Home care professionals' experiences of successful implementation, use and competence needs of robot for medication management in Finland.
To describe home care professionals' individual experiences of the implementation, use and competence needs of a robot for medication management in older people's home care. A qualitative focus group interview study. Data were collected during spring and autumn 2021 by semi-structured focus group interviews and analysed using inductive content analysis. The participants were 62 home care professionals working in older people's home care. The successful implementation and use of the robot for medication management consisted of a timely and adequate introduction before the implementation of the robot, the fluent usability of the robot in daily work, and confidence in work competence. There is a need for the reorganization of home care professionals' use of digital solutions to make workflow fluent, prevent burnout and turnover among home care professionals. Professionals' competence should also be developed to ensure that it corresponds to digitalized healthcare. No patient or public contribution.


Characterization and whole-genome sequencing of an extreme arsenic-tolerant Citrobacter freundii SRS1 strain isolated from Savar area in Bangladesh.
Citrobacter freundii SRS1, gram-negative bacteria, were isolated from Savar, Bangladesh. The strain could tolerate up to 80 mmol L-1 sodium arsenite, 400 mmol L-1 sodium arsenate, 5 mmol L-1 manganese sulfate, 3 mmol L-1 lead nitrate, 2.5 mmol L-1 cobalt chloride, 2.5 mmol L-1 cadmium acetate, and 2.5 mmol L-1 chromium chloride. The whole-genome sequencing revealed that the genome size of C. freundii SRS1 is estimated to be 5.4 Mb long, and the G + C content is 51.7%. The genome of C. freundii SRS1 contains arsA, arsB, arsC, arsD, arsH, arsR, and acr3 genes for arsenic resistance; czcA, czcD, cbiN, and cbiM genes for cobalt resistance; chrA and chrB genes for chromium resistance; mntH, sitA, sitB, sitC, and sitD genes for manganese resistance; and zntA gene for lead and cadmium resistance. This novel acr3 gene has never previously been reported in any C. freundii strain except SRS1. A set of 130 completely sequenced strains of C. freundii was selected for phylogenomic analysis. The phylogenetic tree showed that the SRS1 strain is closely related to the C. freundii 62 strain. Further analyses of the genes involved in metal and metalloid resistance might facilitate identifying the mechanisms and pathways involved in high metal resistance in the C. freundii SRS1 strain.


Lamotrigine update and its use in mood disorders.
To provide a qualitative, systematic update and review of the pharmacology, pharmacokinetics, efficacy in mood disorders, adverse effects, and costs of lamotrigine. Citations obtained from MEDLINE searches (1985-September 2001) using lamotrigine as a text word, articles identified in reference lists of pertinent articles, abstracts presented at conferences, and research data from GlaxoSmithKline. English-language articles were considered for possible inclusion. Each title and abstract was examined to determine whether the publication contained up-to-date information relevant to the objective. Twenty clinical trials that provided data on response rates in mood disorders were tabulated. Lamotrigine's primary action is to modulate voltage-gated sodium channels. Evidence suggests that it decreases glutamate transmission, directly reduces calcium influx, mildly blocks transmitter reuptake, and alters intracellular mechanisms of resting transmitter release. The average half-life of lamotrigine is approximately 24 hours, but decreases to approximately 7.4 hours when used concurrently with phenytoin, and increases to approximately 59 hours with valproic acid. Seven of the 20 clinical trials were randomized, double-blind, and controlled. Existing data are inadequate to evaluate lamotrigine use in major depression. The pooled response rates for patients with depressed, manic, mixed, and rapid cycling bipolar disorder were similar, ranging from 52% to 63%. Adverse effects are infrequent when the drug is used alone, but become more frequent when lamotrigine is combined with other anticonvulsants. While most rashes are mild, approximately 1 in 500 patients develops exfoliative dermatitis. A slow upward dose titration is recommended to reduce the incidence of serious rash, but this may delay the attainment of adequate dosage for 6 weeks. Lamotrigine has positive effects on cognitive function, but occasionally produces insomnia. Lamotrigine costs 2-4 times more than lithium, carbamazepine, and generic valproic acid. When efficacy, adverse effects, and cost are considered, lamotrigine should probably be reserved as a second-line agent for bipolar depression.


Influence of age, sex, and type of exercise on the efficacy of creatine supplementation on lean body mass: A systematic review and meta-analysis of randomized clinical trials.
Creatine supplementation has been shown to increase measures of lean body mass (LBM); however, there often is high heterogeneity across individual studies. Therefore, the aim of this study was to systematically review and meta-analyze randomized controlled trials (RCTs) investigating creatine supplementation on LBM. Subanalyses were performed based on age, sex, and type of exercise. Based on PRISMA guidelines, we searched the following databases: Pubmed, SPORTDiscus, Web of Science, and Scopus (PROSPERO register: CRD42020207122) until May 2022. RCTs for investigation of creatine supplementation on LBM were included. Animal studies and studies on individuals with specific diseases were excluded. Thirty-five studies were included, with 1192 participants. Overall (i.e., inclusion of all studies with and without exercise training interventions) revealed that creatine increased LBM by 0.68 kg (95% confidence interval [CI], 0.26-1.11). Subanalyses revealed greater gains in LBM when creatine was combined with resistance training (mean difference [MD], 1.10 kg; 95% CI, 0.56-1.65), regardless of age. There was no statistically significant effect of creatine on LBM when combined with mixed exercise (MD, 0.74 kg; 95% CI, -3.89 to 5.36) or without exercise (MD, 0.03 kg; 95% CI, -0.65 to 0.70). Further subanalyses found that males on creatine increased LBM by 1.46 kg (95% CI, 0.47-2.46), compared with a non-significant increase of 0.29 kg (95% CI, -0.43 to 1.01) for females. In conclusion, the addition of creatine supplementation to a resistance training program increases LBM. During a resistance training program, males on creatine respond more favorably than females.


Lightweight nanoporous metal hydroxide-rich zeotypes.
Nanoporous materials have important industrial applications as molecular sieves, catalysts and in gas separation and storage. They are normally produced as moderately dense silicates (SiO(2)) and aluminosilicates making their specific capacities for the uptake and storage of gases, such as hydrogen, relatively low. Here we report the synthesis and characterization of lightweight, nanoporous structures formed from the metal hydroxide Be(OH)(2) in combination with relatively low levels of framework phosphate or arsenate. Three new zeotype structures are described, constructed mainly of Be(OH)(4) tetrahedra bridged through hydroxide into three-membered rings; these units link together to produce several previously unknown zeotype cage types and some of the most structurally complex, nanoporous materials ever discovered. These materials have very low densities between 1.12 and 1.37 g cm(-3) and theoretical porosities of 63-68% of their total volume thereby yielding very high total specific pore volumes of up to 0.60 cm(3) g(-1).


Detection of anti-tat antibodies in CSF of individuals with HIV-associated neurocognitive disorders.
Despite major advances in the development of antiretroviral therapies, currently available treatments have no effect on the production of HIV-Tat protein once the proviral DNA is formed. Tat is a highly neurotoxic and neuroinflammatory protein, but its effects may be modulated by antibody responses against it. We developed an indirect enzyme-linked immunosorbent assay and measured anti-Tat antibody titers in CSF of a well characterized cohort of 52 HIV-infected and 13 control individuals. We successfully measured anti-Tat antibodies in CSF of HIV-infected individuals with excellent sensitivity and specificity, spanning a broad range of detection from 10,000 to over 100,000 relative light units. We analyzed them for relationship to cognitive function, CD4 cell counts, and HIV viral load. Anti-Tat antibody levels were higher in those without neurocognitive dysfunction than in those with HIV-associated neurocognitive dysfunction (HAND) and in individuals with lower CD4 cell counts and higher viral loads. We provide details of an assay which may have diagnostic, prognostic, or therapeutic implications for patients with HAND. Active viral replication may be needed to drive the immune response against Tat protein, but this robust immune response against the protein may be neuroprotective.


[Eclampsia at the University hospital Yalgado of Ouagadougou (Burkina Faso) from 1 April 2013 to 31 March 2014].
The objective of this study was to describe the epidemiological, clinical, therapeutic and prognostic aspects of the eclampsia in the obstetrics and gynecology department at the University Teaching Hospital Yalgado Ouedraogo of Ouagadougou. It has been a descriptive crosssectional study over a period of 12 months from 1 April 2013 to 31 March 2014. The main criterion for inclusion in our sample was the occurrence of seizures in a pregnant more than 20 weeks of gestation or recently delivered with elevation of blood pressure and the presence of albumin in the urine. The patients were followed from the onset of the crisis until hospital discharge. Data were collected and analyzed using Epi Info 3.5.1. The significance level of 5% was used for data comparison. We identified 203 cases of eclampsia for 6063 deliveries that to say a frequency of 3.3%. The average age of patients was 27.5 years [14-46]. In socio-demographic terms, patients were housewives in 62.5% of cases, the average rate of the past-deliver number was 4.2 [0-11] and 47.7% of patients were living as married. Clinically, they were referred in 72.4% of cases and were initially admitted into the service for elevation of blood pressure in 40.3% of cases. The mean gestational age was 31.5 weeks [23-41]; diastolic blood pressure exceeded 110 mmHg in 63.1% of cases. Therapeutically, all the patients benefited from a treatment based in anticonvulsant by magnesium sulfate and antihypertensive therapy by nicardipine, clonidine or alpha-methyl-dopa. Maternal prognosis was marked by significant morbidity in 46 cases (22.6%) and mortality in 13 patients that to say a fatality rate of 6.4%. The fetal one was dominated by a perinatal lethality in 31.5% of the cases. Eclampsia is a major cause of maternal and perinatal mortality in the University Teaching Hospital of Ouagadougou. The adoption of strategies for screening during antenatal consultations and early management should contribute to the reduction of the mortality in the mother and child couple in Burkina Faso.


New Spirostane from a Fungus Neohelicomyces hyalosporus and Its Bioactivity.
A new spirostane, namely neohelicomyine B (1), together with six known steroids (2-7) were isolated from the fermentation of fungus Neohelicomyces hyalosporus. The structures of these compounds were elucidated by extensive analyses of spectroscopic methods including 1D and 2D NMR and HR-ESI-MS. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction. The bioactivities of compounds 1-7 were evaluated using cellular assays. Compound 1 displayed moderate cytotoxicity against HepG2 cells (hepatoma cells) with IC50 value of 8.4±2.1 μM. Compound 7 also exhibited cytotoxic activity against HepG2 cells with the IC50 value of 3.0±0.2 μM.


An fMRI investigation of memory encoding in PTSD: influence of symptom severity.
Previous studies have shown memory deficits in Post-Traumatic Stress Disorder (PTSD) patients, as well as abnormal patterns of brain activity, especially when retrieving trauma-related information. This study extended previous findings by investigating the neural correlates of successful memory encoding of trauma-unrelated stimuli and their relationship with PTSD symptom severity. We used the subsequent memory paradigm, in the context of event-related functional magnetic resonance imaging, in 27 PTSD patients to identify the brain regions involved in the encoding of fearful and neutral faces. Symptom severity was assessed by the Clinically Administered PTSD Scale (CAPS) scores. It was found that memory performance was negatively correlated with CAPS scores. Furthermore, a negative correlation was observed between CAPS scores and ventral medial prefrontal cortex (vmPFC) activity elicited by the subsequently forgotten faces. Finally, symptom severity predicted the contribution of the amygdala to the successful encoding of fearful faces. These results confirm the roles of the vmPFC and the amygdala in PTSD and highlight the importance of taking into account individual differences when assessing the behavioural and neural correlates of the disorder.


Effects of some ergot derivatives in bone marrow of mice.
The in vivo chromosomal damaging properties of some ergot derivatives were investigated following their administration to male mice. Dihydroergotoxine, ergotamine and methysergide were injected in doses of 25, 50 and 100 mg/kg. Significant numbers of aberrations were observed in bone marrow preparations after treatment with the higher doses. Almost all the damage was in the form of chromatid aberrations. No exchange figures were observed, neither were other anamalies, such as nondisjunction or anti-mitotic activity. This frequency of damage was about 7- to 10-fold less than that produced by the powerful alkylating agent, cyclophosphamide. Thus the ergot derivatives were concluded to have weak chromosomal damaging effects in vivo only in very high doses.


A Pattern Recognition Tool for Medium-resolution Cryo-EM Density Maps and Low-resolution Cryo-ET Density maps.
Cryo-electron microscopy (Cryo-EM) and cryo-electron tomography (cryo-ET) produce 3-D density maps of biological molecules at a range of resolution levels. Pattern recognition tools are important in distinguishing biological components from volumetric maps with the available resolutions. One of the most distinct characters in density maps at medium (5-10 Å) resolution is the visibility of protein secondary structures. Although computational methods have been developed, the accurate detection of helices and β-strands from cryo-EM density maps is still an active research area. We have developed a tool for protein secondary structure detection and evaluation of medium resolution 3-D cryo-EM density maps which combines three computational methods (SSETracer, StrandTwister, and AxisComparison). The program was integrated in UCSF Chimera, a popular visualization software in the cryo-EM community. In related work, we have developed BundleTrac, a computational method to trace filaments in a bundle from lower resolution cryo-ET density maps. It has been applied to actin filament tracing in stereocilia with good accuracy and can be potentially added as a tool in Chimera.


Bovine leukemia virus DNA associated with breast cancer in women from South Brazil.
Breast cancer is a neoplastic condition with a high morbidity and mortality amongst women worldwide. Recent data linking bovine leukemia virus (BLV) with breast cancer has been contested already. Our study investigated the presence of BLV genome in healthy (n = 72) and cancerous (n = 72) paraffin-embedded samples of breast tissues from women in south Brazil. BLV DNA was found most frequently (30.5%) in breast cancer tissue than in healthy breast (13.9%) (Odds ratio = 2.73; confidence interval = 1.18-6.29; p = 0.027). In contrast, antibodies to BLV were found in a very small percentage of healthy blood donors. There was no association between BLV DNA and other tumor prognostic biological markers such as hormonal receptors, HER2 oncoprotein, proliferation index, metastasis in sentinels lymph nodes, and tumor grade and size. Our findings suggest that BLV should be considered a potential predisposing factor to breast cancer in women.


Microwave thermal balloon angioplasty in the atherosclerotic rabbit.
We evaluated the angiographic and histologic response of the coronary vessels of the atherosclerotic rabbit to microwave thermal balloon angioplasty. Sixteen rabbits with atherosclerosis of the external iliac arteries following a high fat diet and endothelial denudation were treated with either CBA or MBA. Four weeks following angioplasty angiography was repeated, and following the death of the animals, the vessels treated were excised for histologic evaluation. In vessels with MBA with peak temperatures of 85 degrees C there was an increase in luminal diameter immediately postangioplasty, from 1.66 +/- 0.32 mm to 2.54 +/- 0.23 mm (p < 0.05). The diameter at 4 weeks (2.29 +/- 0.74 mm) remained increased compared with the preangioplasty diameter (p < 0.05). With microwave angioplasty at 70 degrees C there was an increase in luminal diameter, from 1.92 +/- 0.37 mm to 2.40 +/- 0.22 mm (p < 0.05) immediately postangioplasty. This increase in diameter was not sustained at 4 weeks (1.86 +/- 0.28 mm). In the vessels treated with CBA there was no significant increase in diameter noted either immediately postangioplasty or at 4 weeks postangioplasty. In the thermally treated vessels, histologic evaluation revealed a loss of lipid-laden cells; it also revealed the formation of a concentric hypocellular fibrotic layer. Microwave thermal balloon angioplasty at 85 degrees C results in enhancement of the immediate and delayed response to angioplasty. Modification of the proliferative response to angioplasty may be accomplished with this modality.


Apolipoprotein E4 inhibits, and apolipoprotein E3 promotes neurite outgrowth in cultured adult mouse cortical neurons through the low-density lipoprotein receptor-related protein.
The apolipoprotein E4 (apoE4) genotype is a major risk factor for Alzheimer's disease (AD); however, the mechanism is unknown. We previously demonstrated that apoE isoforms differentially modulated neurite outgrowth in embryonic neurons and in neuronal cell lines. ApoE3 increased neurite outgrowth whereas apoE4 decreased outgrowth, suggesting that apoE4 may directly affect neurons in the brain. In the present study we examined the effects of apoE on neurite outgrowth from cultured adult mouse cortical neurons to examine if adult neurons respond the same way that embryonic cells do. The results from this study demonstrated that (1) cortical neurons derived from adult apoE-gene knockout (apoE KO) mice have significantly shorter neurites than neurons from adult wild-type (WT) mice; (2) incubation of cortical neurons from adult apoE KO mice with human apoE3 increased neurite outgrowth, whereas human apoE4 decreased outgrowth in a dose-dependent fashion; (3) the isoform specific effects were abolished by incubation of the neurons with either receptor associated protein (RAP) or lactoferrin, both of which block the interaction of apoE-containing lipoproteins with the low-density lipoprotein receptor-related protein (LRP). These data suggest a potential mechanism whereby apoE4 may play a role in regenerative failure and accelerate the development of AD.


Rapid detection of lineage IV peste des petits ruminants virus by real-time RT-PCR.
Peste des petits ruminants virus (PPRV) is the cause agent of peste des petitis ruminants (PPR). A novel lineage IV PPRV has reemerged in China in 2013 and 2014. Mass vaccination was implemented in most provinces in China. In order to detect lineage IV PPRV in clinical samples and to distinguish rapidly it from the other lineages PPRVs, a real-time RT-PCR assay was developed. This assay showed high sensitivity, specificity and efficiency in differentiating the lineage IV PPRV from others. The performance of this assay was evaluated by positive clinical samples of lineage IV viruses. This new real-time RT-PCR assay will facilitate epidemiological investigations and rapid differentiatial diagnosis in areas where lineage IV viruses are circulating.


Furosemide during sustained left atrial hypertension in functionally anephric dogs: intravascular and extravascular pulmonary fluid volumes. V.
The response of intravascular (PBV) and extravascular (EVLW) pulmonary fluid volume was examined using double-indicator techniques (thermal-green dye) in 11 open-chest anesthetized dogs during the production of sustained left atrial (LA) hypertension by a LA balloon over a period of 195 min. In 6 of these animals data were also acquired after the intravenous administration of furosemide (1 mg/kg). The renal effects of the diuretic were blocked by tying off the ureters and the vascular supply of both kidneys. Left atrial pressure (N = 11) was abruptly increased from 2.2 +/- 2.1 mm Hg to 30.2 +/- 4.0 mm Hg (P less than 0.01) and maintained at that level for 120 min. Data were obtained prior to pressure elevation, immediately upon pressure elevation, and then every 60 min for a total of 120 min. At that point EVLW had increased (8.1 +/- 0.8 cc/kg at control to 21.7 +/- 2.0 cc/kg at 120 min, P less than 0.001), as had PBV (6.2 +/- 2.1 cc/kg to 9.1 +/- 3.1 cc/kg P less than 0.01). After furosemide injection (N = 6), LA pressure declined (mean peak reduction of approximately 6 mm Hg at 60-75 min, P less than 0.01), aortic and pulmonary arterial pressure both declined (P less than 0.01). However, EVLW remained unchanged, though PBV decreased significantly (peak decrease at 75 min after furosemide administration of 2.0 +/- 0.4 cc/kg, P less than 0.01). In the untreated dogs, EVLW continued to climb (P less than 0.05 vs treated dogs at 75 min postfurosemide).(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of the prevalence, lesion, and depth of osteoarthritic changes in the patella.
The aim of this study was to determine the prevalence, type of lesion, and depth of osteoarthritic (OA) changes in the patella. One hundred and forty-six cadaveric knees were included in this study with an median age of 83 years (54-97). Patella OA lesion was classified using Han's method: Type 1, no or minimal lesion; Type 2, medial facet lesion without involvement of the ridge; Type 3, lateral facet lesion without involvement of the ridge; Type 4, lesion involvement of the ridge; Type 5, medial facet lesion with involvement of the ridge, Type 6, lateral facet lesion with involvement of the ridge; and Type 7, Global lesion. The depth of OA evaluation was performed following Outerbridge's classification. OA lesions were observed as follows: (Type 1) 31%, (Type 2) 16%, (Type 3) 3%, (Type 4) 12%, (Type 5) 22%, (Type 6) 2%, and (Type 7) 14%. Outerbridge's classification of over Grade 2 OA depth was observed in 63.7% of subjects. A significant difference of patella OA type in gender was observed. Severe patella OA occurred in female subjects. Greater depth of OA was observed in Types 5 and 7. Most OA occurred in the medial facet of the patella including the ridge. Isolated OA in the lateral facet of the patella was observed in only 2% of all knees. There is a risk of patella OA in female subjects. Patella OA occurred mainly on the medial side. Isolated OA in the lateral facet of the patella was rare. 63.7% of subjects had patella OA. Controlled laboratory study, Level III.


Vesicostomy vs primary ablation for posterior urethral valves: always a difference in outcome?
A vesicostomy is believed to have a detrimental effect in boys with posterior urethral valves compared to primary valve ablation. We compared the outcomes of boys managed by initial vesicostomy with those undergoing primary fulguration. The outcomes of 54 boys (23 vesicostomy, 31 primary valve fulguration) over 1 year of age who had not undergone renal transplant were considered. Outcome parameters identified were ultrasound findings, continence status, glomerular filtration rate (GFR) and 1-year creatinine. Dryness was defined as completely dry both day and night with no need to wear pads. Results are presented with 95% confidence intervals. Ultrasound examinations were normal in 9/19 (47.4%) of the vesicostomy group and 11/24 (45.8%) of the fulguration group. Graded ultrasound results were not significantly different (p=0.24). The vesicostomy patients were more often dry (79% vs 64%, p=0.43). The vesicostomy group had on average higher GFR (95.26 vs 85.79) and lower 1-year creatinine (49.58 vs 52.46) values. After accounting for age differences between groups, there was no significant difference in the GFR and 1-year creatinine values (p=0.16 and p=0.87, respectively). There was a tendency for the major outcomes to be more favourable in the vesicostomy group. Although trends were non-significant, confidence intervals were wide and potential differences of clinical importance could not be discounted.


Biofilm formation and extracellular polymeric substance (EPS) production by Bacillus haynesii and influence of hexavalent chromium.
Biofilm-forming bacteria play a key role in the removal of heavy metals including hexavalent chromium [Cr(VI)] from contaminated sites. In this study, biofilm-forming B. haynesii was examined for extracellular polymeric substances (EPS) production and hexavalent chromium [Cr(VI)] reduction potential. Exposure of B. haynesii with Cr(VI) (12.5-100 mg L-1) for 48 h enhanced pellicle dry weight (20-24%), cell-size (5.1-23.2%) and cell granularity (8.5-19.2%). Also, EPS production was increased by 10-35% by promoting the synthesis of protein (94-119%) and polysaccharide (2-33%) components in EPS. Further, the reduction (27.7 %) and distribution (15.87%) of Cr(VI) were mainly mediated by EPS than the other cellular fractions. Findings of the study suggest that the EPS from B. haynesii was efficiently reduced to Cr(VI) present in aqueous medium and the potential of the organism can be further explored for the mitigation of Cr(VI) contamination.


An overview of key pretreatment processes employed for bioconversion of lignocellulosic biomass into biofuels and value added products.
The hunt for alternative sources of energy generation that are inexpensive, ecofriendly, renewable and can replace fossil fuels is on, owing to the increasing demands of energy. One approach in this direction is the conversion of plant residues into biofuels wherein lignocellulose, which forms the structural framework of plants consisting of cellulose, hemicellulose and lignin, is first broken down and hydrolyzed into simple fermentable sugars, which upon fermentation form biofuels such as ethanol. A major bottleneck is to disarray lignin which is present as a protective covering and makes cellulose and hemicellulose recalcitrant to enzymatic hydrolysis. A number of biomass deconstruction or pretreatment processes (physical, chemical and biological) have been used to break the structural framework of plants and depolymerize lignin. This review surveys and discusses some major pretreatment processes pertaining to the pretreatment of plant biomass, which are used for the production of biofuels and other value added products. The emphasis is given on processes that provide maximum amount of sugars, which are subsequently used for the production of biofuels.


Nitric oxide and its implications in skin homeostasis and disease - a review.
The recent identification of the nitric oxide synthase (NOS) pathway in various cell types in the skin has provided important insight into the molecular mechanisms underlying regulatory and homeostatic functions of the skin. Many studies also point to perturbations or defects in the signaling cascade of nitric oxide (NO) and reactive nitrogen intermediates as key players in skin disease pathogenesis. A critical role for NO is now established for a subset of human skin diseases, and new mechanism-based therapies may be available in the near future. This remarkable progress and the implications it may have for common forms of skin disease are reviewed here.


Shigellosis with resultant septic shock and renal failure.
Septic shock is a rare, potentially life-threatening complication of bacterial dysentery. The clinical presentation of septic shock includes hypotension, bleeding, hypoxia, acidosis, and jaundice. Historically gram-negative organisms were the most frequent cause of nosocomial bloodstream infections. However isolation of gram-positive organisms has become increasingly frequent with Staphylococcus species accounting for over one half of all nosocomial bloodstream pathogens. Bacterial dysentery is an acute diarrheal illness characterized by abdominal cramping, fever, and the production of mucoid, bloody stools. Laboratory findings include positive stool culture and increased leukocytes in direct fecal exam. Chemistry and hematology values may be abnormal. The disease is usually self-limiting but administration of antibiotics and rehydration therapy may be warranted in severe cases. This case study describes a 53 year old male who presented with diarrhea and diabetic acidosis and subsequently developed respiratory distress and renal failure due to shigellosis. Discussion of disease pathogenesis and treatment are provided.


Compound composite odontoma with unusual number of denticles - A rare entity.
Compound odontoma is stated to be a hamartomatous lesion rather than a true odontogenic tumour. It has an unknown etiology and often suspected when there are retained deciduous teeth in children. Early detection and surgical enucleation of the tumour is recommended to prevent impaction of unerupted teeth. In this index case, multiple denticles or rudimentary teeth, numbering 37 were enucleated from the maxillary anterior region of a 17-year old male, which makes this case unusual. Evidence of concrescence, fusion and dilaceration were observed in the denticles enucleated, the size of which varied from 4 mm to 12.5 mm.


Calcium antagonists suppress experimental allergic neuritis (EAN).
We examined the influence of Ca++ antagonist drugs on immune response and the clinical course of experimental allergic neuritis (EAN). The Ca++ antagonists verapamil and flunarizine suppressed actively induced EAN in Lewis rats in a dose-dependent fashion when given continuously by osmotic pumps from the day of immunization. If given from onset of clinical signs, day 10 after immunization, verapamil alone had therapeutic effects. The beneficial effects of the drugs seem to be mediated primarily by an action on the autoimmune response, since in vitro lymphocyte proliferation in response to nervous tissue antigens was dose-dependently inhibited by both drugs, whereas the in vitro conductivity of demyelinated sciatic nerve was not significantly affected by the Ca++ antagonists. The suppressive effect on lymphocyte proliferation could partially be bypassed by protein kinase C activating phorbol ester alone or in combination with the Ca++ ionophore ionomycin, confirming a non-toxic effect of the Ca++ antagonists on lymphocytes.


Genetic polymorphism of complement component C8.
Extensive genetic polymorphism of complement component C8 was demonstrated by isoelectric focusing of serum or plasma samples followed by immunoblotting procedures. Using these methods, we could detect both alpha-gamma (C81) and beta (C82) chain polymorphisms in the same gel. Two-dimensional (2D) electrophoresis of C8 immunoprecipitates was used to obtain further information of the C8 patterns. Evidence was obtained that the C81 polymorphism resides in the structural gene of the C8 alpha chain. Both C8 systems show autosomal, chiefly codominant inheritance, and the distribution of phenotypes agrees with the Hardy-Weinberg equilibrium. Our findings suggest at least five different alleles in the C81 system; the gene frequencies of the two most common ones, C81*A and C81*B being 0.59 and 0.39, respectively. In C82 we found evidence for at least three codominant alleles, the gene frequencies for the two most common ones, C82*B and C82*A being 0.94 and 0.05, respectively. In addition, family studies disclosed the existence of a null allele, C82*Q0.


Characterization and mitigation of the fouling of flat-sheet ceramic membranes for direct filtration of the coagulated domestic wastewater.
Ceramic membranes allow a high filtration flux with a low fouling propensity. Direct filtration of municipal wastewater using flat-sheet ceramic membranes (FSCM) is an attractive and promising technology for wastewater treatment and resource recovery. Urgent need is to determine the fouling behavior of FSCM and its optimal cleaning strategy in direct filtration applications. This study was conducted on pre-coagulation of sewage with FeCl3 (20 mg Fe/L) or polyaluminum chloride (15 mg Al/L), followed by FSCM filtration at around 1.0 m/d (as high as 41.7 L/m2-h in flux). The results showed that the coagulation-FSCM filtration removed chemical oxygen demand and total phosphorus by up to 90.0% and 99.9%, respectively. The pollutants (organics and nutrients) in the sewage influent were concentrated into the sludge for potential resource recovery. Without pre-coagulation, foulants easily entered the membrane pores, causing rapid membrane fouling. Chemically enhanced coagulation greatly decreased the membrane fouling rate by aggregating various foulants into flocs. Fouled membranes were effectively renewed by physical means, such as water flushing and sonication, or a short period of chemical backwashing with NaOH, HCl or oxidizing agents. The study revealed the fouling mechanisms of FSCM in sewage filtration and developed effective cleaning strategies for its long-term operation.


The five-items memory screen-extended variant: A tool for assessing memory.
The detection of memory impairment is an important part of dementia screening. However, the scope of memory measures in current screening batteries is limited. There is a need for a short yet sensitive instrument for early detection of memory impairment that could serve as a complement to existing globally oriented screening tests, for example, Mini-Mental State Examination (MMSE). To that end, the current study investigates the sensitivity and psychometric properties of the memory screening instrument The Five-Items Memory Screen -Extended Variant (FIMS-XV). Hundred and forty-five participants included in the Gothenburg Mild Cognitive Impairment Study-27 patients with subjective cognitive impairment (SCI), 73 with mild cognitive impairment (MCI), and 45 with mild dementia-underwent cognitive screening including the MMSE and FIMS-XV. Ninety participants also underwent extensive neuropsychological testing. The FIMS-XV showed high internal consistency and strong correlations with established neuropsychological memory tests. Both the FIMS-XVdelayed recall score and the FIMS-XV total score differentiated mild dementia patients from patients with SCI and MCI. The FIMS-XV shows promise as a sensitive tool for screening for memory impairment in all putative phases of dementia.


Lithium regulates adult hippocampal progenitor development through canonical Wnt pathway activation.
Neural stem cells give rise to new hippocampal neurons throughout adulthood, and defects in neurogenesis may predispose an individual to mood disorders, such as major depression. Our understanding of the signals controlling this process is limited, so we explored potential pathways regulating adult hippocampal progenitor (AHP) proliferation and neuronal differentiation. We demonstrate that the mood stabilizer lithium directly expands pools of AHPs in vitro, and induces them to become neurons at therapeutically relevant concentrations. We show that these effects are independent of inositol monophosphatase, but dependent on Wnt pathway components. Both downregulation of glycogen synthase kinase-3beta, a lithium-sensitive component of the canonical Wnt signaling pathway, and elevated beta-catenin, a downstream component of the same pathway produce effects similar to lithium. In contrast, RNAi-mediated inhibition of beta-catenin abolishes the proliferative effects of lithium, suggesting that Wnt signal transduction may underlie lithium's therapeutic effect. Together, these data strengthen the connection between psychopharmacologic treatment and the process of adult neurogenesis, while also suggesting the pursuit of modulators of Wnt signaling as a new class of more effective mood stabilizers/antidepressants.


Different approaches for estimating measurement uncertainty: An effective tool for improving interpretation of results.
The estimation of measurement uncertainty (MU) in clinical laboratories is of crucial importance in improving laboratory testing quality and correctly interpreting results. However, it is difficult for clinical laboratories to reliably estimate MU since current guidelines and standards fail to clearly define and harmonize methods to be used for this purpose. To propose a model for MU estimation in relation to test interpretation on the basis of three different scenarios. MU estimation was evaluated regard to the inclusion of imprecision and bias components for different test purposes. Three scenarios were identified. The expanded uncertainty values were: 0.56 ng/L and 1.86 ng/L for troponin I at levels 4.95 ng/L and 20.60 ng/L, respectively; 9.4 μmol/L and 27.2 μmol/L for creatinine at levels 121.0 μmol/L and 390.0 μmol/L, respectively. 0.2 mmol/L and 0.3 mmol/L for potassium at levels 4.03 mmol/L and 6.35 mmol/L, respectively; 0.36 mmol/L for glucose at level of around 6 mmol/L. These values represent MU results estimated for the three scenarios, which contemplate test results used for 1a) short term patient monitoring, 1b) longer term patient monitoring, 2) comparison with reference intervals and 3) comparison with a clinical decision point. Goal-based measurement uncertainty estimation in clinical laboratories provides an opportunity to improve laboratory testing quality and reduce risk in the interpretation of clinical results.


Pneumotaxic mechanisms in the non-human primate: effect of the N-methyl-D-aspartate (NMDA) antagonist ketamine.
We tested the possible involvement of N-methyl-D-aspartate (NMDA) receptors in the central inspiratory-termination mechanism in non-human primates. Inspiratory bursts were recorded from the phrenic nerve in Macaca fascicularis monkeys paralyzed and ventilated by means of a servoventilator driven by the inspiratory discharge of the phrenic nerve. The central inspiratory termination mechanism was tested by withholding lung inflation. This transiently suppressed the vagal feedback from the lungs which produces inspiratory off-switching independent from the central mechanism. Under anaesthesia with ketamine, a potent NMDA antagonist, non inflation increased inspiratory time to 4s (1s with lungs inflated) whereas no such effect was observed during halothane anaesthesia. We conclude that the termination of inspiration in primates is controlled via central mechanisms in which NMDA receptors are involved.


WIPI β-propellers function as scaffolds for STK11/LKB1-AMPK and AMPK-related kinase signaling in autophagy.
The article discusses new findings on the role of the 4 human WIPI proteins at the onset of macroautophagy/autophagy. New insights revealing a circuit scaffold function of WIPI β-propellers that interconnect autophagy signaling control with appropriate autophagosome formation are summarized.


Effect of two exogenous plant growth regulators on the color and quality parameters of seedless table grape berries.
Some red-pink table grape varieties, cultivated in warm climates, can fail in achieving the right level of anthocyanins responsible for the intense and uniform red color of berries. Nowadays, this is becoming an important technological issue in the Mediterranean area, which may result in decreasing market acceptance and potential economic value of table grape. Usually, plant growth regulators or phytohormones, such as S-ABA, can overcome this problem because they drive the accumulation of anthocyanins over the ripening season. Harpin proteins (HrP), which enhance the plant disease resistance, may be supposed to stimulate the anthocyanins biosynthesis in grape skin if applied close to veraison. Therefore, this research aimed at comparing the effect of HrP and S-ABA over the anthocyanin and color improvement of Crimson Seedless table grape grown in Southern Italy. For the first time, the exogenous treatment with HrP showed as effective as the less sustainable S-ABA one in favoring the anthocyanin accumulation, leading to peonidin-3-O-glucoside, cyanidin-3-O-glucoside, and malvidin-3-O-glucoside values up to 4 folds higher than control grapes and giving rise to a greater concentration of the more stable acylated anthocyanins. Overall, the color of berries was improved but keeping high the other quality characteristics.


Transient congenital hypothyroidism after topical iodine in pregnancy and lactation.
A 6 week old girl with transient congenital hypothyroidism is described. The hypothyroidism was associated with multiple applications of povidone iodine during pregnancy and lactation. This case illustrates the potential hazard of using topical solutions containing iodine during pregnancy and lactation.


High proximal pouch esophageal atresia with vertebral, rib, and sternal anomalies: an additional component to the VATER association.
The base of the proximal esophageal pouch in babies born with esophageal atresia varies in location from the low cervical region to the upper third of the mediastinum, but the relevance of this finding to the VATER association is not known. The initial radiographs and hospital records of 42 newborns with esophageal atresia and a distal tracheoesophageal fistula treated in the Newborn Special Care Unit of the Yale-New Haven Hospital between 1977 and 1986 were examined to (1) determine the location of the base of the upper esophageal pouch on its superimposed vertebral body; (2) identify coexisting VATER associated anomalies; and (3) detect the presence of vertebral, rib, or sternal anomalies. Ten of 11 babies with the upper esophageal pouch at the first thoracic vertebra or above had additional VATER defects including vertebral, rib, or sternal anomalies. These patients also required staged repair or circular myotomy for wide gap esophageal atresia and were at greater risk of anastomotic leak, stricture, or gastroesophageal reflux requiring fundoplication. High proximal pouch esophageal atresia accompanied by vertebral, rib, and sternal anomalies constitutes a heretofore unrecognized high risk group with the VATER association.


Cold and warm infusion of Ringer's acetate in healthy volunteers: the effects on haemodynamic parameters, transcapillary fluid balance, diuresis and atrial peptides.
The effects of Ringer's acetate (RAc) infusion with different temperatures, 18 degrees C compared to 36 degrees C, were studied in 20 healthy volunteers. An infusion volume of 20% of the estimated extracellular volume was given over 45 min. Before and after the RAc infusion, interstitial colloid osmotic pressure and interstitial fluid hydrostatic pressure were measured on the lateral part of the thorax and in the lower leg. Blood sampling and pressure measurements were performed through a cannula placed in the left radial artery, and arterial oxygen saturation was measured by pulse oximetry. Atrial peptides ANF (99-126) and ANF (1-98) in plasma were measured as indicators of volume loading. Cold RAc infusion increased mean arterial pressure from 82 (s.d. +/- 7) to 96 (s.d. +/- 9) mmHg (10.9-12.8 kPa) at the end of the infusion with a simultaneous fall in heart rate. Warm RAc infusion gave no changes in blood pressure or heart rate. The arterial oxygen saturation during the infusion of cold RAc was higher than during warm RAc infusion. Cold infusion produced the expected haemodilution with a fall in erythrocyte volume fraction (EVF) from 0.39 (+/- 0.03) to 0.33 (+/- 0.03) and a fall in plasma colloid osmotic pressure (COPp) from 21.7 (+/- 1.1) mmHg to 15.0 (+/- 1.3) mmHg (2.9-2.0 kPa). Warm infusion induced a nearly identical haemodilution. Interstitial colloid osmotic pressure fell from 11.6 (+/- 2.3) mmHg to 8.9 (+/- 2.7) mmHg (1.5-1.2 kPa) after warm infusion while cold infusion gave no changes. The changes in interstitial fluid hydrostatic pressure were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)


The efficacy of tobramycin in the treatment of ulcerative colitis.
This paper reports a double-blind placebo-controlled trial of oral tobramycin in acute ulcerative colitis. Eighty-four patients with an acute relapse of ulcerative colitis were randomized to receive oral tobramycin or placebo for 1 week as an adjunct to steroid therapy. At endpoint, 31 of 42 (74%) in the tobramycin group achieved complete symptomatic remission compared with 18 of 42 (43%) in the placebo group (P = 0.008). The tobramycin group achieved better histological scores (P less than 0.05) at endpoint. These findings show that treatment with oral tobramycin improves the short-term outcome of patients with ulcerative colitis in relapse.


Clinical Characteristics Associated With Secondary Generalization in Patients With Ocular Myasthenia Gravis: A Systematic Review and Meta-analysis.
Ocular myasthenia gravis (OMG) is an autoimmune disorder resulting in ocular symptoms such as diplopia and ptosis. The proportion of patients who convert to secondary generalized myasthenia gravis (SGMG) reported in the literature has been varied. The aim of this systematic review was to determine the clinical characteristics of patients with OMG and the proportion of SGMG conversion. We conducted an electronic database search for randomized controlled trials, prospective nonrandomized studies, observational studies, and retrospective studies in EMBASE, CENTRAL, MEDLINE, and Web of Science. We included studies with patients with OMG who initially presented with ocular symptoms and signs only and were seen in clinical practice, reporting on the characteristics and outcomes of SGMG. We excluded studies with pediatric and congenital myasthenia gravis populations. Eligible studies included articles written in any language and containing data on patients with OMG. The main outcome measured was the proportion of patients with OMG who converted to SGMG and risk factors associated with secondary generalization of OMG. Two independent reviewers screened titles and abstracts and extracted data from full texts, reporting findings according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodology was evaluated using the Joanna Briggs Institute critical appraisal forms. PROSPERO registration number: CRD2021285257. Thirty-one studies were included in the quantitative and qualitative analysis. The proportion of generalization ranged from 11% to 84%. The pooled proportion was 39% (95% CI 32%-47%, I 2 = 95.86%, p < 0.001 unweighted, low certainty). The pooled risk ratio of female sex for conversion to SGMG was 1.06 (95% CI 0.96-1.17, I 2 = 0% p = 0.614, 21 studies included, very low certainty), and the pooled risk ratio of acetylcholine receptor (AChR) positivity was 1.30 (95% CI 1.05-1.56, I 2 = 0% p = 0.455, 16 studies included, very low certainty). Risk factors such as female sex and anti-AChR positivity have been identified to have possible associations with SGMG, but there are not enough quality observational studies. There is a need for a prospective global database of patients with OMG, including all countries with different populations.


Porcine ISG15 modulates the antiviral response during pseudorabies virus replication.
Pseudorabies virus (PRV) is one of the most vital pathogens of swine, leading to huge economic losses to the pig industry. Functioning in innate immunity, type-I interferon (IFN) plays a vital role in initial stage of viral infection. ISG15, an IFN-stimulated ubiquitin-like protein, is highly increased during virus infection and participates in the IFN-mediated antiviral immune response. However, limited attention has been paid to the functional role of porcine ISG15 (pISG15) in PRV infection. In this study, we generated a PK15 inducible cell line stably expressing the pISG15 gene and investigated the potential anti-PRV response of pISG15. We demonstrated that pISG15 was upregulated in an early stage of PRV infection, and pISG15 overexpression efficiently inhibited PRV replication by reducing the viral titers and mRNA levels of PRV, and also increased expression of IFN-β and activation of the ISRE promoter. However, knockdown of pISG15 by siRNA did not affect PRV replication, and potentiated IFN-I-mediated signaling, resulting in an increase in antiviral response in the process of PRV infection. The results showed that pISG15 has a potential immunodulatory role in cellular antiviral response against PRV.


Preparing for the next outbreak: A review of indices measuring outbreak preparedness, vulnerability, and resilience.
The COVID-19 pandemic has highlighted the need for relevant metrics describing the resources and community attributes that affect the impact of communicable disease outbreaks. Such tools can help inform policy, assess change, and identify gaps to potentially reduce the negative outcomes of future outbreaks. The present review was designed to identify available indices to assess communicable disease outbreak preparedness, vulnerability, or resilience, including articles describing an index or scale developed to address disasters or emergencies which could be applied to addressing a future outbreak. This review assesses the landscape of indices available, with a particular focus on tools assessing local-level attributes. This systematic review yielded 59 unique indices applicable to assessing communicable disease outbreaks through the lens of preparedness, vulnerability, or resilience. However, despite the large number of tools identified, only 3 of these indices assessed factors at the local level and were generalizable to different types of outbreaks. Given the influence of local resources and community attributes on a wide range of communicable disease outcomes, there is a need for local-level tools that can be applied broadly to various types of outbreaks. Such tools should assess both current and long-term changes in outbreak preparedness with the intent to identify gaps, inform local-level decision makers, public policy, and future response to current and novel outbreaks.


Internal anal sphincter function following lateral internal sphincterotomy for anal fissure: a long-term manometric study.
Anal fissure is a common and painful disorder. Its relation to hypertonic anal sphincter is controversial. The most common surgical treatment of chronic anal fissure is lateral internal sphincterotomy. The aim of this study was to evaluate long-term manometric results of sphincter healing following lateral internal sphincterotomy. Between 2000 and 2003, 50 patients with anal fissure were included in this study and underwent sphincterotomy; 12 healthy patients served as controls. All patients with anal fissure underwent manometric evaluation using a 6-channel perfusion catheter. All patients were examined 1 month before surgery and 1, 3, 6, and 12 months following surgery. The control group had 3 manometric evaluations 6 months apart. The mean basal resting pressure before surgery was 138 +/- 28 mm Hg. One month after surgery, the pressure dropped to 86 +/- 15 mm Hg (P < 0.0001) and gradually rose to a plateau at 12 months (110 +/- 18 mm Hg, P < 0.0001). At 12 months, the manometric pressure was significantly lower than the baseline (P < 0.0001). However, manometric measurements in the fissure group were still significantly higher than in the control group (110 +/- 18 versus 73 +/- 4.8 mm Hg, P < 0.0001). All patients were free of symptoms at the 12-month follow-up. Lateral internal sphincterotomy caused a significant decline in the resting anal pressure. During the first year following surgery, the tone of the internal anal sphincter gradually increased, indicating recovery, but still remained significantly lower than before surgery. However, postoperative resting pressures were higher than those in the control, and no patient suffered any permanent problems with incontinence, so this decrease may not be clinically significant.


Author Correction: GPU-Accelerated GLRLM Algorithm for Feature Extraction of MRI.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Nucleotide sequence of the EcoRI-F fragment of adenovirus 2 genome.
Using the DNA sequence method of Maxam and Gilbert the entire nucleotide sequence of the adenovirus 2 EcoRI-F fragment was determined. Information contained in that nucleotide sequence, which is 1743 base pairs long, is interpreted with respect to the mapping and processing of the three mRNAs partly encoded by the EcoRI-F fragment. A method to rapidly determine the cleavage site of restriction endonucleases is also reported.


A randomized, placebo-controlled laboratory study of the effects of D-cycloserine on craving in cocaine-dependent individuals.
D-Cycloserine (DCS), a partial glutamate N-methyl-D-aspartate (NMDA) receptor agonist, enhances extinction of conditioned fear responding; preliminary data suggest that it may facilitate extinction of drug cue reactivity. This study investigates DCS effects on cocaine cue craving and drug use in cocaine-dependent subjects. Thirty-two subjects were randomly assigned to receive (1) DCS only, (2) DCS before sessions 1 and 3, placebo (PBO) before session 2, or (3) PBO only 15-min before each of 3 1-h cocaine cue exposure sessions conducted 1 day apart. Craving ratings were obtained before, during, and after sessions. Drug use and cue-induced craving were assessed 1 week after the last cue session. Repeated presentation of cocaine cues resulted in decreased craving both within and between sessions. DCS did not facilitate extinction learning and may have enhanced craving. The group that received three doses of DCS had significantly higher craving than the PBO group at the baseline ratings taken before sessions 2 and 3, as well as significantly higher cue-induced craving at follow-up. The group that received two doses of DCS did not differ from the PBO group. There were no group differences in postextinction cocaine use. The reduction of cocaine cue reactivity in the PBO group suggests that the study procedures were sufficient to produce extinction. Under these conditions, DCS did not facilitate extinction and may have enhanced craving. Further studies of glutamatergic agents and extinction in cocaine dependence should include consideration of procedural variables that could have a major impact on study outcomes.


A differentiation program induced by bone morphogenetic proteins 4 and 7 in endodermal epithelial cells provides the molecular basis for efficient nutrient transport by the chicken yolk sac.
The mammalian yolk sac provides nutrients for the growing fetus during critical early developmental processes such as neural tube closure, which precedes the functional maturation of the placenta. In contrast, oviparous species such as the chicken rely solely on the yolk sac for transfer of nutrients from the yolk to the developing embryo. However, the molecular mechanisms that provide the yolk sac with nutrient transfer competence remain poorly understood. We demonstrate that the chicken endodermal epithelial cells (EEC), which are in close contact with the yolk, gain their nutrient-transport competence by a paracrine crosstalk with the blood-vessel forming mesodermal cell layer. Bone morphogenetic proteins (BMP) 4 and 7 produced by ectodermal and mesodermal cell layers likely initiate a differentiation program of EECs during the transition from the area vitellina to the area vasculosa. BMPs, by inducing SMAD signaling, promote the up-regulation of endocytic receptor expression and thereby provide the EECs with the molecular machinery to produce triglyceride-rich lipoprotein particles. This paracrine signaling cascade may constitute the basis for the EEC-mediated mechanism underlying the efficient uptake, degradation, resynthesis, and transfer of yolk-derived nutrients into the embryonic circulation, which assures proper energy supply and development of the growing fetus.


Quality of warfarin therapy and risk of stroke, bleeding, and mortality among patients with atrial fibrillation: results from the nationwide FinWAF Registry.
The most important management strategy in atrial fibrillation (AF) patients is preventing stroke with oral anticoagulants. Warfarin is still used as a first-line anticoagulant, although non-vitamin K antagonist oral anticoagulants are currently recommended to manage AF. Using a large, unselected national sample of AF patients, we evaluated the relationships between quality of warfarin therapy and the risks of thromboembolism, bleeding complications, and mortality. The nationwide FinWAF study included 54 568 AF patients taking warfarin. Time in the therapeutic range (TTR) was calculated on a continuous basis using the Rosendaal method and international normalized ratio values over the previous 60 days. Adjusted Cox proportional hazard models were prepared for different TTR levels and major clinical end points. The mean age of patients was 73.1 years (standard deviation 10.8), and 47% were female. The mean follow-up time was 3.2 ± 1.6 years (median 3.4). In the TTR groups of ≤40%, 60-70%, 70-80%, and >80%, the annual risk of stroke was 9.3%, 4.7%, 4.6%, and 3.1%; bleeding events 7.5%, 4.5%, 4.3%, and 2.6%; and overall mortality 20.9%, 8.5%, 6.4%, and 3.1%, respectively. All differences among the TTR groups were highly significant (p < 0.001). The quality of warfarin treatment was strongly associated with the risk of stroke and the prognosis of AF patients. Patient outcomes continued to improve with increasing TTR values up to a TTR ≥80%; therefore, the target for the TTR should exceed 80% instead of the traditional range of at least 60-70%. Copyright © 2017 John Wiley & Sons, Ltd.


Role of fibroblast growth factors in organ regeneration and repair.
In its broad sense, regeneration refers to the renewal of lost cells, tissues or organs as part of the normal life cycle (skin, hair, endometrium etc.) or as part of an adaptive mechanism that organisms have developed throughout evolution. For example, worms, starfish and amphibians have developed remarkable regenerative capabilities allowing them to voluntarily shed body parts, in a process called autotomy, only to replace the lost parts afterwards. The bizarre myth of the fireproof homicidal salamander that can survive fire and poison apple trees has persisted until the 20th century. Salamanders possess one of the most robust regenerative machineries in vertebrates and attempting to draw lessons from limb regeneration in these animals and extrapolate the knowledge to mammals is a never-ending endeavor. Fibroblast growth factors are potent morphogens and mitogens that are highly conserved among the animal kingdom. These growth factors play key roles in organogenesis during embryonic development as well as homeostatic balance during postnatal life. In this review, we provide a summary about the current knowledge regarding the involvement of fibroblast growth factor signaling in organ regeneration and repair. We also shed light on the use of these growth factors in previous and current clinical trials in a wide array of human diseases.


Postmenopausal Osteoporosis: The Role of Lifestyle in Maintaining Bone Mass and Reducing Fracture Risk.
Postmenopausal osteoporosis is a significant contributor to morbidity and mortality. Medications can provide effective treatment but their use can be complicated by side effects. This case illustrates the role that diet, supplements, and specific exercises can play in preventing and treating bone loss and reducing fracture risk.


Complex elbow dislocation with ipsilateral segmental fracture of radius and ulna in a young boy: a complex injury with multiple fractures.
Complex elbow dislocation1 (fracture of lateral condyle and avulsion fracture of medial epicondyle) with ipsilateral segmental fracture of radius and ulna without distal neurovascular deficit following machinery rolling belt injury in a 14 years boy presenting to emergency room of BP Koirala Institute of Health Sciences, is reported due to its complex nature of injury and good outcome after adequate follow up. The literature is reviewed for complex elbow dislocation to show its rarity.


Upper and lower bounds for correlations in 2 X 2 tables--revisited.
The correlation coefficient (r) between two dichotomous variables requires a different interpretation from that of the customary correlation between normally distributed continuous variables, since perfect correlation is usually not +1 or -1. The maximum and minimum possible correlations between two dichotomous variables depend on the marginal distributions. An example using data on smoking and lung cancer illustrates that what appears to be a small correlation in the usual sense may in fact be quite large in relation to the maximum possible. Similarly, the interpretation of R2 as the proportion of variance of the dependent variable that is explained by the independent variable(s) is subject to the same consideration. This paper describes the calculation of the upper and lower limits of r for two dichotomous variables. The problem of interpreting R2 in linear regression and the use of R2 for variable selection in stepwise regression applied to dichotomous data are also discussed and illustrated.


The application of relational theory towards a deeper understanding of emotional variables in language education.
At the heart of the relational theory, which stems from psychological studies, is the contention that the human mind is formed within interpersonal relationships. In the present paper, the aim is to show that the same goes for emotions. More importantly, in educational settings, the relationships between and among the individuals especially the teacher-student relationships lead to the emergence of different emotions. The present paper shows how the relational theory can be used in the second language acquisition domain to explain the development of different L2 emotions that learners experience while interactively involved in acquiring a second language in class. What is mostly emphasized in this paper is the teacher-student relationships that occur in L2 classes and accommodate the L2 emotions. The related literature on teacher-student relationships and emotional development in L2 classrooms is reviewed, and insightful remarks are provided for L2 teachers, teacher trainers, learners, and researchers.


Symptomatic atherosclerotic vascular disease and graft survival in primary kidney transplant recipients - Observational analysis of the united network of organ sharing database.
The aim of this study was to investigate whether symptomatic atherosclerotic vascular disease (SAVD) was associated with graft survival in primary kidney transplant recipients. Recipient atherosclerotic vascular disease is associated with increased mortality rates amongst renal transplant patients. However, its relationship with graft survival has not been well studied. This retrospective observational analysis was performed using data for adult kidney transplant recipients between 11/09/2000 and 28/02/2020 extracted from the UNOS national organ transplantation database. Patients were divided into two groups based on recipient history of symptomatic atherosclerotic disease (angina or peripheral vascular disease). Risk-adjusted outcomes were assessed by multivariate Cox regression analysis adjusting for both donor and recipient characteristics. 11,771 adult kidney transplant recipients from the UNOS database were eligible for analysis (1543 had a history of SAVD, 10,228 did not have a history of SAVD). After adjusting for confounders, positive SAVD status was associated with an adverse effect on graft survival at both 1 year (HR 1.35, p < 0.001) and 10 years (HR 1.15, p < 0.001). SAVD should be considered an independent risk factor for poor prognosis in patients undergoing kidney transplant.


Diffusion-weighted MRI and in-phase/opposed-phase sequences in the assessment of bone tumors.
To evaluate the role of diffusion-weighted apparent diffusion coefficient (ADC) and in-phase/opposed-phase sequences in the differentiation of benign and malignant osseous tumors. At 1.5T, routine sequences were compared to diffusion-weighted and in-phase/opposed-phase in 63 patients. Routine sequence magnetic resonance imaging (MRI) scoring, mean ADC value, and in-phase/opposed-phase signal intensity ratio (SIR) was obtained. Statistical analysis included significance, receiver operating characteristic (ROC), and linear correlation between the three parameters. In all, 38 patients had malignant tumors and 25 patients had benign tumors. Benign and malignant tumors showed different routine sequence scores (P < 0.001). Mean ADC of the benign lesions ranged 0.9-3.2 × 10(-3) mm(2) /sec of mean ± SD (1.9 ± 0.6). In malignant tumors, the mean ADC ranged 0.6-1.9 × 10(-3) mm(2) /sec of mean ± SD (1.1 ± 0.4) (P < 0.0001). There was a possible differentiation between malignant and benign tumors at a threshold of 1.1 × 10(-3) mm(2) /sec of sensitivity and specificity of 94.1% and 70.3%, respectively. SIR for benign tumors ranged 0.2-1.0 of mean ± SD (0.6 ± 0.3). For malignant lesions SIR ranged 0.4-1.2 of mean ± SD (0.8 ± 0.3). Benign and malignant tumors show statistically significant SIR at P < 0.022 with possible differentiation at a threshold of 0.75 of sensitivity and specificity of 70.3% and 76.5%, respectively. Simple linear correlation between both ADC and SIR was significant at P < 0.01 with correlation coefficient (r) = 0.45. Diffusion-weighted and in-phase/opposed-phase imaging might be used in addition to conventional MRI as a routine tool for differentiation of benign and malignant tumors. J. Magn. Reson. Imaging 2016;44:565-572.


Transcriptomic and metabolic analyses reveal salvage pathways in creatine-deficient AGAT(-/-) mice.
Skeletal muscles require energy either at constant low (e.g., standing and posture) or immediate high rates (e.g., exercise). To fulfill these requirements, myocytes utilize the phosphocreatine (PCr)/creatine (Cr) system as a fast energy buffer and shuttle. We have generated mice lacking L-arginine:glycine amidino transferase (AGAT), the first enzyme of creatine biosynthesis. These AGAT(-/-) (d/d) mice are devoid of the PCr/Cr system and reveal severely altered oxidative phosphorylation. In addition, they exhibit complete resistance to diet-induced obesity, which is associated with a chronic activation of AMP-activated protein kinase in muscle and white adipose tissue. The underlying metabolic rearrangements have not yet been further analyzed. Here, we performed gene expression analysis in skeletal muscle and a serum amino acid profile of d/d mice revealing transcriptomic and metabolic alterations in pyruvate and glucose pathways. Differential pyruvate tolerance tests demonstrated preferential conversion of pyruvate to alanine, which was supported by increased protein levels of enzymes involved in pyruvate and alanine metabolism. Pyruvate tolerance tests suggested severely impaired hepatic gluconeogenesis despite increased availability of pyruvate and alanine. Furthermore, enzymes of serine production and one-carbon metabolism were significantly up-regulated in d/d mice, indicating increased de novo formation of one-carbon units from carbohydrate metabolism linked to NAD(P)H production. Besides the well-established function of the PCr/Cr system in energy metabolism, our transcriptomic and metabolic analyses suggest that it plays a pivotal role in systemic one-carbon metabolism, oxidation/reduction, and biosynthetic processes. Therefore, the PCr/Cr system is not only an energy buffer and shuttle, but also a crucial component involved in numerous systemic metabolic processes.


Design of highly efficient phosphor-converted white light-emitting diodes with color rendering indices (R1 - R15) ≥ 95 for artificial lighting.
Phosphor-converted white light-emitting diodes (pc-WLEDs) are excellent energy-efficient light sources for artificial lighting applications. One goal of artificial lighting is to make objects/images look natural - as they look under the sunlight. The ability of a light source to accurately render the natural color of an object is gauged by the parameter - color rendering index (CRI). A conventional pc-WLED has an average CRI ~ 80, which is very low for accurate color reproduction. To utilize the pc-WLEDs for artificial lighting applications, all the CRI points (R1 - R15) should be above 95. However, there is a trade-off between CRI and luminous efficacy (LER), and it is challenging to increase both CRI and LER. Herein we propose a novel LED package (PKG) design to achieve CRI points ≥95 and efficiency ~100 lm/W by introducing two blue LEDs and a UV LED in combination with green and red phosphors. The silicone encapsulant, the current through the LEDs, and the green/red phosphor ratio were optimized for achieving high CRI and LER. Our re-designed LED PKG will find applications in stadium lighting as well as for ultra-high-definition television production where high CRI points are required for the artificial light source.


Role of α5* nicotinic acetylcholine receptors in the effects of acute and chronic nicotine treatment on brain reward function in mice.
Allelic variation in the α5 nicotinic acetylcholine receptor (nAChR) subunit gene, CHRNA5, increases vulnerability to tobacco addiction. Here, we investigated the role of α5* nAChRs in the effects of nicotine on brain reward systems. Effects of acute (0.03125-0.5 mg/kg SC) or chronic (24 mg/kg per day; osmotic minipump) nicotine and mecamylamine-precipitated withdrawal on intracranial self-stimulation (ICSS) thresholds were assessed in wild-type and α5 nAChR subunit knockout mice. Noxious effects of nicotine were further investigated using a conditioned taste aversion procedure. Lower nicotine doses (0.03125-0.125 mg/kg) decreased ICSS thresholds in wild-type and α5 knockout mice. At higher doses (0.25-0.5 mg/kg), threshold-lowering effects of nicotine were diminished in wild-type mice, whereas nicotine lowered thresholds across all doses tested in α5 knockout mice. Nicotine (1.5 mg/kg) conditioned a taste aversion to saccharine equally in both genotypes. Mecamylamine (5 mg/kg) elevated ICSS thresholds by a similar magnitude in wild-type and α5 knockout mice prepared with minipumps delivering nicotine. Unexpectedly, mecamylamine also elevated thresholds in saline-treated α5 knockout mice. α5* nAChRs are not involved in reward-enhancing effects of lower nicotine doses, the reward-inhibiting effects of nicotine withdrawal, or the general noxious effects of higher nicotine doses. Instead, α5* nAChRs regulate the reward-inhibiting effects nicotine doses that oppose the reward-facilitating effects of the drug. These data suggest that disruption of α5* nAChR signaling greatly expands the range of nicotine doses that facilitate brain reward activity, which may help explain the increased tobacco addiction vulnerability associated with CHRNA5 risk alleles.


Chiral separation of the β2-sympathomimetic fenoterol by HPLC and capillary zone electrophoresis for pharmacokinetic studies.
The development of methods for the separation of the enantiomers of fenoterol by chiral HPLC and capillary zone electrophoresis (CZE) is described. For the HPLC separation precolumn fluorescence derivatization with naphthyl isocyanate was applied. The resulting urea derivatives were resolved on a cellulose tris(3,5-dimethylphenylcarbamate)-coated silica gel column employing a column switching procedure. Detection was carried out fluorimetrically with a detection limit in the low ng/mL range. The method was adapted to the determination of fenoterol enantiomers in rat heart perfusates using liquid-liquid extraction. As an alternative a CE method was used for the direct separation of fenoterol enantiomers comparing different cyclodextrin derivatives as chiral selectors.


Room-Temperature Synthesized Cd-Doped Cs3 Cu2 I5 : Stable and Excitation-Wavelength Dependent Dual-Color Emission for Advanced Anti-Counterfeiting.
With the development of intellectual properties, concern about advanced anti-counterfeiting is accumulating, which conventional single-modal luminescence can no longer satisfy. As one of rapidly developing 0D materials, copper-based perovskite shows great potential to realize multiple luminescent centers for complex emissions. In this work, Cd was doped into Cs3 Cu2 I5 and showed resultant emission at 560 nm which surprisingly showed a red-shifted excitation peak from that of intrinsic self-trapped emission, resulting in excitation-wavelength dependent emission. When the excitation wavelength increased from 290 nm to 330 nm, the emission of Cd-doped Cs3 Cu2 I5 changed from deep blue to cold white and finally yellow. Afterwards, Cd-doped Cs3 Cu2 I5 was mixed with polystyrene to prepare anti-counterfeiting ink for silk-screen printing. Meanwhile, Cd-doped Cs3 Cu2 I5 maintains outstanding stability after doping, no matter under ambient, continuous UV radiation or high-temperature environment. The intensity can be almost totally recovered after heating-and-cooling cycles. This study lays groundwork for future research into multiple luminescent center manipulation in 0D materials.


New practice parameters: what does the evidence say?
The American Academy of Neurology recently has published two practice parameters pertaining to children and adolescents with headache. The first focuses attention on the appropriate evaluation of the child with recurrent headache and reviews the data regarding laboratory investigation, electroencephalography (EEG), and neuroimaging. Routine laboratory investigation and EEG are not recommended. Neuroimaging is not recommended for children with recurring headaches and a normal neurologic examination unless there are historic features to suggest the recent onset of severe headache, change in the type of headache, or associated features that suggest neurologic dysfunction. If there are abnormalities on the neurologic examination (eg, focal findings, signs of increased intracranial pressure, significant alteration of consciousness) or the coexistence of seizures, then neuroimaging is recommended. The second parameter evaluates relevant data regarding the acute and preventive therapies for pediatric migraine.


Quantitative Proteome-Property Relationships (QPPRs). Part 1: finding biomarkers of organic drugs with mean Markov connectivity indices of spiral networks of blood mass spectra.
Numerical parameters of the molecular networks, also referred as Topological Indices or Connectivity Indices (CIs), have been used in Bioorganic and Medicinal Chemistry to find Quantitative Structure-Activity, Property or Toxicity Relationship (QSAR, QSPR and QSTR) models. QSPR models generally use CIs as inputs to predict the biological activity of compounds. However, the literature does not evidence a great effort to find QSAR-like models for other biologically and chemically relevant systems. For instance, blood proteome constitutes a protein-rich information reservoir, since the serum proteome Mass Spectra (MS) represents a potential information source for the early detection of Biomarkers for diseases and/or drug-induced toxicities. The concept of mass spectrum network (MS network) for a single protein is already well-known. However, there are no reported results on the use of CIs for a MS network of a whole proteome to explore MS patterns. In this work, we introduced for the first time a novel network representation and the CIs for the MS of blood proteome samples. The new network bases on Randic's Spiral network have been previously introduced for protein sequences. The new MS CIs, called here Spiral Markov Connectivity (SMC(k)) of the MS Spiral graph can be calculated with the software MARCH-INSIDE, combining network and Markov model theory. The SMC(k) values could be used to seek QSAR-like models, called in this work Quantitative Proteome-Property Relationships (QPPRs). We calculate the SMC(k) values for 62 blood samples and fit a QPPR model by discriminating proteome MS, typical of individuals susceptible to suffer drug-induced cardiotoxicity from control samples. The accuracy, sensitivity, and specificity values of the QPPR model were between 73.08% and 87.5% in training and validation series. This work points to QPPR models as a powerful tool for MS detection of biomarkers in proteomics.


Utilization of gum polysaccharide of Araucaria heterophylla and Azadirachta indica for encapsulation of cyfluthrin loaded super paramagnetic iron oxide nanoparticles for mosquito larvicidal activity.
Surface engineering of super paramagnetic iron oxide nanoparticles (SPIONs) favor the tagging of any molecule or compound onto it, encapsulating them with a biopolymer make them biocompatible and favor slow release of loaded molecules. Recovery of SPIONs is easier as they obey to external magnetic field. In this study, SPIONS were used for mosquito larvicidal activity after surface engineered with oleic acid to favor the tagging of Cyfluthrin (mosquito larvicidal agent), it was then encapsulated with gum polysaccharide derived from Azadirachta indica and Araucaria heterophylla. Every stage of coreshell formation was microscopically and spectroscopically characterized. The coreshell SPIONs produced using Azadirachta indica and Araucaria heterophylla gum derived polysaccharide encapsulation were found to be the size around 80 nm. Thus, prepared coreshell SPIONs was subjected for mosquito larvicidal activity against Culex sp. The coreshell SPIONs was efficiently killing the mosquito larva and its impact was studied by percentage mortality studies.


Comparative brain architecture of the European shore crab Carcinus maenas (Brachyura) and the common hermit crab Pagurus bernhardus (Anomura) with notes on other marine hermit crabs.
The European shore crab Carcinus maenas and the common hermit crab Pagurus bernhardus are members of the sister taxa Brachyura and Anomura (together forming the taxon Meiura) respectively. Both species share similar coastal marine habitats and thus are confronted with similar environmental conditions. This study sets out to explore variations of general brain architecture of species that live in seemingly similar habitats but belong to different major malacostracan taxa and to understand possible differences of sensory systems and related brain compartments. We examined the brains of Carcinus maenas, Pagurus bernhardus, and three other hermit crab species with immunohistochemistry against tyrosinated tubulin, f-actin, synaptic proteins, RF-amides and allatostatin. Our comparison showed that their optic neuropils within the eyestalks display strong resemblance in gross morphology as well as in detailed organization, suggesting a rather similar potential of processing visual input. Besides the well-developed visual system, the olfactory neuropils are distinct components in the brain of both C. maenas and P. bernhardus as well as the other hermit crabs, suggesting that close integration of olfactory and visual information may be useful in turbid marine environments with low visibility, as is typical for many habitats such as, e.g., the Baltic and the North Sea. Comparing the shape of the olfactory glomeruli in the anomurans showed some variations, ranging from a wedge shape to an elongate morphology. Furthermore, the tritocerebrum and the organization of the second antennae associated with the tritocerebrum seem to differ markedly in C. maenas and P. bernhardus, indicating better mechanosensory abilities in the latter close to those of other Decapoda with long second antennae, such as Astacida, Homarida, or Achelata. This aspect may also represent an adaptation to the "hermit lifestyle" in which competition for shells is a major aspect of their life history. The shore crab C. maenas, on the other hand seems to rely much less on mechanosensory information mediated by the second antennae but in water, the visual and the olfactory senses seem to be the most important modalities.


A novel wastewater-based epidemiology indexing method predicts SARS-CoV-2 disease prevalence across treatment facilities in metropolitan and regional populations.
There is a need for wastewater based epidemiological (WBE) methods that integrate multiple, variously sized surveillance sites across geographic areas. We developed a novel indexing method, Melvin's Index, that provides a normalized and standardized metric of wastewater pathogen load for qPCR assays that is resilient to surveillance site variation. To demonstrate the utility of Melvin's Index, we used qRT-PCR to measure SARS-CoV-2 genomic RNA levels in influent wastewater from 19 municipal wastewater treatment facilities (WWTF's) of varying sizes and served populations across the state of Minnesota during the Summer of 2020. SARS-CoV-2 RNA was detected at each WWTF during the 20-week sampling period at a mean concentration of 8.5 × 104 genome copies/L (range 3.2 × 102-1.2 × 109 genome copies/L). Lag analysis of trends in Melvin's Index values and clinical COVID-19 cases showed that increases in indexed wastewater SARS-CoV-2 levels precede new clinical cases by 15-17 days at the statewide level and by up to 25 days at the regional/county level. Melvin's Index is a reliable WBE method and can be applied to both WWTFs that serve a wide range of population sizes and to large regions that are served by multiple WWTFs.


Model-based Bayesian inference of the ventilation distribution in patients with cystic fibrosis from multiple breath washout, with comparison to ventilation MRI.
Indices of ventilation heterogeneity (VH) from multiple breath washout (MBW) have been shown to correlate well with VH indices derived from hyperpolarised gas ventilation MRI. Here we report the prediction of ventilation distributions from MBW data using a mathematical model, and the comparison of these predictions with imaging data. We developed computer simulations of the ventilation distribution in the lungs to model MBW measurement with 3 parameters: σV, determining the extent of VH; V0, the lung volume; and VD, the dead-space volume. These were inferred for each individual from supine MBW data recorded from 25 patients with cystic fibrosis (CF) using approximate Bayesian computation. The fitted models were used to predict the distribution of gas imaged by 3He ventilation MRI measurements collected from the same visit. The MRI indices measured (I1/3, the fraction of pixels below one-third of the mean intensity and ICV, the coefficient of variation of pixel intensity) correlated strongly with those predicted by the MBW model fits (r=0.93,0.88 respectively). There was also good agreement between predicted and measured MRI indices (mean bias ± limits of agreement: I1/3:-0.003±0.118 and ICV:-0.004±0.298). Fitted model parameters were robust to truncation of MBW data. We have shown that the ventilation distribution in the lung can be inferred from an MBW signal, and verified this using ventilation MRI. The Bayesian method employed extracts this information with fewer breath cycles than required for LCI, reducing acquisition time required, and gives uncertainty bounds, which are important for clinical decision making.


Characterization of low- and high-affinity glucose transports in the yeast Kluyveromyces marxianus.
Glucose transport in the yeast Kluyveromyces marxianus proceeds by two functionally and presumably structurally distinct transporters depending on the carbon source of the culture medium. In lactose-grown cells, glucose was taken up through a high-affinity H+-sugar symporter (Km = 0.09 mM), whereas a low-affinity transporter (Km = 3.5 mM) was utilized in glucose-grown cells. The two transporters exhibited different substrate specificities. Galactose was demonstrated to be a selective substrate of the H+-glucose symporter (Km = 0.14 mM) and did not significantly enter glucose-grown cells. Fructose was a preferential substrate of the low-affinity carrier (Km = 3.5 mM), but it entered lactose-grown cells through a high-affinity H+-fructose symporter distinct from the H+-glucose one. Other putative substrates of the two glucose transporters were identified by competition experiments. 2-Deoxyglucose recognized both carriers with a similar affinity, while the non-phosphorylatable analogues 6-deoxyglucose, 3-O-methylglucose and D-fucose exhibited a 10-30 fold preference for the high-affinity transporter.


Ultrasound guided vascular access site management and left ventricular pacing are associated with improved outcomes in contemporary transcatheter aortic valve replacement: Insights from the OxTAVI registry.
To identify clinical and procedural practice predictors of avoidable complications during transcatheter aortic valve replacement (TAVR). TAVR is evolving as a viable strategy for treatment of aortic stenosis (AS). Vascular complications, major bleeding, or pericardial tamponade may be influenced by procedural practice. The Oxford TAVR (OxTAVI) prospective registry was retrospectively analyzed to identify predictors of avoidable procedural complications in a contemporary cohort of transfemoral TAVR between January 2015 and September 2018. The primary endpoint was defined as a hierarchic composite of in-hospital mortality, pericardial effusion/cardiac tamponade, major bleeding, and vascular access complications. Individual components of the primary endpoint have been analyzed separately. Five-hundred-twenty-nine patients underwent transfemoral TAVR using contemporary techniques during the study period and were enrolled in the OxTAVI registry. Female sex and high frailty were associated with a higher risk of death, major bleeding, vascular complication or pericardial tamponade. The use of ultrasound (US) guidance for vascular access management was independently associated with a reduced composite primary endpoint (OR = 0.35, CI:0.14-0.86, p = .02) after adjustment for clinical confounders, largely driven by a threefold reduction in vascular access complication (OR = 0.29, CI:0.15-0.55, p < .001). Performing rapid pacing via the left ventricle guidewire (LV-GW) was associated with a significant decrease in the risk of cardiac tamponade/pericardial effusion (OR = 0.19, CI:0.05-0.66, p = .009). US-guided vascular access management and rapid pacing via the LV-GW are important determinants of reduced procedural complications during TAVR.


Supported lysozyme for improved antimicrobial surface protection.
Surface protection against biofilms is still an open challenge. Current strategies rely on coatings that are meant to guarantee antiadhesive or antimicrobial effects. While it seems difficult to ensure antiadhesion in complex media and against all the adhesive arsenal of microbes, strategies based on antimicrobials lack from sustainable functionalization methodologies to allow the perfect efficiency of the grafted molecules. Here we used the high affinity ligand-receptor interaction between biotin and streptavidin to functionalize surfaces with lysozyme, an enzyme that degrades the bacterial peptidoglycan cell wall. Biotinylated lysozyme was grafted on surfaces coated with streptavidin receptors. Using atomic force microscopy (AFM)-based single molecule force spectroscopy, we showed that grafting through ligand-receptor interaction allows the correct orientation of the enzyme on the substrate for enhanced activity towards the microbial target. The antibacterial efficiency was tested against Micrococcus luteus and revealed that surface protection was improved when lysozyme was grafted through the ligand-receptor interaction. These results suggest that bio-molecular interactions are promising for a sustainable grafting of antimicrobial agents on surfaces.


A description of two morphologic patterns of aortic fatty streaks, and a hypothesis of their pathogenesis.
Two morphologic patterns of fatty streak were identified on examination of 74 aortas from the Pathobiological Determinants of Atherosclerosis in Youth study. Pattern 1, which predominated in 78% of aortas, is characterized by broad bands of intense stain which extend to the proximal edge of ostia. Pattern 2, which predominated in 11%, is characterized by less intense staining which is concave to the associated ostium. Pattern 1 predominated in older subjects and smokers. Aging and smoking decrease arterial elasticity, thereby decreasing the volume and duration of retrograde blood flow in diastole. Doppler ultrasonography of the posterior intercostal arteries and aorta in 42 healthy subjects revealed that retrograde blood flow in late systole/early diastole is normal in subjects in the 15-34 age group. Transition from retrograde to antegrade flow was associated with transient blood stasis. This stasis should prolong the residence time of lipid-rich particles, enhancing diffusion into the vessel wall. A region of lower flow velocity was noted in the periostial region in all patients during diastole. The anatomic, hemodynamic, and risk factor data suggest that the morphology of fatty streaks is determined by interaction of retrograde with antegrade blood flow as modulated by arterial elasticity.


Glutathione reductase-deficient erythrocytes as host cells of malarial parasites.
BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] and its less toxic derivative HeCNU [1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea] are clinically-used antitumour drugs. In erythrocytes BCNU is a highly specific inhibitor of the enzyme glutathione reductase [H. Frischer and T. Ahmad, J. Lab. clin. Med. 89, 1080 (1977)]. When treating erythrocytes in vitro, 50% enzyme inhibition was obtained with 1 microM BCNU or 3 microM HeCNU within 2 hr. The two drugs were used for preparing red cell populations with various levels of glutathione reductase activity; complete inhibition (greater than or equal to 98%) was only achieved when the medium contained glucose as a source of reducing equivalents. The erythrocytes were then tested in drug-free media as host cells for the malaria parasite Plasmodium falciparum. In the range of 0-300 mU/ml cells, there was a correlation between glutathione reductase activity and parasite growth; erythrocytes with an activity of less than 20 mU/ml did not serve as host cells for P. falciparum at all although these erythrocytes were viable. When the culture medium was supplemented with 20 mM glutathione (GSH), parasite growth was normal irrespective of the glutathione reductase level in the erythrocytes. This is consistent with the finding that poisoning glutathione reductase led to a 10-fold decrease of the cytosolic GSH level. Our results corroborate the concept that intraerythrocytic inhibition of glutathione reductase mimicks the biochemistry of drug-sensitive glucose-6-phosphate dehydrogenase deficiency (favism), an inherited condition which confers protection from malaria.


Are Financial Payments From the Pharmaceutical Industry Associated With Physician Prescribing? : A Systematic Review.
Financial payments from the drug industry to U.S. physicians are common. Payments may influence physicians' clinical decision making and drug prescribing. To evaluate whether receipt of payments from the drug industry is associated with physician prescribing practices. MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science, and EconLit were searched without language restrictions. The search had no limiting start date and concluded on 16 September 2020. Studies that estimated the association between receipt of industry payments (exposure) and prescribing (outcome). Pairs of reviewers extracted the primary analysis or analyses from each study and evaluated risk of bias (ROB). Thirty-six studies comprising 101 analyses were included. Most studies (n = 30) identified a positive association between payments and prescribing in all analyses; the remainder (n = 6) had a mix of positive and null findings. No study had only null findings. Of 101 individual analyses, 89 identified a positive association. Payments were associated with increased prescribing of the paying company's drug, increased prescribing costs, and increased prescribing of branded drugs. Nine studies assessed and found evidence of a temporal association; 25 assessed and found evidence of a dose-response relationship. The design was observational, 21 of 36 studies had serious ROB, and publication bias was possible. The association between industry payments and physician prescribing was consistent across all studies that have evaluated this association. Findings regarding a temporal association and dose-response suggest a causal relationship. National Cancer Institute.


An animal model for the study of the function of pregnancy-specific beta 1-glycoprotein and pregnancy zone protein: a review.
Two pregnancy-associated murine proteins, PAMP-1 and PAMP-2, have been found to be immunologically cross-reacting analogues to the human proteins pregnancy zone protein (PZP) and pregnancy-specific beta 1-glycoprotein (SP-1), respectively. In this study, the physiochemical and biological properties of the proteins are compared and the effect on pregnancy of administration of monospecific antibodies against the proteins is reported.


Functional antagonism between Sall4 and Plzf defines germline progenitors.
Transcription factors required for formation of embryonic tissues often maintain their expression in adult stem cell populations, but whether their function remains equivalent is not clear. Here we demonstrate critical and distinct roles for Sall4 in development of embryonic germ cells and differentiation of postnatal spermatogonial progenitor cells (SPCs). In differentiating SPCs, Sall4 levels transiently increase and Sall4 physically interacts with Plzf, a transcription factor exclusively required for adult stem cell maintenance. Mechanistically, Sall4 sequesters Plzf to noncognate chromatin domains to induce expression of Kit, a target of Plzf-mediated repression required for differentiation. Plzf in turn antagonizes Sall4 function by displacing Sall4 from cognate chromatin to induce Sall1 expression. Taken together, these data suggest that transcription factors required for embryonic tissue development postnatally take on distinct roles through interaction with opposing factors, which hence define properties of the adult stem cell compartment.


Treatment assessment by monitoring parasite load in skin biopsies from patients with cutaneous leishmaniasis, using quantitative nucleic acid sequence-based amplification.
Current diagnostic methods for cutaneous leishmaniasis (CL) have low sensitivity or are not useful for treatment follow-up. We previously described the quantitative nucleic acid sequence-based amplification (QT-NASBA) method as a sensitive and specific assay for detection and quantification of Leishmania parasites in skin biopsies. This assay could be a valuable instrument for monitoring response to treatment of CL and identifying treatment failures at an early stage. QT-NASBA results of skin biopsies at the end and 6 weeks after treatment from patients with proven CL on various treatment regimens were compared with clinical outcome. The QT-NASBA assay measured the parasite load in skin biopsies before, at the end and 6 weeks after treatment. The results were compared with treatment outcome (clinical cure, delayed healing response or treatment failure) up to 6 months after treatment. In total, 137 skin biopsies were obtained from 53 patients. A positive QT-NASBA result 6 weeks after treatment was significantly associated with treatment failure/delayed healing up to 6 months (P < 0.001). The positive predictive value (PPV) was 100% and the negative predictive value (NPV) was 92% (95% CI 82-100%). QT-NASBA results at the end of treatment and clinical outcome showed a less significant association (P < 0.05), with a PPV of 46% (95% CI 16-75% and an NPV of 89% (95% CI 79-99%). The QT-NASBA assay is a useful instrument to monitor parasite load in skin biopsies of patients with CL 6 weeks after treatment and can help to predict clinical outcome.


A new strategy for accelerated extraction of target compounds using molecularly imprinted polymer particles embedded in a paper-based disk.
In this study, a general simple and inexpensive method is introduced for the preparation of a paper-based selective disk-type solid phase extraction (SPE) technique, appropriate for fast and high throughput monitoring of target compounds. An ion exchange molecularly imprinted polymer (MIP) was synthesized for the extraction and analysis of acesulfame, an anthropogenic water quality marker. Acesulfame imprinting was used as an example for demonstrating the benefits of a nanosized, swellable MIP extraction sorbents integrated in an on-site compatible concept for water quality monitoring. Compared with an 8 mL standard SPE cartridge, the paper-based MIP disk (47 mm ø) format allowed (1) high sample flow rates up to 30 mL•min-1 without losing extraction efficiency (2) extracting sample volumes up to 500 mL in much shorter times than with standard SPE, (3) the reuse of the disks (up to 3 times more than SPE cartridge) due to high robustness and an efficient post-cleaning, and (4) reducing the sampling time from 100 minutes (using the standard SPE format) to about 2 minutes with the MIP paper disk for 50 mL water sample. Different parameters like cellulose fiber/polymer ratios, sample volume, sample flow-rate, washing, and elution conditions were evaluated and optimized. Using developed extraction technique with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) analysis, a new protocol was established that provides detection and quantification limits of 0.015 μg•L-1 and 0.05 μg•L-1 , respectively. The developed paper disks were used in-field for the selective extraction of target compounds and transferred to the laboratory for further analysis.