Multidomain interventions for sarcopenia and cognitive flexibility in older adults for promoting healthy aging: a systematic review and meta-analysis of randomized controlled trials.

The global population is undergoing rapid aging, making physical activity a crucial element in preventing mortality and lowering the risk of Alzheimer's disease. Age-related declines in muscle mass and cognitive abilities significantly contribute to frailty and dependency. Thus, this study focuses on a meticulous analysis of the protective effects of multidomain interventions, an emerging resource combating age-related declines. It seeks to underscore their profound impact on cognitive flexibility and sarcopenia, highlighting their pivotal role in mitigating the adverse effects of aging. To identify relevant randomized controlled trials up to November 2023, we reviewed eight online academic databases, following PERSiST guidelines, PRISMA reporting system, and PICOs criteria. Meta-analyses on selected functional outcomes utilized a random-effects model, including the Timed Up and Go Test, Sit to Stand Test, Victoria Stroop Test, and Trail Making Test. Out of 2082 scrutinized articles, 17 were included in the systematic review, and 8 in the meta-analysis. Positive effects (p = 0.05, I2 = 57%; 95% CI - 0.63 to - 0.05) were observed in cognitive flexibility for certain interventions. Similarly, interventions addressing muscle strength demonstrated improvements in the Sit to Stand Test for the exercise group compared to the control group (p = 0.02, I2 = 0%; 95% CI - 0.63 to - 0.05). These findings underscore the importance of incorporating physical activity as a primary component of public health interventions for promoting healthy aging and reducing the burden of age-related diseases. Future interventions may explore more homogeneous approaches and evaluate the impact of thrice multidomain weekly sessions.

Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer.

Background: There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC. Patients and methods: In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m2 intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS). Results: A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P = 0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P = 0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P = 0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%). Conclusions: Vinflunine 280 mg/m2 q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m2 merits evaluation. ClinicalTrials.gov: NCT01091168.

What do Spaniards read about the prudent use of anti-microbial agents and what do they really do?

OBJECTIVES: The prudent use of antibiotics (PUA) is promoted not only by public information campaigns, but also in the printed media and on websites. This study assesses the correspondence between PUA information in the Spanish printed media and on websites and the messages put out by national campaigns. Spaniards' use of antibiotics following the campaigns was also analysed. METHODS: A two-phase descriptive study was carried out. First, antibiotics-related news in the Spanish printed media (January 2007-May 2009) and institutional and news media websites (March-May 2009) were systematically reviewed using a data collection tool. In addition, a telephone survey on antibiotics-related knowledge and behaviours was carried out with a random sample of 1526 people living in Spain who had recently received medical care. RESULTS: In total, 29 news items containing nine different messages were identified. All the messages were similar to those promoted by the campaigns. The survey showed that even after the campaigns, relevant gaps in knowledge about the PUA persist, particularly among men (p = .005), those living in rural areas (p = .02) and the elderly (p < .001). Keeping left-over antibiotics was associated with ignorance about the association between antibiotic use and resistance (OR 3.1, 95% CI 2.3-4.2). Also, patients who ask their doctor about drug interactions are less likely to self-medicate (p = .04). CONCLUSIONS: The information reaching the Spanish public via the media seems to be similar to the messages transmitted by public information campaigns. Nevertheless, there appears to be considerable room for improvement. Promoting an active role in patients might reduce self-medication.

3D phantom for image quality assessment of mammography systems.

Objective.To present an innovative approach for the design of a 3D mammographic phantom for medical equipment quality assessment, estimation of the glandular tissue percentage in the patient's breast, and emulation of microcalcification (µC) breast lesions.Approach.Contrast-to noise ratio (CNR) measurements, as well as spatial resolution and intensity-to-glandularity calibrations under mammography conditions were performed to assess the effectiveness of the phantom. CNR measurements were applied to different groups of calcium hydroxyapatite (HA) and aluminum oxide (AO)µCs ranging from 200 to 600µm. Spatial resolution was characterized using an aluminum plate contained in the phantom and standard linear figures of merit, such as the line spread function and modulation transfer function (MTF). The intensity-to-glandularity calibration was developed using an x-ray attenuation matrix within the phantom to estimate the glandular tissue percentage in a breast with a compressed thickness of 4 cm.Main results.For the prototype studied, the minimum confidence level for detecting HAµCs is 95.4%, while for AOµCs is above 68.3%. It was also possible to determine that the MTF of the commercial mammography machine used for this study at the Nyquist frequency is 41%. Additionally, a one-to-one intensity-to-glandularity calibration was obtained and verified with Monte-Carlo simulation results.Significance.The phantom provides traditional arrangements presented in accreditation phantoms, which makes it competitive with available devices, but excelling in regarding affordability, modularity, and inlays distribution. Moreover, its design allows to be positioned in close proximity to the patient's breast during a medical screening for a simultaneous x-ray imaging, such that the features of the phantom can be used as reference values to specify characteristics of the real breast tissue, such as proportion of glandular/adipose composition and/orµC type and size lesions.

Myotonic dystrophy type 1: 13 years of experience at a tertiary hospital. Clinical and epidemiological study and genotype-phenotype correlation.

INTRODUCTION: The incidence of myotonic dystrophy type 1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). METHODS: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (> 1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (> 1000). RESULTS: The incidence of DM1 was 20.61 cases per million person-years (95% CI, 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ = -0.547; 95% CI, -0.610 to -0.375; P < .001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. CONCLUSIONS: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.

A study of fatty acid binding protein 4 in HIV-1 infection and in combination antiretroviral therapy-related metabolic disturbances and lipodystrophy.

OBJECTIVE: The aim of the study was to determine circulating levels of fatty acid binding protein 4 (FABP-4) in a cohort of HIV-1-infected patients treated with combination antiretroviral therapy (cART) and to investigate the relationships between FABP-4 levels and insulin resistance, dyslipidaemia, lipodystrophy and levels of proinflammatory adipocytokines in these patients. METHODS: A total of 282 HIV-1-infected patients treated with stable cART for at least 1 year (132 with lipodystrophy and 150 without) and 185 uninfected controls (UCs) were included in the study. Anthropometric parameters were determined. Plasma levels of FABP-4, soluble tumour necrosis factor receptors 1 and 2 (sTNF-R1 and sTNF-R2), interleukin-18 (IL-18), IL-6, adiponectin and leptin were also analysed. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). Subcutaneous adipose tissue mRNA expression of proinflammatory cytokines was assessed in 38 patients (25 with lipodystrophy and 13 without) by real-time polymerase chain reaction (PCR). RESULTS: The plasma FABP-4 concentration was significantly higher in patients with lipodystrophy than in those without (P=0.012). FABP-4 concentration was positively correlated with body mass index (BMI), HOMA-IR, and the concentrations of insulin, total cholesterol, triglycerides, sTNF-R1, leptin and IL-18, but showed a negative correlation with high-density lipoprotein (HDL) cholesterol and adiponectin concentrations. After adjusting for age, sex and BMI, the odds ratio (OR) for risk of lipodystrophy was found to be significantly increased for those with the highest levels of FABP-4 [OR 0.838, 95% confidence interval (CI) 0.435-1.616 for medium FABP-4 vs. OR 2.281, 95% CI 1.163-4.475 for high FABP-4]. In a stepwise regression model, FABP-4 was independently associated with HOMA-IR after controlling for clinical and inflammatory parameters (P=0.004). Moreover, a positive relationship was observed in patients with lipodystrophy between subcutaneous adipose tissue CD68 expression and FABP-4 plasma levels (r=0.525; P=0.031). CONCLUSIONS: cART-treated HIV-1-infected patients with lipodystrophy have a systemic overproduction of FABP-4, which is closely linked to insulin resistance and inflammatory markers in subcutaneous adipose tissue.

Myotonic dystrophy type1: 13years of experience at a tertiary hospital. Clinical and epidemiological study and genotype-phenotype correlation. / Distrofia miotónica tipo1: 13años de experiencia en un hospital terciario. Estudio clínico y epidemiológico. Correlación genotipo-fenotipo.

INTRODUCTION: The incidence of myotonic dystrophy type1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). METHODS: Retrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (>1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (>1000). RESULTS: The incidence of DM1 was 20.61 cases per million person-years (95%CI: 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ=-0.547; 95%CI: -0.610 to -0.375; P<.001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. CONCLUSIONS: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.

Epidemiology of tuberculosis in the Americas: the Stop TB strategy and the millennium development goals.

BACKGROUND: Tuberculosis (TB), a preventable and curable disease, remains a major public health threat in the poorest regions of the Americas. The DOTS strategy was implemented to control TB in the region in 1993, and the new Stop TB strategy, emphasizing high-quality DOTS expansion, in 2006. OBJECTIVES: To describe TB epidemiology in the region of the Americas from 1994 to 2005 and to analyze the progress made towards and prospects for achieving Goal 6 of the Millennium Development Goals (MDGs) by 2015. METHODS: TB incidence, mortality and prevalence rates as well as DOTS coverage and DOTS treatment success rates were collated from the World Health Organization (WHO) databases from 1994 to 2005. RESULTS: DOTS coverage and DOTS treatment success rates rose steadily from 1994 to 2005, with 88% of the population covered under DOTS by 2005, and an 80% success rate by the end of 2004. The TB incidence, prevalence and mortality rates have also decreased steadily from 1994 to date, but differ with respect to the various scenarios. CONCLUSIONS: With the exception of some countries, further reduction in TB incidence, prevalence and deaths by 2015 is possible. Widespread implementation of DOTS should continue in order to meet WHO targets and attain the MDGs.

Scaling up collaborative TB-HIV activities in Latin America.

TB-HIV collaborative activities are one of the cornerstones of TB control in the Stop TB strategy. Since 2003, most countries in Latin America and the Caribbean have been gradually implementing TB-HIV collaborative activities; however, limited information is currently available on the degree of implementation. This study is therefore aimed at describing to what degree TB-HIV collaborative activities are being implemented in 17 countries selected for the study. These countries were asked to complete a semi-structured questionnaire. An analysis of this questionnaire revealed that the challenges for TB-HIV collaboration lie in the fields of human resources, surveillance and HIV testing of TB patients.

Gut bacterial composition in a mouse model of Parkinson's disease.

The mechanism of neurodegeneration in Parkinson's disease (PD) remains unknown but it has been hypothesised that the intestinal tract could be an initiating and contributing factor to the neurodegenerative processes. In PD patients as well as in animal models for PD, alpha-synuclein-positive enteric neurons in the colon and evidence of colonic inflammation have been demonstrated. Moreover, several studies reported pro-inflammatory bacterial dysbiosis in PD patients. Here, we report for the first time significant changes in the composition of caecum mucosal associated and luminal microbiota and the associated metabolic pathways in a rotenone-induced mouse model for PD. The mouse model for PD, induced by the pesticide rotenone, is associated with an imbalance in the gut microbiota, characterised by a significant decrease in the relative abundance of the beneficial commensal bacteria genus Bifidobacterium. Overall, intestinal bacterial dysbiosis might play an important role in both the disruption of intestinal epithelial integrity and intestinal inflammation, which could lead or contribute to the observed alpha-synuclein aggregation and PD pathology in the intestine and central nervous system in the oral rotenone mouse model of PD.

Defining the optimal sequence for the systemic treatment of metastatic breast cancer.

Metastatic breast cancer is a heterogeneous disease that presents in varying forms, and a growing number of therapeutic options makes it difficult to determine the best choice in each particular situation. When selecting a systemic treatment, it is important to consider the medication administered in the previous stages, such as acquired resistance, type of progression, time to relapse, tumor aggressiveness, age, comorbidities, pre- and post-menopausal status, and patient preferences. Moreover, tumor genomic signatures can identify different subtypes, which can be used to create patient profiles and design specific therapies. However, there is no consensus regarding the best treatment sequence for each subgroup of patients. During the SABCC Congress of 2014, specialized breast cancer oncologists from referral hospitals in Europe met to define patient profiles and to determine specific treatment sequences for each one. Conclusions were then debated in a final meeting in which a relative degree of consensus for each treatment sequence was established. Four patient profiles were defined according to established breast cancer phenotypes: pre-menopausal patients with luminal subtype, post-menopausal patients with luminal subtype, patients with triple-negative subtype, and patients with HER2-positive subtype. A treatment sequence was then defined, consisting of hormonal therapy with tamoxifen, aromatase inhibitors, fulvestrant, and mTOR inhibitors for pre- and post-menopausal patien ts; a chemotherapy sequence for the first, second, and further lines for luminal and triple-negative patients; and an optimal sequence for treatment with new antiHER2 therapies. Finally, a document detailing all treatment sequences, that had the agreement of all the oncologists, was drawn up as a guideline and advocacy tool for professionals treating patients with this disease.

[Magnetic resonance imaging with spectroscopy, perfusion and cerebral diffusion in the diagnosis of brain tumours]. / Resonancia magnética con espectroscopia, perfusión y difusión cerebral en el diagnóstico de los tumores cerebrales.

AIM: We review three of the most important functional techniques in magnetic resonance imaging, it means spectroscopy, perfusion and diffusion; we do emphasize in its applications, particularly in the diagnostic and treatment of brain tumors. First, we discuss the physical principles and results interpretation of each technique. After that, we discuss its major applications. DEVELOPMENT AND CONCLUSIONS: Choline containing compounds using contralateral creatine and choline for normalization or ipsilateral N-acetyl-aspartate appeared to correlate best with the degree of tumor infiltration, regardless o tumor histological grade. Magnetic resonance spectroscopy imaging (MRSI) seems more accurate than conventional magnetic resonance imaging (MRI) in defining indistinct tumor boundaries and quantifying the degree of tumor infiltration. MRSI is the choice of site within a lesion for biopsy and use in image-guided therapy, including definition of radiation ports. Angiogenesis, and increased vascular permeability, are characteristic of cerebral neoplasms; these processes can be imaged using perfusion MRI. Most commonly, tumor perfusion is measured using rapid gradient T2-weighted imaging during bolus injection of gadolinium dimeglumine gadopentetate. Care has to be taken to avoid blood-brain barrier leakage affecting perfusion results. Pharmacokinetic models are available for estimation of blood-brain permeability. Cerebral blood volume increases with tumor grade, and maybe helpful in identifying tumor recurrence, and peri-tumoral edema, and distinguishing malignant from benign lesions.

Ribociclib plus letrozole in early breast cancer: A presurgical, window-of-opportunity study.

OBJECTIVES: Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC). This study assessed the biological activity of ribociclib (LEE011; CDK4/6 inhibitor) plus letrozole compared with single-agent letrozole in the presurgical setting. MATERIALS AND METHODS: Postmenopausal women (N = 14) with resectable, HR+, human epidermal growth factor receptor 2-negative (HER2-) early BC were randomized 1:1:1 to receive 2.5 mg/day letrozole alone (Arm 1), or with 400 or 600 mg/day ribociclib (Arm 2 or 3). Circulating tumor DNA and tumor biopsies were collected at baseline and, following 14 days of treatment, prior to or during surgery. The primary objective was to assess antiproliferative response per Ki67 levels in Arms 2 and 3 compared with Arm 1. Additional assessments included safety, pharmacokinetics, and genetic profiling. RESULTS: Mean decreases in the Ki67-positive cell fraction from baseline were: Arm 1 69% (range 38-100%; n = 2), Arm 2 96% (range 78-100%; n = 6), Arm 3 92% (range 75-100%; n = 3). Decreased phosphorylated Rb levels and CDK4, CDK6, CCND2, CCND3, and CCNE1 gene expression were observed following ribociclib treatment. Ribociclib and letrozole pharmacokinetic parameters were consistent with single-agent data. The ribociclib plus letrozole combination was well tolerated, with no Grade 3/4 adverse events over the treatment. CONCLUSION: The results suggest absence of a drug-drug interaction between ribociclib and letrozole and indicate ribociclib plus letrozole may reduce Ki67 expression in HR+, HER2- BC (NCT01919229).

Asymmetries in hemispheric control of attention in schizophrenia.

Investigators have long suggested that schizophrenia might be related to an impairment in the regulation of attention. In this report, the performance of schizophrenic patients was compared with nonschizophrenic control subjects in their ability to direct visual attention. In the first experiment, patients were distinguished from controls by a slower response to a target in the right visual field than to a target in the left visual field when attention was not first directed to the target location. In the second experiment, patients were distinguished from controls by a stronger bias in favor of symbolic information over language information about spatial direction. In both experiments, the patients demonstrated deficits in attention similar to patients from previous studies who had unilateral lesions of the left hemisphere. The identification of performance abnormalities using tasks that are simple, have dissectable cognitive components, have been related to discrete neural systems, and control for nonspecific variables provide the basis for constructing reasonable hypotheses about the cognitive psychology and functional neuroanatomy of schizophrenia.

[Uncommon case of Mycobacterium bovis brain abscess complicated by suppurative fistula]. / Caso insólito de absceso cerebral por Mycobacterium bovis complicado con fístula supurativa.

TITLE: Caso insólito de absceso cerebral por Mycobacterium bovis complicado con fístula supurativa.

Neural correlates of self-induced dysphoria.

OBJECTIVE: The authors explored the question of whether acute, transient changes in mood are reflected in activation of discrete neuronal systems in the human brain. METHOD: Using positron emission tomography, they measured the regional cerebral blood flow (CBF) of seven psychiatrically healthy subjects under two conditions. During the control condition the subjects were resting with their eyes closed. During the active condition, with their eyes still closed, they were asked to imagine or recall a situation that would make them feel very sad. They were explicitly asked to experience sadness and to avoid any feelings of anger or anxiety. RESULTS: There were significant differences in regional CBF measured during the control condition and during the active condition, particularly in the inferior and orbitofrontal cortices. Women showed bilateral inferior and orbitofrontal activation, but men displayed predominantly left-sided activation in these areas. CONCLUSIONS: The authors conclude that the inferior and orbitofrontal cortices play an important role in normal emotional cognitive processes.

Neurons in Alzheimer disease emerge from senescence.

A number of cell cycle markers are associated with the selective neuronal pathology found in Alzheimer disease. However, the significance of such cell cycle markers is clouded by duplicity of function in that many such proteins are also involved in apoptosis and/or DNA repair following oxidative damage. To clarify whether or not neurons in Alzheimer disease do in fact emerge from a quiescent status, with subsequent entry into the G1 phase of the cell cycle, in this study we focused on a family of MORF4-related proteins that are associated with emergence from senescence. Our results show that many neurons in vulnerable regions of Alzheimer disease brain, but not in control brain, have increased MORF4-related proteins indicating re-entry into the cell cycle. Immunoblot analysis showed a specific disease-related increase in a 52 kDa protein that is likely the human homologue of the MORF4-related transcription factor. The novel localization of such a transcriptional activating protein to selectively vulnerable neurons in Alzheimer disease provides compelling evidence for mitotic re-entry as part of the pathogenesis of neuronal dysfunction and death in Alzheimer disease.

Hemispheric differences in processing tone frequency and amplitude modulations.

Transient frequency and amplitude modulations (FMs, AMs) of sound are requisite to speech recognition. We recorded whole-head magnetoencephalographic signals from seven subjects to binaural 620 ms 667 Hz tones, with 3, 30, or 300 ms FMs or AMs in the beginning or middle of the tone. Responses were significantly larger and earlier for FMs than AMs, for rapid than slow modulations, and for modulations at the beginning (BEG) than in the middle (MID) of the sound. BEG 3 ms FMs elicited strongest signals in the left and MID 3 ms FMs in the right hemisphere. Fast MID modulations produced significantly stronger responses in the right than left hemisphere. These differences may reflect different functions of the left and right hemisphere in speech perception.