Genetic polymorphisms and risk of recurrent deep venous thrombosis in young people: prospective cohort study.

OBJECTIVE: To determine the incidence of deep venous thrombosis (DVT) recurrence in young people, and its association with some genetic polymorphisms (FV G1691A, FII G20210A, MTHFR C677T, PAI-1 4G/5G). DESIGN: Prospective cohort study. METHODS: A database was established prospectively to follow-up a cohort of unselected patients who had had a first episode of objectively proven DVT under the age of 40 years. All patients had DNA analysis for heritable thrombophilia. We excluded patients with deficiency of antithrombin, protein C or protein S, malignant disease, antiphospholipid syndrome, or a requirement for long-term antithrombotic treatment. The end-point was objective evidence of symptomatic DVT recurrence. RESULTS: Eighty-seven patients were enrolled in the study. Mean duration of follow-up was 4.07 years. At 2 years, the cumulative recurrence rate was 19.3%. The risk of risk was not related to presence or absence of laboratory evidence of genetic polymorphisms: FV G1619A (HR 1.26 [95%CI: 0.64-2.46]; p = 0.51), FII G20210A (HR 0.81 [95%CI: 0.35-1.89]; p = 0.62), MTHFR C677T (HR 1.26 [95%CI: 0.56-2.81]; p = 0.58), PAI-1 4G/5G (0.84 [95%CI: 0.35-2.05]; p = 0.71). CONCLUSION: In this study, the risk of recurrent deep venous thrombosis in young people was not related with the presence of FV G1691A, FII G20210A, MTHFR C677T or PAI-1 4G/5G polymorphisms.     

Retinal photoreceptor fine structure in the velvet cichlid (Astronotus ocellatus).

Summary The structure and arrangement of the retinal photoreceptors of the velvet cichlid fish (Astronotus ocellatus) have been studied by light and electron microscopy. Rods, single cones and double (twin) cones are present. In the light-adapted state, rods are very tall cells that reach deep into the retinal epithelial (RPE) layer. The long outer segment is composed of discs of uniform diameter displaying one or two incisures. The rod inner segment shows a distal ellipsoid of mitochondria, and then narrows dramatically in the myoid region. Rod nuclei are electron dense and located deep in the outer nuclear layer. Rod synaptic spherules are small and show two to three invaginated synaptic sites as well as superficial synapses. Single cones are similar to the individual members of a double cone and all display a short tapering outer segment, a large ellipsoid of mitochondria and a myoid rich in rough endoplasmic reticulum, polysomes, Golgi zones and autophagic vacuoles. Double cones have extensive subsurface cisternae along their entire contiguous surfaces. Cone nuclei are large and vesicular and located close to or through the external limiting membrane. The synaptic pedicles of cones are larger, more electron lucent, and display more invaginated (ribbon) synapses as well as conventional (superficial) synaptic sites than do the rod spherules. Rod photoreceptors certainly undergo retinomotor movements and it is probable that cones do as well. In the light-adapted state the cone photoreceptors are arranged in a repeating square mosaic pattern with one single cone surrounded by four double (twin) cones.     

IFN-alpha enhances CD40 ligand-mediated activation of immature monocyte-derived dendritic cells

Type I IFN are immune modulatory cytokines that are secreted during early stages of infection. Type I IFN bridge the innate and the adaptive immune system in humans and mice. We compared the capacity of type I and II IFN to induce the functional maturation of monocyte-derived dendritic cells (MoDC). Extending our earlier observation that type I IFN promote DC maturation, we report that these cytokines also enhance DC differentiation by augmenting CD40 ligand (CD40L)-induced cytokine secretion by MoDC. Type I IFN alone were poor inducers of MoDC maturation as compared with other stimuli. They up-regulated the expression of HLA-DR, CD80, CD86, partially CCR7 but not CD83, partially reduced antigen-uptake function, increased the levels of IL-12p35 mRNA, and prolonged surface expression of peptide-MHC class I complexes for presentation to cytotoxic T lymphocytes, but did not induce migration towards CCL21 chemokine. However, type I IFN were potent co-factors for CD40L-mediated function. Here, they enhanced CD40L-mediated IL-6, IL-10 and IL-12p70 secretion. Furthermore, when combined with IL-1beta and/or IL-4, IFN-alpha2a type I IFN increased CD40L-mediated IL-12p70 production by 2- to 3-fold, and biased the IL-12 p40/p70 ratio towards the IFN-gamma inducing p70 heterodimer, this correlating with higher levels of IFN-gamma secretion by allogeneic T cell subsets and NK cells. Our results suggest that the rapid expression of CD40L, IFN and IL-1beta at sites of infection and inflammation can act in concert on immature DC, thereby linking innate and adaptive immune responses. In this way, type I IFN play a dual role as DC maturation factors and enhancers of CD40L-mediated DC activation.     

The heat stable antigen (CD24) is not required for the generation of CD4+ effector and memory T cells by dendritic cells in vivo

Previous work has established that CD24 is a costimulatory molecule for T-cell clonal expansion. Studies using CD24 -/- mice demonstrated that CD24 plays a critical role in the CD28-independent immune response against virus and soluble antigens. The role of CD24 on dendritic cells (DCs) has not been reported. Here, we compare the CD24(+/+) and CD24(-/-) DCs in the induction of initial clonal expansion and elicitation of memory CD4(+) T cells in vivo. Our results demonstrate that the CD24 expressed on DCs is essential neither for the induction of initial T-cell clonal expansion nor for elicitation of memory activity of primed T cells in vivo.     

Gestational Women’s Perceptions About the Harms of Cigarette and E-Cigarette Use During Pregnancy

Objectives

The purpose of this study was to examine differences between perceived harm of cigarette and electronic cigarette (e-cigarette) use while pregnant and differences between healthcare providers’ communication about these products during pregnancy.

Methods

A convenience sample of gestational women (n?=?218; ages 18–45) living in the US completed an online survey between May and December 2017. Participants reported perceived likelihood of adverse health outcomes (e.g., low birth weight, sudden infant death syndrome) among infants/children born to mothers who used cigarettes/e-cigarettes. T-tests and two-way ANOVAs examined differences between risk perceptions of using cigarettes/e-cigarettes while pregnant based on pregnancy status (previously pregnant, currently pregnant, future pregnant). Chi-square analyses examined differences between healthcare provider communication about cigarette/e-cigarette use during pregnancy.

Results

Overall, participants believed adverse health outcomes were significantly more likely to be caused by maternal use of cigarettes than e-cigarettes. Participants who planned to be pregnant reported higher endorsement that smoking combustible cigarettes would cause a miscarriage (p?<?.05) or increased blood pressure (p?<?.05) for a child than currently pregnant participants. Participants reported healthcare providers asked about (p?<?.05), advised them not to use (p?<?.001), and talked to them about health effects of smoking combustible cigarettes while pregnant (p?<?.001) significantly more than e-cigarettes.

Conclusions for Practice

Healthcare providers working with pregnant women should perform the 5As behavioral intervention method to provide pregnant women with tobacco cessation care. They should also discuss the absolute harm nicotine exposure (via cigarettes or e-cigarettes) can have on fetal health and development.

     

Frailty,Race/Ethnicity,Functional Status,and Adverse Outcomes After Total Hip/Knee Arthroplasty: A Moderation Analysis

BackgroundAlthough frailty has been shown to be associated with adverse outcomes in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), prior studies have not examined how race/ethnicity might moderate these associations. We aimed to assess race/ethnicity as a potential moderator of the associations of frailty and functional status with arthroplasty outcomes.MethodsThe National Surgical Quality Improvement Program was queried for patients who underwent THA or TKA from 2011 to 2017. Frailty was assessed using the modified frailty index. Regression analyses were conducted to examine associations connecting frailty/functional status with 30-day readmission, adverse discharge, and length of stay (LOS). Further analyses were conducted to investigate race/ethnicity as a potential moderator of these relationships.ResultsWe identified 219,143 TKA and 130,022 THA patients. Frailty and nonindependent functional status were positively associated with all outcomes (P < .001). Compared to White non-Hispanic patients, Black non-Hispanic patients had higher odds for all outcomes after TKA (P < .001) and for adverse discharge/longer LOS after THA (P < .001). Similar associations were observed for Hispanics for the adverse discharge/LOS outcomes. Race/ethnicity moderated the effects of frailty in TKA for all outcomes and in THA for adverse discharge/LOS. Race/ethnicity moderated the effects of nonindependent function in TKA for adverse discharge/LOS and on LOS alone for THA.ConclusionDisparities for Black non-Hispanic and Hispanic patients persist for readmission, adverse discharge, and LOS. However, the effects of increasing frailty and nonindependent functional status on these outcomes were the most pronounced among White non-Hispanic patients.     

Australia's notifiable diseases status, 2002: Annual report of the National Notifiable Diseases Surveillance System.

There were 57 infectious diseases notifiable at the national level in Australia in 2002. States and territories reported 100,278 cases of infectious diseases to the National Notifiable Diseases Surveillance System (NNDSS), a fall of 4 per cent compared to the number of notifications in 2001. In 2002, the most frequently notified diseases were, sexually transmitted infections (31,929 reports, 32% of total notifications), gastrointestinal infections (26,708 reports, 27% of total notifications) and bloodborne infections (23,741, 24%). There were 11,711 (12% of total) cases of vaccine preventable diseases, 3,052 (3% of total) cases of vectorborne diseases, 1,155 (1% of total) cases of zoonotic infections, two cases of quarantinable diseases (Vibrio cholerae O1) and 1,980 cases of other bacterial diseases, notified to NNDSS. Compared to 2001, notifications of sexually transmitted infections increased by 16 per cent and gastrointestinal infections by 2 per cent while bloodborne infections fell by 18 per cent. The number of notifications of chlamydial infection and Q fever were the highest since 1991 and 1995 respectively. By contrast, the number of notification for hepatitis A and measles were the lowest since 1991. For other notifiable diseases, the number of notifications was within the range of the five years between 1997 and 2002 (range = five-year mean plus or minus two standard deviations). This report also includes 2002 summary data on communicable diseases from other surveillance systems including the Laboratory Virology and Serology Reporting Scheme and sentinel general practitioner schemes.