[Sugar transport regulation in vitro by new calcium ionophores].
The influence of calcium ionophores--tenoyltrifluoroacetate (TTFA) and divaleryldibenzo-18-crown-6(divaleryl) on the glucose consumption, D-xylose transport and glycogen content in rat diaphragm was studied. TTFA caused a clear dose-dependent inhibition of carbohydrate transport and glycogenolysis stimulation. Divaleryl, on the other hand, raised glucose consumption, D-xylose transport without influencing glycogen content. Exclusion of Ca++ from incubation medium increased the TTFA inhibiting effect on glucose consumption, decreased its glycogenolytic effect and removed divaleryl induced stimulation of glucose transport. Mechanisms of calcium ionophore action and a possible role of intracellular Ca2+ in carbohydrate transport are discussed.


Intraocular Pressure and Medication Burden With Cataract Surgery Alone, or Cataract Surgery Combined With Trabecular Bypass or Goniotomy.
When compared with cataract surgery in glaucoma patients, trabecular micro-bypass and goniotomy resulted in a large decrease in the incidence of intraocular pressure (IOP) spikes, a modest effect on IOP, and a minimal effect on medication burden. To compare changes in IOP and ocular hypotensive medications in 3 surgical cohorts: cataract surgery, cataract surgery with trabecular micro-bypass (cataract/trabecular), and cataract surgery with goniotomy (cataract/goniotomy). We included 138 eyes diagnosed with open-angle glaucoma: (1) 84 eyes with cataract surgery alone, (2) 25 eyes with cataract/trabecular surgery, and (3) 29 eyes with cataract/goniotomy surgery. We compared the groups for postoperative IOP and the number of ocular hypotensive medications. We adjusted for preoperative IOP, and preoperative and postoperative number of ocular hypotensive medications. We defined an IOP spike as IOP ≥21 mm Hg and 10 mm Hg higher than preoperative on postoperative day 1. All 3 surgeries showed a decrease in IOP (P≤0.004) and medication burden (P≤0.001) at 3 and 6 months postoperatively when compared with their own preoperative baselines. When compared with cataract surgery alone, cataract/trabecular and cataract/goniotomy had similar IOP lowering at 1 month postoperatively, and variable results at 3 and 6 months. The change in ocular hypotensive medications was not statistically different between the surgical groups at any postoperative visit. Cataract/trabecular and cataract/goniotomy decreased IOP on postoperative day 1, and had relative risk reduction of ~70% for IOP spikes (P≤0.001 for both). Trabecular micro-bypass and goniotomy when added to cataract surgery resulted in a large decrease in IOP spikes, a modest effect on IOP, and a minimal effect on medication burden when compared with cataract surgery alone in glaucoma patients.


Learning a Probabilistic Boolean Network model from biological pathways and time-series expression data.
The problem of inferring a stochastic model for gene regulatory networks is addressed here. The prior biological data includes biological pathways and time-series expression data. We propose a novel algorithm to use both of these data to construct a Probabilistic Boolean Network (PBN) which models the observed dynamics of genes with a high degree of precision. Our algorithm constructs a pathway tree and uses the time-series expression data to select an optimal level of tree, whose nodes are used to infer the PBN.


Regulatory mechanism of circular RNAs in neurodegenerative diseases.
Neurodegenerative disease is a collective term for a category of diseases that are caused by neuronal dysfunction, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Circular RNAs (circRNAs) are a class of non-coding RNAs without the 3' cap and 5' poly(A) and are linked by covalent bonds. CircRNAs are highly expressed in brain neurons and can regulate the pathological process of neurodegenerative diseases by affecting the levels of various deposition proteins. This review is aiming to suggest that the majority of circRNAs influence neurodegenerative pathologies mainly by affecting the abnormal deposition of proteins in neurodegenerative diseases. We systematically summarized the pathological features of neurodegenerative diseases and the regulatory mechanisms of circRNAs in various types of neurodegenerative diseases. Neurodegenerative disease main features include intercellular ubiquitin-proteasome system abnormalities, changes in cytoskeletal proteins, and the continuous deposition of insoluble protein fragments and inclusion bodies in the cytoplasm or nucleus, resulting in impairment of the normal physiological processes of the neuronal system. CircRNAs have multiple mechanisms, such as acting as microRNA sponges, binding to proteins, and regulating transcription. CircRNAs, which are highly stable molecules, are expected to be potential biomarkers for the pathological detection of neurodegenerative diseases such as AD and PD. In this review, we describe the regulatory roles and mechanisms of circRNAs in neurodegenerative diseases and aim to employ circRNAs as biomarkers for the diagnosis and treatment of neurodegenerative diseases.


[Superior mesenteric artery (SMAS/AMS) syndrome and its management].
Authors describe the case of patient with duodenal obstruction, caused by compression of the third part of duodenum by superior mesenteric artery so called, superior mesenteric artery syndrome (SAMS). They describe clinical course of illness and the way of surgical treatment. Pointing to their perioperative doubts resulting in a way of surgical treatment. In disscussion they describe etiology, diagnostical course, clinical picture and surgical management of patient with SAMS.


Genesis of resting microglia in the gray matter of mouse hippocampus.
The genesis of resting microglia in the gray matter of mouse hippocampus was studied by 3H-thymidine autoradiography in combination with electron microscopy. Newborn mice were injected with 3H-thymidine singly or repeatedly at different postnatal stages, and killed shortly after the injection or after various intervals. Tissue specimens of the hippocampus at CA1 and CA2 were processed for light and electron microscopic autoradiography. The results showed that at least 91% of glial cells in the stratum radiatum of the hippocampus are produced after birth. About three-fourths of astroglia in this area are produced before the sixth postnatal day, and a larger part of resting microglia are formed after the ninth postnatal day. Morphological transition can be traced from either proliferating cells in the stratum radiatum at late postnatal days to resting microglia, or from those in early postnatal days to astroglia. A continuous morphological transition was observed between the proliferating cells at the late postnatal days (microglial production period) and those at the early postnatal days (astroglial production period). The latter retain some fine structural characteristics similar to small glioblasts in the subependymal layer. These findings strongly suggest that resting microglia, as well as astroglia, are derived from glioblasts, and are of neurectodermal origin.


Panic attacks and risk of incident cardiovascular events among postmenopausal women in the Women's Health Initiative Observational Study.
Previous studies have documented an association of depression and phobic anxiety with cardiovascular morbidity and mortality, but little is known about the cardiovascular sequelae of panic anxiety. To determine whether panic attacks are associated with risk of cardiovascular morbidity and mortality in postmenopausal women. Prospective cohort survey. Ten clinical centers of the 40-center Women's Health Initiative. A total of 3369 community-dwelling, generally healthy postmenopausal women (aged 51-83 years) enrolled between 1997 and 2000 in the Myocardial Ischemia and Migraine Study who completed a questionnaire about occurrence of panic attacks in the previous 6 months. Cardiovascular/cerebrovascular outcomes (fatal and nonfatal myocardial infarction and stroke) and all-cause mortality were ascertained after a mean of 5.3 years of follow-up. A 6-month history of full-blown panic attacks, endorsed by 10% of postmenopausal women in this cohort, was associated with both coronary heart disease (hazard ratio, 4.20; 95% confidence interval, 1.76-9.99) and the combined end point of coronary heart disease or stroke (hazard ratio, 3.08; 95% confidence interval, 1.60-5.94) after controlling for multiple potential confounders. The hazard ratio for all-cause mortality, excluding those with a history of cardiovascular/cerebrovascular events, was 1.75 (95% confidence interval, 1.04-2.94). Panic attacks are relatively common among postmenopausal women and appear to be an independent risk factor for cardiovascular morbidity and mortality in older women.


Enduring to gain new perspective: a grounded theory study of the experience of perinatal bereavement in Black adolescents.
Black adolescents in the US experience perinatal loss at a higher rate than other races and ethnicities. The experience of eight Black urban adolescents through the first 3 months after perinatal loss was studied using grounded theory. The process of "enduring to gain new perspective" began with "denying and hesitating" when surprised by unplanned pregnancy but led to "getting ready for this whole new life," followed by shock of "suffering through the loss," "all that pain for nothing," and "mixed emotions going everywhere." Over time, the adolescents began "reaching out for support" and eventually "preserving the memory and maintaining relationship," "searching for meaning and asking why," and "gaining new perspective on life." Parallels are noted to extant bereavement theory.


Diffusion-Tensor MRI Based Skeletal Muscle Fiber Tracking.
A skeletal muscle's function is strongly influenced by the internal organization and geometric properties of its fibers, a property known as muscle architecture. Diffusion-tensor magnetic resonance imaging-based fiber tracking provides a powerful tool for non-invasive muscle architecture studies, has three-dimensional sensitivity, and uses a fixed frame of reference. Significant advances have been made in muscle fiber tracking technology, including defining seed points for fiber tracking, quantitatively characterizing muscle architecture, implementing denoising procedures, and testing validity and repeatability. Some examples exist of how these data can be integrated with those from other advanced MRI and computational methods to provide novel insights into muscle function. Perspectives are offered regarding future directions in muscle diffusion-tensor imaging, including needs to develop an improved understanding for the microstructural basis for reduced and anisotropic diffusion, establish the best practices for data acquisition and analysis, and integrate fiber tracking with other physiological data.


Cosmetic Injection of Illicit Foreign Materials: Imaging Features and Patterns of Migration in 413 Cases.
The injection of illicit, non-regulated foreign materials is increasingly common and has negative consequences relative to the inflammatory process that ensues. To identify anatomical and imaging characteristics after the cosmetic injection of illicit foreign materials. A retrospective review of clinical and imaging records was performed. The issues analyzed were anatomical site, type of the injected substance, imaging method to aid in diagnosis, and patterns of migration. Data on 413 patients were collected. Most patients were female with a mean age of 44 years. The most commonly infiltrated region were the buttocks (n = 284; 53.58%) followed by the breast (n = 99; 18.67%). Magnetic resonance imaging was the most used method for diagnosis in those patients with an imaging study (159 out of 168). The most frequent depth of foreign material detected by imaging was the muscular plane (n = 103; 61.30%). Migration was detected in 56.55% of patients with an imaging study. Most infiltrated substances were unknown; biopolymers were the most commonly identified substances. Migration rates varied from 9% to 29%; rates comparison according to type of substance wasn't statistically significant (p = 0.712). Migration was more common when the depth of infiltration was in muscle (77.66%) compared to subcutaneous tissue (23.4%); this difference was statistically significant (p < 0.0001). Deep infiltration is related to greater migration rates, apparently regardless of the substance used.


Direct composite resin restorations: a review of some clinical procedures to achieve predictable results in posterior teeth.
The interest of patients in having tooth-colored restorations and the development of techniques and materials that make these restorations easier have contributed to make the esthetic restoration of posterior teeth popular. The direct use of composites in posterior teeth is a technique-sensitive procedure. Some difficulties, nevertheless, can be overcome or at least minimized by a heedful clinician by paying thorough attention to the various stages of the restorative technique. The present article seeks to review some concepts about this adhesive restorative procedure and to illustrate the possibilities of the technique with clinical reports. The direct posterior composite restorative technique offers the possibility of closely matching the natural optical characteristics of the lost tooth structure. Aimed at showing the potential of this technique, this article presents two step-by-step case reports and also reviews some concepts related to these clinical procedures.


Retinal microvascular abnormalities in major depression.
The aim of our study was to find a possible association between retinal microvascular abnormality and major depression in a non-geriatric population. The participants with major depression were hospitalised at the University Hospital in Hradec Kralove, Department of Psychiatry. Retinal images were obtained using a stationary Fundus camera FF450 by Zeiss and a hand-held camera by oDocs. Fifty patients (men n=18, women n=32) aged 16 to 55 (men's average age 33.7±9.9 years, women's average age 37.9±11.5 years) were compared with fifty mentally healthy subjects (men n=28, women n=22) aged 18 to 61 (men's average age 35.3±9.2 years, women's average age 36.6±10.6 years) in a cross-sectional design. The patients were diagnosed with a single depressive episode (n=26) or a recurrent depressive disorder (n=24) according to the ICD-10 classification. Our results confirmed significant microvascular changes in the retina in patients with depressive disorder in comparison to the control group of mentally healthy subjects, with significantly larger arteriolar (P<0.0001) as well as venular (P<0.001-0.0001) calibres in major depression. According to the literature, acute and chronic neuroinflammation is associated with changes in microvascular form and function. The endothelium becomes a major participant in the inflammatory response damaging the surrounding tissue and its function. Because the retina and brain tissue share a common embryonic origin, we suspect similar microvascular pathology in the retina and in the brain in major depression. Our results may contribute to a better understanding of depression etiopathogenesis and to its personalized treatment.


Serological evidence of duck Tembusu virus infection in free-grazing ducks, Thailand.
Duck Tembusu virus (DTMUV) has been reported in ducks raised in farming system since its emergence in 2010. No information is available on DTMUV infection in free-grazing ducks, which are commonly raised and widespread in several Asian countries. To determine the presence of DTMUV infection in free-grazing ducks in Thailand, retrospective serum samples collected from 1,000 free-grazing ducks during 2008-2015 were tested for DTMUV infection. Our result showed that 91 (9.10%) were positive for DTMUV neutralizing antibodies and DTMUV seropositive ducks have been detected in Thailand since 2008. To further investigate the seroprevalence and geographic distribution of DTMUV infection in free-grazing ducks in Thailand, a cross-sectional serological survey of DTMUV was conducted in 2016. Of 1,200 free-grazing ducks in the 60 flocks from 20 provinces located in the major free-grazing duck raising areas of Thailand, 365 (30.42%) were positive for DTMUV neutralizing antibodies and 56 flocks (93.33%) had at least one DTMUV seropositive duck. Additionally, DTMUV seropositive ducks were observed in all provinces tested. In conclusion, our data demonstrated the presence of DTMUV infection in free-grazing ducks since 2008 and widespread DTMUV infection in free-grazing ducks in Thailand with a relatively high seroprevalence. These findings suggest the potential role of free-grazing ducks in the dissemination of DTMUV and highlight the necessity of systemic DTMUV surveillance in free-grazing ducks in addition to farm ducks for early detection, prevention, and control of this emerging disease.


[Topiramate therapy in patients with refractory epilepsy].
The purpose of this study was to examine the result of administrating topiramate (TPM) to patients with epilepsy that is refractory to treatment with two or more antiepileptic agents. A total of 50 patients were evaluated, 90% of which had partial seizures (simple partial, complex partial and partial with secondary generalisation) and the remaining 10% suffered from generalised seizures. The most frequent aetiology was that which corresponded to the symptoms (52% of the cases). 98% of the patients were treated with two or three drugs. TPM was added with a dosage interval between 75 and 550 mg and follow-up visits were carried out throughout a period of nine months. 12 patients remained seizure-free for at least the first three months of the study; in 20 patients the number of seizures decreased by 50% or more; in 14 patients no changes were observed, and in the other four there was an increase in the number of seizures. The best results were obtained in cases of seizures with an idiopathic aetiology, while complex partial seizures offered the worst results. We also analysed the factors that might exert an influence on the different degrees of response. TPM was effective in all kinds of seizures. 24% of the patients became seizure free, and the total percentage of respondents rose to 64%. No patients dropped out of the study because of intolerance to the drugs.


A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration.
Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization.


Anisotropic charge Kondo effect in a triple quantum dot.
We predict that an anisotropic charge Kondo effect appears in a triple quantum dot, when the system has twofold degenerate ground states of (1,1,0) and (0,0,1) charge configurations. Using bosonization and refermionization methods, we find that at low temperature the system has the two different phases of massive charge fluctuations between the two charge configurations and vanishing fluctuations, which are equivalent with the Kondo-screened and ferromagnetic phases of the anisotropic Kondo model, respectively. The phase transition is identifiable by electron conductance measurement, offering the possibility of experimentally exploring the anisotropic Kondo model. Our charge Kondo effect has a similar origin to that in a negative-U Anderson impurity.


Air-stimulated ATP release from keratinocytes occurs through connexin hemichannels.
Cutaneous ATP release plays an important role in both epidermal stratification and chronic pain, but little is known about ATP release mechanisms in keratinocytes that comprise the epidermis. In this study, we analyzed ATP release from cultured human neonatal keratinocytes briefly exposed to air, a process previously demonstrated to trigger ATP release from these cells. We show that exposing keratinocytes to air by removing media for 15 seconds causes a robust, long-lasting ATP release. This air-stimulated ATP release was increased in calcium differentiated cultures which showed a corresponding increase in connexin 43 mRNA, a major component of keratinocyte hemichannels. The known connexin hemichannel inhibitors 1-octanol and carbenoxolone both significantly reduced air-stimulated ATP release, as did two drugs traditionally used as ABC transporter inhibitors (glibenclamide and verapamil). These same 4 inhibitors also prevented an increase in the uptake of a connexin permeable dye induced by air exposure, confirming that connexin hemichannels are open during air-stimulated ATP release. In contrast, activity of the MDR1 ABC transporter was reduced by air exposure and the drugs that inhibited air-stimulated ATP release had differential effects on this transporter. These results indicate that air exposure elicits non-vesicular release of ATP from keratinocytes through connexin hemichannels and that drugs used to target connexin hemichannels and ABC transporters may cross-inhibit. Connexins represent a novel, peripheral target for the treatment of chronic pain and dermatological disease.


Quality-of-life effects of screening mammography in Norway.
Mammography screening may save women from dying of breast cancer, although it has not been shown to reduce all-cause mortality. Screening also leads to overdiagnosis and many false positive mammograms aggravating women's quality-of-life. Quality adjusted life years (QALY) analyses of mammography screening have so far, calculated life years gained assuming that all prevented breast cancer deaths translate into a reduction in all-cause mortality. We calculated net QALYs in two hypothesized cohorts of 100,000 Norwegian women; one screened biennially from age 50 to 69 years and one not screened. We followed both cohorts to age 85 years. We used EQ-5D and an alternative equity weighted QALY instrument to estimate utility losses. In the screening cohort, we assumed 20% false positive tests during screening, different levels of overdiagnosis (20-75%) and different levels of breast cancer mortality reduction (10-30%). We assumed that reductions in breast cancer mortality only to a limited extent (20, 50 or 80%), resulted in reductions in all-cause mortality. We calculated both undiscounted and discounted (4%) QALYs. Assuming that 50% of the reduction in breast cancer mortality translated to a reduction in all-cause mortality and using estimated levels of benefits and harms in modern screening programs (50-75% overdiagnosis and 10% reduction in breast cancer mortality), undiscounted equity weighted QALY loss varied from 437 to 875 per 100,000 women. Using the levels of benefit and harms as reported in 30-40 years old randomized trials (30% overdiagnosis and 15% reduction in breast cancer mortality), undiscounted equity weighted QALY gain was 535 per 100,000. Net QALY in modern mammography screening in Norway is negative. Results could also be representative for Sweden, Denmark, UK and the US.


Anticardiolipin antibodies in concurrent poststreptococcal glomerulonephritis and autoimmune hemolytic anemia: A case report.
We present a case of acute post-streptococcal glomerulonephritis (APSGN) with autoimmune hemolytic anemia (AIHA). Along with the classic findings of APSGN, the patient had a positive direct antiglobulin test and an anticardiolipin antibody without any typical clinical manifestations of antiphospholipid syndrome (APS). This case raises questions of the relationship between Streptococcus and the development of autoimmune hemolytic anemia in children. Our case highlights the possibility that the streptococcal infections in this patient might be responsible for her anemia, either in setting of underlying antiphospholipid antibodies, or in having triggered the development of pathogenic antibodies, which subsequently leads to the clinical evolution of hemolysis. It is presumed that in our case, the anticardiolipin antibody induced by streptococcal infection may play a direct role in the clinical evolution of AIHA.


[Evaluation of results after repeated radical surgery for differentiated thyroid cancer].
Total thyroidectomy is the treatment of choice in thyroid cancer. Unfortunately, the diagnosis is not always established before the first operation and the secondary radical surgery is necessary. The aim of this study was to analyze the effectiveness of secondary surgery in differentiated thyroid carcinoma. The randomized group of 768 patients with differentiated thyroid carcinoma, treated in Oncology Center Institute in Gilwice between 1986 and 1997 was analyzed. Among them 474 persons (56%) - 398 females and 76 males (median age 44 years) were operated more than once in different clinics in Poland. They were compared with 136 persons operated by less radical approach. Negative histobiological risk factors were noted in 4% to 33% of cases. Cervical lymph node metastases were observed in 18% of patients. Distant metastases occurred in 3% of cases. 373 persons were treated with 131(I). All patients administered hormonal therapy to suppress TSH. After secondary operation the rate of cancer foci was 28% (when radicalization was performed durning one year after primary surgery) and 56% when it was done later. This difference was statistically significant (p=0,0002). Locoregional recurrence was observed in 5% of patients. In the entire examined group the actual 5-year-survival was 98% and 10-year-survival was 92%. Complete remission was observed in 80% of patients. The incidence of multifocality in 1/3 of cases and the presence of neoplasm in the re-operated thyroid gland in 1/4 of cases have substantiated the decision for secondary surgery. The delay in radicalization surgery of more than 12 months has doubled the risk of multifocality in thyroid gland remnants. Our results have confirmed the necessity of the secondary surgery after nonradical primary thyroid resection in differentiated thyroid carcinoma.


Kupffer cell-expressed membrane-bound TNF mediates melphalan hepatotoxicity via activation of both TNF receptors.
Isolated hepatic perfusion of nonresectable liver cancer using the combination of TNF and melphalan can be associated with a treatment-related hepatotoxicity. We investigated whether, apart from TNF, also melphalan is cytotoxic in primary murine liver cells in vitro and investigated mediators, mode of cell death, and cell types involved. Melphalan induced a caspase-dependent apoptosis in hepatocytes, which was not seen in liver cell preparations depleted of Kupffer cells. Neutralization of TNF prevented melphalan-induced apoptosis and liver cells derived from mice genetically deficient in either TNFR 1 or 2, but not from lpr mice lacking a functional CD95 receptor, were completely resistant. Cell-cell contact between hepatocytes and Kupffer cells was required for apoptosis to occur. Melphalan increased membrane-bound but not secreted TNF in Kupffer cells and inhibited recombinant TNF-alpha converting enzyme in vitro. Melphalan induced also severe hepatotoxicity in the isolated recirculating perfused mouse liver from wild-type mice but not from TNFR 1 or 2 knockout mice. In conclusion, this study shows that melphalan elicits membrane TNF on Kupffer cells due to inhibition of TNF processing and thereby initiates apoptosis of hepatocytes via obligatory activation of both TNFRs. The identification of this novel mechanism allows a causal understanding of melphalan-induced hepatotoxicity.


Comparison of Phytochemical Composition, Antibacterial, and Antifungal Activities of Extracts from Three Organs of Pistacia lentiscus from Saudi Arabia.
This in vitro study focused on the antimicrobial activity of methanolic and aqueous extracts of three organs (stems, roots, and leaves) of Pistacia lentiscus against nine bacterial species, two fungal, and one yeast strain. A comparative study of the yield, high-performance liquid chromatography (HPLC) composition, and polyphenol content of the different extracts was conducted. The obtained data showed that the yield of the methanolic extracts (between 13% and 33.3%) was greater than that of the aqueous extracts (between 10% and 18%). The highest yield recorded was in the presence of the methanolic leaf extract, followed by the stem and root extracts. Methanolic extracts are richer in polyphenols than aqueous extracts. Indeed, the highest content was observed in the leaf methanolic extract (28.4 mg GAE/g), followed by the stem (2.96 mg GAE/g), and then the root (2.62 mg GAE/g). HPLC revealed variability in the chemical compositions of the different methanolic extracts. The leaf extract was richer in phenolic acids and flavonoids than the stem and root extracts. Regarding antimicrobial activity, it was concluded that the different methanolic extracts of lentisk were more active than the aqueous extracts. In addition, the different methanolic extracts exhibited antimicrobial activity against all tested strains, despite their morphology and Gram-staining. Indeed, the maximum inhibition zones and the minimum inhibitory concentrations for the bacterial strains sensitive to the different methanolic extracts of the mastic tree were in the range of 7 to 11 mm and 12.5 to 25 µg/mL, respectively. In addition, these extracts showed greater inhibitory activity against the tested fungal strains (A. niger and A. flavus) and yeast (C. albicans) than against the bacterial strains. These extracts can be used to treat antimicrobial infections and as food preservatives.


Optimized determination of calcium in grape juice, wines, and other alcoholic beverages by atomic absorption spectrometry.
This paper describes a study of the different methods of sample preparation for the determination of calcium in grape juice, wines, and other alcoholic beverages by flame atomic absorption spectrometry; results are also reported for the practical application of these methods to the analysis of commercial samples produced in Spain. The methods tested included dealcoholization, dry mineralization, and wet mineralization with heating by using different acids and/or mixtures of acids. The sensitivity, detection limit, accuracy, precision, and selectiviy of each method were established. Such research is necessary because of the better analytical indexes obtained after acid digestion of the sample, as recommended by the European Union, which advocates the direct method. In addition, although high-temperature mineralization with an HNO3-HCIO4 mixture gave the best analytical results, mineralization with nitric acid at 80 degrees C for 15 min gave the most satisfactory results in all cases, including those for wines with high levels of sugar and beverages with high alcoholic content. The results for table wines subjected to the latter treatment had an accuracy of 98.70-99.90%, a relative standard deviation of 2.46%, a detection limit of 19.0 microg/L, and a determination limit of 31.7 microg/L. The method was found to be sufficiently sensitive and selective. It was applied to the determination of Ca in grape juice, different types of wines, and beverages with high alcoholic content, all of which are produced and widely consumed in Spain. The values obtained for Ca were 90.00 +/- 20.40 mg/L in the grape juices, 82.30 +/- 23.80 mg/L in the white wines, 85.00 +/- 30.25 mg/L in the sweet wines, 84.92 +/- 23.11 mg/L in the red wines, 85.75 +/- 27.65 mg/L in the rosé wines, 9.51 +/- 6.65 mg/L in the brandies, 11.53 +/- 6.55 mg/L in the gin, 7.3 +/- 6.32 mg/L in the pacharán, and 8.41 +/- 4.85 mg/L in the anisettes. The method is therefore useful for routine analysis in the quality control of these beverages.


Narrative Retell Assessment Using "Frog" Stories: A Practice-Based Research Speech-Language Pathology Partnership Exploring Story Equivalency.
Narrative abilities are an important part of everyday conversation, playing a key role in academic settings, at home, and in social interactions. As narrative assessments are an effective method for identifying children falling below age expectations, it has been recommended they be included as a routine part of clinical language assessments. It is important that assessments meet the needs of clinicians and their practice. The current study is a practice-based research partnership, where research questions arose from a partnership with school-based speech-language pathologists (SLPs). Working together, SLPs and researchers evaluated a bespoke narrative retell assessment tool. The current study examined recall of events in two wordless picture books, in order to evaluate story equivalency and determine if the tool was appropriate for progress monitoring. These findings were then used to develop local norms. Two hundred sixty-three students were recruited across 12 schools in kindergarten, Grade 1, and Grade 2. Students completed the narrative retell task, retelling either One Frog Too Many or Frog Goes to Dinner, followed by answering 10 comprehension questions related to story events. A significant effect of story was found for both main and supporting events recalled, but not for total events recalled. Total events recalled were found to be predicted by grade only. An examination of percent events recalled revealed four main and four supporting events in each story that were potentially misclassified. Reanalysis following reallocation revealed no significant effect of story for main or supporting events recalled. Normative values for each grade were created using percentile ranks of total events recalled. Through a practice-based research partnership, researchers and clinicians worked collaboratively to evaluate a tool, adapt its use, and improve evidence-based practice in a manner that was appropriate and met the needs for the clinical context.


Successful treatment of propofol-related infusion syndrome in critically ill patient receiving low-dose propofol infusion: a case report.
Propofol is widely used to sedate agitated patients in intensive care units. However, it can cause a rare but fatal complication, propofol-related infusion syndrome (PRIS). The pathophysiology of PRIS is not clear, and there is no definitive diagnosis and treatment. We report a successfully treated case of PRIS in a critically ill patient receiving low-dose propofol infusion. A 59-year-old male patient complaining of sudden chest pain repeatedly collapsed in an ambulance and the emergency room, and veno-arterial extracorporeal membrane oxygenation was delivered. He was diagnosed with a total occluded left anterior descending coronary artery in coronary angiography. On day 20, he showed arrhythmia, increased creatinine kinase (CK), and increased CK-MB and troponin I, accompanied by unstable hemodynamic status despite high-dose vasopressors. He was administered propofol for 20 days at an average dose of 1.3 mg/kg/hr owing to issues with agitation and ventilator synchrony. We strongly suspected PRIS and immediately discontinued propofol infusion, and he was successfully treated with aggressive supportive care. PRIS can occur in patients administered propofol for a prolonged period at low doses. Thus, clinicians should use propofol with caution for PRIS and change to alternative sedatives for long-term sedation.


Prevalence of Middle Mesial Canals and Isthmi in the Mesial Root of Mandibular Molars: An In Vivo Cone-beam Computed Tomographic Study.
Many studies have investigated the morphology of the mandibular molar, but the prevalence of the middle mesial (MM) canal in the mesial root of the mandibular molar is still the subject of controversy. In addition, in previous literature, a true MM canal has not been clearly distinguished from an isthmus between the mesiobuccal and mesiolingual canals. Therefore, the objectives of this study were 2-fold: METHODS: Ninety limited field of view cone-beam computed tomographic scans were observed. One hundred twenty-two mature mandibular first and second molars with no previous root canal treatment, no root resorption, and intact crowns were retrospectively evaluated. Data regarding the sex, age, presence of MM canals, and number of root canals in the mesial root were recorded. Of the 122 teeth, 20 (16.4%) had true MM canals. The prevalence of MM canals was 26% in first molars and 8% in second molars (P < .05). The frequency of isthmi in the mesial roots was 64.7%. The frequency of isthmi was higher in second molars, but the difference was not statistically significant (P > .05). This study showed a high prevalence of mandibular molars with MM canals or isthmi. The detection and biomechanical cleaning of these areas during nonsurgical or surgical root canal treatment are critical.


Temperature dependence of ultraweak photon emission in fibroblastic differentiation after irradiation with artificial sunlight.
Yield of ultraweak photon emission in a cell culture model for biophotonic measurements using fibroblastic differentiation depended on the temperature of photonic measurement. The ultraweak photon emission of medium was significantly higher at 37 degrees C than at 25 degrees C and after UVB-irradiation this difference was even more pronounced. While with cells in the medium no temperature dependence could be determined in unirradiated samples, after UVB-irradiation of cells an increase of biophotonic emission was observed in postmitotic fibroblasts. While after several UVB exposures normal cells begin to absorb the ultraviolet light, cells from patients with the disease Xeroderma Pigmentosum loose this capacity. In view that fibroblasts play an essential role in skin aging, skin carcinogenesis and wound healing, the biophotonic model using the fibroblastic differentiation system provides to be a new and powerful non-invasive tool for the development of skin science.


A rare case of acute abdomen: torsionated ovarian myoma.
Ovarian leiomyoma is a rare ovarian tumor and also rare cause of acute abdomen. A 64 year old, postmenopausal woman applied to our clinic with severe acute abdominal pain. On abdominal examination, there were abdominal tenderness, defense and rebound. On ultrasonographic examination, we detected a 6 cm of pelvic mass. Because she had acute abdomen we performed laparotomy by midline incision and excised a 6cm ovarian mass on right ovary. The mass had been reported as ovarian leiomyoma on frozen section by pathology department.


Single Lipid Molecule Dynamics on Supported Lipid Bilayers with Membrane Curvature.
The plasma membrane is a highly compartmentalized, dynamic material and this organization is essential for a wide variety of cellular processes. Nanoscale domains allow proteins to organize for cell signaling, endo- and exocytosis, and other essential processes. Even in the absence of proteins, lipids have the ability to organize into domains as a result of a variety of chemical and physical interactions. One feature of membranes that affects lipid domain formation is membrane curvature. To directly test the role of curvature in lipid sorting, we measured the accumulation of two similar lipids, 1,2-Dihexadecanoyl-sn-glycero-3-phosphoethanolamine (DHPE) and hexadecanoic acid (HDA), using a supported lipid bilayer that was assembled over a nanopatterned surface to obtain regions of membrane curvature. Both lipids studied contain 16 carbon, saturated tails and a head group tag for fluorescence microscopy measurements. The accumulation of lipids at curvatures ranging from 28 nm to 55 nm radii was measured and fluorescein labeled DHPE accumulated more than fluorescein labeled HDA at regions of membrane curvature. We then tested whether single biotinylated DHPE molecules sense curvature using single particle tracking methods. Similar to groups of fluorescein labeled DHPE accumulating at curvature, the dynamics of single molecules of biotinylated DHPE was also affected by membrane curvature and highly confined motion was observed.


Patients' and dentists' perceptions of tele-dentistry at the time of COVID-19. A questionnaire-based study.
COVID-19 has had a significant impact on dentistry in unforeseen ways, including a substantial rise in the development and implementation of video consultations. The research aimed to investigate dentists' and patients' attitudes towards dental video consultations (tele-dentistry) and to identify potential ways to improve the experience. A cross-sectional, pre-post design, online survey was carried out with patients' and dentists' before and after video consultations. A total of 249 participants accessed the survey and 228 of them consented to take part in the study and answered the online questions. Participants' attitudes towards video consultations were assessed using a questionnaire constructed by a multidisciplinary team of periodontists and psychologists. The measure assessed the perceived efficacy of the video consultations on patients and the dental team. Video consultations were performed to risk assess, triage and manage remotely via a video link out at (deleted name of institution as double blinded peer review) via NHS England's Attend Anywhere platform. The majority of patients strongly agreed and were satisfied using tele-dentistry in the five domains which we explored: the ease, comprehensiveness and helpfulness of the video consultations and the anxiety and satisfaction levels of the patient. Dentists and students alike felt more confident and competent after having carried out a video consultation. The majority of clinicians found the tele-dentistry platform helpful and easy to perform. Just over 70% of patients strongly agreed that the video consultation ran smoothly and 75.7% strongly agreed that they were comfortable accessing the consultation from home rather than travelling in for the consultation. Just under 80% of patients stated that they would recommend the video consultation. This study shows that tele-dentistry may be a valid option to help service providers and dental patients, as it seems to be well accepted by both patients and dentists. JM to typesetter. Patients' and dentists' perceptions of Tele-Dentistry at the time of COVID-19. A questionnaire-based study. To our knowledge this is one of the first studies evaluates perceptions of patients and clinicians before and after a tele-dentistry encounter in and across different dental departments. The majority of survey participants expressed positive views towards tele-dentistry across all domains including ease and comprehensiveness of the video consultation, perceived helpfulness and anxiety and satisfaction of the patient. Dentists appear to be competent and confident to carry out these video consultations and find them to be helpful and easy to complete. As a result, we suggest readers adopt tele-dentistry in their daily activities to help patients and clinicians alike.


Changes in the rumen bacterial microbiome of cattle exposed to ponderosa pine needles.
Consumption of ponderosa pine needles, as well as needles and bark from a number of other trees, can cause abortions in cattle. The abortifacient compounds in these trees are labdane resin acids, including isocupressic acid and agathic acid. Previous research has demonstrated that cattle conditioned to pine needles metabolize the labdane resin acids more quickly than naïve cattle. The results from that study indicated that changes had occurred in the rumen of conditioned cattle. Therefore, in this study, the changes that occurred in the rumen bacterial microflora of cattle during exposure to ponderosa pine needles were evaluated. Cattle were dosed with ground pine needles twice daily for 7 d. Rumen samples were collected on d 0, 3, 7, and 14 (7 d after treatment stopped) and ruminal bacterial microbiome analyses were performed. There were 372 different genera of bacteria identified in the rumen samples. Principal coordinate analysis indicated that there was a significant difference in the rumen bacterial composition between the time points. There were 18 genera that increased in abundance from d 0 to d 7. Twenty three genera decreased in abundance from d 0 to d 7. The results from this study demonstrated that exposure of cattle to pine needles caused a clear shift in the rumen microbiome composition. In general, this shift lasted less than 1 wk post exposure, which indicates that any prophylactic treatment to manipulate the ruminal metabolism of the abortifacient compounds in pine needles would need to be continuously administered to maintain the necessary microbial composition in the rumen.


The use of 18-fluoro-dihydroxyphenylalanine and 18-fluorodeoxyglucose positron emission tomography scanning in the assessment of metaiodobenzylguanidine-negative phaeochromocytoma.
123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy scanning is commonly used in the imaging of phaeochromocytoma (and paraganglioma) to confirm the site of disease and whether any spread has occurred. However, 123I-MIBG imaging is negative in 15% of cases of benign phaeochromocytoma and around 50% of cases of malignant phaeochromocytoma. In recent years, positron emission tomography (PET) scanning using various different radiotracers has been shown to be a good alternative or supplementary investigation in phaeochromocytoma. We present the cases of four patients with symptoms and signs suggestive of phaeochromocytoma, but who had negative 123I-MIBG scans, and illustrate the usefulness of 18-fluoro-dihydroxyphenylalanine PET scanning in their assessment. In one of the patients, we illustrate how fluorodeoxyglucose PETscanning can provide useful information about the extent of malignant disease. These illustrative cases lend further support for the use of PET scanning in the assessment of phaeochromocytoma and suggest that it may have a particularly important role in the investigation of patients in whom 123I-MIBG scanning is negative.


Secular trends and associated factors of age at natural menopause in Taiwanese women.
Age at natural menopause (ANM) is considered an indicator for chronic disease and mortality risk in later life. Research suggests that ANM appears to vary across geographic regions and ethnicities. The aim of this study was to explore the secular trends and factors associated with ANM in Taiwanese women. We used data from three cross-sectional phases of the Nutrition and Health Survey in Taiwan. In all, 4,111 women aged 35 years and over were included. Information on ANM and sociodemographics, lifestyle, and health factors were collected using household questionnaires. A Cox proportional-hazards model was used to determine the association of ANM with relevant factors, and a life table method was used to estimate median ANM. Life table method estimated the median ANM to be 50 years. ANM was getting later for women born in younger cohorts (hazard ratio [HR] 0.87 per 10-year difference, 95% confidence interval [CI] 0.81-0.95). ANM was also later among women who achieved higher educational levels (HR 0.91 per one-category difference, 95% CI 0.86-0.96) and who had been married (HR 0.64, 95% CI 0.42-0.96). ANM occurred later for parous than for nulliparous women. Multivariable analysis found no significant associations of ANM with age at menarche, smoking, or alcohol drinking. The results suggest that women in the younger cohorts, with higher educational levels, and who are parous and married may have later ANM. The trend effect of secular time and educational levels on ANM may reflect the influences of socioeconomic/nutritional status in their childhood or throughout their lifetime.


Novel simulations to determine the impact of superficial perineal structures on vaginal delivery.
This study's aim was to determine whether the inclusion of superficial perineal structures in a finite-element simulation of vaginal delivery impacts the pubovisceral muscle and perineal body, two common sites of birth-related injury. The hypothesis, inferred from prevailing literature, was that these structures would have minimal influence (differences less than ±10%). Two models were made using the Visible Human Project's female cadaver to create a rigid, fixed pelvis, musculature held by spring attachments to that pelvis, and a rigid, ellipsoidal fetal head prescribed with an inferior displacement to simulate delivery. Injury site stretch ratios and fetal head and perineal body displacements and angles of progression were compared between the Omitted Model (which excluded the superficial perineal structures as is common practice) and the Included Model (which included them). Included Model stretch ratios were +107%, -9.84% and -14.6% compared to Omitted Model perineal body and right and left pubovisceral muscles, respectively. Included Model peak perineal body inferior displacement was +72.5% greater while similar anterior-posterior displacements took longer to reach. These results refute our hypothesis, suggesting superficial perineal structures impact simulations of vaginal delivery by inhibiting perineal body anterior-posterior displacement, which stretches and inferiorly displaces the perineal body.


Pattern formation in reverse filtration combustion.
Using a pore-network simulator we study pattern formation in reverse filtration combustion in porous media. The two-dimensional pore network includes all relevant pore-level mechanisms, including heat transfer through the pore space and the solid matrix, fluid and mass transfer through the pore space, and reaction kinetics of a solid fuel embedded in the pores. Both adiabatic and nonadiabatic cases are considered, the latter modeled with the inclusion of heat losses from the pore network to the ambient. The simulation results show the development of unstable, fingered patterns of the burned fuel, similar to previously reported in the literature in the related problem of reverse combustion in a Hele-Shaw cell. We study the sensitivity of the patterns obtained on a number of parameters, including the Peclet number. The results on finger spacing and finger width are analyzed in terms of a selection principle, similar to that used in the theory for unstable Laplacian growth.


Emissions and Exposures Associated with the Use of an Inconel Powder during Directed Energy Deposition Additive Manufacturing.
Additive manufacturing (AM) has been linked to potential exposure-related health risks, however, there is a paucity of sufficient research. This study aimed to supply information regarding emissions and exposure during directed energy deposition (DED) AM using inconel 718, with the main constituents being nickel, chromium, and cobalt. By using standardized occupational hygiene methods, the measurement strategy consisted of a combined approach, including powder characterization, particle emission monitoring, and personal exposure monitoring of AM operators. Powder characterization of virgin and used powder indicated no significant difference in particle size, shape, or elemental composition. Particle number emissions ranged between 102 and 105 p/cm3 for submicron particles (<1 µm in size). There was no significant difference in the particle emission rate between the three phases of AM or the two types of DED machines (p > 0.05). The particle emission rate for submicron particles peaked at 2.8 × 109 p/min. Metals of concern to human health were detected during the AM process but were considerably lower than the relevant exposure limits. This study confirms particle emissions, predominantly in the submicron range, above the background concentration during DED AM and, although insignificant in terms of potential health effects, AM operators are exposed to detectable concentrations of the metal constituents of inconel.


Influence of TMAO and urea on the structure of water studied by inelastic X-ray scattering.
We present a study on the influence of the naturally occurring organic osmolytes tri-methylamine N-oxide (TMAO) and urea on the bulk structure of water using X-ray Raman scattering spectroscopy. Addition of TMAO is known to stabilize proteins in otherwise destabilizing aqueous urea solutions. The experimental X-ray Raman scattering spectra change systematically with increasing solute concentration revealing different effects on the structure of water due to the presence of the two osmolytes. Although these effects are distinct for both molecular species, they have mutually compensating influences on the spectra of the ternary water-TMAO-urea mixtures. This compensation effect seen in the spectra vanishes only at the highest studied ternary concentration of 4 M : 4 M (TMAO : urea). Our experiment shows that the hydrogen-bonding structure of water remains rather intact in the presence of the aforementioned osmolytes if both of them are present.


Exploring the Relationship Between Substance Use and Allostatic Load in a Treatment/Research Cohort and in a US Probability Sample (NHANES 2009-2016).
Allostatic load, an operationalization for cumulative strain on physiology from adaptation (allostasis) to stress over a lifetime, can manifest as damage to cardiovascular, neuroendocrine, and metabolic systems. The concept of allostatic load may be particularly useful in research on substance-use disorders (SUDs) because SUD researchers have sought to better understand the relationship between chronic stressors and drug use. Theoretical models hold that SUDs can be conceptualized as a spiral toward a state of persistent allostasis (i.e., allostasis so persistent as to represent homeostasis at a new, unhealthy set point). Regardless of the extent to which those models are accurate, increased allostatic load could be a mechanism by which frequent drug administration increases risk for adverse outcomes. We conducted two secondary analyses to evaluate allostatic load in the context of drug use, including alcohol use, in a locally recruited sample with a high proportion of illicit substance use (N = 752) and in a nationally representative sample from the NHANES 2009-2016. We hypothesized that after controlling for age and other potential confounds, people with longer histories of drug use would have higher allostatic-load scores. Multiple regression was used to predict allostatic load from participants' drug-use histories while controlling for known confounds. In the locally recruited sample, we found that longer lifetime use of cocaine or opioids was related to increased allostatic load. In NHANES 2009-2016, we found few or no such associations. Lengthy histories of problematic non-medical substance use may facilitate more rapid increases in allostatic load than aging alone, and, together with findings from previous investigations, this finding suggests increased risk for chronic disease.


Small Au clusters oxidation: an ab initio study.
We have performed ab initio calculations in the Density Functional Theory framework on unsupported small gold clusters with size ranging from three to seven atoms. In our calculations we have introduced a single O2 molecule on different places around the cluster surface, and in both parallel and perpendicular position with respect to the cluster surface. We have found that the oxygen molecule bonds in-plane with the bidimensional Au cluster when the number of Au atoms is even, and it will be adsorbed off-plane if the number of Au atoms is odd. The latter case, despite not presenting a true chemical bonding, has great stability due to spin pairing and electrostatic interactions, and the structures will be distorted respect to the geometry of their pure Au cluster equivalents.


[Biochemical manifestations of the poisoning of larvae of Aedes aegypti (Insecta, Diptera) by the delta-endotoxin of Bacillus thuringiensis israelensis. I. Hemolymph carbohydrates].
The glycemia of 4th instar larvae of Aedes aegypti (Diptera Culicidae) was determined over a 30 min to 36 hrs period following their immersion in water containing 0.00-0.01-0.02-0.1-1.0 mg per liter of a 12,000 I. U. per mg preparation of the delta-endotoxin of Bacillus thuringiensis israelensis. Seven major carbohydrate fractions were separated in the haemolymph, among which glycogen, trehalose and glucose were identified; the most concentrated of the 4 remaining unknown fractions, exhibits a similar chromatographic behavior but different chemical properties than glucuronic acid. The glycogen fraction shows two large amplitude peaks at 1 hr 30 and 6 hrs with 0.1 mg/l, whereas with the 2 lower doses (0.01 and 0.02 mg/l) a first drop from 30 min to 1 hr is followed by a peaking at 12 hrs. The haemolymph trehalose concentrations of intoxicated larvae increase relatively to controls 2 hrs after incubation with the lower dose; by contrast, they decrease with the 2 higher doses. The glucosemia increases in all cases, but more markedly with the higher dose as soon as 1 hr following the treatment. A positive correlation was found over the whole treatment duration between the glucosemia nd the trehalosemia of control larvae. The regression slope of this relationship decreases with increasing toxin doses and turns to negative values with 0.1 and 1.0 mg/l. These observations suggest the hypothesis that a uncontrolled increase of trehalase activity develops according to the increasing stages of intoxication. This clearly differenciates the effects of the B. T. i toxin from those of parasites, such as Fungi, Sporozoans or Nematodes in Mosquitoes.


Takotsubo cardiomyopathy and arrhythmic risk: the dark side of the moon.
"Takotsubo" cardiomyopathy (TTC) is a clinical disorder usually triggered by intense emotional and/or physical stress, characterized by reversible severe localized left ventricular wall dyskinesia, transient changes of ST segment, without significant coronary artery stenoses, that can mimic acute myocardial infarction. Although TTC is well known to have a good mid- and long-term prognosis, arrhythmic risk is increasingly recognized and we could provide, in view of the available literature, a mean for a prognostic stratification and some practical suggestions for management of these "vulnerable" patients. Further studies with randomized trials will be needed to prove the optimal treatment of TTC. TTC, generally considered a benign syndrome, should be reconsidered as a clinical condition at high risk for lethal arrhythmias in a subpopulation with QTc > 500 msec in acute phase. The studies about arrhythmias and TTC are based on case reports. TTC may present with sudden cardiac death: this results in a probable underestimate of the real arrhythmic risk. TTC is one of the causes of acquired long QT syndrome and could be a trigger able to unmask latent silent or inapparent congenital long QT syndrome. All factors that can exacerbate QT prolongation should be promptly removed. In the case of marked bradycardia and/or TdP should be implant a temporary pacemaker. In most cases, due to the transient nature of the syndrome, it is reasonable to recommend only beta-blocker therapy at discharge, despite the absence of randomized trials. If there are high-risk factor for long QT syndrome (QTc post-TCM > 500 ms, prior syncope, previous cardiac arrests) thought should be given an indication to ICD implant.


An ecological study on the association between universal health service coverage index, health expenditures, and early childhood caries.
Universal health care (UHC) may assist families whose children are most prone to early childhood caries (ECC) in accessing dental treatment and prevention. The purpose of this study was to determine the association between UHC, health expenditure and the global prevalence of ECC. Health expenditure as percentage of gross domestic product, UHC service coverage index, and the percentage of 3-5-year-old children with ECC were compared among countries with various income levels using one-way analysis of variance (ANOVA). Three linear regression models were developed, and each was adjusted for the country income level with the prevalence of ECC in 3-5-year-old children being the dependent variable. In model 1, UHC service coverage index was the independent variable whereas in model 2, the independent variable was the health expenditure as percentage of GDP. Model 3 included both independent variables together. Regression coefficients (B), 95% confidence intervals (CIs), P values, and partial eta squared (ƞ2) as measure of effect size were calculated. Linear regression including both independent factors revealed that health expenditure as percentage of GDP (P < 0.0001) was significantly associated with the percentage of ECC in 3-5-year-old children while UHC service coverage index was not significantly associated with the prevalence of ECC (P = 0.05). Every 1% increase in GDP allocated to health expenditure was associated with a 3.7% lower percentage of children with ECC (B = - 3.71, 95% CI: - 5.51, - 1.91). UHC service coverage index was not associated with the percentage of children with ECC (B = 0.61, 95% CI: - 0.01, 1.23). The impact of health expenditure on the prevalence of ECC was stronger than that of UHC coverage on the prevalence of ECC (ƞ2 = 0.18 vs. 0.05). Higher expenditure on health care may be associated with lower prevalence of ECC and may be a more viable approach to reducing early childhood oral health disparities than UHC alone. The findings suggest that currently, UHC is weakly associated with lower global prevalence of ECC.


[Interactions between enterocytes and lymphocytes in the pathogenesis of celiac disease].
MHC antigens are positioned in the centre of the interactions between enterocytes and lymphocytes in the pathogenesis of coeliac disease. This disease is associated with the presence of specific alleles of MHC-class II genes. Class-II-gene products being present also on enterocytic membranes play an important role in the presentation of antigens and might lead in coeliac patients to an extraordinarily effective stimulation of CD4+ and/or CD8+ cells which induce damage to the intestinal epithelium by various mechanisms. Additionally so-called CD4-CD8-gamma/delta + lymphocytes might act cytotoxically on enterocytes. The typical HLA-haplotype, however, is found also in many healthy persons. Thus the presence of specific MHC molecules is not the only requirement for susceptibility to gliadins. Furthermore, a virus infection (cross reactivity with gliadins?) as an additional factor can not be considered to be sufficient for expression of coeliac disease. Results were presented demonstrating that gliadins affect undifferentiated enterocytes arguing for a role of additional enterocytic factors in the pathogenesis of the disorder. The findings suggest that gliadins interfere with late post-translational processes in the biosynthesis of sucrase-isomaltase. The integration of this effect into the pathogenetic mechanism of coeliac disease remains to be clarified.


Investigating the effects of a penetrating vessel occlusion with a multi-scale microvasculature model of the human cerebral cortex.
The effect of the microvasculature on observed clinical parameters, such as cerebral blood flow, is poorly understood. This is partly due to the gap between the vessels that can be individually imaged in humans and the microvasculature, meaning that mathematical models are required to understand the role of the microvasculature. As a result, a multi-scale model based on morphological data was developed here that is able to model large regions of the human microvasculature. From this model, a clear layering of flow (and 1-dimensional depth profiles) was observed within a voxel, with the flow in the microvasculature being driven predominantly by the geometry of the penetrating vessels. It also appears that the pressure and flow are decoupled, both in healthy vasculatures and in those where occlusions have occurred, again due to the topology of the penetrating vessels shunting flow between them. Occlusion of a penetrating arteriole resulted in a very high degree of overlap of blood pressure drop with experimentally observed cell death. However, drops in blood flow were far more widespread, providing additional support for the theory that pericyte controlled regulation on the capillary scale likely plays a large part in the perfusion of tissue post-occlusion.


Syringomycin action gene SYR2 is essential for sphingolipid 4-hydroxylation in Saccharomyces cerevisiae.
The Saccharomyces cerevisiae gene SYR2, necessary for growth inhibition by the cyclic lipodepsipeptide syringomycin E, is shown to be required for 4-hydroxylation of long chain bases in sphingolipid biosynthesis. Four lines of support for this conclusion are presented: (a) the predicted Syr2p shows sequence similarity to diiron-binding membrane enzymes involved in oxygen-dependent modifications of hydrocarbon substrates, (b) yeast strains carrying a disrupted SYR2 allele produced sphingoid long chain bases lacking the 4-hydroxyl group present in wild type strains, (c) 4-hydroxylase activity was increased in microsomes prepared from a SYR2 overexpression strain, and (d) the syringomycin E resistance phenotype of a syr2 mutant strain was suppressed when grown under conditions in which exogenous 4-hydroxysphingoid long chain bases were incorporated into sphingolipids. The syr2 strain produced wild type levels of sphingolipids, substantial levels of hydroxylated very long chain fatty acids, and the full complement of normal yeast sphingolipid head groups. These results show that the SYR2 gene is required for the 4-hydroxylation reaction of sphingolipid long chain bases, that this hydroxylation is not essential for growth, and that the 4-hydroxyl group of sphingolipids is necessary for syringomycin E action on yeast.


The new therapeutic choice of tranexamic acid solution in treatment of erythematotelangiectatic rosacea.
Erythematotelangiectatic rosasea is a common,chronic, relapsing disease characterized mainly by vascular components, for which many therapies may exist but with limited efficacy. We decided to test the efficacy of tranexamic acid when applied topically on the affected areas.,Tranexamic acid is an antifibrinolytic,thus we considered it could be effective at this type of rosacea. This is an unblinded study. We included 20 patients, having erythematotelangiectatic rosacea. All patients were women between 27 and 65 years-old. We divided the patients in two groups,the first group was treated only with tranexamic acid solution (Transamin inj/sol 500 mg/5 mL) infused wet dressing for 20 minutes, and the second group was treated with microneedling simultaneously with tranexamic acid solution topical application followed by tranexamic acid solution infused dressing therapy,every 15 days for four sessions. The improvement assecion was outlined according to the Investigator Global Assessment of Rosacea Severity Score (IGA-RSS) and the use of clinical photos and dermoscopy. All patients were improved in the end of the therapy. There was statistically significant improvement, 2 units IGA-RSS in the first group, whereas 3 units IGA-RSS in the second group. The improvement lasted more than four months. The tolerability of the use of tranexamic acid was also asessed. According to our results a new really promising simple, safe and cheap treatment option targeting mainly to the vascular net and the erythema of rosacea is proposed.


FRET-Modulated Multihybrid Nanoparticles for Brightness-Equalized Single-Wavelength Barcoding.
Semiconductor quantum dots (QDs) are the most versatile fluorophores for Förster resonance energy transfer (FRET) because they can function as both donors and acceptors for a multitude of fluorophores. However, a complete understanding of multidonor-multiacceptor FRET networks on QDs and their full employment into advanced fluorescence sensing and imaging have not been accomplished. Here, we provide a holistic photophysical analysis of such multidonor-QD-multiacceptor FRET systems using time-resolved and steady-state photoluminescence (PL) spectroscopy and Monte Carlo simulations. Multiple terbium complex (Tb) donors (1-191 units) and Cy5.5 dye acceptors (1-60 units) were attached to a central QD, and the entire range of combinations of FRET pathways was investigated by Tb, QD, and Cy5.5 PL. Experimental and simulation results were in excellent agreement and could disentangle the distinct contributions of hetero-FRET, homo-FRET, and dye dimerization. The FRET efficiency was independent of the number of Tb donors and dependent on the number of Cy5.5 acceptors, which could be used to independently adapt the PL intensity by the number of Tb donors and the PL lifetime by the number of Cy5.5 acceptors. We used this unique tuning capability to prepare Tb-QD-Cy5.5 conjugates with distinct QD PL lifetimes but similar QD PL intensities. These brightness-equalized multihybrid FRET nanoparticles were applied to optical barcoding via three time-gated PL intensity detection windows, which resulted in simple RGB ratios. Direct applicability was demonstrated by an efficient RGB distinction of different nanoparticle-encoded microbeads within the same field of view with both single-wavelength excitation and detection on a standard fluorescence microscope.


Comparison of retrograde intramedullary nailing and bridge plating in the treatment of extra-articular fractures of the distal femur.
The aim of this study was to compare retrograde intramedullary nailing (RIMN) and bridge plating for the treatment of extra-articular distal femur fractures. The study retrospectively examined 15 patients (13 males and 2 females; mean age: 36 years, range: 17 to 55 years) who underwent bridge plating and 13 patients (11 males and 2 females; mean age: 31.1 years, range: 17 to 49 years) who underwent RIMN for the treatment of extra-articular distal femur fractures between 2007 and 2012. Functional results were evaluated using the Sanders criteria. The mean follow-up time was 31.3 (range: 20 to 46) months and 26.7 (range: 18 to 62) months in the plate and the nail groups, respectively. Mean duration until union was 25.7 (range: 12 to 72) weeks in the plate group and 22.3 (range: 12 to 52) weeks in the nail group. Nonunion was observed in 2 patients in the plate group and in 1 in the nail group, delayed union in 3 patients in the plate and 2 in the nail groups, malalignment (>10°) in 2 patients in the plate group and 1 in the nail group and implant failure in 1 patient in the plate group. Excellent/good functional results were obtained in 12 and 10 patients in the plate and the nail groups, respectively. No significant difference was found between the groups in terms of duration of union, complications and functional results (p>0.05). Bridge plating and RIMN have similar results in the treatment of extra-articular distal femur fractures. Both methods can be applied to all fractures, with the exception of Gustilo-Anderson Type 3B and C open fractures.


Gonadotropin-releasing hormone-1 neuronal activity is independent of cyclic nucleotide-gated channels.
Pulsatile release of GnRH-1 is essential for secretion of gonadotropin hormones. The frequency of GnRH-1 pulses is regulated during the reproductive cycle by numerous neurotransmitters. Cyclic nucleotide-gated (CNG) channels have been proposed as a mechanism to integrate the cAMP signal evoked by many neurotransmitters. This study reports the expression of the CNGA2 subunit in GnRH-1 neurons obtained from mouse nasal explants and shows the ability of GnRH-1 neurons to increase their activity in response to forskolin (activator of adenylyl cyclases), or 3-isobutyl-1-methylxanthine (inhibitor of phosphodiesterases) even after removal of gamma-aminobutyric acid (A)-ergic input. Next, the endogenous activity of adenylyl cyclases was evaluated as a component of the oscillatory mechanism of GnRH-1 neurons. Inhibition of endogenous activity of adenylyl cyclases did not alter GnRH-1 activity. The potential involvement of CNGA2 subunit in basal or induced activity was tested on GnRH-1 neurons obtained from CNGA2-deficient mice. Without up-regulation of CNGA1 or CNGA3, the absence of functional CNGA2 did not alter either the endogenous GnRH-1 neuronal activity or the response to forskolin, negating CNG channels from cAMP-sensitive mechanisms leading to changes in GnRH-1 neuronal activity. In addition, the potential role of CNGA2 subunit in the synchronization of calcium oscillations previously described was evaluated in GnRH-1 neurons from CNGA2-deficient explants. Synchronized calcium oscillations persisted in CNGA2-deficient GnRH-1 neurons. Taken together, these results indicate that CNGA2 channels are not necessary for either the response of GnRH-1 neurons to cAMP increases or the basal rhythmic activity of GnRH-1 neurons.


Sterol requirement of Mycoplasma capricolum.
Mycoplasmas require an external source of sterol for growth. For Mycoplasma capricolum this requirement is met not only by cholesterol but also by the methylcholestane derivatives lanosterol, cycloartenol, 4,4-dimethylcholesterol, and 4beta-methylcholestanol. Cholesteryl methyl ether and 3alpha-methylcholestanol serve equally well as sterol supplements. None of the growth-supporting sterol derivatives tested was metabolically modified. The unusual acceptance of diverse cholestane derivatives by a mycoplasma species contrasts with the structural attributes thought to be necessary for sterol function in eukaryotic membranes.


Targeting the vascular endothelial growth factor pathway in the treatment of human malignancy.
Over 30 years ago, it was proposed that blocking new blood vessel formation would significantly inhibit solid tumor growth and hence, limit cancer progression. Efforts guided by this philosophy have resulted in a better understanding of the molecular basis of tumor angiogenesis. The first successful therapeutic to emerge from this work, an antibody (bevacizumab) targeting the vascular endothelial growth factor (VEGF), was recently approved for the treatment of colorectal cancer. Additional positive clinical data with bevacizumab in the treatment of breast and lung carcinoma have also been reported. These clinical achievements have validated the approach of anti-angiogenesis therapy for cancer and provided further confirmation for antibodies as a therapeutic class in this disease. Nevertheless, important unanswered questions with regard to preclinical and clinical results of VEGF pathway inhibitors remain. For example, preclinical models with a number of VEGF pathway inhibitors suggest that these agents would have significant clinical activity on their own; yet, clinical activity in patients with bevacizumab or other VEGF pathway inhibitors as monotherapy have been disappointing. Moreover, while bevacizumab is approved for the treatment of colorectal cancer in combination with cytotoxics, the mechanism for the benefits of this combination are still poorly understood, with a number of viable mechanisms under active experimental evaluation. The 3-8-month survival benefit in colorectal cancer patients treated with bevacizumab is a positive step forward. However, improving our understanding of the mechanism for these effects, as well as the mechanism underlying the inability as yet to achieve greater effects, is needed in order to follow up on the positive clinical results with improved strategies. This review discusses the experimental results surrounding the current status of our understanding of the mechanism of action of VEGF signaling inhibitors, and the potential for utilizing these agents in the future so that clinical benefits will be measured in years rather than months.


All-Endoscopic Modified Krackow Suture for Proximal Hamstring Repair.
Surgical repair of proximal hamstring injuries can relieve pain and restore lower extremity function in active individuals. Whereas traditional surgical techniques are performed via an open approach, more recent endoscopic proximal hamstring repair techniques have proven safe, effective, and potentially associated with fewer complications than open repair. One theorized disadvantage of existing endoscopic techniques is reduced security at the suture-tendon interface, as compared to open surgery, during which a running suture technique, such as a Krackow stitch, may be employed. In this article, we present a technique for increasing suture purchase by performing an all-endoscopic, running, locking stitch during proximal hamstring repair.


Cardiovascular and renal multimorbidity increase risk of atrial fibrillation in the PREVEND cohort.
Atrial fibrillation (AF) is a condition that occurs in the presence of comorbidities. With the accumulation of comorbidities (multimorbidity), some combinations may more often occur together than others. Information on the impact of clustering of these on incident AF is sparse. We aimed to investigate clustering of cardiovascular and renal comorbidities and study the association between comorbidity clusters and incident AF. We used the community-based Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort in which 8592 individuals participated. Latent class analysis was performed to assess clustering of 10 cardiovascular and renal comorbidities. We excluded individuals with prior AF or missing ECG data, leaving 8265 individuals for analysis (mean age 48.9±12.6 years, 50.2% women). During 9.2±2.1 years of follow-up, 251 individuals (3.0%) developed AF. A model with three clusters was the optimal model, with one cluster being young (44.5±10.8 years) and healthy, carrying a low (1.0%) risk of incident AF; one cluster being older (63.0±8.4 years) and multimorbid, carrying a high (16.2%) risk of incident AF and a third middle-aged (57.0±11.3 years), obese and hypertensive cluster carrying an intermediate risk (5.9%) of incident AF. While the prevalence of the comorbidities differed between classes, no clear combination(s) of comorbidities was observed within the classes. We identified three clusters of comorbidities in individuals in the community-based PREVEND cohort. The three clusters contained different amount of comorbidities carrying different risks of incident AF. However, there were no differences between the clusters regarding specific combination(s) of comorbidities.


Monte Carlo simulations of the phase separation of a copolymer blend in a thin film.
Monte Carlo simulations were carried out to study the phase separation of a copolymer blend comprising an alternating copolymer and/or block copolymer in a thin film, and a phase diagram was constructed with a series of composed recipes. The effects of composition and segregation strength on phase separation were discussed in detail. The chain conformation of the block copolymer and alternating copolymer were investigated with changes of the segregation strength. Our simulations revealed that the segment distribution along the copolymer chain and the segregation strength between coarse-grained beads are two important parameters controlling phase separation and chain conformation in thin films of a copolymer blend. A well-controlled phase separation in the copolymer blend can be used to fabricate novel nanostructures.


Accetability of orbital prostheses.
This study was made to determine if those patients apparently dissatisfied with an orbital prosthesis might accept an eye patch more readily. The study included 27 patients who were seen during the past 8 years. A total of 60 orbital and eye patch proshteses were prepared for the patients. Eighteen patients responded to the questionnaire. Twelve of these patients are presently wearing their prostheses, and five of them are not. Reasons given by the patients for not using their prostheses were discomfort, lack of retention, skin irritation due to daily application and removal of the adhesive, change in defect, ill-fitting prostheses, and surgical reconstruction of the site. The study shows that given a choice, 67% of the patients would prefer the orbital prosthesis. Seventy-five percent of the patients who had an eye patch would prefer an orbital prosthesis.


Wider than Thought Phylogenetic Occurrence of Apicortin, A Characteristic Protein of Apicomplexan Parasites.
Apicomplexan parasites cause serious illnesses, including malaria, in humans and domestic animals. The presence of apicortins is predominantly characteristic of this phylum. All the apicomplexan species sequenced contain an apicortin which unites two conserved domains: DCX and partial p25alpha. This paper identifies novel apicortin orthologs in silico and corrects in several cases the erroneous sequences of hypothetical apicortin proteins of Cryptosporidium, Eimeria, and Theileria genera published in databases. Plasmodium apicortins, except from Plasmodium gallinaceum, differ significantly from the other apicomplexan apicortins. The feature of this ortholog suggests that only orthologs of Plasmodiums hosted by mammals altered significantly. The free-living Chromerida, Chromera velia, and Vitrella brassicaformis, contain three paralogs. Their apicomplexan-type and nonapicomplexan-type apicortins might be "outparalogs." The fungal ortholog, Rozella allomycis, found at protein level, and the algal Nitella mirabilis, found as Transcriptome Shotgun Assembly (TSA), are similar to the known Opisthokont (Trichoplax adhaerens, Spizellomyces punctatus) and Viridiplantae (Nicotiana tabacum) ones, since they do not contain the long, unstructured N-terminal part present in apicomplexan apicortins. A few eumetazoan animals possess apicortin-like (partial) sequences at TSA level, which may be either contaminations or the result of horizontal gene transfer; in some cases the contamination has been proved.


[Light response process and simulation of Dendrocalamopsis oldhami in the process of gradual water loss.]
The photosynthesis response of the leaves of 2-year-old potted Dendrocalamopsis oldhami seedlings under continuous and multistage soil moisture was measured and analyzed by using a porta-ble photosynthetic system (Li-6400) during the natural water consumption process from artificial watering to saturated soil water. The results showed that there was less obvious photoinhibition in leaves of D. oldhami grown in the region where the relative soil water content (SRWC) was from 53.5% to 95.6%. There was a higher net photosynthetic rate in relative water deficit environment with the relative soil water content from 53.5% to 69.6%. When SRWC was below 33.6%, there was a significant photoinhibition. When the relative soil water changed, the Pn max value simulated by rectangular hyperbola model was much higher than measured value. The simulated light saturation point (LSP) value fitted by the rectangular hyperbola model, the non-rectangular hyperbola model and the exponential model was much lower than the measured value, and the simulation of the light-response curve under extreme water shortage conditions had larger differences between the fitted values and the observed data. Both the stomatal limitation value (Ls) and water use efficiency (WUEinst) showed a similar response process as the relative soil water decreased. Both of them increased first and then decreased, with the maximum value appeared in the range of 53.5%≤SRWC≤69.6%. Such a result showed a similarity and representative with the Pn max of photosynthesis light-response processes under changing soil moisture. The optimal humidity management range of SRWC for normal photosynthesis in leaves of D. oldhami was from 53.5% to 69.6%. In addition, it had good adaptability to higher soil water content (69.6%≤SRWC≤95.6%). Rectangular hyperbola modified model could well simulate the light-response of photosynthesis under different soil water conditions (23.1%≤SRWC≤95.6%), while the other three models had their own limitations.


Using the Random Forest for Identifying Key Physicochemical Properties of Amino Acids to Discriminate Anticancer and Non-Anticancer Peptides.
Anticancer peptides (ACPs) represent a promising new therapeutic approach in cancer treatment. They can target cancer cells without affecting healthy tissues or altering normal physiological functions. Machine learning algorithms have increasingly been utilized for predicting peptide sequences with potential ACP effects. This study analyzed four benchmark datasets based on a well-established random forest (RF) algorithm. The peptide sequences were converted into 566 physicochemical features extracted from the amino acid index (AAindex) library, which were then subjected to feature selection using four methods: light gradient-boosting machine (LGBM), analysis of variance (ANOVA), chi-squared test (Chi2), and mutual information (MI). Presenting and merging the identified features using Venn diagrams, 19 key amino acid physicochemical properties were identified that can be used to predict the likelihood of a peptide sequence functioning as an ACP. The results were quantified by performance evaluation metrics to determine the accuracy of predictions. This study aims to enhance the efficiency of designing peptide sequences for cancer treatment.


Requirements of New Vaccines against Novel Influenza Viruses.
The currently available influenza vaccines were developed in the 1930s through the 1960s using technologies that were state-of-the art for the times. Decades of advancement in virology and immunology have provided the tools for making better vaccines against influenza virus. Among young children, live attenuated vaccine had significantly better efficacy than inactivated vaccine. An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective, safe vaccine for children 12 to 59 months of age who do not have a history of asthma or wheezing. Otherwise, MF59 adjuvanted influenza vaccine, ATIV was well tolerated in healthy young children and elderly after each of 3 doses and induced greater, longer-lasting, and broader immune responses than a nonadjuvanted trivalent inactivated influenza vaccine, TIV. The enhanced immunogenicity of the adjuvanted vaccine was most evident in very young children and for the B vaccine strain. In case of AS03 ATIV, the safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza. A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail. In conclusion, current improved influenza vaccines are; in the problem target groups are children aged 6-24 months and people over 65 years old of age. Only ATIV has shown significantly greater efficacy than TIV, and its safe.


Potential Mechanisms of Hematological Adverse Drug Reactions in Patients Receiving Clozapine in Combination With Proton Pump Inhibitors.
Clozapine is a second-generation antipsychotic which has proven efficacy in treating the symptoms of schizophrenia. Although clozapine therapy is associated with a number of adverse drug reactions, it is frequently used. One of the most common adverse drug reactions is gastroesophageal reflux disease which is an indication for treatment with proton pump inhibitors (PPIs). Coadministration of clozapine and PPIs increases the risk of hematological adverse drug reactions, including neutropenia and agranulocytosis. The mechanism in idiosyncratic agranulocytosis is not dose related and involves either a direct toxic or an immune-allergic effect. It is suspected that the clozapine metabolites nitrenium ion and N-desmethylclozapine may cause apoptosis or impair growth of granulocytes. Formation of N-desmethylclozapine is correlated with activity of the cytochrome P450 enzymes 1A2 and 3A4 (CYP1A2 and CYP3A4). Nitrenium ion is produced by the flavin-containing monooxygenase system of leukocytes. A drug interaction between clozapine and a PPI is a consequence of the induction of common metabolic pathways either by the PPI or clozapine. Findings to date suggest that indirect induction of flavin-containing monooxygenase by omeprazole through the aryl hydrocarbon receptor increases the expression of the enzyme mRNA and in the long term may cause the increase in activity. Moreover, induction of CYP1A2, especially by omeprazole and lansoprazole, may increase the serum concentration of N-desmethylclozapine, which can accumulate in lymphocytes and may achieve toxic levels. Another hypothesis that may explain hematological adverse drug reactions is competitive inhibition of CYP2C19, which may contribute to increased serum concentrations of toxic metabolites.


Treatment design, health outcomes, and demographic categories in the literature on minimum wages and health.
This literature review analyzes studies from the US, Canada, the UK, and Europe from inception to April 1, 2021 and focuses on treatment designs, health outcomes, demographic categories and data issues. Study designs are classified as treatment-effect-on-the-treated (7 studies), intent-to-treat (37), and what may be called possible-effects-on-anyone (10). Treatment-effects-on-the-treated designs are best for addressing the longstanding question: does income affect health or vice versa? I argue that they are also better for estimating the overall effect of minimum wages on health. Health outcomes are grouped into seven broad categories, such as overall physiological health and behavior, and 33 narrow categories, such as self-rated health and smoking. Demographic categories include gender, race/ethnicity, and age. The preponderance of evidence suggests that studies relying on the treatment-effect-on-the-treated and possible-effects-on-anyone designs find minimum wages improve health; there is no preponderance of evidence for overall health within intent-to-treat designs. With respect to specific health outcomes and demographic categories, there is no preponderance of evidence, except for improving infant and child health. One data issue concerns whether either intent-to-treat or possible-effects-on-everyone studies are reliable given that likely more than 70 % of people in their samples earn substantially above minimum wages thereby favoring the null hypothesis. Treatment-effect-on-the-treated designs are likely the best designs, and findings are largely consistent in showing that minimum wages improve some measures of health, for example, financial anxiety.


Role of quorum sensing and antimicrobial component production by Serratia plymuthica in formation of biofilms, including mixed biofilms with Escherichia coli.
We have previously characterized the N-acyl-l-homoserine lactone-based quorum-sensing system of the biofilm isolate Serratia plymuthica RVH1. Here we investigated the role of quorum sensing and of quorum-sensing-dependent production of an antimicrobial compound (AC) on biofilm formation by RVH1 and on the cocultivation of RVH1 and Escherichia coli in planktonic cultures or in biofilms. Biofilm formation of S. plymuthica was not affected by the knockout of splI or splR, the S. plymuthica homologs of the luxI or luxR quorum-sensing gene, respectively, or by the knockout of AC production. E. coli grew well in mixed broth culture with RVH1 until the latter reached 8.5 to 9.5 log CFU/ml, after which the E. coli colony counts steeply declined. In comparison, only a very small decline occurred in cocultures with the S. plymuthica AC-deficient and splI mutants. Complementation with exogenous N-hexanoyl-l-homoserine lactone rescued the wild-type phenotype of the splI mutant. The splR knockout mutant also induced a steep decline of E. coli, consistent with its proposed function as a repressor of quorum-sensing-regulated genes. The numbers of E. coli in 3-day-old mixed biofilms followed a similar pattern, being higher with S. plymuthica deficient in SplI or AC production than with wild-type S. plymuthica, the splR mutant, or the splI mutant in the presence of N-hexanoyl-l-homoserine lactone. Confocal laser scanning microscopic analysis of mixed biofilms established with strains producing different fluorescent proteins showed that E. coli microcolonies were less developed in the presence of RVH1 than in the presence of the AC-deficient mutant.


Stenosing Tenosynovitis of the Flexor Hallucis Longus Tendon Associated with the Plantar Capsular Accessory Ossicle at the Interphalangeal Joint of the Great Toe.
This report presents a case of stenosing tenosynovitis of the flexor hallucis longus tendon associated with the plantar capsular accessory ossicle at the interphalangeal joint of the great toe, which was confirmed by intraoperative observation and was successfully treated with surgical resection of the ossicle. As the plantar capsular accessory ossicle was not visible radiographically due to the lack of ossification, ultrasonography was helpful for diagnosing this disorder.


Differences in lumbar spine load due to posture and upper limb external load.
As the lumbar region of the spine is particularly predisposed to musculoskeletal disorders, the aim of this article was to assess lumbar spine load on the basis of an accurate model of this part of the body. The model was developed with the finite element method and the energy criterion for optimising muscle work. Computer calculations confirmed that stresses and compression forces in intervertebral discs increased with an increase in the load force and that they were significantly larger in the bent forwards posture than in the erect posture. This result clearly shows that lifting light objects and the erect posture are important elements in minimising spine load.


Inhibition of bombesin-stimulated gastrin release from isolated canine G cells by bombesin antagonists.
This study investigated the effects of two putative bombesin antagonists, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P and [Leu13-psi-CH2NH-Leu14]bombesin, on bombesin-stimulated gastrin release from isolated canine G cells following short-term culture. Canine antral tissue was dispersed by sequential collagenase and EDTA treatment, and counterflow elutriation was used to enrich for G cells. Plates were seeded with 2 x 10(6) cells/mL in each well and cultured for 2 days prior to testing. Gastrin-containing and somatostatin-containing cells were identified by immunocytochemistry using the biotin-avidin-peroxidase method and accounted for 8.5 and 1%, respectively, of adhered cells. Basal gastrin secretion was 1.91 +/- 0.48% of total cell content. After a 2-h incubation period, bombesin (0.01-100 pM) stimulated gastrin release in a concentration-dependent fashion. The substance P analog, at a concentration of 1 microM, modestly inhibited bombesin-stimulated gastrin release from canine G cells. This analog also produced weak stimulation of basal gastrin release. In contrast, the bombesin analog, at a concentration of 1 microM, did not affect basal gastrin secretion. The bombesin analog completely blocked bombesin-stimulated gastrin release from 0.01 to 1 pM and produced greater than 50% inhibition at higher doses. The ability of the bombesin analog to directly inhibit bombesin-stimulated gastrin release from cultured canine G cells underscores its usefulness in studies involving the role of bombesin and its mammalian counterpart, gastrin-releasing peptide, in the control of gastrin cell function.


Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex.
The infrequent occurrence of septic shock in patients with inherited deficiencies of the terminal complement components experiencing meningococcal disease led us to suspect that the terminal complement complex is involved in vascular leakage. To this end, the permeabilizing effect of the cytolytically inactive soluble terminal complement complex (SC5b-9) was tested in a Transwell system measuring the amount of fluorescein-labeled BSA (FITC-BSA) leaked through a monolayer of endothelial cells. The complex caused increased permeability to FITC-BSA after 15 min as opposed to the prompt response to bradykinin (BK). The effect of SC5b-9 was partially reduced by HOE-140 or CV-3988, two selective antagonists of BK B2 and platelet-activating factor receptors, respectively, and was completely neutralized by the mixture of the two antagonists. Also, DX-88, a specific inhibitor of kallikrein, partially inhibited the activity of SC5b-9. The permeabilizing factor(s) released after 30 min of incubation of endothelial cells with SC5b-9 caused a prompt leakage of albumin like BK. Intravital microscopy confirmed both the extravasation of circulating FITC-BSA across mesenteric microvessels 15 min after topical application of SC5b-9 and the complete neutralization by the mixture of HOE-140 and CV-3988. SC5b-9 induced opening of interendothelial junctions in mesenteric endothelium documented by transmission electron microscopy.