[Generalized peritonitis of non-traumatic colonic origin. Reflexions on 62 cases].
The authors analyze sixty-two cases of acute generalized peritonitis with a non-traumatic colonic etiology. They point out that the prognosis depends on three main factors: the age of the patient, the time spent in diagnosis and the therapeutic difficulties. They recommend a gastrographin colonic enema to obtain earlier diagnosis, in the absence of radiological evidence of pneumoperitoneum, in elderly patients presenting with abdominal signs. They also recommend multistage surgical management combining effective drainage of the abdominal cavity with resection of the perforated segment of the colon, whenever there is extensive damage to the colon, or in the presence of a tumor. In their view, conservative surgery should be confined to strictly selected cases not involving tissue resection. These indications are essential if a satisfactory result is to be achieved.


Effect of adjunctive use of green tea dentifrice in periodontitis patients - A Randomized Controlled Pilot Study.
Green tea is known to possess anti-inflammatory, antibacterial and antioxidant activities. This study evaluated the effect of a locally prepared green tea dentifrice on specific parameters assessing gingival inflammation and severity of periodontal disease, when used as an adjunct to scaling and root planing (SRP) in the management of chronic periodontitis by comparing with a fluoride-triclosan-containing control dentifrice. Thirty patients, with mild to moderate chronic periodontitis, were randomly allocated into two treatment groups, 'test' and 'control' after initial SRP. The test group was given green tea dentifrice with instructions on method of brushing, while the control group received a commercially available fluoride and triclosan containing dentifrice. Clinical parameters of Gingival Index (GI), Plaque Index (PI), percentage of sites with bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL) along with biochemical parameters of total antioxidant capacity (TAOC) and glutathione-S-transferase (GST) activity in gingival crevicular fluid (GCF) were recorded at baseline line and 4 weeks post-SRP. Intragroup analysis at 4 weeks showed statistically significant improvements of GI, PI, BOP, PD, CAL and TAOC in both groups. GST activity however, was increased only in the test group. At the end of the study period, the test group showed statistically significant improvements in GI, BOP, CAL, TAOC and GST levels compared to the control group. On comparison with fluoride-triclosan dentifrice, green tea showed greater reduction of gingival inflammation and improved periodontal parameters. Green tea dentifrice may serve as a beneficial adjunct to non-surgical periodontal therapy.


Phase behavior and free interfaces of a lattice-gas nematic-liquid-crystal model.
The phase behavior of a mesogenic lattice-gas model consisting of molecules located at the sites of a three-dimensional cubic lattice has been studied using grand canonical Monte Carlo simulations. When two neighboring sites are occupied, the molecules interact via a potential composed of an isotropic lattice-gas (LG) term and an anisotropic Humphries-Luckhurst-Romano (HLR) term [Mol. Phys. 42, 1205 (1981)]. The LGHLR model is shown to exhibit either nematic-isotropic, nematic-vapor (NV), and isotropic-vapor (IV) coexistence or just nematic-isotropic fluid coexistence, depending on the strength of the isotropic term. The liquid-vapor (i.e., NV and IV) interfaces were studied using canonical Monte Carlo simulations. By controlling the strength of the term that governs the anisotropy in the attractive forces, either planar or homeotropic anchoring is observed at the NV interface. The temperature dependencies of the density and order parameter profiles across the interfaces are determined for these two anchoring geometries.


Parental Death Across the Life Course, Social Isolation, and Health in Later Life: Racial/Ethnic Disadvantage in the U.S.
Bereavement is a risk factor for poor health, yet prior research has not considered how exposure to parental death across the life course may contribute to lasting social isolation and, in turn, poor health among older adults. Moreover, prior research often fails to consider the racial context of bereavement in the United States wherein Black and Hispanic Americans are much more likely than White Americans to experience parental death earlier in life. The present study uses longitudinal data from the Health and Retirement Study (HRS; 1998-2016) to consider linkages of parental death, social isolation, and health (self-rated health, functional limitations) for Black, Hispanic, and White older adults. Findings suggest that exposure to parental death is associated with higher levels of isolation, greater odds of fair/poor self-rated health, and greater odds of functional limitations in later life. Moreover, social isolation partially explains associations between parental bereavement and later-life health. These patterns persist net of psychological distress-an additional psychosocial response to bereavement. Racial inequities in bereavement are central to disadvantage: Black and Hispanic adults are more likely to experience a parent's death earlier in the life course, and this differential exposure to parental death in childhood or young adulthood has implications for racial and ethnic inequities in social isolation and health throughout life.


Structure of the S100A4/myosin-IIA complex.
S100A4, a member of the S100 family of Ca2+-binding proteins, modulates the motility of both non-transformed and cancer cells by regulating the localization and stability of cellular protrusions. Biochemical studies have demonstrated that S100A4 binds to the C-terminal end of the myosin-IIA heavy chain coiled-coil and disassembles myosin-IIA filaments; however, the mechanism by which S100A4 mediates myosin-IIA depolymerization is not well understood. We determined the X-ray crystal structure of the S100A4Δ8C/MIIA(1908-1923) peptide complex, which showed an asymmetric binding mode for the myosin-IIA peptide across the S100A4 dimer interface. This asymmetric binding mode was confirmed in NMR studies using a spin-labeled myosin-IIA peptide. In addition, our NMR data indicate that S100A4Δ8C binds the MIIA(1908-1923) peptide in an orientation very similar to that observed for wild-type S100A4. Studies of complex formation using a longer, dimeric myosin-IIA construct demonstrated that S100A4 binding dissociates the two myosin-IIA polypeptide chains to form a complex composed of one S100A4 dimer and a single myosin-IIA polypeptide chain. This interaction is mediated, in part, by the instability of the region of the myosin-IIA coiled-coil encompassing the S100A4 binding site. The structure of the S100A4/MIIA(1908-1923) peptide complex has revealed the overall architecture of this assembly and the detailed atomic interactions that mediate S100A4 binding to the myosin-IIA heavy chain. These structural studies support the idea that residues 1908-1923 of the myosin-IIA chain heavy represent a core sequence for the S100A4/myosin-IIA complex. In addition, biophysical studies suggest that structural fluctuations within the myosin-IIA coiled-coil may facilitate S100A4 docking onto a single myosin-IIA polypeptide chain.


Weekly minutes of moderate to vigorous physical activity is associated with movement quality in overweight and obese older adults, independent of age.
Physical activity can improve function and decrease healthcare spending among overweight and obese older adults. Although unstructured physical activity has been related to cardiometabolic improvements, the relationship between unstructured activity and movement quality is unclear. This study aimed to evaluate the association of amount of unstructured free-living moderate-vigorous physical activity (MVPA) with measures of movement quality in overweight and obese older adults. The association of MVPA with movement quality was assessed in 165 overweight and obese older adults (Age: 77.0(8.0) years; Body mass index (BMI): 29.2(5.3) kg/m2). Participants performed overground walking, the Figure of 8 Walk test, and the Five-Times Sit to Stand. Weekly physical activity was measured using a waist-worn Actigraph activity monitor. Movement quality during straight path [gait speed (ρ = 0.30, p < 0.01), stride length (ρ = 0.33, p < 0.01), double-limb support time (ρ = -0.26, p < 0.01), and gait symmetry (ρ = 0.17, p = 0.02)] and curved path [F8W time (ρ = -0.22, p < 0.01) and steps (ρ = -0.22, p < 0.01)] walking were associated with weekly minutes of MVPA after controlling for age. Five-Times Sit to Stand performance was not significantly associated with weekly minutes of MVPA (ρ = -0.10, p = 0.13). Older adults with high BMIs who are less active also demonstrate poorer movement quality, independent of age. Physical activity engagement and task-specific training should be targeted in interventions to promote healthy aging, decrease falls, and delay disability development. Future work should consider the interconnected nature of movement quality with physical activity engagement and investigate if targeting one influences the other.


The diagnostic value of biomarkers (AshTest) for the prediction of alcoholic steato-hepatitis in patients with chronic alcoholic liver disease.
The aim was to identify a panel of biomarkers (AshTest) for the diagnosis of alcoholic steato-hepatitis (ASH), in patients with chronic alcoholic liver disease. Biomarkers were assessed in patients with an alcohol intake>50 g/d, in a training group, and in two validation groups. Diagnosis of ASH (polymorphonuclear infiltrate and hepatocellular necrosis) and its histological severity (four classes: none, mild, moderate and severe) were assessed blindly. Two hundred and twenty-five patients were included, 70 in the training group, 155 in the validation groups, and 299 controls. AshTest was constructed using a combination of the six components of FibroTest-ActiTest plus aspartate aminotransferase. The AshTest area under the ROC curves for moderate-severe ASH was 0.90 in the training group, 0.88 and 0.89 in the validation groups. The median AshTest value was 0.005 in controls, 0.05 in patients without or with mild ASH, 0.64 in moderate, and 0.84 in severe ASH grade 3, (P<0.05 between all groups). At a 0.50 cut-off, the sensitivity of AshTest was 0.80 and the specificity was 0.84. In heavy drinkers, AshTest is a simple and non-invasive quantitative estimate of alcoholic hepatitis. The use of AshTest may reduce the need for liver biopsy, and therefore allow an earlier treatment of alcoholic hepatitis.


[Primary structure and species specificity of immunopoietins].
A model involving quasicyclization of protein molecules following the stepwise reactions of limited proteolysis was developed. On the basis of the model new active sites were detected in immunoglobulins of various species as well as chemical synthesis of the sites was carried out. The new group of the substances was designated as immunopoietins. The primary structure of various species immunoglobulins was analyzed and evolutional stability of the immunopoietin structure was shown.


The first genetic map of the American cranberry: exploration of synteny conservation and quantitative trait loci.
The first genetic map of cranberry (Vaccinium macrocarpon) has been constructed, comprising 14 linkage groups totaling 879.9 cM with an estimated coverage of 82.2 %. This map, based on four mapping populations segregating for field fruit-rot resistance, contains 136 distinct loci. Mapped markers include blueberry-derived simple sequence repeat (SSR) and cranberry-derived sequence-characterized amplified region markers previously used for fingerprinting cranberry cultivars. In addition, SSR markers were developed near cranberry sequences resembling genes involved in flavonoid biosynthesis or defense against necrotrophic pathogens, or conserved orthologous set (COS) sequences. The cranberry SSRs were developed from next-generation cranberry genomic sequence assemblies; thus, the positions of these SSRs on the genomic map provide information about the genomic location of the sequence scaffold from which they were derived. The use of SSR markers near COS and other functional sequences, plus 33 SSR markers from blueberry, facilitates comparisons of this map with maps of other plant species. Regions of the cranberry map were identified that showed conservation of synteny with Vitis vinifera and Arabidopsis thaliana. Positioned on this map are quantitative trait loci (QTL) for field fruit-rot resistance (FFRR), fruit weight, titratable acidity, and sound fruit yield (SFY). The SFY QTL is adjacent to one of the fruit weight QTL and may reflect pleiotropy. Two of the FFRR QTL are in regions of conserved synteny with grape and span defense gene markers, and the third FFRR QTL spans a flavonoid biosynthetic gene.


The low-level laser on acute myositis in rats.
To analyze the effects of the low-level laser therapy in the acute myositis induced in rats. Twelve rats were subjected to bilateral ovariectomy for inducing osteoporosis. After surgery, they were divided into two groups: Ovariectomy-control group (G1, n=6), receiving 0.5 ml distilled water by gavage for 30 days, and Ovariectomy plus mastruz group (G2, n=6), receiving 0.5 ml of the hydroalcoholic extract of mastruz at 10% concentration (50mg) daily, for the same period. Then, the blood of the animals was collected for further biochemical analysis (liver function) and tibia and liver were removed for histological and histomorphometric analyses. In the MT group there was a statistic significant decrease in the number of inflammatory cells, related to the MI group (p<0.05), increase in the fibroblastic proliferation, when compared to groups C and MI related to MT group (p<0.01) and statistic significant edema regression (p=0.0400) in the MT group The low-level laser therapy was efficient in the reduction of the inflammatory process, increase of the fibroblastic proliferation and the reduction of the edema.


High-grade Endometrial Carcinoma With a Hepatoid Carcinoma-like Component.
Endometrial carcinoma with hepatoid differentiation is rare and <20 reported cases have been reported as endometrial hepatoid carcinoma (EHC). We present a case of EHC associated with serous carcinoma in a 76-yr-old Japanese woman. The hepatoid component showed trabecular, pseudoglandular, and diffuse proliferation of hepatoid cells. The hepatoid cells were positive for α-fetoprotein, Hep-Per-1, glypican 3, and HNF-1β, weakly and focally positive for SALL4, and negative for PAX8. Both of the serous and hepatoid components showed overexpression of p53. The serum α-fetoprotein on postoperative day 5 was 3691 ng/mL. The postoperative course has remained uneventful for 4 yr. These findings suggested that EHC developed from serous carcinoma by acquiring hepatocytic features and losing Müllerian features. Both serous and hepatoid components showed p53 overexpression, suggesting they share a TP53 mutation as a common primary driver.


PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution.
Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targeted-panel testing (n = 6), whole-exome sequencing (n = 5), or Sanger sequencing (n = 1). Based on the clinical and molecular features, this cohort segregated into three distinct groups: (a) severe focal overgrowth due to low-level but highly activating (hotspot) mutations, (b) predominantly brain overgrowth and less severe somatic overgrowth due to less-activating mutations, and (c) intermediate phenotypes (capillary malformations with overgrowth) with intermediately activating mutations. Sixteen of 29 PIK3CA mutations were novel. We also identified constitutional PIK3CA mutations in 10 patients. Our molecular data, combined with review of the literature, show that PIK3CA-related overgrowth disorders comprise a discontinuous spectrum of disorders that correlate with the severity and distribution of mutations.


Anti-tumor and anti-metastatic roles of cordycepin, one bioactive compound of Cordyceps militaris.
Public interest in complementary and alternative medicine has been increased worldwide, due to its wide applications in cancer prevention and treatment. Cordycepin is one of the most common and crucial types of complementary and alternative medicine. Cordycepin (3'-deoxyadenosine), a derivative of adenosine, was first isolated from medicine drug Cordyceps militaris. Cordycepin has been widely used as one compound for antitumor, which has been found to exert antiangiogenic, anti-metastatic, and antiproliferative effects, as well as inducing apoptosis. However, the mechanism of its anti-tumor activity is not well known. This review will clarify anti-tumor mechanisms of Cordycepin, which regulate signaling pathways related with tumor growth and metastasis. Cordycepin inhibit tumor growth via upregulating tumor apoptosis, inducing cell cycle arrest and targeting cancer stem cells (CSCs). Cordycepin regulates tumor microenvironment via suppressing tumor metastasis-related pathways. Thus, Cordycepins may be one of important supplement or substitute medicine drug for cancer treatment.


Failure of phenotypic characteristics to distinguish between carrier and invasive isolates of Staphylococcus epidermidis.
Thirty carrier and 29 invasive Staphylococcus epidermidis isolates were analysed for production of slime, extracellular enzymes and antibiotic resistance. Evaluation of slime production was by two methods which gave differing results, but both showed no difference between the two groups of isolates. Exoenzyme production by the two groups of isolates was also similar, and the only differences were shown in resistance to some antibiotics; carrier isolates were more resistant to novobiocin and cephalothin, but resistance to chloramphenicol, tunicamycin, teicoplanin, penicillin, ampicillin and tetracycline was similar in both groups. Cluster analysis based on exoenzyme production showed no consistent difference between invasive and carrier isolates, with the lowest similarity coefficient over 88% (except for one isolate). Consequently, none of the characteristics studied was useful in differentiating potentially invasive isolates.


Analysis of transcription of the exotoxin A gene of Pseudomonas aeruginosa.
Analysis of RNA isolated from Pseudomonas aeruginosa PA103 and PAKS grown under Fe2+-limiting (0.08 microgram/ml) and Fe2+-sufficient (10 micrograms/ml) conditions demonstrated that exotoxin A (ETA) expression is regulated by Fe2+ at the level of transcription. S1 nuclease mapping revealed two 5' termini of the tox transcript, 89 base pairs (bp) (S1A) and 62 bp (S1B) 5' to the ETA initiation codon. There appeared to be no consensus promoter sequence for either tox transcript. An 8-bp direct repeat was found 5' to the start of transcript S1A. Transcript S1B mapped 8 bp upstream of a dodecamer sequence conserved between the ETA and phospholipase C genes of P. aeruginosa. Multicopy plasmids in which the expression of ETA is directed from the Escherichia coli trp promoter (ptrpETA-RSF1010) or the tox promoter (pCMtox) were constructed and mobilized into a Tox-P. aeruginosa strain, WR5. WR5 synthesized and secreted high levels of ETA when it was expressed from the E. coli trp promoter; however, the synthesis of ETA from its own promoter in this strain was very low. These and other data suggest that the expression of ETA is under a positive control mechanism. A fusion of the ETA promoter fragment to lacZ was constructed. Use of this fusion plasmid revealed that this DNA fragment directed the synthesis of beta-galactosidase in E. coli at very low levels and that the synthesis of beta-galactosidase from this fusion in E. coli was not regulated by Fe2+.


The prevalence of constipation at admission and after 1 week of palliative care: a multi-center study.
To assess the prevalence and intensity of constipation in advanced-cancer patients referred to palliative care, and to assess changes after 1 week of specialist palliative care. This was a prospective multi-center study in advanced patients for a period of 1 year. At admission (T0), age, gender, primary tumor, concomitant diseases, Karnofsky status, Palliative prognostic score (PaP), Edmonton Symptom Assessment scale (ESAS), Memorial Delirium Assessment Scale (MDAS), and bowel function index (BFI) were collected. In BFI, high values represent severe constipation. The use of medication was also recorded, as well as possible causes of constipation. The same parameters were recorded 1 week after admission for palliative care (T7). A total of 246 patients were screened for constipation. The mean BFI at T0 was 42.4 (SD = 26.92). One hundred and sixty-three patients (66.3%) had a BFI >28. The mean BFI at T7 was 35.7 (SD = 28.8), with a significant decrease from T0 to T7 (p = .000). A significant decrease of BFI in patients with a BFI >28 was reported (p = .000). In patients with a BFI ≤28 there was a significant worsening of constipation (p = .000). In patients with a BFI >28 at T0 there was a significant increase in the use of laxatives at T7 in comparison with patients having a BFI ≤28 (p = .002). In patients with a BFI ≤28 at T0, who had a significant worsening of BFI (Δ > 12), the use of laxatives was significantly lower in comparison to patients who had a BFI >28 (p = .000). In the multivariate analysis, dehydration and the use of benzodiazepines were independently associated with higher BFI scores. Constipation is present in approximately two-thirds of patients, and is principally associated with dehydration and the use of benzodiazepines. Patients with normal bowel function at initial assessment may see a worsening in their condition a week later due to lack of prevention or subsequent under-treatment.


Social factors and quality of life aspects on frailty syndrome in community-dwelling older adults: the VERISAÚDE study.
Frailty is a multidimensional clinical geriatric syndrome that may be reversed in its early stages. Most studies have paid attention to its physical or phenotypic boundaries, however, little is known about the social aspects surrounding this geriatric syndrome. The study examined the relationship between socio-demographic factors, social resources, quality of life and frailty in older adults. This cross-sectional study included a representative sample (n = 749) of adults aged ≥65 years enrolled in forty-three senior centers located in North-West Spain. Socio-demographic data, social resources by the Older Americans Resources and Services Scale, quality of life by the World Health Organization's Quality of Life measure-brief version (WHOQOL-BREF), and frailty status diagnosed by the Frailty phenotype were measured. Female gender, age older than 75 years, single marital status, a poor quality of life, and low scores in the physical health domain of the WHOQOL-BREF were the main determinants of being non-robust. Together, these variables explained 24.4% of the variance. Age between 80 and 89 years, and a poor quality of life were the main determinants for non-robust men, whilst the physical health domain of the WHOQOL-BREF was the single main determinant for women. Our study found evidence that physical frailty is associated with social determinants and several quality of life domains. More research on this understudied topic is needed to avoid healthcare expenditures and improve the quality of life of non-robust elders.


Antibiotic prescription for endodontic infections: a survey of Brazilian Endodontists.
To investigate antibiotic prescribing habits reported by Brazilian endodontists in specific clinical situations. Brazilian endodontists (n = 13 853) were invited to answer an online questionnaire. The questionnaire consisted of two parts: the first part contained personal data such as age, gender, years of experience and location of endodontic practice; the second part included questions regarding their behaviour when prescribing antibiotics in dental practice. The subjects provided their registration number in the Regional Council of Dentistry (RCD) to prevent duplication of data. Data were collected and analysed by SPSS 17.0 (SPSS, Inc., Chicago, IL, USA). Chi-square and Fisher's exact tests were used to test the significance of possible associations (P < 0.05). From the 13 853 questionnaires, a total of 615 were answered (4.44%). The first-choice antibiotic was amoxicillin (81.5%), followed by amoxicillin + clavulanic acid (30.7%). For acute apical abscesses with intra- and extraoral diffuse swelling, fever and trismus, 90.1% reported they would prescribe antibiotics, whilst 88.1% reported they would prescribe antibiotics even without extraoral swelling, fever and trismus, and 20.5% would prescribe antibiotics in cases of chronic apical periodontitis, and sinus tract. The first-choice antibiotics varied by age of dentist (P < 0.001) and time elapsed since their endodontic graduation (P = 0.001). Many endodontists reported prescribing antibiotics in situations where they would not be indicated. Likewise, the general administration of antibiotics was longer in duration than necessary, reinforcing the need of continuous education regarding the use of antibiotics.


A novel family of minimal PMRI cyclic peptides as versatile scaffolds for generating new molecular topology.
The surface loops of proteins and active peptides are implicated in the activation of biological responses upon recognition by enzymes and receptors. Obviously, it is of interest to investigate these loops as potential leads for drug discovery. Currently, there is an urgent need for novel, general, and conformationally definite cyclic peptidomimetic scaffolds capable to mimic small portions of the protein surface. In this respect, 13-membered ring peptidomimetics can be considered privileged structures, since they represent the smallest possible systems that can retain all of the features of organized protein structures, such as single H-bonded alfa-helix loops and different kind of turns. In the present work, we report a novel family of 13-membered ring cyclic peptidomimetics based on a minimal PMRI (partially modified retro-inverse) peptide strategy; in particular, we describe the synthesis and the conformational analysis of a representative member of the family. These scaffolds have been designed to permit easy introduction in a combinatorial fashion of a range of pharmacophores that possess a diversity of structure, function, and 3D disposition.


Preference-based index measurement of health-related quality of life: when does it reflect only arbitrary settings of the researcher?
In health economics, health-related quality of life (HRQoL) is often assessed by means of preference-based index measurement instruments (e.g. EQ-5D, SF-6D, HUI). Each instrument of this kind consists of (1) a multi-attribute classification system for distinguishing health states and (2) a scoring function which assigns a valuation to each health state distinguished within the classification system. Scoring functions are often produced according to the so-called statistical approach which consists of two steps: (1) the valuations of some of the health states of the classification system are empirically determined and (2) the scoring function values for all health states are estimated from the empirically determined valuations using a theoretical model, i.e. an index model. This approach can run into problems because the empirically determined valuations necessarily contain arbitrary settings. This article is concerned with how these arbitrary settings together with the index model affect the final scoring function values. It is shown that for many conceivable index models the final scoring function values have no empirical meaning. Only additive models with a free additive constant are appropriate for representing the information contained in the empirically determined valuation. Only these models should be used within the statistical approach.


Inter-Institutional Partnerships Propel A Successful Collaborative Undergraduate Degree Program In Chemistry.
Small private liberal arts colleges are increasingly tuition-dependent and mainly attract students by creating student-centered learning communities. On the other hand, larger universities tend to be trendsetters where its faculty tend to seek intellectual independence and are involved in career focused cutting-edge research. The Institutional Development Awards (IDeA) and Experimental Program to Stimulate Competitive Research (EPSCoR) are federal-state-university partnerships that builds basic research infrastructure and coax the state-wide higher education institutions to collaborate with each other in order to enhance their competitiveness. As a result in Delaware, Wesley College instituted curricular and operational changes to launch an undergraduate program in biological chemistry where its students take three upper division chemistry courses and can choose to participate in annual summer undergraduate internships at nearby Delaware State University.


Effect of exogenous vitamin E on proliferation and cytokine production in peripheral blood mononuclear cells from patients with tuberculosis.
Micronutrient deficiencies are frequently associated with tuberculosis (TB) worldwide. We tested the effect of exogenous vitamin E on proliferation and cytokine production of peripheral blood mononuclear cells (PBMC) from TB patients and healthy purified protein derivative (PPD)+ volunteers. Proliferation was stimulated with mycobacterial antigen (PPD) and evaluated by the incorporation of tritiated thymidine in PBMC cultured with or without 50 microm-vitamin E for 6 d. Cytokine production (IL-2 and interferon (IFN)-gamma) was determined by intracellular cytokine staining and by ELISA in the supernatant of PBMC stimulated for 24 h with phytohaemagglutinin or PPD. Our results show that culture with vitamin E increased (P < or = 0.05 ) the antigen-induced proliferation of PBMC in TB patients but not in healthy PPD+ volunteers. No significant changes in the number of cytokine-producing cells or in the production of IFN-gamma were observed with vitamin E treatment. These results indicate that vitamin E may enhance the antigen-specific in vitro response of PBMC from TB patients.


Immunoepidemiology of meningococcal disease in military recruits. II. Blocking of serum bactericidal activity by circulating IgA early in the course of invasive disease.
The potential role of IgA antibody to Neisseria meningitidis, which blocks bacteriolysis by IgG and IgM, in producing the susceptible state in military recruits, a population at greater than expected risk, was investigated in 28 patients with meningococcal disease. IgA was removed from acute-phase sera by immunoadsorption; IgG was separated by ion-exchange, and IgM by gel-filtration chromatography. The bactericidal activity of acute-phase sera, before and after removal of IgA, and of IgG and IgM fractions from the sera, was tested against each of the homologous infecting strains. Bactericidal activity, the correlate of protective immunity, was deficient in 24 of 28 unabsorbed sera, but uniformly present after the removal of IgA in a median titer of 1:16. IgM accounted for all or nearly all of the bactericidal activity. IgG was largely inactive. Susceptibility to meningococcal disease may be affected by the blocking of bactericidal IgM by circulating IgA.


A Ca(2+)-dependent cysteine protease is associated with anoxia-induced root tip death in maize.
Imposition of anoxia on maize (Zea mays cv. B73) seedlings for 48 h or longer led to the death of the root tip. The necrosis extended into the root axis during postanoxic treatment, leading to the mortality of 30-50% of the seedlings. Using zymography, protease profiles in the root tissues of anoxic seedlings were studied. O2 deprivation for 24 h or longer repressed pre-existing protease activities and induced a novel soluble enzyme in the roots. The anoxia-induced protease (AIP) activity was predominant in the root apex at 24 h of anoxia and, subsequently, became the most abundant soluble activity in the root axis as well. The induction of AIP and its in vitro renaturation were Ca(2+)-dependent. Inhibitor sensitivity studies indicated that AIP is a cysteine protease. In SDS-acrylamide gels, the enzyme activity migrated as a 23.5 kDa polypeptide. The anoxic induction of the activity was repressed by cycloheximide treatment, suggesting that new protein synthesis was required for the AIP appearance. Excision of the root tip (de-tipping) before anoxia led to a superior recovery of seedlings from stress injury. De-tipped seedlings showed lesser root damage and an increased production of lateral roots compared to intact seedlings. Furthermore, the superior anoxia tolerance of de-tipped seedlings was associated with a decreased AIP activity. Thus, the appearance of AIP activity in the root tip at 24 h of anoxia was spatially and temporally associated with the root tissue death. These studies further indicate that the root tip elimination early during anoxia may provide an adaptive advantage.


Transcranial direct current stimulation (tDCS) for improving aphasia in patients after stroke.
Stroke is one of the leading causes of disability worldwide. Aphasia among stroke survivors is common. Current speech and language therapy (SLT) strategies have only limited effectiveness in improving aphasia. A possible adjunct to SLT for improving SLT outcomes might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability and hence to improve aphasia. To assess the effects of tDCS for improving aphasia in patients after stroke. We searched the Cochrane Stroke Group Trials Register (April 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, March 2012), MEDLINE (1948 to March 2012), EMBASE (1980 to March 2012), CINAHL (1982 to March 2012), AMED (1985 to April 2012), Science Citation Index (1899 to April 2012) and seven additional databases. We also searched trials registers and reference lists, handsearched conference proceedings and contacted authors and equipment manufacturers. We included only randomised controlled trials (RCTs) and randomised controlled cross-over trials (from which we only analysed the first period as a parallel group design) comparing tDCS versus control in adults with aphasia due to stroke. Two review authors independently assessed trial quality and extracted the data. If necessary, we contacted study authors for additional information. We collected information on dropouts and adverse events from the trials. We included five trials involving 54 participants. None of the included studies used any formal outcome measure for measuring functional communication, that is measuring aphasia in a real-life communicative setting. All five trials measured correct picture naming as a surrogate for aphasia. There was no evidence that tDCS enhanced SLT outcomes. No adverse events were reported and the proportion of dropouts was comparable between groups. Currently there is no evidence of the effectiveness of tDCS (anodal tDCS, cathodal tDCS) versus control (sham tDCS). However, it appears that cathodal tDCS over the non-lesioned hemisphere might be the most promising approach.


Transjugular intrahepatic portosystemic shunt (TIPS) for Budd-Chiari syndrome or portal vein thrombosis: review of indications and problems.
The aim of this study was to evaluate the role of transjugular intrahepatic portosystemic shunt (TIPS) in patients who present with portal vein thrombosis (PVT) or Budd-Chiari Syndrome (BCS). Nine patients with recent PVT and four patients with BCS underwent TIPS. The diagnosis was confirmed by color Doppler ultrasound and by angiogram in most patients. Patients were followed clinically and had TIPS checked periodically for patency. The end point was mortality, subsequent surgical shunting or orthotopic liver transplantation (OLT). TIPS was placed in 13 of 15 (87%) patients with BCS or PVT. The mean decrease in pressure gradient was 56%. Median and mean follow-up were 14 months and 16.9 months. Procedure related complications occurred in two of 13 (15%), both in the PVT group. Direct procedural mortality was one of 13 (8%). The majority of patients with PVT (five of eight) underwent OLT. Of the remaining three, one patient subsequently developed a cavernous transformation of portal vein but is stable, one patient is stable, without further variceal bleeding, and one patient died because of multiple organ failure. In patients with BCS, three of four (75%) did well with TIPS, but one patient required immediate surgical shunting after occlusion of the TIPS. Two patients underwent OLT and the fourth patient is stable 2 yr later but has cirrhosis on biopsy. In patients with BCS, TIPS placement is effective and can be used as a bridge to liver transplantation. TIPS in the noncavernous PVT group should only be recommended when cirrhosis and uncontrollable variceal bleeding are present.


A high-density consensus map of barley linking DArT markers to SSR, RFLP and STS loci and agricultural traits.
Molecular marker technologies are undergoing a transition from largely serial assays measuring DNA fragment sizes to hybridization-based technologies with high multiplexing levels. Diversity Arrays Technology (DArT) is a hybridization-based technology that is increasingly being adopted by barley researchers. There is a need to integrate the information generated by DArT with previous data produced with gel-based marker technologies. The goal of this study was to build a high-density consensus linkage map from the combined datasets of ten populations, most of which were simultaneously typed with DArT and Simple Sequence Repeat (SSR), Restriction Enzyme Fragment Polymorphism (RFLP) and/or Sequence Tagged Site (STS) markers. The consensus map, built using a combination of JoinMap 3.0 software and several purpose-built perl scripts, comprised 2,935 loci (2,085 DArT, 850 other loci) and spanned 1,161 cM. It contained a total of 1,629 'bins' (unique loci), with an average inter-bin distance of 0.7 +/- 1.0 cM (median = 0.3 cM). More than 98% of the map could be covered with a single DArT assay. The arrangement of loci was very similar to, and almost as optimal as, the arrangement of loci in component maps built for individual populations. The locus order of a synthetic map derived from merging the component maps without considering the segregation data was only slightly inferior. The distribution of loci along chromosomes indicated centromeric suppression of recombination in all chromosomes except 5H. DArT markers appeared to have a moderate tendency toward hypomethylated, gene-rich regions in distal chromosome areas. On the average, 14 +/- 9 DArT loci were identified within 5 cM on either side of SSR, RFLP or STS loci previously identified as linked to agricultural traits. Our barley consensus map provides a framework for transferring genetic information between different marker systems and for deploying DArT markers in molecular breeding schemes. The study also highlights the need for improved software for building consensus maps from high-density segregation data of multiple populations.


Profile Hidden Markov Models Are Not Identifiable.
Profile Hidden Markov Models (HMMs) are graphical models that can be used to produce finite length sequences from a distribution. In fact, although they were only introduced for bioinformatics 25 years ago (by Haussler et al., Hawaii International Conference on Systems Science, 1993), they are arguably the most commonly used statistical model in bioinformatics, with multiple applications, including protein structure and function prediction, classifications of novel proteins into existing protein families and superfamilies, metagenomics, and multiple sequence alignment. The standard use of profile HMMs in bioinformatics has two steps: first a profile HMM is built for a collection of molecular sequences (which may not be in a multiple sequence alignment), and then the profile HMM is used in some subsequent analysis of new molecular sequences. The construction of the profile thus is itself a statistical estimation problem, since any given set of sequences might potentially fit more than one model well. Hence, a basic question about profile HMMs is whether they are statistically identifiable, which means that no two profile HMMs can produce the same distribution on finite length sequences. Indeed, statistical identifiability is a fundamental aspect of any statistical model, and yet it is not known whether profile HMMs are statistically identifiable. In this paper, we report on preliminary results towards characterizing the statistical identifiability of profile HMMs in one of the standard forms used in bioinformatics.


Nano-sized emission from commercially available paints used for indoor surfaces during drying.
Consumers worry about the presence of nano-particles in paints and the risk of exposure. As a result, the paint industry now omits marketing paints as containing nanoparticles. The industry claims that no nanoparticles are released into the indoor environment; this, however, has yet to be documented. In this study, the emission of nano-sized emission from four indoor paints was investigated. The emission was studied for both base and full-pigmented versions of the paints, which consisted of three water-borne acrylic paints and one solvent-borne alkyd paint. All experiments were performed twice in a 6.783 m3 stainless-steel test chamber under standardized conditions (22.98 °C, 50.08% RH, air exchange rate 0.48 h-1). Emissions during the paint-drying period were measured using a TSI Fast Mobility Particle Sizer (FMPS) measuring the number concentration of nano-particles and the size distribution in the range 5.6-560 nm. The results from the solvent-borne paint showed the highest concentration, with a mean concentration of 3.2·105 particles/cm3 and a maximum of 1.4·106 particles/cm3. This paint also had the smallest particle size distribution, with 9.31 nm particles as the most dominant particle size. The results from this study showed that the exposure to nanoparticles for the residents evaluated over a 7 or 28 day period was low and that interior paints are probably not very important when it comes to identifying products that release nano-particles into indoor environments.


A double-masked randomized crossover study comparing the effect of latanoprost/timolol and brimonidine/timolol fixed combination on intraocular pressure and ocular blood flow in patients with primary open-angle glaucoma or ocular hypertension.
Ocular blood flow dysregulation has been implicated in the pathogenesis of glaucoma. Whereas the effect of single antiglaucoma substances on ocular blood flow has been addressed in various experiments, evidence for fixed combinations is sparse. In the present study, we set out to compare the effects of latanoprost 0.005%/timolol 0.5% (LT) fixed combination and brimonidine 0.2%/timolol 0.5% (BT) fixed combination on intraocular pressure (IOP) and ocular blood flow. In the present study, which followed a randomized, double-masked 2-way crossover design, 16 patients with primary open-angle glaucoma and 2 patients with ocular hypertension were included. The patients underwent a 6-week treatment with LT and a 6-week treatment with BT after a washout for previous antiglaucoma medication. Optic nerve head blood flow (ONHBF) was measured using laser Doppler flowmetry; retrobulbar flow velocities were measured using color Doppler imaging in the ophthalmic artery, the central retinal artery, and the posterior ciliary arteries. IOP was measured at 8 AM, 12 PM, and 4 PM. The mean baseline IOP was 25.3±2.8 mmHg. Both drugs were equally effective in reducing IOP (LT: -35.0%±10.0%; BT: -33.6%±8.8%, P=0.463 between groups). In addition, no difference in ocular perfusion pressure was observed between the 2 treatment groups (P=0.1, between groups). Neither LT nor BT altered ONHBF (P=0.4, baseline vs. treatment) and no effect on flow velocities in the retrobulbar vessels was seen with either of the 2 treatments. In the present study, a 6-week treatment with LT or BT was equally effective in reducing IOP. In addition, none of the administered drugs induced a significant effect on ocular blood flow parameters.


Just Keep Rolling?-An Encompassing Review towards Accelerated Vaccine Product Life Cycles.
In light of the recent pandemic, several COVID-19 vaccines were developed, tested and approved in a very short time, a process that otherwise takes many years. Above all, these efforts have also unmistakably revealed the capacity limits and potential for improvement in vaccine production. This review aims to emphasize recent approaches for the targeted rapid adaptation and production of vaccines from an interdisciplinary, multifaceted perspective. Using research from the literature, stakeholder analysis and a value proposition canvas, we reviewed technological innovations on the pharmacological level, formulation, validation and resilient vaccine production to supply bottlenecks and logistic networks. We identified four main drivers to accelerate the vaccine product life cycle: computerized candidate screening, modular production, digitized quality management and a resilient business model with corresponding transparent supply chains. In summary, the results presented here can serve as a guide and implementation tool for flexible, scalable vaccine production to swiftly respond to pandemic situations in the future.


Occupational Risk Factors for Tuberculosis Among Healthcare Workers in KwaZulu-Natal, South Africa.
Tuberculosis is a known occupational hazard for healthcare workers (HCWs), especially in countries with a high burden of tuberculosis. It is estimated that HCWs have a 2- to 3-fold increased risk of developing tuberculosis compared with the general population. The objective of this study was to identify occupational risk factors for tuberculosis among HCWs in 3 district hospitals with specialized multidrug-resistant tuberculosis wards in KwaZulu-Natal, South Africa. We conducted a case-control study of HCWs diagnosed with tuberculosis between January 2006 and December 2010. Cases and controls were asked to complete a self-administered questionnaire regarding potential risk factors for tuberculosis. Of 307 subjects selected, 145 (47%) HCWs responded to the questionnaire; 54 (37%) tuberculosis cases and 91 (63%) controls. Cases occurred more frequently among clinical staff 46% (n = 25) and support staff 35% (n = 19). Thirty-two (26% [32/125]) HCWs were known to be infected with human immunodeficiency virus (HIV), including 45% (21/54) of cases. HCWs living with HIV (odds ratio [OR], 6.35; 95% confidence interval [CI], 3.54-11.37) and those who spent time working in areas with patients (OR, 2.24; 95% CI, 1.40-3.59) had significantly greater odds of developing tuberculosis, controlling for occupation, number of wards worked in, and household crowding. HIV was the major independent risk factor for tuberculosis among HCWs in this sample. These findings support the need for HCWs to know their HIV status, and for HIV-infected HCWs to be offered antiretroviral therapy and isoniazid preventive therapy. Infection prevention and control should also be improved to prevent transmission of tuberculosis in healthcare settings to protect both HCWs and patients.


Implementation of Procedure-Specific Opioid Guidelines: A Readily Employable Strategy to Improve Consistency and Decrease Excessive Prescribing Following Orthopaedic Surgery.
Evidence-based, procedure-specific guidelines for prescribing opioids are urgently needed to optimize pain relief while minimizing excessive opioid prescribing and potential opioid diversion in our communities. A multidisciplinary panel at our institution recently developed procedure-specific guidelines for discharge opioid prescriptions for common orthopaedic surgical procedures. The purpose of this study was to evaluate postoperative opioid prescription quantities, variability, and 30-day refill rates before and after implementation of the guidelines. This retrospective cohort study was conducted at a single academic institution from December 2016 to March 2018. Guidelines were implemented on August 1, 2017, with a recommended maximum opioid prescription quantity for 14 common orthopaedic procedures. Patients who underwent these 14 procedures during the period of December 2016 to May 2017 made up the pre-guideline cohort (n = 2,223), and patients who underwent these procedures from October 2017 to March 2018 made up the post-guideline cohort (n = 2,300). Opioid prescription quantities were reported as oral morphine equivalents (OME), with medians and interquartile ranges (IQRs). Four levels were established for recommended prescription maximums, ranging from 100 to 400 OME. In the pre-guideline cohort, the median amount of prescribed opioids across all procedures was 600 OME (IQR, 390 to 863 OME), which decreased by 38% in the post-guideline period, to a median of 375 OME (IQR, 239 to 400 OME) in the post-guideline cohort (p < 0.001). The 30-day refill rate did not change significantly, from a rate of 24% in the pre-guideline cohort to 25% in the post-guideline cohort (p = 0.43). Multivariable analysis demonstrated that guideline implementation was the factor most strongly associated with prescriptions exceeding guideline maximums (odds ratio [OR] = 9.9; p < 0.001). Age groups of <80 years (OR = 2.0 to 2.4; p < 0.001) and males (OR = 1.2; p = 0.025) were also shown to have higher odds of exceeding guideline maximums. Procedure-specific guidelines are capable of substantially decreasing opioid prescription amounts and variability. Furthermore, the absence of change in refill rates suggests that pain control remains similar to pre-guideline prescribing practices. Evidence-based guidelines are a readily employable solution that can drive rapid change in practice and enhance the ability of orthopaedic surgeons to provide responsible pain management.


Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology.
Ocular lens development entails epithelial to fiber cell differentiation, defects in which cause congenital cataract. We report the first single-cell multiomic atlas of lens development, leveraging snRNA-seq, snATAC-seq, and CUT&RUN-seq to discover novel mechanisms of cell fate determination and cataract-linked regulatory networks. A comprehensive profile of cis- and trans-regulatory interactions, including for the cataract-linked transcription factor MAF, is established across a temporal trajectory of fiber cell differentiation. Further, we divulge a conserved epigenetic paradigm of cellular differentiation, defined by progressive loss of H3K27 methylation writer Polycomb repressive complex 2 (PRC2). PRC2 localizes to heterochromatin domains across master-regulator transcription factor gene bodies, suggesting it safeguards epithelial cell fate. Moreover, we demonstrate that FGF hyper-stimulation in vivo leads to MAF network activation and the emergence of novel lens cell states. Collectively, these data depict a comprehensive portrait of lens fiber cell differentiation, while defining regulatory effectors of cell identity and cataract formation.


Surrogate Decision Makers' Perspectives on Family Members' Prognosis after Intracerebral Hemorrhage.
Surrogate communication with providers about prognosis in the setting of acute critical illness can impact both patient treatment decisions and surrogate outcomes. To examine surrogate decision maker perspectives on provider prognostic communication after intracerebral hemorrhage (ICH). Semistructured interviews were conducted and analyzed qualitatively for key themes. Surrogate decision makers for individuals admitted with ICH were enrolled from five acute care hospitals. Fifty-two surrogates participated (mean age = 54, 60% women, 58% non-Hispanic white, 13% African American, 21% Hispanic). Patient status at interview was hospitalized (17%), in rehabilitation/nursing facility (37%), deceased (38%), hospice (4%), or home (6%). Nineteen percent of surrogates reported receiving discordant prognoses, leading to distress or frustration in eight cases (15%) and a change in decision for potentially life-saving brain surgery in three cases (6%). Surrogates were surprised or confused by providers' use of varied terminology for the diagnosis (17%) (e.g., "stroke" vs. "brain hemorrhage" or "brain bleed") and some interpreted "stroke" as having a more negative connotation. Surrogates reported that physicians expressed uncertainty in prognosis in 37%; with physician certainty in 56%. Surrogate reactions to uncertainty were mixed, with some surrogates expressing a negative emotional response (e.g., anxiety) and others reporting understanding or acceptance of uncertainty. Current practice of prognostic communication in acute critical illness has many gaps, leading to distress for surrogates and variability in critical treatment decisions. Further work is needed to limit surrogate distress and improve the quality of treatment decisions.


Longitudinal in vivo monitoring of callus remodeling in BMP-7- and Zoledronate-treated fractures.
Pharmacological interventions that combine pro-anabolic and anti-catabolic drugs to treat recalcitrant fractures have shown remarkable efficacy in augmenting the regenerative response. Specifically, in rodent models of fracture repair, treatment with BMP-7 and Zoledronate (ZA) has almost uniformally resulted in complete union. However, delayed remodeling may be problematic for ZA-treated fractures. The increase in newly formed bone is substantial but if translated in humans, delayed remodeling may delay functional recovery. Our objective was to determine if, and to what extent, bone morphogenetic protein (BMP) (in synergistically administered BMP-7 + ZA) can modulate the delayed hard callus remodeling caused by ZA. Callus remodeling in BMP-7-only and BMP-7 + ZA-treated osteotomies were monitored using in vivo µCT to follow the progression of healing at 6-week intervals over 24 weeks in an open femoral fracture rat model. None of the groups recovered baseline cortical bone volumes within 24 weeks post-osteotomy. Treatment prolonged the remodeling phase but the kinetics of remodeling appeared to differ between BMP and BMP + ZA groups. However, the mechanical characteristics were largely restored. Callus/bone volumes in BMP-only treated fractures peaked as early as week 3 suggesting that remodeling is stimulated prematurely. However, this rate of remodeling was not maintained as BMP-7 was found to exhibit negligible changes in callus/bone volumes between weeks 6 and 18, whereas declines in callus/bone volumes were present at these time points in the BMP-7 + ZA group. Our findings suggest that inclusion of ZA as an anti-catabolic agent may not be detrimental to the regenerative process despite a prolonged remodeling phase.


Liquiritigenin attenuates high glucose-induced mesangial matrix accumulation, oxidative stress, and inflammation by suppression of the NF-κB and NLRP3 inflammasome pathways.
Oxidative stress, inflammation, and hyperglycemia are considered to play crucial roles in the pathogenesis and progression of diabetic nephropathy (DN). Liquiritigenin, one of the flavonoid compounds, has been shown to possess anti-inflammatory, anti-hyperlipidemic, and anti-oxidative properties. Our study aimed to explore the effects of liquiritigenin on high glucose (HG)-induced extracellular matrix (ECM) accumulation, oxidative stress and inflammatory response and delineate the underlying mechanism. In our study, glomerular mesangial cells (HBZY-1) were co-treated with various doses of liquiritigenin and HG. We found that HG, but not normal glucose or mannitol, promoted the proliferation of HBZY-1 cells, which was suppressed by liquiritigenin. Liquiritigenin inhibited HG-induced ECM accumulation in HBZY-1 cells by reducing the expressions and production of collagen IV (Col IV) and fibronectin (FN). Moreover, liquiritigenin attenuated HG-induced oxidative stress, as evidenced by the decreased MDA content and NADPH oxidase 4 (NOX4) expression, and the increased SOD activity in HBZY-1 cells. Liquiritigenin suppressed HG-induced inflammatory response, as demonstrated by the reduced expressions and secretion of interleukin (IL)-6 and IL-1β in HBZY-1 cells. Furthermore, we found that liquiritigenin inhibited HG-induced activation the nuclear factor-kappa B (NF-κB) and nod-like receptor protein 3 (NLRP3) inflammasome pathways. In conclusion, these results demonstrated that liquiritigenin attenuated HG-induced ECM accumulation, oxidative stress, and inflammation by suppression of the NF-κB and NLRP3 inflammasome pathways, suggesting that liquiritigenin might be a promising therapeutic agent for preventing the development of DN.


A scoping review of adult survivors' experiences of shame following sexual abuse in childhood.
Shame following childhood sexual abuse (CSA) can be intensely painful and destructive to one's sense of self and place in the world. Organised around an internalised core belief of worthlessness, extreme shame presents as a major therapeutic challenge in therapy with many CSA survivors. A range of clinical and empirical literature, alongside recounts of survivors lived experience, shows that shame is an effect of CSA for many survivors. Yet research has rarely focused specifically on survivors' qualitative or lived experiences of shame. This article reports the results of a scoping review of the empirical research investigating adult survivors' experiences of shame following sexual abuse in their childhood. Conducted in March 2018, the search strategy involved on-line searches of English language, peer review and select grey literature repositories for articles published up to the end of 2017. Of the 28 peer reviewed studies included in the review, only three studies specifically investigate adult survivors lived experiences of shame. The synthesised findings from the studies identify five themes demonstrating the pervasive and detrimental influence of shame following CSA: (1) Psychological effects and trauma symptoms; (2) Relationships and social connections and disconnections; (3) Disclosure; (4) Self concept; and, (5) The process of recovery. These findings resonate with conceptual literature and broader research on the influence of shame following violence and highlight areas for future research and clinical practice. This scoping review identifies three key gaps: a need for further research across specific populations and groups; research evaluating therapeutic interventions responding to shame; and research that specifically investigates adult survivors' lived experiences of shame following CSA.


BrainMap taxonomy of experimental design: description and evaluation.
Coordinate-based, voxel-wise meta-analysis is an exciting recent addition to the human functional brain mapping literature. In view of the critical importance of selection criteria for any valid meta-analysis, a taxonomy of experimental design should be an important tool for aiding in the design of rigorous meta-analyses. The coding scheme of experimental designs developed for and implemented within the BrainMap database provides a candidate taxonomy. In this study, the BrainMap experimental-design taxonomy is described and evaluated by comparing taxonomy fields to data-filtering choices made by subject-matter experts carrying out meta-analyses of the functional imaging literature. Fifteen publications reporting a total of 46 voxel-wise meta-analyses were included in this assessment. Collectively these 46 meta-analyses pooled data from 351 publications, selected for experimental similarity within each meta-analysis. Filter implementations within BrainMap were graded by ease-of-use (A-C) and by stage-of-use (1-3). Quality filters and content filters were tabulated separately. Quality filters required for data entry into BrainMap were classed as mandatory (five filters), being above the use grading system. All authors spontaneously adopted the five mandatory filters in constructing their meta-analysis, indicating excellent agreement on data quality among authors and between authors and the BrainMap development team. Two non-mandatory quality filters (group size and imaging modality) were applied by all authors; both were Stage 1, Grade A filters. Field-of-view filters were the least-accessible quality filters (Stage 3, Grade C); two field-of-view filters were applied by six and four authors, respectively. Authors made a total of 115 content-filter choices. Of these, 78 (68%) were Stage 1, Grade A filters; 16 (14%) were Stage 2, Grade A; and 21 (18%) were Stage 2, Grade C. No author-applied filter was absent from the taxonomy.


[Survival and the quality of life in extrahospital cardiorespiratory arrest].
There are few data in Spain on out-of-hospital cardiac arrest and the efficacy of emergency systems. The objectives of the present study were to evaluate an emergency system, comparing survival at hospital discharge according to the origin, cardiac or non-cardiac, of cardiac arrest in out-of-hospital critically ill patients, and to describe the quality of life of the survivors. Prospective study on 282 patients treated during 1995 and 1996 by ICU ambulances units of the Andalusian Public Health Emergency Company (061) in Granada, Almería and El Ejido-Poniente (Spain). The Utstein style was followed, gathering the mortality at different times up to 6 months after hospital discharge and the origin (cardiac/non-cardiac) of the arrest. Quality of life 6 months after discharge was collected among survivors. Advanced cardiopulmonary resuscitation (CPR) was applied to 176 (62.4%) patients. The survival rate to discharge was 4.9% for patients with cardiac etiology (7/142 x 100) and 5.9% for those with non-cardiac etiology (2/34 x 100), with non-significant differences between the two groups. An optimal quality of life in all domains, except for pharmacological dependence in seven, was found in the eight survivors 6 months after hospital discharge. The origin (cardiac/non-cardiac) of out-of-hospital cardiac arrest is not associated with survival at hospital discharge. The survivors exhibit an optimal quality of life 6 months after discharge.


Effects of cinnamaldehyde on PGE2 release and TRPV4 expression in mouse cerebral microvascular endothelial cells induced by interleukin-1beta.
Cinnamaldehyde is a principle compound isolated from Guizhi-Tang (GZT), which is a famous traditional Chinese medical formula used to treat influenza, common cold and other pyretic conditions. Transient receptor potential vanilloid subtype 4 (TRPV4) is expressed in the anterior hypothalamus and may act as thermosensor. The purpose of the present study was to investigate the effects of cinnamaldehyde on the production of prostaglandin E2 (PGE2) and the expression of TRPV4 in mouse cerebral microvascular endothelial cell strain (b.End3). In the research work, the b.End3 cells were cultured in DMEM medium containing interleukin-1beta (IL-1beta) in the presence or absence of ruthenium red (RR), a kind of known TRPV4 inhibitor, or different concentrations of cinnamaldehyde. The results suggested that IL-1beta significantly increase production of PGE2 and cinnamaldehyde evidently decrease IL-1beta-induced PGE2 production, while RR showed no inhibitory effect on PGE2 production. Moreover, it was identified that TRPV4 was expressed at the mRNA and protein levels in b.End3 cells. IL-1beta could up-regulate the expression of TRPV4, RR and cinnamaldehyde could down-regulate the high expression of mRNA and protein of TRPV4 by IL-1beta induced in b.End3 cells. In conclusion, cinnamaldehyde decreased the production of PGE2 and the expression of TRPV4 in b.End3 cells induced by IL-1beta.


Characterizing cardiovascular risk in women with polycystic ovary syndrome: more than the sum of its parts?
Polycystic ovary syndrome (PCOS), a condition of irregular menses and androgen excess, is the most common endocrinopathy of young women. Insulin resistance is a well-established feature among many women with PCOS, even in the nonobese. Therefore, it is not surprising that PCOS is frequently associated with cardiovascular risk factors and the metabolic syndrome. However, it is not known whether PCOS is an independent risk factor for atherosclerosis and cardiovascular (CV) events or whether CV risk is attributable to associated risk factors. We review previous studies on CV risk and disease in women with PCOS, describing the pitfalls and challenges in ascribing CV risk to PCOS. Women with PCOS might be partly reassured that their relative risk approximates that of the metabolic syndrome (RR 1.5) and also strongly counseled at the individual level about the greatest potential threat to their CV health, the development of type 2 diabetes.


Multiscale adaptive generalized estimating equations for longitudinal neuroimaging data.
Many large-scale longitudinal imaging studies have been or are being widely conducted to better understand the progress of neuropsychiatric and neurodegenerative disorders and normal brain development. The goal of this article is to develop a multiscale adaptive generalized estimation equation (MAGEE) method for spatial and adaptive analysis of neuroimaging data from longitudinal studies. MAGEE is applicable to making statistical inference on regression coefficients in both balanced and unbalanced longitudinal designs and even in twin and familial studies, whereas standard software platforms have several major limitations in handling these complex studies. Specifically, conventional voxel-based analyses in these software platforms involve Gaussian smoothing imaging data and then independently fitting a statistical model at each voxel. However, the conventional smoothing methods suffer from the lack of spatial adaptivity to the shape and spatial extent of region of interest and the arbitrary choice of smoothing extent, while independently fitting statistical models across voxels does not account for the spatial properties of imaging observations and noise distribution. To address such drawbacks, we adapt a powerful propagation-separation (PS) procedure to sequentially incorporate the neighboring information of each voxel and develop a new novel strategy to solely update a set of parameters of interest, while fixing other nuisance parameters at their initial estimators. Simulation studies and real data analysis show that MAGEE significantly outperforms voxel-based analysis.


Effects of low phosphate intake on bone and mineral metabolism in rats: evaluation by biochemical markers and pyridinium cross-link formation in bone.
We have investigated the changes in biochemical markers and in pyridinium cross-links in bone in hypophosphatemic rats. Six-week-old female Wistar rats were divided into two groups (normal diet and a phosphate-deficient diet) and fed for 8 weeks. A low phosphate intake caused a significant difference in the concentrations of osteocalcin and alkaline phosphatase with advancing rachitis as well as an increase in bone resorption marker concentrations in urine. Femur biochemical analysis revealed a significant (p < 0.005) increase in deoxypyridinoline per mole collagen in the phosphate-deficient group which suggested that urinary excretions of pyridinium cross-links might reflect not only bone resorption but also increased pyridinium cross-links in bone matrix collagen. Our results demonstrate that a low phosphate intake causes an increase of pyridinium cross-link formation as well as a discrepancy between the circulation levels of alkaline phosphatase and osteocalcin with advancing rachitis. These alterations induced by low phosphate intake should be considered when interpreting the values of biochemical markers.


[Evaluation and validation of quality care indicators relative to empowerment in complex chronic disease].
The purpose of the study was to identify, validate and rank, through multi-attribute hierarchical analysis, indicators of quality of care related to the empowerment of patients having a chronic complex illness, or their natural care givers. This methodological study was carried within case management and was theoretically based on the quality model of Donabedian (1980) and the empowerment theory of Zimmerman (1995), while also drawing from values underlying nursing practise described by the health promotion model of Allen (1977). Two groups of professional and one group of non professional were considered. Using the DELPHI technique and interviews, the study has 1) provided an evaluation model for quality of care comprising 239 elements (12 main attributes, 75 secondary attributes and 152 indicators), 2) allowed its validation, and 3) its ranking by experts. The discussion encompasses theoretical, empirical and methodological considerations.


Leukotactic factors elaborated by virus-infected tissues.
Infection of chick embryos wih either Newcastle disease virus or mumps virus and infection of BGM cell cultures with mumps virus result in the elaboration of chemotactic activity for neutrophils and macrophages. These factors cannot be found in lysates of uninfected cells. They do not appear to be associated with the viral particles per se, but rather are present in virus-free supernates from infected fluids. Ultracentrifugal studies of the neutrophil chemotactic activity in allantoic fluid of embryos infected with the two different viruses indicate a similar biphasic distribution of activity, while fluid from the mammalian cell cultures shows a single zone of leukotactic activity, further suggesting that the infected cell, rather than the virus, is responsible for the leukotactic activity. Virus-infected cells also release a substance(s) which is itself not leukotactic but which can interact with human C3 or C5 to generate such activity. This leukotactic factor-generating substance is similar to that reported in another virus-infected cell system. It is postulated that the leukotactic factors elaborated as a result of virus infection of cells may play a protective role in vivo.


Tobacco cessation education for pharmacists: Face-to-face presentations versus live webinars.
OBJECTIVE To assess the perceived effectiveness of tobacco cessation continuing education for pharmacists in face-to-face presentation versus live webinar modalities. METHODS A continuing pharmacy education (CPE) activity, Do Ask, Do Tell: A Practical Approach to Smoking Cessation, was offered in face-to-face and live webinar modalities. Following the activity, participants completed a brief questionnaire that assessed the anticipated impact of the activity on their smoking cessation counseling practices. RESULTS Of the 1,088 CPE participants, 819 (75%) attended a face-to-face presentation and 269 (25%) participated in a live webinar. Posttraining self-rated ability to address tobacco use was similar between groups ( P = 0.38), and both the face-to-face and live webinar groups reported a significant difference between pre- and posttraining abilities ( P < 0.05 for both groups). Attendees of the face-to-face presentation reported higher likelihoods of providing each of the individual tasks required to provide an effective, brief tobacco cessation intervention ( P < 0.05 for each task). CONCLUSION These data suggest that more value exists in face-to-face education than live webinars when personal and interactive skills are the focus of the activity.


Curcumin for malaria therapy.
Malaria remains a major global health concern. New, inexpensive, and effective antimalarial agents are urgently needed. Here we show that curcumin, a polyphenolic organic molecule derived from turmeric, inhibits chloroquine-resistant Plasmodium falciparum growth in culture in a dose dependent manner with an IC(50) of approximately 5 microM. Additionally, oral administration of curcumin to mice infected with malaria parasite (Plasmodium berghei) reduces blood parasitemia by 80-90% and enhances their survival significantly. Thus, curcumin may represent a novel treatment for malarial infection.


Total knee replacement in patients older than 85 years.
Between 1987 and 1995, 62 unilateral total knee replacements performed in patients older than 85 years (mean age, 87 years) were followed up for a minimum of 2 years (range, 2-11 years, mean, 5.4 years). This group represented 3.8% of all the total knee replacements performed during the same time. The majority of the patients were women with osteoarthritis. There was a 70% preoperative cardiac disease comorbidity. Overall, confusion after surgery was greater in this older group than in the patients younger than 85 years of age, however, confusion was lower in the group of patients who had epidural anesthesia as compared with those patients who had surgery under general anesthesia. The mean knee score at followup was 89 points and the mean pain score was 43 points (of 50 points). The mean flexion was 114 degrees. Seventy-five percent of these elderly patients still required the use of a cane for walking outdoors compared with 18% of the patients who were younger than 85 years. More than 855 of the older patients could travel independently to socialize and shop after surgery. Seventy-six percent of the patients were living independently or in senior retirement housing after surgery. Only two of the patients required living accommodations in a nursing home. One third of the patients still could drive their own car after surgery. Quality of life improvement was markedly increased in this elderly group of patients. The results of this study indicate that total knee replacement still is a valuable procedure even for this elderly group, and most of these patients returned to a more functional lifestyle.


If I told you that there is no need for yellow fever vaccine booster would you still come to the travel clinic?: a cross-sectional study.
Yellow Fever (YF) immunization required a single dose vaccine with boosters every 10 years. After International Health Regulation (IHR) amendment annex 7 (July 2016), it was accepted that a single dose confers lifelong immunity. Since pre-travel advice is as important as vaccination when traveling, it is essential to clarify why travelers come to a travel health consultation, with the possibility of IHR amendment having a negative impact on travelers' health. This study aims to describe travelers' reasons to come to a pre-travel consultation in Lisbon and if they would return if they wouldn't need the YF vaccine booster. An observational cross-sectional study was conducted during 5 months in the waiting room of Instituto de Higiene e Medicina Tropical travel clinic in Lisbon, Portugal. Travelers were asked about sociodemographic characteristics, destination country, travel duration and reasons to travel in an anonymous self-administered questionnaire. A total of 1043 travelers agreed to participate in the study. Although 61.0% (627/1028) did not come to the clinic to get the YF vaccine, from those who did, 36.7% (133/362) would not come and 12.9% (47/362) didn't knew if they would come if the vaccine would not be necessary. The IHR amendment may have a negative impact on travel clinic attendance and on travelers´ health.


Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation.
Amyotrophic lateral sclerosis (ALS), a multifactorial disease characterized by diffuse motor neuron degeneration, has proven to be a difficult target for stem cell therapy. The primary aim of this study was to determine the long-term effects of intravenous mononuclear human umbilical cord blood cells on disease progression in a well-defined mouse model of ALS. In addition, we rigorously examined the distribution of transplanted cells inside and outside the central nervous system (CNS), migration of transplanted cells to degenerating areas in the brain and spinal cord, and their immunophenotype. Human umbilical cord blood (hUCB) cells (10(6)) were delivered intravenously into presymptomatic G93A mice. The major findings in our study were that cord blood transfusion into the systemic circulation of G93A mice delayed disease progression at least 2-3 weeks and increased lifespan of diseased mice. In addition, transplanted cells survived 10-12 weeks after infusion while they entered regions of motor neuron degeneration in the brain and spinal cord. There, the cells migrated into the parenchyma of the brain and spinal cord and expressed neural markers [Nestin, III Beta-Tubulin (TuJ1), and glial fibrillary acidic protein (GFAP)]. Infused cord blood cells were also widely distributed in peripheral organs, mainly the spleen. Transplanted cells also were recovered in the peripheral circulation, possibly providing an additional cell supply. Our results indicate that cord blood may have therapeutic potential in this noninvasive cell-based treatment of ALS by providing cell replacement and protection of motor neurons. Replacement of damaged neurons by progeny of cord blood stem cells is probably not the only mechanism by which hUCB exert their effect, since low numbers of cells expressed neural antigens. Most likely, cord blood efficacy is partially due to neuroprotection by modulation of the autoimmune process.


Purification and biochemical characterization of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate-sensitive L-glutamate receptors of pig brain.
Two preparations of glutamate receptors were purified from the synaptic junctions of pig brain by a combination of detergent solubilization, anion-exchange chromatography, wheat-germ agglutinin affinity chromatography and sedimentation through sucrose gradients. These preparations were enriched in specific L-[3H]glutamate binding activity (> 5000 pmol of glutamate binding sites/mg of protein), and the rank order of ligand affinity for binding to these preparations was: quisqualate > 6-cyano-7- nitroquinoxaline-2,3-dione > alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) > L-glutamate > kainate > > N-methyl-D-aspartate approximately L-2-amino-4-phosphonobutyrate. SDS/PAGE analysis revealed that more than 80% of the protein in either of these preparations appeared as a single protein band of 106 kDa. Two-dimensional gel electrophoresis further revealed that these 106 kDa proteins consisted of a series of acidic proteins which were recognized by antibodies against rat AMPA receptor subunits. These 106 kDa proteins were also recognized by wheatgerm agglutinin and concanavalin A; in addition, peptide N-glycosidase F treatment of these preparations decreased their size to 99 kDa. Our results suggest that the putative glutamate receptors isolated here are likely to belong to the AMPA subtype of glutamate receptors in pig brain. Using the purification procedure reported here, 5 micrograms of AMPA receptor proteins can be isolated from 250 g of pig brain tissue.


Breathing pattern during acute respiratory failure and recovery.
The objective of this study was to compare the breathing pattern of patients who failed to wean from mechanical ventilation to the pattern during acute respiratory failure. We hypothesized that a similar breathing pattern occurs under both conditions. Breathing pattern, mouth occlusion pressure (P[0.1]) and maximum inspiratory pressure (P[I,max]) were measured in 15 patients during acute respiratory failure, within 24 h of the institution of mechanical ventilation, and in 49 patients during recovery, when they were ready for discontinuation from mechanical ventilation. The following indices were calculated: rapid shallow breathing index (respiratory frequency/tidal volume (fR/VT)); rapid shallow breathing-occlusion pressure index (ROP = P[0.1 x fR/VT]); P(0.1)/P(I,max); and effective inspiratory impedance (P[0.1]/VT/(inspiratory time (tI)). Patients who failed to wean (n=11) had a similar ROP,fR/VT and P(0.1)/P(I,max) to those with acute respiratory failure despite a significantly reduced P(0.1)/VT/tI, the value of which was comparable to that of patients who weaned successfully (n=38). The P(I,max) of patients who failed to wean was similar to that of patients who weaned successfully. We conclude that patients who failed to wean had a breathing pattern similar to that during acute respiratory failure, despite a reduced mechanical load on the respiratory muscles and a relatively adequate inspiratory muscle strength. This suggests that strategies that enhance respiratory muscle endurance may facilitate weaning.


The role of eosinophils in sepsis and acute respiratory distress syndrome: a scoping review.
Septic shock and acute respiratory distress syndrome (ARDS) are characterized by a dysregulated immune host response that may respond to steroid therapy. Eosinophils contribute to type 2 inflammation that often responds to steroid therapy; their role in immune dysregulation and outcomes in sepsis and ARDS is unclear. A systematic search of Cochrane Library, MEDLINE, and EMBASE was performed from inception to 9 September 2020. The search comprised the following terms: eosinophils, sepsis, septic shock, and ARDS. Two reviewers independently screened abstracts and texts and extracted data on disease severity and clinical outcomes. Thirty-nine studies were identified: 30 evaluated serum eosinophil count in sepsis, one evaluated eosinophil activity in sepsis, three assessed bronchoalveolar lavage (BAL) eosinophil count in ARDS, four assessed eosinophil activity in ARDS, and one assessed peripheral eosinophil count in ARDS. Eleven studies showed an association between eosinopenia and sepsis, and eight studies found persistent eosinopenia at > 48 hr of intensive care unit admission to predict mortality and readmission in septic patients. Three studies found BAL eosinophil count to be low in ARDS, although one found that levels rose in late-phase ARDS. Three studies found eosinophil activity markers in BAL to be high in ARDS and correlate with ARDS severity. Persistent peripheral eosinopenia is a marker of bacterial sepsis and is independently associated with poor outcomes. Bronchoalveolar lavage eosinophil counts are low in early-phase ARDS, but increase in late-phase ARDS, while elevated markers of eosinophil activity correlate with ARDS severity. Further studies understanding the mechanisms leading to eosinopenia in sepsis and increased eosinophil activity in ARDS are needed.


[Fatty acid makeup changes in the luminescent bacteria, Photobacterium mandapamensis, in periodic cultivation].
The fatty acid composition of the luminescent bacterium Photobacterium mandapamensis and its spontaneous dark mutant was studied in dynamics. Lipids of the both strains extracted with a methanol -- chloroform mixture contained the following fatty acids: lauric, tridecanoic, myristic, tetradecenic, pentadecanoic, pentadecenic, palmitic, palmitoleic, heptadecanoic, C17-cyclopropanoic, stearic, octadecenic, and nonadecanoic. The content of palmitoleic acid was the highest (57% of the total). Not all of the acids changed their content in the same direction during batch cultivation of the luminescent and dark strains. The content of palmitoleic acid fell to 49.2% of the total in the luminescent culture at the point of its maximal luminescence, but it increased to 63.8% in the dark strain at the corresponding growth phase.


Low-dose vasopressin in the treatment of vasodilatory septic shock.
Despite appropriate therapy, refractory hypotension often occurs in septic shock. A double-blinded placebo controlled clinical trial was performed to assess the role of low-dose vasopressin (VP) as a pressor agent in septic shock. Patients admitted to a trauma intensive care unit with vasodilatory septic shock were randomized to receive either VP at 0.04 U/min (n = 5) or placebo (n = 5). Vasodilatory septic shock was defined as a need for catecholamine agents to maintain a mean arterial pressure more than or equal to 70 mm Hg, despite a cardiac index more than 2.5 L/min and a minimal pulmonary artery wedge pressure more than 12 mm Hg. After 1 hour of initiation of the study drug, attempts to discontinue norepinephrine, phenylephrine, and/or dopamine, in respective order, were undertaken provided that the mean arterial pressure remained more than or equal to 70 mm Hg. A vasopressin infusion increased systolic arterial pressure (98 +/- 5 to 125 +/- 8 mm Hg, p < 0.008) because of peripheral vasoconstriction (systemic vascular resistance increased from 878 +/- 218 to 1,190 +/- 213 dynes/s per cm(-5) p < 0.05). Arterial pressure and systemic vascular resistance were statistically unaffected in the placebo group. Before study termination, measured at 24 hours after drug initiation, two patients in the placebo group died of refractory hypotension. However, all patients receiving VP survived the 24-hour study period and had all other catecholamine pressors withdrawn and blood pressure maintained solely with a low-dose VP infusion. A VP infusion improved arterial pressure and permitted the withdrawal of catecholamine vasopressors. VP is a useful agent in the treatment of refractory septic shock.


Absence of left ventricular hypertrophy in severe isolated aortic stenosis and preserved left ventricular systolic function.
Recent evidence challenges the paradigm that left ventricular hypertrophy (LVH) is required to preserve left ventricular systolic performance in severe aortic stenosis (AS). The study aims were to determine the clinical, echocardiographic and prognostic implications in a cohort of patients with symptomatic severe AS, a preserved left ventricular ejection fraction (LVEF), and an absence of LVH. Echocardiographic, clinical, aortic valve replacement (AVR)-related and all-cause death data were analyzed in 512 patients (253 males, 259 females; mean age 78.4 +/- 10.3 years) with severe AS and a preserved LVEF. Of these patients, 21% were enrolled prospectively, and the mean follow up was 40.4 +/- 32.5 months. By using the American Society of Echocardiography equation for left ventricular mass calculation, LVH was shown to be present in 330 patients (63%) and absent from 182 (36%). Typically, patients without LVH had a larger body surface area, were more often male, had a larger aortic valve area index (AVAi), and had similar LVEFs and rates of AVR as compared to those with LVH. A total of 59 deaths (32.4%) occurred among patients without LVH, and 134 (40.6%) among those with LVH (p = 0.07). When the left ventricular mass index (LVMi) was analyzed as a continuous variable, in both unadjusted and adjusted models for demographics, clinical characteristics, medications, AVAi, LVEF, and systemic vascular resistance, no association was found between LVMi and survival (p = 0.26). However, only patients with a normal LVMi and relative wall thickness had a survival benefit when compared to those with any pattern of abnormal left ventricular geometry (p = 0.01). LVH was absent in more than one-third of patients with severe AS, and was not associated with worse outcomes. A normal left ventricular geometry was associated with lower mortality rates, while AVR was associated with prolonged survival, regardless of LVMi. Mechanisms other than compensatory hypertrophy appear capable of offsetting the adverse effects of afterload excess in AS.


Benzoic acid as a selector-modulator in the synthesis of MIL-88B(Cr) and nano-MIL-101(Cr).
The concentration of benzoic acid was found to exercise efficient control over the formation of either MIL-101(Cr) or MIL-88B(Cr) under otherwise similar hydrothermal synthetic conditions. Nanocrystals of MIL-101(Cr) with ∼100 nm average size and excellent SBET = 3467 m2 g-1 are obtained at lower concentrations of benzoic acid, while at higher concentrations the microparticulated MIL-88B(Cr) product is formed. Hereby a new efficient synthetic method towards the elusive MIL-88B(Cr), yet reported only once without synthetic details, is proposed. The obtained MIL-88B(Cr) has an interesting and potentially valuable property of retaining its high-volume form (Vcell ∼ 2000 Å3) after thermal activation. The degassing of MIL-88B(Cr) in a vacuum at 250 °C yields a porous material with a SBET area of 1136 m2 g-1, which is around the theoretical maximum. The transition to the denser 'closed' form (Vcell ∼ 1500 Å3) occurs only at 350 °C, when all of the benzoate/benzoic acid, hindering the process, is removed.


[Preventive analgesia and early postoperative period in ambulatory orthopedic surgeries in children].
The purpose of the case study was to compare the adequacy of anesthetic management and the specificity of the early postoperative course with preventive analgesia (group 1) and without it (group 2). Preventive analgesia comprised diclofenac, 50-75 mg/kg in intramuscular injections made 1 h before surgery, and microdoses of ketamine, 1.0 mg/kg in intramuscular injections 0.3 mg/kg in intravenous injections as a component of premedication. In as far as the hemodynamic course is concerned, both types of anesthesia were adequate. The main differences were registered in the assessment of the early postoperative period. An earlier awakening was observed in group 1, which we attributed to a more valuable antinociceptive protection and to lower doses of ketamine (group 1--3.2 mg/kg; group 2--4.3 mg/kg). According to the results the preventive analgesia method reduces significantly the postoperative pain and anxiety, which makes the administration of additional analgetics advisable and cuts the child's stay in one-day hospital.


Identifying information needs among children and teens living with haemophilia.
Transitioning from one life stage to the next can be difficult, but for those living with a chronic condition, it can be even more challenging. Children and adolescents with haemophilia need help to manage transitions while dealing with the complications of their disorder. The National Haemophilia Foundation (NHF), headquartered in New York City, has an extensive information centre on bleeding disorders, but it was not clear how much material existed on the topic of transition. The objectives of this project were to (i) assess the availability of literature about transition for children and adolescents living with haemophilia, (ii) determine which transition issues were the most relevant and (iii) develop and test information products that would address those transition issues. An inventory of NHF's resources and an environmental scan over the Internet was performed. Focus groups were conducted to determine messaging. Video prototypes containing messages were created, tested by focus groups and revised. The literature search yielded limited information available on transition for children and adolescents with haemophilia. Results of the formative research indicated that adolescents wanted more information on sports participation and disclosure of their condition (e.g. to peers, teachers, coaches, health care providers). Video was found to be the preferred delivery format. Children and adolescents living with haemophilia need information to help them transition through life. As a result of this study, two educational products were produced, but several more are recommended to guide these individuals in making healthy transitions into adulthood.


Adhesive bonding of dental luting cements; influence of surface treatment.
Tensile bond strength of four different luting cements to smooth dentin surfaces was measured. A chisel edged, stainless steel ring was cemented to the butt end of a dentin cylinder. The dentin was polished to a plane and smooth surface before cementation. The cements were also applied to dentin surfaces that were treated with a pumice slurry, etched with different acid solutions, or covered with different liners. The results showed that the polycarboxylate cement had a tensile bond strength to smooth, untreated dentin of approximately 4 MN/m2. The zinc phosphate and EBA cements had a bond strength of 0,6 MN/m2 and the composite resin cement had no measurable bond to untreated dentin. All dentin treatments showed in general a decreasing effect on the bond strength of zinc phosphate, polycarboxylate and EBA cements, whereas that of composite resin cement showed a slight increase.


Late life depression and incident activity limitations: influence of gender and symptom severity.
Mental disorders, especially depression, are one of the principal causes of disablement. Previous research has been limited partly due to the failure to take into account sub-syndromal states and the very large number of candidate mediating and confounding factors. Longitudinal associations between baseline depressive symptomatology and activity limitations were examined in a community-dwelling elderly cohort of 3191 participants. Mixed logistic models were used to determine associations between mild or severe depressive symptoms (Center for Epidemiologic Studies-Depression Scale, CES-D), and 7-year incident disability on four limitation scales assessing instrumental and basic activities of daily living, mobility using the Rosow and Breslau scale, and social restriction. In men, mild depressive symptomatology was associated with increased incident limitations on instrumental activities of daily living (IADL) (odds ratio (OR) (95% CI)=5.07 (2.25-11.42)). In women, severe depressive symptomatology was related to social restriction (OR (95% CI)=2.36 (1.31-4.25)), IADL (OR (95% CI)=1.89 (1.13-3.15)) and activities of daily living (OR (95% CI)=11.15 (3.43-36.23)). Men and women with a 2-year increase in CES-D score were highly at risk for social restriction and limitations in mobility and IADL. Depression is an independent predictor of disability in the elderly population; the relation is gender-dependent and varies with symptom load.


AlphaFold modeling of nepovirus 3C-like proteinases provides new insights into their diverse substrate specificities.
The majority of picornaviral 3C proteinases (3Cpro) cleavage sites possess glutamine at the P1 position. Plant nepovirus 3C-like proteinases (3CLpro) show however much broader specificity, cleaving not only after glutamine, but also after several basic and hydrophobic residues. To investigate this difference, we employed AlphaFold to generate structural models of twelve selected 3CLpro, representing six substrate specificities. Generally, we observed favorable correlations between the architecture and charge of nepovirus proteinase S1 subsites and their ability to accept or restrict larger residues. The models identified a conserved aspartate residue close to the P1 residue in the S1 subsites of all nepovirus proteinases examined, consistent with the observed strong bias against negatively-charged residues at the P1 position of nepovirus cleavage sites. Finally, a cramped S4 subsite along with the presence of two unique histidine and serine residues explains the strict requirement of the grapevine fanleaf virus proteinase for serine at the P4 position.


Mitochondrial protection restores renal function in swine atherosclerotic renovascular disease.
The mechanisms responsible for renal injury in atherosclerotic renovascular disease (ARVD) are incompletely understood, and few therapeutic options are available to reverse it. We hypothesized that chronic renal damage involves mitochondrial injury, and that mitochondrial protection would reduce renal fibrosis and dysfunction in ARVD pigs. Domestic pigs were studied after 10 weeks of ARVD or sham, treated for the last 4 weeks with daily subcutaneous injections (5 days/week) of vehicle or Bendavia (0.1 mg/kg), a tetrapeptide that preserves cardiolipin content in the mitochondrial inner membrane. Single-kidney haemodynamics and function were studied using fast-computer tomography, oxygenation using blood oxygen level-dependent magnetic resonance imaging, microvascular architecture, oxidative stress, and fibrosis ex vivo. Cardiolipin content was assessed using mass spectrometry and staining. Renal endothelial function was studied in vivo and ex vivo. In addition, swine renal artery endothelial cells incubated with tert-butyl hydroperoxide were also treated with Bendavia. Stenotic-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) decreased in ARVD + Vehicle compared with normal (318.8 ± 61.0 vs. 553.8 ± 82.8 mL/min and 48.0 ± 4.0 vs. 84.0 ± 3.8 mL/min, respectively) associated with loss of cardiolipin, intra-renal microvascular rarefaction, and hypoxia. Bendavia restored cardiolipin content in ARVD and improved vascular density, oxygenation, RBF (535.1 ± 24.9 mL/min), and GFR (86.6 ± 11.2 mL/min). Oxidative stress and fibrosis were ameliorated, and renovascular endothelial function normalized both in vivo and in vitro. Preservation of mitochondrial cardiolipin attenuated swine stenotic-kidney microvascular loss and injury, and improved renal oxygenation, haemodynamics, and function. These observations implicate mitochondrial damage in renal deterioration in chronic experimental ARVD, and position the mitochondria as a central therapeutic target.