-dimensional porous scaffolds play an important role in tissue engineering and regenerative medicine. Structurally, these porous scaffolds should have an open and interconnected porous architecture to facilitate a homogeneous cell distribution. Moreover, the scaffolds should be mechanically strong to support new tissue formation. We developed a novel type of funnel-like collagen sponge using embossing ice particulates as a template. The funnel-like collagen sponges could promote the homogeneous cell distribution, ECM production and chondrogenesis. However, the funnel-like collagen sponges deformed during cell culture due to their weak mechanical strength. To solve this problem, we reinforced the funnel-like collagen sponges with a knitted poly(D,L-lactic-co-glycolic acid) (PLGA) mesh by hybridizing these two types of materials. The hybrid scaffolds were used to culture bovine articular chondrocytes. The cell adhesion, distribution, proliferation and chondrogenesis were investigated. The funnel-like structure promoted the even cell distribution and homogeneous ECM production. The PLGA knitted mesh protected the scaffold from deformation during cell culture. Histological and immunohistochemical staining and cartilaginous gene expression analyses revealed the cartilage-like properties of the cell/scaffold constructs after in vivo implantation. The hybrid scaffold, composed of a funnel-like collagen sponge and PLGA mesh, would be a useful tool for cartilage tissue engineering.


Epithelioid haemangioendothelioma of the rib--a case report.
Epithelioid haemangioendothelioma is a rare primary malignant tumour of the bone that accounts for less than 1% of all primary bone malignancies. The case discussed here is of a 35 years old male who presented with gradually increasing left infrascapular mass attached to 10th rib. X-ray showed an expansile lytic lesion in 10th rib. On FNA the diagnOsis of fibrous dysplasia or fibrous-histiocytic lesions was suggested. The lesion was excised along with adjacent rib. Histopathological examination showed features of epithelioid haemangioendothelioma. Immunohistochemistry revealed focal factor VIII related antigen positivity.