Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial.

BACKGROUND: Insulin icodec (icodec) is a basal insulin analogue suitable for once-weekly dosing. ONWARDS 4 aimed to assess the efficacy and safety of once-weekly icodec compared with once-daily insulin glargine U100 (glargine U100) in individuals with long-standing type 2 diabetes on a basal-bolus regimen. METHODS: In this 26-week, phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial, adults from 80 sites (outpatient clinics and hospital departments) across nine countries (Belgium, India, Italy, Japan, Mexico, the Netherlands, Romania, Russia, and the USA) with type 2 diabetes (glycated haemoglobin [HbA1c] 7·0-10·0%) were randomly assigned (1:1) to receive once-weekly icodec or once-daily glargine U100 combined with 2-4 daily bolus insulin aspart injections. The primary outcome was change in HbA1c from baseline to week 26 (non-inferiority margin of 0·3 percentage points). The primary outcome was evaluated in the full analysis set (ie, all randomly assigned participants). Safety outcomes were evaluated in the safety analysis set (ie, all participants randomly assigned who received at least one dose of trial product). This trial is registered with ClinicalTrials.gov, NCT04880850. FINDINGS: Between May 14 and Oct 29, 2021, 746 participants were screened for eligibility, of whom 582 (78%) were randomly assigned (291 [50%] to icodec treatment and 291 [50%] to glargine U100 treatment). Participants had a mean duration of type 2 diabetes of 17·1 years (SD 8·4). At week 26, estimated mean change in HbA1c was -1·16 percentage points in the icodec group (baseline 8·29%) and -1·18 percentage points in the glargine U100 group (baseline 8·31%), showing non-inferiority for icodec versus glargine U100 (estimated treatment difference 0·02 percentage points [95% CI -0·11 to 0·15], p<0·0001). Overall, 171 (59%) of 291 participants in the icodec group and 167 (57%) of 291 participants in the glargine U100 group had an adverse event. 35 serious adverse events were reported in 22 (8%) of 291 participants in the icodec group and 33 serious adverse events were reported in 25 (9%) of 291 participants receiving glargine U100. Overall, combined level 2 and level 3 hypoglycaemia rates were similar between treatment groups. No new safety concerns were identified for icodec. INTERPRETATION: In people with long-standing type 2 diabetes on a basal-bolus regimen, once-weekly icodec showed similar improvements in glycaemic control, with fewer basal insulin injections, lower bolus insulin dose, and with no increase in hypoglycaemic rates compared with once-daily glargine U100. Key strengths of this trial include the use of masked continous glucose monitoring; the high trial completion rate; and the inclusion of a large, diverse, and multinational population. Limitations include the relatively short trial duration and the open-label design. FUNDING: Novo Nordisk.

Is there a role for magnetic resonance imaging in cesarean scar pregnancy after the first trimester?

Magnetic resonance imaging (MRI) can provide additional information in cases of cesarean scar pregnancy beyond the first trimester. MRI and 3D reconstructions can demonstrate the relationships between the uterus, cervix, bladder, and placenta, improving the spatial perspective of the pelvic anatomy in cases requiring surgical management. MRI and 3D reconstructions can also provide more comprehensive images for parental counseling, virtual and face-to-face multidisciplinary team discussion, and medical record storage.

Talaromyces marneffei isolated from nasal swabs in Portugal.

Mycobiota are essential to the health of any living being, creating a balanced and complex interaction between bacteria, the immune system, and the tissue cells of the host. Talaromyces marneffei (also known as Penicillium marneffei) is a dimorphic fungus, endemic in South Asia, which often causes a life-threatening systemic fungal infection (called penicilliosis), particularly in immunocompromised hosts. Nasal swabs from 73 healthy volunteers were analysed to characterize their mycobiota, through its cultural characteristics, morphology, and molecular methods (PCR). All volunteers were also asked to answer to an anonymous questionnaire. Three women were positive (and asymptomatic) for T. marneffei. One of them was reported to have lupus. This study contributes to improving our knowledge about human normal mycobiota, identifying mycotic agents that may cause complicated systemic infections (as T. marneffei), especially in immunosuppressed patients, as well as other possible risk factors of exposure or prognosis.

• Talaromyces marneffei is a zoonotic fungus that may be responsible for life-threatening systemic infections in immune-comprised patients. • Talaromyces marneffei was identified in nasal swabs from asymptomatic volunteers. • This suggests that this fungus may be part of the nasal normal mycobiota of some humans.

Crosstalk between estrogen, dendritic cells, and SARS-CoV-2 infection.

The novel coronavirus disease 2019 (Covid-19) first appeared in Wuhan and has so far killed more than four million people worldwide. Men are more affected than women by Covid-19, but the cellular and molecular mechanisms behind these differences are largely unknown. One plausible explanation is that differences in sex hormones could partially account for this distinct prevalence in both sexes. Accordingly, several papers have reported a protective role of 17ß-estradiol during Covid-19, which might help explain why women appear less likely to die from Covid-19 than men. 17ß-estradiol is the predominant and most biologically active endogenous estrogen, which signals through estrogen receptor α, estrogen receptor ß, and G protein-coupled estrogen receptor 1. These receptors are expressed in mature cells from the innate and the adaptive immune system, particularly on dendritic cells (DCs), suggesting that estrogens could modulate their effector functions. DCs are the most specialized and proficient antigen-presenting cells, acting at the interface of innate and adaptive immunity with a powerful capacity to prime antigen-specific naive CD8+ T cells. DCs are richly abundant in the lung where they respond to viral infection. A relative increase of mature DCs in broncho-alveolar lavage fluids from Covid-19 patients has already been reported. Here we will describe how SARS-CoV-2 acts on DCs, the role of estrogen on DC immunobiology, summarise the impact of sex hormones on the immune response against Covid-19, and explore clinical trials regarding Covid-19.

Promising natural products for the treatment of cutaneous leishmaniasis: A review of in vitro and in vivo studies.

Although there are available treatments for cutaneous leishmaniasis (CL), the drugs used are far from ideal, toxic, and costly, in addition to the challenge faced by the development of resistance. Plants have been used as a source of natural compounds with antileishmanial action. However, few have reached the market and become phytomedicines with registration in regulatory agencies. Difficulties related to the extraction, purification, chemical identification, efficacy, safety, and production in sufficient quantity for clinical studies, hinder the emergence of new effective phytomedicines against leishmaniasis. Despite the difficulties reported, the major research centers in the world see that natural products are a trend concerning the treatment of leishmaniasis. The present work consists of a literature review of articles with in vivo studies, covering the period from January 2011 to December 2022, providing an overview of promising natural products for CL treatment. The papers show encouraging antileishmanial action of natural compounds with reduced parasite load and lesion size in animal models, suggesting new strategies for the treatment of the disease. The results reported in this review show advances in using natural products as safe and effective formulations, which can stimulate clinical studies to establish clinical therapy. In conclusion, the information in this review article serves as a preliminary basis for establishing a therapeutic protocol for future clinical trials that can validate the safety and efficacy of natural compounds, providing the development of affordable and safe phytomedicines for the treatment of CL.

Prenatal diagnosis of closed gastroschisis: What to expect in the most severe form of gastroschisis? Case report and literature review.

Closed gastroschisis (CG) and vanishing gastroschisis (VG) are the most severe forms of evolution of the malformation. In this case, a fetus presented with gastroschisis at 13 weeks, and the gastroschisis was not visualized at 22 weeks of gestation. Distal ileum, cecum, and ascending colon atresia were diagnosed at surgery, and the child is fully enteral-fed at 5 months of age. In a literature review of 43 cases of prenatal diagnosis of CS-VG, intrauterine death occurred in 4.5% of cases. 79.6% of the cases underwent surgical treatment. Of these cases, 20% of cases died due to complications of treatment, 26% were still under treatment and 54% are alive with enteral feeding. In 77% of the cases, the closure of the umbilical ring occurred after 26 weeks of gestation and the absence of prenatal diagnosis of CG-VG during pregnancy has a risk of 71% of death.

Anti-Algics in the Therapeutic Response of Breast and Urological Cancers.

The effect of anti-algics on tumor progression and the overall survival of patients is controversial and remains unclear. Herein, we disclose the in vitro effects of the local anesthetics lidocaine, ropivacaine, and levobupivacaine on breast (MCF7), prostate (PC3, LNCaP), and bladder (TCCSUP, HT1376) cancer cell lines, both as monotherapy and in combination with standard-of-care therapeutics. Assays for cell proliferation, viability, death profile, and migration were performed. Additionally, we explored the clinical outcomes of opioid use through a cross-sectional study involving 200 metastatic prostate cancer patients. The main clinical data collected included the type of opioid therapy administered, dosage, treatment duration, disease progression, and overall survival. Results obtained demonstrate that treatment with local anesthetics has a promising selective anti-tumor effect on these types of cancer, with higher effects when associated with docetaxel. This points out the use of local anesthetics as an added value in the treatment of prostate carcinoma patients. Alternatively, chronic opioid use was correlated with reduced overall survival (p < 0.05) and progression-free survival (p < 0.05) at each treatment line in the observational study. While these results provide valuable insights, larger prospective studies are imperative to comprehensively evaluate the clinical impact of opioid analgesics in prostate cancer patients.

Molluscicidal and Cercaricidal Effects of Myrciaria floribunda Essential Oil Nanoemulsion.

Schistosomiasis is a tropical disease transmitted in an aqueous environment by cercariae from the Schistosoma genus. This disease affects 200 million people living in risk areas around the world. The control of schistosomiasis is realized by chemotherapy, wastewater sanitation, health education, and mollusk control using molluscicidal agents. This work evaluates the effects of a nanoemulsion containing essential oil from Myrciaria floribunda leaves as a molluscicidal and cercaricidal agent against Biomphalaria glabrata mollusks and Schistosoma mansoni cercariae. The Myrciaria floribunda essential oil from leaves showed nerolidol, ß-selinene, 1,8 cineol, and zonarene as major constituents. The formulation study suggested the F3 formulation as the most promising nanoemulsion with polysorbate 20 and sorbitan monooleate 80 (4:1) with 5% (w/w) essential oil as it showed a smaller droplet size of approximately 100 nm with a PDI lower than 0.3 and prominent bluish reflection. Furthermore, this nanoemulsion showed stability after 200 days under refrigeration. The Myrciaria floribunda nanoemulsion showed LC50 values of 48.11 µg/mL, 29.66 µg/mL, and 47.02 µg/mL in Biomphalaria glabrata embryos, juveniles, and adult mollusks, respectively, after 48 h and 83.88 µg/mL for Schistosoma mansoni cercariae after 2 h. In addition, a survival of 80% was observed in Danio rerio, and the in silico toxicity assay showed lower overall human toxicity potential to the major compounds in the essential oil compared to the reference molluscicide niclosamide. These results suggest that the nanoemulsion of Myrciaria floribunda leaves may be a promising alternative for schistosomiasis control.

Definition of low disease activity state based on the SLE-DAS: derivation and validation in a multicentre real-life cohort.

OBJECTIVES: To derive and validate a definition of low disease activity (LDA) for SLE based on the SLE Disease Activity Score (SLE-DAS), in a real-life multicentre cohort of SLE patients. METHODS: Derivation was conducted using data from a monocentric cohort of SLE (Portugal), and validation was performed in a multicentre cohort (Italy, France and Spain). The Lupus Low Disease Activity State (LLDAS) was used as comparator. We applied receiver operating characteristics curve analysis against the LLDAS to determine the cut-off of SLE-DAS for LDA using bootstrap methodology. In a second step, we tested a definition of SLE-DAS LDA that included: (i) the statistically derived SLE-DAS upper threshold for LDA and (ii) prednisone dose ≤7.5 mg/day. In the multicentre validation cohort, we assessed the classification performance of this SLE-DAS LDA definition. RESULTS: We included 774 patients, 300 in the derivation and 474 in the validation cohort. In the derivation cohort, the optimal cut-off to identify patients in LLDAS was SLE-DAS ≤2.48, presenting an area under the curve of 0.965 (95% CI 0.935, 0.994). When applied to the multicentre validation cohort, the SLE-DAS LDA definition showed a sensitivity of 97.1% and a specificity of 97.7% for LLDAS and an almost perfect agreement (Cohen's Kappa = 0.933; P < 0.001). McNemar's test found no significant differences between the two definitions (P = 0.092). CONCLUSION: The SLE-DAS LDA is a validated, accurate and easy-to-use definition for classifying SLE patients in LDA state.

Speaking the language of lipids: the cross-talk between plants and pathogens in defence and disease.

Lipids and fatty acids play crucial roles in plant immunity, which have been highlighted over the past few decades. An increasing number of studies have shown that these molecules are pivotal in the interactions between plants and their diverse pathogens. The roles played by plant lipids fit in a wide spectrum ranging from the first physical barrier encountered by the pathogens, the cuticle, to the signalling pathways that trigger different immune responses and expression of defence-related genes, mediated by several lipid molecules. Moreover, lipids have been arising as candidate biomarkers of resistance or susceptibility to different pathogens. Studies on the apoplast and extracellular vesicles have been highlighting the possible role of lipids in the intercellular communication and the establishment of systemic acquired resistance during plant-pathogen interactions. From the pathogen perspective, lipid metabolism and specific lipid molecules play pivotal roles in the pathogen's life cycle completion, being crucial during recognition by the plant and evasion from the host immune system, therefore potentiating infection. Studies conducted in the last years have contributed to a better understanding of the language of lipids during the cross-talk between plants and pathogens. However, it is essential to continue exploring the knowledge brought up to light by transcriptomics and proteomics studies towards the elucidation of lipid signalling processes during defence and disease. In this review, we present an updated overview on lipids associated to plant-pathogen interactions, exploiting their roles from the two sides of this battle.

Diffuse dermal angiomatosis: a rare cause of painful ulceration in renal insufficiency.

Diffuse dermal angiomatosis is a rare, benign, reactive cutaneous vascular proliferation that has been reported in the context of end-stage renal failure and can rarely be associated with arteriovenous fistulas. We report a striking clinical resolution following prompt diagnosis and subsequent arteriovenous fistula reversal. This case further demonstrates that accurate diagnosis is particularly rewarding since correct therapeutic approach can be curative.

Contact allergy to antifungals: Results of a 12-year retrospective study.

BACKGROUND: Contact allergy has been reported as a side effect of topical antifungals (TAFs), although most evidence has come from small case series. OBJECTIVE: To investigate the frequency and associated factors of contact allergy to TAFs. METHODS: We performed a retrospective analysis of the data of the Contact Allergy Unit of a University Dermatology Department between January 2009 and April 2021. From a cohort of 3788 patients tested in our unit, aimed testing was performed in 482 patients using TAFs from Chemotechnique Diagnostics (Vellinge, Sweden), allergEAZE, and, in some cases, commercial preparations 'as is'. RESULTS: Contact allergy to antifungals was found in 27 patients (0.71% of consecutively tested patients and 5.6% of those who had aimed testing). Foot and leg eczema were the clinical presentation in 12 (44.4%) and 10 (37.0%) patients, respectively. Positive reactions were observed mostly with econazole nitrate 1% alcohol (51.9%), miconazole 1% alcohol (48.9%), tioconazole 28% solution (40.7%), and clotrimazole 5% pet. (18.5%). Fifteen patients (55.6%) had sensitization to more than one antifungal. CONCLUSIONS: Contact allergy to antifungals was uncommon and occurred mostly associated with foot dermatitis. Most patients were sensitized to more than one chemical, particularly to azoles, which may limit future choices of TAF treatment.

Development of colorimetric cellulose-based test-strip for the rapid detection of antibodies against SARS-CoV2 virus.

Given the pandemic situation, there is an urgent need for an accurate test to monitor antibodies anti-SARS-CoV-2, providing crucial epidemiological and clinical information to monitor the evolution of coronavirus disease in 2019 (COVID-19) and to stratify the immunized and asymptomatic population. Therefore, this paper describes a new cellulose-based test strip for rapid and cost-effective quantitative detection of antibodies to SARS-CoV2 virus by colorimetric transduction. For this purpose, Whatman paper was chemically modified with sodium metaperiodate to introduce aldehyde groups on its surface. Subsequently, the spike protein of the virus is covalently bound by forming an imine group. The chemical control of cellulose paper modification was evaluated by Fourier transform infrared spectroscopy, thermogravimetry and contact angle analysis. Colorimetric detection of the antibodies was performed by a conventional staining method using Ponceau S solution as the dye. Color analysis was performed after image acquisition with a smartphone using Image J software. The color intensity varied linearly with the logarithm of the anti-S concentration (from 10 ng/mL to 1 µg/mL) in 500-fold diluted serum samples when plotted against the green coordinate extracted from digital images. The test strip was selective in the presence of nucleocapsid antibodies, urea, glucose, and bovine serum albumin with less than 15% interference, and detection of antibodies in human serum was successfully performed. Overall, this is a simple and affordable design that can be readily used for mass population screening and does not require sophisticated equipment or qualified personnel. Supplementary Information: The online version contains supplementary material available at 10.1007/s10570-022-04808-y.

Virtual segmentation of three-dimensional ultrasound images of morphological structures of an ex vivo ectopic pregnancy inside a fallopian tube.

Ex vivo ultrasound (US) of human tissues has been used for decades on the study of the acoustic physical aspects of the US, to the study of the morphology of the organs. Using three-dimensional (3D) US, we demonstrate the possibilities to study surgical specimens from gynecological conditions. 3D images of the surgical specimen were collected and virtually segmented according to the contrast of its images, providing a 3D image of the ectopic pregnancy and its effects on the fallopian tube.

The Potential Effect of Lidocaine, Ropivacaine, Levobupivacaine and Morphine on Breast Cancer Pre-Clinical Models: A Systematic Review.

Breast cancer (BC) is one of the most common types of cancer and the second leading cause of death in women. Local anaesthetics (LAs) and opioids have been shown to influence cancer progression and metastasis formation in several pre-clinical studies. However, their effects do not seem to promote consensus. A systematic review was conducted using the databases Medline (via PubMed), Scopus, and Web of Science (2010 to December 2021). Search terms included "lidocaine", "ropivacaine", "levobupivacaine", "morphine", "methadone", "breast cancer", "breast carcinoma" and "breast neoplasms" in diverse combinations. The search yielded a total of 784 abstracts for initial review, 23 of which met the inclusion criteria. Here we summarise recent studies on the effect of analgesics and LAs on BC cell lines and animal models and in combination with other treatment regimens. The results suggest that local anaesthetics have anti-tumorigenic properties, hence their clinical application holds therapeutic potential. Regarding morphine, the findings are conflicting, but this opioid appears to be a tumour-promoting agent. Methadone-related results are scarce. Additional research is clearly required to further study the mechanisms underlying the controversial effects of each analgesic or LA to establish the implications upon the outcome and prognosis of BC patients' treatment.

Anxiety and Depression from Childhood to Young Adulthood: Trajectories and Risk Factors.

This study aimed to (1) evaluate how population levels of anxiety and depression grow and correlate from middle childhood through early adulthood, and (2) determine whether sex, family socioeconomic status, parental education, academic achievement, learning disabilities, or externalizing symptoms predict anxiety and/or depression levels and growth trajectory. We used two longitudinal samples (N = 445, 448) of Portuguese children. Mean depression levels increased from mid-childhood through adolescence before stabilizing in early adulthood and were most strongly predicted by academic achievement and learning disabilities. Mean anxiety levels increased until adolescence before decreasing across early adulthood and were most strongly predicted by academic achievement, learning disabilities, and externalizing symptoms. Quadratic models of growth fit best for both depression and anxiety, and depression and anxiety growth trajectories were strongly correlated. Though anxiety and depression trajectories differ in pattern and predictors, the two are highly interrelated and pathways to comorbid anxiety and depression should be characterized.

Reliability and Validity of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): Portuguese Version.

This study examined the test-retest reliability, consensual, convergent and divergent validities, sensitivity, specificity, positive and negative predictive values, and accuracy of the Portuguese version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). Eighty-nine children/adolescents (65 psychiatric outpatients and 24 healthy controls) were interviewed with K-SADS-PL and completed measures of depressive and anxiety symptoms. The child's parent/caretaker completed the Child Behavior Checklist. Good to excellent values were obtained for test-retest reliability and consensual validity. For the convergent validity, moderate correlations between the K-SADS-PL and the corresponding self-report measures were observed. Divergent validity was acceptable for the K-SADS-PL diagnoses. The lowest values of sensitivity, specificity, and accuracy of the K-SADS-PL were 88, 88, and 91, respectively. The Portuguese version of K-SADS-PL proved to be a valid and reliable assessment instrument for children and adolescents, and was sensitive, specific and accurate when diagnosing mood, anxiety, adjustment, and attention-deficit/hyperactivity disorders.

Dry Dosage Forms of Add-Value Bioactive Phenolic Compounds by Supercritical CO2-Assisted Spray-Drying.

Every year, grapevine pruning produces huge amounts of residue, 90% of which are from vine shoots. These are a rich source of natural antioxidants, mostly phenolic compounds, which, when properly extracted, can give rise to added-value products. However, their lack of solubility in aqueous media and high susceptibility to thermal and oxidative degradation highly limit their bioavailability. Encapsulation in suitable carriers may have a positive impact on their bioavailability and bioactivity. Previous data on vine-shoot extraction have identified gallic acid (GA) and resveratrol (RSV) as the main phenolic compounds. In this work, model dry powder formulations (DPFs) of GA and RSV using hydroxypropyl cellulose (HPC) as carriers were developed using Supercritical CO2-Assisted Spray Drying (SASD). A 32 full factorial Design of Experiments investigated the solid and ethanol contents to ascertain process yield, particle size, span, and encapsulation efficiency. Amorphous powder yields above 60%, and encapsulation efficiencies up to 100% were achieved, representing excellent performances. SASD has proven to be an efficient encapsulation technique for these phenolic compounds, preserving their antioxidation potential after three months in storage with average EC50 values of 30.6 µg/mL for GA-DPFs and 149.4 µg/mL for RSV-DPF as assessed by the scavenging capacity of the DPPH radical.

Increased Body Fat and Organic Acid Anions Production Are Associated with Larger Kidney Size in ADPKD.

Background and Objectives: A high body mass index (BMI) is associated with the progression of autosomal dominant polycystic kidney disease (ADPKD). However, body fat (BF), which is another adiposity marker, has not yet been studied. Excessive weight may promote elevation in the endogenous synthesis of organic acid (OA) anions. Accordingly, we aimed to investigate the possible association of the aforementioned markers with kidney volume and renal function in patients with ADPKD. Materials and Methods: We conducted a retrospective cohort study of adult ADPKD outpatients involving clinical, serum, and urinary laboratorial data and body composition assessments retrieved from their medical records. BF was estimated by skinfold thickness (mm) on the non-dominant arm and was considered as normal or high for each sex. Total kidney volume (TKV) and height-adjusted volume (htTKV) were measured by magnetic resonance imaging. The annual estimated glomerular filtration rate (eGFR) slope was analyzed during a median follow-up time of 6 (5.0-7.0) years to calculate rapid progression (decline in renal function ≥2.5 mL/min/year over 5 years). Results: A total of 104 patients were included (41.9 ± 11.9 years old, 38.5% men), with 62.5% of the patients classified as high BF. The High BF group presented higher levels of OA, glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), 24 h urinary sodium (UNa), and htTKV, and lower eGFR than those with a normal BF. In the multivariate linear regression, the associated variables with TKV were high BF, OA and BMI (std. ß 0.47, p < 0.05; std. ß 0.36, p = 0.001; std. ß 0.25, p = 0.01, respectively). In the binary logistic regression, when adjusted for potential confounders, UNa was the only parameter associated with an increased risk of eGFR decline ≥2.5 mL/min/year (OR 1.02, 95% CI 1.01-1.03, p = 0.02). Conclusions: Increased body fat and endogenous production of organic acid anions are associated with larger kidney size in ADPKD but not with a decline in renal function.

miRNA profiling of human naive CD4 T cells links miR-34c-5p to cell activation and HIV replication.

Cell activation is a vital step for T-cell memory/effector differentiation as well as for productive HIV infection. To identify novel regulators of this process, we used next-generation sequencing to profile changes in microRNA expression occurring in purified human naive CD4 T cells in response to TCR stimulation and/or HIV infection. Our results demonstrate, for the first time, the transcriptional up-regulation of miR-34c-5p in response to TCR stimulation in naive CD4 T cells. The induction of this miR was further consistently found to be reduced by both HIV-1 and HIV-2 infections. Overexpression of miR-34c-5p led to changes in the expression of several genes involved in TCR signaling and cell activation, confirming its role as a novel regulator of naive CD4 T-cell activation. We additionally show that miR-34c-5p promotes HIV-1 replication, suggesting that its down-regulation during HIV infection may be part of an anti-viral host response.