Low incidence of toxoplasma infection during pregnancy and in newborns in Sweden

To estimate the burden of disease due to congenital toxoplasmosis in Sweden the incidence of primary infections during pregnancy and birth prevalence of congenital toxoplasmosis in 40978 children born in two regions in Sweden was determined. Women possibly infected during pregnancy were identified based on: 1, detection of specific IgG based on neonatal screening of the phenylketonuria (PKU) card blood spot followed by retrospective testing of stored prenatal samples to detect women who acquired infection during pregnancy and follow up of their children to 12 months; 2, detection of specific IgM on the PKU blood spot. The birth prevalence of congenital toxoplasmosis was 0·73/10000 (95% CI 0·15–2·14) (3/40978). The incidence of primary infection during pregnancy was 5·1/10000 (95% CI 2·6–8·9) susceptible pregnant women. The seroprevalence in the southern part was 25·7% and in the Stockholm area 14·0%. The incidence of infection during pregnancy was low, as the birth prevalence of congenital toxoplasmosis. Neonatal screening warrants consideration in view of the low cost and feasibility

Presence of sensory nerve corpuscles in the human corpus and cervix uteri during pregnancy and labor as revealed by immunohistochemistry

BACKGROUND: The uterus is exposed to changes such as enlargement and distension during pregnancy and labor. In these processes and in the process of cervical ripening, proprioceptive information is likely to be of great importance. Therefore, we wanted to study the possible existence of sensory nerve corpuscles in uterine corpus and cervix during pregnancy and labor. Studies on this aspect have not previously been perfomed. METHODS: Biopsies were taken from the upper edge of the hysterotomy during caesarean section at term (n = 8), in labor (n = 5) and from the corresponding area in the non-pregnant uterus after hysterectomy (n = 7). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial cryostat sections were prepared for immunohistochemistry using polyclonal antibodies against nerve growth factor receptor p75, protein gene product 9.5 and S-100. RESULTS: Structures with the characteristics of sensory nerve corpuscles were observed in several specimens after staining for p75, PGP 9.5 and S-100. They were observed in specimens of the non-pregnant corpus and cervix and also in specimens of the pregnant cervix before onset of labor. However, they were absent in all specimens during labor. CONCLUSION: Sensory corpuscles have here for the first time been detected in the human corpus and cervix uteri. Studies on the importance of the corpuscles in relation to the protective reflex actions that occur in the uterus during pregnancy should be performed in the future

NfL as a biomarker for neurodegeneration and survival in Parkinson disease

OBJECTIVE: To determine if Neurofilament Light chain protein in cerebrospinal fluid (cNfL); a sensitive biomarker of neuroaxonal damage, reflects disease severity or can predict survival in Parkinson's disease (PD). METHODS: We investigated if disease severity, phenotype or survival in patients with new-onset PD correlates with cNfL concentrations around the time of diagnosis in the population-based NYPUM study cohort (n = 99). A second, larger new-onset PD cohort (n = 194) was used for independent validation. Association of brain pathology with the cNfL concentration was examined using striatal dopamine transporter imaging and repeated diffusion tensor imaging, at baseline, 1 and 3 years. RESULTS: Higher cNfL in the early phase of PD was associated with greater severity of all cardinal motor symptoms except tremor, in both cohorts, and with shorter survival and impaired olfaction. cNfL concentrations above the median of 903 ng/L conferred an overall 5.8 times increased hazard of death, during follow-up. After adjustment for age and sex, higher cNfL correlated with striatal dopamine transporter uptake deficits and lower fractional anisotropy in diffusion tensor imaging of several axonal tracts. CONCLUSIONS: cNfL shows usefulness as a biomarker of disease severity and to predict survival in PD. The present results indicate that the cNfL concentration reflects the intensity of the neurodegenerative process, which could be of importance in future clinical trials. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with PD, cNFL concentrations are associated with more severe disease and shorter survival

Invasive disease caused by Haemophilus influenzae in Sweden 1997–2009; evidence of increasing incidence and clinical burden of non‐type b strains

Introduction of a conjugated vaccine against encapsulated Haemophilus influenzae type b (Hib) has led to a dramatic reduction of invasive Hib disease. However, an increasing incidence of invasive disease by H. influenzae non‐type b has recently been reported. Non‐type b strains have been suggested to be opportunists in an invasive context, but information on clinical consequences and related medical conditions is scarce. In this retrospective study, all H. influenzae isolates ( n  =   410) from blood and cerebrospinal fluid in three metropolitan Swedish regions between 1997 and 2009 from a population of approximately 3 million individuals were identified. All available isolates were serotyped by PCR ( n  =   250). We observed a statistically significant increase in the incidence of invasive H. influenzae disease, ascribed to non‐typeable H. influenzae (NTHi) and encapsulated strains type f (Hif) in mainly individuals >60 years of age. The medical reports from a subset of 136 cases of invasive Haemophilus disease revealed that 48% of invasive NTHi cases and 59% of invasive Hif cases, respectively, met the criteria of severe sepsis or septic shock according to the ACCP/SCCM classification of sepsis grading. One‐fifth of invasive NTHi cases and more than one‐third of invasive Hif cases were admitted to intensive care units. Only 37% of patients with invasive non‐type b disease had evidence of immunocompromise, of which conditions related to impaired humoral immunity was the most common. The clinical burden of invasive non‐type b H. influenzae disease, measured as days of hospitalization/100 000 individuals at risk and year, increased significantly throughout the study period.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87052/1/j.1469-0691.2010.03417.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/87052/2/CLM_3417_sm_FigS1.pd

Immunodepletion in xenotransplantation

Xenograft transplantation is perhaps the most immunologically difficult problem in transplantation today. An overwhelming hyperacute rejection reaction (HAR) occurs within minutes of organ implantation. Preformed antibodies are thought to initiate this process. We used a pig-to-dog renal xenograft transplant model and investigated methods of decreasing the severity of hyperacute rejection. Female pigs weighing 15-20 kg were used as donors. Recipients were mongrel dogs weighing 15-25 kg. Experimental dogs were all given a number of treatments of IgG depletion using an antibody removal system (Dupont-Excorim). This machine immunoadsorbs plasma against a column containing immobilized staphylococcal protein A, which is known to bind the IgG Fc receptor. An 84% reduction in the IgG levels and a 71% reduction in IgM levels was achieved. Postoperative assessment was made of urine output, time to onset of HAR, and histopathological examination of the rejected kidneys. Although cross-matches between donor lymphocytes and recipient sera remained strongly positive in the treated dogs, there was a two- to fourfold reduction in the titers. The time to onset of HAR was prolonged in the experimental group, and the urine output was increased slightly. The histopathologic changes in the experimental group generally showed signs of HAR, but of less intensity than in the nonimmunodepleted control group. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Gender differences in Parkinson's disease: A clinical perspective

Available data indicate that there are gender differences in many features of Parkinson's disease (PD). Precise identification of the gender differences is important to tailor treatment, predict outcomes, and meet other individual and social needs in women and men with PD. The aim of this study was to review the available clinical data on gender differences in PD. Original articles and meta‐analyses published between 1990 and 2016 systematically exploring gender differences in PD were reviewed. There is slight male preponderance in incidence and prevalence of PD. PD starts earlier in men. Women tend to be more prone to develop tremor‐dominant PD but are less rigid than men. Motor improvement after deep brain stimulation is equal in both sexes, but women tend to show better improvement in activities of daily living. Furthermore, women with PD show better results on tests for general cognitive abilities, outperform men in verbal cognitive tasks, show more pain symptoms, and score higher on depression scales. It seems, however, that the differences in cognition, mood, and pain perception are not disease specific as similar gender differences can be found in healthy subjects and in other neurological conditions. Despite PD being the most frequently studied movement disorder, studies investigating gender differences in PD are still scarce with most of the studies being cross‐sectional. Good‐quality, prospective, longitudinal studies analyzing gender differences in PD and comparing them to matched healthy controls are needed in order to properly address the issues of gender differences in PD

Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction Are Altered in Parkinson's Disease and Related Disorders

Background: Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects. Objective: To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders. Methods: Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n1 = 51, n2 = 101), corticobasal degeneration (CBD) (n1 = 11, n2 = 3), progressive supranuclear palsy (PSP) (n1 = 22, n2 = 21), multiple system atrophy (MSA) (n1 = 31, n2 = 26), and healthy control (HC) (n1 = 48, n2 = 30) participants, as well as Alzheimer's disease (AD) (n2 = 23) patients in the second cohort. Results: Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate = −0.025 to −0.038, P < 0.05) and cognitive decline (NPTX2; β-estimate = 0.32, P = 0.021). Conclusions: These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Delivering effective care through mobile apps:Findings from a multi-stakeholder design science approach

In this paper, we use a design science approach to develop a mobile app for lung cancer patients that facilitates their interactions with their clinicians, manages and reports on their health status, and provides them access to medical information/education. This paper contributes to the information systems literature by demonstrating the value of design science research to co-create solutions that advance health care outcomes through technological innovations. The design process engaged a diverse cast of experts and methods, such as a survey of oncologists and cancer patients, a workshop, roundtables and interviews with leading patient and clinician association representatives and focus groups, including two panels each of clinicians and cancer patients. Our approach also develops actionable knowledge that is grounded in evidence from the field, including design guidelines that recapitulate what we learned from the design-testing-redesign cycles of our artefact

Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts

BACKGROUND: The magnitude of the association between Helicobacter pylori and incidence of gastric cancer is unclear. H pylori infection and the circulating antibody response can be lost with development of cancer; thus retrospective studies are subject to bias resulting from classifi- cation of cases as H pylori negative when they were infected in the past. AIMS: To combine data from all case control studies nested within prospective cohorts to assess more reliably the relative risk of gastric cancer associated with H pylori infection.To investigate variation in relative risk by age, sex, cancer type and subsite, and interval between blood sampling and cancer diagnosis. METHODS: Studies were eligible if blood samples for H pylori serology were collected before diagnosis of gastric cancer in cases. Identified published studies and two unpublished studies were included. Individual subject data were obtained for each. Matched odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the association between H pylori and gastric cancer. RESULTS: Twelve studies with 1228 gastric cancer cases were considered. The association with H pylori was restricted to noncardia cancers (OR 3.0; 95% CI 2.3–3.8) and was stronger when blood samples for H pylori serology were collected 10+ years before cancer diagnosis (5.9; 3.4–10.3). H pylori infection was not associated with an altered overall risk of cardia cancer (1.0; 0.7–1.4). CONCLUSIONS: These results suggest that 5.9 is the best estimate of the relative risk of non-cardia cancer associated with H pylori infection and that H pylori does not increase the risk of cardia cancer. They also support the idea that when H pylori status is assessed close to cancer diagnosis, the magnitude of the non-cardia association may be underestimated