Extreme Age Research Articles

Neuroproteomics of cognitively healthy centenarians in the context of aging and Alzheimer's disease.

Aging is often accompanied by neurodegenerative diseases such as Alzheimer's disease (AD), and their associated neuropathological hallmarks. Few individuals are able to maintain cognitive health until extreme ages, such as cognitively healthy centenarians, despite displaying substantial pathology in their brains. Here we report on a unique and large single-center proteomics study providing insight into proteome changes occurring with AD and aging. We investigate which mechanisms could be involved in maintaining cognitive health at extreme ages in the presence of pathology. We performed quantitative proteomics on middle temporal lobe tissue for a cohort of 61 non-demented and 91 AD individuals across the age-continuum, and 58 centenarians from the 100-plus Study. We performed enrichment analyses for cell-types and GO-terms using multiple approaches (Figure 1). We identified 3,448 proteins, among which proteins associated with AD Braak stage or age. 472 proteins were associated with Braak stages, independent of age. Cell-type enrichment revealed that with increasing Braak stages, the abundance of astrocytic proteins increased while the abundance of neuronal proteins decreased. Among centenarians we identified 13 proteins that that differ in abundance from AD cases with the same Braak stage (IV). These included ubiquitin, cytoskeletal and synaptic proteins. Additionally, we identified 174 age-related proteins in non-demented controls. Of these, 97 were expressed in centenarians at levels different from those predicted for their age. Cell-type enrichment revealed that the abundance of oligodendrocytic proteins decreased with age, whereas the abundance of astrocytic proteins was increased with age and Braak stage. Progressive AD stages are associated with increased abundance of astrocytic- and lower abundance of neuronal proteins, while healthy aging is associated with a lower abundance of oligodendrocytic proteins and higher abundance of astrocytic proteins. In this study we identified proteins in the centenarians that deviate in level from prediction based on age. How these proteins act on cognition needs to be investigated further. Centenarian-specific proteins at Braak stage IV may indicate mechanisms protecting against cognitive decline, whereas the centenarian-specific age-related proteins might indicate processes that prevent adverse brain aging.

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Clinicopathological characteristics in women with breast cancer in extreme ages in Greece: A single centre experience

Abstract Introduction Breast cancer is the most common malignancy in Greek women. The highest incidence occurs in patients aged 40–70 years. However, the emergence of the disease in women under 40 and over 80 years old is a significant problem in everyday practice, because of the diagnostic and therapeutic challenges for these age groups. The objective of this study is to investigate clinicopathological characteristics of Greek women under 40 and over 80 diagnosed with breast cancer during 2019–2020 in a specialized Breast Cancer Surgical Centre, as well as the pathological characteristics of their disease and the therapeutic measures applied to these women. Aim of the study The aim of this study is to compare clinical and pathological characteristics of breast cancer in a group of Greek premenopausal women younger than 40 years of age with a group of elderly women older than 80 years old, who were treated in a surgical breast centre in Greece during the last two years. Patients and Methods During the last 2 years, 21 women under 40 and 22 women older than 80 were diagnosed with breast cancer in our Centre. Results Invasive ductal adenocarcinoma was the most frequent histological type for both Groups: Most younger women underwent surgery followed by chemotherapy, while the majority of older patients received hormonal therapy after surgery. Conclusions There were no statistically significant differences between women under 40 and women over 80 in the study sample regarding their clinicopathological characteristics. However, younger women underwent more therapeutic modalities (i.e.adjuvant treatments in addition to surgery) than older ones.

Antimicrobial Resistance Pattern of Bacterial Meningitis Among Patients in Quetta, Pakistan.

IntroductionBacterial meningitis (BM) is a lethal infectious disease that persists as a substantial cause of morbidity and mortality. The antimicrobial drug resistance in BM pathogens poses a major threat to the community while raising challenges for clinicians. For the first time, we elucidate the incidence rate of BM and its drug resistance among the population of Quetta, Balochistan.MethodsA cross-sectional study was conducted (from January 2018 to March 2021) among meningitis patients admitted to government hospitals in Quetta. The cerebrospinal fluid (CSF) specimen was collected and processed for microbiological and cytological analysis. Bacterial isolates were identified and confirmed using phylogenetic analysis of the 16S rRNA gene.ResultsWe found 35.9% (321/894) confirmed cases of BM among the population of Quetta, Balochistan. The identified bacterial isolates comprised Streptococcus pneumoniae 14.7% (130/894), Staphylococcus aureus 6.9% (61/894), Neisseria meningitidis 5.7% (51/894), Haemophilus influenzae 2.5% (22/894), Escherichia coli 4.5% (40/894), and Klebsiella pneumoniae 1.9% (17/894). A high percentage in male patients of 20.8% (186/894) was identified as compared to female patients of 15.1% (135/894). Extreme age groups such as infants (age range: 1 month to 1 year) and adults (age range: 61 years to 99 years) with low immunity were critically affected by BM. Clinical parameters such as abnormal CSF appearance, pH, and high WBCs in BM patients with endocarditis as the underlying disease were significantly at elevated risk of fatal outcome. 16S rRNA gene phylogenetic analysis confirmed the evolutionary similarity of isolated strains with prevailing pathogenic strains in Asia. Furthermore, age was identified as a significant risk factor for clinical outcomes.ConclusionThe majority of the identified BM patients belonged to rural areas with limited health-care facilities and paramedic staff. The high case fatality rate 11% demonstrates increased antibiotic resistance among BM isolates, thereby stimulating its devastation in underdeveloped regions. Timely detection and intensive treatment of BM may improve critical outcomes in patients.

Mortalidad materna un Problema Multifactorial de Salud Pública – Hospital Belén de Trujillo (Factores de Riesgo)

The present study aims to determine the factors significantly associated with maternal mortality, it is a retrospective observational study, of cases and controls, two groups were formed: Case Group (63): pregnant women who leave the hospital alive, registered in the General Office of Epidemiology of the Hospital and in the Perinatal Computer System 2000 (SIP 2000), and Control Group (315): pregnant women who leave the hospital alive, registered in the Perinatal Computer System 2000 (SIP 2000). The chi-square test was used in the bivariate analysis and the OR and its 95% CI were used as a statistician. It is concluded that the most significant factors among the socioeconomic factors: The non-origin of the Trujillo district (OR = 2.04), Studies until primary (OR = 6.82), Distance to the hospital greater than 10 km (OR = 4.47) and time elapsed until reaching the major hospital 10 minutes (OR = 2.22); Among the gyneco-obstetric factors significant to explain maternal mortality we find: extreme age (OR = 2.43), Multiparity (OR = 4.19), Non-term delivery (OR = 4.26), lack of prenatal control ( OR = 5.4), similarly, Preeclampsia / Eclampsia (OR = 5.76), and Placenta previa (OR = 10.61).

Mobilization and fractionation of Ti-Nb-Ta during exhumation of deeply subducted continental crust

The behavior of Ti-Nb-Ta is crucial to reveal the genesis of island arc magmatism. However, mobilization and fractionation of Ti-Nb-Ta in subduction zone settings remain poorly understood. The discovery of felsic veins rich in coarse-grained rutile within retrograde eclogite of the North Qaidam UHP metamorphic belt provides a unique and novel opportunity to study age variation during rutile formation and alteration, as well as Ti-Nb-Ta mobility and fractionation during fluid/melt-rock interaction. Rutile high-resolution elemental mapping, and U-Pb bulk grain (ID-TIMS), and in-situ U-Pb geochronology have been utilized to focus on the properties of rutile in both, felsic vein and retrograde eclogite host to gain insight into possible similarities and differences. Three groups of rutile were distinguished according to its host rock, trace elements signature, and genetical connection to ilmenite: eclogite-hosted rutile (Rt-1), felsic vein-hosted rutile not associated with ilmenite (Rt-2a), and associated with ilmenite (Rt-2b). Field evidence and rutile trace elements characteristics document the source of vein-hosted rutile to be mainly derived from the eclogite during fluid/melt-rock interaction. Principal Component Analysis reveals that Nb, Ta, Sn, and W are more enriched in Rt-2a compared to Rt-1; Rt-2b has higher Nb, U, and Hf than Rt-2a. High-resolution mapping across large rutile grains shows the enrichment of high field strength elements (HFSEs) in rutile near to ilmenite, which indicates a HFSEs back diffusion from the rutile–ilmenite boundary during the replacement of rutile by ilmenite. The Nb/Ta ratios of Rt-2a are lower than those of Rt-1, which result from different partition coefficients of Nb and Ta during fluid/melt-rock interaction. The diffusion-influenced rutile exhibits suprachondritic Nb/Ta ratios and demonstrates that diffusion of Nb in rutile is higher than that of Ta under identical P-T conditions. Rutiles Rt-1 and Rt-2a yield consistent 206Pb/238U ages of 426–423 Ma, which is similar to the 433 ± 3 Ma determined by ID-TIMS results of bulk rutile grains. This indicates that Ti-Nb-Ta must have been mobilized during the exhumation of deeply subducted continental crust. However, the diffusion-influenced rutile shows a large variation of ages compared to the rutile not associated with ilmenite, demonstrating that the back-diffusion may affect the U-Pb system in rutile. Therefore, when rutile is partially altered into ilmenite or titanite, its dating should be used with caution. Thus, this study demonstrates volume diffusion is a very important geological process to result in extreme HFSEs fractionation and age variation of rutile on the mineral scale. The rutile aggerates that occur in the felsic veins in 3–5 m distance to the adjacent retrograde eclogite suggest that Ti-Nb-Ta-rich melts/fluids were transported over a distance of at least several meters and that rutile does not represent a residual phase of the Na-Si-Al-, F- and CH4-bearing fluid/melt environment that formed during anatexis of the subducted continental crust. The formation of rutile-rich aggregates during the generation, transport, and crystallization of subducted continental crust-derived melts/fluids in the deep roots of orogenic belts may be a critical trigger for the depletion of HFSEs in arc magmatic rocks during the formation of the continental crust.

Narrating the New Age of EXtREmes

Narrating the New Age of EXtREmes

Molecular dating of the blood pigment hemocyanin provides new insight into the origin of animals.

The Neoproterozoic included changes in oceanic redox conditions, the configuration of continents and climate, extreme ice ages (Sturtian and Marinoan), and the rise of complex life forms. A much-debated topic in geobiology concerns the influence of atmospheric oxygenation on Earth and the origin and diversification of animal lineages, with the most widely popularized hypotheses relying on causal links between oxygen levels and the rise of animals. The vast majority of extant animals use aerobic metabolism for growth and homeostasis; hence, the binding and transportation of oxygen represent a vital physiological task. Considering the blood pigment hemocyanin (Hc) is present in sponges and ctenophores, and likely to be present in the common ancestor of animals, we investigated the evolution and date of Hc emergence using bioinformatics approaches on both transcriptomic and genomic data. Bayesian molecular dating suggested that the ancestral animal Hc gene arose approximately 881Ma during the Tonian Period (1000-720Ma), prior to the extreme glaciation events of the Cryogenian Period (720-635Ma). This result is corroborated by a recently discovered fossil of a putative sponge ~890Ma and modern molecular dating for the origin of metazoans of ~1,000-650Ma (but does contradict previous inferences regarding the origin of Hc ~700-600Ma). Our data reveal that crown-group animals already possessed hemocyanin-like blood pigments, which may have enhanced the oxygen-carrying capacity of these animals in hypoxic environments at that time or acted in the transport of hormones, detoxification of heavy metals, and immunity pathways.

Chronopharmacology in Therapeutic Drug Monitoring-Dependencies between the Rhythmics of Pharmacokinetic Processes and Drug Concentration in Blood.

The objective of the optimization of pharmacotherapy compliant with the basic rules of clinical pharmacology is its maximum individualization, ensuring paramount effectiveness and security of the patient’s therapy. Thus, multiple factors that are decisive in terms of uniqueness of treatment of the given patient must be taken into consideration, including, but not limited to, the patient’s age, sex, concomitant diseases, special physiological conditions (e.g., pregnancy, lactation, extreme age groups), polypharmacotherapy and polypragmasia (particularly related to increased risk of drug interactions), and patient’s phenotypic response to the administered drug with possible genotyping. Conducting therapy while monitoring the concentration of certain drugs in blood (Therapeutic Drug Monitoring; TDM procedure) is also one of the factors enabling treatment individualization. Furthermore, another material, and yet still a marginalized pharmacotherapeutic factor, is chronopharmacology, which indirectly determines the values of drug concentrations evaluated in the TDM procedure. This paper is a brief overview of chronopharmacology, especially chronopharmacokinetics, and its connection with the clinical interpretation of the meaning of the drug concentrations determined in the TDM procedure.

Some of Earth’s longest-lived fish show how to reach extreme ages

Some of Earth’s longest-lived fish show how to reach extreme ages

Prevalence of Thrombocytopenia Among Iron Deficiency Anemia in Arab Population in Qatar

Prevalence of Thrombocytopenia among Iron Deficiency Anemia in Arab population in QatarINTRODUCTION / BACKGROUNDIron deficiency anemia is a common cause of anemia, and account for almost half of the causes of all anemias. It is well known and common that iron deficiency anemia can be with thrombocytosis, A study reviewed 450 patients with a diagnosis of anemia between 2002 and 2006 was performed in which 143 of them were having IDA found that 31% of them were having associated thrombocytosis (4).A retrospective study conducted in Turkey found that Iron deficiency anemia and thrombocytopenia found in 13 from 615 patients (2.1%) (5). IDA and thrombocytopenia are found in certain ethnicity where we don t have data from studies about Arab Population.Materials and MethodsWe retrospectively reviewed the electronic medical records of patients attended hematology/ IV iron room clinics with the diagnosis of IDA over 2 years from the period between December 2017 to December 2019 in Hamad Medical Corporation, Qatar. Complete blood count and iron parameters were collected and analyzed. Thrombocytopenia was defined as Platelet count of less than 150 × 109/L. Statistical analysis was done using mean and SD and paired t test to compare variables after versus before treatment.Depending on previous studies available in the literature, the prevalence of IDA and thrombocytopenia reported from the study done in Turkey (2.1%), based on this we expect the prevalence estimates in Arab population is 3% (with margin of error +/- %) and confidence level 95%, the required sample size needed would be a total of 1744 participants +- 0.8. The adequate sample size was determined using the following statistical equation:Inclusion Criteria: •Arab Female who is diagnosed with iron deficiency anemia or iron depleted and receive iron therapy.Exclusion criteria: •Extreme age less than 18 and above 65•Any chronic organ dysfunction or failure•Previous bariatric surgery or gastrostomy•Malignancy (Known or discovered at any time during study follow up)Results:Out of 1752 cases of IDA, 39 cases had thrombocytopenia, (2.2 %) (table 1) with mean age of 41.38. The mean Platelet count was 108 x 10^9 in patients with thrombocytopenia while it was 325 x 10^9 in non-thrombocytopenia patients. Platelets count mean increased to 179 x 10^9 after iron replacement (p < 0.05). Analysis of thrombocytopenia according to nationalities was obtained which showed 28 cases among Qatari's (2.2%), 4.1 % in Egyptians, 3.8% in Yemenis, 3.1% Sudanese, 2.9%,2.7% in Jordanian and Syrian respectively and 1.1% in other nationalities (table 2).Discussion:Qatar is multinational country with large number of expatriates working in it. In our study thrombocytopenia occurred in 39 cases out of 1752 cases included in the study which represent 2.2% of them. Most of our patients were of Qatari nationality 1327 in which 28 cases of thrombocytopenia were found, with 3.8 % in Egyptian the 2nd most common Arab residents in Qatar. Further analysis according to nationalities revealed 3.1%, 2.9%, 2.7% in Yemenis, Sudanese and Jordanian patients, with 1.1% in other patients from other Arab nationalities.Comparison of blood parameters including platelet count before and after iv iron therapy were obtained which showed mean platelet count was 108 x 10^9 which increased to 179 x 10^9 after iron therapy, The mechanisms for the thrombocytopenia associated with IDA are not well established, although iron plays a critical role both in the synthesis of platelets and in the regulation of thrombopoiesis.Other blood parameters including WBC, ANC, Lymphocyte count showed decremental responses after iron therapy with WBC dropped from 6.3 to 6.1, ANC from 3.5 to 2.7 and lymphocyte count from 1.9 to 1.8 in thrombocytopenic patients.Conclusion:The prevalence of thrombocytopenia among IDA in Qatar was 2.2%, which normalized after iv iron therapy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

MGUS and Chip: Two Faces, but Not of the Same Medal

Clonal, pre-clinical expansions of hematopoietic cells are increasingly recognized. Clonal hematopoiesis of indeterminate potential (CHIP) has been recently described. It is characterized by the presence of mutations usually involved in myeloid neoplasia in people without any sign of hematological malignancy. Well before CHIP, another pre-clinical clonal expansion has been described for plasma cells (PC) based on the presence of a serum monoclonal protein, namely monoclonal gammopathy of undetermined significance (MGUS). Despite both being frequent, the association between these two bone marrow (BM) clonal entities has not been determined yet. Since the incidence of MGUS and CHIP rises with age reaching >10% of people >70y, we analyzed a unique oldest-old population dataset to define a possible association between these two different BM clonal disorders.We analyzed a cohort of 777 patients with a median age of 91 years (range, 81 - 104), significantly higher than previous studies on MGUS. 579 (74.5%) were females and 198 (25.5%) males. CHIP was assessed in all but 45 through sequencing of a myeloid specific gene panel. Serum protein electrophoresis was available in all of them to assess the prevalence of MGUS. The prevalence of CHIP and MGUS were 17.5% (128/732) and 9.5% (74/777), respectively. Importantly, CHIP and MGUS did not associate in our cohort but rather showed a non-significant trend towards anti-correlation (Fisher's Exact test, p-val = 0.09). We then tested associations with different clinical and laboratory features, finding that, as expected, MGUS associated with higher concentration of gamma-globulins (Wilcoxon test, p-val = 0.01414), but also with absolute lower levels of albumin (Wilcoxon test, p-val = 0.01398). No significant association was found with the mean corpuscular value (MCV), hemoglobin levels or age. These results were confirmed by a logistic univariate model, in which also the male gender resulted associated with the presence of a monoclonal component with borderline significance. Then, to further corroborate our results we performed univariate linear regression analyses. Given that CHIP and MGUS are mainly considered two aging conditions, we investigated in linear regression models the impact of age, as a continuous variable, on other clinical features. In particular, we observed that the increase of age was significantly correlated with lower albumin levels (F-stat: 1.921e+04, Adj R-squared: 0.9288, p-val: < 2.2e-16), decreasing hemoglobin concentration (F-stat: 1.434e+05, Adj R-squared: 0.9898, p-val < 2.2e-16), increasing levels of gamma-globulins (F-stat: 9.21e+04, Adj R-squared: 0.9843, p-val < 2.2e-16) and higher MCV (F-stat: 18.04, Adj R-squared: 0.01144, p-val 2.3e-05). Then, a significant anti-correlation between gamma-globulin and serum albumin levels was also confirmed (F-stat: 2.807e+04, Adj R-squared: 0.9501, p-val < 2.2e-16). Finally, we implemented two different multivariate logistic models using as independent variables the presence or absence of MGUS or CHIP, respectively. In these models, the presence of a monoclonal component was only positively associated with a higher level of gamma-globulins (Est: 0.16238, p-val = 0.00079) and not with increasing age (Est: 0.02680, p-val = 0.31819). Interestingly, the presence of an MGUS confirmed a tendency to an anti-correlation with the presence of CHIP (Est: -0.78959, p-val = 0.06468). On the contrary, CHIP as independent variable resulted significantly correlated with increasing age (Est: 0.07396, p-val = 0.00021). The spectrum of mutations in CHIP cases with or without MGUS was not significantly different, with DNMT3A and TET2 being the most frequently mutated genes.Our study shows that, in a large cohort of oldest-old patients, CHIP and MGUS are not correlated but follow two seemingly independent patterns, showing a tendency to a mutual exclusivity and associating with different clinical and laboratory values. One limitation of our study is the skewing towards female sex, where MGUS is less prevalent, but this is explained by the cohort's median age knowing that females have a longer expected life. Based on this, our findings that CHIP but not MGUS increased with age in our cohort suggest different selective pressures in this extreme age range. These results warrant further investigation as to whether there could be age-specific drivers for MGUS, and their clinical relevance. DisclosuresBolli: Amgen: Honoraria; Takeda: Honoraria; Janssen: Consultancy, Honoraria; Celgene/BMS: Consultancy, Honoraria.

The Great Prehistoric Art Swindle: André Breton and Palaeolithic Cave Painting

At Pech Merle in 1952, André Breton provoked a controversial incident by damaging a Palaeolithic wall painting that he suspected to be a fake. This episode provides an insight into the contested status of prehistoric sites in post-war France and the theoretical and ideological implications of their cultural mobilization. Such sites allowed for a disavowal of wartime trauma and supported the reaffirmation of French national identity and its civilizing mission by locating the birthplace of human culture on French soil. Yet their extreme age also threw into relief the relative fragility of the recently invented nation-state. Breton's vandalism cast doubt on the models of cultural progress and pre-eminence that sought to instrumentalize prehistoric art but failed to appreciate the subversiveness of its ‘deep’ history. Ironically, however, Breton's scepticism ultimately enhanced the subversive dimension of archaeology by allowing it to demonstrate the authenticity and age of cave art.

Outcomes in Nonagenarians with Hip Fractures Treated Conservatively and Surgically.

Introduction:We aimed to assess the clinical outcomes in nonagenarians following a hip fracture. We also further investigated the factors that influence these outcomes, such as method of treatment (operative versus conservative), co-morbidities, and pre-morbid function.Materials and methods:We studied 65 nonagenarians that were identifiable from our hospital hip fracture database. We reviewed various parameters of these patients admitted after sustaining a hip fracture (neck of femur or intertrochanteric) and investigated how these parameters affected patient outcomes. The main outcomes studied were: inpatient morbidity, and mortality at one year.Results:Inpatient morbidity was more likely in patients with an ASA grade of 3 to 5. Urinary tract infection was the most common medical complication. The 1-year mortality was 15.4% and was significantly influenced by advancing age. Surgically managed patients had a 1-year mortality rate (14.3%) slightly less than non-operative patients (17.4%). Post injury mobility was significantly better in those who received operative treatment with 63% of surgical cases regaining ambulatory status versus 7% of conservatively managed patients.Conclusions:We presented the outcomes of hip fractures in an extreme age group in the population. In nonagenarians with hip fractures surgery was associated with a 1-year mortality rate of 14.3% which is comparable to the general hip fracture population and less than the mortality rate of conservatively managed patients (17.4%). The primary advantage of surgery would be that two-thirds of patients return to ambulatory status. This information is useful to counsel patients and their families especially since the elderly are often more fearful of surgical intervention.

BIOLOGICAL AGE: METHODOLOGY FOR DETERMINING

The analytical review is devoted to the methodology for quantifying age-related changes, namely, the determination of biological age (BA). In contrast to the chronological age (CA), which is the same for all people born at the same time, BA can vary significantly and characterizes the rate of aging. Diagnostics of accelerated aging is of great clinical importance, as it allows predicting the development of age-related pathology. In addition, the BA calculation is used to assess various effects on the body, including geroprotectors. To calculate BA, a set of biomarkers of aging (BMA) is used. The most accurate method for determining BA is by measuring the methylation of certain genes (Horvath clock). However, this method is not available for clinical practice yet. Therefore, the development of BA models based on clinical BMS remains relevant. In addition, there is a need to assess the degree of age-related changes at the level of individual functional systems of the body (functional age). The list of BMA available for use in clinical practice is given in this review. The requirements are given that allow using the indicator of age-related changes as BMA. The main methods for calculating BV are multiple linear regression (MLR), principal component analysis (PCA), Klemera and Doubal method (KDM), and neural network analysis. The criteria for assessing the quality of the BA model are described in this review. The MLR method, due to its simplicity, is most often used in clinical practice, however, it has a significant drawback, namely, the systematic error in calculating age, which is most pronounced in the extreme age groups. The article provides a method for correcting this error developed by the authors. The methodology of using MLR to obtain a formula for determining BA from a dataset BMA is described in detail. The theoretical foundations of the use of neural network algorithms for assessing the rate of aging are presented. The use of neural networks for assessing BA has shown their high efficiency by all criteria, in particular, the absence of a systematic error inherent in MLR-based methods. Keywords: biological age, biomarkers of aging, calculation methods.

Traumatic Brain Injury: An Age-Dependent View of Post-Traumatic Neuroinflammation and Its Treatment.

Traumatic brain injury (TBI) is a leading cause of death and disability all over the world. TBI leads to (1) an inflammatory response, (2) white matter injuries and (3) neurodegenerative pathologies in the long term. In humans, TBI occurs most often in children and adolescents or in the elderly, and it is well known that immune responses and the neuroregenerative capacities of the brain, among other factors, vary over a lifetime. Thus, age-at-injury can influence the consequences of TBI. Furthermore, age-at-injury also influences the pharmacological effects of drugs. However, the post-TBI inflammatory, neuronal and functional consequences have been mostly studied in experimental young adult animal models. The specificity and the mechanisms underlying the consequences of TBI and pharmacological responses are poorly understood in extreme ages. In this review, we detail the variations of these age-dependent inflammatory responses and consequences after TBI, from an experimental point of view. We investigate the evolution of microglial, astrocyte and other immune cells responses, and the consequences in terms of neuronal death and functional deficits in neonates, juvenile, adolescent and aged male animals, following a single TBI. We also describe the pharmacological responses to anti-inflammatory or neuroprotective agents, highlighting the need for an age-specific approach to the development of therapies of TBI.

Carriage of Multidrug-Resistant Bacteria in Healthy People: Recognition of Several Risk Groups.

The increase in multidrug-resistant (MDR) bacteria in hospitalized people and the hospital environment has been thoroughly documented. In contrast, little is known about their presence in the community. However, increasing evidence is showing a high level of carriage in people without infectious signs. Colonized people can later develop infections due to MDR bacteria and may be able to transmit them to susceptible people (the number of which is increasing worldwide), for example, people with comorbidities such as diabetes, cancer, or inflammatory diseases and those in extreme age groups. Risk factors for the acquisition of MDR bacteria are as follows: (1) residence or travel in countries with high levels of MDR bacteria; (2) occupational risks such as health workers or people with close contact with animals (farmers, veterinarians) who frequently use antibiotics; and (3) comorbidities. Eradication is rather difficult and, thus far, has not shown clear-cut results. Preventive measures will be important in the future with a reinforcement of hygienic measures not only in the hospital, but also in the community.

End-of-life targeted degradation of DAF-2 insulin/IGF-1 receptor promotes longevity free from growth-related pathologies.

Preferably, lifespan-extending therapies should work when applied late in life without causing undesired pathologies. Reducing insulin/insulin-like growth factor (IGF)-1 signaling (IIS) increases lifespan across species, but the effects of reduced IIS interventions in extreme geriatric ages remains unknown. Using the nematode Caenorhabditis elegans, we engineered the conditional depletion of the DAF-2/insulin/IGF-1 transmembrane receptor using an auxin-inducible degradation (AID) system. This allowed for the temporal and spatial reduction in DAF-2 protein levels at time points after which interventions such as RNAi become ineffective. Using this system, we found that AID-mediated depletion of DAF-2 protein surpasses the longevity of daf-2 mutants. Depletion of DAF-2 during early adulthood resulted in multiple adverse phenotypes, including growth retardation, germline shrinkage, egg retention, and reduced brood size. By contrast, AID-mediated depletion of DAF-2 post-reproduction, or specifically in the intestine in early adulthood, resulted in an extension of lifespan without these deleterious effects. Strikingly, at geriatric ages, when 75% of the population had died, AID-mediated depletion of DAF-2 protein resulted in a doubling in lifespan. Thus, we provide a proof-of-concept that even close to the end of an individual's lifespan, it is possible to slow aging and promote longevity.

Current Trends of Gram-negative Bacteremia in a State of North India, the Forthcoming Challenges IGMC Shimla

Background: Vascular endothelial dysfunction plays a critical role in the evolution of sepsis there is an increase in vascular permeability leading to coagulation abnormalities and subsequent dysfunction of major organs.1 Bloodstream infections are a cause of life-threatening complications in all age groups of the population especially the extreme age groups who are very much prone to the risk. Antibiotic usage is associated with bacteremia, septicemia, and mortality through many factors. We are aware that Gram-negative bacteria due to many causes are becoming increasingly resistant to the currently used antimicrobial therapy. Here, in this study, we report the incidence and etiology and of the Gram-Negative bacterial isolates and their clinical significance from our tertiary care institute located in the Northern part of India.&#x0D; Materials and Methods: Prospective Observational Study conducted in the Department of Microbiology IGMC Shimla for a tenure of one year to determine the incidence and etiology of Gram-negative bacterial isolates and their antimicrobial resistance profile. All the blood culture samples received in the Department of Microbiology IGMC Shimla for culture by Bactec Bd fx from July 2015 to June 2016 were included in the study except for falling in the exclusion criteria. The blood culture was observed in the Bactec bd fx system for at least 5 days before they are reported as sterile.&#x0D; Results: Among the total 1275 cultures which were positive for bacteria, 931(73.02%) were positive for Gram-negative bacteria. Among the total of 931culture that were positive for Gram-negative bacteria, The Non-fermenter group of organisms was isolated in 292(31.36%) cultures, followed by E. coli 266(28.57%). Among the total of 931 cultures positive for GNB, a maximum of 335 (35.98%) belonged to 0-1 year. Among them, 574 (61.65%) were males while 357 (38.35%) were females.&#x0D; Conclusion: Nonfermenter group was the commonest organism among Gram-negative isolates. Infants were more commonly positive as compared to another age group. Males were more commonly culture positive as compared to females among gram-negative isolates.

738Health Status and Quality of Life of Indigenous Elderly Population of Bangladesh

Abstract Background Indigenous people, although constitute 1.8% of the country’s population, are one of the most deprived communities of Bangladesh in all sectors. This study was conducted to explore the health status and quality of life of indigenous elderly of Bangladesh as there is scarcity of knowledge regarding this. Methods A mixed-method approach was deployed on October,2019 in Sylhet-division of Bangladesh. A cross-sectional survey was conducted among 400 indigenous elderlies from 8 tea-gardens and ten in-depth-interviews were conducted with health-service providers of tea-garden health-facilities. Results Of the indigenous elderly-respondents, majority (79.5%) were suffering from any kind of chronic diseases. Visual difficulty was found predominant (74%) among the chronic conditions, followed by locomotion difficulty (49%) and gastrointestinal problem (41%). Extreme age, being male, living alone and low family income were significantly associated with suffering from chronic conditions. Furthermore, having chronic condition and extreme-age was found to be significantly associated with low quality of life. Health-service providers identified lack of logistical support in health-facilities, economic crisis and lack of awareness as the causes of poor health-status and health-seeking behavior of the indigenous elderly. Conclusions Indigenous older men in extreme old age are more vulnerable to adverse health conditions and poor quality of life. Health literacy and health seeking behaviour is poor among indigenous older adults generally and there is a huge gap in the health services and social supports available to them. Key messages Indigenous, Older population, Bangladesh.