Terra incognita—cerebellar contributions to neuropsychiatric and cognitive dysfunction in behavioral variant frontotemporal dementia

Although converging evidence has positioned the human cerebellum as an important relay for intact cognitive and neuropsychiatric processing, changes in this large structure remain mostly overlooked in behavioral variant frontotemporal dementia (bvFTD), a disease which is characterized by cognitive and neuropsychiatric deficits. The present study assessed whether degeneration in specific cerebellar subregions associate with indices of cognition and neuropsychiatric performance in bvFTD. Our results demonstrate a relationship between cognitive and neuropsychiatric decline across various domains of memory, language, emotion, executive, visuospatial function, and motivation and the degree of gray matter degeneration in cerebellar lobules V–VII. Most notably, bilateral cerebellar lobule VII and the posterior vermis emerged as distinct for memory processes, the right cerebellar hemisphere underpinned emotion, and the posterior vermis was highlighted in language dysfunction in bvFTD. Based on cortico-cerebellar connectivity maps, these findings in the cerebellum are consistent with the neural connections with the cortices involved in these domains in patients with bvFTD. Overall, the present study underscores the significance of cortical-cerebellar networks associated with cognition and neuropsychiatric dysfunction in bvFTD

Identifying malnutrition in emergency general surgery:systematic review

Background: Emergency general surgery practice is high risk. Surgery is a key part of treatment, with resultant catabolic stress and frequent need for nutritional support. The aim of this study was to examine the current methods of defining and determining malnutrition in emergency general surgery. This included examining the use of nutrition screening and assessment tools and other measures of malnutrition.Methods: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, trial registries, and relevant journals published between January 2000 and January 2022 were searched for studies of adult patients with any emergency general surgery diagnosis, managed conservatively or operatively, with an assessment of nutritional status. Mixed populations were included if more than 50 per cent of patients were emergency general surgery patients or emergency general surgery results could be separately extracted. Studies in which patients had received nutritional support were excluded. The protocol was registered with PROSPERO, the international prospective register of systematic reviews (CRD42021285897).Results: From 6700 studies screened, 324 full texts were retrieved and 31 were included in the analysis. A definition of malnutrition was provided in 23 studies (75 per cent), with nutritional status being determined by a variety of methods. A total of seven nutrition screening tools and a total of nine ‘assessment’ tools were reported. To define malnutrition, the most commonly used primary or secondary marker of nutritional status was BMI, followed by albumin level.Conclusion: Wide variation exists in approaches to identify malnutrition risk in emergency general surgery patients, using a range of tools and nutrition markers. Future studies should seek to standardize nutrition screening and assessment in the emergency general surgery setting as two discrete processes. This will permit better understanding of malnutrition risk in surgical patients

Incidence of human brucellosis in the Kilimanjaro Region of Tanzania in the periods 2007-2008 and 2012-2014

Background: Brucellosis causes substantial morbidity among humans and their livestock. There are few robust estimates of the incidence of brucellosis in sub-Saharan Africa. Using cases identified through sentinel hospital surveillance and health care utilization data, we estimated the incidence of brucellosis in Moshi Urban and Moshi Rural Districts, Kilimanjaro Region, Tanzania, for the periods 2007–2008 and 2012–2014. Methods: Cases were identified among febrile patients at two sentinel hospitals and were defined as having either a 4-fold increase in Brucella microscopic agglutination test titres between acute and convalescent serum or a blood culture positive for Brucella spp. Findings from a health care utilization survey were used to estimate multipliers to account for cases not seen at sentinel hospitals. Results: Of 585 patients enrolled in the period 2007–2008, 13 (2.2%) had brucellosis. Among 1095 patients enrolled in the period 2012–2014, 32 (2.9%) had brucellosis. We estimated an incidence (range based on sensitivity analysis) of brucellosis of 35 (range 32–93) cases per 100 000 persons annually in the period 2007–2008 and 33 (range 30–89) cases per 100 000 persons annually in the period 2012–2014. Conclusions: We found a moderate incidence of brucellosis in northern Tanzania, suggesting that the disease is endemic and an important human health problem in this area

Risk factors for human brucellosis in northern Tanzania

Little is known about the epidemiology of human brucellosis in sub-Saharan Africa. This hampers prevention and control efforts at the individual and population levels. To evaluate risk factors for brucellosis in northern Tanzania, we conducted a study of patients presenting with fever to two hospitals in Moshi, Tanzania. Serum taken at enrollment and at 4–6 week follow-up was tested by Brucella microagglutination test. Among participants with a clinically compatible illness, confirmed brucellosis cases were defined as having a ≥ 4-fold rise in agglutination titer between paired sera or a blood culture positive for Brucella spp., and probable brucellosis cases were defined as having a single reciprocal titer ≥ 160. Controls had reciprocal titers < 20 in paired sera. We collected demographic and clinical information and administered a risk factor questionnaire. Of 562 participants in the analysis, 50 (8.9%) had confirmed or probable brucellosis. Multivariable analysis showed that risk factors for brucellosis included assisting goat or sheep births (Odds ratio [OR] 5.9, 95% confidence interval [CI] 1.4, 24.6) and having contact with cattle (OR 1.2, 95% CI 1.0, 1.4). Consuming boiled or pasteurized dairy products was protective against brucellosis (OR 0.12, 95% CI 0.02, 0.93). No participants received a clinical diagnosis of brucellosis from their healthcare providers. The under-recognition of brucellosis by healthcare workers could be addressed with clinician education and better access to brucellosis diagnostic tests. Interventions focused on protecting livestock keepers, especially those who assist goat or sheep births, are needed

High-frequency water quality monitoring in an urban catchment: hydrochemical dynamics, primary production and implications for the Water Framework Directive

This paper describes the hydrochemistry of a lowland, urbanised river-system, The Cut in England, using in situ sub-daily sampling. The Cut receives effluent discharges from four major sewage treatment works serving around 190,000 people. These discharges consist largely of treated water, originally abstracted from the River Thames and returned via the water supply network, substantially increasing the natural flow. The hourly water quality data were supplemented by weekly manual sampling with laboratory analysis to check the hourly data and measure further determinands. Mean phosphorus and nitrate concentrations were very high, breaching standards set by EU legislation. Though 56% of the catchment area is agricultural, the hydrochemical dynamics were significantly impacted by effluent discharges which accounted for approximately 50% of the annual P catchment input loads and, on average, 59% of river flow at the monitoring point. Diurnal dissolved oxygen data demonstrated high in-stream productivity. From a comparison of high frequency and conventional monitoring data, it is inferred that much of the primary production was dominated by benthic algae, largely diatoms. Despite the high productivity and nutrient concentrations, the river water did not become anoxic and major phytoplankton blooms were not observed. The strong diurnal and annual variation observed showed that assessments of water quality made under the Water Framework Directive (WFD) are sensitive to the time and season of sampling. It is recommended that specific sampling time windows be specified for each determinand, and that WFD targets should be applied in combination to help identify periods of greatest ecological risk. This article is protected by copyright. All rights reserved

Risk factors for human acute leptospirosis in northern Tanzania

Introduction: Leptospirosis is a major cause of febrile illness in Africa but little is known about risk factors for human infection. We conducted a cross-sectional study to investigate risk factors for acute leptospirosis and Leptospira seropositivity among patients with fever attending referral hospitals in northern Tanzania. Methods: We enrolled patients with fever from two referral hospitals in Moshi, Tanzania, 2012–2014, and performed Leptospira microscopic agglutination testing on acute and convalescent serum. Cases of acute leptospirosis were participants with a four-fold rise in antibody titers, or a single reciprocal titer ≥800. Seropositive participants required a single titer ≥100, and controls had titers <100 in both acute and convalescent samples. We administered a questionnaire to assess risk behaviors over the preceding 30 days. We created cumulative scales of exposure to livestock urine, rodents, and surface water, and calculated odds ratios (OR) for individual behaviors and for cumulative exposure variables. Results: We identified 24 acute cases, 252 seropositive participants, and 592 controls. Rice farming (OR 14.6), cleaning cattle waste (OR 4.3), feeding cattle (OR 3.9), farm work (OR 3.3), and an increasing cattle urine exposure score (OR 1.2 per point) were associated with acute leptospirosis. Conclusions: In our population, exposure to cattle and rice farming were risk factors for acute leptospirosis. Although further data is needed, these results suggest that cattle may be an important source of human leptospirosis. Further investigation is needed to explore the potential for control of livestock Leptospira infection to reduce human disease

Progression in behavioral variant frontotemporal dementia:A longitudinal study

Importance: A gap in the literature exists regarding progression in behavioral variant frontotemporal dementia (BVFTD). Guidance is needed concerning markers that will enable clinicians to discriminate FTD more effectively from phenocopies and to identify factors that determine progression and thereby prognosis.  Objectives: To observe longitudinal outcomes and progression in probable and possible BVFTD in accordance with international diagnostic criteria and to identify features that may aid clinicians to prognosticate better in cases of possible BVFTD.  Design, Setting, and Participants: Longitudinal cohort study performed in a specialist tertiary FTD research clinic. Fifty-eight consecutive patients were followed up longitudinally from January 1, 2008, through December 31, 2013, and classified as having possible, probable, or definite BVFTD at presentation and latest review. Final follow-up was completed on December 31, 2013, and data were analyzed from January 1 to August 1, 2014.  Main Outcomes and Measures: Clinical, pathological, genetic, neuropsychological, and neuroimaging data were analyzed to categorize patients, to compare differences between groups with changed and unchanged diagnoses, to determine rates of progression in BVFTD, and to identify prognostic features in possible BVFTD.  Results: At presentation, 38 of the 58 patients fulfilled criteria for probable BVFTD; of these, 36 continued to satisfy probable criteria or underwent conversion to definite criteria over time. The remaining 20 patients satisfied possible criteria only, and 11 of these patients changed categories over time to probable or definite BVFTD and showed progression on cognitive and functional measures (termed changed status). Of these 11 patients, 8 (73%) carried the C9orf72 expansion. A positive family history, memory impairment, and clinical abnormalities at presentation were key features of progression (P < .05). A continuum of neuropsychological scores, progression rates, and atrophy severity emerged across patients in probable, possible, changed status, and nonchanged status groups; patients with probable BVFTD exhibited the most severe abnormalities.  Conclusions and Relevance: Behavioral variant FTD shows variable progression over time. Clinicians can use a detailed neurologic and cognitive assessment to identify key predictive features of progression when faced with possible BVFTD, whereas a diagnosis of probable BVFTD is accurate in a clinical setting

Blood-Brain Barrier Breakdown in the Aging Human Hippocampus

The blood-brain barrier (BBB) limits entry of blood-derived products, pathogens, and cells into the brain that is essential for normal neuronal functioning and information processing. Post-mortem tissue analysis indicates BBB damage in Alzheimer’s disease (AD). The timing of BBB breakdown remains, however, elusive. Using an advanced dynamic contrast-enhanced MRI protocol with high spatial and temporal resolutions to quantify regional BBB permeability in the living human brain, we show an age-dependent BBB breakdown in the hippocampus, a region critical for learning and memory that is affected early in AD. The BBB breakdown in the hippocampus and its CA1 and dentate gyrus subdivisions worsened with mild cognitive impairment that correlated with injury to BBB-associated pericytes, as shown by the cerebrospinal fluid analysis. Our data suggest that BBB breakdown is an early event in the aging human brain that begins in the hippocampus and may contribute to cognitive impairment

Estimating acute human leptospirosis incidence in northern Tanzania using sentinel site and community behavioural surveillance

Many infectious diseases lack robust estimates of incidence from endemic areas, and extrapolating incidence when there are few locations with data remains a major challenge in burden of disease estimation. We sought to combine sentinel surveillance with community behavioural surveillance to estimate leptospirosis incidence. We administered a questionnaire gathering responses on established locally relevant leptospirosis risk factors and recent fever to livestock‐owning community members across six districts in northern Tanzania and applied a logistic regression model predicting leptospirosis risk on the basis of behavioural factors that had been previously developed among patients with fever in Moshi Municipal and Moshi Rural Districts. We aggregated probability of leptospirosis by district and estimated incidence in each district by standardizing probabilities to those previously estimated for Moshi Districts. We recruited 286 community participants: Hai District (n = 11), Longido District (59), Monduli District (56), Moshi Municipal District (103), Moshi Rural District (44) and Rombo District (13). The mean predicted probability of leptospirosis by district was Hai 0.029 (0.005, 0.095), Longido 0.071 (0.009, 0.235), Monduli 0.055 (0.009, 0.206), Moshi Rural 0.014 (0.002, 0.049), Moshi Municipal 0.015 (0.004, 0.048) and Rombo 0.031 (0.006, 0.121). We estimated the annual incidence (upper and lower bounds of estimate) per 100,000 people of human leptospirosis among livestock owners by district as Hai 35 (6, 114), Longido 85 (11, 282), Monduli 66 (11, 247), Moshi Rural 17 (2, 59), Moshi Municipal 18 (5, 58) and Rombo 47 (7, 145). Use of community behavioural surveillance may be a useful tool for extrapolating disease incidence beyond sentinel surveillance sites