[Study on the toxicological effect of chloropropanols on rats].
Toxicological effect of 3-chloro-1,2-propanediol on rats were studied to provide scientific basis for assessing the effect of Chloropropanols on human health. 170 SD rats were divided randomly into 8 groups and the dose of 0, 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 16.0 mg/kg 3-chloro-1,2-propanediol were given to rats for 90 days by gavages per day, respectively. The weight and food efficiency, hematology and clinical chemistry, NAG, GGT and total protein in urine, sperm number, sperm survive rate and sperm aberration rate, the LDH and LDH-X activity in testis, rate of organ/weight and histopathological analysis were measured. The results showed that different dose of 3-chloro-1,2-propanediol did not has adverse effect on body weight, food efficiency, Hb, red cell, white cell, serum AST, ALT, creatine, ALP, LDH, total protein and albumin, urine GGT and total protein, LDH activity in testis. At the dose of 4.0, 8.0 and 16.0 mg/kg group, the activity of NAG in urine and the rate of kidney/weight was significantly increased compared with negative control groups; the pathological changes in kidney were observed in the same groups, and the sperm number was also significantly decreased. At the dose of 8.0 and 16.0 mg/kg group, sperm survive rate and the X-LDH activity were significantly decreased and pathological changes were also observed in testis and caudal epididymis. It was concluded that the activity of NAG in urine and sperm number is the sensitive biological effective marker. Because urine is a kind of convenient available biological material, NAG activity in urine is a good biological effective marker for assessing effect of Chloropropanols on health. If the NAG activity can be used as sensitive marker for assessment on human health need to be tested further in human study.


Comparison of efficacy between triamcinolone acetonide and triamcinolone hexacetonide for intraarticular therapy in juvenile idiopathic arthritis: a retrospective analysis.
There are many FDA-approved corticosteroid preparations available for intra-articular injection, however triamcinolone hexacetonide is not one of them. It was the intraarticular drug of choice among pediatric rheumatologists up until approximately a decade ago, when production of this medication ceased. It can be obtained in the United States and Canada via importation from Europe, but it is not FDA-approved at this time. We wish to compare the duration of remission of intraarticular triamcinolone hexacetonide (TH) with that of triamcinolone acetonide (TA) in children with juvenile idiopathic arthritis (JIA) and demonstrate its safety in this population. This retrospective chart review included 39 patients with JIA who received intraarticular corticosteroid injections (IACIs) from September 2018 to September 2019. These patients were reviewed and their life-time injections with either TH (41 joints) or TA (124 joints) was noted through May 30, 2021. Patients with concomitant systemic therapy initiation were excluded. The primary outcome was time to relapse. Relapse was defined by the presence of arthritis on physical examination by an attending rheumatologist. Kaplan-Meier curves and a log-rank test were constructed to compare the probability of time to relapse between IACI injections. Additionally, mixed effects cox regression models were constructed to account for multiple injections per participant. Kaplan-Meier estimator of median relapse time in months was higher for TH. Based on the log-rank test, TA joints had a higher probability of experiencing a relapse during the study time (p value < 0.001). The hazard of time to relapse was reduced when comparing TH to TA in both unadjusted and adjusted mixed effects cox regression models [unadjusted hazard ratio (95% confidence interval): 0.184 (0.089, 0.381); adjusted hazard ratio (95% confidence interval): 0.189 (0.092, 0.386)]. TH has longer duration of action than TA and is associated with less systemic side effects. It should be considered the drug of choice for intraarticular corticosteroid injections in children with JIA.


Identification of Malassezia pachydermatis from healthy and diseased human skin.
Malassezia pachydermatis is the only species in the genus Malassezia that is classically considered to be zoophilic. This yeast is only occasionally isolated from human skin, although it has been found to cause septic epidemics, especially in neonates. The aim of our study was to investigate the prevalence of M. pachydermatis on the skin of patients with Malassezia-associated diseases and of healthy subjects. One hundred and sixty skin scrapings from patients with pityriasis versicolor (PV), seborrhoeic dermatitis (SD), psoriasis (PS) and healthy individuals, forty each, were inoculated into Sabouraud dextrose agar and into modified Dixon agar. The yeasts isolated were identified according to their macroscopic and microscopic features and physiological properties. M. globosa was the most commonly isolated species in lesional skin of PV (65%) and PS (55%), M. restricta in lesional skin of SD (27.5%), while M. sympodialis was the predominant species recovered from healthy skin, representing 30% of the isolates. Zoophilic species, M. pachydermatis was identified in only one case, from the lesional skin of SD. The results of our study confirm that M. pachydermatis is not a member of the normal human flora and its presence on human skin is rare and indicates transmission from an external source.


Incidence of bloodstream infections in a speciality hospital in Kuwait: 8-year experience.
To determine the frequency of isolation and antibiotic-susceptibility patterns of clinically significant bacterial pathogens isolated from blood. The study was conducted over a period of 8 years (1995-2002) at Infectious Diseases Hospital (IDH), Kuwait. Demographic and clinical data were obtained from medical records. 18,535 blood cultures were analyzed. Disk diffusion method was used to perform antibiotic-susceptibility testing. Minimum inhibitory concentrations of 9 antimicrobials were determined using E-test. Double disk (potentiation) test and E-test ESBL strips were used to detect the production of extended-spectrum beta-lactamases (ESBLs). Salmonella spp. and Brucella spp. were predominant blood isolates, and represented 60.6 and 30.0% of all clinically significant episodes of bloodstream infections, respectively. Among the Salmonella, Salmonella enterica serotypes typhi and paratyphi A were most frequently isolated. The percentage of multidrug resistance (MDR) among them varied from 22 to 51%. A high percentage (40%) of MDR S. enterica serotypes typhi and paratyphi A also showed reduced susceptibility to ceftriaxone and ciprofloxacin. During the study period, Salmonella spp. and Brucella spp. were predominant blood isolates. MDR S. enterica serotypes typhi and paratyphi A, with reduced susceptibility to ceftriaxone and ciprofloxacin, are among the most frequent causes of bloodstream infections in IDH, suggesting the need to monitor their susceptibility.


Bone remodeling and individual-based implant therapy.
There has been a strong movement in implant dentistry to immediately load implants at time of placement. This movement has been generated by implant manufacturers, who have acceded to patient wishes for faster function and fewer surgeries. Immediate function has been a therapy for tooth extraction and implant replacement and for implant loading at the time of implant placement in edentulous sites. Bone is a dynamic connective tissue and its reaction to surgery is in response to modeling and remodeling. In this paper, the literature of bone remodeling is reviewed, with emphasis on various parameters that modulate this process and have an impact on the healing period of osseointegration and the prognosis for immediate or delayed loading of dental implants. These parameters define a bone phenotype characteristic of each individual. I suggest a new therapeutic concept for implant dentistry that I call "individualized implant therapy".


Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development.
Bacteria use a process called quorum sensing to communicate and orchestrate collective behaviours, including virulence factor secretion and biofilm formation. Quorum sensing relies on the production, release, accumulation and population-wide detection of signal molecules called autoinducers. Here, we develop concepts to coat surfaces with quorum-sensing-manipulation molecules as a method to control collective behaviours. We probe this strategy using Staphylococcus aureus. Pro- and anti-quorum-sensing molecules can be covalently attached to surfaces using click chemistry, where they retain their abilities to influence bacterial behaviours. We investigate key features of the compounds, linkers and surfaces necessary to appropriately position molecules to interact with cognate receptors and the ability of modified surfaces to resist long-term storage, repeated infections, host plasma components and flow-generated stresses. Our studies highlight how this surface approach can be used to make colonization-resistant materials against S. aureus and other pathogens and how the approach can be adapted to promote beneficial behaviours of bacteria on surfaces.


Molecular diagnosis of homozygous myotonic dystrophy in two asymptomatic sisters.
The genetic defect underlying myotonic dystrophy (DM) has been identified as the expansion of an unstable trinucleotide repeat sequence, and this discovery has led to new approaches to diagnosis and genetic counselling in families with the disorder. We report the genetic analysis of a consanguineous DM family in which two asymptomatic sisters had been shown to be homozygous for the 'at risk' haplotype. PCR analysis of the region spanning the trinucleotide expansion demonstrated that both sisters possessed two alleles with repeat sizes normally seen in minimally affected patients. Extensive clinical examination failed to demonstrate any of the symptoms of DM in these women. The implications of this finding, both for understanding the disease mechanism, and for genetic counselling in such situations are discussed.


Private physicians and the provision of contraceptives to adolescents.
Data from a national sample of private physicians show that 86 percent of obstetrician-gynecologists, general practitioners and pediatricians are willing to prescribe contraceptive methods to adolescent women. However, only 59 percent are willing to serve unmarried minors without parental consent. The obstetrician-gynecologists are more likely to provide contraceptives than the other two specialists, and are likely to have fewer policy restrictions. Although pediatricians are the least willing to prescribe contraceptives (only 32 percent say they would do so for a 15-year-old patient), they are the most likely to refer such patients to other sources of care (61 percent of those who will not provide primary contraceptive care do so). The parental consent requirements that physicians set for contraceptive services are somewhat related to state policies. Seventy-five percent of physicians who provide contraceptive care for adolescents and who practice in states that clearly authorize minors to give their own consent for family planning services will serve unmarried minors on their own consent, compared with 62 percent in states without explicit minor consent laws. Physicians practicing in the Southwest are the most likely to provide contraceptive services to unmarried patients younger than 18, while those in the North are least likely to do so (88 and 67 percent, respectively). Ninety percent of private physicians who prescribe contraceptives for adolescent women will prescribe the pill, but smaller proportions will make the diaphragm or IUD available (61 and 23 percent, respectively). Among the physicians surveyed, the average fee that an adolescent would have to pay for an initial contraceptive visit, including laboratory tests, is $37. Of those who accept teenage contraceptive patients, only 53 percent will accept Medicaid reimbursement and only one percent indicate that they will instead provide free services to adolescents who cannot afford to pay the fee.


A comparison of the prevalence of autoantibodies in individuals with chronic hepatitis C and those with autoimmune hepatitis: the role of interferon in the development of autoimmune diseases.
Viral hepatitis due to hepatitis C virus results in chronic liver disease in more than 70% of individuals infected with the virus. Hepatitis C virus is also thought to be the cause of autoimmune chronic hepatitis, type II. The only treatment for chronic hepatitis C is interferon (IFN). IFN is both an antiviral agent and an up regulator of the cellular immune system. The latter effect is non-specific. Thus, IFN diffusely activates the cellular immune system and can initiate new autoimmune diseases in patients treated with it. To determine the prevalence of autoantibodies in patients with chronic hepatitis C and in patients with autoimmune hepatitis and to determine the incidence of new onset autoimmune disease in IFN-treated subjects with chronic hepatitis C, the records of 323 unselected patients with chronic hepatitis were reviewed. A total of 203 patients with a mean age of 45.7 +/- 0.8, ranging 18-81 with either HCV disease or autoimmune hepatitis, were identified and studied. One hundred sixty-two patients with chronic hepatitis C defined by elevations of serum alanine aminotransferase (ALT) for at least 6 months, the presence of detectable anti-HCV (HCV; second generation enzyme immunoassay [EIA2], a positive recombinant immunoblot assay [RIBA], the presence of HCV-RNA by PCR in serum and an abnormal biopsy consistent with chronic hepatitis C) were identified. Each was also negative for HbsAg, HbeAg and anti-Delta. Forty-one patients with a putative autoimmune chronic hepatitis (AIH) diagnosed on the basis of serologic positivity for classical autoantibodies (ANA and anti-smooth muscle antibodies), tissue typing (B8, Dr3 positive), characteristic liver biopsy findings and the absence of anti-HCV and HCV-RNA in serum were identified. The records of both of these groups of patients were reviewed for the following antibodies: anti-nuclear antibodies (ANA), antimitochondrial antibodies (AMA), anti-liver-kidney microsomal antibody (LKM), anti-smooth muscle antibodies (SMA), anti-microsomal antibodies (MSA). The rate of ANA positivity was 63% in both groups; the rate of SMA positivity was 65% in patients with HCV infection (group I) and 63% in patients with AIH (group II). AMA was positive in 4% of the subjects in group I and 50% of the subjects in group II; anti-LKM antibodies were absent in all 91 HCV cases and were present in 4% of the cases in group II; MSA positivity was present in 17% of group I and 10% of group II. Eighty-one of the one hundred sixty-two patients (50%) with chronic hepatitis C received IFN treatment at a dose of 5 MU SQ daily for 6 months. Thirty-two of these eighty-one patients (42 females and 39 males with a mean age of 45.0 +/- 1.3, ranging from 18 to 81 yr.) had at least two autoantibodies detectable prior to the IFN therapy (subgroup 1) and 49 had one or no identifiable autoantibodies (subgroup 2) present prior to IFN therapy. No significant differences in the interferon response rate defined by HCV-RNA negativity and normalization of serum ALT levels at the end of therapy was noted between those with autoantibodies and those without autoantibodies. Fifteen of the interferon-treated patients developed a clinical manifestation of a new onset autoimmune disease during the course of their interferon treatment. Six of the fifteen patients belonged to subgroup 1 (n = 32) and the remaining 9 patients to subgroup 2 (n = 49) (p > 0.05). None were managed by discontinuing the interferon. Most required some form of specific treatment.(ABSTRACT TRUNCATED)


[Comparison of the IFA, ELISA IgG, ELISA IgM, IHA and the direct agglutination tests in Toxoplasma gondii serology].
In this study, toxoplasma antibodies were evaluated by using IFA, ELISA IgG, ELISA IgM, IHA and direct agglutination test in serum samples obtained from reproductive women. The specificity, sensitivity, unit costing and timing of tests compared with IFA test. In this evaluation IFA test are used. ELISA IgG specificity 98%, sensitivity 97.5%; IHA specificity 90%, sensitivity 97.5%; direct agglutination specificity 92%, sensitivity 95% have been found.


[Studies on defense effects of recombinant human granulocyte colony-stimulating factor (G-CSF) to infections. II. Priming effect for superoxide production by human neutrophil].
In present study, we have investigated superoxide (O2-) production from human neutrophils by recombinant human granulocyte colony-stimulating factor (G-CSF) using the microtiter plate for the purpose of being close to the inflammatory site. G-CSF by itself did not induce the release of O2- in human neutrophil on either Fetal Bovine Serum (FBS)-coated plate or plate uncoated with FBS, even if neutrophils were exposed for maximum 3 hr. However, the optimal concentration of G-CSF (50 ng/ml) was able to prime human neutrophils with enhance of O2- release stimulated by the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP) from 10(-6) to 10(-8) M, but not by the non chemoattractant such as phorbol myristate acetate (PMA), concanavalin A, and ionomycin. These findings indicate that G-CSF might enhance bactericidal activity of neutrophils by priming them penetrating into the inflammatory site.


Correlations between personality factors and coronary artery disease: from type A behaviour pattern to type D personality.
During the last 50 years, many studies have analysed the correlations between personality factors, behavioural pattern, personality type, psychiatric disorders and coronary artery disease (CAD). Although consistent evidence of causal association between CAD and major depressive disorders does exist, the role and importance of personality factors and character traits in CAD development and manifestations are still debatable. We reported the most important studies from the literature on type A behaviour pattern (TABP), the first correlated to CAD. After the initial enthusiasms, large clinical trials raised doubts about the role of TABP as CAD risk factor. We reported subsequent researches aimed at extracting from TABP components predisposing to atherosclerosis, such as hostility and anger. Finally, we analysed a recent personality type (type D) introduced in 1995 and identified as a negative prognostic factor in CAD patients.


Enhanced carnosine (beta-alanyl-L-histidine) breakdown and histamine metabolism following treatment with compound 48/80.
We have previously suggested that carnosine may serve as a reservoir for histidine to be used as a source of histamine in the trauma response of rats. In this study we report the effect of stimulation of histamine-forming capacity by compound 48/80 on muscle carnosinase (C'ASE) and histidine decarboxylase (HDC) activities as well as on muscle carnosine and histamine concentrations. Male rats (180 g) were injected i.p. with 5 mg/kg bw of compound 48/80 and C'ASE and HDC activities as well as carnosine, histidine and histamine concentrations were monitored over a 72 h period post-injection. This treatment resulted in an 120% increase in muscle HDC activity and an 110% increase in muscle histamine concentration at 15 min post-injection, followed by an 80% increase in muscle C'ASE activity at 1 h and a 100% reduction in muscle carnosine concentration at 24 h post-injection when compared to control animals injected with 0.9% saline. Histidine concentration was not affected by treatment. The time frame of response, a rapid increase in muscle HDC activity and in muscle histamine concentration followed by an increase in muscle C'ASE activity and a later decrease in muscle carnosine concentration, suggests that carnosine is hydrolysed to liberate histidine and that carnosine, as a reservoir for histidine, is mobilized to maintain a constant muscle concentration of histidine for histamine synthesis.


Secretion of both IL-2 and IL-4 by tumor cells results in rejection and immunity.
The generation of a therapeutic immune response to malignancy is critically dependent on the inherent immunogenicity of the tumor. Our study demonstrates that secretion of both interleukin-2 (IL-2) and IL-4 by a seemingly nonimmunogenic tumor abrogates tumorigenicity, and mice that have rejected the genetically modified tumor are immune to challenges with the parental tumor. The induction of immunity by the IL-2/IL-4-secreting tumor was significantly better than that achieved with the admixture of tumor cells and the classic adjuvant, Corynebacterium parvum. To elicit a primary immune response, the majority of cells needed to secrete both cytokines. Ad-mixture of IL-2-secreting cells with IL-4-secreting cells did not result in tumor cell rejection. The IL-2/IL-4-secreting tumor cells were efficiently rejected in animals immunosuppressed by total body irradiation. Depletion of CD4+ or CD8+ T cells did not abrogate rejection of the tumor cells, but the animals depleted of CD4 cells failed to generate protective immunity. Our study demonstrates that secretion of the combination of IL-2 and IL-4 significantly enhances tumor immunogenicity. The requirement of cells secreting both cytokines suggests an intricate mechanism different from the mere presence of both cytokines at the tumor-inoculation site.


[Feasibility of thoracoscopic pulmonary metastasectomy].
With the developments in endoscopic surgery and the advances of radiological techniques, thoracoscopic pulmonary metastasectomy has been used more and more widely. This study was to evaluate the feasibility of thoracoscopic resection of pulmonary metastases. The clinical data of 17 patients who underwent thoracoscopic pulmonary metastasectomy were retrospectively analyzed. All pulmonary metastases in the 17 patients were peripherally located and encountered during follow-up after treatment of primary disease. Metastases at other sites were excluded. Among the 17 cases of metastases, 10 were solitary metastasis, 4 were unilateral multiple metastases, 3 were bilateral metastases. All patients underwent thoracoscopic wedge resection. No major complications, operative mortality, and port site metastasis presented. Postoperative locoregional relapse occurred in 5 patients, in which 4 patients had multiple metastases, the rest 1 patient with soft tissue sarcoma underwent a second thoracoscopic resection of recurrent pulmonary lesion. The 1-, 3-, and 5-year survival rates were 77.3%, 53.1%, and 34.8%, respectively. Thoracoscopic resection is feasible and effective for patients with a solitary pulmonary metastasis, especially when the lesion is smaller than 3 cm and peripherally located. Bilateral pulmonary metastases may also be resected by primary thoracoscopic operation.


A NOVEL TECHNIQUE FOR EXTRACTION OF DROPPED BROKEN HAPTICS OF HARD POSTERIOR CHAMBER INTRAOCULAR LENS.
To report a novel technique for extraction of dropped haptics of hard posterior chamber intraocular lens. A 58-year-old woman had undergone cataract extraction, and while implanting the posterior chamber intraocular lens it was dislocated in the anterior vitreous, and the cataract surgeon, tried to remove it by the anterior approach, but he succeeded to remove the optic part only, leaving the haptics dropped, then he referred the case after giving topical and systemic medications to control intraocular inflammation and, the case was prepared for pars plana vitrectomy, then injection of perfluorodecaline to keep the haptics away from the posterior pole then by 23 G vitrectomy probe and, the use of vacuum only, the haptics were removed and the perfluorodecaline was removed. After extraction of both haptics by 23 G vitrectomy probe, the case was implanted by a hard polymethylmethacrylate posterior chamber intraocular lens on the sulcus, and postoperatively, the inflammatory signs were subsided and her visual acuity was improved, without any posterior segment complications. Dropped haptic of hard posterior chamber intraocular lens can be removed successfully with 23 G vitrectomy probe.


A Fully Integrated Arduino-Based System for the Application of Stretching Stimuli to Living Cells and Their Time-Lapse Observation: A Do-It-Yourself Biology Approach.
Mechanobiology has nowadays acquired the status of a topic of fundamental importance in a degree in Biological Sciences. It is inherently a multidisciplinary topic where biology, physics and engineering competences are required. A course in mechanobiology should include lab experiences where students can appreciate how mechanical stimuli from outside affect living cell behaviour. Here we describe all the steps to build a cell stretcher inside an on-stage cell incubator. This device allows exposing living cells to a periodic mechanical stimulus similar to what happens in physiological conditions such as, for example, in the vascular system or in the lungs. The reaction of the cells to the periodic mechanical stretching represents a prototype of a mechanobiological signal integrated by living cells. We also provide the theoretical and experimental aspects related to the calibration of the stretcher apparatus at a level accessible to researchers not used to dealing with topics like continuum mechanics and analysis of deformations. We tested our device by stretching cells of two different lines, U87-MG and Balb-3T3 cells, and we analysed and discussed the effect of the periodic stimulus on both cell reorientation and migration. We also discuss the basic aspects related to the quantitative analysis of the reorientation process and of cell migration. We think that the device we propose can be easily reproduced at low-cost within a project-oriented course in the fields of biology, biotechnology and medical engineering.


When does MMR loss occur during HNPCC progression?
Inactivation of DNA mismatch repair (MMR) is the hallmark of hereditary nonpolyposis colorectal cancer (HNPCC) and sporadic colorectal cancers with microsatellite instability (MSI+). MMR loss results in a markedly elevated mutation rate, and many MS mutations are found in MSI+ cancers. In theory, it is possible to estimate the interval between MMR loss and cancer removal by counting numbers of cancer MS mutations--the more MS mutations, the longer the intervals since MMR loss. Using this somatic molecular clock approach, MMR loss is estimated to precede transformation (clonal expansion) and likely occurs in normal appearing colon. Surprising, ages at MMR loss are more consistent with MMR loss as a relatively late event during progression to MSI+ cancer.


IRES-Mediated Protein Translation Overcomes Suppression by the p14ARF Tumor Suppressor Protein.
Internal ribosome entry sites (IRES elements) have attracted interest in cancer gene therapy because they can be used in the design of gene transfer vectors that provide bicistronic co-expression of two transgene products under the control of a single promoter. Unlike cellular translation of most mRNAs, a process that requires a post-translational 5' modification of the mRNA known as the cap structure, IRES-mediated translation is independent of the cap structure. The cellular conditions that may intervene to modulate IRES-mediated, cap-independent versus cap-dependent translation, however, remain poorly understood, although they could be critical to the choice of gene transfer vectors. Here we have compared the effects of the p14ARF (Alternate Reading Frame) tumor suppressor, a translational suppressor frequently overexpressed in cancer, on cap-dependent translation versus cap-independent translation from the EMCV viral IRES often used in bicistronic gene transfer vectors. We find that ectopic overexpression of p14ARF suppresses endogenous and ectopic cap-dependent protein translation, consistent with other studies. However, p14ARF has little or no effect on transgene translation initiated within an IRES element. This suggests that transgenes placed downstream of an IRES element will retain efficient translation of their gene products in the presence of high levels of ectopic or endogenous p14ARF, a finding that could be particularly relevant to therapeutic gene therapy strategies for cancer.


Cat-scratch disease. Bacteria in skin at the primary inoculation site.
Cat-scratch disease is a zoonotic infection characterized by a skin papule at the site of the scratch followed by regional lymphadenitis. Recently, small gram-negative pleomorphic bacilli were demonstrated in sections of lymph node from patients with the disease. We now report identical bacteria in the primary inoculation site of three patients with cat-scratch disease. Lymph nodes from two of these patients also contained the same bacilli. Identical bacteria in both skin and lymph nodes from these patients are further evidence that the bacilli are the cause of cat-scratch disease. In early infections, biopsy of the primary site of inoculation and demonstration of bacilli may replace excision and histologic examination of lymph node in establishing the diagnosis of cat-scratch disease.


Aminoindanes--the next wave of 'legal highs'?
Due to its closed ring system, 2-aminoindane is a conformationally rigid analogue of amphetamine. Internet websites offering synthetic compounds as 'research chemicals' have recently been advertising 5,6-methylenedioxy-2-aminoindane (MDAI), 5, 6-methylenedioxy-N-methyl-2-aminoindane (MDMAI), 5-iodo-2-aminoindane (5-IAI), and 5-methoxy-6-methyl-2-aminoindane (MMAI). The chemistry, pharmacology, and toxicological aspects of this new class of psychoactive substances are reviewed, as these could become the next wave of 'legal highs'.


Fecal microbiota transplantation does not alter bacterial translocation and visceral adipose tissue inflammation in individuals with obesity.
Visceral adipose tissue inflammation is a fundamental mechanism of insulin resistance in obesity and type 2 diabetes. Translocation of intestinal bacteria has been suggested as a driving factor for the inflammation. However, although bacterial DNA was detected in visceral adipose tissue of humans with obesity, it is unclear to what extent this is contamination or whether the gut microbiota is causally involved. Effects of fecal microbiota transplantation (FMT) on bacterial translocation and visceral adipose tissue inflammation in individuals with obesity and insulin resistance were assessed. Eight individuals with clinically severe obesity (body mass index [BMI] >35 kg/m2) and metabolic syndrome received lean donor FMT 4 weeks prior to elective bariatric surgery. The participants were age-, sex-, and BMI-matched to 16 controls that underwent no fecal transplantation. Visceral adipose tissue was collected during surgery. Bacterial translocation was assessed by 16S rRNA gene sequencing of adipose tissue and feces. Pro-inflammatory cytokine expression and histopathological analyses of visceral adipose tissue were performed to assess inflammation. Fecal microbiota transplantation significantly altered gut microbiota composition. Visceral adipose tissue contained a very low quantity of bacterial DNA in both groups. No difference in visceral bacterial DNA content between groups was observed. Also, visceral expression of pro-inflammatory cytokines and macrophage infiltration did not differ between groups. No correlation between inflammatory tone and bacterial translocation was observed. Visceral bacterial DNA content and level of inflammation were not altered upon FMT. Thus, bacterial translocation may not be the main driver of visceral adipose tissue inflammation in obesity.


High altitude pulmonary edema in mountain climbers.
Every year thousands of ski, trekking or climbing fans travel to the mountains where they stay at the altitude of more than 2500-3000m above sea level or climb mountain peaks, often exceeding 7000-8000m. High mountain climbers are at a serious risk from the effects of adverse environmental conditions prevailing at higher elevations. They may experience health problems resulting from hypotension, hypoxia or exposure to low temperatures; the severity of those conditions is largely dependent on elevation, time of exposure as well as the rate of ascent and descent. A disease which poses a direct threat to the lives of mountain climbers is high altitude pulmonary edema (HAPE). It is a non-cardiogenic pulmonary edema which typically occurs in rapidly climbing unacclimatized lowlanders usually within 2-4 days of ascent above 2500-3000m. It is the most common cause of death resulting from the exposure to high altitude. The risk of HAPE rises with increased altitude and faster ascent. HAPE incidence ranges from an estimated 0.01% to 15.5%. Climbers with a previous history of HAPE, who ascent rapidly above 4500m have a 60% chance of illness recurrence. The aim of this article was to present the relevant details concerning epidemiology, pathophysiology, clinical symptoms, prevention, and treatment of high altitude pulmonary edema among climbers in the mountain environment.


Microfabricated blood vessels undergo neoangiogenesis.
The greatest ambition and promise of tissue engineering is to manufacture human organs. Before "made-to-measure" tissues can become a reality [1-3], however, three-dimensional tissues must be reconstructed and characterized. The current inability to manufacture operational vasculature has limited the growth of engineered tissues. Here, free-standing, small diameter blood vessels with organized cell layers that recapitulate normal biological functionality are fabricated using microfluidic technology. Over time in culture, the endothelial cells form a monolayer on the luminal wall and remodel the scaffold with human extracellular matrix proteins. After integration into three-dimensional gels containing fibroblasts, the microvessels sprout and generate extended hollow branches that anastomose with neighboring capillaries to form a network. Both the microfabricated vessels and the extended sprouts support perfusion of fluids and particles. The ability to create cellularized microvessels that can be designed with a diameter of choice, produced by the meter, and undergo angiogenesis and anastomoses will be an extremely valuable tool for vascularization of engineered tissues. To summarize, ultraviolet (UV) photo-crosslinkable poly(ethylene glycol) and gelatin methacrylate polymers used in combination with sheath-flow microfluidics allow for the fabrication of small diameter blood vessels which undergo neoangiogenesis as well as other developmental processes associated with normal human blood vessel maturation. Once mature, these vessels can be embedded; perfused; cryogenically stored and respond to stimuli such as chemokines and shear stresses to mimic native human blood vessels. The applications range from tissue-on-chip systems for drug screening, characterization of normal and pathologic processes, and creation and characterization of engineered tissues for organ repair.


Melanin extract from Gallus gallus domesticus promotes proliferation and differentiation of osteoblastic MG-63 cells via bone morphogenetic protein-2 signaling.
Gallus gallus domesticus (GD) is a natural mutant breed of chicken in Korea with an atypical characterization of melanin in its tissue. This study investigated the effects of melanin extracts of GD on osteoblast differentiation and inhibition of osteoclast formation. The effects of the melanin extract of GD on human osteoblast MG-63 cell differentiation were examined by evaluating cell viability, osteoblast differentiation, and expression of osteoblast-specific transcription factors such as bone morphogenetic protein 2 (BMP-2), small mothers against decapentaplegic homologs 5 (SMAD5), runt-related transcription factor 2 (RUNX2), osteocalcin and type 1 collagen (COL-1) by reverse transcription-polymerase chain reaction and western blotting analysis. We investigated the inhibitory effect of melanin on the osteoclasts formation through tartrate-resistant acid phosphatase (TRAP) activity and TRAP stains in Raw 264.7 cell. The melanin extract of GD was not cytotoxic to MG-63 cells at concentrations of 50-250 µg/mL. Alkaline phosphatase (ALP) activity and bone mineralization of melanin extract-treated cells increased in a dose-dependent manner from 50 to 250 µg/mL and were 149% and 129% at 250 µg/mL concentration, respectively (P < 0.05). The levels of BMP-2, osteocalcin, and COL-1 gene expression were significantly upregulated by 1.72-, 4.44-, and 2.12-fold in melanin-treated cells than in the control cells (P < 0.05). The levels of RUNX2 and SMAD5 proteins were higher in melanin-treated cells than in control vehicle-treated cells. The melanin extract attenuated the formation of receptor activator of nuclear factor kappa-B ligand-induced TRAP-positive multinucleated RAW 264.7 cells by 22%, and was 77% cytotoxic to RAW 264.7 macrophages at a concentration of 500 µg/mL. This study provides evidence that the melanin extract promoted osteoblast differentiation by activating BMP/SMADs/RUNX2 signaling and regulating transcription of osteogenic genes such as ALP, type I collagen, and osteocalcin. These results suggest that the effective osteoblastic differentiation induced by melanin extract from GD makes it potentially useful in maintaining bone health.


Underscoring the importance of advance care planning.
Advance care planning is an essential part of routine medical care. It is a billable, iterative process that can result in the completion of advance directives and medical orders, offering NPs the opportunity to assure goal-concordant care for their patients at the end of life.


Nanocapsules prepared from amorphous polyesters: effect on the physicochemical characteristics, drug release, and photostability.
The influence of the polymeric amorphous materials on the physicochemical and drug release properties of drug-loaded nanocapsules as well as their role on the protection of the entrapped drug against the degradation induced by UV radiation was evaluated. Nanocapsules were prepared by interfacial deposition of preformed polymer (PLA, PLGA 50:50, and PLGA 85:15) using clobetasol propionate as the drug model. In vitro drug release was evaluated by the dialysis bag method. Photochemical stability was studied under UVA radiation. After preparation, all formulations presented nanometric mean size (180-200 nm), polydispersity index below 0.20, acid pH, negative zeta potential, and encapsulation efficiency close to 100%. Clobetasol propionate-loaded PLGA nanocapsules presented a lower physicochemical stability, showing a high drug leakage during 3 months of storage. In vitro studies showed biphasic drug release from all nanocapsules (according to an anomalous transport) and no influence of the hydrophilic characteristics of the amorphous polymeric material on the release rate. The photostability of clobetasol propionate under UVA radiation was improved by its incorporation into PLA and PLGA nanocapsules showing that besides semicrystalline polymers, amorphous polymers could also efficiently protect nanoencapsulated drugs against UV radiation.


Cerium-based cytochemical method for detection of ouabain-sensitive, potassium-dependent p-nitrophenylphosphatase activity at physiological pH.
We have developed a new cytochemical method for detecting the ouabain-sensitive, potassium-dependent p-nitrophenylphosphatase (K-NPPase) activity of the sodium-potassium-activated adenosine triphosphatase (Na-K ATPase) complex. The incubation medium contains p-nitrophenylphosphate (p-NPP) as substrate, cerium chloride as capture agent, Tricine buffer, MgCl2, and KCl. Tricine buffer protected against the medium turbidity caused by non-enzymatic reaction at pH 7.5. Biochemically, the accumulation of p-nitrophenol and phosphate in the reaction precipitate was proportionally related to the enzyme concentration. Ultracytochemically, the reaction products of the K-NPPase activity were localized as fine and uniform electron-dense deposits in the cytoplasmic side of specialized basolateral plasma membranes of cells of kidney distal convoluted tubules, secretory cells of salt gland, and marginal cells of stria vascularis. This method has the advantage of being useful at physiological pH.


Neighborhood violence and health: the mediating role of loneliness among two ethnic groups in Israel.
Neighborhood violence is associated with poor health, but the mechanisms explaining this association are still unknown. This study seeks to examine the role of loneliness as a mediator of the association between neighborhood violence and health among two ethnic groups (Arabs and Jews) in Israel. A representative survey was conducted among adult residents (1903 Arabs and 2726 Jews) of four Israeli towns: two Arab towns, one Jewish town and one mixed town. A stratified sample of households by residential area, age and sex, was selected in each town. Mediation models were tested using Hayes' PROCESS procedure. Traffic violations, juvenile delinquency and vandalism were reported by more than 50% of Arab residents, relative to about 25-30% of Jewish residents. Loneliness mediated the association between neighborhood violence and health, with a full serial mediation for mental health and a partial serial mediation for physical health. Findings indicate that Arab towns are characterized by severe neighborhood violence. The association between neighborhood violence and physical health was fully dependent on the mediators among both ethnic groups. Future studies should use prospective designs with objective measures of health and violence to validate our cross-sectional findings.


Optimal Facility-Location.
Dr. Christoph Witzgall, the honoree of this Symposium, can count among his many contributions to applied mathematics and mathematical operations research a body of widely-recognized work on the optimal location of facilities. The present paper offers to non-specialists a sketch of that field and its evolution, with emphasis on areas most closely related to Witzgall's research at NBS/NIST.


A new algorithm for the evaluation of recurrent pregnancy loss redefining unexplained miscarriage: review of current guidelines.
Couples with recurrent pregnancy loss (RPL) are often referred to reproductive specialists to help determine the reason for their repeated losses. This review will help to develop a strategy that is effective in providing a diagnosis, efficient to administer, and cost-effective to the healthcare system. International societies have published different recommendations for the evaluation of RPL, they consider it appropriate to initiate an evaluation after two (or three) clinical miscarriages. On the contrary, the clinician who follows these guidelines will only be able to offer a possible explanation to fewer than half of the couples being evaluated. Recently, genetic testing of miscarriage tissue using 24-chromosome microarray (CMA) analysis at the time of the second pregnancy loss coupled with testing based on society guidelines has been shown provide an explanation in more than 90% of cases. New guidelines for the complete evaluation of RPL should consider adding 24-CMA testing on the miscarriage tissue. Providing couples with an explanation for recurrent loss assists them in dealing with the loss and discourages the clinician from instituting unproven therapies. Truly unexplained pregnancy loss can be reduced to less than 10% with this new algorithm. Incorporation of these strategies will result in significant cost savings to the healthcare system.


Effects of cinitapride on gastric ulceration and secretion in rats.
The aim of the present study was to examine the effects of cinitapride, a novel prokinetic benzamide-stimulating gastrointestinal motility agent, on gastric secretion and ulceration in rats and elucidate some possible vascular and anti-oxidant mechanisms of such protection. Male Wistar rats. Cinitapride (CNT, Lab. Almirall, S.A.) (0.25, 0.5, and 1 mg/kg) and 5-hydroxytryptamine (5-HT, Sigma Chemical Co., St. Louis, MO, USA) (10 mg/kg), administered intraperitoneally (i.p.). Gastric ulceration was induced by instillation of 1 mL/100 g animal of 50% (v/v) ethanol in distilled water and by pylorus-ligated rat model. Gastric microvascular changes, and the activity of myeloperoxidase (as a marker of neutrophil infiltration) and glutathione peroxidase (an important enzyme in scavenging of lipid peroxides) were determined. The results were compared with those of 5-HT. The data were evaluated using Student's t-test for paired data and the non-parametric Mann-Whitney U-test. In 4 h pyloric-ligated animals, i.p. CNT did not significantly reduce the incidence of gastric mucosal damage, and no significant differences were found in the values of total volume and acidity. However, CNT caused a marked and dose-dependent reduction of haemorrhagic lesions induced by 50% v/v ethanol. These protective effects were specifically related to a reduction of neutrophil infiltration. CNT at the dose of 1 mg/kg raised the decreased glutathione peroxidase activity to the control level. In contrast, pretreatment with 5-HT worsened the ethanol-induced erosions, but did not significantly induce any gastric microvascular changes. However, the myeloperoxidase activity rose markedly and the glutathione peroxidase levels decreased significantly in the mucosa injured by 50% v/v ethanol. This study demonstrates a new gastroprotective feature of CNT that could be partly explained not only through reduction of neutrophil toxicity but also by an increased synthesis of free-radical scavenging enzymes such as glutathione peroxidase. Furthermore, it is likely that serotonergic-dependent mechanisms are also involved via 5-HT2-receptor blockade and 5-HT1 receptor activation.


Brain malformations and mutations in α- and β-tubulin genes: a review of the literature and description of two new cases.
The aim of this study was to determine the frequency of mutations in tubulin genes (TUBB2B, TUBA1A, and TUBB3) in patients with malformations of cortical development (MCDs) of unknown origin. In total, 79 out of 156 patients (41 males, 38 females; age range 8mo-55y (mean age 13y 3mo, SD 11y 2mo) with a neuroradiological diagnosis of MCDs were enrolled in the study. The 77 excluded patients were excluded for the following reasons: suspected or proven diagnosis of pre- or perinatal ischaemic insult (n=13); syndromic disease (n=10); congenital infection (n=14); pregnancy complicated by twin-to-twin transfusion syndrome (n=2); proven mutations in known genes (n=13); poor magnetic resonance imaging (MRI) quality, or lack of informed consent (n=25). A genetic analysis of the TUBA1A, TUBB2B and TUBB3 genes was carried out by direct sequencing of the coding regions of the relevant genes for each participant. Previously described patients with mutations in the TUBB2B and TUBA1A genes were reviewed; clinical and neuroradiological findings were compared and discussed. Two novel heterozygous mutations were detected: a heterozygous mutation in exon 4 of the TUBA1A gene (c.1160C>T) in a 5-year-old female with microcephaly, severe intellectual disability, and absence of language, and a c.1080 _1084del CCTGAinsACATCTTC in exon 4 of the TUBB2B gene in a 31-year-old female with microcephaly, spastic tetraparesis, severe intellectual disability, and scoliosis. Different types of cortical abnormalities, cerebellar vermis hypoplasia, and optic nerve hypoplasia/atrophy were detected on MRI. Dysmorphisms of the basal ganglia and the hippocampi with abnormalities of the midline commissural structures were present in both cases. The consistent presence of hypoplastic and disorganized white matter tracts suggests that, in addition to defects in neuronal migration, disruption of axon growth and guidance is a peculiar feature of tubulin-related disorders.


[Joint manifestations in sarcoidosis].
The commonest type of joint involvement in sarcoidosis is the acute arthritis of the L ofgren syndrome. This usually precedes the erythema nodosum and regresses in a few weeks. Arthritis without erythema nodosum is less common and has a much more variable presentation. Chronic sarcoid polyarthritis is very rare and does not usually cause bone erosion or deformation. It is usually associated with involvement of other organs. In children, sarcoid polyarthritis may resemble Still's disease. The entity of sarcoid sacro iliitis is discussed. Rare cases of sarcoid spondylodiscitis simulating bacterial spondylodiscitis have been described.


Serum testosterone levels and other determinants of sperm retrieval in microdissection testicular sperm extraction.
Microdissection testicular sperm extraction (microTESE) has become the standard of care for sperm retrieval in non-obstructive azoospermia (NOA) patients. Understanding the significant determinants of microTESE outcomes may result in improvements in sperm retrieval rates and provide better-informed clinical decisions. This is a clinical retrospective study conducted through chart review of 421 NOA patients who underwent microTESE between August 2009 and July 2015 in a tertiary-care referral hospital. Clinical, biochemical and histopathological characteristics were collected. Normal serum testosterone level was defined as testosterone >9.9 nmol/L. Multiple logistic regression was used to identify determinants of microTESE in the studied population. A P<0.05 was considered significant. Sperms were successfully retrieved in 39.4% of cases. The average testosterone level was 11.51±7.40 and 11.67±6.42 in patients with successful and unsuccessful microTESE, respectively (P=0.820). No significant association was found between serum testosterone level and sperm motility and amount. Of all variables, histological subtype remained to be the most significant determinant of microTESE outcomes in the examined population, with hypospermatogenesis having over a 3-fold higher odd of successful microTESE than sertoli-cell only. Serum testosterone level appears to have no significant association with microTESE outcomes in NOA. The underlying histological pattern is a significant determinant of the procedure's success.


Stubborn rectal prolapse in systemic sclerosis.
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder. Anorectal involvement might typically cause fecal incontinence and rarely rectal prolapse. Here we report three female patients, who were admitted with a mean history of 10 years suffering from SSc. All patients presented with the initial symptom of anal incontinence, in all cases this was associated with rectal intussusception or rectal prolapse. The three women faced prolapse recurrence, independent of the initial procedure. After surgical removal of the prolapse, the incontinence remained. In SSc rectal prolapse syndrome might occur at an earlier age, and a primary prolapse of the ventral aspect of the rectal wall seems to be typical for this disease. If patients with prior diagnosis of SSc appear with third degree of fecal incontinence, it is suspected to be associated with rectal prolapse. The prolapse recurrence rate after surgery in SSc patients is high.


Theoretical Upper and Lower Limits for Normalized Bandwidth of Digital Phase-Locked Loop in GNSS Receivers.
Determining the loop noise bandwidth and the coherent integration time is essential and important for the design of a reliable digital phase-locked loop (DPLL) in global navigation satellite system (GNSS) receivers. In general, designers set such parameters approximately by utilizing the well-known fact that the DPLL is stable if the normalized bandwidth, which is the product of the integration time and the noise bandwidth, is much less than one. However, actual limit points are not fixed at exactly one, and they vary with the loop filter order and implementation method. Furthermore, a lower limit on the normalized bandwidth may exist. This paper presents theoretical upper and lower limits for the normalized bandwidth of DPLL in GNSS receivers. The upper limit was obtained by examining the stability of DPLL with a special emphasis on the digital integration methods. The stability was investigated in terms of z-plane root loci with and without the consideration of the computational delay, which is a delay induced by the calculation of the discriminator and the loop filter. The lower limit was analyzed using the DPLL measurement error composed of the thermal noise, oscillator phase noise, and dynamic stress error. By utilizing the carrier-to-noise density ratio threshold which indicates the crossing point between the measurement error and the corresponding threshold, the lower limit of the normalized bandwidth is obtained.


Hamstring strength recovery after hamstring tendon harvest for anterior cruciate ligament reconstruction: a comparison between graft types.
The purpose of this study was to investigate hamstring strength after harvest of 1 or 2 hamstring tendons for anterior cruciate ligament reconstruction. We recruited 50 individuals who had returned to regular sporting activity to participate in a comparative study at a mean of 32.5 months after anterior cruciate ligament reconstructive surgery (30 in semitendinosus-gracilis group and 20 in semitendinosus group). Isokinetic hamstring strength (at 60 degrees/s and 180 degrees/s with the peak torque and torque produced at 60 degrees, 90 degrees, and 105 degrees of knee flexion recorded) and isometric hamstring strength (at 30 degrees, 90 degrees, and 105 degrees of knee flexion) were measured, and the standing knee flexion angle was used to evaluate functional hamstring strength recovery. No significant differences between the groups were found in any of the isometric or isokinetic strength measures or in the standing knee flexion angle. No relation was found between the standing knee flexion angle and the isometric hamstring strength results obtained at 105 degrees of knee flexion (r(2) = 0.034). These findings show that the choice of hamstring tendon graft-that is, semitendinosus alone or semitendinosus and gracilis-is unlikely to significantly influence postoperative hamstring strength outcomes in athletes returning to sports postoperatively. Both graft choices showed strength deficits of between 3% and 27% compared with the nonoperated limb, indicating that hamstring strength deficits persist despite successful completion of rehabilitation. The results also show that the standing knee flexion angle should not be used as a surrogate clinical measure of hamstring strength. Level III, retrospective comparative study.


Conditional Activation of NF-κB Inducing Kinase (NIK) in the Osteolineage Enhances Both Basal and Loading-Induced Bone Formation.
Studies from global loss-of-function mutants suggest that alternative NF-κB downstream of NF-κB inducing kinase (NIK) is a cell-intrinsic negative regulator of osteogenesis. However, the interpretation of the osteoblast and/or osteocyte contribution to the bone phenotype is complicated by simultaneous osteoclast defects in these models. Therefore, we turned to a transgenic mouse model to investigate the direct role of NIK in the osteolineage. Osx-Cre;NT3 animals (NT3-Cre +), which bear a constitutively active NIK allele (NT3) driven by Osx-Cre, were compared with their Cre-negative, Control (Ctrl) littermates. NT3-Cre + mice had elevated serum P1NP and CTX levels. Despite this high turnover state, µCT showed that constitutive activation of NIK resulted in a net increase in basal bone mass in both cortical and cancellous compartments. Furthermore, NT3-Cre + mice exhibited a greater anabolic response following mechanical loading compared with controls. We next performed RNA-Seq on nonloaded and loaded tibias to elucidate possible mechanisms underlying the increased bone anabolism seen in NT3-Cre + mice. Hierarchical clustering revealed two main transcriptional programs: one loading-responsive and the other NT3 transgene-driven. Gene ontology (GO) analysis indicated a distinct upregulation of receptor, kinase, and growth factor activities including Wnts, as well as a calcium-response signature in NT3-Cre + limbs. The promoters of these GO-term associated genes, including many known to be bone-anabolic, were highly enriched for multiple κB recognition elements (κB-RE) relative to the background frequency in the genome. The loading response in NT3-Cre + mice substantially overlapped (>90%) with Ctrl. Surprisingly, control animals had 10-fold more DEGs in response to loading. However, most top DEGs shared between genotypes had a high incidence of multiple κB-RE in their promoters. Therefore, both transcriptional programs (loading-responsive and NT3 transgene-driven) are modulated by NF-κB. Our studies uncover a previously unrecognized role for NF-κB in the promotion of both basal and mechanically stimulated bone formation. © 2019 American Society for Bone and Mineral Research.


Interaction between SIRT1 and non-coding RNAs in different disorders.
SIRT1 is a member of the sirtuin family functioning in the process of removal of acetyl groups from different proteins. This protein has several biological functions and is involved in the pathogenesis of metabolic diseases, malignancy, aging, neurodegenerative disorders and inflammation. Several long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs) have been found to interact with SIRT1. These interactions have been assessed in the contexts of sepsis, cardiomyopathy, heart failure, non-alcoholic fatty liver disease, chronic hepatitis, cardiac fibrosis, myocardial ischemia/reperfusion injury, diabetes, ischemic stroke, immune-related disorders and cancers. Notably, SIRT1-interacting non-coding RNAs have been found to interact with each other. Several circRNA/miRNA and lncRNA/miRNA pairs that interact with SIRT1 have been identified. These axes are potential targets for design of novel therapies for different disorders. In the current review, we summarize the interactions between three classes of non-coding RNAs and SIRT1.


Race differences in activity, fitness, and BMI in female eighth graders categorized by sports participation status.
The purpose of this study was to identify racial differences in physical activity (PA), fitness, and BMI in female 8th-grade sports participants and nonparticipants. Girls from 31 South Carolina middle schools (N = 1,903, 48% White; mean age = 13.6 +/- 0.63) reported PA and previous year sports-team participation, completed a submaximal fitness test, and had height and weight measured. Sports team participation was positively associated with PA and negatively associated with television viewing and BMI, in a dose-response manner. Compared with Whites, African-Americans reported less PA and more television viewing, and had greater BMI scores. Whereas PA intervention programs that incorporate a sports-team component could benefit all girls, African-American girls could be specifically targeted because of their lower physical activity.


Comparison of physical, public and human assets as determinants of socioeconomic inequalities in contraceptive use in Colombia - moving beyond the household wealth index.
Colombia is a lower-middle income country that faces the challenge of addressing health inequalities. This effort includes the task of developing measures of socioeconomic position (SEP) to describe and analyse disparities in health and health related outcomes. This study explores the use of a multidimensional approach to SEP, in which socioeconomic inequalities in contraceptive use are investigated along multiple dimensions of SEP. We tested the hypothesis that provision of Public capital compensated for low levels of Human capital. This study used the 2005 Colombian Demographic and Health Survey (DHS) dataset. The outcome measures were 'current non-use' and 'never use' of contraception. Inequalities in contraceptive behaviour along four measures of SEP were compared: the Household wealth index (HWI), Physical capital (housing, consumer durables), Public capital (publicly provided services) and Human capital (level of education). Principal component analysis was applied to construct the HWI, Physical capital and Public capital measures. Logistic regression models were used to estimate relative indices of inequality (RII) for each measure of SEP with both outcomes. Socio-economic inequalities among rural women tended to be larger than those among urban women, for all measures of SEP and for both outcomes. In models mutually adjusted for Physical, Public and Human capital and age, Physical capital identified stronger gradients in contraceptive behaviour in urban and rural areas (Current use of contraception by Physical capital in urban areas RII 2.37 95% CI (1.99-2.83) and rural areas RII 3.70 (2.57-5.33)). The impact of women's level of education on contraceptive behaviour was relatively weak in households with high Public capital compared to households with low Public capital (Current use of contraception in rural areas, interaction p = < 0.001). Reduced educational inequalities attributable to Public capital were partly explained by differences in household wealth but not at all by health insurance cover. A multidimensional approach provides a framework for disentangling socioeconomic inequalities in contraceptive behaviour. We provide evidence that material circumstances indexed by Physical capital are important socioeconomic determinants while higher provision of Public capital may compensate for low levels of Human capital with respect to modern contraceptive behaviour.


Accurate exploration of synergistic thermal effect: Low-grade-heat-promoted charge recombination coupled with spherical incidence for efficient sunlight-driven photocatalysis.
The major objective of the emerging photo-thermo-catalysis is using waste heat to boost the photocatalytic reaction, especially that powered by sunlight. Because of the complex composition of light-intensity-dependent apparent activation energies, the issue that principally hinders the synergistic thermal effect to photocatalysis has hardly been accurately explored. In this work, by virtue of mutual match of theoretical simulation and experimental behaviors, we demonstrate that photocatalytic reaction rates exhibit a sensitively positive correlation with temperature under weak illumination, in which charge recombination predominates the rate-determining step of semiconductor-cocatalyst interfacial electron transfer. Under high-intensity irradiation, however, the aggravation of charge leakage inherently accompanied by thermionic emission severely weakens the synergistic thermal effect or even slows down the reaction by raising the temperature. Inspired by these, we manage to maximize the photocatalytic solar utilization by spherical incidence of sunlight with the assistance of low-grade heat.


Dietary Quercetin Attenuates Adipose Tissue Expansion and Inflammation and Alters Adipocyte Morphology in a Tissue-Specific Manner.
Chronic inflammation in adipose tissue may contribute to depot-specific adipose tissue expansion, leading to obesity and insulin resistance. Dietary supplementation with quercetin or botanical extracts containing quercetin attenuates high fat diet (HFD)-induced obesity and insulin resistance and decreases inflammation. Here, we determined the effects of quercetin and red onion extract (ROE) containing quercetin on subcutaneous (inguinal, IWAT) vs. visceral (epididymal, EWAT) white adipose tissue morphology and inflammation in mice fed low fat, high fat, high fat plus 50 μg/day quercetin or high fat plus ROE containing 50 μg/day quercetin equivalents for 9 weeks. Quercetin and ROE similarly ameliorated HFD-induced increases in adipocyte size and decreases in adipocyte number in IWAT and EWAT. Furthermore, quercetin and ROE induced alterations in adipocyte morphology in IWAT. Quercetin and ROE similarly decreased HFD-induced IWAT inflammation. However, quercetin and red onion differentially affected HFD-induced EWAT inflammation, with quercetin decreasing and REO increasing inflammatory marker gene expression. Quercetin and REO also differentially regulated circulating adipokine levels. These results show that quercetin or botanical extracts containing quercetin induce white adipose tissue remodeling which may occur through inflammatory-related mechanisms.


Contact points between transcription machinery and the fibroin gene promoter deduced by functional tests of single-base substitution mutants.
An efficient method for oligonucleotide-directed mutagenesis was developed to construct a set of site-specific mutations by using a mixture of oligodeoxyribonucleotides. With this method, as high as 40% of the tested clones turned out to be desired mutants. Seven single-point mutants were isolated in the "TATA" box region of the fibroin gene. In vitro transcription experiments showed that single-base transversions at the TATA box (A----T at position -29, T----A or G at -28, A----T at -27, and A----T at -26) resulted in decreased promoter activities, whereas A----G transitions at positions -24 and -23 had no effect. The initiation site of transcription was normal in three down-promoter mutants at positions -28 and -26, but the A----T transversions at positions -29 and -27 induced an additional transcription start from position +4. Using 10 single-point mutants obtained as above or by nitrous acid-induced mutagenesis, we have prepared a pair of heteroduplex DNAs consisting of a mutant strand and the wild-type one. The molecules heterozygous at positions -30, -21, and -20 showed reduced transcription activities when the noncoding strand bears the mutation, whereas that at position -26 gave a low activity when the coding strand carries the mutation. Both types of heteroduplex at positions -29, -28, -27, and -17 exhibited decreased activities. These results suggest a transcription machinery contact to a major groove of the DNA helix at the TATA box and region of position -20.


Absorption and distribution of naproxen in rats orally treated with naproxen betainate sodium salt monohydrate. Comparison with naproxen.
The S-naproxen betainate sodium salt monohydrate (naproxen-betaNa, CAS 104124-26-7, Aprenin) was synthesized to improve bioavailability and tolerability of naproxen. 24 albino rats were treated with naproxen-betaNa (84 mg/kg) and 24 with S-naproxen (naproxen) (50 mg/kg) by the oral route, the doses being equimolar. The animals were sacrificed and naproxen was assayed in timed plasma samples drawn off over a 24-h period and in tissues excised 1 h after administration. Peak concentrations of naproxen proved to be higher with naproxen-betaNa than with naproxen as such. The area under the curve of naproxen concentrations observed with the two administrations overlapped as did concentrations of the drug in the lungs, myocardium and liver. Naproxen concentrations in the gastric wall after naproxen-betaNa proved to be lower than after administration of naproxen as such, which allowed the authors to assume that naproxen-betaNa has a better gastric tolerability.


Ordering of strained islands during surface growth.
We study the morphological evolution of strained islands in growing crystal films by use of a continuum description including wetting, elasticity, and deposition. We report different nonlinear regimes following the elastic instability and tuned by the flux. Increasing the flux, we first find an annealinglike dynamics, then a slower but nonconventional ripening followed by a steady regime, while the island density continuously increases. The islands develop spatial correlations and ordering with a narrow two-peaked distance distribution and ridgelike clusters of islands at high flux.


The Association Between Borderline Dysnatremia and Perioperative Morbidity and Mortality: Retrospective Cohort Study of the American College of Surgeons National Surgical Quality Improvement Program Database.
Hyponatremia and hypernatremia, as conventionally defined (<135 mEq/L and >145 mEq/L, respectively), are associated with increased perioperative morbidity and mortality. However, the effects of subtle deviations in serum sodium concentration within the normal range are not well-characterized. The purpose of this analysis is to determine the association between borderline hyponatremia (135-137 mEq/L) and hypernatremia (143-145 mEq/L) on perioperative morbidity and mortality. A retrospective cohort study was performed using data from the American College of Surgeons National Surgical Quality Improvement Program database. This database is a repository of surgical outcome data collected from over 600 hospitals across the United States. The National Surgical Quality Improvement Program database was queried to extract all patients undergoing elective, noncardiac surgery from 2015 to 2019. The primary predictor variable was preoperative serum sodium concentration, measured less than 5 days before the index surgery. The 2 primary outcomes were the odds of morbidity and mortality occurring within 30 days of surgery. The risk of both outcomes in relation to preoperative serum sodium concentration was modeled using weighted generalized additive models to minimize the effect of selection bias while controlling for covariates. In the overall cohort, 1,003,956 of 4,551,726 available patients had a serum sodium concentration drawn within 5 days of their index surgery. The odds of morbidity and mortality across sodium levels of 130-150 mEq/L relative to a sodium level of 140 mEq/L followed a nonnormally distributed U-shaped curve. The mean serum sodium concentration in the study population was 139 mEq/L. All continuous covariates were significantly associated with both morbidity and mortality (P<.001). Preoperative serum sodium concentrations of less than 139 mEq/L and those greater than 144 mEq/L were independently associated with increased morbidity probabilities. Serum sodium concentrations of less than 138 mEq/L and those greater than 142 mEq/L were associated with increased mortality probabilities. Hypernatremia was associated with higher odds of both morbidity and mortality than corresponding degrees of hyponatremia. Among patients undergoing elective, noncardiac surgery, this retrospective analysis found that preoperative serum sodium levels less than 138 mEq/L and those greater than 142 mEq/L are associated with increased morbidity and mortality, even within currently accepted "normal" ranges. The retrospective nature of this investigation limits the ability to make causal determinations for these findings. Given the U-shaped distribution of risk, past investigations that assume a linear relationship between serum sodium concentration and surgical outcomes may need to be revisited. Likewise, these results question the current definition of perioperative eunatremia, which may require future prospective investigations.


Systemic lupus erythematosus, following prodromal idiopathic thrombocytopenic purpura, presenting with skin lesions resembling malignant atrophic papulosis.
Systemic lupus erythematosus (SLE) is an autoimmune disease. Its incidence in the UK is approximately 1 per 10 000. Cutaneous involvement, encompassing acute, subacute and chronic disease, occurs in over two-thirds of cases, and can often be the first clue to diagnosis. We describe a highly unusual case of SLE occurring after prodromal idiopathic thrombocytopenic purpura (ITP) and presenting with skin lesions more typical of malignant atrophic papulosis, a rare and often fatal vasculopathy. Such a combination of rare features emphasizes the potential for complexity in this multisystem disease.


Standardization of Operator-Dependent Variables Affecting Precision and Accuracy of the Disk Diffusion Method for Antibiotic Susceptibility Testing.
Parameters like zone reading, inoculum density, and plate streaking influence the precision and accuracy of disk diffusion antibiotic susceptibility testing (AST). While improved reading precision has been demonstrated using automated imaging systems, standardization of the inoculum and of plate streaking have not been systematically investigated yet. This study analyzed whether photometrically controlled inoculum preparation and/or automated inoculation could further improve the standardization of disk diffusion. Suspensions of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 of 0.5 McFarland standard were prepared by 10 operators using both visual comparison to turbidity standards and a Densichek photometer (bioMérieux), and the resulting CFU counts were determined. Furthermore, eight experienced operators each inoculated 10 Mueller-Hinton agar plates using a single 0.5 McFarland standard bacterial suspension of E. coli ATCC 25922 using regular cotton swabs, dry flocked swabs (Copan, Brescia, Italy), or an automated streaking device (BD-Kiestra, Drachten, Netherlands). The mean CFU counts obtained from 0.5 McFarland standard E. coli ATCC 25922 suspensions were significantly different for suspensions prepared by eye and by Densichek (P < 0.001). Preparation by eye resulted in counts that were closer to the CLSI/EUCAST target of 10(8) CFU/ml than those resulting from Densichek preparation. No significant differences in the standard deviations of the CFU counts were observed. The interoperator differences in standard deviations when dry flocked swabs were used decreased significantly compared to the differences when regular cotton swabs were used, whereas the mean of the standard deviations of all operators together was not significantly altered. In contrast, automated streaking significantly reduced both interoperator differences, i.e., the individual standard deviations, compared to the standard deviations for the manual method, and the mean of the standard deviations of all operators together, i.e., total methodological variation.


hUC-MSCs Attenuate Acute Graft-Versus-Host Disease through Chi3l1 Repression of Th17 Differentiation.
Mesenchymal stem cells (MSCs) have already demonstrated definitive evidence of their clinical benefits in acute graft-versus-host disease (aGvHD) and other inflammatory diseases. However, the comprehensive mechanism of MSCs' immunomodulation properties has not been elucidated. To reveal their potential immunosuppressive molecules, we used RNA sequencing to analyze gene expression in different tissue-derived MSCs, including human bone marrow, umbilical cord, amniotic membrane, and placenta, and found that chitinase-3-like protein 1 (Chi3l1) was highly expressed in human umbilical cord mesenchymal stem cells (hUC-MSCs). We found that hUC-MSCs treated with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) exhibited increased expression of Chi3l1 and concurrently repressed T-helper 17 cell (Th17) differentiation through inhibition of signal transducer and activator of transcription 3 (STAT3) activation. Furthermore, Chi3l1 knockdown hUC-MSCs exhibited impaired therapeutic efficacy in aGvHD mice with an increased inflammatory response by promoting Th17 cell differentiation, including an increase in IL-17A in the spleen, intestine, and serum. Collectively, these results reveal a new immunosuppressive molecule, Chi3l1, in hUC-MSCs in the treatment of aGvHD that regulates Th17 differentiation and inhibits STAT3 activation. These novel insights into the mechanisms of hUC-MSC immunoregulation may lead to the consistent production of hUC-MSCs with strong immunosuppressive functions and thus improved clinical utility.


Preventive therapy of herpes labialis associated with trigeminal surgery.
Acyclovir was shown to limit herpes simplex reactivation in a controlled trial to prevent herpes labialis after surgical intervention for trigeminal neuralgia. Of 14 patients receiving acyclovir, unambiguous herpes labialis developed in only one, compared with 12 of 16 in the placebo group.


Dermatofibrosarcoma Protuberans in a Patient With Cowden Syndrome: Revisiting the PTEN and PDGF Pathways.
PTEN hamartoma tumor syndrome, of which Cowden syndrome (CS) is the most recognized variant, is characterized by multiple benign and malignant tumors of ectodermal, mesodermal, and endodermal origins, secondary to germline mutation in the phosphatase and tensin homolog (PTEN) gene. Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive malignant fibroblastic/myofibroblastic tumor of the skin, characterized by the t(17:22)(q22:q13) translocation resulting in fusion of the COL1A1 and PDGFB genes. An association between CS and DFSP has not been reported in the literature to date. The authors have encountered a male patient with CS and a history of DFSP that developed adjacent to a sclerotic fibroma on the parietal scalp, both excised at age 7. He presented at age 21 with an enlarging pink nodule at the same site on the parietal scalp. Excision revealed a dermal and subcutaneous storiform spindle cell proliferation with fat entrapment and positive staining for CD34, consistent with DFSP. Fluorescence in situ hybridization confirmed PDGFB gene rearrangement. PTEN expression in the patient's recurrent DFSP was nearly absent when compared with that of sporadic DFSP. To our knowledge, this is the first report of DFSP in a patient with CS. Although the association is likely to be coincidental, the authors revisited the PTEN and the PDGF pathways to speculate any possible interplay of the 2 conditions on a molecular level.


Phosphite shifts physiological and hormonal profile of Monterey pine and delays Fusarium circinatum progression.
Fusarium circinatum is the causal agent of pitch canker disease affecting Pinus spp. and Pseudotsuga menziesii worldwide. Under strict quarantine measures, alternative approaches for disease control are necessary. Phosphite (Phi) salts are known for their fungicidal activity and as plant resistance elicitors; however, its potential is yet to be acknowledged in the Pinus-F. circinatum model. The main aim of this study was to assess whether the application of a Phi-based commercial formulation would delay the progression of the pitch canker on Pinus radiata plants, and on the in vitro fungal growth. In vitro assays were performed using different Phi concentrations (1% and 4%) and a non-treated control (0%), and repeated in vivo using inoculated and non-inoculated plants. Plant physiological parameters and hormonal content were evaluated. Phi was effective at inhibiting in vitro mycelial growth in a dose dependent manner. Regardless of fungal inoculation, Phi application induced positive effects on plant performance, despite phytotoxic effects found at 4%. Fusarium circinatum infection led to a reduction in gas exchange and chlorophyll fluorescence (Fv/Fm and φPSII), while proline and hormone (JA, ABA and SA) levels increased. Phi was effective in delaying disease symptom development in a dose dependent manner, concurrent with in vitro observations: gas exchange and chlorophyll fluorescence (Fv/Fm) were unaffected; proline, MDA and ABA decreased; electrolyte leakage and total soluble sugars increased. This suggests a direct (pathogen growth inhibition) and indirect (host defense priming) action of Phi, showing that Phi represents a potential strategy to control F. circinatum infection.


Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action.
Topical microbicides to stop sexually transmitted diseases, such as herpes simplex virus type 2 (HSV-2), are urgently needed. The emerging field of nanotechnology offers novel suitable tools for addressing this challenge. Our objective was to study, in vitro and in vivo, antiherpetic effect and antiviral mechanisms of several polyanionic carbosilane dendrimers with anti-HIV-1 activity to establish new potential microbicide candidates against sexually transmitted diseases. Plaque reduction assay on Vero cells proved that G2-S16, G1-S4, and G3-S16 are the dendrimers with the highest inhibitory response against HSV-2 infection. We also demonstrated that our dendrimers inhibit viral infection at the first steps of HSV-2 lifecycle: binding/entry-mediated events. G1-S4 and G3-S16 bind directly on the HSV-2, inactivating it, whereas G2-S16 adheres to host cell-surface proteins. Molecular modeling showed that G1-S4 binds better at binding sites on gB surface than G2-S16. Significantly better binding properties of G1-S4 than G2-S16 were found in an important position for affecting transition of gB trimer from G1-S4 prefusion to final postfusion state and in several positions where G1-S4 could interfere with gB/gH-gL interaction. We demonstrated that these polyanionic carbosilan dendrimers have a synergistic activity with acyclovir and tenofovir against HSV-2, in vitro. Topical vaginal or rectal administration of G1-S4 or G2-S16 prevents HSV-2 transmission in BALB/c mice in values close to 100%. This research represents the first demonstration that transmission of HSV-2 can be blocked by vaginal/rectal application of G1-S4 or G2-S16, providing a step forward to prevent HSV-2 transmission in humans.


Relationship Between Alcohol Intolerance and Aspirin-Exacerbated Respiratory Disease (AERD): Systematic Review.
Previous studies have suggested that patients with aspirin-exacerbated respiratory disease (AERD) have a high likelihood of alcohol intolerance. The purpose of this systematic review is to identify if there is sufficient evidence to confirm this correlation and the impact of medical therapy on subsequent alcohol tolerance. PubMed, EMBASE, SCOPUS, EBSCO, Google Scholar, Cochrane Library, and Grey literature. We also performed snowballing on the identified observational studies (OS) for additional data. A systematic review was conducted from 1968 to 2022 to identify those studies describing AERD symptomatology triggered by alcohol intake. The primary outcome was to analyze the current literature for the association between alcohol intolerance and AERD symptoms. The secondary outcome looked for improvement in alcohol tolerance after aspirin desensitization or biological therapy. A total of 775 studies were identified and 40 abstracts were evaluated. From these, 5 studies met the inclusion criteria. Of the 5 manuscripts, there was 1 case-control, 2 cohort, and 2 cross-sectional studies. A total of 522 participants with AERD and a history of alcohol consumption were included, with 52.8% reporting at least 1 sinopulmonary exacerbation after alcohol intake. One of 3 studies noted improvement in alcohol tolerance after medical therapy with aspirin desensitization. The current literature suggests that patients with AERD have a high risk of alcohol intolerance. Additionally, aspirin desensitization may improve alcohol tolerance in this patient population.


A novel high throughput 1536-well Notch1 γ -secretase AlphaLISA assay.
The Notch pathway plays a crucial role in cell fate decisions through controlling various cellular processes. Overactive Notch signal contributes to cancer development from leukemias to solid tumors. γ-Secretase is an intramembrane protease responsible for the final proteolytic step of Notch that releases the membrane-tethered Notch fragment for signaling. Therefore, γ-secretase is an attractive drug target in treating Notch-mediated cancers. However, the absence of high throughput γ-secretase assay using Notch substrate has limited the identification and development of γ- secretase inhibitors that specifically target the Notch signaling pathway. Here, we report on the development of a 1536- well γ-secretase assay using a biotinylated recombinant Notch1 substrate. We effectively assimilated and miniaturized this newly developed Notch1 substrate with the AlphaLISA detection technology and demonstrated its robustness with a calculated Z' score of 0.66. We further validated this optimized assay by performing a pilot screening against a chemical library consisting of ~5,600 chemicals and identified known γ-secretase inhibitors e.g. DAPT, and Calpeptin; as well as a novel γ-secretase inhibitor referred to as KD-I-085. This assay is the first reported 1536-well AlphaLISA format and represents a novel high throughput Notch1-γ-secretase assay, which provides an unprecedented opportunity to discover Notch-selective γ-secretase inhibitors that can be potentially used for the treatment of cancer and other human disorders.


Phosphodiesterase inhibitors for the treatment of pulmonary hypertension.
The pulmonary vascular bed is both a source of and target for a number of vasoactive factors. Among the most important for pulmonary vascular homeostasis are factors that utilise cyclic guanosine monophosphate (cGMP) as an intracellular second messenger. These include nitric oxide and the natriuretic peptide family (atrial, brain and C-type natriuretic peptides). In the search for therapeutic strategies that engage the cGMP signalling pathway for the treatment of pulmonary arterial hypertension (PAH), inhibition of cGMP metabolism by phosphodiesterase type 5 (PDE5)-targeted compounds has proven most successful to date. One PDE5 inhibitor, sildenafil, has been shown to improve pulmonary haemodynamics and exercise capacity in patients with PAH and is now an approved treatment. Others are under investigation. An interesting, although still tentative, observation is the potential of sildenafil to reduce pulmonary vascular resistance without adversely affecting ventilation-perfusion matching. Another is the expression of phosphodiesterase type 5 in the hypertrophied right ventricle. These data suggest that phosphodiesterase type 5 inhibitors may have effects that distinguish them from other treatments for pulmonary hypertension and merit further study.


Passive vibration control: a structure-immittance approach.
Linear passive vibration absorbers, such as tuned mass dampers, often contain springs, dampers and masses, although recently there has been a growing trend to employ or supplement the mass elements with inerters. When considering possible configurations with these elements broadly, two approaches are normally used: one structure-based and one immittance-based. Both approaches have their advantages and disadvantages. In this paper, a new approach is proposed: the structure-immittance approach. Using this approach, a full set of possible series-parallel networks with predetermined numbers of each element type can be represented by structural immittances, obtained via a proposed general formulation process. Using the structural immittances, both the ability to investigate a class of absorber possibilities together (advantage of the immittance-based approach), and the ability to control the complexity, topology and element values in resulting absorber configurations (advantages of the structure-based approach) are provided at the same time. The advantages of the proposed approach are demonstrated through two case studies on building vibration suppression and automotive suspension design, respectively.


The Complex Dynamics of Resources and Maintaining Factors in Social Networks for Alcohol-Use Disorders: A Cross-Sectional Study.
Systemic therapy considers the complex dynamics of relational factors and resources contributing to psychological symptoms. Negative maintaining factors have been well researched for people suffering from Alcohol-use Disorders (AUD). However, we know little about the complex dynamics of these negative factors and resources. We interviewed fifty-five participants suffering or fully remitted from Alcohol-use disorders in this cross-sectional study (M = 52 years; 33% female). The interviews focused on relational factors (e.g., social support and social negativity) referring to a Support Social Network and a Craving Social Network (CSN). The CSN included all significant others who were associated with craving situations. We compared the network characteristics of the group suffering from Alcohol-use Disorders (n = 38) to a fully remitted control group (n = 17). The abstinent group with full remission named on average fewer individuals in the CSNs. They had lower social negativity mean scores in the Support Social Network compared to the non-remitted group (d = 0.74). In the CSN, the mean scores of social support were significantly higher than the median for both groups (d = 2.50). These findings reveal the complex interplay of relational patterns contributing to the etiology, maintenance, and recovery from Alcohol-use disorders. A successful recovery can be linked to increased social resources and reduced relations associated with craving. However, craving-associated relations represent an important source of social support. Future research should investigate this ambivalence for the systemic perspective on the explanation and treatment of Alcohol-use disorders.


[Evaluation of 2 immunologic techniques (ELISA, DIF) for the diagnosis of Giardia lamblia in feces].
Two immunology techniques (ELISA and DIF) were evaluated for the detection of Giardia lamblia in faeces, using microscopic examination as reference method. Stool specimens from 378 patients were studied, in our laboratory for detection of G. lamblia. All were examined visually by microscope after carrying out the concentration technique with Para-Pak Macro-Con (Meridian Diagnostics, Cincinnati, Ohio). The ELISA technique (Giardia Celisa Test Cellabs Diagnostics PTY LTD, Brookvale, Australia) was used on the 378 faeces specimens and 294 of them were processed also by DIF (Giardia-Cel IF Test, from the same commercial supplier). A total of 16 positive visual detections was obtained. Bot the ELISA and DIF techniques showed an excellent sensitivity (100% for both) and specificity (97.5% and 98.5%) respectively, as well as a negative predictive value of 100% for ELISA and DIF, whilst the positive predictive value is reduced to 79% in DIF and 64% in ELISA. From our point of view, both tests are of utility for the screening of carriers, for epidemiological analyses, for the study of outbreaks of diarrhoea due to contaminated waters, as well as non-invasive methods for diagnosis in suggestive clinics with negative microscopic examinations.


Strategies for primary and secondary prevention of Lyme disease.
Lyme disease (borreliosis) incidence continues to increase despite a growing knowledge of primary and secondary prevention strategies. Primary prevention aims to reduce the risk of tick exposure and thereby decrease the incidence of new Lyme disease cases. Secondary prevention targets the development of disease or reduces disease severity among people who have been bitten by infected ticks. Numerous prevention strategies are available, and although they vary in cost, acceptability and effectiveness, uptake has been universally poor. Research in areas where Lyme disease is endemic has demonstrated that despite adequate knowledge about its symptoms and transmission, many people do not perform behaviors to reduce their risk of infection. New prevention strategies should aim to increase people's confidence in their ability to carry out preventive behaviors, raise awareness of desirable outcomes, and aid in the realization that the necessary skills and resources are available for preventive measures to be taken. In this article we evaluate the prevention and treatment strategies for Lyme disease, and discuss how these strategies can be implemented effectively. As many patients with Lyme disease develop arthritis and are referred to rheumatologists it is important that these health-care providers can educate patients about disease-prevention strategies.


[Antitumor properties of a liposomal form of a differentiation factor HLDF fragment in cultured cells].
Cytotoxic properties of a liposomal form of the HLDF6 hexapeptide, representing an HL-60 cell differentiation factor fragment, have been studied on a murine primary lymphosarcoma cell culture. It is established that the liposomal HLDF6 peptide is capable of inhibiting proliferation and enhancing death of the cells of both LS and RLS lymphosarcoma strains distinguished by their sensitivity to cytostatic agents. The effect of the preparation is determined by its antiproliferative and apoptogenic actions on the cells. Free HLDF6 peptide showed a lower cytotoxic activity with respect to the tumor cells as compared to the liposomal preparation.


Corticotropin-releasing factor receptor 2 is a tonic suppressor of vascularization.
Angiogenesis is regulated by means of a balance between activators and inhibitors. However, little is known regarding the regulation of the quiescent state of adult vessels. Corticotropin-releasing factor receptor 2 (CRFR2) is found in both endothelial and smooth muscle cells (SMCs) in the vasculature, where its function has remained elusive. We have investigated the role of CRFR2 as a determinant of tissue vascularization by comparing control and CRFR2-deficient mice with immunohistological and morphometric techniques. To define the mechanisms responsible for CRFR2 inhibition of angiogenesis, we have also examined in vitro the effect of ligand activation on cell proliferation, cell cycle protein phosphorylation, and capillary tube formation. Our results demonstrate that mice deficient for CRFR2 become hypervascularized postnatally. Activation of this receptor in vitro results in reduced vascular endothelial growth factor (VEGF) release from SMCs, an inhibition of SMC proliferation, and inhibition of capillary tube formation in collagen gels. Treatment of a subcutaneously injected gel matrix with a CRFR2 agonist inhibits growth factor-induced vascularization. Western blots show that cell cycle retinoblastoma protein, which is essential for cell cycle progression, is decreased by CRFR2 agonist treatment in SMCs. These results suggest that CRFR2 is a critical component of a pathway necessary for tonic inhibition of adult neovascularization. CRFR2 may be a potential target for therapeutic modulation of angiogenesis in cancer and ischemic cardiovascular disease.


The glutaeus maximus muscle flap in the management of persistent perineal sinus.
Delayed healing of the perineal wound is a common complication following proctectomy for inflammatory bowel disease. A persistent sinus requires wide and adequate drainage, but the resulting large cavity with rigid walls may take more than a year to heal. Mobilization of a viable flap of gluctaeus maximus muscle to fill the cavity allows healing within a few weeks.


Delivering Traumatic Brain Injury to Larval Zebrafish.
We describe a straightforward, scalable method for administering traumatic brain injury (TBI) to zebrafish larvae. The pathological outcomes appear generalizable for all TBI types, but perhaps most closely model closed-skull, diffuse lesion (blast injury) neurotrauma. The injury is delivered by dropping a weight onto the plunger of a fluid-filled syringe containing zebrafish larvae. This model is easy to implement, cost-effective, and provides a high-throughput system that induces brain injury in many larvae at once. Unique to vertebrate TBI models, this method can be used to deliver TBI without anesthetic or other metabolic agents. The methods simulate the main aspects of traumatic brain injury in humans, providing a preclinical model to study the consequences of this prevalent injury type and a way to explore early interventions that may ameliorate subsequent neurodegeneration. We also describe a convenient method for executing pressure measurements to calibrate and validate this method. When used in concert with the genetic tools readily available in zebrafish, this model of traumatic brain injury offers opportunities to examine many mechanisms and outcomes induced by traumatic brain injury. For example, genetically encoded fluorescent reporters have been implemented with this system to measure protein misfolding and neural activity via optogenetics.


Increased plasma, biliary, and hepatic cholesterol precursors in pigs with ileal autotransplantation-induced malabsorption of cholesterol and bile acids.
Small-bowel transplantation impairs intestinal absorptive function for unknown reasons. The proportions of plasma, biliary, and hepatic cholesterol precursors to cholesterol were determined by gas-liquid chromatography after resection of the proximal 75% of the porcine jejunoileum (n = 15) and autotransplantation of the remaining ileum (n = 15) and were related to in vivo absorption and fecal excretion of cholesterol. Ileal autotransplantation significantly decreased serum (18%; P < 0.05) and liver (7.6%; P < 0.05) cholesterol content, the esterification percentage of serum cholesterol (5.1%; P < 0.0001), and the total amount of cholesterol absorbed (48%; P < 0.05) and increased fecal excretion of bile acids (108%; P < 0.0001), net cholesterol elimination (53%; P < 0.001), and the proportions of plasma (207%; P < 0.0001), biliary (183%; P < 0.0001), and hepatic (114%; P < 0.0001) cholesterol precursors. The increases were most striking for the side-chain-saturated demethylated sterols, cholesterol and lathosterol, and monomethyl sterols, whose bile/liver and plasma/liver ratios were increased in the autotransplantation group. Plasma, biliary, and hepatic precursor proportions were positively related to each other and similarly correlated with fecal bile acids and the net elimination of cholesterol in feces. These findings suggest that ileal autotransplantation in pigs with proximal gut resection increased the levels of cholesterol precursor sterols in plasma, bile, and liver mainly due to a bile-acid-malabsorption-induced increase in hepatic synthesis of cholesterol. Enhanced secretion of cholesterol precursors from the liver into the plasma and bile may have contributed to their increased values during the increased rate of cholesterogenesis.


The new vaccine frontier.
Vaccines are one of the greatest public health achievements and have had a tremendous impact on people's health and survival around the world. Nevertheless, highly prevalent infectious disease threats unresponsive to traditional immunization strategies, emerging and re-emerging threats, and non-communicable diseases amenable to immunization remain critical global health challenges. Scientific advances will reveal solutions, but it will take political, social and economic commitment from all stakeholders for these solutions to achieve their health protection benefit among the people who need them most.


Comparison between bupivacaine and etidocaine in lumbar epidural block for urological surgery.
Lumbar epidural blocks produced by 17 ml of etidocaine 1% or bupivacaine 0.5%, both with adrenaline (5 mug/ml), have been compared in a double-blind trial in 40 patients, all scheduled for elective urological surgery. The onset time and segmental spread of analgesia, tested by pinprick and thermal pain, seemed to be slightly shorter with etidocaine (not statistically significant). The duration of analgesia and the blood-pressure changes were comparable with both drugs. The incidence and intensity of motor block were higher with etidocaine.