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Background The HIV pandemic continues to cause a high burden of morbidity and mortality due to delayed diagnosis. Histoplasmosis is prevalent in Latin America and Colombia, is difficult to diagnose and has a high mortality. Here we determined the clinical characteristics and risk factors of histoplasmosis in people living with HIV (PLWH) in Pereira, Colombia. Materials and methods This was a retrospective cross-sectional study (2014–2019) involving two tertiary medical centers in Pereira, Colombia. People hospitalized with HIV were included. Histoplasma antigen detection was performed in urine samples. Probable histoplasmosis was defined according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. Results 172 HIV-infected patients were analyzed. Histoplasmosis was confirmed in 29% (n = 50/172) of patients. The logistic regression analysis showed that the risk factors for histoplasmosis were pancytopenia (OR 4.1, 95% CI 1.6–10.3, P = 0.002), 46 IU/L (OR 3.2, 95% CI 1.3–8, P = 0.010). Conclusions Histoplasmosis is highly prevalent in hospitalized patients with HIV in Pereira, Colombia. The clinical findings are nonspecific, but there are some clinical abnormalities that can lead to suspicion of the disease, early diagnosis and prompt treatment. Urine antigen detection is useful for diagnosis, but is not widely available. An algorithmic approach is proposed for low-resource clinical settings.

Geriatricians and others must embrace the emerging field of geroscience. Until recently geroscience research was pursued in laboratory animals, but now this field requires specialized expertise in the care of vulnerable older patients with multiple chronic diseases and geriatric syndromes, the population likely to benefit the most from emerging therapies. While chronological aging measures the inevitable passage of clock time that occurs equally for everyone, biological aging varies among individuals, and importantly, it is modifiable. Advances in our understanding of biological aging, the discovery of strategies for modifying its rate, and an appreciation of aging as a shared risk factor for chronic diseases have jointly led to the Geroscience Hypothesis. This hypothesis states that interventions modifying aging biology can slow its progression-resulting in the delay or prevention of the onset of multiple diseases and disorders. Here we wish to report on the Third Geroscience Summit held at National Institutes of Health on November 4-5, 2019, which highlighted the importance of engaging other disciplines including clinicians. Involvement by scientists with expertise in clinical trials, health outcomes research, behavioral and social sciences, health policy, and economics is urgently needed to translate geroscience discoveries from the bench to clinical care and health policy. Adding to the urgency of broadening this geroscience coalition is the emergence of biological aging as one the most important modifiable factors of COVID-19, combined with the inability of our society to once again recognize and confront aging as a priority and opportunity when facing these types of public health emergencies.

Durante casi un ano, la raza humana se ha visto sacudida por la aparicion de un nuevo coronavirus conocido como SARS-CoV-2, el cual se origino en China y desde alli se ha dispersado por casi todas ...

Introduction: Histoplasmosis is an opportu­nistic granulomatous fungal infection. Peritoneal histoplasmosis (PH) is a rare form of dissem­inated histoplasmosis (DH).Case description: A 44-year-old male pa­tient with history of HIV infection, systemic lupus erythematosus with lupus nephritis, and chronic kidney disease on peritoneal dialysis, presented with recurrent ascites without clear etiology in the serial study of ascitic fluid. Con­trast computed tomography of the abdomen showed a nonspecific peritoneal nodule, for which laparoscopy and biopsy were performed, identifying Histoplasma capsulatum infection. The subject received 15 days of in-hospital treatment with amphotericin B deoxycholate with good evolution, no recurrence of ascites, and indefinite outpatient management with itraconazole.Discussion: The first case of PH was described in 1970 but this is the first case reported in Co­lombia. Most cases of PH have been associated with peritoneal dialysis. Its diagnosis is based on the study of ascitic fluid and its treatment follows the guidelines of other forms DH.Conclusions: PH is a rare entity that requires high clinical suspicion, especially in immuno­compromised patients.

Introduction: Congenital fibrinogen disorders are rare conditions in which there are quantitative and qualitative alterations of factor I; the vast majority of patients are asymptomatic.Case presentation: A 19-year-old female patient with a history of congenital hypofibrinogenemia presented with spontaneous vulvar hematoma along with hypotension, tachycardia, stupor and hematoma of 20cm in the right labium majus. On admission, the young woman had hemoglobin 6.6 g/dL, fibrinogen 74 mg/dL and prolonged clotting times. She received red blood cells transfusion and cryoprecipitates, followed by surgical drainage and intravenous fibrinogen replacement, adjusting the dose according to fibrinogen levels in plasma. The patient presented progressive improvement without hemorrhagic recurrence and fibrinogen levels within the target values until hospital discharge.Discussion: Afibrinogenemia and hypofibrin­ogenemia are part of the quantitative factor I disorders; in the first case, there is total absence of circulating fibrinogen, and in the second case the levels are below 150 mg/dL. Sponta­neous vulvar hematoma as a severe hemorrhagic manifestation is not frequent in symptomatic patients; its treatment is based on fibrinogen replacement in an individualized manner and surgical management when required.Conclusion: Hypofibrinogenemia is a rare dis­ease, and fibrinogen replacement is one of the mainstays of treatment.

The data on COVID-19 is clear on at least one point: Older adults are most vulnerable to hospitalization, disability and death following infection with the novel coronavirus. Therefore, therapeutically addressing degenerative aging processes as the main risk factors appears promising for tackling the present crisis and is expected to be relevant when tackling future infections, epidemics and pandemics. Therefore, utilizing a geroscience approach, targeting aging processes to prevent multimorbidity, via initiating broad clinical trials of potential geroprotective therapies, is recommended.

Introducción: se define neumomediastino espontáneo (NE) a la presencia de aire en el intersticio mediastinal. Es una entidad rara, considerada benigna y autolimitada que afecta, en la mayoría de los casos, a adultos jóvenes. Su diagnóstico es clínico y radiológico.Descripción del caso: hombre de 21 años de edad con tos y expectoración verdosa de cuatro días, síntomas asociados a disnea, dolor torácico, fiebre y enfisema subcutáneo supraclavicular bilateral. La radiografía tórax sugirió neumomediastino, el cual fue confirmado por tomografía. El paciente fue hospitalizado para observación y tratamiento. Luego de una evolución positiva, fue dado de alta al sexto día.Discusión: el NE es un diagnóstico diferencial en pacientes que consultan por dolor torácico y disnea. Su prevalencia es inferior a 0.01% y su mortalidad es baja. Debe sospecharse en pacientes con dolor torácico y enfisema subcutáneo al examen físico. Entre 70 y 90% de los casos pueden identificarse mediante radiografía de tórax, mientras que su confirmación puede obtenerse a través de tomografía de tórax. En la mayoría de casos no requiere estudios adicionales.Conclusión: el NE es una causa poco conocida de dolor torácico agudo, rara vez se tiene en cuenta como diagnóstico diferencial; es auto limitado y tiene buen pronóstico.

Although the field of frailty research has expanded rapidly, it is still a nascent concept within the clinical specialties. Frailty, conceptualized as increased vulnerability to stressors because of significant depletion of physiological reserves, predicts poorer outcomes in several medical specialties, including cardiology, HIV care, nephrology, and in the behavioral and social sciences. Incorporation of frailty assessment and frailty research into the specialties is hindered by a lack of a consensus definition, by the proliferation of measurement tools, inadequate understanding of the biology of frailty, and lack of validated clinical algorithms for patients who have frailty. In 2015, the American Geriatrics Society, the National Institute on Aging (NIA) and the Alliance for Academic Internal Medicine held a conference for awardees of the NIA sponsored ‘Grants for Early Medical/Surgical Specialists Transition into Aging Research (GEMSSTAR)’1 program to review the current state of the knowledge regarding frailty in the sub-specialties, as well as to highlight key examples of integrating frailty research into the medical specialties. Key research questions to advance frailty research into specialty medicine are proposed.

Senescence is a tumor suppressor mechanism activated in stressed cells to prevent replication of damaged DNA. Senescent cells have been demonstrated to play a causal role in driving aging and age-related diseases using genetic and pharmacologic approaches. We previously demonstrated that the combination of dasatinib and the flavonoid quercetin is a potent senolytic improving numerous age-related conditions including frailty, osteoporosis and cardiovascular disease. The goal of this study was to identify flavonoids with more potent senolytic activity.A panel of flavonoid polyphenols was screened for senolytic activity using senescent murine and human fibroblasts, driven by oxidative and genotoxic stress, respectively. The top senotherapeutic flavonoid was tested in mice modeling a progeroid syndrome carrying a p16Of the 10 flavonoids tested, fisetin was the most potent senolytic. Acute or intermittent treatment of progeroid and old mice with fisetin reduced senescence markers in multiple tissues, consistent with a hit-and-run senolytic mechanism. Fisetin reduced senescence in a subset of cells in murine and human adipose tissue, demonstrating cell-type specificity. Administration of fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan.The natural product fisetin has senotherapeutic activity in mice and in human tissues. Late life intervention was sufficient to yield a potent health benefit. These characteristics suggest the feasibility to translation to human clinical studies. FUND: NIH grants P01 AG043376 (PDR, LJN), U19 AG056278 (PDR, LJN, WLL), R24 AG047115 (WLL), R37 AG013925 (JLK), R21 AG047984 (JLK), P30 DK050456 (Adipocyte Subcore, JLK), a Glenn Foundation/American Federation for Aging Research (AFAR) BIG Award (JLK), Glenn/AFAR (LJN, CEB), the Ted Nash Long Life and Noaber Foundations (JLK), the Connor Group (JLK), Robert J. and Theresa W. Ryan (JLK), and a Minnesota Partnership Grant (AMAY-UMN#99)-P004610401-1 (JLK, EAA).

Aging is the major risk factor for both the development of chronic diseases and loss of functional capacity. Geroscience provides links among the biology of aging, the biology of disease, and the physiology of frailty, three fields where enormous progress has been made in the last few decades. While, previously, the focus was on the role of aging in susceptibility to disease and disability, the other side of this relationship, which is the contribution of disease to aging, has been less explored at the molecular/cellular level. Indeed, the role of childhood or early adulthood exposure to chronic disease and/or treatment on accelerating aging phenotypes is well known in epidemiology, but the biological basis is poorly understood. A recent summit co-organized by the National Institutes of Health GeroScience Interest Group and the New York Academy of Sciences explored these relationships, using three chronic diseases as examples: cancer, HIV/AIDS, and diabetes. The epidemiological literature clearly indicates that early exposure to any of these diseases and/or their treatments results in an acceleration of the appearance of aging phenotypes, including loss of functional capacity and accelerated appearance of clinical symptoms of aging-related diseases not obviously related to the earlier event. The discussions at the summit focused on the molecular and cellular relationships between each of these diseases and the recently defined molecular and cellular pillars of aging. Two major conclusions from the meeting include the desire to refine an operational definition of aging and to concomitantly develop biomarkers of aging, in order to move from chronological to physiological age. The discussion also opened a dialogue on the possibility of improving late-life outcomes in patients affected by chronic disease by including age-delaying modalities along with the standard care for the disease in question.

Recently discovered interventions that target fundamental aging mechanisms have been shown to increase life span in mice and other species, and in some cases, these same manipulations have been shown to enhance health span and alleviate multiple age-related diseases and conditions. Aging is generally associated with decreases in resilience, the capacity to respond to or recover from clinically relevant stresses such as surgery, infections, or vascular events. We hypothesize that the age-related increase in susceptibility to those diseases and conditions is driven by or associated with the decrease in resilience. Thus, a test for resilience at middle age or even earlier could represent a surrogate approach to test the hypothesis that an intervention delays the process of aging itself. For this, animal models to test resilience accurately and predictably are needed. In addition, interventions that increase resilience might lead to treatments aimed at enhancing recovery following acute illnesses, or preventing poor outcomes from medical interventions in older, prefrail subjects. At a meeting of basic researchers and clinicians engaged in research on mechanisms of aging and care of the elderly, the merits and drawbacks of investigating effects of interventions on resilience in mice were considered. Available and potential stressors for assessing physiological resilience as well as the notion of developing a limited battery of such stressors and how to rank them were discussed. Relevant ranking parameters included value in assessing general health (as opposed to focusing on a single physiological system), ease of use, cost, reproducibility, clinical relevance, and feasibility of being repeated in the same animal longitudinally. During the discussions it became clear that, while this is an important area, very little is known or established. Much more research is needed in the near future to develop appropriate tests of resilience in animal models within an aging context. The preliminary set of tests ranked by the participants is discussed here, recognizing that this is a first attempt.

Over the past decade, a large number of discoveries have shown that interventions (genetic, pharmacological, and nutritional) increase the lifespan of invertebrates and laboratory rodents. Therefore, the possibility of developing antiaging interventions for humans has gone from a dream to a reality. However, it has also become apparent that we need more information than just lifespan to evaluate the translational potential of any proposed antiaging intervention to humans. Information is needed on how an intervention alters the “healthspan” of an animal, that is, how the physiological functions that change with age are altered. In this report, we describe the utility and the limitations of assays in mice currently available for measuring a wide range of physiological functions that potentially impact quality of life. We encourage investigators and reviewers alike to expect at minimum an overall assessment of health in several domains across several ages before an intervention is labeled as “increasing healthspan.” In addition, it is important that investigators indicate any tests in which the treated group did worse or did not differ statistically from controls because overall health is a complex phenotype, and no intervention discovered to date improves every aspect of health. Finally, we strongly recommend that functional measurements be performed in both males and females so that sex differences in the rate of functional decline in different domains are taken into consideration.

Resumen Objetivo Describir la prevalencia de enfermedades reumaticas en una cohorte de pacientes con infeccion por VIH y sus caracteristicas demograficas y clinicas. Pacientes y metodos Estudio descriptivo de corte transversal de una cohorte de 1.712 pacientes con infeccion por VIH, en un hospital universitario, seguidos desde enero del 2005 hasta septiembre del 2013. Resultados Se encontro una prevalencia de enfermedades reumaticas del 5,2% (n = 89 casos), el 24% de sexo femenino y el 76% de sexo masculino. Edad promedio ± desviacion estandar 45 ± 11 anos. Las enfermedades encontradas fueron: artritis reactiva 15% (n = 14), artrosis 15% (n = 14), purpura trombocitopenica inmune 11% (n = 10), otras 59% (n = 53). El tiempo promedio entre el diagnostico de VIH y la condicion reumatica fue de 73 ± 66 meses. Dentro de las comorbilidades se encontraron: dislipidemia 39% (n = 43), hepatitis B 17% (n = 19), lipodistrofia 11% (n = 12), herpes zoster 10% (n = 11) e hipotiroidismo 9% (n = 10). Conclusiones Se presenta informacion respecto a las comorbilidades reumaticas en una cohorte de pacientes con infeccion por VIH. Como se ha documentado en otras series, la artritis reactiva fue la enfermedad reumatica mas frecuente junto con osteoartrosis. Nuestro estudio evidencia una tendencia hacia el envejecimiento de los pacientes con VIH gracias a un mejor control de la enfermedad, con el uso de terapia antirretroviral, lo cual aumenta la prevalencia de osteoartrosis.

Metabolic interventions involving undernutrition but not malnutrition (e.g., caloric restriction, CR) are effective strategies for improving both health and longevity in species ranging from lower organisms to nonhuman primates. Initial human trials to test the effects of sustained, reduced energy intake have yielded promising health benefits. Through intense research efforts in understanding the molecular mechanisms of CR, three cellular pathways have now been identified although the precise details remain unknown. More recently, circadian regulation has been recognized as a novel mediator for CR effects in mice. Harnessing the molecular insights into CR, novel nutritional interventions and pharmacological application of CR mimetics have been tested showing great promise in simultaneously improving metabolic function and providing overall health benefits. Additional research is needed to identify efficacious therapeutics that can be safely and practically translated to human studies in promoting healthspan.

Age is by far the major risk factor for most chronic diseases. This has been common knowledge since time immemorial. Aging encompasses the biological changes most often seen as declines of function and increasing burden of disease. The close linkage of these two has led people to believe that aging, like age, is immutable. It is only recently that research into the basic molecular and cellular mechanisms of aging has led to potential interventions that increase lifespan and appear to increase healthspan, as well. Geroscience is an interdisciplinary field that aims to understand the relationship between the biology of aging and the biology of age-related diseases. The “geroscience hypothesis” posits that manipulation of aging will delay (in parallel) the appearance or severity of many chronic diseases because these diseases share the same underlying major risk factor (age). The hope is that this will lead to health improvements in the older population with perhaps greater efficiency than can be achieved through the successful cure and management of diseases of aging as they arise individually or as comorbidities. With those concepts in mind, the Geroscience Interest Group (GSIG) was launched as a trans-institute interest group within the NIH in November 2012. Here, we discuss the genesis of the trans-NIH group and the most salient activities that have occurred in the last 5 years.

Introducción: el infarto pulmonar ocurre entre un 29 y un 32% de pacientes con tromboembolismo pulmonar (TEP). Por su parte, la infección de un infarto pulmonar complica aproximadamente del 2 al 7% de los casos, lo que hace que el infarto pulmonar infectado sea una entidad poco frecuente.Descripción del caso: mujer de 49 años con dolor pleurítico en hemitórax izquierdo, irradiado a región dorsal, asociado a disnea y edema doloroso de miembro inferior izquierdo de dos días de evolución. Dos semanas antes de su ingreso la paciente sufrió trauma de rodilla izquierda, el cual que requirió intervención quirúrgica; sin embargo, por motivos desconocidos, no recibió profilaxis anti trombótica. En el examen físico se encontró taquicardia, taquipnea y edema doloroso con eritema en pierna izquierda. Al existir alta sospecha de tromboembolia pulmonar se inició anticoagulación y se solicitó angiotomografía de tórax, con la cual fue posible confirmar el diagnóstico. Durante su evolución, la paciente experimentó signos de respuesta inflamatoria sistémica, deterioro respiratorio. Se realizó tomografía de control sugestiva de infarto pulmonar infectado. Se inició antibiótico y la paciente mejoró de forma progresiva; después de esta mejora, fue dada de alta para continuar anticoagulación y seguimiento ambulatorios.Conclusiones: el infarto pulmonar es una complicación frecuente en pacientes con TEP. Por lo tanto, debe sospecharse infarto pulmonar infectado en pacientes con deterioro clínico y respuesta inflamatoria sistémica. La diferencia radiológica entre infarto pulmonar y neumonía no es fácil de identificar, su enfoque diagnóstico es clínico y el tratamiento anticoagulante y antimicrobiano debe iniciarse de manera oportuna.

Population aging is unprecedented, without parallel in human history, and the 21st century will witness even more rapid aging than did the century just past. Improvements in public health and medicine are having a profound effect on population demographics worldwide. By 2017, there will be more people over the age of 65 than under age 5, and by 2050, two billion of the estimated nine billion people on Earth will be older than 60 (http://unfpa.org/ageingreport/). Although we can reasonably expect to live longer today than past generations did, the age-related disease burden we will have to confront has not changed. With the proportion of older people among the global population being now higher than at any time in history and still expanding, maintaining health into old age (or healthspan) has become a new and urgent frontier for modern medicine. Geroscience is a cross-disciplinary field focused on understanding the relationships between the processes of aging and age-related chronic diseases. On October 30-31, 2013, the trans-National Institutes of Health GeroScience Interest Group hosted a Summit to promote collaborations between the aging and chronic disease research communities with the goal of developing innovative strategies to improve healthspan and reduce the burden of chronic disease.

In humans, loss of resilience precedes the development of frailty by decades. As such, measurements of resilience could potentially be used as predictors of healthspan. While advances have been made in studying resilience in the psychosocial domain, resilience to physical challenges has been largely unexplored. Important questions remain that need addressing: when does resilience to specific challenges begin to decline? Which molecular/cellular mechanisms are engaged by different challenges? Which resilience measures are most informative of the overall health of the organisms? And most importantly: which (if any) measures of resilience are predictive of future health/longevity? For many of these questions, and for future mechanistic and interventional studies, studies in humans are limiting. For this reason, the NIA has started a program to study resilience in mice that should help answer the questions above. The presentation will focus on the conceptual basis for the project, and the state of the science.

In recent years, applications in the Google Play Store have been targets for attackers. Hackers have used a slew of techniques to analyze and modify Android developers' apps. Attackers are modifying app content so they can take advantage of unknowing users. They are also analyzing app content so they can create clones of legitimate apps. Using techniques like reverse engineering, debugging attacks, and dynamic library manipulation, attackers are hacking android apps. We chose to test these techniques against certificate pinning, a method used to authenticate SSL/TLS certificates to prevent MiTM attacks. The research we conducted focused on: (1) Finding apps from the Google Play Store that employ certificate pinning as a security measure for its communications. (2) Studying the three different methods (debugging attacks, reverse engineering, and dynamic library manipulation) used for bypassing certificate pinning on Android Devices. (3) Testing the apps with each tool to see if we could bypass the certificate pinning. (4) After determining the effectiveness of the three methods, we decided to research and develop practices that would allow developers to harden their applications. Our objective is to show these deterrents succeed at protecting against these attacks.

The National Institutes of Health (NIH) Geroscience Interest Group (GSIG) sponsored workshop, The Role of Inflammation in Age-Related Disease, was held September 6th-7th, 2012 in Bethesda, MD. It is now recognized that a mild pro-inflammatory state is correlated with the major degenerative diseases of the elderly. The focus of the workshop was to better understand the origins and consequences of this low level chronic inflammation in order to design appropriate interventional studies aimed at improving healthspan. Four sessions explored the intrinsic, environmental exposures and immune pathways by which chronic inflammation are generated, sustained, and lead to age-associated diseases. At the conclusion of the workshop recommendations to accelerate progress toward understanding the mechanistic bases of chronic disease were identified.

Research on the biology of aging has accelerated rapidly in the last two decades. It is now at the point where translation of the findings into useful approaches to improve the health of the elderly population seems possible. In trying to fill that gap, a new field termed geroscience will be articulated here that attempts to identify the biological underpinnings for the age-dependency of most chronic diseases. Herein, I will review the major conceptual issues leading to the formulation of geroscience as a field, as well as give examples of current areas of inquiry in which basic aging biology research could lead to therapeutic approaches to address age-related chronic diseases, not one at a time, but most of them in unison.

Aging is associated with a deterioration of the acute phase response to inflammatory challenges. However, the nature of these defects remains poorly defined. We analyzed the hepatic inflammatory response after intraperitoneal administration of lipopolysaccharide (LPS) given to Fisher 344 rats aged 6, 15, and 22-23 months. Induction of the acute phase proteins (APPs), haptoglobin, alpha-1-acid glycoprotein, and T-kininogen was reduced and/or retarded with aging. Initial induction of interleukin-6 in aged rats was normal, but the later response was increased relative to younger counterparts. An exacerbated hepatic injury was observed in aged rats receiving LPS, as evidenced by the presence of multiple microabscesses in portal tracts, confluent necrosis, higher neutrophil accumulation, and elevated serum levels of alanine aminotransferase, relative to younger animals. Our results suggest that aged rats displayed a reduced expression of APPs and increased hepatic injury in response to the inflammatory insult.

Kinins are vasoactive peptides released from precursors called kininogens, and serum levels of both T- and K-kininogens increase dramatically as rats age. Kinin release is tightly regulated, and here we show that serum kinin levels also increase with age, from 63 +/- 16 nmol/L in young Fisher 344 rats to 398 +/- 102 nmol/L in old animals. Both K- and T-kininogens contribute sequentially to this increase, with the increase in middle-aged animals being driven primarily by K-kininogen, whereas the further augmentation in older rats occurs by increasing T-kininogen. By measuring ERK activation, we show that aorta endothelial cells from old animals are hyporesponsive to exogenous bradykinin. However, if serum kinin levels are experimentally decreased by lipopolysaccharide treatment, then the endothelial response to bradykinin is re-established. These results indicate that serum levels of kinins increase with age, whereas the responsiveness of target cells to kinins is reduced in these same animals.

Trasylol is a trade mark for Aprotinin, sold at 1.4 mg protein/ml. It is commercialized by Bayer AG, Grubenstrasse 6, CH-8045 Zurich, Switzerland.