Caregivers' psychosocial assessment for identifying HIV-infected infants at risk of poor treatment adherence: an exploratory study in southern Mozambique.

Psychosocial support (PSS) to caregivers of HIV-infected infants on antiretroviral treatment (ART) is crucial to ensure ART adherence and sustained long-term viral suppression in children. A specific approach including tools to monitor and understand adherence behavior and risk factors that prevent optimal treatment compliance are urgently needed. This qualitative exploratory study, conducted in southern Mozambique, monitored the infants' viral response trajectories during 18 months follow-up, as a measure of adherence, reviewed the caregiver's PSS session notes and the answers to a study questionnaire, to analyze whether the standard PSS checklist applied to infants' caregivers can identify barriers influencing their adherence. Only 9 of 31 infants had sustained virologic response. Reported factors affecting adherence were: difficulties in drugs administration, shared responsibility to administer treatment; disclosure of child's HIV status to family members but lack of engagement; mother's ART interruption and poor viral response. In conclusion, we found that the standard PSS approach alone, applied to caregivers, was lacking focus on many relevant matters that were identified by the study questionnaire. A comprehensive patient-centered PSS package of care, including an adherence risk factor monitoring tool, tailored to caregivers and their children must be developed.

Reasons for non-disclosure of HIV-Positive status to healthcare providers: a mixed methods study in Mozambique.

BACKGROUND: Non-disclosure of known HIV status by people living with HIV but undergoing HIV testing leads to waste of HIV testing resources and distortion of estimates of HIV indicators. In Mozambique, an estimated one-third of persons who tested positive already knew their HIV-positive status. To our knowledge, this study is the first to assess the factors that prevent people living with HIV (PLHIV) from disclosing their HIV-positive status to healthcare providers during a provider-initiated counseling and testing (PICT) campaign. METHODS: This analysis was nested in a larger PICT cross-sectional study performed in the Manhiça District, Southern Mozambique from January to July 2019, in which healthcare providers actively asked patients about their HIV-status. Patients who tested positive for HIV were crosschecked with the hospital database to identify those who had previously tested positive and were currently or previously enrolled in care. PLHIV who did not disclose their HIV-positive status were invited to participate and provide consent, and were interviewed using a questionnaire designed to explore barriers, patterns of community/family disclosure, and stigma and discrimination. RESULTS: We found that 16.1% of participants who tested positive during a PICT session already knew their HIV-positive status but did not disclose it to the healthcare provider. All the participants reported previous mistreatment by general healthcare providers as a reason for nondisclosure during PICT. Other reasons included the desire to know if they were cured (33.3%) or to re-engage in care (23.5%). Among respondents, 83.9% reported having disclosed their HIV-status within their close community, 48.1% reported being victims of verbal or physical discrimination following their HIV diagnosis, and 46.7% reported that their HIV status affected their daily activities. CONCLUSION: Previous mistreatment by healthcare workers was the main barrier to disclosing HIV-positive status. The high proportion of those disclosing their HIV status to their community but not to healthcare providers suggests that challenges with patient-provider relationships affect this care behavior rather than social stigma and discrimination. Improving patient-provider relationships could increase trust in healthcare providers, reduce non-disclosures, and help optimize resources and provide accurate estimates of the UNAIDS first 95 goal.

Optimizing the World Health Organization algorithm for HIV vertical transmission risk assessment by adding maternal self-reported antiretroviral therapy adherence.

BACKGROUND: The World Health Organization (WHO) risk assessment algorithm for vertical transmission of HIV (VT) assumes the availability of maternal viral load (VL) result at delivery and early viral control 4 weeks after initiating antiretroviral treatment (ART). However, in many low-and-middle-income countries, VL is often unavailable and mothers' ART adherence may be suboptimal. We evaluate the inclusion of the mothers' self-reported adherence into the established WHO-algorithm to identify infants eligible for enhanced post-natal prophylaxis when mothers' VL result is not available at delivery. METHODS: We used data from infants with perinatal HIV infection and their mothers enrolled from May-2018 to May-2020 in Mozambique, South Africa, and Mali. We retrospectively compared the performance of the WHO-algorithm with a modified algorithm which included mothers' adherence as an additional factor. Infants were considered at high risk if born from mothers without a VL result in the 4 weeks before delivery and with adherence <90%. RESULTS: At delivery, 143/184(78%) women with HIV knew their status and were on ART. Only 17(12%) obtained a VL result within 4 weeks before delivery, and 13/17(76%) of them had VL ≥1000 copies/ml. From 126 women on ART without a recent VL result, 99(79%) had been on ART for over 4 weeks. 45/99(45%) women reported suboptimal (< 90%) adherence. A total of 81/184(44%) infants were classified as high risk of VT as per the WHO-algorithm. The modified algorithm including self-adherence disclosure identified 126/184(68%) high risk infants. CONCLUSIONS: In the absence of a VL result, mothers' self-reported adherence at delivery increases the number of identified infants eligible to receive enhanced post-natal prophylaxis.

Color stability of repairs on bis-acryl resin submitted to thermal aging and immersion in beverages.

OBJECTIVE: Defects/bubbles can occur during the manufacture of bis-acryl resin provisional restorations, requiring repair or new prosthesis. This study evaluated the color stability of bis-acryl resin specimens repaired, aging, and immersioned in beverages. MATERIAL AND METHODS: Eighty disks were made of bis-acryl resin. Twenty disks were not repaired (BCR), 20 disks were repaired with the same bis-acryl resin (BCR-BCR), 20 disks were repaired with flowable resin (BCR-FR), and 20 disks received an adhesive layer prior to flowable resin repair (BCR-AFR). Coordinates L*a*b* were obtained. Ten disks from each group were thermocycled (5000 cycles) and the others were immersed in coffee with sugar (n = 5) and cola-based soft drinks (n = 5) for 7 days. Color, lightness, chroma, and hue differences were calculated by the CIEDE2000 formula, analyzed by two-way analysis of variance. Multiple comparisons were made with the Tukey's HSD test (α = .05). RESULTS: BCR-FR group presented the highest color differences (5.6) between groups repaired (P < .001). BCR-BCR group showed the smallest color differences (0.9) after aging (P = .003), but the greatest variation between T0 and T1 (about 1 ΔE). BCR-ARF immersed in coffee showed the greatest color differences (20.6) (P < .001). CONCLUSIONS: Aging and immersion altered the colorimetric behavior of repairs, especially after the use of coffee. CLINICAL IMPLICATIONS: Repairs are indicated when defects and bubbles are present in the surface of the bis-acryl resin provisional restorations after its manufacture. However, they may present noticeable color changes, especially when the use of coffee is frequent.

Esthetic and functional rehabilitation of bilateral congenital absence of maxillary lateral incisors: Minimally invasive surgical and prosthetic approach.

OBJECTIVE: Congenital absence of maxillary lateral incisors is a frequent clinical challenge which must be solved by a multidisciplinary approach in order to obtain an esthetic and functional restorative treatment. Noninvasive treatments, that are in accordance with the patients' expectations, should be the first therapeutic alternative. If the deciduous tooth is present, minimally invasive dental extraction followed by immediate dental implant placement and provisional restoration is indicated. In this restorative treatment, an adequate emergency profile can be achieved by peri-implant soft-tissue-conditioning techniques. Moreover, the association of restorative materials, such as composite resins and dental ceramics, provides more predictable esthetic results. CLINICAL CONSIDERATIONS: The present case report presents a rehabilitation of bilateral congenital absence of maxillary lateral incisors through a multidisciplinary approach. Dental implants, long-term provisional restoration, tooth bleaching, minimally veneered high-translucent monolithic zirconia crowns, feldspathic veneers, and composite restorations were used by the dental team to achieve the expected functional and esthetic outcomes. CONCLUSIONS: Different treatment modalities are available for the rehabilitation of congenital absence of teeth. However, it is important that a dental team consider performing minimally invasive treatments, as many of these treatments are done on young patients. CLINICAL SIGNIFICANCE: Patient-centered treatments involving minimally invasive approaches in a multidisciplinary environment would be appropriate in order to achieve predictable results.

Color stability of a bis-acryl composite resin subjected to polishing, thermocycling, intercalated baths, and immersion in different beverages.

OBJECTIVE: To evaluate the color of a bis-acryl resin after polishing, aging, and colorants. MATERIALS AND METHODS: From the 140 disks obtained, 35 were not polished (NP), 35 were polished with 3-µm (3P), 35 with 3- and 1-µm (1P), and 35 with 3-, 1-, and 0.5-µm sized particles (05P). Five disks of each group were thermocycled for 20, 100, and 200 cycles. Sixty disks were thermocycled and kept in beverages (tea, wine, and coffee) after four cycles. Sixty disks were immersed in the beverages for 24 hours, a week, and a month. The coordinates L*a*b* were measured and the color differences were analyzed by ANOVA. The lightness, chroma, and hue differences were evaluated by repeated measures ANOVA. Comparisons were made with Tukey's test (α = 0.05). RESULTS: Similar behaviors were observed between 3P and 05P groups (1.53 and 1.95ΔE00 ) (P < .05). The NP group submitted to 200 cycles showed the biggest color differences (3.02) (P = .003). The greatest color differences were observed in the NP group submitted to immersion in coffee (8.30) and wine (7.93) (P < .05). CONCLUSIONS: The polished surfaces were the least stained. Coffee and wine provided the greatest color changes, both for baths and immersions. CLINICAL SIGNIFICANCE: Polishing of provisional surfaces restorations made of bis-acrylic resin is essential to minimize staining caused by aging and use of colorants, regardless of the particle size present in the polishing paste. The contact with coffee and red wine should be avoided, especially for clinical times greater than 1 week.

Two-Dimensional Identification of Fetal Tooth Germs.

OBJECTIVE: To demonstrate the efficiency and applicability of two-dimensional ultrasonography in the identification of tooth germs and in the assessment of potential pathology. DESIGN: Observational, descriptive, cross-sectional study. SETTING: Prenatal Diagnosis Unit of Centro Hospitalar de Vila Nova de Gaia / Espinho-Empresa Pública in Portugal. PATIENTS: A total of 157 white pregnant women (median age, 32 years; range, 14 to 47 years) undergoing routine ultrasound exams. MAIN OUTCOME MEASURE(S): Description of the fetal tooth germs, as visualized by two-dimensional ultrasonography, including results from prior fetal biometry and detailed screening for malformations. RESULTS: In the first trimester group, ultrasonography identified 10 tooth germs in the maxilla and 10 tooth germs in the mandible in all fetuses except for one who presented eight maxillary tooth germs. This case was associated with a chromosomal abnormality (trisomy 13) with a bilateral cleft palate. In the second and third trimesters group, ultrasonography identified a larger range of tooth germs: 81.2% of fetuses showed 10 tooth germs in the maxilla and 85.0% of fetuses had 10 tooth germs in the mandible. Hypodontia was more prevalent in the maxilla than in the mandible, which led us to use qualitative two-dimensional ultrasonography to analyze the possible association between hypodontia and other variables such as fetal pathology, markers, head, nuchal, face, and spine. CONCLUSIONS: We recommend using this method as the first exam to evaluate fetal morphology and also to help establish accurate diagnosis of abnormalities in pregnancy.

IRAK4 gene polymorphism and odontogenic maxillary sinusitis.

OBJECTIVES: This study aimed to evaluate whether a specific interleukin-1 receptor-associated kinase-4 (IRAK4) gene polymorphism had any influence on the development of changes in maxillary sinus, particularly in the presence of etiological factors of dental origin. MATERIALS AND METHODS: The study population included 153 Portuguese Caucasians that were selected from a database of 504 retrospectively analysed computed tomography (CT) scans. A genetic test was performed, and a model was created through logistic analysis and regression coefficients. The statistical methodologies included were the independent Chi test, Fisher's exact test, binary logistic regression and the receiver operating characteristic (ROC) curve. RESULTS: The estimated prevalence of IRAK4 gene polymorphism found in a Portuguese Caucasian population was 26.8 % (CI 95%) [20.1, 34.7 %]. A model to predict the inflammatory response in the maxillary sinus in the presence etiological factors of dental origin was constructed. This model had the following as variables: previously diagnosed sinusitis, sinus pressure symptoms, cortical bone loss observed on CT, positive genetic test result and radiographic examination that revealed the roots of the teeth communication with the maxillary sinus, which are interpreted as risk factors. CONCLUSIONS: The constructed model should be considered an initial clinical tool. The area under the ROC curve found, AUC = 0.91, revealed that the model correctly predicts the outcome in 91.1% of cases. CLINICAL RELEVANCE: The clinical relevance of this study lies in trying to achieve a potential tool (a model) that may assist the clinician in the implementation of suitable dental treatment plans in complex cases, with probable involvement of the maxillary sinus.

CT maxillary sinus evaluation--A retrospective cohort study.

BACKGROUND: Proximity of the dental roots to the sinus floor makes dental disease a probable cause of maxillary sinusitis. The aim of this study was to find out if maxillary sinus pathologic changes were more prevalent in patients with dental disease and to evaluate the performance of computed tomography (CT) in analyzing and detecting apical periodontitis and other odontogenic causes on the maxillary sinusitis etiology in a Portuguese Caucasian population. MATERIAL AND METHODS: Retrospective cohort study. The total sample of 504 patients and their CT was included in this study. The patients were from a private dental clinic, specializing in oral surgery, where the first complaint was not directly related to sinus disease, but with dental pathology. For each patient, the etiological factors of maxillary sinusitis and the imaging CT findings were analyzed. All the axial, coronal and sagittal CT slices were evaluated and general data were registered. The latter was selected based on the maxillary sinus CT published literature. RESULTS: 32.40% of patients presented normal sinus (without any etiological factor associated), 29.00% showed presence of etiological and imaging findings in the maxillary sinus, 20.60% had only imaging changes in the maxillary sinus and 18.00% of patients presented only etiological factors and no change in the maxillary sinus. CONCLUSIONS: Radiological imaging is an important tool for establishing the diagnosis of maxillary sinus pathology. These results indicate that the CT scan should be an excellent tool for complement the odontogenic sinusitis diagnosis.

Accelerated CD8+ T cell maturation in infants with perinatal HIV infection.

In perinatal HIV infection, early antiretroviral therapy (ART) initiation is recommended but questions remain regarding infant immune responses to HIV and its impact on immune development. Using single cell transcriptional and phenotypic analysis we evaluated the T cell compartment at pre-ART initiation of infants with perinatally acquired HIV from Maputo, Mozambique (Towards AIDS Remission Approaches cohort). CD8+ T cell maturation subsets exhibited altered distribution in HIV exposed infected (HEI) infants relative to HIV exposed uninfected infants with reduced naive, increased effectors, higher frequencies of activated T cells, and lower frequencies of cells with markers of self-renewal. Additionally, a cluster of CD8+ T cells identified in HEI displayed gene profiles consistent with cytotoxic T lymphocytes and showed evidence for hyper expansion. Longitudinal phenotypic analysis revealed accelerated maturation of CD8+ T cells was maintained in HEI despite viral control. The results point to an HIV-directed immune response that is likely to influence reservoir establishment.

Enhancing HIV positivity yield in southern Mozambique: The effect of a Ministry of Health training module in targeted provider-initiated testing and counselling.

In Mozambique, targeted provider-initiated HIV testing and counselling (PITC) is recommended where universal PITC is not feasible, but its effectiveness depends on healthcare providers' training. This study aimed to evaluate the effect of a Ministry of Health training module in targeted PITC on the HIV positivity yield, and identify factors associated with a positive HIV test. We conducted a single-group pre-post study between November 2018 and November 2019 in the triage and emergency departments of four healthcare facilities in Manhiça District, a resource-constrained semi-rural area. It consisted of two two-month phases split by a one-week targeted PITC training module ("observation phases"). The HIV positivity yield of targeted PITC was estimated as the proportion of HIV-positive individuals among those recommended for HIV testing by the provider. Additionally, we extracted aggregated health information system data over the four months preceding and following the observation phases to compare yield in real-world conditions ("routine phases"). Logistic regression analysis from observation phase data was conducted to identify factors associated with a positive HIV test. Among the 7,102 participants in the pre- and post-training observation phases (58.5% and 41.5% respectively), 68% were women, and 96% were recruited at triage. In the routine phases with 33,261 individuals (45.8% pre, 54.2% post), 64% were women, and 84% were seen at triage. While HIV positivity yield between pre- and post-training observation phases was similar (10.9% (269/2470) and 11.1% (207/1865), respectively), we observed an increase in yield in the post-training routine phase for women in triage, rising from 4.8% (74/1553) to 7.3% (61/831) (Yield ratio = 1.54; 95%CI: 1.11-2.14). Age (25-49 years) (OR = 2.43; 95%CI: 1.37-4.33), working in industry/mining (OR = 4.94; 95%CI: 2.17-11.23), unawareness of partner's HIV status (OR = 2.50; 95%CI: 1.91-3.27), and visiting a healer (OR = 1.74; 95%CI: 1.03-2.93) were factors associated with a positive HIV test. Including these factors in the targeted PITC algorithm could have increased new HIV diagnoses by 2.6%. In conclusion, providing refresher training and adapting the current targeted PITC algorithm through further research can help reach undiagnosed PLHIV, treat all, and ultimately eliminate HIV, especially in resource-limited rural areas.

HIV care retention in three multi-month ART dispensing: a retrospective cohort study in Mozambique.

OBJECTIVE: Evaluate the effect of three multimonth dispensing (3MMD) of antiretroviral therapy (ART) on HIV care retention in southern Mozambique. DESIGN: Retrospective cohort study. METHODS: We analyzed routine health data from people with HIV (PWH) aged 10 years old and older who started ART between January 2018 and March 2021. Individuals were followed until December 2021. Cox proportional-hazards models were used to compare attrition (lost to follow-up, death, and transfer out) between 3MMD and monthly ART dispensing. Results were stratified by time on ART before 3MMD enrolment: 'early enrollers' (<6 months on ART) and 'established enrollers' (≥6 months on ART), and age groups: adolescents and youth (AYLHIV) (10-24 years) and adults (≥25 years). RESULTS: We included 7378 PWH (25% AYLHIV, 75% adults), with 59% and 62% enrolled in 3MMD, respectively. Median follow-up time was 11.3 [interquartile range (IQR): 5.7-21.6] months for AYLHIV and 10.2 (IQR: 4.8-20.9) for adults. Attrition was lower in PWH enrolled in 3MMD compared with monthly ART dispensing, in both established (aHR AYLHIV = 0.65; 95% CI: 0.54-0.78 and aHR adults = 0.50; 95% confidence interval (CI): 0.44-0.56) and early enrollers (aHR AYLHIV = 0.70; 95% CI: 0.58-0.85 and aHR adults = 0.63; 95% CI: 0.57-0.70). Among individuals in 3MMD, male gender (aHR = 1.30; 95% CI: 1.18-1.44) and receiving care in a medium-volume/low-volume healthcare facility (aHR = 1.18; 95% CI: 1.03-1.34) increased attrition risk. Conversely, longer ART time before 3MMD enrolment (aHR = 0.93; 95% CI: 0.92-0.94 per 1 month increase) and age at least 45 years (aHR = 0.77, 95% CI: 0.67-0.89) reduced risk of attrition. CONCLUSION: 3MMD improves retention in care compared with monthly dispensing among established and early enrollers, although to a lesser extent among the latter.

Aerobic Fitness as an Important Moderator Risk Factor for Loneliness in Physically Trained Older People: An Explanatory Case Study Using Machine Learning.

BACKGROUND: Loneliness in older people seems to have emerged as an increasingly prevalent social problem. OBJECTIVE: To apply a machine learning (ML) algorithm to the task of understanding the influence of sociodemographic variables, physical fitness, physical activity levels (PAL), and sedentary behavior (SB) on the loneliness feelings of physically trained older people. MATERIALS AND METHODS: The UCLA loneliness scale was used to evaluate loneliness, the Functional Fitness Test Battery was used to evaluate the correlation of sociodemographic variables, physical fitness, PAL, and SB in the loneliness feelings scores of 23 trained older people (19 women and 4 men). For this purpose, a naive Bayes ML algorithm was applied. RESULTS: After analysis, we inferred that aerobic fitness (AF), hand grip strength (HG), and upper limb strength (ULS) comprised the most relevant variables panel to cause high participant loneliness with 100% accuracy and F-1 score. CONCLUSIONS: The naive Bayes algorithm with leave-one-out cross-validation (LOOCV) predicted loneliness in trained older with a high precision. In addition, AF was the most potent variable in reducing loneliness risk.

Longitudinal analysis of innate immune system in infants with perinatal HIV infection until 18 months of age.

With the advent of antiretroviral therapy (ART), perinatal HIV infection is declining globally but prevalence in Sub-Saharan Africa is still greater than other nations. The relationship of HIV replication in early infancy and the developing immune system is not well understood. In this study, we investigated cellular components of the innate immune system including Natural Killer (NK) cells, monocytes, and Dendritic Cells (DC) in a cohort of HIV exposed infected (HEI) and age-matched HIV exposed uninfected (HEU) infants from Mozambique. Study entry was at the first visit after delivery at age 1-2 months for HIV diagnosis and initiation of ART. Phenotypic analysis by multi-parameter flow cytometry revealed an expansion of total NK cells and the dysfunctional, CD56-CD16+, NK cell subset; increased activation in monocytes and DC; and higher levels of inflammatory homing receptor CCR5 on circulating DC subsets in the HEI infants. NKG2A, an inhibitory receptor for NK cytolytic function, was reduced in HEI compared to HEU and positively correlated with pre-ART viral load (VL) while expression of CCR2, the inflammatory homing receptor, on NK was negatively correlated with VL. Other subsets exhibited positive correlations with VL including the frequency of intermediate monocytes amongst total monocytes. Longitudinal analysis of VL indicated suboptimal ART adherence in HEI. Regardless of level of viral suppression achieved, the frequencies of specific innate immune subsets in HEI were normalized to HEU by 18m. These data support the notion that in early life, NK cells play a role in virus control and should be explored for functional attributes that are effective against HIV at this time during development. Overall, our study provides high resolution overview of the innate immune system during perinatal HIV infection.

B-cell immunity and vaccine induced antibody protection reveal the inefficacy of current vaccination schedule in infants with perinatal HIV-infection in Mozambique, Africa.

BACKGROUND: Despite antiretroviral treatment (ART), immune dysfunction persists in children with perinatal HIV infection (HEI). Here we investigated the impact of HIV status on maternal antibody (Ab) passage, long-term vaccine induced immunity and B-cell maturation. METHODS: 46 HIV Exposed Uninfected (HEU), 43 HEI, and 15 HIV unexposed uninfected (HUU) infants were vaccinated with 3 doses of DTaP-HepB-Hib-PCV10-OP at 2, 3, and 4 months at Matola Provincial Hospital, Maputo, Mozambique. Tetanus toxoid specific (TT) IgG, HIV Ab and B-cell phenotype characteristics were evaluated at entry, pre-ART, 5, 10, and 18 months in this longitudinal cohort study. FINDINGS: Baseline (maternal) plasma TT Ab levels were significantly lower in HEI compared to both HEU and HUU and a faster decay of TT Ab was observed in HEI compared to HEU with significantly lower TT Ab levels at 10 and 18 months of age. TT unprotected (UP) (≤0.1 IU/mL) HEI showed higher HIV-RNA at entry and higher longitudinal HIV viremia (Area Under the Curve) compared to TT protected (P) HEI. A distinct HIV-Ab profile was found at entry in HEI compared to HEU. B-cell phenotype showed a B-cell perturbation in HEI vs HEU infants at entry (mean age 40.8 days) with lower transitional CD10+CD19+ B-cells and IgD+CD27- naive B-cells and an overall higher frequency of IgD-CD27- double negative B-cell subsets in HEI. INTERPRETATION: B-cell perturbation, presenting with higher double negative IgD-CD27- B-cells was observed in neonatal age and may play a major role in the B-cell exhaustion in HEI. The ability to maintain TT protective Ab titers over time is impaired in HEI with uncontrolled viral replication and the current vaccination schedule is insufficient to provide long-term protection against tetanus. FUNDING: This work was supported by: NIH grant to SP (5R01AI127347-05); Children's Hospital Bambino Gesú (Ricerca corrente 2019) to NC, and Associazione Volontari Bambino Gesù to PP.

HIV-1 reservoir evolution in infants infected with clade C from Mozambique.

BACKGROUND: The persistence of HIV-1-infected cells during antiretroviral therapy is well documented but may be modulated by early initiation of antiretroviral therapy in infants. METHODS: Here, we longitudinally analyzed the proviral landscape in nine infants with vertical HIV-1 infection from Mozambique over a median period of 24 months, using single-genome, near full-length, next-generation proviral sequencing. RESULTS: We observed a rapid decline in the frequency of intact proviruses, leading to a disproportional under-representation of intact HIV-1 sequences within the total number of HIV-1 DNA sequences after 12-24 months of therapy. In addition, proviral integration site profiling in one infant demonstrated clonal expansion of infected cells harboring intact proviruses and indicated that viral rebound was associated with an integration site profile dominated by intact proviruses integrated into genic and accessible chromatin locations. CONCLUSION: Together, these results permit rare insight into the evolution of the HIV-1 reservoir in infants infected with HIV-1 and suggest that the rapid decline of intact proviruses, relative to defective proviruses, may be attributed to a higher vulnerability of genome-intact proviruses to antiviral immunity. Technologies to analyze combinations of intact proviral sequences and corresponding integration sites permit a high-resolution analysis of HIV-1 reservoir cells after early antiretroviral treatment initiation in infants.

The zinc fingers of the SR-like protein ZRANB2 are single-stranded RNA-binding domains that recognize 5' splice site-like sequences.

The alternative splicing of mRNA is a critical process in higher eukaryotes that generates substantial proteomic diversity. Many of the proteins that are essential to this process contain arginine/serine-rich (RS) domains. ZRANB2 is a widely-expressed and highly-conserved RS-domain protein that can regulate alternative splicing but lacks canonical RNA-binding domains. Instead, it contains 2 RanBP2-type zinc finger (ZnF) domains. We demonstrate that these ZnFs recognize ssRNA with high affinity and specificity. Each ZnF binds to a single AGGUAA motif and the 2 domains combine to recognize AGGUAA(N(x))AGGUAA double sites, suggesting that ZRANB2 regulates alternative splicing via a direct interaction with pre-mRNA at sites that resemble the consensus 5' splice site. We show using X-ray crystallography that recognition of an AGGUAA motif by a single ZnF is dominated by side-chain hydrogen bonds to the bases and formation of a guanine-tryptophan-guanine "ladder." A number of other human proteins that function in RNA processing also contain RanBP2 ZnFs in which the RNA-binding residues of ZRANB2 are conserved. The ZnFs of ZRANB2 therefore define another class of RNA-binding domain, advancing our understanding of RNA recognition and emphasizing the versatility of ZnF domains in molecular recognition.

Customized root-analogue dental implants - Procedure and errors associated with image acquisition, treatment, and manufacturing technology in an experimental study on a cadaver dog mandible.

The global market for dental implants is constantly evolving. To overcome the limitations of conventional strategies - invasive surgeries and bone loss around the implant-, new approaches, namely the development of CAD/CAM customized implants, are emerging as promising solutions for replacing missing teeth, thus avoiding destruction of bone by drilling it. Despite the efforts that are being carried out, the designing, including image acquisition, and manufacturing efficacy of such rehabilitation therapy is not easily found in the literature. In this sense, this research work aimed to assess the errors associated with the image acquisition, treatment and manufacturing of Customized Root-Analogue Implants (CRAI). The experimental procedure, carried out in a dog cadaveric mandible, encompassed the image acquisition and treatment and the subsequent manufacturing of four different CRAI. Two Image acquisition methods (CBCT and X-ray), and different software for their treatment were used, and the final CRAI were manufactured by Computer Numerical Control. Results revealed the CBCT scan allowed to properly visualize the original teeth contours. However, all the obtained teeth geometries presented smaller surface areas when compared to the original teeth indicating however a systematic predictable error. On the other hand, when comparing the surface area of the digital and the manufactured teeth, very small differences were observed, which indicates that the CNC manufacturing technique is a promising solution for such applications. When placing the produced CRAI in the dog mandible it was possible to observe a lack of congruency between the CRAI and bone, mainly due to image acquisition process errors and the destruction of the periodontal ligament during the soft tissues removal process. Thus, CBCT images seem to be a feasible route to design root-analogue implants, and, if needed, a compensation strategy for the systematic image acquisition error may be implemented.

Tuberculosis in children with severe acute malnutrition.

INTRODUCTION: With growing attention globally to the childhood tuberculosis epidemic after decades of neglect, and with the burden of severe acute malnutrition (SAM) remaining unacceptably high worldwide, the collision of these two diseases is an important focus for improving child health. AREAS COVERED: This review describes the clinical and public health implications of the interplay between tuberculosis and SAM, particularly for children under the age of five, and identifies priority areas for improved programmatic implementation and future research. We reviewed the literature on PubMed and other evidence known to the authors published until August 2021 relevant to this topic. EXPERT OPINION: To achieve the World Health Organization's goal of eliminating deaths from childhood tuberculosis and to improve the abysmal outcomes for children with SAM, further research is needed to 1) better understand the epidemiologic connections between child tuberculosis and SAM, 2) improve case finding of tuberculosis in children with SAM, 3) assess unique treatment considerations for tuberculosis when children also have SAM, and 4) ensure tuberculosis and SAM are strongly addressed in decentralized, integrated models of providing primary healthcare to children.

Viral Response among Early Treated HIV Perinatally Infected Infants: Description of a Cohort in Southern Mozambique.

Early initiation of antiretroviral therapy and adherence to achieve viral load suppression (VLS) are crucial for reducing morbidity and mortality of perinatally HIV-infected infants. In this descriptive cohort study of 39 HIV perinatally infected infants, who started treatment at one month of life in Mozambique, we aimed to describe the viral response over 2 years of follow up. VLS ≤ 400 copies/mL, sustained VLS and viral rebound were described using a Kaplan-Meier estimator. Antiretroviral drug transmitted resistance was assessed for a sub-group of non-VLS infants. In total, 61% of infants reached VLS, and 50% had a rebound. Cumulative probability of VLS was 36%, 51%, and 69% at 6, 12 and 24 months of treatment, respectively. The median duration of VLS was 7.4 months (IQR 12.6) and the cumulative probability of rebound at 6 months was 30%. Two infants had resistance biomarkers to drugs included in their treatment regimen. Our findings point to a low rate of VLS and high rate of viral rebound. More frequent viral response monitoring is advisable to identify infants with rebound and offer timely adherence support. It is urgent to tailor the psychosocial support model of care to this specific age group and offer differentiated service delivery to mother-baby pairs.