The chemokine CXCL13 in acute neuroborreliosis

Objective Recent studies have suggested an important role of the B cell chemoattractant CXCL13 in acute neuroborreliosis (NB). Our aim was to confirm the diagnostic role of CXCL13 and to evaluate its relevance as a therapy response and disease activity marker in NB. Methods CXCL13 was measured in cerebrospinal fluid (CSF) and serum of patients with NB (n = 28), systemic borreliosis (SB, n = 9), Guillaine-Barre syndrome (GBS, n = 11), Bell's palsy (BP, n = 19), other cranial nerve palsies (CNP, n = 5), cephalgia (C, n = 20), bacterial CNS infections (B-CNS-I, n = 16) and viral CNS infections (V-CNS-I, n = 18). For follow-up studies, serial sample pairs were evaluated from 25 patients with NB (n = 56), 11 with B-CNS-I (n = 25) and 14 with V-CNS-I (n = 36). Results CSF-CXCL13 was significantly elevated in NB compared with other neurological diseases (p<0.001). Using receiver operating characteristic analysis, 337 ng/g was determined as a cut-off with a sensitivity of 96.4% and a specificity of 96.9%. Of all the parameters investigated, CSF CXCL13 showed the fastest response to antibiotic therapy, decreasing significantly (p = 0.008) within 1 week. In untreated patients, CSF CXCL13 was elevated in patients with a short duration of disease. Borrelia burgdorferi antibody index showed no significant (p = 0.356) change over follow-up. Conclusions The study confirms the relevance of CXCL13 as a diagnostic biomarker of NB and suggests that CSF CXCL13 in NB is linked to duration of disease and could be a marker of disease activity and response to antibiotic therapy

Applying New Research Criteria for Diagnosis of Early Alzheimer's Disease: Sex and Intelligence Matter

Alzheimer's disease (AD) can be diagnosed according to new research criteria proposed recently (Dubois et al., 2007). Diagnosis is made on grounds of episodic memory deficits and one pathological biomarker: cerebrospinal fluid (CSF) or structural/functional imaging. Goal was to investigate the dependence of episodic memory function on material (verbal, visuospatial), gender and premorbid intellectual ability (IQ). The new research criteria of AD were applied retrospectively using data of 68 patients (Mini-Mental-Status Examination, MMSE ≥ 22) from a university memory clinic. Women with lower IQ performed worse on visuospatial episodic memory than women with higher IQ and men with the same IQ. Thus, women with lower IQ appear to be particularly vulnerable to visuospatial episodic memory deficits despite similar CSF tau values indicating a similar activity of the neurodegenerative process. Gender, premorbid IQ, and visuospatial material need to be considered in the assessment of episodic memory breakdown applying the newly proposed research criteria for the diagnosis of AD

Implementation of the Rome statute in Kenya : legal and institutional challenges in relation to the change from dualism to monism

Magister Legum - LLMThe new Kenyan constitution has introduced an immediate monist approach of implementing international legal standards. Accordingly, the transformation from dual to monism will necessitate a discussion of theories of incorporation of international instruments into national laws. This will set the basis of what method Kenya should follow. This paper attempts to address potential procedural problems with implementing the Rome Statute in a new monist Kenya and will argue that as a precautionary measure during the country’s transition any deviation, by the court, from national law will require articulation and justification under an international framework. It will include a review of the Kenyan International Crimes Act 2003 (ICA) and its adoption into the domestic law of Kenya. It will also include examination of previous situations where domestic courts have applied international law standards in domestic trials before and after the monist Constitution of 2010. This paper aims at assessing the key challenges to the effective implementation of the Rome Statute in Kenya both objectively and substantively. It examines the challenges facing the Kenyan courts in relation to the exercise of universal jurisdiction and the criminalization of international crimes. It will seek to point out the weaknesses and conflict between the Kenyan constitution, The International Crimes Act and the Rome Statute. The ICA was silent on some aspects of the Rome Statute and the paper will attempt to discuss these issues and what they portend in the implementation of the Rome statute in monism. It will also discuss the effect of the new constitution on the practical operation of the Rome Statue. The operational capacity of institutions mandated with practical implementation of the Rome Statute will be examined. It will further seek to ascertain whether the laws and policies reflect Kenya’s commitment to international criminal justice. By way of conclusion, the paper will create a possible inventory of issues, which might arise in Kenya’s prosecution of International crimes under the Rome Statute, and suggestions on how such issues could best be addressed

Associations between multiple sclerosis and incidence of heart diseases : Systematic review and meta-analysis of observational studies

Background: Observational studies have described associations between multiple sclerosis (MS) and heart diseases, but the results were mixed. Methods: Medline, Embase, and Cochrane CENTRAL were searched up to 5 October 2020 according to a protocol (PROSPERO registration number CRD42020184493). We included longitudinal non-randomized studies of exposure comparing the incidence of acquired heart diseases between people with multiple sclerosis (pwMS) and people without multiple sclerosis. We used ROBINS-E and the GRADE approach to assess risk of bias and the certainty of evidence, respectively. Data were pooled using random-effect models. Results: Of 5,159 studies, nine studies met the inclusion criteria. MS was associated with an increased risk for myocardial infarction (HR 1.6, 95% CI 1.2 to 2.0, I2 86%, n = 1,209,079) and heart failure (HR 1.7, 95% CI 1.3 to 2.2, I2 49%, n = 489,814). The associations were more pronounced among women and younger people in subgroup analyses. We found no difference for ischemic heart disease (HR 1.0, 95% CI 0.8 to 1.4, I2 86%, n = 679,378) and bradycardia (HR 1.5, 95% CI 0.4 to 5.0, I2 50%, n = 187,810). The risk of atrial fibrillation was lower in pwMS (HR 0.7, 95% CI 0.6 to 0.8, I2 0%, n = 354,070), but the risk of bias was high, and the certainty of evidence was rated as very low. One study found more cases of infectious endocarditis among pwMS (HR 1.2, 95% CI 1.0 to 1.4, n = 83,712). Conclusions: Myocardial infarction and heart failure should be considered in people with multiple sclerosis during follow-up examinations

Exogenous re-infection by a novel Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis in a child from The Gambia

We report a case of an infant who experienced exogenous re-infection of Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis after apparently successful antibiotic treatment with ceftriaxone. eBURST analysis revealed that isolates from the two episodes of meningitis belonged to hypervirulent ST63 and ST3321 clonal complexes respectively

A Tuberculin Skin Test Survey and the Annual Risk of Mycobacterium tuberculosis Infection in Gambian School Children.

BACKGROUND: A Tuberculin skin test (TST) survey was conducted to assess the prevalence of latent TB Infection (LTBI) and to estimate the annual risk of M. tuberculosis infection (ARTI) in Gambian school children. The results are expected to contribute to understanding of Tuberculosis epidemiology in The Gambia. METHODS: This was a nationwide, multi-cluster survey in children aged 6-11 years. Districts, 20 of 37, were selected by probability proportional to size and schools by simple random sampling. All TST were performed using the Mantoux method. Height and weight measurements were obtained for all participants. We calculated prevalence of LTBI using cut-off points of 10mm, the mirror and mixture modelling methods. RESULTS: TST readings were completed 13,386 children with median age of 9 years (interquartile range [IQR] 8-10 years). Mixture analysis yielded a cut-off point of 12 mm, and LTBI prevalence of 6.9% [95%CI 6.47-7.37] and the ARTI was 0.75% [95%CI 0.60-0.91]. LTBI was associated gender and urban residence (p <0.01). Nutritional status was not associated with non-reactive TST or sizes of TST indurations. ARTI did not differ significantly by age, gender, BCG vaccination or residence. CONCLUSIONS: This estimates for LTBI prevalence and ARTI were low but this survey provides updated data. Malnutrition did not affect estimates of LTBI and ARTI. Given the low ARTI in this survey and the overlapping distribution of indurations with mixture modelling, further surveys may require complementary tests such as interferon gamma release assays or novel diagnostic tools

Safety and in vivo immune assessment of escalating doses of oral laquinimod in patients with RRMS

Background Laquinimod is an oral immunomodulator in clinical development to treat relapsing-remitting multiple sclerosis (RRMS). Laquinimod is in clinical development for the treatment of multiple sclerosis and Huntington Disease (HD). The objective of this study is to assess the safety, tolerability, pharmacokinetics (PK) and cytoimmunologic effects following escalating doses of laquinimod in patients with RRMS. Methods One hundred twelve patients were randomly assigned to laquinimod/placebo in a series of separate dose- escalating cohorts starting from a daily oral dose of 0.9 mg/1.2 mg escalating to 2.7 mg, in 0.3 mg increments. Results Twenty-eight patients received placebo and 84 received laquinimod ranging from 0.9 to 2.7 mg. No deaths occurred. One serious adverse event (SAE) of perichondritis was reported, which was unrelated to laquinimod (0.9 mg). There was no increased incidence of adverse events (AEs) with escalating doses. Laquinimod-treated patients showed more abnormal laboratory levels in liver enzymes, P-amylase, C-reactive protein (CRP), and fibrinogen, but most shifts were clinically non- significant. The exposure of laquinimod was dose proportional and linear in the tested dose range. An immunological substudy showed significant dose- dependent decreases in 6-sulpho LacNAc + dendritic cell (slanDC) frequency following laquinimod compared to placebo. Conclusion Laquinimod doses up to 2.7 mg were safely administered to patients with RRMS. An in vivo effect of laquinimod on the innate immune system was demonstrated. Trial registration EudraCT Number: 2009-011234-99. Registered 23 June 2009

Standard of Living, Well-Being and Community Development: The Case of Botswana

There is considerable evidence in literature that suggests that the concept of standard of living has tended to be predicated on the notion of income alone. However, exploring this concept further, evidence suggests that the notion of standard of living goes beyond simply looking at income to include Gross Domestic Product (GDP), life expectancy, and economic opportunities available to individuals. This suggests that in a given country, when the above-mentioned ‘components’ are accessible to individuals, the expectation is that these will translate into realization of meaningful standards of living and wellbeing. This chapter seeks to explore how standard of living and well-being in Botswana have metamorphosed over time, from the pre-colonial period, through the early years of independence and the time of the discovery of diamonds, up to the present. Additionally, the article examines how community development initiatives across the country, have impacted standard of living and wellbeing of the population. The chapter concludes by suggesting strategies the government of Botswana could adopt in efforts to strengthen community development, with a view, ultimately, to further improve standard of living and wellbeing of the country’s population