Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women.

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).

Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.

BACKGROUND: Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear. METHODS: We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total. HIV-1 testing was performed every 4 weeks. The VRC01 80% inhibitory concentration (IC80) of acquired isolates was measured with the TZM-bl assay. RESULTS: Adverse events were similar in number and severity among the treatment groups within each trial. Among the 2699 participants in HVTN 704/HPTN 085, HIV-1 infection occurred in 32 in the low-dose group, 28 in the high-dose group, and 38 in the placebo group. Among the 1924 participants in HVTN 703/HPTN 081, infection occurred in 28 in the low-dose group, 19 in the high-dose group, and 29 in the placebo group. The incidence of HIV-1 infection per 100 person-years in HVTN 704/HPTN 085 was 2.35 in the pooled VRC01 groups and 2.98 in the placebo group (estimated prevention efficacy, 26.6%; 95% confidence interval [CI], -11.7 to 51.8; P = 0.15), and the incidence per 100 person-years in HVTN 703/HPTN 081 was 2.49 in the pooled VRC01 groups and 3.10 in the placebo group (estimated prevention efficacy, 8.8%; 95% CI, -45.1 to 42.6; P = 0.70). In prespecified analyses pooling data across the trials, the incidence of infection with VRC01-sensitive isolates (IC80 <1 µg per milliliter) per 100 person-years was 0.20 among VRC01 recipients and 0.86 among placebo recipients (estimated prevention efficacy, 75.4%; 95% CI, 45.5 to 88.9). The prevention efficacy against sensitive isolates was similar for each VRC01 dose and trial; VRC01 did not prevent acquisition of other HIV-1 isolates. CONCLUSIONS: VRC01 did not prevent overall HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates provided proof-of-concept that bnAb prophylaxis can be effective. (Supported by the National Institute of Allergy and Infectious Diseases; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 ClinicalTrials.gov numbers, NCT02716675 and NCT02568215.).

Association of TLR8 Variants in Sex-Based Clinical Differences in Patients with COVID-19.

The host immune response might confer differential vulnerability to SARS-CoV-2 infection. The Toll-like receptor 8 (TLR8), could participated for severe COVID-19 outcomes. To investigated the relationship of TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G with COVID-19 outcomes and with biochemical parameters. A cross-sectional study of 830 laboratory-confirmed COVID-19 patients was performed, and classified into mild, severe, critical, and deceased outcomes. The TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G polymorphisms were genotyped. A logistic regression analysis was performed to determinate the association with COVID-19. A stratified analysis was by alleles was done with clinical and metabolic markets. In all outcomes, men presented the highest ferritin levels compared to women (P < 0.001). LDH levels were significantly different between sex in mild (P = 0.003), severe (P < 0.001) and deceased (P = 0.01) COVID-19 outcomes. The GGG haplotype showed an Odds Ratio of 1.55 (Interval Confidence 95% 1.05-2.32; P = 0.03) in men. Among patients with severe outcome, we observed that the carriers of the GGG haplotype had lower Ferritin, C-reactive protein and LDH levels than the CAA carriers (P < 0.01). After further stratified by sex, these associations were also seen in the male patients, except for D-dimer. Interestingly, among men patients, we could observe associations between TLR8 haplotypes and Ferritin (P < 0.001), D-dimer (P = 0.04), C-reactive protein, and Lactate dehydrogenase in mild (P = 0.04) group. Our results suggest that even though TLR8 haplotypes show a significant association with COVID-19 outcomes, they are associated with clinical markers in COVID-19 severity.

Compact Wideband Groove Gap Waveguide Bandpass Filters Manufactured with 3D Printing and CNC Milling Techniques.

This paper presents for the first time a compact wideband bandpass filter in groove gap waveguide (GGW) technology. The structure is obtained by including metallic pins along the central part of the GGW bottom plate according to an n-order Chebyshev stepped impedance synthesis method. The bandpass response is achieved by combining the high-pass characteristic of the GGW and the low-pass behavior of the metallic pins, which act as impedance inverters. This simple structure together with the rigorous design technique allows for a reduction in the manufacturing complexity for the realization of high-performance filters. These capabilities are verified by designing a fifth-order GGW Chebyshev bandpass filter with a bandwidth BW = 3.7 GHz and return loss RL = 20 dB in the frequency range of the WR-75 standard, and by implementing it using computer numerical control (CNC) machining and three-dimensional (3D) printing techniques. Three prototypes have been manufactured: one using a computer numerical control (CNC) milling machine and two others by means of a stereolithography-based 3D printer and a photopolymer resin. One of the two resin-based prototypes has been metallized from a silver vacuum thermal evaporation deposition technique, while for the other a spray coating system has been used. The three prototypes have shown a good agreement between the measured and simulated S-parameters, with insertion losses better than IL = 1.2 dB. Reduced size and high-performance frequency responses with respect to other GGW bandpass filters were obtained. These wideband GGW filter prototypes could have a great potential for future emerging satellite communications systems.

Transcranial Direct Current Stimulation in the Treatment of Gait Disturbance in Post-Stroke Patients: An Overview of Systematic Reviews.

INTRODUCTION: Transcranial direct current stimulation (tDCS) is a promising technique for brain modulation after a cerebrovascular accident (CVA). This treatment modality has been previously studied in the recovery of patients. The aim of this review is to analyse the evidence for the application of tDCS in the recovery of gait disturbance in stroke patients. METHODS: This review was conducted according to the recommendations of the PRISMA statement. Three different electronic databases were searched for relevant results: PubMed, Scopus, and Cochrane, from 2015 to January 2022. We included reviews and meta-analyses that only considered randomised controlled trials (RCTs) that investigated the effects of transcranial direct current stimulation, in combination or not with other physiotherapy treatments, compared to no treatment, usual care, or alternative treatment on gait recovery. Our primary outcomes of interest were walking speed, mobility, and endurance; secondary outcomes included motor function. RESULTS: Thirteen studies with a total of 195 RCTs were included. Data on population, outcome measures, protocols, and outcomes were extracted. The Amstar-2 scale and the GRADE system of certainty of evidence were used. Only one study received high certainty of evidence, 5 received low certainty of evidence, and 7 received critically low certainty of evidence. Moderate to low-quality evidence showed a beneficial effect of tDCS on gait parameters, but not significantly. CONCLUSIONS: Although the tDCS produces positive changes in gait recovery in spatio-temporal parameters such as mobility, endurance, strength, and motor function, there is insufficient evidence to recommend this treatment. Higher-quality studies with larger sample sizes are needed for stronger conclusions.

HIV RNA Screening Reduces Integrase Strand Transfer Inhibitor Resistance Risk in Persons Receiving Long-Acting Cabotegravir for HIV Prevention.

BACKGROUND: The HPTN 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was superior to tenofovir-disoproxil fumarate/emtricitabine for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP). Integrase strand transfer inhibitor (INSTI) resistance-associated mutations (RAMs) were detected in some participants with HIV infection. We used a low viral load INSTI genotyping assay to evaluate the timing of emergence of INSTI RAMs and assessed whether HIV screening with a sensitive RNA assay would have detected HIV infection before INSTI resistance emerged. METHODS: Single-genome sequencing to detect INSTI RAMs was performed for samples with viral loads <500 copies/mL from 5 participants with previously identified INSTI RAMs and 2 with no prior genotyping results. RESULTS: Major INSTI RAMs were detected in all 7 cases. HIV RNA testing identified infection before major INSTI RAMs emerged in 4 cases and before additional major INSTI RAMs accumulated in 1 case. Most INSTI RAMs were detected early when the viral load was low and CAB concentration was high. CONCLUSIONS: When using CAB-LA PrEP, earlier detection of HIV infection with a sensitive RNA assay may allow for earlier treatment initiation with the potential to reduce INSTI resistance risk. Further studies are needed to evaluate the value and feasibility of HIV RNA testing with CAB-LA PrEP.

Outpatient prescription patterns of COVID-19 drugs in the metropolitan area of Mexico City.

BACKGROUND: We aimed to describe the use of drugs with apparent efficacy in ambulatory patients with confirmed COVID-19 and the relationship of Google Trends searches with prescriptions and the total number of COVID-19 cases in Mexico City. METHODS: Between March 2020 and February 2021, we surveyed 350 patients confirmed to have COVID-19 across 3 hospitals in Mexico City for their ambulatory prescriptions. We analysed the correlation between prescription patterns of 4 drugs with apparent efficacy against COVID-19, Google Trends searches for these drugs, and the overall number of confirmed COVID-19 cases in Mexico City. RESULTS: We included 350 patients, of whom 59% were women with a median age of 38 years (interquartile range, 29-51), and 72% had a bachelor's degree or higher. There were ambulatory medical prescriptions in 172 (49%) patients, and self-prescriptions were reported in 99 (28%) patients. The prescription rate was high for hydroxychloroquine/azithromycin (19%) and dexamethasone (25%). There was a decrease in the prescription of hydroxychloroquine (P < 0.001) and a strong positive correlation between hydroxychloroquine (r = 0.66; 95% confidence interval, 0.11-0.90; P = 0.02) prescription and online searches for hydroxychloroquine. There was a strong positive correlation between online searches for azithromycin, dexamethasone, ivermectin, and vitamin D and the number of confirmed COVID-19 cases. CONCLUSIONS: During the COVID-19 pandemic, there was a high proportion of prescriptions for hydroxychloroquine/azithromycin and dexamethasone despite their unproven efficacy. Analysis of Google Trends showed a strong correlation between the overall number of confirmed COVID-19 cases and searches for such drugs, suggesting a higher rate of prescriptions. Analysis of online searches could thus help to actively survey public health behaviours in the future.

Unexpected Presence of Blastocystis Subtype 1-3 DNA in Human Vaginal and Sperm Samples Coinfected with Trichomonas vaginalis.

There have been few reports on extra-enteric infections by Blastocystis STs and none have been molecularly identified in samples from human reproductive organs. We report for the first time the identification of 3 different subtypes of Blastocystis (ST1-3) in vaginal and sperm samples, from patients infected with Trichomonas vaginalis. Blastocystis STs were identified by PCR-sequencing and by phylogenetic inferences using 28 vaginal swab samples and 7 sperm samples from patients trichomoniasis. Blastocystis STs were identified in 6 of 28 vaginal swabs (21.4%) and in 3 of 7 sperm samples (42.8%). In both biological samples, STs 1-3 were found; one vaginal sample showed subtype co-infection with ST1 and ST3. High genetic variation was observed in the sequences obtained and no specific clustering in the phylogenetic trees was detected. Most of the haplotypes identified were placed far from the main dispersal centers. Our finding suggested that incorrect cleaning of the genital area or a contamination by combination of anal and vaginal intercourse.

Association between cycle threshold (Ct ) values and clinical and laboratory data in inpatients with COVID-19 and asymptomatic health workers.

In-house assays for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), are feasible alternatives, particularly in developing countries. Cycle threshold (Ct ) values obtained by qRT-PCR were compared with clinical and laboratory data from saliva of inpatients with COVID-19 and asymptomatic health workers (AHW) were studied. Saliva specimens from 58 inpatients confirmed by qRT-PCR for SARS-CoV-2 using nasopharyngeal specimens, and 105 AHW were studied by qRT-PCR using three sets of primers for the N (N1, N2, and N3) gene of SARS-CoV-2, according to the CDC Diagnostic Panel protocol, showing a positivity of 88% for inpatients and 8% for AHW. Bivariate analysis revealed an association between Ct < 38.0 values for N2 and mechanical ventilation assistance among patients (p = .013). In addition, values of aspartate-transaminase, lactate dehydrogenase, and ferritin showed significant correlations with Ct values of N1 and N3 genes in inpatients. Therefore, our results show that Ct values correlate with some relevant clinical data for inpatients with COVID-19.

Immunosenescence profile and expression of the aging biomarker (p16INK4a) in testicular cancer survivors treated with chemotherapy.

BACKGROUND: Cytotoxic chemotherapy can cure advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy. METHODS: Case-control exploratory study of TCS treated with chemotherapy (≥3 BEP cycles, disease-free ≥3 months) compared with age matched healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. CDKN2A/p16INK4a expression in T cells was measured using qPCR. The percentage of lymphocyte subpopulations and the CDKN2A/p16INK4a expression in TCS were compared with the control group using the Wilcoxon signed-rank test. RESULTS: We included 16 cases and 16 controls. The median age was 27 years (minimum 24, maximum 54) and the median time on surveillance was 26.5 months (minimum 3, maximum192). TCS had a lower percentage of total T cells and CD4+ T cells in total lymphocytes. Among the CD4+ T lymphocytes, TCS had less naïve CD4+ and increased memory CD4+ cells. Within the CD8+ T lymphocytes, TCS exhibited a decrease in the percentage of naïve cells and an increase in CD8 + CD45RA + CD57+ cells. TCS also exhibited decreased memory CD19+ B cells compared to the controls. The relative expression of CDKN2A/p16INK4a in T cells was increased in TCS (mean 1.54; 95% CI of the mean: 1.074-2.005; p = 0.048). CONCLUSION: In this exploratory study, TCS showed increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype that has been associated with immunosenescence. Further studies are warranted to define the clinical implications of these alterations in TCS.

Flexible UHF RFID Tag for Blood Tubes Monitoring.

Low-cost and flexible radio frequency identification (RFID) tag for automatic identification, tracking, and monitoring of blood products is in great demand by the healthcare industry. A robust performance to meet security and traceability requirements in the different blood sample collection and analysis centers is also required. In this paper, a novel low-cost and flexible passive RFID tag is presented for blood sample collection tubes. The tag antenna is based on two compact symmetrical capacitive structures and works at the ultra-high frequency (UHF) European band (865 MHz-868 MHz). The tag antenna is designed considering the whole dielectric parameters such as the blood, substrate and tube. In this way, it operates efficiently in the presence of blood, which has high dielectric permittivity and loss. Measurement results of the proposed tag have confirmed simulation results. The measured performance of the tag shows good matching in the desired frequency band, leading to reading ranges up to 2.2 m, which is 4.4 times higher than typical commercial tags. The potential of this tag as a sensor to monitor the amount of blood contained in clinic tubes is also demonstrated. It is expected that the proposed tag can be useful and effective in future RFID systems to introduce security and traceability in different blood sample collection and analysis centers.

Primary Cutaneous Mucormycosis Caused by Rhizopus oryzae: A Case Report and Review of Literature.

Mucormycosis is an invasive infection caused by opportunistic fungi. Rhizopus, Lichtheimia, Mucor and Rhizomucor are the most common isolated genera. Primary cutaneous mucormycosis is usually related to traumatic injuries, but immunocompromised cases are associated with underlying conditions such as diabetes mellitus and malignancies. The treatment of choice is surgical debridement and liposomal amphotericin B. We present a 40-year-old male with fever and a painful necrotic lesion on the middle back and history of poorly controlled diabetes mellitus. Rhizopus oryzae was isolated and identified using an internal transcribed spacer regions ITS1 and ITS2. An initial good response to treatment was observed; however, 7 days later a diabetic ketoacidosis due to poor adherence to treatment caused a lethal outcome.

The obesity paradox in stroke: impact on mortality and short-term readmission.

BACKGROUND: The aim of the present study was to assess the association of obesity with the mortality of hospitalized patients with acute stroke and the risk of readmission in less than 30 days. METHODS: A retrospective chart review of a cohort of consecutive patients admitted with stroke as the primary reason for discharge in Spain between January 1, 2005, and December 31, 2011, was performed. Patients with a diagnosis of obesity were identified. The mortality and readmittance indexes of obese patients were compared against the subpopulation without theses diagnosis. RESULTS: A total of 201,272 stroke admittances were analyzed, and 14,047 (7.0%) diagnosis of obesity were identified. In-hospital global mortality reached 14.9%, and readmittance risk was 5.9%. Obese patients showed a lower in-hospital mortality risk (odds ratio [OR], .71; 95% confidence interval [CI], .67-.76) and early readmittance risk (OR, .89; 95% CI, .82-.96) than the nonobese even after adjusting for possible confounding factors. CONCLUSIONS: Obesity in those hospitalized for stroke is associated with reduced in-hospital mortality risk and early readmittance.

Frequency of hypoglycemia and its impact on length of stay, mortality, and short-term readmission in patients with diabetes hospitalized in internal medicine wards.

OBJECTIVE: To evaluate whether hypoglycemia is associated with increases in length of stay (LOS), inpatient mortality, and readmission among patients with diabetes hospitalized in internal medicine wards. METHODS: A retrospective cohort study was carried out using the Basic Minimum Data Set registry of the Spanish National Health System, which contains clinical and administrative information for every patient discharged from system hospitals. The analysis included patients discharged between January 2005 and December 2010 and had a primary (i.e., reason for the admission) or secondary diagnosis of diabetes and a secondary diagnosis of hypoglycemia. The associations between hypoglycemia and the study outcomes (mortality, readmission, and LOS) were evaluated using multivariate and multilinear regression models that included age, sex, and the Charlson index as covariates. RESULTS: During the study period, 3,361,104 patients were admitted to internal medicine wards in the National Health System. Of these, 921,306 (27.4%) had diagnoses of diabetes, and among these patients, 46,408 (5%) had secondary hypoglycemia. A total of 4,754 (10.2%) patients with secondary hypoglycemia died during their hospital stays, compared with 83,508 (9.5%) patients without hypoglycemia. The multivariate/multilinear regression models demonstrated significant associations between the presence of secondary hypoglycemia and greater inpatient mortality (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.20-1.28), a greater likelihood of readmission (OR 1.20, 95% CI 1.17-1.23), and an increased LOS (ß 1.24, 95% CI 1.15-1.35). CONCLUSION: Hypoglycemia in patients with diabetes hospitalized in internal medicine wards is associated with increases in the LOS, inpatient mortality, and early readmission.

The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes.

Introduction: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes. Methods: To evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity). Results: According to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02). Discussion: Our data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

Elevated Levels of Cytotoxicity, Cytokines, and Anti-SARS-CoV-2 Antibodies in Mild Cases of COVID-19.

Current evidence shows higher production of cytokines and antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) in severe and critical cases of Coronavirus Disease 2019 (COVID-19) in comparison with patients with moderate or mild disease. A recent hypothesis proposes an important role of genotoxicity and cytotoxicity in the induction of the cytokine storm observed in some patients at later stages of the disease. Interestingly, in this study, we report significantly higher levels of interleukin (IL)-1ß, IL-6, MCP-1, and IL-4 cytokines in mild COVID-19 patients versus severe cases, as well as a high frequency of karyorrhexis (median [Me] = 364 vs. 20 cells) and karyolysis (Me = 266 vs. 52 cells) in the mucosal epithelial cells of both groups of patients compared with uninfected individuals. Although we observed higher levels of anti-SARS-CoV-2 IgM and IgG antibodies in COVID-19 patients, IgM antibodies were significantly higher only in mild cases, for the N and the S viral antigens. High levels of IgG antibodies were observed in both mild and severe cases. Our results showed elevated concentrations of proinflammatory and anti-inflammatory cytokines in mild cases, which may reflect an active innate immune response and could be related to the higher IgM and IgG antibody levels found in those patients. In addition, we found that SARS-CoV-2 infection induces cytotoxic damage in the oral mucosa, highlighting the importance of studying the genotoxic and cytotoxic events induced by infection and its role in the pathophysiology of COVID-19.

Implication of myddosome complex genetic variants in outcome severity of COVID-19 patients.

BACKGROUND/PURPOSE(S): During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world. METHODS: We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. RESULTS: A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio = 1.98 (95% IC = 1.04-3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG + GG vs. AA), we observed an Odd Ratio = 1.70 (95% CI = 1.02-2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04-3.21) with critical, and Odd Ratio = 2.44 (95% CI = 1.21-4.9) with deceased outcomes. CONCLUSION: To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.

Imported malaria in pregnancy in Madrid.

BACKGROUND: Malaria in pregnancy is associated with maternal and foetal morbidity and mortality in endemic areas, but information on imported cases to non-endemic areas is scarce.The aim of this study was to describe the clinical and epidemiological characteristics of malaria in pregnancy in two general hospitals in Madrid, Spain. METHODS: Retrospective descriptive study of laboratory-confirmed malaria in pregnant women at the Fuenlabrada University Hospital and the Príncipe de Asturias University Hospital, in Madrid, over a six- and 11-year period, respectively. Relevant epidemiological, clinical and laboratory data was obtained from medical records. RESULTS: There were 19 pregnant women among 346 malaria cases (5.4%). The average age was 27 years. The gestational age (trimester) was: 53% 3rd, 31% 1st, 16% 2nd. All but one were multigravidae. Three were HIV positive. All were sub-Saharan immigrants: two were recently arrived immigrants and seventeen (89%) had visited friends and relatives. None had taken prophylaxis nor seeked pre-travel advice. PRESENTATION: 16 symptomatic patients (fever in fourteen, asthenia in two), three asymptomatic. Median delay in diagnosis: 7.5 days. Laboratory tests: anaemia (cut off Hb level 11 g/dl) 78.9% (mild 31.6%, moderate 31.6%, severe 15.8%) thrombocytopaenia 73.7%, hypoglycaemia 10.5%. All cases were due to Plasmodium falciparum, one case of hyperparasitaemia. Quinine + clindamycin prescribed in 84%. OUTCOMES: no severe maternal complications or deaths, two abortions, fifteen term pregnancies, no low-birth-weight newborns, two patients were lost to follow-up. CONCLUSIONS: Though cases of malaria in pregnancy are uncommon, a most at risk group is clearly defined: young sub-Saharan mothers visiting friends and relatives without pre-travel counselling and recently-arrived immigrants. The most common adverse maternal and foetal effects were anaemia and stillbirth. Given that presentation can be asymptomatic, malaria should always be considered in patients with unexplained anaemia arriving from endemic areas. These findings could help Maternal Health programme planners and implementers to target preventive interventions in the immigrant population and should create awareness among clinicians.

Increased Rate of Protease Inhibitor-resistance Associated Mutations in Human Immunodeficiency Viruses Infecting Mexicans who Had Been Living Abroad.

BACKGROUND: Migrants face multiple barriers to accessing health services and antiretroviral therapy (ART). We tested the hypothesis that HIV-infected ART-experienced Mexicans with a history of residence in the U.S. have a higher rate of viral drug-resistance associated mutations (RAMs) versus those without such a history. METHODS: Viral genotypic resistance tests obtained from 336 HIV-infected Mexican patients throughout the country were analysed for the presence of viral-RAMs and its rate was compared between migrants and non-migrants. Adjustment for potential confounders was done though a multivariate analysis. RESULTS: Eighty-four Mexicans who had lived for at least 3 months in the U.S. were more likely to have three or more protease inhibitor (PI)-major RAMs (aOR = 2.47; 95% CI = 1.06-5.76; p < 0.05) than in 252 individuals without this background, independently of the time spent on ART. CONCLUSIONS: A migration background is associated with a higher likelihood of the emergence of HIV variants with decreased susceptibility to several PI.