Natural Killer T-like Cells: Immunobiology and Role in Disease.

CD56+ T cells are generally recognized as a distinct population of T cells and are categorized as NKT-like cells. Although our understanding of NKT-like cells is far from satisfactory, it has been shown that aging and a number of disease situations have impacted these cells. To construct an overview of what is currently known, we reviewed the literature on human NKT-like cells. NKT-like cells are highly differentiated T cells with "CD1d-independent" antigen recognition and MHC-unrestricted cell killing. The genesis of NKT-like cells is unclear; however, it is proposed that the acquisition of innate characteristics by T cells could represent a remodeling process leading to successful aging. Additionally, it has been shown that NKT-like cells may play a significant role in several pathological conditions, making it necessary to comprehend whether these cells might function as prognostic markers. The quantification and characterization of these cells might serve as a cutting-edge indicator of individual immune health. Additionally, exploring the mechanisms that can control their killing activity in different contexts may therefore result in innovative therapeutic alternatives in a wide range of disease settings.

Type 2 and type 3 innate lymphoid cells at the maternal-fetal interface: implications in preterm birth.

BACKGROUND: Preterm birth (PTB) is one of the major causes of neonatal morbidity and mortality worldwide. It is commonly accepted that the act of giving birth is the final step in a proinflammatory signaling cascade, orchestrated by an intrauterine milieu coupled to hormonal cues. Consequently, the inflammatory process plays a pivotal role during the pathogenesis of human labor, both in term and preterm deliveries. The ability of innate lymphoid cells (ILCs) to act as pro-inflammatory mediators arose the interest to study their role in normal and pathological pregnancies. The aim of this work was to analyze the relative frequencies of ILCs subsets in pregnancy and the levels of IL-4, IL-17, IL-22, and IFN-γ as inflammatory mediators. Accordingly, we hypothesized that changes in the proportions of ILCs subpopulations could be related to preterm birth. METHODS: We analyzed 15 full-term delivery samples and six preterm delivery samples. In the full-term group (FTB) peripheral blood was taken during routine blood analysis, on 3 occasions: 1st, 2nd and 3rd trimester. After delivery, peripheral blood, cord blood and placenta were collected. In PTB group, peripheral blood samples were obtained on two occasions: before and 24 h after treatment with progesterone. We used flow cytometry to analyze ILCs in maternal peripheral blood, placenta, and cord blood samples. Maternal peripheral blood and cord blood samples were analyzed by enzyme-linked immunosorbent assay for IL-4, IL-17, IL-22, and IFN-γ plasma levels at the time of labor. RESULTS: We observed significantly increased relative frequencies of ILC2 and ILC3 in the decidua, as well as an increase of ILC2 in cord blood samples in PTB group, compared to FTB samples. We also found a decrease in IFN-γ in peripheral blood samples of the PTB group, suggesting a functional withdrawal. Additionally, IL-4, IL-17, IL-22 levels were similar in PTB and FTB groups, denoting a relevant role in mediating labor. CONCLUSION: Our results suggest that ILC2 and ILC3 play a role in PTB by mediating an inflammatory response. Further work is necessary to evaluate the importance of ILCs in the regulation of labor.

Coronally advanced flap achieved higher esthetic outcomes without a connective tissue graft for the treatment of single gingival recessions: a 4-year randomized clinical trial.

OBJECTIVES: Limited long-term data are available when comparing the esthetic outcomes of coronally advanced flap (CAF) with or without a connective tissue graft (CTG). The aim of this study was to compare the 4-year esthetic outcomes of CAF vs CAF + CTG for the treatment of isolated maxillary gingival recessions. MATERIAL AND METHODS: Forty-eight patients were randomly assigned for treatment either with CAF (control; N = 24) or to CAF + CTG (test group; N = 24). Patients were followed after the surgery until the final evaluation. A professional esthetic evaluation was performed using the Root coverage Esthetic Score (RES). Recession reduction, mean root coverage, and complete root coverage were also evaluated. RESULTS: Forty-two patients completed the study at the 4-year recall. A significant recession reduction was evident at 4 years, without significant intergroup differences. The CAF group showed a statistically significant higher final RES compared with the CAF + CTG group (9.14 ± 1.08 vs 7.25 ± 1.29, respectively, p < 0.001). Regarding the individual components of RES, gingival margin and marginal tissue contour were significantly higher in the CAF group compared with that in the CAF + CTG group. CONCLUSIONS: CAF presented with a significantly higher overall esthetic score than CAF + CTG, and in the individual RES components of marginal tissue contour and gingival margin after 4 years. CLINICAL RELEVANCE: CAF without the addition of CTG provided higher esthetic outcomes for the treatment of isolated gingival recessions.

Activated double-negative T cells (CD3+CD4-CD8-HLA-DR+) define response to renal denervation for resistant hypertension.

PURPOSE: To explore the cellular immune response of patients with resistant hypertension treated with renal denervation (RDN). METHODS AND RESULTS: Twenty-three patients were included and blood samples were obtained in six timings, pre and post procedure. Response was evaluated at six-months and one year and was observed in 69.6% and 82.6% of patients, respectively. Absolute values of HLA-DR+ double negative (DN) T cells were significantly lower in the group of 'responders' at one year, and interaction between the timings were found in three T cell subsets (T CD4, T CD8 and naïve T CD8 cells), with the 'responders' tending to present with lower absolute values and little inter-timing variation. CONCLUSIONS: 'Responders' significantly present with lower absolute values of activated DN T cells and have lower and more stable values of total T CD8+, CD4+, and naïve T CD8+ cells. These cell types may be able to predict response to RDN.

A revision of the conductive hearing loss in Cranium 4 from the Middle Pleistocene site of Sima de los Huesos (Burgos, Spain).

Pathological conditions have been previously documented in the Middle Pleistocene Sima de los Huesos hominins from northern Spain, and several of these have clear behavioral implications. Within this fossil assemblage, Cranium 4 shows bilateral external auditory exostoses which have been preliminarily interpreted as causing a significant hearing loss in this individual. If confirmed, this would be the oldest recorded case of deafness in human history and could have important implications for the antiquity of this condition, as well as social interactions. To further investigate this case, the current study presents 3D reconstructions of the entire outer and middle ear, based on computed tomography scans of both temporal bones in Cranium 4. We established the degree of stenosis in both external auditory canals, showing that in both cases the degree of stenosis is less than 52% of the original cross-sectional area of each canal. Based on clinical studies in living humans, the buildup of wax due to the degree of stenosis in Cranium 4 is unlikely to have caused frequent external ear infections. In addition, we estimated the pattern of sound power transmission up to 5 kHz in both ears relying on a comprehensive model developed in the bioengineering literature and which has been applied previously to the Sima de los Huesos hominins. The model was modified to account for the peculiar shape of the pathological external ear canals in Cranium 4. The results show that this pathology had little to no influence on the sound power transmission in this individual. Thus, we conclude that the exostoses present in both ears of Cranium 4 did not significantly affect their hearing.

The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation.

Immune surveillance seems to represent an effective tumor suppressor mechanism. However, some cancer cells survive and become variants, being poorly immunogenic and able to enter a steady-state phase. These cells become functionally dormant or remain hidden clinically throughout. Neoplastic cells seem to be able to instruct immune cells to undergo changes promoting malignancy. Radiotherapy may act as a trigger of the immune response. After radiotherapy a sequence of reactions occurs, starting in the damage of oncogenic cells by multiple mechanisms, leading to the immune system positive feedback against the tumor. The link between radiotherapy and the immune system is evident. T cells, macrophages, Natural Killer cells and other immune cells seem to have a key role in controlling the tumor. T cells may be dysfunctional and remain in a state of T cell exhaustion, nonetheless, they often retain a high potential for successful defense against cancer, being able to be mobilized to become highly functional. The lack of clinical trials on a large scale makes data a little robust, in spite of promising information, there are still many variables in the studies relating to radiation and immune system. The clarification of the mechanisms underlying immune response to radiation exposure may contribute to treatment improvement, gain of life quality and span of patients.

Type 1 diabetes in children is not a predisposing factor for oral yeast colonization.

Type 1 diabetes mellitus (T1D) is considered a risk factor associated with oral yeast infections. The aim of this study was to evaluate the yeast oral carriage (in saliva and mucosal surface) of children with T1D and potential relation with host factors, particularly the subset of CD4+ T cells. Yeasts were quantified and identified in stimulated saliva and in cheek mucosal swabs of 133 diabetic T1D and 72 healthy control subjects. Salivary lymphocytes were quantified using flow cytometry. The presence of yeasts in the oral cavity (60% of total patients) was not affected by diabetes, metabolic control, duration of the disease, salivary flow rate or saliva buffer capacity, by age, sex, place of residence, number of daily meals, consumption of sweets or frequency of tooth brushing. Candida albicans was the most prevalent yeast species, but a higher number of yeast species was isolated in nondiabetics. T1D children with HbA1c ≤ 7.5 (metabolically controlled) presented higher number of CD4+ T salivary subsets when compared with the other groups of children (non-diabetic and nonmetabolically controlled) and also presented the highest number of individuals without oral yeast colonization. In conclusion, T1D does not predisposes for increased oral yeast colonization and a higher number of salivary CD4+T cells seems to result in the absence of oral colonization by yeasts.

The importance of radiotherapy on diffuse large B cell lymphoma treatment: a current review.

Diffuse large B cell lymphoma is recognized as a heterogeneous group of hematological malignancies; two main subtypes germinal center B and activated B cells are well defined although 15% of patients remain with unclassifiable disease. R-CHOP treatment has proven to provide very effective results in limited or advanced stage of the disease. However, treatment solely involving R-CHOP submits the patient to possible chemotherapy-induced toxicities, which may be avoided with the use of radiotherapy. Patients with early stage localized disease or who are particularly unresponsive to chemotherapy may be more suitable for mixed modality treatment with R-CHOP and consolidative radiotherapy. Although radiotherapy is being slowly phased out by other treatment strategies including chemotherapy and therapeutic drugs, it is still a highly important method of treatment. The different forms of radiotherapy can be used alongside these "new-age" treatment strategies to further improve prognostic outcomes and overall survival rates. The establishment of radiotherapy as a treatment strategy provides a highly beneficial prognostic advantage in early stage, localized disease.

Does progesterone administration in preterm labor influence Treg cells?

OBJECTIVES: The aim of this study was to determine if the actions of progesterone on preterm labor are accomplished through modulation of the percentage of regulatory T-cells (Treg). METHODS: The study was a cohort pilot study made in a single center tertiary obstetrical unit with women in preterm labor arrested with tocolytic treatment. Variation of the number and percentage of Treg cells obtained from peripheral blood samples of women with preterm labor were calculated by flow cytometry, before and after progesterone administration. RESULTS: In the paired samples for each patient, there was a significant difference in the Treg cell pool after progesterone treatment, with an increase in both their percentage (48.9 vs. 53; P=0.07) and absolute number (14.8 vs. 56.5 cells/µL; P=0.046). CONCLUSIONS: This research demonstrated a considerable increase in the Treg cell pool after progesterone treatment. This indicates a possible mechanism for progesterone treatment benefits in preterm labor, potentially increasing its more rational use.

Histomorphometric Evaluation of Ridge Preservation With and Without Connective Tissue Graft Over Buccal Plate Using Different Types of Bone Substitute: An Animal Study.

PURPOSE: The aim of this investigation was to assess the efficacy of using subepithelial connective tissue graft (CTG) over the buccal plate in conjunction with 2 different bone graft materials in fresh extraction sites. MATERIALS AND METHODS: Five mongrel dogs were used. Bilateral third (P3) mandibular premolars were extracted atraumatically. Animals were randomly divided in the 4 experimental groups: no CT (NCT) + anorganic bovine bone (ABB), NCT + biphasic calcium phosphate (BCP), CT + ABB, and CT + BCP. This study evaluated tissue healing at 15, 30, 60, 90, and 120 days after socket preservation, using histologic and histomorphometric analyses. RESULTS: The main finding showed that all groups presented similar results with minor differences regardless of the use of CTG and type of bone substitute. A greater amount of residual graft particles was found when ABB was used. No differences in the histologic and histomorphometric analysis were found when comparing the use of CTG with NCTG for ridge preservation procedure. CONCLUSION: Within the limitations of this animal study, the use of CTG to overbuild the buccal plate at time of tooth extraction did not affect the quality of bone regeneration.

Association of -1082 interleukin-10 gene polymorphism in Peruvian adults with chronic periodontitis.

OBJECTIVES: The aim of this study was to assess association of the -1082 IL-10 gene polymorphism with chronic periodontitis CP in a Peruvian population. STUDY DESIGN: Samples of venous blood and DNA were obtained from 106 Peruvian subjects: a) 53 periodontally healthy; and b) 53 with CP. The association of the -1082 IL-10 promoter sequences was assessed by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Student's t test were used to assess the clinical parameters, as well as the χ2 test and the odds ratio (OR), with 95% confidence intervals (CI) used performed for estimates regarding genotype and allele frequencies. RESULTS: There were statistically significant differences between groups regarding the mean bleeding on probing, mean attachment level and mean probing depth (p < 0.00001) indicating that the matching based on the evaluated groups was adequate. The χ2 test found a statistically significant imbalance of genotypes between groups (p = 0.0172). The prevalence of CP was significantly higher in subjects harboring at least one A allele at position -1082 (AA and GA genotypes) in comparison to patients with the GG genotype (OR = 2.96; CI: 0.52; 5.41; p = 0.0099). Equally, subjects with the AA genotype were significantly associated to a diagnosis of CP (OR = 2.71; CI: 0.38; 5.04; p = 0.0231). On the other hand, subjects presenting a healthy periodontal status presented at least one G allele in comparison with the AA genotype (OR = 0.37; CI: 0.05, 0.69; p = 0.0231). For subjects with the GG genotype, the same positive association was observed (OR = 0.34; CI: 0.06, 0.62; p = 0.0099). There were no significant differences between groups amongst subjects with the GA genotype (OR = 1.19; CI: 0.22, 2.16; p = 0.6774). CONCLUSIONS: Within the limits of this study, IL-10 gene polymorphism at position -1082 does not appear to be associated to CP. Conversely, subjects with AA genotype seem to be at an increased risk of developing CP.

Proximal Medial Gastrocnemius Recession for Recalcitrant Plantar Fasciitis.

BACKGROUND: Recalcitrant plantar fasciitis (RPF) is characterized by its unresponsiveness to conservative treatments, and its surgical management remains controversial. Although there is some evidence to suggest that gastrocnemius recession can be an effective treatment for RPF, no large series of patients with mid- to long-term follow-up has been published. The objective of this study was to compare physical performance, as measured by the Foot and Ankle Ability Measure activities of daily living score (FAAM-ADL), and pain levels before and 1 year after undergoing proximal medial gastrocnemius recession (PMGR) as a treatment for RPF. Additionally, we aimed to assess this cohort of patients in the mid- to long-term follow-up. METHODS: This retrospective cohort study included 167 patients who underwent PMGR to address RPF between 2009 and 2021. Patients were examined with the FAAM ADL, visual analog scale (VAS) and satisfaction scores at baseline, 1 year, and at the end of follow-up. Other variables recorded were weight, duration of symptoms until surgery, time between surgery to substantial clinical improvement, calf power and Silfverskiold test, and postoperative complications. RESULTS: We observed that before surgery patients had an FAAM-ADL score of 22.5 (SD 11.1) and a VAS score of 8.6 (SD 9.3). One year after surgery, patients had an FAAM-ADL score of 89 (SD 17) and VAS of 1.33 (SD 2) (P < .01). We also observed that the FAAM-ADL score in the long-term follow-up (>12.5 years) group had a median of 86.4 (SD 22.6), the VAS score was 1.90 (SD 2.84), and the patient satisfaction score had a median of 1 (interquartile range 0-1). Regarding complications, we observed 1 lateral gastrocnemius recession and 1 sural nerve neuritis. CONCLUSION: Our study provides substantial evidence supporting the use of PMGR as an effective treatment for RPF. The long-term follow-up and large sample size of our series contribute to the existing literature on this topic.

Performance of Cardiovascular Physical Exam Skills by Internal Medicine Residents.

BACKGROUND: Few studies have assessed the ability of internal medicine residents to perform a cardiovascular physical examination using real patients. METHODS: First year internal medicine interns from 2 large academic medical centers in Maryland examined the same patient with aortic insufficiency as part of the Assessment of Physical Examination and Communication Skills (APECS). Interns were assessed on 5 clinical domains: physical exam technique, identifying physical signs, generating a differential diagnosis, clinical judgment, and maintaining patient welfare. Spearman's correlation test was used to describe associations between clinical domains. Preceptor comments were examined to identify common errors in physical exam technique and identifying physical signs. RESULTS: One hundred nine interns examined the same patient with aortic insufficiency across 14 APECS sessions. Only 58 interns (53.2%) correctly identified the presence of a diastolic murmur, and only 52 interns (47.7%) included aortic insufficiency on their differential diagnosis. There was a significant and positive correlation between physical exam technique and identification of the correct physical findings (r = 0.42, P < .001). Both technique (r = 0.34, P = .003) and identifying findings (r = 0.42, P < .001) were significantly associated with generating an appropriate differential diagnosis. Common errors in technique included auscultating over the gown, timing the cardiac cycle with the radial pulse, and failing to palpate for the apical impulse. CONCLUSIONS: Internal medicine interns had variable skills in performing and interpreting the cardiovascular physical exam. Improving cardiovascular exam skills would likely lead to increased identification of relevant cardiovascular findings, inform clinical decision making and improve overall patient care.

Acquired STAT4 deficiency as a consequence of cancer chemotherapy.

Signal Transducer and Activator of Transcription 4 (STAT4) is a transcription factor that is activated by IL-12 signaling and promotes Th1-cell differentiation and IFN-γ production. Defective IFN-γ production because of STAT4 mRNA and protein deficiency occurs after autologous stem cell transplantation for lymphoma. In the present study, we investigated the mechanisms of STAT4 deficiency in lymphoma patients. The tumor-bearing state is not responsible, because STAT4 levels were not significantly different in PBMCs obtained from healthy control subjects compared with those from lymphoma patients before treatment. STAT4 protein levels were significantly decreased in PBMCs and T cells obtained from lymphoma patients after standard-dose chemotherapy. Furthermore, treatment of control PBMC cultures or a natural killer cell line with chemotherapy drugs in vitro also resulted in reduced STAT4 protein and diminished, IL-12-induced IFN-γ production. Translation of STAT4 protein was not impaired in chemotherapy-treated cells, whereas the STAT4 protein half-life was significantly reduced. Chemotherapy drugs promoted the ubiquitination and proteasomal degradation of STAT4. Treatment with the proteasome inhibitor bortezomib reversed chemotherapy-induced STAT4 deficiency and defective IFN-γ production. We conclude that acquired STAT4 deficiency in lymphoma patients is a consequence of treatment with chemotherapy, results that have important implications for the design of optimal immunotherapy for lymphoma.

Can botanic gardens serve as refuges for taxonomic and functional diversity of Odonata? The case of the botanic garden of Castilla-La Mancha (Spain).

In a scenario with declining biodiversity and habitat loss, botanic gardens could serve as refuges for invertebrates, but the opportunities they offer for animal conservation are still poorly understood. Odonata is a good model group for conservation studies, because it includes threatened species and responses to habitat disturbance are well documented. In this study, we assessed the role of the botanic garden of Castilla-La Mancha in Spain as a refuge for members of Odonata by analysing their taxonomic and functional diversity. We explored if the small size of the botanic garden might constrain the taxonomic diversity of Odonata and if low habitat diversity might limit their functional diversity. We sampled adult Odonata from five water bodies along a gradient of human impact and characterized the Odonata communities based on 12 functional traits in Odonata. We used a species-area relationship to control for differences in the size of water bodies. Compared with natural lakes, the Odonata communities contained less species and their functional diversity was lower in the botanic garden ponds, where generalist species were basically hosted. Despite these limitations, the botanic garden ponds hosted the number of species expected for natural water bodies with the moderate surface area and functional diversity, thereby demonstrating that they are a valuable habitat for Odonata in an urban environment. Appropriate management involving the removal of exotic fish and habitat diversification, including creating lotic environments, would increase the taxonomic and functional diversity of Odonata in this urban system. Supplementary Information: The online version contains supplementary material available at 10.1007/s10201-022-00704-3.

Identification of Glaucoma in Diabetics Using the Laguna-ONhE Colourimetric Method and OCT Spectralis.

BACKGROUND: Previous retrospective results are evaluated prospectively and blinded. METHODS: A total of 221 eyes previously classified as normal (G1), 279 as moderate risk of glaucoma (G2) and 217 as high risk (G3) according to the Globin Discriminant Function (GDF) Laguna-ONhE index were examined with OCT Spectralis- Results: In G1, the Bruch's Membrane Opening Minimum Rim Width (BMO-MRW) was 332 ± 55 microns; in G2, it was 252 ± 47 (p < 0.0001); and in G3, 231 ± 44 (p < 0.0001). In G1, the 1% and 5% percentiles were 233 and 248, respectively; in G2, they were lower in 28.80% and 42.29% of cases, respectively; and in G3, in 50.23% and 63.59% of cases, respectively. Most of the cases were normal-tension glaucomas. Laguna-ONhE indices showed a curvilinear correlation with BMO-MRW results. The Retinal Nerve Fibre Layer (RNFL) showed a poor relationship with BMO. Assuming G1 to be truly normal, BMO-MRW would have a Receiver operating characteristic (ROC) curve area of 0.901 for G2 and G3 and 0.651 for RNFL. A significant reduction in pixels corresponding to vessels was found in G2 and G3 vs. G1 (p < 0.0001). CONCLUSIONS: In some cases, these defects appear to be mainly glaucomatous, and in others, they are associated with diabetic microangiopathy. In normal tension glaucoma, RNFL defects may be less severe than those inside the nerve.

Optic disc area frequency distribution in a large sample of retinographic images.

OBJECTIVE: To describe a new method to estimate the frequency distribution of optic nerve disc area, using digital retinographic images. METHODS AND ANALYSIS: We analysed 492 023 fundus images obtained with seven fundus cameras, mainly in Caucasian subjects. They were grouped by resolution and zoom. They were automatically segmented by identifying the inner edge of the Elschnig scleral ring. For this purpose, a neural network trained by deep learning previously described was used. The number of pixels contained within the segmentation and their frequency distribution were calculated. The results of each camera, using different number of images, were compared with the global results using the Kolmogorov-Smirnov test to confront frequency distributions. RESULTS: The frequency distribution was non-Gaussian, more limited in small sizes than in large ones. If the median is assigned a theoretical value of 1.95 mm2, the 1th, 5th, 25th, 50th, 75th, 95th and 99th percentiles would correspond to 1.29, 1.46, 1.73, 1.95, 2.20, 2.64 and 3.03 mm2 in all the dataset. The overall differences were significant for the smaller series, but for each percentile their mean value was only 0.01 mm2 and the maximum 0.10 mm2, so they can be considered similar for practical purposes in all cameras. CONCLUSION: By automatically segmenting the edges of the optic nerve and observing the frequency distribution of the number of pixels it delimits, it is possible to estimate the frequency distribution of the disc area in the population as a whole and that of each individual case.

Glaucoma Incidence and Progression in Diabetics: The Canary Islands Study Using the Laguna ONhE Application.

Background: Laguna ONhE provides a globin distribution function (GDF), in which a glaucoma discriminator based on deep learning plays an important role, and there is also an optimized globin individual pointer (GIP) for progression analysis. Methods: Signs of optic nerve glaucoma were identified in 1,124,885 fundus images from 203,115 diabetics obtained over 15 years and 117,813 control images. Results: A total of 743,696 images from 313,040 eyes of 173,661 diabetics were analysed. Some exclusions occurred due to excessive illumination, poor quality, or the absence of optic discs. Suspicion of glaucoma was reported in 6.70%, for an intended specificity of 99% (GDF < −15). More signs of glaucoma occur in diabetics as their years of disease increase, and after age 60, compared to controls. The GIP detected progression (p < 0.01) in 2.59% of cases with 4 controls and in 42.6% with 14 controls was higher in cases with lower GDF values. The GDF was corrected for the disc area and proved to be independent of it (r = 0.001925; p = 0.2814). Conclusions: The GDF index suggests a higher and increasing glaucoma probability in diabetics over time. Doubling the number of check-ups from four to eight increases the ability to detect GIP index progression by a factor of 5.

Cost of care for asylum seekers and refugees entering the United States: The case of volunteer medical providers in El Paso, Texas.

BACKGROUND: Between October 2018, and February 2020, the United States saw an unprecedented increase in the number of asylum seekers and refugees arriving unexpectedly at international crossings along the US-Mexico Border. Many of these migrants needed proper medical attention, and consequently created significant pressure on local health systems. In El Paso, Texas, volunteer clinicians, collaborating closely with religious organizations and non-governmental organizations, provided outpatient medical care for the new arrivals; the county hospital provided in-patient care at local tax payers' expense. The objective of this study was to estimate costs of healthcare services offered by these volunteers in order to formulate sustainable and appropriate healthcare policies to address the needs of refugees and asylum seekers in the United States. METHODS: A mixed methods approach was used including personal interviews with stakeholders, and follow up surveys with volunteer clinicians. The cost analysis was done from the payer perspective using Medicaid reimbursement rates. RESULTS: Total costs of care provided to asylum seekers and refugees varied between $1.9MM to $4.4MM during the study period. The number of patient visits was estimated at 15,736 to 19,236, and cost per patient ranged between $99 and $281. Most common conditions treated by volunteer providers were abdominal pain, dermatological conditions, headaches, dehydration and hypertension. CONCLUSIONS: This is the first study looking at the cost of healthcare for refugees and asylum seekers provided by volunteer clinicians, in a binational context. The resources invested by volunteer providers were significant, and essential to meet medical needs of migrant populations. Without appropriate financial support, a strategy relying on volunteer and local community resources will prove unsustainable in the long term. Findings from this study will help formulate federal and local policies to support local health systems along the US-Mexico Border in providing care to future migrations into the United States.

Dynamics of Soluble Factors and Double-Negative T Cells Associated with Response to Renal Denervation in Resistant Hypertension Patients.

The role of the immune system, and hence inflammation, in the pathophysiology of hypertensive patients is not clear. Until now, most clinical and biochemical parameters have failed to predict a positive response to renal denervation (RDN). Our aim was to evaluate the immune response in a cohort of patients treated by RDN, through the analysis of cytokine, chemokine, and growth factor behavior. A population of 21 resistant hypertension patients, treated by RDN, was evaluated at six months and one year. Response was defined as a drop of ≥5 mmHg in ambulatory blood pressure monitoring. Sixty-seven percent and 81% of patients clinically responded after six months and one year, respectively. There were no complications or safety issues. Plasmatic levels of 45 cytokine, chemokine, and growth factors were quantified at four different times, pre- and post-procedure. Baseline characteristics were similar between groups, except that active smoking was more frequent in non-responders at one year. Regulated on activation, normal T cell expressed, and secreted (RANTES/CCL5) levels were significantly lower in responders, both at baseline and at 30 days (p = 0.037), and a level ≤15,496 pg/mL was the optimal cutoff, for prediction of a response. IL-15, IL-17A, IL-27, and leukemia inhibitory factor varied significantly in time, with an acute rise being observed 24 h after RDN. Our group has previously showed that HLA-DR+ double-negative (DN) T cells were significantly lower in responders. There was a positive correlation between IL-13, -27, and -4, and DN T cells, and a negative correlation between the latter and SDF-1α and TNF-α, at baseline. Low plasmatic levels of the chemokine RANTES/CCL5 was the most significant result associated with RDN response and may help to identify the best candidates among patients with true resistant hypertension. Pro-inflammatory cytokines correlated negatively with DN T cells in responders, a finding compatible with an enhanced inflammatory milieu present in this extremely high cardiovascular risk cohort.