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We conducted a development and standardization of an IgG ELISA assay for serological detection of human orthohantavirus infections using the recombinant antigen rLECH13 produced in bacterial and derived from the LECHV. The evaluation and standardization were carried out by analyzing serum samples from a total of 50 patients with confirmed Hantavirus Pulmonary Syndrome (HPS) diagnosis through the reference technique, 50 negative sera, and 53 patients with other medical conditions. The data from the assay analysis showed a diagnostic sensitivity value of 95% and a diagnostic specificity of 80%. The high sensitivity of this novel assay leads us to conclude that rLECH13 is a feasible option for use in the immunodiagnostic of orthohantavirus infection. Additionally, it is crucial to have an antigen that can be produced under conditions that do not require highly complex laboratories. Furthermore, the new assay is cost-effective, reproducible, and demonstrates excellent performance., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

We explore through the lens of distant reading the evolution of discourse on Jews in France during the XIX century. We analyze a large textual corpus including heterogeneous sources-literary works, periodicals, songs, essays, historical narratives-to trace how Jews are associated to different semantic domains, and how such associations shift over time. Our analysis deals with three key aspects of such changes: the overall transformation of embedding spaces, the trajectories of word associations, and the comparative projection of different religious groups over different, historically relevant semantic dimensions or streams of discourse. This allows to show changes in the association between words and semantic domains (referring e.g. to economic and moral behaviors), the evolution of stereotypes, and the dynamics of bias over a long time span characterized by major historical transformations. We suggest that the analysis of large textual corpora can be fruitfully used in a dialogue with more traditional close reading approaches-by pointing to opportunities of in-depth analyses that mobilize more qualitative approaches and a detailed inspection of the sources that distant reading inevitably tends to aggregate. We offer a short example of such a dialogue between different approaches in our discussion of the Second Empire transformations, where we mobilize the historian's tools to start disentangling the complex interactions between changes in French society, the nature of sources, and representations of Jews. While our example is limited in scope, we foresee large potential payoffs in the cooperative interaction between distant and close reading., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer LL declared a past collaboration with one of the authors SS to the handling editor., (Copyright © 2022 Levis Sullam, Minello, Tripodi and Warglien.)

Since the identification of Junin virus in the 1950s, many studies were carried out in wild rodents within the endemic area of the Argentine Hemorrhagic Fever (AHF) that recorded also the activity of the lymphocytic choriomeningitis virus (LCMV) and the Latino virus (LATV). The absence of confirmed cases of AHF since the 1990s in the department of Rio Cuarto, Córdoba province, promoted ecoepidemiological surveillance of infection of Calomys musculinus (Junin virus reservoir) and the search of reservoirs of the other mammarenaviruses. During two years of seasonal sampling, with a capture, mark and release system, 857 rodents were captured, corresponding 57.3% to the rodent reservoirs: C. musculinus, C. venustus and Mus musculus, being the first the most abundant species. Antibodies were detected and the three viral agents were molecularly characterized, showing a prevalence of infection of 3.5% (9/254) for Junin virus, 100% (3/3) for LCMV and 24.1% (21/87) for LATV. In conclusion, we demonstrated Junin virus circulation in its rodent reservoir in a region considered historic for AHF with potential risk for the population and the spatio-temporal co-circulation of the three mammarenaviruses in the central region of Argentina.

Zika Virus (ZIKV) is an RNA virus that belongs to the Flavivirus (FV) genus. In the last years, several unique characteristics of ZIKV among FV have been revealed, as the multiple routes of transmission and its ability to reach different human tissues, including the central nervous system. Thus, one of the most intriguing features of ZIKV biology is its ability to cross diverse complex biological barriers. The main aim of this study is to contribute to the understanding of the still unclear mechanisms behind this viral activity. We investigated an African strain and two South American ZIKV isolates belonging to the Asian lineage, in order to characterize possible differences regarding their ability to disturb intercellular junctions. The Asian isolates correspond to an imported (Venezuelan) and an autochthonous (Argentinian) ZIKV strain for which there is still no data available. We focused on occludin and DLG1 expression as markers of tight and adherent junctions, respectively. For this, we applied a quantitative immunofluorescence assay that can ascertain alterations in the cell junction proteins expression in the infected cells. Our findings indicated that the different ZIKV strains were able to reduce the levels of both polarity proteins without altering their overall cell distribution. Moreover, the grade of this effect was strain-dependent, being the DLG1 reduction higher for the African and Asian Venezuelan isolates and, on the contrary, occludin down-regulation was more noticeable for the Argentinian strain. Interestingly, among both junction proteins the viral infection caused a relative larger reduction in DLG1 expression for all viruses, suggesting DLG1 may be of particular relevance for ZIKV infections. Taken together, this study contributes to the knowledge of the biological mechanisms involved in ZIKV cytopathogenesis, with a special focus on regional isolates., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Steam sterilization has been used for decades to effectively kill microbial contaminants in a variety of medical and commercial settings. One of the most critical aspects of safe operations in biosafety level 3 biocontainment laboratories (BSL-3) is the effective inactivation of biological select agents in the waste generated in these environments. The Instituto Nacional de Enfermedades Virales Humanas "Dr. Julio I. Maiztegui" (INEVH, Pergamino, Argentina) is an institute that offers epidemiological surveillance, production of biological reagents, and production of biologicals for human use and studies of reservoirs and vectors. Some of the activities need to be done in a BSL-3 that provides biocontainment, ensuring that the materials are decontaminated before they leave the facility. The objective of this study was to design and validate a decontamination procedure for biological waste from the BSL-3 facility that guarantees steam sterilization processes., Methods: The amount and the distribution of biological waste into the autoclave and other physical parameters were defined and evaluated by calculating lethalities., Results: We evaluated autoclave basic factory programmed cycles, and it was concluded that the sterilization autoclave cycle was not efficient for decontamination of waste. A new simulated load distribution had to be defined., Discussion: The results demonstrated that autoclave factory default settings can be inadequate for sterilizing highly infectious waste, depending of types of waste, such as animal carcass and animal bed waste., Conclusion: These results of the validation process can set the standard to the design of waste management protocols to ensure effective treatment of highly infectious biological waste., (© ABSA International 2020.)

Background: We developed a 6-month educational intervention addressing menopause and management of menopausal symptoms called "My Health e Vet to Enable And Negotiate for Shared decision-making" or MEANS. MEANS is offered through secure messaging via the My Health e Vet patient portal system. Materials and Methods: Women veterans aged 45-60 years registered at the Miami, West Palm Beach, and Orlando Veterans Affairs Healthcare Systems (VAHS). Intervention group: women in the Miami VAHS enrolled in My Health e Vet who were sent an invitation, agreed to participate, and completed the baseline survey. Comparison group: women from the Miami, West Palm Beach, and Orlando VAHS who responded to the baseline survey. Results: The intervention group enrolled 269 women at Miami VAHS: average age 53.2 years; 42.4% white, 43.1% black, and 24.2% Hispanic; 95.9% already used My Healthe Vet. The Comparison group had 590 women: average age 53.8 years; 70.8% white, 20.7% black, and 10.2% Hispanic; 57.6% already used My Healthe Vet. Conclusions: The differences between the intervention and comparison groups likely represent the regional demographic variations and the disparate recruitment techniques adopted for the two groups. Using within- and between-group comparisons at the end of the 6-month intervention, this novel project will evaluate the feasibility of a patient portal intervention on knowledge and shared decision-making regarding menopause among racially and ethnically diverse women. The study highlights the scalable and enormous potential for patient portals in nonurgent chronic disease management and shared decision-making, important in the existing health care climate, wherein "meaningful use" of electronic health records is mandated. Because of the COVID-19 pandemic, medical care has abruptly changed to telehealth and this approach to patient education is more relevant now than ever before. This quality improvement project's registration number is ClinicalTrials.gov ID: NCT03109145., Competing Interests: No competing financial interests exist., (© Avi Lamba et al., 2020; Published by Mary Ann Liebert, Inc.)

Histoplasmosis is a worldwide systemic endemic mycosis caused by several cryptic species included within the Histoplasma capsulatum complex. Domestic and wild mammals are susceptible to infection by this fungus and could be used as indicators of its presence in the environment. The aim of the study was to identify the natural reservoirs of H. capsulatum in the Argentinean Humid Pampas eco-region analyzing a wildlife frozen-tissue collection and trace its distribution patterns over time and space. Tissue samples from 34 small wild mammals caught in the Humid Pampas were analyzed using two molecular markers: 100 kDa protein coding gene (Hcp100) and ITS1 rDNA. Results showed that 32.4% of them were infected with H. capsulatum and its DNA was detected in 5/17 Calomys laucha; 3/6 Calomys musculinus; 1/5 Akodon azarae, 1/3 Monodelphis dimidiata; and 1/2 Didelphis albiventris. In the single specimen studied of Cavia aperea, no H. capsulatum DNA was detected. This is the first H. capsulatum infection report in C. laucha and C. musculinus rodents and M. dimidiate opossum which proves that tissue collections are an important source of material for epidemiological studies of endemic disease over time.

Background: Menopause is a time often fraught with changes and symptoms, which may require difficult choices and decision-making. During this period, women would benefit from a better understanding and in-depth discussions with providers regarding menopause, associated conditions, and appropriate therapy. Patient portals offer a potential means to improve knowledge and shared decision-making (SDM) about menopause. Materials and Methods: This protocol article explores the feasibility of using the secure messaging (SM) function of the Veterans Affairs (VA) Patient Portal, "My Health e Vet" to implement an educational intervention and measure its impact on knowledge and SDM in the management of menopause. Results: This is a quality improvement pilot study in which women veterans of menopausal age in the Miami VA are offered an educational intervention via a patient portal, while women veterans in two neighboring VA facilities are not. Intervention participants receive weekly SMs with information on menopause symptoms, and treatment. After 6-months, all participants are surveyed on menopause knowledge, SDM, and satisfaction with the program. Conclusion: This study is among the first to assess the impact of an innovative patient portal intervention to improve knowledge and SDM between patients and providers regarding menopause. If successful, our program will add to the "meaningful use" of patient portals and offer a scalable and timely resource for SDM about menopause.

The cricetid rodent Oligoryzomys longicaudatus is the species host of Andes virus (ANDV) which causes hantavirus pulmonary syndrome in southern Argentina and Chile. Population density, behavioral interactions, and spacing patterns are factors that affect viral transmission among wild rodents. We predict that the highest prevalence of hantavirus antibody positive would be found among wounded, reproductive males and that, at high population densities, wounded, reproductive males would be dispersers rather than resident individuals. The study was conducted seasonally from October (spring) 2011 to October (spring) 2013 in a shrubland habitat of Cholila, Argentina. During each trapping session, we classified captured O. longicaudatus as resident or disperser individuals, estimated population density, and recorded wounds as an indicator of aggression among individuals. We obtained blood samples from each individual for serological testing. We used generalized linear models to test the statistical significance of association between antibody prevalence, and sex, resident/dispersal status, wounds and trapping session. The highest proportion of seropositive O. longicaudatus individuals was among wounded reproductive males during periods of the greatest population density, and the characteristics of seroconverted individuals support that transmission is horizontal through male intrasexual competition. A positive association between dispersing individuals and hantavirus antibody was detected at high population density. Our study design allowed us to obtain data on a large number of individuals that are seroconverted, enabling a better understanding of the ecology and epidemiology of the ANDV host system.

The importance of Zika virus (ZIKV) has increased noticeably since the outbreak in the Americas in 2015, when the illness was associated with congenital disorders. Although there is evidence of sexual transmission of the virus, the mosquito Aedes aegypti is believed to be the main vector for transmission to humans. This species of mosquito has not only been found naturally infected with ZIKV, but also has been the subject of study in many vector competence assays that employ different strains of ZIKV around the world. In Argentina, the first case was reported in February 2016 and a total of 278 autochthonous cases have since been confirmed, however, ZIKV virus has not been isolated from any mosquito species yet in Argentina. In order to elucidate if Argentinian Ae. aegypti populations could be a possible vector of ZIKV, we conducted vector competence studies that involved a local strain of ZIKV from Chaco province, and a Venezuelan strain obtained from an imported case. For this purpose, Ae. aegypti adults from the temperate area of Argentina (Buenos Aires province) were fed with infected blood. Body, legs and saliva were harvested and tested by plaque titration on plates of Vero cells for ZIKV at 7, 11 and 14 days post infection (DPI) in order to calculate infection, transmission, and dissemination rates, respectively. Both strains were able to infect mosquitoes at all DPIs, whereas dissemination and transmission were observed at all DPIs for the Argentinian strain but only at 14 DPI for the Venezuelan strain. This study proves the ability of Ae. aegypti mosquitoes from Argentina to become infected with two different strains of ZIKV, both belonging to the Asian lineage, and that the virus can disseminate to the legs and salivary glands., Competing Interests: The authors have declared that no competing interests exist.

To identify and predict situations of increased risk of orthohantavirus infection in humans, it is necessary to study the relationships between the virus and its rodent hosts. The present study investigated orthohantavirus infection in an assemblage of wild Sigmodontinae rodents of the Paraná Delta, Argentina, and providing new evidence of host-switching events. Rodents belonging to the species Oxymycterus rufus (n = 187), Akodon azarae (n = 82), Oligoryzomys flavescens (n = 80), Oligoryzomys nigripes (n = 47), Scapteromys aquaticus (n = 38), Deltamys kempi (n = 7) and Holochilus brasiliensis (n = 2) were captured at 4 sampling sites during 20 trapping sessions. Blood samples were analyzed by IgG ELISA and livers by a nested reverse transcription PCR for the diagnosis of orthohantavirus infection. The amplified products of the S and M orthohantavirus genomes were sequenced and analyzed to determine similarities with species of the Orthohantavirus genus. The species of the Oligoryzomys positive to the virus were confirmed by amplifying and sequencing the complete cyt b gene. Of the 443 serum samples analyzed by IgG ELISA, A. azarae presented the highest host-specific prevalence value (10/82, 12.2%) followed by Ol. nigripes (4/47, 8.5%) and Ox. rufus (1/187, 0.5%). All the sero-positive Ol. nigripes (n = 4) were positive to the amplification of the S and M segments of the Lechiguanas genotype (98% nucleotide identity for both segments). This is surprising given that Ol. nigripes has been previously associated with Juquitiba genotype, not Lechiguanas. The latter is generally associated with Ol. flavescens, which in our study were all sero-negative. In addition, the association Ox. rufus - Pergamino genotype found here is, to our knowledge, novel and another potential evidence of host-switching considering that Pergamino has been originally associated with A. azarae. These findings contribute to the building evidence that contradicts the one-genotype-one-reservoir species premise in the association between rodent reservoirs and orthohantaviruses, and supports the hypothesis that the community structure of sympatric host species may contribute to orthohantavirus dynamics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

After the first fracture, the risk of subsequent fractures increases significantly. Medical treatment can reduce the risk of a second fracture by about 50%, but many older adults do not receive osteoporosis medication following their first fracture. This observational study aimed to understand primary care management patterns of older adults after osteoporotic fractures at the Miami Veterans Affairs (VA) Healthcare System. A retrospective review of 219 fracture cases selected by International Classification of Disease (ICD-9) codes between October 2015 and September 2016 identified 114 individuals age ≥50 years who had a non-traumatic fracture code entered in their medical record for the first time. Among them, 72 (63%) did not undergo a bone mineral density (BMD) test or receive treatment in the 12 months following their fracture. Of the 40 individuals who had a BMD test post-fracture, 17 (100%) received or were considered for anti-osteoporosis treatment if their T-score indicated osteoporosis (T-score ≤-2.5), but only 8/23 (35%) if the T-score was >-2.5. Physicians are more likely to prescribe osteoporosis therapy based on a BMD T-score diagnosis of osteoporosis, rather than a clinical diagnosis of osteoporosis based on a low-trauma fracture. A change in practice patterns is necessary to decrease the incidence of fractures.

Recent prolonged droughts and catastrophic wildfires in the western United States have raised concerns about the potential for forest mortality to impact forest structure, forest ecosystem services, and the economic vitality of communities in the coming decades. We used the Community Land Model (CLM) to determine forest vulnerability to mortality from drought and fire by the year 2049. We modified CLM to represent 13 major forest types in the western United States and ran simulations at a 4-km grid resolution, driven with climate projections from two general circulation models under one emissions scenario (RCP 8.5). We developed metrics of vulnerability to short-term extreme and prolonged drought based on annual allocation to stem growth and net primary productivity. We calculated fire vulnerability based on changes in simulated future area burned relative to historical area burned. Simulated historical drought vulnerability was medium to high in areas with observations of recent drought-related mortality. Comparisons of observed and simulated historical area burned indicate simulated future fire vulnerability could be underestimated by 3% in the Sierra Nevada and overestimated by 3% in the Rocky Mountains. Projections show that water-limited forests in the Rocky Mountains, Southwest, and Great Basin regions will be the most vulnerable to future drought-related mortality, and vulnerability to future fire will be highest in the Sierra Nevada and portions of the Rocky Mountains. High carbon-density forests in the Pacific coast and western Cascades regions are projected to be the least vulnerable to either drought or fire. Importantly, differences in climate projections lead to only 1% of the domain with conflicting low and high vulnerability to fire and no area with conflicting drought vulnerability. Our drought vulnerability metrics could be incorporated as probabilistic mortality rates in earth system models, enabling more robust estimates of the feedbacks between the land and atmosphere over the 21st century., (© 2018 John Wiley & Sons Ltd.)

Anthropogenic environmental changes arising from settlement and agriculture include deforestation and replacement of natural vegetation by crops providing opportunities for pathogen spillover from animals to humans. This study aimed to investigate the prevalence of rodent-borne virus infections in seven rural settlements from Midwestern Brazil. Of the 466 individuals tested 12 (2.57%) were reactive for orthohantavirus and 3 (0.64%) for mammarenavirus. These rural settlers lived under unfavorable infrastructure, socioeconomic disadvantages, and unsanitary conditions, representing a risk for rodent-borne infections. Development of public policies towards the improvement of health, sanitation and awareness of rodent-borne diseases in improvised camps and settlements is imperative, in order to reduce morbidity and mortality caused by these diseases.

Hantavirus cardiopulmonary syndrome (HPS) has gained importance in Latin America as an emerging disease, with reports of about 4000 HPS cases; however, this is probably an underestimate because of limited surveillance programs and diagnostic tools to confirm HPS. In order to address this issue and develop better serosurveillance capability, we evaluated three recombinant peptides from the Necoclí virus (NECV) nucleocapsid in antibody-capture ELISA. We cloned and expressed antigens representing the whole NECV nucleocapsid protein (NECV-rN), the immunodominant domain (NECV-rN100), and a serospecific domain (NECV-rN428), and then we compared these antigens in ELISA to detect IgG antibodies to NECV in human sera. We evaluated human sera collected during two epidemiological studies from the area where NECV was discovered. The first group included 609 sera from healthy individuals, and the second one included 89 samples from patients with undifferentiated febrile illness. In these two groups, hantavirus infection had previously been determined by the presence of IgG to Maciel virus (MCLV), a hantavirus closely related to NECV. The number of IgG-positive sera was higher using the Necoclí ELISA with the rN100 protein, which detected antibodies in a higher percentage of healthy individuals, 129/609 (21.2%), as well as in febrile patients, 11/89 (12.3%). In contrast, using MCLV ELISA, 8 of 609 (1.3%) and 4 of 89 (4.5%) samples from healthy and febrile patients, respectively, were seropositive. The agreement between the NECV and MCLV ELISA assays was ≥ 82.3%; however, the kappa indices were weak but statistically significant for rN (0.251 CI; 0.138-0.365) and rN100rN (0.153 CI; 0.084-0.223). The weak kappa indices were attributed to decreased MCLV ELISA assay sensitivity. These results suggest that NECV rN and rN100 have increased specificity and could be further validated for improved diagnosis of hantavirus infections.

The literature on the reproductive health and healthcare of women Veterans has increased dramatically, though there are important gaps. This article aims to synthesize recent literature on reproductive health and healthcare of women Veterans. We updated a literature search to identify manuscripts published between 2008 and July 1, 2017. We excluded studies that were not original research, only included active-duty women, or had few women Veterans in their sample. Manuscripts were reviewed using a standardized abstraction form. We identified 52 manuscripts. Nearly half (48%) of the new manuscripts addressed contraception and preconception care ( n  = 15) or pregnancy ( n  = 10). The pregnancy and family planning literature showed that (1) contraceptive use and unintended pregnancy among women Veterans using VA healthcare is similar to that of the general population; (2) demand for VA maternity care is increasing; and (3) women Veterans using VA maternity care are a high-risk population for adverse pregnancy outcomes. A recurrent finding across topics was that history of lifetime sexual assault and mental health conditions were highly prevalent among women Veterans and associated with a wide variety of adverse reproductive health outcomes across the life course. The literature on women Veterans' reproductive health is rapidly expanding, but remains largely observational. Knowledge gaps persist in the areas of sexually transmitted infections, infertility, and menopause., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The increasing number and older age of women Veterans receiving care at Veterans Health Administration (VHA) requires health-care providers to adjust to their changing patient population. We explored women Veterans' self-reported knowledge of menopause, current/preferred sources of menopausal health information, and perceptions/barriers regarding treatment of menopausal symptoms. Three focus groups were conducted at two South Florida VHA facilities in 2014, which included 30 women Veterans (aged 45-60 years) who visited VHA primary care clinics at least once in the past year. Participants reported using various sources to obtain general and menopausal health information, particularly family, friends, and the internet. Some women also had discussions with their health-care providers, but believed not all VHA providers were knowledgeable about menopause. Most preferred older female providers, thinking they were better informed about menopausal issues. Women favored complementary/alternative therapies and were against using hormone therapy (HT) for symptom relief, although they felt they were insufficiently informed about HT. Menopausal-age women are the fastest growing group at VHA. To provide better care and enhance their experiences, the VHA must educate all primary care providers about menopausal care and strive to address women Veterans' menopausal concerns and preferences.

Background: Cancer related fatigue (CRF), reported in about 90% of breast cancer patients receiving chemotherapy, and has a profound impact on physical function, psychological distress and quality of life. Although several etiological factors such as anemia, depression, chronic inflammation, neurological pathology and alterations in metabolism have been proposed, the mechanisms of CRF are largely unknown., Methods: We conducted a pilot, prospective, case-control study to estimate the magnitude of change in thyroid function in breast cancer patients from baseline to 24 months, compared to cancer-free, age-matched controls. Secondary objectives were to correlate changes in thyroid function and obesity over time with fatigue symptoms scores in this patient population., Results: The proportion of women with breast cancer who developed subclinical or overt hypothyroidism (TSH >4.0 mIU/L) from baseline to year 1 was significantly greater compared to controls (9.6% vs. 5%; p=0.02). Subjects with breast cancer reported significantly worse fatigue symptoms than age-matched controls, as indicated by higher disruption indices (p<0.001 at baseline, p=0.02 at year 1, p=0.09 at year 2). Additionally, a significant interaction effect on disruption index score (p=0.019), general level of activity over time (p=0.006) and normal work activity (p= 0.002) was observed in the subgroup of women with BMI>30., Conclusion: Screening breast cancer patients for thyroid function status at baseline and serially post-treatment to evaluate the need for thyroid hormone replacement may provide for a novel strategy for treating chemotherapy-induced fatigue., Competing Interests: CONFLICTS OF INTEREST To date, the results of this study have not been reported elsewhere. No authors listed in this manuscript have direct or indirect commercial financial incentive associated with publishing the article.

Background: Randomized clinical trials (RCTs) conducted among heart failure (HF) patients have reported that mobile technologies can improve HF-related outcomes. Our aim was to conduct a meta-analysis to evaluate m-Health's impact on healthcare services utilization, mortality, and cost., Methods: We searched MEDLINE, Cochrane, CINAHL, and EMBASE for studies published between 1966 and May-2017. We included studies that compared the use of m-Health in HF patients to usual care. m-Health is defined as the use of mobile computing and communication technologies to record and transmit data. The outcomes were HF-related and all-cause hospital days, cost, admissions, and mortality., Results: Our search strategy resulted in 1,494 articles. We included 10 RCTs and 1 quasi-experimental study, which represented 3,109 patients in North America and Europe. Patient average age range was 53-80 years, New York Heart Association (NYHA) class III, and Left Ventricular Ejection Fraction <50%. Patients were mostly monitored daily and followed for an average of 6 months. A reduction was seen in HF-related hospital days. Nonsignificant reductions were seen in HF-related cost, admissions, and mortality and total mortality. We found no significant differences for all-cause hospital days and admissions, and an increase in total cost., Conclusions: m-Health reduced HF-related hospital days, showed reduction trends in total mortality and HF-related admissions, mortality and cost, and increased total costs related to more clinic visits and implementation of new technologies. More studies reporting consistent quality outcomes are warranted to give conclusive information about the effectiveness and cost-effectiveness of m-Health interventions for HF.

Purpose: Veterans with dementia and their caregivers in remote areas may not have access to specialists to provide diagnosis, treatment, and education. The purpose of this clinical demonstration project was to examine the feasibility, acceptability, and impact of a video consultations clinic for veterans with dementia or memory complaints and their caregivers., Methods: The dementia clinical video telehealth (CVT) consultation clinic was established to identify, diagnose, and treat dementia in veterans at sites distant from the main medical center. A geriatrician at the main facility provided video consultation to patients and caregivers at seven satellite facilities. Diagnoses made and services provided were recorded after the initial consultation. Patient and caregiver satisfaction with the CVT clinic were assessed., Findings: Ninety-four patients were evaluated in the CVT dementia clinic (average age = 74.7; average Mini-Mental State Exam = 24.4). Forty patients had a prior dementia diagnosis, 15 received a new dementia diagnosis, and 20 a new mild cognitive impairment diagnosis. Of the remaining patients evaluated for memory complaints, seven were found to have depression, three had hearing loss, and three had traumatic brain injury. After CVT consultation, common referrals included social work (n = 43), neuropsychology (n = 36), and brain imaging (n = 26). Patients and caregivers expressed high satisfaction with the video consultation and 90% of caregivers indicated they would rather use CVT than travel to see the specialist in person., Conclusions: Video consultation was well accepted by both dementia patients and caregivers. CVT may facilitate timely diagnosis and management and provide support for rural dementia patients and caregivers.

We describe an outbreak of hantavirus pulmonary syndrome in the Burruyacú Department, Province of Tucumán. The detection in 2016 of a case of hantavirosis affecting a 23-year-old woman, considered at that time to be the first case occurred in that province, promoted a thorough epidemiological study. The investigation allowed the retrospective detection of another case occurred one month earlier in a 5-year-old child in the same Department. In both cases, the infection was confirmed by serology (case 1 at days 4 and 7 of disease onset, case 2 at day 4) and the viral genotype was characterized as HU39694. The contacts of both cases were serologically negative for hantavirus. The rodents captured in the area belonged to genus Akodon, genus Calomys and species Mus musculus. Oligoryzomys, the known reservoir for this viral genotype, was not found. Specific anti-hantavirus antibodies were not detected in the captured rodents. Given that the patients had not visited hantavirus endemic areas and their contacts were negative for hantavirus, we infer that the patients were locally exposed to fluids of infected rodents during their usual social or recreational outdoor activities. In conclusion, we demonstrate that hantavirus HU39694 -a genotype until now considered to be restricted to the Central Pampas of the country- is circulating in the North Western province of Tucumán. The endemic area of hantavirosis is thus expanded to this province but the viral reservoir in the area has not yet been identified.

Purpose: The American College of Physicians (ACP) published a set of guidelines on how to prevent fractures in men and women with low bone density or osteoporosis. As the population ages, the overall risk of fractures increases, thus burdening the health care system. These guidelines review current evidence for osteoporosis management, providing an update to the previous 2008 ACP's guidelines., Methods: The ACP put forth 6 recommendations addressing the complexities in osteoporosis management based on evidence available through October 2016 with a focus on bisphosphonates, calcium, vitamin D, and estrogen. Evidence was graded according to recommended strength by using the ACP standard methods., Findings: The ACP recommends anti-osteoporosis therapy with 1 of 3 bisphosphonates (alendronate, risedronate, or zoledronic acid) or denosumab in patients with osteoporosis, while excluding anabolic therapies, and recommends against raloxifene. Although bisphosphonates are the mainstay of treatment, anabolic therapy and raloxifene may be used in specific situations. Pharmacologic therapy is recommended for 5 years, oversimplifying length of therapy and failing to promote an individualized patient-centered care approach. Moreover, abrupt discontinuation of denosumab is associated with a decline in bone mineral density (BMD), which must be addressed. Routine monitoring of BMD by dual x-ray absorptiometry is not endorsed during treatment, which leads to underrecognition of management issues. Pharmacologic treatment with bisphosphonates for male osteoporosis is recommended, although therapies such as denosumab and teriparatide are excluded. Finally, the ACP recommends treatment for women aged ≥65 years at high risk for fracture with osteopenia after a discussion of patient preferences, fracture risk profile, and medications., Implications: Osteoporosis management is complex. The 2017 ACP guidelines address challenges faced by clinicians but oversimplify more complex issues. These are among a number of guidelines that are available for osteoporosis management, which may be used in combination with other sources to assist clinicians with diagnostic and management strategies., (Published by Elsevier Inc.)

Background: Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair., Methods: This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.5 ± 7.3) with frailty. The primary endpoint was incidence of treatment-emergent serious adverse events (TE-SAEs) at 1-month postinfusion. Secondary endpoints included physical performance, patient-reported outcomes, and immune markers of frailty measured at 6 months postinfusion., Results: No therapy-related TE-SAEs occurred at 1 month. Physical performance improved preferentially in the 100M-group; immunologic improvement occurred in both the 100M- and 200M-groups. The 6-minute walk test, short physical performance exam, and forced expiratory volume in 1 second improved in the 100M-group (p = .01), not in the 200M- or placebo groups. The female sexual quality of life questionnaire improved in the 100M-group (p = .03). Serum TNF-α levels decreased in the 100M-group (p = .03). B cell intracellular TNF-α improved in both the 100M- (p < .0001) and 200M-groups (p = .002) as well as between groups compared to placebo (p = .003 and p = .039, respectively). Early and late activated T-cells were also reduced by MSC therapy., Conclusion: Intravenous allo-hMSCs were safe in individuals with aging frailty. Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome. Given the excellent safety and efficacy profiles demonstrated in this study, larger clinical trials are warranted to establish the efficacy of hMSCs in this multisystem disorder., Clinical Trial Registration: www.clinicaltrials.gov: CRATUS (#NCT02065245)., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)-based therapy in patients with aging frailty., Methods: In this nonrandomized, dose-escalation study, patients received a single intravenous infusion of allo-hMSCs: 20-million (n = 5), 100-million (n = 5), or 200-million cells (n = 5). The primary endpoint was incidence of any treatment-emergent serious adverse events measured at 1 month postinfusion. The secondary endpoints were functional efficacy domains and inflammatory biomarkers, measured at 3 and 6 months, respectively., Results: There were no treatment-emergent serious adverse events at 1-month postinfusion or significant donor-specific immune reactions during the first 6 months. There was one death at 258 days postinfusion in the 200-million group. In all treatment groups, 6-minute walk distance increased at 3 months (p = .02) and 6 months (p = .001) and TNF-α levels decreased at 6 months (p < .0001). Overall, the 100-million dose showed the best improvement in all parameters, with the exception of TNF-α, which showed an improvement in both the 100- and 200-million groups (p = .0001 and p = .0001, respectively). The 100-million cell-dose group also showed significant improvements in the physical component of the SF-36 quality of life assessment at all time points relative to baseline., Conclusions: Allo-hMSCs are safe and immunologically tolerated in aging frailty patients. Improvements in functional and immunologic status suggest that ongoing clinical development of cell-based therapy is warranted for frailty., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hantavirus infection is an acute zoonosis that clinically manifests in two primary forms, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is endemic in Europe and Russia, where the mild form of the disease is prevalent in the Tatarstan region. HPS is endemic in Argentina, as well as other countries of North and South American. HFRS and HPS are usually acquired via the upper respiratory tract by inhalation of virus-contaminated aerosol. Although the pathogenesis of HFRS and HPS remains largely unknown, postmortem tissue studies have identified endothelial cells as the primary target of infection. Importantly, cell damage due to virus replication, or subsequent tissue repair, has not been documented. Since no single factor has been identified that explains the complexity of HFRS or HPS pathogenesis, it has been suggested that a cytokine storm may play a crucial role in the manifestation of both diseases. In order to identify potential serological markers that distinguish HFRS and HPS, serum samples collected during early and late phases of the disease were analyzed for 48 analytes using multiplex magnetic bead-based assays. Overall, serum cytokine profiles associated with HPS revealed a more pro-inflammatory milieu as compared to HFRS. Furthermore, HPS was strictly characterized by the upregulation of cytokine levels, in contrast to HFRS where cases were distinguished by a dichotomy in serum cytokine levels. The severe form of hantavirus zoonosis, HPS, was characterized by the upregulation of a higher number of cytokines than HFRS (40 vs 21). In general, our analysis indicates that, although HPS and HFRS share many characteristic features, there are distinct cytokine profiles for these diseases. These profiles suggest a strong activation of an innate immune and inflammatory responses are associated with HPS, relative to HFRS, as well as a robust activation of Th1-type immune responses. Finally, the results of our analysis suggest that serum cytokines profiles of HPS and HFRS cases are consistent with the presence of extracellular matrix degradation, increased mononuclear leukocyte proliferation, and transendothelial migration.

Introduction: The lymphocytic choriomeningitis virus is an Old World arenavirus that infects Mus musculus, and can cause congenital hydrocephalus, chorioretinitis and multisystemic failure in transplant human recipients. Although the disease has not been clinically diagnosed in Colombia yet, there have been reports of infection with the Pichindé virus in rodents from Cauca and Valle del Cauca departments, and with the Guanarito virus in rodents from Córdoba department., Objective: To identify the lymphocytic choriomeningitis virus from Mus musculus captured in the municipality of Sincelejo., Materials and Methods: We evaluated 80 samples of plasma by ELISA using antigen from lymphocytic choriomeningitis virus. Additionally, a nested RT-PCR was performed to seropositive and seronegative samples for the S-segment., Results: We found a 10% seroprevalence (8/80) and the viral genome was detected in 16 brain samples; the alignment (BLAST) and the phylogenetic analysis (MrBayes, version 3.2.2) confirmed the presence of the lymphocytic choriomeningitis virus., Conclusion: The results indicated that human infection with the lymphocytic choriomeningitis virus in humans could occur in the urban area of Sincelejo, although no cases have been reported so far.

Objectives: To determine the effectiveness of vitamin D supplementation in preventing decline in physical function in older men., Design: Randomized, double-blind, placebo-controlled clinical trial., Setting: Single-center study conducted at a Veterans Affairs Healthcare System., Participants: Sedentary men aged 65 to 90 (mean 72.4 ± 6.8) with baseline 25-hydroxyvitamin D (25(OH)D levels of less than 30 ng/mL and Short Physical Performance Battery (SPPB) test scores of 9 or less (N = 130)., Intervention: Daily capsule containing cholecalciferol 4,000 IU daily or placebo for 9 months., Measurements: Main outcomes were SPPB score and gait speed., Results: After the intervention, serum 25(OH)D increased from 23.1 ± 5.0 ng/mL to 46.2 ± 12.7 ng/mL in the cholecalciferol group and from 22.5 ± 5.3 ng/mL to 24.0 ± 7.2 ng/mL in the placebo group. At study end, improvements in SPPB score and gait speed were not significantly greater in men receiving cholecalciferol than in those receiving placebo. No differences were found in adverse events or numbers of falls., Conclusion: Daily cholecalciferol 4,000 IU for 9 months resulted in significant increases in 25(OH)D concentrations, but achieving these higher levels did not result in improvements in SPPB score or gait speed. These data do not support prescribing vitamin D supplements to older sedentary men to prevent physical function decline., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

Hantaviruses are etiologic agents of a zoonotic disease transmitted mainly from wild rodents to humans, causing Hemorrhagic Fever with Renal Syndrome in Eurasia and the Hantavirus Cardiopulmonary Syndrome in the Americas (HCPS), reaching a lethality rate of 40% in Brazil. Hantavirus diagnostic and seroprevalence are often based on the presence of IgM and IgG antibodies against the virus. Here we propose a rapid test assay able to identify hantavirus antibodies with sensibility and specificity similar to ELISA assays. We analyzed five groups of samples, including healthy human population and small mammals of endemic areas, suspected cases of HCPS, patients with non-related infections and a serum panel from a different geographical region. The test presented good rates of sensibility (87-100%) and specificity (97-100%) for all groups, being a promising tool suitable for both rodent and human hantavirus epidemiological surveys., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.

Arenavirus Sabiá was originally isolated from a fatal human infection in Brazil, and after the occurrence of the second fatal human case in São Paulo state, epidemiologic and virologic studies were performed in the area where the patient lived, aiming at the identification of the Sabiá natural rodent reservoir. A broadly cross-reactive enzyme-linked immunosorbent assay (ELISA) was used to screen for antibody-positive samples. Antibodies to arenavirus were detected in two of the 55 samples of Calomys tener, and from these results, samples of rodents were analyzed by a broad RT-PCR assay. RT-PCR amplification detected arenavirus sequences in five of the 55 C. tener samples, and sequencing showed that this virus is a distinct form of Sabiá virus. Thus, we describe here the evidence for the circulation of a new arenavirus in Brazil (proposed name Pinhal virus) and its genetic characterization compared to other arenaviruses. This study also suggests C. tener as a probable rodent reservoir for this virus and associates this new virus with the lineage C of New World arenaviruses. Although we have defined some characteristics of this virus, so far, there is no evidence of its involvement in human disease.