Total Synthesis and Biological Mode of Action of WAP-8294A2: A Menaquinone-Targeting Antibiotic.
WAP-8294A2 (lotilibcin, 1) is a potent antibiotic with superior in vivo efficacy to vancomycin against methicillin-resistant Staphylococcus aureus (MRSA). Despite the great medical importance, its molecular mode of action remains unknown. Here we report the total synthesis of complex macrocyclic peptide 1 comprised of 12 amino acids with a β-hydroxy fatty-acid chain, and its deoxy analogue 2. A full solid-phase synthesis of 1 and 2 enabled their rapid assembly and the first detailed investigation of their functions. Compounds 1 and 2 were equipotent against various strains of Gram-positive bacteria including MRSA. We present evidence that the antimicrobial activities of 1 and 2 are due to lysis of the bacterial membrane, and their membrane-disrupting effects depend on the presence of menaquinone, an essential factor for the bacterial respiratory chain. The established synthetic routes and the menaquinone-targeting mechanisms provide valuable information for designing and developing new antibiotics based on their structures.


Effects of Some Lamiaceae Species on NO Production and Cell Injury in Hydrogen Peroxide-induced Stress.
Nitric oxide (NO) is a key mediator that plays an important role in pathogenesis of various chronic diseases like Alzheimer's disease and Parkinson's disease. Additionally, there is a great attitude for finding natural compounds, which could control and inhibit NO production in pathological conditions. Therefore, we were encouraged to investigate the effects of some Lamiaceae species on NO production and cell injury during oxidative stress in PC12 cells. In this study, cell death determined by MTT assay and NO levels were evaluated using Griess assay. PC12 cells were exposed to total metanolic extracts of three Scutellaria and one Nepeta species. The results revealed that Nepeta laxiflora (N. laxiflora) could protect PC12 cells from hydrogen proxide-induced oxidative stress and all of the plants inhibited NO production in that condition except Scutellaria tournefortii (Sc. tournefortii). In addition, Scutellaria multicaulis (Sc. multicaulis) was meanwhile subjected to fractionation using different organic solvents. The dichloromethan and ethyl acetate fractions of Sc. multicaulis could protect PC12 cells from oxidative stress injury. However, NO production was restrained by the hexane and dichloromethane fractions. Considering the results, N. laxiflora, Scutellaria nepetifolia (Sc. nepetifolia), and Sc. multicaulis are good candidates for further investigations in neuroprotection and anti-inflammation studies.


[Statistical survey of malignant skin tumors during the first five years of cases treated at the Dermatological Clinic of Shimane Medical University Hospital].
A statistical survey of malignant skin tumors has been carried out involving the outpatients seen at the Dermatological Clinic of Shimane Medical University Hospital during the period between October, 1979 and October, 1984. Out of 9,702 patients seen, 51 were found to have a malignant skin tumor or, statistically, 0.53% of all patients. The number and type of the malignant skin tumor were as follows: squamous cell carcinoma, 16; basal cell epithelioma, 7; Bowen's disease, 6; Paget's disease, 1; a metastatic carcinoma of the skin, 4; a malignant melanoma, 5; a malignant lymphoma, 10; leukemia, 1 and a multicentric reticulohistiocytoma, 1. reticulohistiocytoma, 1.


Ionic liquids as unique solvents in one-pot synthesis of 4-(n,2,2,2-tetranitroethylamino)-3-R-furazans.
An efficient two-step one-pot protocol for the synthesis of N-nitrated trinitroethylamino furazans in an ionic liquid has been developed involving the condensation of aminofurazans with trinitroethanol and the N-nitration of an intermediate Mannich base. Trinitroethylnitramino derivatives have been synthesized and characterized by multinuclear NMR spectroscopy and X-ray crystallography. A role of the N,2,2,2-tetranitroethylamino group for stabilization of the high-density crystal-packing motif is described. The performance calculations gave detonation pressures and velocities for the furazan derivatives in a range of about 31-36 GPa and 8330-8745 ms(-1), respectively, which makes them competitive energetic materials. Furthermore, due to the positive oxygen balance, the compounds could be potential oxidizers for energetic formulations.


Detection of spliced mRNA from human bocavirus 1 in clinical samples from children with respiratory tract infections.
Human bocavirus 1 (HBoV1) is a parvovirus associated with respiratory tract infections (RTIs) in children, but a causal relation has not yet been confirmed. To develop a qualitative reverse transcription PCR to detect spliced mRNA from HBoV1 and to determine whether HBoV1 mRNA correlated better with RTIs than did HBoV1 DNA, we used samples from HBoV1 DNA-positive children, with and without RTIs, to evaluate the test. A real-time reverse transcription PCR, targeting 2 alternatively spliced mRNAs, was developed. HBoV1 mRNA was detected in nasopharyngeal aspirates from 33 (25%) of 133 children with RTIs but in none of 28 controls (p<0.001). The analytical sensitivity and specificity of the test were good. Our data support the hypothesis that HBoV1 may cause RTIs, and we propose that HBoV1 mRNA could be used with benefit, instead of HBoV1 DNA, as a diagnostic target.


Asymptomatic bacteriuria in elderly humans is associated with increased levels of circulating TNF receptors and elevated numbers of neutrophils.
Low-grade inflammatory activity is strongly associated with age-associated diseases such as atherosclerosis, dementia, type-2 diabetes, sarcopenia, and osteoporosis and predicts mortality risk in elderly populations. The aim of the current study was to investigate if asymptomatic bacteriuria in elderly humans was associated with inflammation. Midstream clean-catch urine culture was collected from consecutive, elderly patients at admission to a department of internal medicine due to functional disability. Forty patients (age 70-91 years) were selected and included in the current study; 20 subjects had positive urine culture and 20 sex- and age-matched subjects had negative urine culture. Inclusion criteria were temperature below 37.8 degrees C, no clinical signs of infection and no current antibiotic treatment. Patients with asymptomatic bacteriuria had significantly increased levels of circulating tumor necrosis factor receptors (sTNFR-I) and a higher number of neutrophils in the blood compared to the group without bacteriuria. Thus, the present study provides some support for the hypothesis that asymptomatic urinary infections are associated with low-grade immune activity in frail, elderly humans.


The effect of Sargassum fusiforme polysaccharide extracts on vibriosis resistance and immune activity of the shrimp, Fenneropenaeus chinensis.
Immunostimulants are valuable for control of shrimp diseases and the immunostimulatory effects of some polysaccharide additives for shrimp have been reported. In this study, the Sargassum fusiforme polysaccharide extract (SFPSE) was assessed as a feed additive when supplemented in the diet (0%, 0.5%, 1.0%, and 2.0%) for juvenile shrimp, Fenneropenaeus chinensis, in order to study the effects of SFPSE on vibriosis resistance and immune activity. Shrimp were cultured in the same pond with cages. The body weight, survival, the cumulative mortality after injection with Vibrio harveyi (30 microl V. harveyi suspension at 9.3 x 10(7) CFU ml(-1) per shrimp), the total haemocyte counts (THCs), the protein concentration and the phenoloxidase (PO) activity in supernatant of haemolymph, the lysozyme (LSZ) and superoxide dismutase (SOD) activity in muscle of the shrimp were assayed after 14 days feeding period. The results indicated that shrimp survival under the stress of V. harveyi was affected by the dietary SFPSE. The shrimp treated with 1.0% and 0.5% SFPSE displayed significantly lower cumulative mortalities after being injected with V. harveyi suspension 24 and 30 h later, respectively, compared with that of the control. However, cumulative mortality of 2.0% SFPSE treatment was not significantly different from that of the control. There was no significant difference of cumulative mortality between 0.5% and 1.0% SFPSE treatment groups. The immune activities of the shrimp also were affected by dosage of dietary SFPSE. The THCs of the shrimp rose with increasing SFPSE dosage. The protein concentration and PO activity in supernatant of haemolymph as well as muscular LSZ activity first rose then dropped with increasing SFPSE dosage. The protein concentration in supernatant of haemolymph appeared a maximum of 167.46 mg ml(-1) in 1.0% SFPSE treatment. The PO activity and LSZ activity reached the peaks as 13.20 U and 3.21 U mgprot(-1) in 0.5% SFPSE treatment, respectively. SOD activity of the shrimp was not significantly affected by dietary SFPSE. It is therefore suggested that oral administration of SFPSE at an optimal level of 0.5% and 1.0% for 14 days effectively improved vibriosis resistance and enhanced immune activity of the shrimp in general.


Nonencephalitogenic CD4-CD8- V alpha 2V beta 8.2+ anti-myelin basic protein rat T lymphocytes inhibit disease induction.
Recently there has been a number of reports suggesting that CD4-CD8- T cells participate in the processes of inflammatory reaction. In an attempt to delineate the distinctive functions of double negative (DN) T lymphocytes in an autoimmune-induced disease, we isolated and cloned such T cells, along with control CD4+ cells, from Lewis rats immunized with guinea-pig myelin basic protein in CFA. Both clones proliferated in response to the guinea-pig myelin basic protein and its synthetic encephalitogenic peptide, and expressed the same TCR V genes homologous to the mouse V alpha 2 and V beta 8.2 families that appear to be the defining entity of experimental autoimmune encephalomyeltis (EAE). Moreover, the TCR D and J region gene products of the DN cell were found to be similar to another encephalitogenic rat T cell clone. The two T clones did not differ markedly in their ability to produce TNF and IL-2 and to adhere to vascular wall-derived extracellular matrix- and laminin-coated plates. Surprising, therefore, was the finding that, although the CD4+ T lymphocytes were capable of inducing EAE, the DN cells did not elicit disease but rather inhibited subsequent EAE induction. Thus, TCR V alpha 2V beta 8.2 and its junctional region gene products are not the only prerequisite segment for a T cell to become encephalitogenic. We suggest that the important determinants of the T cell ability to induce disease are features of the T cell, other than or in addition to, the T cell receptor.


[Analysis of phytosterol contents in food plant materials and Chinese traditional medicines].
To analyze the phytosterol content in food plant materials and Chinese traditional herbal medicines commonly used in China. 18 kinds of food plant materials and 32 kinds of Chinese traditional herbal medicines, which were commonly used in functional food, were chosen as samples. The contents of beta-sitosterol, campesterol, stigmasterol, beta-sitostanol were analyzed by GC methods and the percent of each ingredient were calculated. The contents of phytosterols in 18 kinds of food plant materials were from 14.8 mg/100 g to 208.3 mg/100 g, while the content of phytosterols in 32 Chinese traditional herbal medicines were from 9.4 mg/100 g to 280.3 mg/100 g. In most samples, beta-sitosterol is the largest part of total phytosterol. Phytosterols were existed in 50 kinds of food plant materials and Chinese traditional herbal medicines commonly used in functional food, maybe phytosterol is an important functional ingredient in some plant materials.


Flow cytometric assay detecting cytotoxicity against human endogenous retrovirus antigens expressed on cultured multiple sclerosis cells.
Damage of target cells by cytotoxicity, either mediated by specific lymphocytes or via antibody-dependent reactions, may play a decisive role in causing the central nervous system (CNS) lesions seen in multiple sclerosis (MS). Relevant epitopes, antibodies towards these epitopes and a reliable assay are all mandatory parts in detection and evaluation of the pertinence of such cytotoxicity reactions. We have adapted a flow cytometry assay detecting CD107a expression on the surface of cytotoxic effector cells to be applicable for analyses of the effect on target cells from MS patients expressing increased amounts of human endogenous retrovirus antigens. MS patients also have increased antibody levels to these antigens. The target cells are spontaneously growing peripheral blood mononuclear cells (PBMCs) of B cell lineage, expressing human endogenous retrovirus HERV epitopes on their surface. Polyclonal antibodies against defined peptides in the Env- and Gag-regions of the HERVs were raised in rabbits and used in antibody-dependent cell-mediated cytotoxicity (ADCC) -assays. Rituximab® (Roche), a chimeric monoclonal antibody against CD20 expressed primarily on B cells, was used as control antibody. Without antibodies this system is suitable for analyses of natural killer cell activity. In optimization of the assay we have used effector lymphocytes from healthy donors. The most effective effector cells are CD56(+) cells. CD8(+) T cells also express CD107a in ADCC. Using the adapted assay, we demonstrate significant ADCC activity to target cells expressing HERV epitopes, and additionally a low level of NK activity.


Increased Tolerance to Photoinhibitory Light in Paraquat-Resistant Conyza bonariensis Measured by Photoacoustic Spectroscopy and CO(2)-Fixation.
Tolerance to photoinhibition was compared between a paraquat-resistant and a sensitive biotype of Conyza bonariensis (L.). Cronq. Photoinhibitory damage was measured as a decrease in oxygen evolution or energy storage using photoacoustic spectroscopy, or as a decrease of (14)CO(2)-fixation. Prior to exposure to high fluence rates, both biotypes had similar quantum yields of oxygen evolution and energy storage. After exposure to high intensity light, the resistant biotype continued to evolve oxygen and to store energy with a high quantum yield while both energy storage and oxygen evolution were severely reduced in the sensitive biotype. CO(2)-fixation was less rapidly inhibited in the resistant biotype compared to the sensitive one. The data show that the paraquat resistant biotype with its high constitutive levels of the chloroplast localized enzymes of the oxygen detoxification pathway, is also partially protected from photoinhibition. This supports the theory that an enhanced radical scavenging system can give temporary protection against photooxidative damage from a variety of sources.


Occurrence of Fusarium species and zearalenone in dairy cattle feeds in Vojvodina.
The occurrence of Fusarium spp. and zearalenone (F-2 toxin) in dairy cattle feeds was studied during a period of three years (in all seasons) in Vojvodina. Fusarium species were found to be very common in feeds. They were classified into 11 different species (F. chlamydosporum, F. equiseti, F. flocciferum, F. graminearum, F. lateritium, F. moniliforme, F. oxysporum, F. semitectum, F. solani, F. tabacinum and F. tricinctum). Some of these species are known to produce mycotoxins. The highest distribution of Fusarium spp. was observed in the autumn and spring of the second research year, when 53 and 56% of the feed samples, respectively, were contaminated with them. F. oxysporum and F. moniliforme were the most prevalent species throughout the three-year study. Zearalenone was found in various feed samples at concentrations between 140.00 and 960.00 micrograms/kg in all seasons, except in the summer of the first year, in the winter of the second year and in the autumn of the third research year. Pelleted sugar beet pulp and pelleted malt spent grains were the feeds most contaminated with this toxin. Thirty-five out of the 275 feed samples contained zearalenone and 11 of them were contaminated with zearalenone-producing moulds and zearalenone at the same time.


Disinfestation of stored wheat grain infested with Rhyzopertha dominica by ozone treatment: process optimization and impact on grain properties.
Ozone is a highly oxidative gas that has a long history of safe use as a disinfectant and sanitizer from producers of pharmaceuticals and many other organic compounds. In the current work, disinfestation of stored wheat grain infested with a common insect, Rhyzopertha dominica, was attempted through ozone (O3 ) treatment as an alternative to chemical fumigants. The optimized treatment conditions for ozone fumigation of stored wheat grain were 12% (w/w) grain moisture, 2.5 g m-3 ozone concentration and 8 h of treatment. The mortality of R. dominica adults, pupae, larvae and eggs was 97, 100, 99 and 100%, respectively. Moisture and protein content of the ozone-treated wheat was found to be lower as compared to infested wheat. Microstructural changes in the treated samples were clearly visible on scanning electron microscopy images, whereas minimal changes at the molecular level and of rheological parameters were evident based on Fourier transform infrared spectroscopy peak and rheometry data. Ozone was found to be an effective reagent for disinfestation, aimed at all life stages of R. dominica in stored wheat grain, that leaves no residue behind. Rotational strategies can be applied to obtain increased mortality while maintaining the usability of the grain for different purposes. © 2019 Society of Chemical Industry.


How Does the Measurement of Disability in Low Back Pain Map Unto the International Classification of Functioning, Disability and Health?: A Scoping Review of the Manual Medicine Literature.
The objective of this study was to catalog items from instruments used to measure functioning, disability, and contextual factors in patients with low back pain treated with manual medicine (manipulation and mobilization) according to the International Classification of Functioning, Disability and Health. This catalog will be used to inform the development of an International Classification of Functioning, Disability and Health-based assessment schedule for low back pain patients treated with manual medicine. In this scoping review, we systematically searched MEDLINE, Embase, PsycINFO, and CINAHL. We identified instruments (questionnaires, clinical tests, single questions) used to measure functioning, disability, and contextual factors, extracted the relevant items, and then linked these items to the International Classification of Functioning, Disability and Health. We included 95 articles and identified 1510 meaningful concepts. All but 70 items were linked to the International Classification of Functioning, Disability and Health. Of the concepts linked to the International Classification of Functioning, Disability and Health, body functions accounted for 34.7%, body structures accounted for 0%, activities and participation accounted for 41%, environmental factors accounted for 3.6%, and personal factors accounted for 16%. Most items used to measure functioning and disability in low back pain patient treated with manual medicine focus on body functions, as well as activities and participation. The lack of measures that address environmental factors warrants further investigation.


Hard tick species (Acari: Ixodidae) and infestation in two livestock agroecosystems from Antioquia, Colombia.
Tick infestation affects about 80% of livestock globally while transmitting various pathogens causing high economic losses. This study aimed to determine the degree of tick infestation in two regions, North and Middle Magdalena in Antioquia, Colombia, to identify the ixodid tick species found and the associated risk factors. A cross-sectional study was carried out in 48 farms distributed in six municipalities of Antioquia. Two paddocks and eight bovines per farm were evaluated to estimate tick infestation (adults, nymphs, and larvae). Tick species were identified through a morphological and molecular analysis based on partial sequences of data obtained from DNA molecular markers, two mitochondrial (16S rRNA and COI), and one genomic DNA gene (18S rRNA). A multivariate Poisson regression model was applied to estimate the associated risk factors with ticks in cattle. Rhipicephalus microplus, Amblyomma patinoi and Dermacentor nitens were present in the livestock agroecosystems in the Middle Magdalena region; the highest incidence of tick infestation in cows and paddocks was reported in the municipality of Puerto Triunfo. The livestock agroecosystems in Middle Magdalena were characterized by a higher presence of adult R. microplus in cattle. Larval infestation of R. microplus, followed by D. nitens, was also found in paddocks. The multivariate analysis showed that the origin of cattle was the main risk factor associated with the presence of ticks (i.e., when cattle came from outside the farm). Cattle movement between farms in Middle Magdalena can contribute to the spread of ticks in this region.


[Evaluation of fatty acids and cholesterol intake by a group of students].
The main purpose of this work was the analysis of the composition of fatty acids and cholesterol. The investigation was done among 143 students, with 3-day dietary records method. The research was carried out in the years 2007 and 2008. The average fat intake was 92.7% of RDA. The intakes of saturated, monounsaturated and polyunsaturated fatty acids were 99.4%, 71.2% and 73.3% of recommended levels, respectively. The average intake of cholesterol was in accordance with recommended value 300 mg (91.00%). Intake of fat, fatty acids and cholesterol depended on gender Intake offat, saturated and monounsaturated fatty acids depended on state of health additionally. Intake of saturated fatty acids was different according to place of dwelling. In case of men too much energy from fat (37.9%) was recorded and too much intake of cholesterol (about 58%).


Diffusion on a self-assembled monolayer: molecular modeling of a bound + mobile lubricant.
The diffusion of tricresyl phosphate molecules on an octadecyltrichlorosilane self-assembled monolayer (SAM) was characterized using molecular dynamics simulations. The simulations predict that when placed on the top of a close-packed SAM, the molecules remain mobile on the surface with an isotropic diffusion activation energy of approximately 9 kJ/mol. In contrast, an anisotropic barrier that results from chain tilt within the SAM is predicted for diffusion into a defect created by reducing the alkane chain length within a cylinderical region of the surface. Once in the defect, the molecules become trapped by embedding part of the molecule into the side of the SAM.


[Effect of postoperative complications on nutritional status: therapeutic consequences].
The occurrence of a postoperative complication represents an additional stress factor for patients and leads in many cases rapidly to a malnutrition status. Thus a nutritional support is required as soon as the foreseeable duration of starvation has a longer duration than one week. Considering its lower risk of septic complications and lower cost, enteral feeding should be initiated as soon as possible. Appraisal of caloric needs with standard formulas often leads to inappropriate nutritional management. Therefore the requirements should be assessed by indirect calorimetry if available. Nutritional support is a part of the management of a postoperative septic patient. It must be initiated when initial phase of haemodynamic instability is amended. Branched chain amino acids, medium chain triglycerides and other specific nutrients have failed to demonstrate a real clinical beneficial effect. In case of acute respiratory failure, nutritional support must be cautious with regard to caloric load, as carbohydrates may increase CO2 production and lipids may worsen hypoxaemia. In case of postoperative acute renal failure, nutritional management is facilitated by continuous haemofiltration techniques allowing an unlimited nutrient intake. Solutions containing only essential amino acids are not recommended. During severe acute pancreatitis, enteral feeding is indicated when ileus does not permit the use of the intestinal tract. Jejunal access must be preferred to stomach or duodenum. Lipid emulsions can be used safely if serum triglyceride concentrations remain below 4 g.L-1 during infusion and below 2 g.L-1 between infusions.


Cholecystitis associated with myelomatosis.
A case of myeloma presenting as acute cholecystitis unresponsive to conventional management is reported. The impairment of the immunological response is a well-known aspect of myeloma, although this usually takes the form of recurrent respiratory infections. It is unusual for acute on chronic cholecystitis, a predominantly Gram-negative infection, to present in this way.


Long-term prognosis of 69 patients with dermatomyositis or polymyositis.
To assess the long-term prognosis of dermatomyositis and pol myositis. 69 patients with dermatomyositis or polymyositis were selected according to the diagnostic criteria of Bohan and Peter and were followed up for a minimum of 6.3 years (for surviving patients) (mean 11.6 years). Clinical and biological features, and pulmonary and muscle parameters were considered as prognostic factors for death. Functional disability was assessed using a 4-stage grading system. 30 deaths (43.5%) occurred mainly due to cardiovascular (8), pulmonary (8), carcinomatous (5) and iatrogenic complications (5). Survival rates were 82.6% at 1 year, 73.9% at 2.66, 7% at 5 and 55.4% at 9. Significant prognostic factors for death (Cox model with time-dependent covariates) were old age (p < 0.0001), dysphonia (p < 0.001), pulmonary interstitial fibrosis (p < 0.02), absence of dysphagia (p < 0.02) and asthenia-anorexia (p < 0.05). Dermatomyositis and polymyositis subgroups had slightly different significant prognostic factors for death: old age, cancer, pulmonary interstitial fibrosis and asthenia-anorexia for dermatomyositis; old age, failure to improve muscle strength in response to treatment after one month, and the absence of myalgia as presenting symptom for polymyositis. At the end of the follow-up, 33/39 surviving patients (84.6%) had no or insignificant muscular disability, whereas 3 children were bedridden due to generalized calcinosis. High mortality occurred in the first year, and the survival rate decreased continually up to 9 years. The main prognostic factor for death is old age, but dermatomyositis and polymyositis must be considered separately. General features (pulmonary fibrosis, cancer, asthenia-anorexia) are involved in dermatomyositis, whereas muscular symptoms are the most significant in polymyositis. The long-term functional prognosis was fairly good, except for generalized calcinosis, which tended to occur in childhood dermatomyositis.


Development of a micellar electrokinetic capillary chromatography method for the determination of four naphthalenediols in cosmetics and a comparison with a HPLC method.
A micellar electrokinetic capillary chromatography (MEKC) method with ultraviolet visible (UV) detection was used for the determination of 1,7-naphthalenediol, 2,3-naphthalenediol, 1,5-naphthalenediol, and 2,7-naphthalenediol in cosmetics. The current method for their determination in various cosmetics is high-performance liquid chromatography (HPLC). Separation conditions affecting the MEKC method were optimized as 20 mM Na2 B4 O7 -50mM SDS, pH 9.8, with 22 kV applied voltage and UV detection at 230 nm. Under optimal conditions, electrophoretic analysis was completed in less than 6 min, with limit of detection (LOD) of 0.070-0.19 μg/mL and limit of quantitation (LOQ) of 0.23-0.63 μg/mL. A good linear relationship (r2 > 0.99) was obtained at the range of 0.75-20 μg/mL. Recoveries for the four naphthalenediols in lotion, loose powder, and sun cream are between 91.2-107.2% with relative standard deviation (RSD) less than 4.04%. The method has been successfully applied to the determination of the four naphthalenediols in different kinds of cosmetics. A comparison with HPLC-UV method was also carried out according to the National Standards of the People's Republic of China. The results obtained by MEKC and HPLC methods are comparable, but the proposed MEKC method can help us obtain a much shorter detection time and low cost.


The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system.
The gut microbiota contributes to fat mass and the susceptibility to obesity. However, the underlying mechanisms are not completely understood. To investigate whether the gut microbiota affects hypothalamic and brainstem body fat-regulating circuits, we compared gene expression of food intake-regulating neuropeptides between germ-free and conventionally raised (CONV-R) mice. We found that CONV-R mice had decreased expression of the antiobesity neuropeptide glucagon-like peptide-1 (GLP-1) precursor proglucagon (Gcg) in the brainstem. Moreover, in both the hypothalamus and the brainstem, CONV-R mice had decreased expression of the antiobesity neuropeptide brain-derived neurotrophic factor (Bdnf). CONV-R mice had reduced expression of the pro-obesity peptides neuropeptide-Y (Npy) and agouti-related protein (Agrp), and increased expression of the antiobesity peptides proopiomelanocortin (Pomc) and cocaine- and amphetamine-regulated transcript (Cart) in the hypothalamus. The latter changes in neuropeptide expression could be secondary to elevated fat mass in CONV-R mice. Leptin treatment caused less weight reduction and less suppression of orexigenic Npy and Agrp expression in CONV-R mice compared with germ-free mice. The hypothalamic expression of leptin resistance-associated suppressor of cytokine signaling 3 (Socs-3) was increased in CONV-R mice. In conclusion, the gut microbiota reduces the expression of 2 genes coding for body fat-suppressing neuropeptides, Gcg and Bdnf, an alteration that may contribute to fat mass induction by the gut microbiota. Moreover, the presence of body fat-inducing gut microbiota is associated with hypothalamic signs of Socs-3-mediated leptin resistance, which may be linked to failed compensatory body fat reduction.


Effect of electrocauterization on the inflammation of the conjunctiva in experimental animal model.
Recently, conjunctivochalasis repair surgery using electrocauterization has been gaining popularity. However, patients with electrocauterized conjunctivoplasty tend to complain of more postoperative pain than patients undergoing simple excision with suturing. Therefore, we investigated the effects of electrocauterization on inflammation of the conjunctiva using an experimental animal model and compared these with the effects of simple excision with suturing. Ten New Zealand white rabbits underwent cauterization in the right eyes and excision and suturing in the left eyes. For each eye, we excised or electrocauterized the inferior bulbar conjunctiva, 1 mm in width and 6 mm in length, 2 mm from the limbus. A fine-needle electrode was inserted subconjunctivally, and electrocauterization was performed. In the contralateral eye, the corresponding area was excised and re-approximated with 10-0 nylon sutures. Sutures were removed after 14 days. Tissue samples were obtained at 21 days post-procedure, and inflammatory cells were counted in five randomly selected fields (×200) on hematoxylin-eosin stained slides. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β concentrations in tears were measured using enzyme linked immunosorbent assays. All cauterized eyes demonstrated smooth surface healing without scarring after 5 days, whereas sutured eyes presented with mild edema with some scarring until the suture was removed. The number of inflammatory cells was significantly greater in sutured eyes compared with cauterized eyes (p = 0.035, Mann-Whitney U-test) at 21 days post-procedure. Tear TNF-α and IL-1β concentrations at 21 days were similar in both groups. Electrocauterization for conjunctivoplasty seems to be advantageous in terms of inflammation compared with simple suturing and excision.


Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 mitogen-activated protein kinase activation.
The PAK family of protein kinases has been suggested as a potential target of the Cdc42 and Rac GTPases based on studies in vitro. We show that PAK-3 is activated by Cdc42 in vivo. Both, activated (GTPase-defective) Cdc42 and a constitutively active PAK-3 mutant stimulated the activity of Jun kinase 1 (JNK1) in transfected cells. Activated Cdc42 also stimulated the activity of the related p38 mitogen-activated protein kinase but was a less effective activator of ERK2. The effect of Cdc42 on JNK activity was similar to that of the potent inflammatory cytokine interleukin-1 (IL-1). The observation that a dominant-negative Cdc42 mutant inhibited IL-1 activation of JNK1 indicates a role for Cdc42 in IL-1 signaling. These results suggest that Cdc42 and PAK may mediate the effects of cytokines on transcriptional regulation.


IMpassion132 Phase III trial: atezolizumab and chemotherapy in early relapsing metastatic triple-negative breast cancer.
The PD-L1 inhibitor atezolizumab received US FDA accelerated approval as treatment for PD-L1-positive metastatic triple-negative breast cancer (TNBC). In IMpassion130, combining atezolizumab with first-line nab-paclitaxel for metastatic TNBC significantly improved progression-free survival and showed a clinically meaningful effect on overall survival in patients with PD-L1-positive tumors. The placebo-controlled randomized Phase III IMpassion132 (NCT03371017) trial is evaluating atezolizumab with first-line chemotherapy (capecitabine [mandatory in platinum-pretreated patients] or gemcitabine/carboplatin) for inoperable locally advanced/metastatic TNBC recurring ≤12 months after completing standard (neo)adjuvant anthracycline and taxane chemotherapy. Stratification factors are: visceral metastases, tumor immune cell PD-L1 status and selected chemotherapy. Patients are randomized to atezolizumab 1200 mg or placebo every 3 weeks with the chosen chemotherapy, continued until progression, unacceptable toxicity or withdrawal. The primary end point is overall survival.


Exposure of Polish children to Southampton food colours.
A study published in 2007 showed that the intake of six food colours (the so-called 'Southampton colours') may have an adverse effect on activity and attention in children. The present study set out to assess the exposure of Polish children (3 and 8-9 years old, n = 149) to six of the target colours. Two methods were used to evaluate colour consumption by children: scenario 1 using the maximum permitted levels (MPLs) and actual food consumption data; and scenario 2 using the actual levels in food and actual food consumption data. The data on the actual consumption of food containing the colours was collected using a 7-day questionnaire survey. The results of laboratory analysis of food consumed by children provided data on the actual levels of the colours in food. Consumption of the colours estimated by scenario 1 in any case did not exceed the acceptable daily intakes (ADIs) of the colours in both age groups of children. For more refined colour intake (scenario 2), isolated cases exceeding the ADI were recorded for four colours, but assuming that manufacturers comply with the current legislation on MPL of colours in food, the intake of the colours assessed in scenario 2 should not be a reason for exceeding of ADIs for the target food colours.


In silico model for miRNA-mediated regulatory network in cancer.
Deregulation of gene expression is associated with the pathogenesis of numerous human diseases including cancer. Current data analyses on gene expression are mostly focused on differential gene/transcript expression in big data-driven studies. However, a poor connection to the proteome changes is a widespread problem in current data analyses. This is partly due to the complexity of gene regulatory pathways at the post-transcriptional level. In this study, we overcome these limitations and introduce a graph-based learning model, PTNet, which simulates the microRNAs (miRNAs) that regulate gene expression post-transcriptionally in silico. Our model does not require large-scale proteomics studies to measure the protein expression and can successfully predict the protein levels by considering the miRNA-mRNA interaction network, the mRNA expression, and the miRNA expression. Large-scale experiments on simulations and real cancer high-throughput datasets using PTNet validated that (i) the miRNA-mediated interaction network affects the abundance of corresponding proteins and (ii) the predicted protein expression has a higher correlation with the proteomics data (ground-truth) than the mRNA expression data. The classification performance also shows that the predicted protein expression has an improved prediction power on cancer outcomes compared to the prediction done by the mRNA expression data only or considering both mRNA and miRNA. Availability: PTNet toolbox is available at http://github.com/CompbioLabUCF/PTNet.


Predicting dairy cattle heat stress using machine learning techniques.
The objectives of the study were to use a heat stress scoring system to evaluate the severity of heat stress on dairy cows using different heat abatement techniques. The scoring system ranged from 1 to 4, where 1 = no heat stress; 2 = mild heat stress; 3 = severe heat stress; and 4 = moribund. The accuracy of the scoring system was then predicted using 3 machine learning techniques: logistic regression, Gaussian naïve Bayes, and random forest. To predict the accuracy of the scoring system, these techniques used factors including temperature-humidity index, respiration rate, lying time, lying bouts, total steps, drooling, open-mouth breathing, panting, location in shade or sprinklers, somatic cell score, reticulorumen temperature, hygiene body condition score, milk yield, and milk fat and protein percent. Three different treatments, namely, portable shade structure, portable polyvinyl chloride pipe sprinkler system, or control with no heat abatement, were considered, where each treatment was replicated 3 times with 3 second-trimester lactating cows. Results indicate that random forest outperformed the other 2 methods, with respect to both accuracy and precision, in predicting the sprinkler group's score. Both logistic regression and random forest were consistent in predicting scores for control, shade, and combined groups. The mean probability of predicting non-heat-stressed cows was highest for cows in the sprinkler group. Finally, the logistic regression method worked best for predicting heat-stressed cows in control, shade, and combined. The insights gained from these results could aid dairy producers to detect heat stress before it becomes severe, which could decrease the negative effects of heat stress, such as milk loss.


[Infantile myofibroma and myofibromatosis: clinical and morphologic assessment of eighteen cases].
Infantile myofibroma (myofibromatosis) (IM) is a mesenchymal tumor of soft tissues of the head, extremities and trunk. It is characterized by relapse-free infiltrative growth. It consists of neoplastic myofibroblasts at varying stage of cell differentiation which form multi-structured tumor zones. IM's morphological differentiated diagnosis is established vis-a-vis other varieties of tumor and reactive nodular structures of fibroblasts, primarily, infantile hemangiopericytomas and desmoid fibromatosis. Immunohistological and ultrastructural examination of tumor is required for making correct diagnosis of IM.


Environmental tobacco smoke and breastfeeding duration.
The effect of smoking on breastfeeding duration was investigated in a population-based birth cohort study of 1,098 Brazilian infants. There were few losses to follow-up (3.2%) in the first 6 months. Maternal smoking was strongly associated with breastfeeding duration, even after adjustment for confounding. Compared with nonsmokers, mothers smoking 20 or more cigarettes daily presented an odds ratio of 1.94 for breastfeeding for less than 6 months. Environmental tobacco smoke was also an independent risk factor. After adjustment for maternal smoking and other confounders, households where more than 10 cigarettes were smoked daily by persons other than the mother presented an odds ratio of 1.48 compared with those without smokers. These results remained unchanged after stratification for maternal smoking. This is the first report of a possible effect of environmental tobacco smoke on breastfeeding duration.


[Usefulness of testing histamine release from isolated human basophils in anti-allergic and anti-asthmatic drug assessment].
Histamine release from isolated human basophils test was used to evaluate an activity of: histamine receptors H1 and H2 blockers, agonists of beta-receptors, calcium channel blocking agents, hydrocortisone, and disodium cromoglycate (Intal). The study involved 84 patients hospitalized for the bronchial asthma. Basophils were isolated with Day's technique modified by Shov and Norn. Histamine was measured with Shov's spectrofluorimetric technique. It was found that histamine release from isolated human basophils may be used in both evaluation of the mechanism of action and efficiency of drugs used in allergic diseases therapy.


Association of Planning Target Volume with Patient Outcome in Inoperable Stage III NSCLC Treated with Chemoradiotherapy: A Comprehensive Single-Center Analysis.
Inoperable stage III non-small cell lung cancer (NSCLC) represents a highly heterogeneous patient cohort. Multimodal treatment approaches including radiotherapy have been the new standard of care, with promising outcomes. The planning target volume (PTV), including the primary tumor, involved lymph node stations and safety margins, can vary widely. In order to evaluate the impact of the PTV for overall survival (OS), progression-free survival (PFS) and loco-regional control, we analyzed retrospective and prospective data of 122 consecutive patients with inoperable stage III NSCLC treated with CRT. The majority of patients (93%) received a total dose ≥ 60 Gy and 92% of all patients were treated with concurrent or sequential chemotherapy. Median follow-up for the entire cohort was 41.2 (range: 3.7-108.4) months; median overall survival (OS) reached 20.9 (95% CI: 14.5-27.3) months. PTVs from 500 to 800 ccm were evaluated for their association with survival in a univariate analysis. In a multivariate analysis including age, gender, total radiation dose and histology, PTV ≥ 700 ccm remained a significant prognosticator of OS (HR: 1.705, 95% CI: 1.071-2.714, p = 0.025). After propensity score matching (PSM) analysis with exact matching for Union internationale contre le cancer (UICC) TNM Classification (7th ed.)T- and N-stage, patients with PTV < 700 ccm reached a median PFS and OS of 11.6 (95% CI: 7.3-15.9) and 34.5 (95% CI: 25.6-43.4) months vs. 6.2 (95% CI: 3.1-9.3) (p = 0.057) and 12.7 (95% CI: 8.5-16.9) (p < 0.001) months in patients with PTV ≥ 700 ccm, respectively. Inoperable stage III NSCLC patients with PTV ≥ 700 ccm had significantly detrimental outcomes after conventionally fractionated CRT. PTV should be considered as a stratification factor in multimodal clinical trials for inoperable stage III NSCLC.


Isolated patellar component revision of total knee arthroplasty.
Forty-two knees in 41 patients required isolated patellar component revision of a total knee arthroplasty (TKA). Revision was performed for loosening in 14 knees, wear to metal backing in 13, fracture of the fixation peg in seven, dissociation of polyethylene from metal backing in two, anterior knee pain in two, patellar instability in two, and component malposition with fat pad proliferation in two. Thirty-six knees were evaluated two to eight years after patellar revision. The Hospital for Special Surgery knee scores improved from an average of 71 preoperatively to 81 postoperatively. Eighteen knees were excellent; 12, good; four, fair; and two, poor. Complications associated with patellar revision included late patellar fractures in five knees, patellar instability in three, peroneal nerve palsies in two, patellar polyethylene wear to metal backing in two, infection in one, and extensor lag in one. This seemingly straight-forward procedure is associated with a high complication rate.


Influence of the socio-demographic characteristics of mothers of children aged 3-10 years on their at-home support of fruit and vegetable consumption
The inadequate fruit and vegetable intake is common for adults and children, while for children increasing intake is especially important, as intake during childhood predicts future adulthood intake. The aim of the study was to assess influence of the socio-demographic characteristics of mothers on their athome support of fruit and vegetable consumption in the national Polish sample. The study was conducted in a national representative sample of Polish mothers of children aged 3-10 (n=1200), who were recruited using a random quota sampling (quotas: age, education, region, size of city). They were interviewed using a Computer-Assisted Telephone Interviewing (CATI) method and asked about dietary patterns of their children and their at-home behaviors to support fruit and vegetable consumption, which were afterwards compared in sub-groups stratified for age, educational background, marital status, place of residence, occupational status and total net income in households. For fruits, mothers with lower level of education, from villages/ smaller towns, with no professional job and lower income, more commonly than others, stated, that no support of consumption is needed, as their children eat fruits with no encouragement. For vegetables, either the same situation as for fruits was observed (for mothers with no professional job and lower income), or mothers more commonly than others declared forcing children to consume (for mothers with the lowest level of education). The socio-demographic status of mothers, especially level of education, place of residence, professional job and income, are important factors associated with their at-home support of fruit and vegetable consumption for their children. The groups of mothers with lower level of education, from villages/ smaller towns, with no professional job and lower income were indicated as important target groups to provide them knowledge about the recommended fruit and vegetable intake, as well as recommended parenting style.


Management of aortic dissection.
Patients with aortic dissection are divided into two main groups: those with hypertension and those with syndromes involving hereditary defects of the aortic wall. The common finding in the setting of both Marfan syndrome and hypertension is dilatation of the aorta. The biological events that may lead to dissection are a decrease in the holding power of the internal layer, an increase in blood pressure, or an increase in aortic diameter combined with a decrease in wall thickness. Treatment of established acute type A dissection is still associated with a hospital mortality of greater than 10% and long-term complications from persistent blood flow in the distal false lumen. The main therapeutic challenge is to prevent aortic dissection by screening of aortic root diameter in patients at risk, together with life-long beta-blockade for Marfan patients. In patients with suspected dissection, the preference is for rapid noninvasive diagnosis and early surgical repair to reduce the risk of malperfusion and irreversible organ damage. Results of surgery have improved, with an increasingly conservative approach to repair of the aortic valve with biological glues. Repair is now routinely carried into the aortic arch using improved methods of cerebral protection such as retrograde cerebral perfusion through the superior vena cava. Nevertheless, there remains scope for further innovation in the prevention and treatment of this difficult problem.


Theoretically exact backprojection filtration algorithm for multi-segment linear trajectory.
A theoretically exact backprojection filtration algorithm is proved and implemented for image reconstruction from a multi-segment linear trajectory assuming fan-beam geometry. The reconstruction formula is based on a concept of linear PI-line (L-PI) proposed in our previous work. The proof is completed in two consecutive steps. In the first step, it is proved that theoretically exact image reconstruction can be obtained on an arbitrary L-PI line from an infinite straight-line trajectory. In the second step, it is shown that accurate image reconstruction can be achieved from a multi-segment line trajectory by introducing a weight function to deal with the data redundancy. Numerical implementation and simulation results validate the correctness of our theoretical results.


The current status of bariatric surgery.
As the incidence of obesity continues to rise, increasing numbers of patients are undergoing bariatric surgery to address morbid obesity and weight related health issues. Bariatric procedures aim to reduce dietary intake and/or interfere with food absorption and are now in widespread use but with a huge capacity shortfall leading to a degree of rationing of the resource. Such treatment should be regarded as palliative in that it does not cure the underlying disorder, and guidelines have been produced to define which patients should be considered for this type of surgery, which must be undertaken in a multidisciplinary setting. Long term results show this to be a cost-effective intervention with a durable positive impact on cardiac risk factors and in particular type 2 diabetes and obstructive sleep apnoea, together with a reduction in all cause mortality and malignancy and an improvement in quality of life. Systematic data collection has now started in the UK and will assist in defining the best application of the resource.


[Immunomodulatory effect of tick saliva in pathogen transmission].
Ticks are the most important vectors of pathogens in human and veterinary medicine. These strictly haematophagous acarines produce a saliva containing a variety of bioactive molecules affecting host pharmacology and immunity. This process is vital for hard ticks to prevent rejection by the host during the blood meal that lasts several days. All actors involved in the immunity interplay are impacted by this saliva, the innate immunity being represented by resident and migrating immune cells, as well as the T and B lymphocytes of the adaptive immune system. The skin plays a key role in vector-borne diseases. During the long co-evolution with the tick, the infectious agents benefit from this favorable environment to be transmitted efficiently into the skin and to multiply in the vertebrate host. Therefore, the saliva is an important virulence booster, which enhances substantially their pathogenicity.


Ultrastructure of eggshell and embryological development of Salvator merianae (Squamata: Teiidae).
The objective of this study was to characterize the external morphology of Salvator meriane embryos in different stages of embryonic development and establish a relationship with the ultrastructure of the shell from oviductal transit to hatching. A total of 120 embryos were analyzed to describe their external morphology, and 78 eggs were used for the analysis of the shell. For embryonic development, the series was established according to the total length of the body. We established 40 embryonic stages from the primitive streak. In the early stages, the external morphological features are the C-shaped body, the maxillary, and mandibular fusion processes with the frontal process and the fusion of the forelimb with the digital plate. In the middle stages, the eyelid appears, and there are claws on the toes, cornification of fingers, and the onset of pigmentation. The last stage of embryonic development is characterized by the beginning of the formation of the scales, appear the toenails, and finalize the entire pigmentation. Regarding the relationship that exists with the ultrastructure of the egg during development, it was possible to observe a marked change in the composition of the shell and well-marked compaction during embryonic development, which may be related to the transport of calcium during embryonic ossification. Our results allowed us to show the complete sequence of embryonic development, determining the laying stage for this species. It was possible to establish a relationship with the ultrastructure of the eggshell from the oviductal transit to the moment of hatching.


In vivo bracket retention comparison of a resin-modified glass ionomer cement and a resin-based bracket adhesive system after a year.
Glass ionomer orthodontic adhesives cause less enamel demineralization during fixed orthodontic appliance treatment than do traditional resin-based products. An in vivo randomized clinical trial was performed comparing the clinical performance of a resin-modified glass ionomer (RMGI) adhesive with a no-mix, resin-based (the control) adhesive over a 12-month period. The split-mouth technique was used to analyze bracket retention, bracket failure causes, and mode of failure for both adhesives in 61 patients. Bracket-failure rates were 10% for the RMGI and 4% for the resin-based adhesive. Both adhesives had 4 times more bracket failures when opposing occlusion was present. The resin-based product demonstrated a higher proportion of resin-to-enamel adhesive failures than did the RMGI. Compared with the resin-based adhesive, the RMGI-bracketed teeth showed improved clinical performance, no enamel surface loss, less enamel demineralization, and faster adhesive removal. However, the RMGI had a 2.6 times greater bracket-failure rate than did the resin-based product.


Expression of cytoskeleton components in various Epstein-Barr virus infected cell lines.
It has been shown that viruses can induce alterations in the content and distribution of cytoskeleton structures, particularly actin microfilaments and microtubules. An immunomorphologic study of the cytoskeleton components of various EBV-infected cell lines with expression of different functions of EBV genome has been performed using antibodies to each of its three major components. Intermediate filaments and microtubules were similarly represented in all examined lymphoblastoid cell lines. The distribution of actin microfilaments, on the contrary, differed significantly from cell line to cell line. It is concluded that the morphologic expression of actin might depend on the expression of EBV genome. Furthermore, some of these cell lines might represent a useful substrate for the identification of anticytoskeleton antibodies, mainly anti-actin antibodies, in human sera.


Initial changes in pulpal microvasculature during orthodontic tooth movement: a stereological study.
Any alteration in blood flow or vascular pressure caused by a trauma may damage the pulp tissue. The aim of this study was to evaluate the vascular changes during the initial period of tooth movement. These alterations were assessed in coronal molar pulp tissue of 20 male Wistar rats, 90 days of age, submitted to mesial inclination movement by a closed coil spring, placed from the right maxillary first molar to the maxillary incisors. The animals were divided into three experimental groups of 6, 24, and 72 hours of 0.4 N force application, with five animals in each group, and a control group of five animals without tooth movement. The volume density of blood vessels (V(v)) of the coronal pulp tissue in the experimental groups was calculated by stereology and compared with the control group. The results demonstrated a significant increase in V(v) at 6 hours of 10.2 per cent compared with 7.2 per cent for the control group (P <or= 0.05). At 24 and 72 hours, V(v) was reduced, with values close to those observed for the control group (P > 0.05). These results demonstrate the high capacity of adaptation of the pulp tissue to an aggression, provided the biological limits of tolerance of the pulp are respected.


Combined sedation with midazolam/propofol for gastrointestinal endoscopy in elderly patients.
Although gastrointestinal endoscopy with sedation is increasingly performed in elderly patients, data on combined sedation with midazolam/propofol are very limited for this age group. We retrospectively analyzed 454 endoscopic procedures in 347 hospitalized patients >or= 70 years who had received combined sedation with midazolam/propofol. 513 endoscopic procedures in 397 hospitalized patients < 70 years during the observation period served as controls. Characteristics of endoscopic procedures, co-morbidity, complications and mortality were compared. Elderly patients had a higher level of co-morbidity and needed lower mean propofol doses for sedation. We observed no major complication and no difference in the number of minor complications. The procedure-associated mortality was 0%; the 28-day mortality was significantly higher in the elderly (2.9% vs. 1.0%). In this study on elderly patients with high level co-morbidity, a favourable safety profile was observed for a combined sedation with midazolam/propofol with a higher sensitivity to propofol in the elderly.


Surgical management of female infertility in Ilorin, Nigeria.
Three hundred and seventeen female patients with infertility surgically managed and followed up for four years at the University of Ilorin Teaching Hospital (UITH), Ilorin, Nigeria are presented. 45 (14.2%) of these patients were pregnant. A total of 61 pregnancies were achieved in these patients giving an overall pregnancy rate of 19.24% which is comparable to those reported in literature. In the study period, 68.85% full-term gestations, 14.75% pre-term gestations, 11.48% spontaneous abortions and 4.92% ectopic gestations, occurred. As over 50% of female infertility in sub-Saharan Africa is due to tubo peritoneal disorders/pelvic disease and as the desire for children among African women is very strong, the authors plead for the sustenance of surgery, possibly on selected patients, in the management of female infertility even though the success rate appears small.


A new furanoxanthone from the stem bark of Calophyllum inophyllum.
The stem bark extracts of Calophyllum inophyllum furnished one new furanoxanthone, inophinnin (1), in addition to inophyllin A (2), macluraxanthone (3), pyranojacareubin (4), 4-hydroxyxanthone, friedelin, stigmasterol, and betulinic acid. The structures of these compounds were determined by spectroscopic analysis of 1D and 2D NMR spectral data ((1)H, (13)C, DEPT, COSY, HMQC, and HMBC) while EI-MS gave the molecular mass. The new xanthone, inophinnin (1), exhibited some anti-inflammatory activity in nitric oxide assay.


Cloning and expression of the Na+/H+ exchanger from Amphiuma RBCs: resemblance to mammalian NHE1.
The cDNA encoding the Na+/H+ exchanger (NHE) from Amphiuma erythrocytes was cloned, sequenced, and found to be highly homologous to the human NHE1 isoform (hNHE1), with 79% identity and 89% similarity at the amino acid level. Sequence comparisons with other NHEs indicate that the Amphiuma tridactylum NHE isoform 1 (atNHE1) is likely to be a phylogenetic progenitor of mammalian NHE1. The atNHE1 protein, when stably transfected into the NHE-deficient AP-1 cell line (37), demonstrates robust Na+-dependent proton transport that is sensitive to amiloride but not to the potent NHE1 inhibitor HOE-694. Interestingly, chimeric NHE proteins constructed by exchanging the amino and carboxy termini between atNHE1 and hNHE1 exhibited drug sensitivities similar to atNHE1. Based on kinetic, sequence, and functional similarities between atNHE1 and mammalian NHE1, we propose that the Amphiuma exchanger should prove to be a valuable model for studying the control of pH and volume regulation of mammalian NHE1. However, low sensitivity of atNHE1 to the NHE inhibitor HOE-694 in both native Amphiuma red blood cells (RBCs) and in transfected mammalian cells distinguishes this transporter from its mammalian homologue.


Conformation of cyclic and linear (1 --> 2)-beta-D-glucans in aqueous solution.
The conformations of cyclic (1 --> 2)-beta-D-glucan chains having degree of polymerization (dp) 17 to 24 were characterized by means of small-angle X-ray scattering and Monte Carlo simulation. The results indicate that cyclic (1 --> 2)-beta-D-glucan chains adopt the shape of a doughnut-like ring with a thickness of about 10 A for all the samples. The diameter of the annulus for the cyclic glucan having dp 21 is estimated to be only about 4-5 A. Two linear (1 --> 2)-beta-D-glucans possessing dp 19 and 21 prepared by acid hydrolysis of a cyclic glucan and subsequent fractionation showed different scattering profiles from those obtained for cyclic glucans having the corresponding dp. Although the Monte Carlo simulation does not completely reproduce the scattering profiles observed by small-angle X-ray scattering, linear (1 --> 2)-beta-D-glucans seem to possess a characteristic cylindrical shape with cross-sectional diameters of 11.8 and 13.2 A for linear glucans of dp 19 and 21, respectively.


Psychological Status and Influencing Factors of Hospital Medical Staff During the COVID-19 Outbreak.
The aim of this study was to analyze the psychological status of and its influencing factors in health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) outbreak so as to provide sufficient theory and scientific basis for the formulation and implementation of relevant policies and measures in improving the psychological status of HCWs. During February 1 to February 20, 2020, 1,002 members of the HCWs from Xi'an and Wuhan completed a 12-item questionnaire regarding pressure about the COVID-19 influenza pandemic, along with the 12-item General Health Questionnaire (GHQ-12). The GHQ-12 scale was divided by three points. The positive group was scored more than 3. All data were analyzed by SPSS. More than half of the participants (61.1%) reported psychological distress. The HCWs have sufficient information about the COVID-19 symptoms, prognosis, treatment, infection route, and preventive measures (medians ranged from 6/9 to 8/9). Female, engaged in clinic work less than 7 years, married person, and working in Wuhan were risk factors affecting the psychological status of HCWs (P < 0.05). Psychological distress is common in HCWs during the COVID-19 outbreak. Hospitals and relevant departments should provide psychological support to HCWs, and strict infection control measures should be developed.


Plasma Proteome Profiling of Patients With In-stent Restenosis by Tandem Mass Tag-Based Quantitative Proteomics Approach.
Despite the widespread application of new drug-eluting stents, a considerable portion of patients experience in-stent restenosis (ISR). To date, the pathophysiologic mechanisms of ISR remain poorly understood. In this study, we collected plasma samples from ISR patients (n = 29) and non-ISR patients (n = 36) after drug-eluting stent implantation, as well as from healthy controls (HCs) (n = 32). Our goal was to investigate differences in plasma protein profiles using tandem mass tag (TMT) labeling coupled with liquid chromatography and tandem mass spectrometry. The proteomic data were validated by enzyme-linked immunosorbent assay (ELISA). Bioinformatic analyses were conducted to analyze potential pathways and protein-protein interaction (PPI) involved in ISR. A total of 1,696 proteins were identified, of which 278 differed in protein abundance between non-ISR and HCs, 497 between ISR and HCs, and 387 between ISR and non-ISR, respectively. Bioinformatic analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and PPI, further demonstrated that differentially abundant proteins between ISR and non-ISR are involved in several crucial biological processes and signaling pathways, such as focal adhesion, platelet activation, Rap1 signaling, regulation of actin cytoskeleton, and cholesterol metabolism. Among the identified differentially abundant proteins in ISR, 170 were increased in abundance relative to both non-ISR patients and HCs. Some of these proteins were identified to have critical functions for atherosclerosis development and might be involved in ISR pathology. Among these proteins, 3 proteins with increased abundance including fetuin-B, apolipoprotein C-III (APOC3), and cholesteryl ester transfer protein (CETP) were confirmed by ELISA. This is the first study provided a comprehensive proteomic profile to understand ISR pathology, which may help identify early diagnostic biomarkers and therapeutic targets.


Effect(s) of preterm birth on normal retinal vascular development and oxygen-induced retinopathy in the neonatal rat.
Maturity is a critical factor in the pathogenesis of retinopathy of prematurity (ROP). One widely used method for studying this condition is that of oxygen-induced retinopathy (OIR). The general conditions of an OIR term animal, both at the time of birth and following birth, differ from those of the preterm infant. This, to simulate preterm conditions and to provide a basis for further studies on ROP, we investigated the effect(s) of preterm birth on retinal vascularization using the neonatal rat. Sprague-Dawley (SD) rats were delivered preterm by caesarean section on the day 19 of gestation. Term pups were used as controls. On the day of birth, preterm and term pups were housed under conditions of room air or cyclic oxygen. Retinas of pups housed in room air on days 4, 7, 10, 14, 18 and 22, as well as pups housed in oxygen on days 14, 18, and 22 were whole-mounted and stained with isolectin-B4. On day 18, cross-sections of the retina were cut and stained with hematoxylin and eosin for the identification of preretinal neovascular tufts. Images of avascular and neovascular areas were compared using light and fluorescence microscopy. Preterm pups had significantly larger avascular retinal areas than term rats on the various postnatal days. After exposure to cyclic oxygen, preterm pups demonstrated significantly larger avascular (days 14 and 18) and neovascular areas (day 18) compared with term rats. On day 22, residual retinopathy of preterm pups was greater than that of term pups. Preterm birth of rats, which are comparable in their physiology to humans, had negative effects on retinal vascularization. The impaired retinal vascular development and subsequent vasoproliferation resulting from hyperoxia in preterm pups is more severe and enduring.


Structural snapshots of V/A-ATPase reveal the rotary catalytic mechanism of rotary ATPases.
V/A-ATPase is a motor protein that shares a common rotary catalytic mechanism with FoF1 ATP synthase. When powered by ATP hydrolysis, the V1 domain rotates the central rotor against the A3B3 hexamer, composed of three catalytic AB dimers adopting different conformations (ABopen, ABsemi, and ABclosed). Here, we report the atomic models of 18 catalytic intermediates of the V1 domain of V/A-ATPase under different reaction conditions, determined by single particle cryo-EM. The models reveal that the rotor does not rotate immediately after binding of ATP to the V1. Instead, three events proceed simultaneously with the 120˚ rotation of the shaft: hydrolysis of ATP in ABsemi, zipper movement in ABopen by the binding ATP, and unzipper movement in ABclosed with release of both ADP and Pi. This indicates the unidirectional rotation of V/A-ATPase by a ratchet-like mechanism owing to ATP hydrolysis in ABsemi, rather than the power stroke model proposed previously for F1-ATPase.


Clinical challenge. II. Management of recent onset atrial fibrillation. PAFIT-2 Investigators.
Atrial fibrillation is a very common arrhythmia in patients with structural heart disease, but it also occurs in patients without underlying heart disease. Acute therapy for paroxysmal atrial fibrillation is very dependent on the clinical condition of the patient. Direct current cardioversion is usually the first choice whenever the arrhythmia precipitates heart failure or severe angina, while more stable patients are normally treated with drugs. Most episodes of atrial fibrillation eventually convert to sinus rhythm even in the absence of treatment. Antiarrhythmic drugs can be used to control the ventricular response or to restore sinus rhythm, and several have been tested to assess their ability to convert recent onset atrial fibrillation. The success rate has varied, but generally flecainide and propafenone appear the most effective. Digitalis and calcium channel blockers do not increase the likelihood of reversion but they reduce ventricular rate. Amiodarone has been tested as a possible alternative to flecainide and propafenone. The pros and the cons of these and other drugs in the setting of paroxysmal atrial fibrillation will be discussed. In particular, special emphasis will be given to the differences in the design and in patient selection of the trials that tested antiarrhythmic drugs in paroxysmal atrial fibrillation.


MiR-27-3p regulates TLR2/4-dependent mouse alveolar macrophage activation by targetting PPARγ.
Activation of alveolar macrophages (AMs) and the release of cytokines play critical roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, little is known about the mechanisms of AM activation. miRNAs have recently emerged as key regulators of inflammation and as mediators of macrophage activation and polarization. We identified potential miRNAs related to AM activation using miRNA microarray analysis, which showed that miR-27-3p expression was up-regulated in AMs and the lung tissues of mice exposed to cigarette smoke (CS)/lipopolysaccharide (LPS), and found that miR-27-3p regulated proinflammatory cytokine production and AM polarization depending on TLR2/4 intracellular signaling in AMs. We also found that miR-27-3p controlled TLR2/4 signaling in AMs via targetting the 3'-UTR sequences of peroxisome proliferator-activated receptor γ (PPARγ) and inhibiting PPARγ activation. Moreover, we found that PPARγ activation not only inhibited CS/LPS-induced TLR2/4 expression and miR-27-3p-mediated TLR2/4 signaling cascades involving the nuclear factor-κB (NF-κB), c-Jun NH2-terminal kinase (JNK)/p38, and Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathways in AMs but also ameliorated CS/LPS-induced AM activation and pulmonary inflammation. Our study revealed that miR-27-3p mediated AM activation by the inhibition of PPARγ activation and sensitization of TLR signaling.


Global analysis of a plasmid-cured Shigella flexneri strain: new insights into the interaction between the chromosome and a virulence plasmid.
Shigella flexneri is an important human pathogen that causes dysentery, and remains a significant threat to public health, particularly in developing countries. The virulence of this pathogen is dependent on an acquired virulence plasmid. To investigate the crosstalk between the bacterial chromosome and the exogenous virulence plasmid, a virulence plasmid-cured strain was constructed using plasmid incompatibility. The global patterns of gene expression of this strain compared with the wild-type strain were analyzed using 2-DE combined with MALDI-TOF MS. Most known virulence factors of S. flexneri were identified in the 2-DE gels. Interestingly, the expression of the glycerol 3-phosphate (glp) regulon-encoded proteins was increased when the virulence plasmid was absent. Microarray analysis confirmed that regulation occurred at the transcriptional level. Purification and identification of DNA binding proteins with affinity for the regulatory region of the glp genes revealed that regulation mediated by the virulence plasmid to control the expression of the glp regulon might in turn be mediated by protein GlpR. To our knowledge, this is the first study analyzing the interaction between a pathogen chromosome and a virulence plasmid at the proteomic level.


Attenuated Total Reflection Far-Ultraviolet (ATR-FUV) Spectroscopy is a Sensitive Tool for Investigation of Protein Adsorption.
Attenuated total reflection far-ultraviolet (ATR-FUV) spectra in the 145-250 nm region were studied for four kinds of proteins (two α-helix-rich proteins: bovine serum albumin (BSA) and lysozyme and two β-sheet rich proteins: concanavalin A and γ-globulin) in different solutions (pure water and phosphate buffered saline, or PBS) with different concentrations. All the spectra show a band at 191 nm due to the π-π* transition of amide bonds of the proteins. The wavelength of the band does not change with their second structures, suggesting that the corresponding electronic transition mode is localized and polarized in the direction that is not affected by the difference in the peptide folding. The intensity of the 191 nm band differs with the concentration of salt in the solution, suggesting that the band intensity reflects the adsorption density of a protein on the internal reflection element (IRE) made of a sapphire glass prism. According to the intensity changes of the band at 191 nm, it is revealed that the properties in adsorption are different from one protein to another. It is assumed that there are two types of forces on the protein adsorption: one is that among the molecules and the other is that between a molecule and a substrate. The origin of force includes localized electrostatic polarity and affinity to water. The ions in the solvent give a marked effect on these forces, resulting in the difference in the response to adsorption density against the salt concentration in the solvent.


Vascular diseases and old age mental disorders: an update of neuroimaging findings.
To review neuroimaging findings that have been reported in samples of patients with cardiovascular disorders and their association with the onset of Alzheimer's disease, vascular dementia, depression and bipolar disorder in the elderly and to highlight the implications of these findings to the knowledge about the pathophysiology of psychiatric disorders in old age, as well as their potential clinical implications. Vascular risk factors, such as hypertension, diabetes, dyslipidemia, smoking habits and heart failure, have all been associated with signs of cerebrovascular dysfunction, including structural MRI findings of signal hyperintensities, lacunes and stroke and functional imaging findings of brain regional hypoperfusion and hypometabolism. Such brain abnormalities have been found to increase the risk of onset of psychiatric disorder (depression, bipolar and dementia) in old age. As vascular risk factors are potentially modifiable when detected in midlife, the early characterization of brain changes associated with the presence of cardiovascular diseases holds promise to afford clinical applications in psychiatry, providing new perspectives for the prevention of old age psychiatric disorders.


Treatment of amatoxin poisoning: 20-year retrospective analysis.
Amatoxin poisoning is a medical emergency characterized by a long incubation time lag, gastrointestinal and hepatotoxic phases, coma, and death. This mushroom intoxication is ascribed to 35 amatoxin-containing species belonging to three genera: Amanita, Galerina, and Lepiota. The major amatoxins, the alpha-, beta-, and gamma-amanitins, are bicyclic octapeptide derivatives that damage the liver and kidney via irreversible binding to RNA polymerase II. The mycology and clinical syndrome of amatoxin poisoning are reviewed. Clinical data from 2108 hospitalized amatoxin poisoning exposures as reported in the medical literature from North America and Europe over the last 20 years were compiled. Preliminary medical care, supportive measures, specific treatments used singly or in combination, and liver transplantation were characterized. Specific treatments consisted of detoxication procedures (e.g., toxin removal from bile and urine, and extracorporeal purification) and administration of drugs. Chemotherapy included benzylpenicillin or other beta-lactam antibiotics, silymarin complex, thioctic acid, antioxidant drugs, hormones and steroids administered singly, or more usually, in combination. Supportive measures alone and 10 specific treatment regimens were analyzed relative to mortality. Benzylpenicillin (Penicillin G) alone and in association was the mostfrequently utilized chemotherapy but showed little efficacy. No benefit was found for the use of thioctic acid or steroids. Chi-square statistical comparison of survivors and dead vs. treated individuals supported silybin, administered either as mono-chemotherapy or in drug combination and N-acetylcysteine as mono-chemotherapy as the most effective therapeutic modes. Future clinical research should focus on confirming the efficacy of silybin, N-acetylcysteine, and detoxication procedures.


Exhaustive endurance exercise activates brain glycogen breakdown and lactate production more than insulin-induced hypoglycemia.
Brain glycogen localized in astrocytes produces lactate via cAMP signaling, which regulates memory functions and endurance capacity. Exhaustive endurance exercise with hypoglycemia decreases brain glycogen, although the mechanism underlying this phenomenon remains unclear. Since insulin-induced hypoglycemia decreases brain glycogen, this study tested the hypothesis that hypoglycemia mediates exercise-induced brain glycogen decrease. To test the hypothesis, the effects of insulin- and exhaustive exercise-induced hypoglycemia on brain glycogen levels were compared using the microwave irradiation method in adult Wistar rats. The insulin challenge and exhaustive exercise induced similar levels of severe hypoglycemia. Glycogen in the hypothalamus and cerebellum decreased similarly with the insulin challenge and exhaustive exercise; however, glycogen in the cortex, hippocampus, and brainstem of the exercise group were lower compared with the insulin group. Brain lactate and cAMP levels in the hypothalamus and cerebellum increased similarly with the insulin challenge and exhaustive exercise, but those in the cortex, hippocampus, and brainstem of the exercise group were higher compared with the insulin group. Blood glucose correlated positively with brain glycogen, but the slope of regression lines was greater in the exercise group compared with the insulin group in the cortex, hippocampus, and brainstem, but not the hypothalamus and cerebellum. These findings support the hypothesis that hypoglycemia mediates the exercise-induced reduction in brain glycogen, at least in the hypothalamus and cerebellum. However, glycogen reduction during exhaustive endurance exercise in the cortex, hippocampus, and brainstem is not due to hypoglycemia alone, implicating the role of exercise-specific neuronal activity in brain glycogen decrease.


Effects of Laser Acupuncture Therapy for Patients With Inadequate Recovery From Bell's Palsy: Preliminary Results From Randomized, Double-Blind, Sham-Controlled Study.
Introduction: Inadequate recovery from Bell's palsy exists in a third of patients and results in physical and social impairments. The controversial nature of existing medical treatment options means that novel, alternative approaches are needed. In basic and clinical studies, low-level laser therapy (LLLT) has proven successful in regenerating peripheral nerves. Laser acupuncture therapy (LAT) is a rapidly growing treatment modality; however, its effectiveness for treating chronic Bell's palsy is unknown. The feasibility of this innovative approach is the focus of this pilot study. Methods: A two-armed, parallel, randomized, investigator-subject-assessor-blinded, sham-controlled pilot study was conducted, and 17 eligible subjects were randomly allocated to either LAT (n=8) or sham LAT (n=9). The LAT group received three treatments each week for six weeks (18 sessions), while the sham LAT group received the same procedure but with a sham laser device. The change from baseline to week 6 in the social subscale of the Facial Disability Index (FDI) was the primary outcome. Secondary outcomes were changes in the House-Brackmann facial paralysis scale (HB), the Sunnybrook facial grading system (SB) and a stiffness scale at weeks 3 and 6. Results: A significant difference was shown in the HB score (P=0.0438) between baseline and week 3 and borderline significance was observed in both SB and stiffness scores from baseline to week 6 (P=0.0598 and P=0.0980 respectively). There was no significant difference in the FDI score between baseline and week 6. Conclusion: To the best of our knowledge, this clinical trial is the first such investigation on this topic. Our findings suggest that using LAT may have clinical effects on long-term complications of Bell's palsy and justify further large-scale studies.


Effects of Nutritional Interventions on Cardiovascular Disease Health Outcomes in Aboriginal and Torres Strait Islander Australians: A Scoping Review.
Nutrition interventions can support Aboriginal and Torres Strait Islander peoples to reduce their risk of cardiovascular disease (CVD). This review examines nutritional interventions aiming to improve CVD outcomes and appraises peer-reviewed interventions using an Aboriginal and Torres Strait Islander Quality Appraisal Tool. Five electronic databases and grey literature were searched, applying no time limit. Two reviewers completed the screening, data extraction and quality assessment independently. The study quality was assessed using the South Australian Health and Medical Research Institute and the Centre of Research Excellence in Aboriginal Chronic Disease Knowledge Translation and Exchange Aboriginal and Torres Strait Islander Quality Appraisal Tool (QAT). Twenty-one nutrition programs were included in this review. Twelve reported on anthropometric measurements, ten on biochemical and/or hematological measurements and sixteen on other outcome domains. Most programs reported improvements in measurable CVD risk factors, including reduced body mass index (BMI), waist circumference (WC), weight, blood pressure and improved lipid profiles. Most programs performed well at community engagement and capacity strengthening, but many lacked the inclusion of Indigenous research paradigms, governance and strengths-based approaches. This review highlights the need for contemporary nutrition programs aimed at improving cardiovascular health outcomes to include additional key cultural components.


[Prophylaxis of intraoperative nausea and vomiting with sub-hypnotic dose of propofol during intradural anesthesia in cesarean section].
To determine the preventive and therapeutic effect of 10 mg of propofol administered after delivery on the incidence of intraoperative nausea and vomiting (IONV) during intradural anesthesia for cesarean delivery. Controlled, randomized double blind study of 60 women (ASA I-II) receiving intradural anesthesia for elective or deferred emergency cesarean delivery. The propofol group received 10 mg i.v. immediately after fetal extraction. The control group received an equal volume of Intralipid. The presence of IONV after administration of the prophylactic bolus was treated with a second bolus, and if nausea had not subsided completely after two minutes, treatment was topped up with dehydro-benzoperidol. The control group included 31 women and the propofol group 29, of whom 3 were excluded. Control variables were similar in the two groups. There were no significant differences in the incidence and severity of IONV between the two groups (22.5 versus 23%). The top-up antiemetic drug was used in the same number of patients in each group. Although 10 mg propofol has been described as an effective direct antiemetic, episodes of IONV were neither prevented nor reversed by its use during intradural anesthesia for cesarean delivery.


Regional anaesthesia and analgesia on the front line.
Deployment to a combat zone with the military poses many challenges to the anaesthetist. One of these challenges is the safe, rapid and comfortable initial wound management and repatriation of wounded combat soldiers to their home country or tertiary treatment facility for definitive care and rehabilitation. The current conflict in Afghanistan is associated with injury patterns that differ from wars such as Vietnam or Korea. This report describes the experience of an Australian military anaesthetist and the value of regional anaesthesia and analgesia for the care of the wounded combat soldier


Synthetic Sansanmycin Analogues as Potent Mycobacterium tuberculosis Translocase I Inhibitors.
Herein, we report the design and synthesis of inhibitors of Mycobacterium tuberculosis (Mtb) phospho-MurNAc-pentapeptide translocase I (MurX), the first membrane-associated step of peptidoglycan synthesis, leveraging the privileged structure of the sansanmycin family of uridylpeptide natural products. A number of analogues bearing hydrophobic amide modifications to the pseudo-peptidic end of the natural product scaffold were generated that exhibited nanomolar inhibitory activity against Mtb MurX and potent activity against Mtb in vitro. We show that a lead analogue bearing an appended neopentylamide moiety possesses rapid antimycobacterial effects with a profile similar to the frontline tuberculosis drug isoniazid. This molecule was also capable of inhibiting Mtb growth in macrophages where mycobacteria reside in vivo and reduced mycobacterial burden in an in vivo zebrafish model of tuberculosis.


Comparison of changes in tumor metabolic activity and tumor size during chemotherapy of adenocarcinomas of the esophagogastric junction.
We evaluated the temporal relationship between chemotherapy-induced changes in tumor glucose use and tumor size. Twenty patients with adenocarcinoma of the esophagogastric junction (AEG) were studied by 18F-FDG PET and CT scans before neoadjuvant chemotherapy, 14 d after the initiation of therapy, and 4 wk after the completion of therapy. The relative change in 18F-FDG uptake was more than 2 times larger than the decrease in tumor size at all time points (P<0.01). At 14 d after the initiation of chemotherapy, there was no correlation between the reduction in 18F-FDG uptake and tumor wall thickness. The change in 18F-FDG uptake after 14 d of therapy was significantly correlated with the reduction in tumor size after the completion of therapy. In AEG, changes in tumor metabolism are a more sensitive parameter for assessing the effects of chemotherapy than are changes in tumor size. Early changes in metabolic activity predict the subsequent reduction in tumor size.


Complications of hypertension in men and women seen in a referral outpatient care unit.
To assess the association between sex and left ventricular hypertrophy, stroke, and renal failure in hypertensive patients in a referral outpatient care unit. This study assessed 622 hypertensive patients diagnosed with left ventricular hypertrophy based on electrocardiography, renal failure based on serum creatinine level > or = 1.4 mg/dL, and stroke based on a previous history and physical examination. Logistic regression was used to estimate the odds ratio of the association between sex and target-organ lesions in hypertension adjusted for race, age, and duration of the disease. The mean age of the patients was 48.4 +/- 13.8 years; 74.1% were women, and 84.9% were mulattos or blacks. Almost half of the men and more than 40% of the women had had at least 1 definite event involving a target-organ lesion. The incidence of renal failure was greater among men [adjusted OR (ORa) = 2.73, P= 0.002]. In white patients, the incidence of stroke was significantly (P= 0.017) greater among men (4/33) than among women (0/56), and, in the age group > or = 49 years, the prevalence of left ventricular hypertrophy was significantly greater among men (ORa = 1.99, P= 0.024). The data obtained suggest a greater prevalence of renal failure in men than in women, of stroke in white men than in white women, and of left ventricular hypertrophy in men than in women aged 49 years and above.


Relations between structure and function in rat skeletal muscle fibers.
The fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus muscle of the rat consist of heterogeneous fiber populations. EDL muscle fibers differ in size, mitochondrial content, myoglobin concentration, and thickness of the Z line. The sarcoplasmic reticulum, on the other hand, is richly developed in all fibers, with only small variation. Myofibrils are clearly circumscribed at both the A and I band level. The soleus muscle is composed primarily of fibers with moderate mitochondrial content and myoglobin concentration. In most fibers the sarcoplasmic reticulum is poorly developed, with the exception of the portion of reticulum in phase with the Z line. As a consequence the myofibrillar fields are amply fused together. Contacts between sarcoplasmic reticulum and T system are discontinuous and may occur in the form of "dyads" instead of the typical triad structure. In a small proportion of soleus muscle fibers the organization and development of the sarcoplasmic reticulum is similar to that of EDL muscle fibers, with prominent fenestrated collars at the H band level. In these fibers mitochondria are larger and more abundant. The results are correlated with physiological studies on motor units in the same and in similar rat muscles. It is suggested that the variable structural pattern of rat muscle fibers is related to two distinct physiological parameters, speed of contraction and resistance to fatigue.


Solution-phase hexasaccharide synthesis using glucosyl iodides.
[reaction: see text] Oligosaccharides composed of 1,6-glucosyl residues have been prepared from glucosyl iodides. The reactions are highly stereoselective, giving the alpha-glycosides as the only isolated products in yields ranging from 84% to 94%. Oligomer synthesis can take place in an iterative 1 + 1 + 1 fashion or in a convergent manner where dimer iodides serve as donors for higher order acceptors.


Side effects after phototherapy implementation in addition to fluoxetine or sertraline treatment: a report of two cases.
Serotonergic-type side effects (like diarrhoea, hyperthermia, nausea, confusion) were seen after phototherapy in patients receiving fluoxetine or sertraline. Phototherapy was discontinued and symptoms completely resolved. In the authors' opinion, the symptoms were likely to be associated with specific interaction (serotonin effect potentialisation). To the authors' knowledge this is the first report concerning such an effect.


Incidence and natural history of below-knee deep venous thrombosis in high-risk trauma patients.
Venous thromboembolic disease remains a difficult problem in the trauma patient population. The purpose of this study was to delineate the incidence and natural history of below-knee deep venous thrombosis (BKDVT) in high-risk trauma patients. Patients were stratified into risk categories (low, high, or very high) for deep venous thrombosis on the basis of an institutional practice management guideline and known risk factors. All at-risk patients received either sequential compression devices (SCDs) or subcutaneous heparin (SQH) compounds, and high-risk patients also underwent weekly surveillance by duplex scanning. Very-high-risk patients had prophylactic inferior vena cava (IVC) filter placement. This prospective, observational study examines the duplex results on all high-risk patients. Data regarding method of prophylaxis, the incidence of proximal propagation on serial duplex examinations, and changes in management (anticoagulation or IVC filter placement) were collected on the high-risk patients who developed a BKDVT. Between March 1997 and June 2001, 601 patients were stratified into the high-risk category and underwent a total of 1,109 duplex examinations. Eighty-five patients (14.1%) had 113 BKDVTs. These patients underwent a total of 212 duplex examinations; all patients developed their BKDVTs within 34 days. Weekly incidence was 40 (47.1%), 25 (29.4%), 15 (17.6%), 1 (1.2%), and 4 (4.7%) for weeks 1 through 5, respectively. SCDs, SQH compounds, and SCDs with SQH compounds were used on 73, 3, and 9 patients, respectively. In 4 of 85 (4.7%) patients, the BKDVT propagated proximally to an above-knee location in 4 to 8 days. Two of these patients were anticoagulated, and two underwent placement of an IVC filter. One patient (1.2%) with a BKDVT that had not propagated on duplex study developed a pulmonary embolus. Patients identified as high-risk by our practice management guideline had a 14.1% incidence of a BKDVT; 94.1% were diagnosed within the first 3 weeks of hospitalization. Proximal propagation occurred in 4.7% and led to changes in management. Serial duplex examination of the BKDVT alone, rather than systemic anticoagulation or IVC filter placement, appears to be a reasonable treatment alternative.


Administration of comfort medication at end of life in neonates: effects of weight.
To examine whether a relationship exists between a neonate's weight and the neonate's receipt of comfort medication between four hours prior to elective ventilator withdrawal and death. It was hypothesized that the greater the neonate's weight, the more likely the neonate was to receive comfort medication at end of life. A retrospective chart review. One hundred seventy-one neonates in a midwestern Level III NICU who died after withdrawal of ventilatory support. Of the 171 neonates in the sample, 27.5 percent (n = 47) did not receive comfort medication within the designated time frame; neonates who weighed < 800 g were significantly less likely to receive comfort medication than were their heavier cohorts. In this sample, smaller neonates were given comfort medication less often while they were dying than were their larger counterparts.


Anthocyanin suppresses CoCrMo particle-induced osteolysis by inhibiting IKKα/β mediated NF-κB signaling in a mouse calvarial model.
Wear particle-induced osteolysis and bone resorption have been identified as critical factors of implant failure and total joint revision, in which nuclear factor kappa B (NF-κB) signaling and chronic inflammation have been shown to play key roles. Although anthocyanin is known to have anti-inflammatory function via blocking NF-κB pathway, it is still unclear whether anthocyanin has a protective effect on particle-induced osteolysis. In the present study, we aimed to investigate the detailed effects and the underlying mechanism of anthocyanin on CoCrMo particle-induced osteolysis in a mouse calvavial model. One hundred and twelve male BALB/c mice were divided randomly into four groups: sham group (sham operation and injection with PBS), vehicle group (CoCrMo particle treatment and injection with PBS), low-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.1mg/g/day), and high-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.4mg/g/day). Mice were sacrificed after two weeks, harvesting the calvariae tissue for in depth analysis by micro-CT, histomorphometry, immunohistochemical and molecular biology analysis. As expected, anthocyanin markedly inhibited CoCrMo particle-induced inflammatory infiltration and decreased bone loss in vivo. Anthocyanin also reversed the increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL)/osteoproteger (OPG) and suppressed osteoclast formation in CoCrMo particle-stimulated calvaria. Additionally, anthocyanin significantly reduced the expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the calvaria of CoCrMo-stimulated mice. Furthermore, we confirmed that anthocyanin attenuated osteolysis by blocking NF-κB pathway via inhibiting inhibitor of nuclear factor kappa-B kinase α/β (IKKα/β) phosphorylation. In conclusion, our study demonstrated that anthocyanin can protect against CoCrMo particle-induced inflammatory osteolysis via inhibiting the IKKα/β-NF-κB pathway, and have a potential therapeutic effect on the treatment of wear particle-induced osteolysis.


Physical activity, BMI and body weight perception among 15-year-old boys and girls in Poland in the light of international comparisons.
The wrong subjective assessment of body mass may have consequences for the health, quality of life and proper functioning of adolescents in society. The purpose of the study is to provide a detailed analysis of the discrepancies between the objective and subjective assessment of body mass by 15-year-old boys and girls in Poland against the background of international statistics and to assess the effect of physical activity on the level and directions of these discrepancies. The data concerned 72037 schoolchildren from 42 countries, including 1484 in Poland. The measure of objective body mass was the BMI categorized according to Cole's criteria. Research focused on the relation between the mean BMI and the subjective perception of their body mass by adolescents and the discrepancy in this assessment. In addition, the level of physical activity (MVPA) was taken into account. In Poland the percentage of adolescents with overweight was lower than the international average and amounted to 12.3% vs. 15.2%. The percentage of 15-year-old boys with overweight in Poland is nearly three times higher than girls of the same age (18.7% vs. 6.5%) and is at the mean level for Health Behaviour in School-aged Children (HBSC) countries. According to international statistics, the percentage of adolescents who consider themselves overweight is 32.7%, which is two times higher than the percentage of actual excess body weight. Polish girls are systematically first in the ranking of those who consider themselves too fat. It was demonstrated that Polish girls with a normal BMI for their age who consider themselves too fat are on average slimmer than their peers in other countries. There is a correlation between Moderate-to-Vigorous Physical Activity (MVPA) and the accuracy of self-assessment of body mass and the type of mistakes made in that assessment, which is more clearly marked among boys. There are clear geographical and cultural differences in the level of discrepancies between the objective and subjective assessment of body mass among teenagers. Physical activity modifies these discrepancies.