Blood cancer journal

BACKGROUND: Gait impairments increase with advancing age and can lead to falls and loss of independence. Brain atrophy also occurs in older age and may contribute to gait decline. We aimed to investigate global and regional relationships of cerebral gray and white matter volumes with gait speed, and its determinants step length and cadence, in older people. METHODS: In a population-based study, participants aged >60 years without Parkinson's disease or brain infarcts underwent magnetic resonance imaging and gait measurements using a computerized walkway. Linear regression was used to study associations of total gray and white matter volumes with gait, adjusting for each other, age, sex, height and white matter hyperintensity volume. Other covariates considered in analyses included weight and vascular disease history. Voxel-based morphometry was used to study regional relationships of gray and white matter with gait. RESULTS: There were 305 participants, mean age 71.4 (6.9) years, 54% male, mean gait speed 1.16 (0.22) m/s. Smaller total gray matter volume was independently associated with poorer gait speed (p = 0.001) and step length (p<0.001), but not cadence. Smaller volumes of cortical and subcortical gray matter in bilateral regions important for motor control, vision, perception and memory were independently associated with slower gait speed and shorter steps. No global or regional associations were observed between white matter volume and gait independent of gray matter volume, white matter hyperintensity volume and other covariates. CONCLUSION: Smaller gray matter volume in bilaterally distributed brain networks serving motor control was associated with slower gait speed and step length, but not cadence

Filosofia come stile di vita. Conversazione con Luigi Vero Tarca

OBJECTIVE: To examine factors associated with chronic energy deficiency (CED) and anaemia in disadvantaged Indian adults who are mostly involved in subsistence farming. DESIGN: A cross-sectional study in which we collected information on socio-demographic factors, physical activity, anthropometry, blood haemoglobin concentration, and daily household food intake. These data were used to calculate body mass index (BMI), basal metabolic rate (BMR), daily energy expenditure, and energy and nutrient intake. Multivariable backward stepwise logistic regression was used to assess socioeconomic and lifestyle factors associated with CED (defined as BMI<18 kg/m²) and anaemia. SETTING: The study was conducted in 12 villages, in the Rishi Valley, Andhra Pradesh, India. SUBJECTS: Individuals aged 18 years and above, residing in the 12 villages, were eligible to participate. RESULTS: Data were available for 1178 individuals (45% male, median age 36 years (inter quartile range (IQR 27-50)). The prevalence of CED (38%) and anaemia (25%) was high. Farming was associated with CED in women (2.20, 95% CI: 1.39-3.49) and men (1.71, 95% CI: (1.06-2.74). Low income was also significantly associated with CED, while not completing high school was positively associated with anaemia. Median iron intake was high: 35.7 mg/day (IQR 26-46) in women and 43.4 mg/day (IQR 34-55) in men. CONCLUSIONS: Farming is an important risk factor associated with CED in this rural Indian population and low dietary iron is not the main cause of anaemia. Better farming practice may help to reduce CED in this population

Untersuchungen zur Stabilisierung der frühen postnatalen Adaptationsvorgänge bei Kälbern in Mutterkuhhaltung - ein Beitrag zur Charakterisierung postnataler Anpassungsreaktionen

Ziel dieser Arbeit war es, die sensible Phase der ersten und frühen zweiten Adaptationsphase, von der Geburt bis zur 72. Lebensstunde, bei Kälbern fleischbetonter Rassen in einem geschlossenen Mutterkuhbestand zu untersuchen, um daraus folgend einen Beitrag zur Erstellung von nicht parametrischen Referenzbereichen für klinische und labordiagnostische Parameter für diese Zeitspanne zu leisten. Korrelationen zwischen klinischen und labordiagnostischen Parametern sollten aufgedeckt werden, um so klinisch relevante Beziehungen herstellen zu können Eine Einschätzung der Vitalität anhand leicht zu erhebender ethologischer Befunde, wie erstes Kopfheben post natum, erstes sicheres Stehen und erste Kolostrumaufnahme wurde durchgeführt. Als Probanden standen insgesamt 115 mature Kälber verschiedener Rassen aus einem geschlossenen Mutterkuhbestand zur Verfügung. Die Untersuchung erstreckte sich von der Geburt bis zu 72 Stunden p. n.. Folgende 20 Parameter kamen dabei zur Auswertung: pH, Base Excess, Kohlendioxidpartialdruck, Hä­¡tokrit, Gesamtprotein, Glukose, Triglyzeride, Cholesterin, Harnstoff, Kreatinin, Natrium, Kalium, Chlorid, Magnesium, AST, ALT, AP, GGT, GLDH und CK. Die statistische Auswertung der Ergebnisse wurde unter Berücksichtigung der Faktoren Alter, Rasse, Geschlecht und Geburtsart der Kälber sowie Geburtsziffer des Muttertieres vorgenommen. Die einzelnen Messgrössen bis auf das Plasmachlorid wurden über den Untersuchungszeitraum hochsignifikant (p < 0,001) durch das Alter beeinflusst. Einflí²í³¥ der Rasse zeigten sich im Verlauf des Blut-pH-Wertes (p <= 0,01), des Base Excess (p <= 0,05) sowie der Enzyme ALT (p <= 0,05) und GLDH (p <= 0,05). Das erste sichere Stehen post natum wurde schwach signifikant durch das Geschlecht (p <= 0,05) beeinflusst. Die Parameter pH-Wert (p <= 0,05) und Kohlendioxidpartialdruck (p <= 0,01) im venösen Blut sowie die Blutglukose (p <= 0,01) zeigten bis zum dritten Lebenstag ebenfalls Einflüsse durch das Geschlecht der Kälber. Die Geburtsart übte einen signifikanten Einfluss auf die ethologischen Parameter des ersten Stehens (p <= 0,01) und des ersten Saugens post natum (p <= 0,01) aus, die Einstufung nach APGAR wurde sogar hoch signifikant (p <= 0,001) durch die Geburtsart beeinflusst. Labordiagnostisch konnte ein signifikanter Einfluss auf die CK-Aktivität (p <= 0,01) ermittelt werden. pH-Wert, Kaliumkonzentration und AST-Aktivität erfuhren schwach signifikante (p <= 0,05) Beeinflussungen durch die Art der Geburt. Die Parität der Muttertiere, beeinflusste die Geburtsart signifikant (p <= 0,01). Ebenso wiesen die Serumspiegel des Gesamtproteins (p <= 0,05), von Harnstoff (p <= 0,01), Kalium (p <= 0,05), ALT (p <= 0,05) und GLDH (p <= 0,05) Einflüsse der die Geburtsziffer auf. Im Verlauf der AP-Aktivitäten zeigten sich hoch signifikante Wechselwirkungen (p <= 0,001) mit den verschiedenen Rassen. Das Geschlecht der Kälber wies ebenso hoch signifikante Wechselwirkungen (p <= 0,001) zur GLDH-Aktivität auf. Wechselwirkungen der Geburtsart und der Zeit waren bei den Messgrössen pH-Wert (p <= 0,001), Kohlendioxidpartialdruck (p <= 0,01), Base Excess (p <= 0,001), Hämatokrit (p <= 0,001), Harnstoff (p <= 0,05) und AST-Aktivität (p <= 0,05) statistisch nachweisbar. Auf die Parameter Harnstoff (p <= 0,001), Natrium (p <= 0,05), Kalium (p <= 0,05), Chlorid (p <= 0,05) und ALT-Aktivität (p <= 0,05) waren Wechselwirkungen der Geburtsziffer der Muttertiere von der Geburt bis zur 72. Lebensstunde darstellbar. Die Körpertemperatur der Kälber korrelierte unmittelbar nach der Geburt signifikant (p <= 0,01) mit dem Blut-pH-Wert (r = -0,283) und dem Kohlendioxidpartialdruck (r = +0,284). Zum Base Excess bestand postnatal eine schwach signifikante (p <= 0,05) Korrelation (r = -0,193). Die Blutglukosewerte korrelierten unmittelbar post natum schwach signifikant (p <= 0,05) mit dem Blut-pH (r = -0,207), dem Kohlendioxidpartialdruck (r = +0,089) und dem Base Excess (r = 0,210). Das erste Kopfheben post natum stand in hoch signifikantem (p <= 0,001) Zusammenhang mit der Vitalitätseinschätzung nach APGAR. Das erste Stehen zeigte einen signifikante (p <= 0,01) und der Zeitpunkt der ersten Kolostrumaufnahme noch einen schwach signifikanten (p <= 0,05) Zusammenhang. Zur exakten Einschätzung der labordiagnostisch ermittelten Blutwerte bei neugeborenen Kälbern ist eine vom genauen Alter abhängige Erstellung von Referenzbereichen unter Berücksichtigung nicht parametrischer Referenzbereiche notwendig.The aim of the present study was to illustrate the sensitive time of the first and the early second adaptation period from birth to the 72. hour of life in different races of beef cattle in one herd. Furthermore non parametric reference values for clinical and laboratory diagnostic parameters for this period of adaptation were described. Another aim was to find correlations between clinical and laboratory parameters to show relations of clinical relevance. Ethological findings such as: first raising of the head post natum, first firm standing and colostrum intake were evaluated. For tests, a total of 115 mature calves of different races out of a close suckler cow management system herd was available. The evaluation was made from immediately after birth to 72 hours p. n.. The following 20 parameters were evaluated: pH, base excess, carbondioxide partial pressure, hematocrit, total protein, glucose, triglyceride, cholesterol, uric acid, creatinin, sodium, calium, potassium, chloride, magnesium, AST, ALT, AP, GGT, GLDH and CK. When doing the statistical evaluation of the results factors such as: age, race, sex, kind of birth of the calves as well as the number of births given by the mother cow were considered. The development of the single values over the time period of the research was highly influenced by the age (p <= 0.001). Influence of the race was found during the course of the blood-pH-value (p <= 0.01), of the base excess (p <= 0.05) and also of the enzymes ALT (p <= 0.05) and GLDH (p <= 0.05). The time of first firm standing post natum as a qualifying factor was only weak significantly (p <= 0.05) influenced by the sex. The parameter blood-pH (p <= 0.05), blood glycose (p <= 0.01) and carbondioxide partial pressure (p <= 0.01) also proved influence of the sex of the calves during the first 3 days after birth. The kind of birth had a significant influence on the ethological parameter of the first standing (p <= 0.01) and the first suckling post natum (p <= 0.01). When judging according to APGAR the correlation was even highly significant (p <= 0.001). In the laboratory diagnostics a significant influence on the CK-activity (p <= 0.01) could be found. pH-value, potassium concentration and AST-activity were weak significantly influenced (p <= 0.05) by the kind of birth. The kind of birth was significantly influenced (p <= 0.01) by the fact how often a mother cow already had given birth to calves. The serum level of the total protein (p <= 0.05), of the uric acid (p <= 0.01), potassium (p <=0.05), ALT (p <= 0.05) and GLDH (p <= 0.05) also showed their correlation to the number of birth. During the course of the AP activities of the different races significant interactions became obvious (p <= 0.001). The sex of the calves also showed highly significant interactions (p <= 0.001) towards the GLDH activity. Interactions of the kind and time of birth could also statistically be proven for the parameters: pH value (p <= 0.001), carbondioxide partial pressure (p <= 0.01), base excess (p <= 0.001), hematocrit (p <= 0.001), uric acid (p <= 0.05) and AST activity (p <= 0.05). For the parameters uric acid (p <= 0.001), sodium (p <= 0.05), potassium (p <= 0.05), chloride (p <= 0.05) and AST activity (p <= 0.05), an interaction could be found to the number of births given by the mother cow from the date of birth till the 72nd hour after birth. Correlation was discovered between body temprature and blood glycose to pH, carbondioxide partial pressure and base excess. The body temperature of the calves correlated after birth directly and significantly (p <= 0.01) with the blood-pH-value (r = -0.283) and the carbondioxide partial pressure (r = +0.284). There existed a slightly significant (p <= 0.05) correlation (r = -0.193) to the base excess. The blood glycose values correlated directly post natum slightly significantly (p <= 0.05) with the blood-pH (r = -0.207) with the carbondioxide partial pressure (r = +0.089) and with the base excess (r = 0.210). The first raising of the head post natum was in a highly significant connection (p <= 0.001) with the judgement of the vitality by APGAR. The first standing up showed a significant (p <= 0.01) and the time of first intake of cholostrum still a weak significant (p <=0.05) correlation. For the exact evaluation of the blood values derived from laboratory diagnostics for newly born calves, a table with values referring to the exact age and also considering the non-parameter values must be created

Frailty is associated with cognitive decline independent of cerebral small vessel disease and brain atrophy

BACKGROUND: To examine the effect of frailty on cognitive decline independent of cerebral small vessel disease (cSVD) and brain atrophy, and whether associations between neuropathology and cognition differed depending on frailty status. METHODS: The Tasmanian Study of Cognition and Gait was a population-based longitudinal cohort study with data collected at 3 phases from 2005 to 2012. Participants aged 60-85 were randomly selected from the electoral roll. Various data were used to operationalize a 36-item frailty index (FI) at baseline. Brain MRI was undertaken to obtain baseline measures of neuropathology. A neuropsychological battery was used to assess cognition at each time point. Generalized linear mixed models were used to examine the effect of frailty and MRI measures on cognition over time. The associations between MRI measures and cognition were explored after stratifying the sample by baseline frailty status. All analyses were adjusted for age, sex, and education. RESULTS: A total of 385 participants were included at baseline. The mean age was 72.5 years (standard deviation [SD] 7.0), 44% were female (n = 171). In fully adjusted linear mixed models, frailty (FI × time β -0.001, 95% confidence interval [CI] -0.003, -0.001, p = .03) was associated with decline in global cognition, independent of brain atrophy, and cSVD. The association between cSVD and global cognition was significant only in those with low levels of frailty (p = .03). CONCLUSION: These findings suggest that frailty is an important factor in early cognitive dysfunction, and measuring frailty may prove useful to help identify future risk of cognitive decline

Effectiveness of a scalable group-based education and monitoring program, delivered by health workers, to improve control of hypertension in rural India: A cluster randomised controlled trial

New methods are required to manage hypertension in resource-poor settings. We hypothesised that a community health worker (CHW)-led group-based education and monitoring intervention would improve control of blood pressure (BP). We conducted a baseline community-based survey followed by a cluster randomised controlled trial of people with hypertension in 3 rural regions of South India, each at differing stages of epidemiological transition. Participants with hypertension, defined as BP ≥ 140/90 mm Hg or taking antihypertensive medication, were advised to visit a doctor. In each region, villages were randomly assigned to intervention or usual care (UC) in a 1:2 ratio. In intervention clusters, trained CHWs delivered a group-based intervention to people with hypertension. The program, conducted fortnightly for 3 months, included monitoring of BP, education about hypertension, and support for healthy lifestyle change. Outcomes were assessed approximately 2 months after completion of the intervention. The primary outcome was control of BP (BP < 140/90 mm Hg), analysed using mixed effects regression, clustered by village within region and adjusted for baseline control of hypertension (using intention-to-treat principles). Of 2,382 potentially eligible people, 637 from 5 intervention clusters and 1,097 from 10 UC clusters were recruited between November 2015 and April 2016, with follow-up occurring in 459 in the intervention group and 1,012 in UC. Mean age was 56.9 years (SD 13.7). Baseline BP was similar between groups. Control of BP improved from baseline to follow-up more in the intervention group (from 227 [49.5%] to 320 [69.7%] individuals) than in the UC group (from 528 [52.2%] to 624 [61.7%] individuals) (odds ratio [OR] 1.6, 95% CI 1.2-2.1; P = 0.001). In secondary outcome analyses, there was a greater decline in systolic BP in the intervention than UC group (-5.0 mm Hg, 95% CI -7.1 to -3.0; P < 0.001) and a greater decline in diastolic BP (-2.1 mm Hg, 95% CI -3.6 to -0.6; P < 0.006), but no detectable difference in the use of BP-lowering medications between groups (OR 1.2, 95% CI 0.8-1.9; P = 0.34). Similar results were found when using imputation analyses that included those lost to follow-up. Limitations include a relatively short follow-up period and use of outcome assessors who were not blinded to the group allocation. While the durability of the effect is uncertain, this trial provides evidence that a low-cost program using CHWs to deliver an education and monitoring intervention is effective in controlling BP and is potentially scalable in resource-poor settings globally. The trial was registered with the Clinical Trials Registry-India (CTRI/2016/02/006678)

Profile of and risk factors for poststroke cognitive impairment in diverse ethno-regional groups

OBJECTIVE: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. METHODS: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. RESULTS: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethno-racial groups, some interethnic differences were found in the effects of risk factors on cognition. CONCLUSIONS: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethno-racial differences that warrant attention in the development of prevention strategies.OBJECTIVE: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. METHODS: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. RESULTS: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition. CONCLUSIONS: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.Peer reviewe

The complex genetics of gait speed:Genome-wide meta-analysis approach

Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging

GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium

Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5 × 10−8) and 39 suggestive (P-value< 5 × 10−5) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P-value = 5.20 × 10−10). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth