NK cells control HIV-1 infection of macrophages through soluble factors and cellular contacts in the human decidua.

BACKGROUND: During the first trimester of pregnancy, HIV-1 in utero transmission is rare despite the permissivity of the placenta and the decidua (the uterine mucosa during pregnancy) to infection. In the decidua from the first trimester of pregnancy, macrophages (dMs) are the HIV-1 main target cells. Decidual natural killer (dNK) cells account for 70 % of decidual leukocytes. They display distinct phenotype and functions compared to peripheral NK cells. At the periphery, NK cells are involved in the control of HIV-1 infection. In this study, we investigate whether human decidual natural killer (dNK) cells control dM HIV-1 infection. RESULTS: Autologous cocultures of infected dMs with dNK cells reveal that dNK cells strongly inhibit dM HIV-1 infection. The addition of dNK cells to dMs at different times after infection suggests that the control occurs before the complete establishment of the infection. Double chamber cocultures show that cellular contacts are necessary for an optimal control of infection. Nevertheless, soluble factors secreted by dMs and dNK cells in double chamber cocultures partially inhibit dM HIV-1 infection, indicating that soluble factors have also a role in the control of infection. IFN-γ secretion is increased in infected and uninfected cocultures. We show that IFN-γ is involved in the control of dM HIV-1 infection by dNK cells. CONCLUSIONS: These results demonstrate that human dNK cells inhibit efficiently HIV-1 infection in dMs in vitro, and highlight the role of innate immune determinants in the control of HIV-1 transmission.

Free and bound sodium identification by skin dielectric properties separation algorithm of bioelectrical impedance spectroscopy (spa-BIS) in human skin model.

Free and bound sodium in human skin models have been identified by two proposals: skin's phantom fabrication and skin's dielectric properties separation algorithm of bioelectrical impedance spectroscopy (spa-BIS). Thespa-BIS consist of conductivity-permittivity separation, contact impedance compensation, and a correlation score algorithm based on the vessel with a bipolar electrode. The skin phantom fabrication comprises a recipe combination with temperature-controlled protocol and sodium molarity calculation. In experiments, the human skin models are created to mimic the electrical properties of skin under1MHzwith several different sodium molarities. Based on five types of human skin models with five samples of each group, the free sodium type conductivity and concentration resultsR2=0.9903-following a linear trendline of concentration change in skin tissues theorems with the fRequency range from1kHzto1MHz,while the bound sodium type resultsR2=0.9061-.Thespa-BIS compensate7-16Ωof vessel contact impedance. The dielectric properties of each type have been extracted with less than 10% of the average standard deviation, which is considered an accurate identification method of dermis dielectric properties. The algorithm successfully identifies sodium type: free sodium has a negative, and bound sodium has a positive correlation score trend. As an additional discussion, the different time-dependent effects, the different water content, and different agar content analyses have been provided in this study. As a robust analysis method, thespa-BIS has a prominent performance to replace a23Na-MRI in terms of free and bound sodium identification.

COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.

One year into the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), effective treatments are still needed 1-3 . Monoclonal antibodies, given alone or as part of a therapeutic cocktail, have shown promising results in patients, raising the hope that they could play an important role in preventing clinical deterioration in severely ill or in exposed, high risk individuals 4-6 . Here, we evaluated the prophylactic and therapeutic effect of COVA1-18 in vivo , a neutralizing antibody isolated from a convalescent patient 7 and highly potent against the B.1.1.7. isolate 8,9 . In both prophylactic and therapeutic settings, SARS-CoV-2 remained undetectable in the lungs of COVA1-18 treated hACE2 mice. Therapeutic treatment also caused a dramatic reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg - 1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 had a very strong antiviral activity in the upper respiratory compartments with an estimated reduction in viral infectivity of more than 95%, and prevented lymphopenia and extensive lung lesions. Modelling and experimental findings demonstrate that COVA1-18 has a strong antiviral activity in three different preclinical models and could be a valuable candidate for further clinical evaluation.

The prevalence of horse trypanosomiasis in Sumba Island, Indonesia and its detection using card agglutination tests.

BACKGROUND AND AIM: Horses have a strategic and vital role to play in the lives of the people of Sumba Island, East Nusa Tenggara Province. They act as social animals that are involved in death ceremonies, horse races, and during pasola, thereby supporting tourism, and are given away as dowry in wedding ceremonies. This study aimed to investigate the prevalence of trypanosomiasis among horses in four districts of Sumba Island by examining clinical symptoms and detecting parasites, antibodies, and other factors that are related to Trypanosoma evansi infection in horses. MATERIALS AND METHODS: We studied a total of 211 horses that belonged to 88 clinical hobby breeders. Giemsa-colored smears and serum were examined in order to detect antibodies using card-agglutination tests (CATT). The study was conducted during the rainy season that lasted from January to March 2017. Potential risk factors such as the species, sex, origin of the livestock, how the livestock were maintained, and the farmers' knowledge concerning trypanosomiasis were recorded using questionnaires. Data were collected annually for three years from 2010-2012 and repeatedly analyzed by a Chi-square test. RESULTS: Clinical signs of trypanosomiasis were found in 34 horses; blood smears were examined using Giemsa staining and negative preparations were obtained at a frequency of 0.0% (0/211). The CATT results generally showed that 13.3% (28/211) of the samples were seropositive for antibodies to T. evansi; the highest percentage, 16.67% (8/48), of seropositivity was found in the West Sumba District, and the lowest, 12.0% (5/50), was found in Southwest Sumba. The incidence of trypanosomiasis was higher (75% [21/28]) among female hip horses; horses with 1-5 years of experience were more susceptible to a T. evansi infection (46.4% [13/28]). In general, farmers on Sumba Island knew of trypanosomiasis (89.8% [79/88]), and 69.3% (61/88) of the farmers reported that their livestock was sick. This study was the first serological study conducted on trypanosomiasis in horses of Sumba Island after the surra outbreak in 2010-2012. There were 3% of farmers who were willing to provide the government with information on implementing a prevention program and controlling the spread of surra on the island. CONCLUSION: The diagnoses of surra disease were made based on clinical symptoms and parasitological examinations. CATTs could be used to diagnose T. evansi infection in horses.

A Model for Incident Review Committees in Behavioral Health Settings.

Despite the fact that incident review committees have been a key component of quality improvement in behavioral health settings for decades, specific models of how these committees are structured and operate are not well described. We present a model for an incident review committee that has been implemented in 2 large, academic acute care psychiatric hospitals. We believe the model not only permitted us to efficiently and effectively review untoward incidents, but that it also provided an approach to calibrating standards of care for the institution, engaging physicians in an interdisciplinary effort, promulgating a culture of quality review and improvement throughout the organization, promoting continuity and sustainability of the incident review process, and, most importantly, driving beneficial change in clinical practice. Demonstration of the effectiveness of this model requires formal investigation.

[Retroviral restriction factors : from Fv1 to TRIM5α]. / Les facteurs de restriction rétrovirale : de Fv1 à TRIM5α.

During their evolution, mammals have developed cellular factors interfering with retroviral replication, known as « restriction factors ¼. The prototype of these factors, Fv1, was characterized in the late 60's and blocks MLV infection. Some Fv1-like factors interfering with complex retroviruses, including HIV, have recently been discovered in primate cells. These restriction factors are referred to as Ref1, which blocksMLVreplication in human cells, and Lv1, which blocks the infection of non-human primate cells by various retroviruses, including MLV and HIV. These factors are all saturable by an excess of virus, target the viral capsid and interfere with an early step of viral replication. Lv1 and Ref1 have recently been found to be species-specific variants of a single protein called TRIM5α, a member of the TRIM protein family. The mechanism of action of these factors is still unknown. The existence of natural inhibitors of retroviral infection raises new hopes for the development of therapeutic tools against HIV infection.

The local environment orchestrates mucosal decidual macrophage differentiation and substantially inhibits HIV-1 replication.

Macrophages from the decidua basalis (dM), the main uterine mucosa during pregnancy, are weakly permissive to HIV-1 infection. Here, we investigated the mechanisms underlying this natural control. We show, by using freshly purified decidual macrophages and ex vivo human decidual explants, that the local decidual environment influences dM differentiation and naturally protects these cells from HIV-1 infection. Interferon (IFN)-γ, present in the decidual tissue, contributes to maintenance of the dM phenotype and restricts HIV-1 infection by mechanisms involving the cyclin-dependent kinase inhibitor p21Cip1/Waf1. We also found that activation of Toll-like receptors 7 and 8 expressed by dM reinforces the low permissivity of dM to HIV-1 by restricting viral replication and inducing secretion of cytokines in the decidual environment, including IFN-γ, that shape dM plasticity. A major challenge for HIV-1 eradication is to control infection of tissue-resident macrophages in the female reproductive tract. Our findings provide clues to the development of novel strategies to prevent HIV-1 macrophage infection.

The Growing Regulation of Conversion Therapy.

Conversion therapies are any treatments, including individual talk therapy, behavioral (e.g. aversive stimuli), group therapy or milieu (e.g. "retreats or inpatient treatments" relying on all of the above methods) treatments, which attempt to change an individual's sexual orientation from homosexual to heterosexual. However these practices have been repudiated by major mental health organizations because of increasing evidence that they are ineffective and may cause harm to patients and their families who fail to change. At present, California, New Jersey, Oregon, Illinois, Washington, DC, and the Canadian Province of Ontario have passed legislation banning conversion therapy for minors and an increasing number of US States are considering similar bans. In April 2015, the Obama administration also called for a ban on conversion therapies for minors. The growing trend toward banning conversion therapies creates challenges for licensing boards and ethics committees, most of which are unfamiliar with the issues raised by complaints against conversion therapists. This paper reviews the history of conversion therapy practices as well as clinical, ethical and research issues they raise. With this information, state licensing boards, ethics committees and other regulatory bodies will be better able to adjudicate complaints from members of the public who have been exposed to conversion therapies.

An evaluation of multidisciplinary intervention for chronic fatigue syndrome with long-term follow-up, and a comparison with untreated controls.

Individuals meeting the Fukuda et al definition for chronic fatigue syndrome completed a multidisciplinary assessment that included medical, psychiatric, behavioral, and psychological evaluations. Patients were then offered a comprehensive multidisciplinary intervention that included (1) bringing the patient under optimal medical management; (2) treating any ongoing affective or anxiety disorder pharmacologically; and (3) implementing a comprehensive cognitive-behavioral treatment program. Fifty-one patients proceeded to treatment. The cognitive-behavioral component was carried out through the use of a therapist working with the patients in their own environments. The program was individually tailored to patients, but included (1) structured physical exercise and activation; (2) sleep management strategies; (3) careful activity management; (4) regulation of stimulant intake and reductions in use of symptomatic medications; (5) cognitive intervention designed to deal with patients' beliefs concerning the nature of their disorder; (6) participation of patients' family; and (7) efforts to establish specific vocational and avocational goals. Third parties were encouraged to collaborate cooperatively. Employers were urged to provide employment opportunities and facilitate a graduated but time-targeted return to work. Disability carriers were encouraged to provide interim financial support in the form of disability benefits, support therapeutic intervention, but also to establish a clear time-frame to access to benefits. Of 51 treated patients, 31 returned to gainful employment, 14 were functioning at a level equivalent to employment, and 6 remained significantly disabled. Twenty of the original 71 patients were contacted an average of 33 months later. Patients who had been treated showed good maintenance of gains. Untreated patients showed improvement in only a minority of cases.

Awareness of the response after feedback training for changes in heart rate and sudomotor laterality.

What is the relation between the ability to control visceral responding on a biofeedback task and the ability to report behaviors actually contributing to this performance? Subjects received biofeedback training for unidentified visceral responses and then gave written reports about what they had done to control the feedback displays. Independent judges were given these reports and, on the basis of knowledge about activities known to contribute to visceral activity, were asked to determine the visceral responses for which the subjects had been trained. The reports of subjects who succeeded at bidirectional control of heart rate (Experiment 1) or sudomotor laterality (Experiment 2) showed awareness of behaviors related to feedback as assessed by this procedure, whereas the reports of subjects who failed at bidirectional control did not. Subsequent experiments indicated that these results did not depend on a learning strategy that might have been specific to the initial studies. These findings call into question the view that people are unaware of what they have done to produce the response after training on biofeedback tasks. Earlier studies reporting lack of awareness in biofeedback are discussed in light of factors that affect the measurement of biofeedback learning and response awareness.

Bacteriological sampling of postmortem rooms.

Thirty hospital and coroners' postmortem rooms in the West Midlands were visited over two years. The design, environmental facilities, and hygienic practices were investigated and air exchange rates were measured. Microbiological samples were taken from the environment and from gloves, hands, and protective clothing of staff. Glove punctures were also recorded and a plastic isolator evaluated. Bacterial counts in the air were low and related more to the number of people in the room than to the air exchange rate. There was little evidence of the production of aerosol containing bacteria, although splashing occurred while intestines were being washed out. Surfaces often remained contaminated with Gram negative bacilli after cleaning but numbers were considerably reduced on drying. Decontamination of instruments was satisfactory. A wide range of disinfectants and concentrations was used, but none showed evidence of contamination. Gloves were heavily contaminated after use, and occasionally the hands of the wearer after removal of the gloves. Washing the hands effectively removed residual transient organisms, irrespective of the agent used. The incidence of glove punctures was higher among technicians (38%) than pathologists (12%). The plastic isolator reduced smells and limited environmental contamination but visibility and acceptability were poor. The results of the study suggest that there is little evidence of risk of infection to staff, providing basic hygienic precautions are taken, but consideration should be given to the prevention of glove punctures.

Extended dissociative training of sudomotor response patterns.

Subjects viewed two feedback displays, one depicting skin conductance and the other either respiratory behavior (respiration group) or subtle body movements (movement group). The subject's task was to increase skin conductance and the concomitant activity on integration trials, and to increase conductance while holding the concomitant behavior constant on dissociation trials. All subjects succeeded at integration over 15 sessions of training. In addition, 4 of 5 subjects in the respiration group successfully increased skin conductance on dissociation trials without altering the pre-trial pattern of breathing. However, volar activities (e.g., finger-to-finger contact, finger flexion) were observed on these trials. Volar activities were also adopted on dissociation trials by subjects trained in the movement group. Successful subjects in this group identified volar manipulations that did not affect a sensitive movement transducer. Attempts by subjects to compensate for habituation of conductance responses to deep breaths and finger flexion reduced or reversed within-subject correlations involving these concomitants, on integration and dissociation trials. The results do not support the view that visceral-somatic linkages can be uncoupled through instrumental learning.

The field instructor program: quality control of prehospital care, the first step.

Orientation and evaluation of the new paramedic employee are areas that are frequently overlooked or not performed in a consistent manner. In order to evaluate skills of new employees in a standardized fashion and provide a formal structured orientation, the field instructor program was instituted. Since 1978, 78 people have gone through the program. Sixty-nine (88.5%) successfully completed the course. All of those released in "poor standing" were subsequently dismissed from the paramedic division because of poor medical performance. This program has provided orientation of new paramedics and identified those with serious deficiencies in their practice.

A comprehensive on-line collection system.

In the normal conduct of a clinical drug trial, a considerable time lag exists between the point when drug response data are collected, usually by means of a standard written case report form completed at the time of an individual patient visit, and the time when it is entered into the computer system (and thereafter available for assessment) in the sponsor 's facility. This lag period may range from a matter of days to one or several months. Previous efforts to reduce this time span by providing electronic data entry capability within the clinical investigator's office have generally proven unsatisfactory for reasons of complexity and relative inaccuracy. A recently-developed potential solution to this entire problem will be described. It involves the provision of a microcomputer equipped with sophisticated customized data entry software that offers a means to substantially reduce this long-standing source of delays in the completion of clinical drug trials.

Contingently faded heart rate biofeedback: attempted replication of large-magnitude decreases.

McKinney et al. (1980) reported large-magnitude reductions in heart rate (HR) from resting baseline levels, employing shaping and fading techniques and a reinforcement program in which a secondary reinforcer was awarded both contingently and immediately during training. The four male subjects in this group showed significantly greater HR decreases than a group of four males receiving beat-by-beat analogue HR feedback. The present study compared decreases in HR in 20 male subjects receiving the contingently faded biofeedback procedure to those shown by 10 male subjects for whom reinforcement was contingent on vigilant observation of a visual display, and independent of HR. The former group showed significantly greater decreases in HR that could not be attributed to elevated baseline levels. However, the decreases in HR were not as large as those reported by McKinney et al. (1980). It is argued that future research should assess variables contributing to individual differences in performance.

A pilot study of medication and group therapy for obesity in a group of physicians.

This pilot study evaluated group therapy and the appetite suppressant activity of phenylpropanolamine in a group of juvenile-onset obese physicians. In spite of their educational level and their medical sophistication, they were not previously successfully motivated to lose weight. Twelve obese but otherwise healthy physicians participated in a program using phenylpropanolamine one or two times per day and attending weekly group therapy that focused on weight reduction, dietary compliance, physical appearance, and psychodynamics of obesity. Those who continued participation in both the medication and group discussions showed significant weight loss, an average of 23.3 pounds at the end of 12 weeks, 33.2 pounds at 22 weeks and continued weight loss maintenance for up to two years.

Methods to maximize retention in weight loss studies.

OBJECTIVE: Dropouts from clinical trials decrease quality and increase costs. Free participation, paid participation, and contingency contracting are three study retention methods. Contingency contracting, or depositing a fee to be refunded contingent upon attendance in a clinical trial, has been reported to decrease dropouts without affecting weight loss. These three methods of retention were compared with a commercial weight loss clinic's practice of charging nonrefundable fees. METHODS AND PROCEDURES: Dropouts were compared in two studies testing mazindol, with one study using free care and the other using contingency contracting; two studies testing phenylpropanolamine, one using free care and the other using contingency contracting; and in studies with phenylpropanolamine on file with Thompson Medical Company using free care, paid participation, and contingency contracting. RESULTS: The dropout rate was 50% at 8 weeks in a trial of mazindol with free care vs. 7% for contingency contracting (p<0.001). The two phenylpropanolamine studies gave the same weight losses, but the dropouts were 37% at 8 weeks for free care vs. 11% for contingency contracting (p<0.001). The studies of phenylpropanolamine on file at the Thompson Medical Company had 28% dropouts at 8 weeks using free care vs. 19% for paid participation (p<0.001), and 11% for contingency contracting (p<0.005). Dropouts with contingency contracting (11%) were not different from the commercial weight loss program (13%). DISCUSSION: Contingency contracting can decrease dropouts, improve quality, and decrease costs without affecting weight loss in clinical trials for obesity.

Prehospital care at a major international airport.

Medical emergencies at a major metropolitan airport have a significant impact on prehospital care capabilities for the rest of the community in which the airport is located. Stapleton International Airport in Denver, Colorado, is a facility that in 1985 had 14.4 million passengers and a static employee population of 12,000 to 15,000. In 1981, there were 1,182 ambulance trips to the airport, 40.4% of which did not result in the transport of a patient. The expense of sending an ambulance and fire engine out on such calls was great, and paramedics were out of service for approximately 300 hours on these nontransport cases. In order to improve prehospital services to the airport and the city, a paramedic has been stationed in the concourse at the airport 16 hours a day since 1982. The records for airport paramedic services for the 12 months ending September 1985 were reviewed. Paramedic services were requested for 1,952 patients. Of these, 696 (35.7%) were transported to hospital by ambulance; 115 (5.9%) went by private car; 284 (14.6%) refused any paramedic care or transport; and 857 (43.9%) were released, after base station contact, with instructions to seek definitive care at the final destination. Presenting complaints were classified into 55 categories and the frequencies and dispositions are described. The most common presentations resulting in transport were chest pain, 110 (5.6%); syncope, 60 (3.1%); psychiatric, 57 (2.9%); abdominal pain, 49 (2.5%); seizure, 36 (1.8%); fracture, 31 (1.6%); and cardiac arrest, 29 (1.5%).(ABSTRACT TRUNCATED AT 250 WORDS)