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.

Hyperspectral confocal imaging for high-throughput readout and analysis of bio-integrated microlasers.

Integrating micro- and nanolasers into live cells, tissue cultures and small animals is an emerging and rapidly evolving technique that offers noninvasive interrogation and labeling with unprecedented information density. The bright and distinct spectra of such lasers make this approach particularly attractive for high-throughput applications requiring single-cell specificity, such as multiplexed cell tracking and intracellular biosensing. The implementation of these applications requires high-resolution, high-speed spectral readout and advanced analysis routines, which leads to unique technical challenges. Here, we present a modular approach consisting of two separate procedures. The first procedure instructs users on how to efficiently integrate different types of lasers into living cells, and the second procedure presents a workflow for obtaining intracellular lasing spectra with high spectral resolution and up to 125-kHz readout rate and starts from the construction of a custom hyperspectral confocal microscope. We provide guidance on running hyperspectral imaging routines for various experimental designs and recommend specific workflows for processing the resulting large data sets along with an open-source Python library of functions covering the analysis pipeline. We illustrate three applications including the rapid, large-volume mapping of absolute refractive index by using polystyrene microbead lasers, the intracellular sensing of cardiac contractility with polystyrene microbead lasers and long-term cell tracking by using semiconductor nanodisk lasers. Our sample preparation and imaging procedures require 2 days, and setting up the hyperspectral confocal microscope for microlaser characterization requires <2 weeks to complete for users with limited experience in optical and software engineering.

Modified one-step conservative uterine surgery (MOSCUS) versus cesarean hysterectomy in the management of placenta accreta spectrum: A single-center retrospective analysis based on 619 Vietnamese pregnant women.

OBJECTIVES: To compare maternal outcome measures in surgical management of placenta accreta spectrum (PAS)-the modified one-step conservative uterine surgery (MOSCUS), a new approach at Tu Du Hospital in Vietnam, versus cesarean hysterectomy, and to identify factors that appear to contribute to the successful outcome of the MOSCUS. METHODS: This retrospective study was conducted at Tu Du Hospital in southern Vietnam between January 2019 and December 2020. The study enrolled all pregnant women at more than 28 weeks of pregnancy with a diagnosis of PAS who underwent either a cesarean hysterectomy or a uterus-preserving approach using the MOSCUS method. RESULTS: The prevalence of PAS at our single tertiary referral hospital was 0.4% (619 PAS cases/132 518 births) in 2 years. Among 296 patients, the surgical time duration, estimated blood loss, and red blood cell transfusion in the MOSCUS group (n = 217) were all significantly less than in the cesarean hysterectomy group (n = 79) (152.72 ± 42.23 vs 185.13 ± 58.22 min, 1000 vs 1500 mL, and 500 vs 710 mL, respectively). Intraoperatively, the rate of visceral injuries in the hysterectomy group was higher than that in the MOSCUS group (P < 0.001). However, the rate of postoperative infection was higher in the MOSCUS group than in the cesarean hysterectomy group (P = 0.012). Of a total of 217 cases managed using the MOSCUS management, 24 required a secondary hysterectomy; the success rate was 88.9% (95% confidence interval [CI] 84.3%-93.1%). Some of the primary factors associated with the success of MOSCUS included maternal age less than 35 years, planned surgery, severity of PAS, and estimated blood loss during surgery (odds ratio [OR] 5.16, 95% CI 1.96-13.59; OR 3.05, 95% CI 1.08-8.62; OR 3.62, 95% CI 1.19-10.98; and OR 49.66, 95% CI 11.16-221.02, respectively; P < 0.05). CONCLUSION: MOSCUS is an acceptable alternative to cesarean hysterectomy in many patients diagnosed with PAS. This new surgical management of PAS resulted in the preservation of the uterus, and a favorable outcome in nearly 9 out of 10 pregnant women. We believe that MOSCUS can be safely offered for the management of PAS in referral hospital settings.

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.

Added value of the pulmonary vein pulsatility index and its correlation to neonatal umbilical artery pH in fetal growth restrictions: a Vietnamese matched cohort study.

BACKGROUND: In clinical obstetrics, many guidelines recommended the use of Doppler fetal ductus venosus blood flow to monitor and to manage fetal growth restriction (FGR). The ductus venosus and the pulmonary venous flow pattern of fetuses are similar. Umbilical artery pH (UA pH) is essential in identifying adverse pregnancy outcomes, particularly in fetal growth restriction cases. Nevertheless, the literature indicates that the relationship between pulmonary vein pulsatility index (PVPI) and UA pH in FGR cases has not been well investigated. This study aimed to identify the alteration in PVPI in FGR cases and evaluate the correlation between PVPI and UA pH in FGR newborns. METHODS: This matched cohort study of singleton pregnancies from 28+ 0 to 40+ 0 weeks of gestation without congenital abnormalities included 135 cases of FGR (disease group) and 135 cases of normal growth (control group). The PVPI was measured at the proximal segment of the right or left pulmonary vein, approximately 5 mm from the left atrium wall. The umbilical artery pulsatility index (UAPI) was measured on the free umbilical cord. An elective cesarean section or labor induction are both options for ending the pregnancy, depending on the condition of the mother or fetus. Umbilical artery blood samples were collected within 5 min of delivery for UA pH measurement. SPSS version 20 and Medcalc version 20.1 were used for data analysis. RESULTS: FGR cases had a significantly higher mean fetal PVPI than the control group (1.16 ± 0.26 vs. 0.84 ± 0.16; p < 0.01), and PVPI and UAPI were positively correlated (r = 0.63; p < 0.001). PVPI and UA pH were negatively correlated in FGR patients, with r = -0.68; p < 0.001. The PVPI value on the 95th percentile had a prognostic value of UA pH < 7.20 with a sensitivity of 88.2%, specificity of 66.3%, positive predictive value of 46.9%, and negative predictive value of 94.3%. CONCLUSIONS: There was a statistically significant difference in PVPI values in FGR cases compared to the normal growth group, a positive correlation between PVPI and UAPI, and a negative correlation between PVPI and UA pH. PVPI might have a prognostic meaning in predicting UA pH at birth.

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.

Gemigliptin Alleviates Succinate-Induced Hepatic Stellate Cell Activation by Ameliorating Mitochondrial Dysfunction.

BACKGRUOUND: Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are used clinically as oral antidiabetic agents. Although DPP-4Is are known to ameliorate liver fibrosis, the protective mechanism of DPP-4Is in liver fibrosis remains obscure. In this study, gemigliptin was used to investigate the potential of DPP-4Is to alleviate the progression of liver fibrosis. METHODS: To clarify the effects and mechanisms of gemigliptin, we conducted various experiments in LX-2 cells (immortalized human hepatic stellate cells [HSCs], the principal effectors of hepatic fibrogenesis), which were activated by succinate and exhibited elevated expression of α-smooth muscle actin, collagen type 1, and pro-inflammatory cytokines and increased cell proliferation. In vivo, we examined the effects and mechanisms of gemigliptin on a high-fat, high-cholesterol-induced mouse model of nonalcoholic steatohepatitis (NASH). RESULTS: Gemigliptin decreased the expression of fibrogenesis markers and reduced the abnormal proliferation of HSCs. In addition, gemigliptin reduced the succinate-induced production of mitochondrial reactive oxygen species (ROS), intracellular ROS, and mitochondrial fission in HSCs. Furthermore, in the mouse model of NASH-induced liver fibrosis, gemigliptin alleviated both liver fibrosis and mitochondrial dysfunction. CONCLUSION: Gemigliptin protected against HSC activation and liver fibrosis by alleviating mitochondrial dysfunction and ROS production, indicating its potential as a strategy for preventing the development of liver disease.

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.

The Effects of Irisin on the Interaction between Hepatic Stellate Cell and Macrophage in Liver Fibrosis.

BACKGRUOUND: Hepatic stellate cells (HSCs) are the central players interacting with multiple cell types in liver fibrosis. The crosstalk between HSCs and macrophages has recently become clearer. Irisin, an exercise-responsive myokine, was known to have a potentially protective role in liver and renal fibrosis, especially in connection with stellate cells. This study investigated the effects of irisin on the interaction between HSCs and macrophages. METHODS: Tamm-Horsfall protein-1 (THP-1) human monocytes were differentiated into macrophages, polarized into the inflammatory M1 phenotype with lipopolysaccharide. Lieming Xu-2 (LX-2) cells, human HSCs, were treated with conditioned media (CM) from M1 macrophages, with or without recombinant irisin. HSCs responses to CM from M1 macrophages were evaluated regarding activation, proliferation, wound healing, trans-well migration, contractility, and related signaling pathway. RESULTS: CM from M1 macrophages significantly promoted HSC proliferation, wound healing, transwell migration, and contractility, but not activation of HSCs. Irisin co-treatment attenuated these responses of HSCs to CM. However, CM and irisin treatment did not induce any changes in HSC activation. Further, irisin co-treatment alleviated CM-induced increase of phopho-protein kinase B (pAKT), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1). CONCLUSION: These findings suggested that irisin may play a protective role in the pathogenesis of liver fibrosis, especially when working in the crosstalk between HSCs and macrophages.

Gemigliptin Alleviates Succinate-Induced Hepatic Stellate Cell Activation by Ameliorating Mitochondrial Dysfunction

Background@#Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are used clinically as oral antidiabetic agents. Although DPP-4Is are known to ameliorate liver fibrosis, the protective mechanism of DPP-4Is in liver fibrosis remains obscure. In this study, gemigliptin was used to investigate the potential of DPP-4Is to alleviate the progression of liver fibrosis. @*Methods@#To clarify the effects and mechanisms of gemigliptin, we conducted various experiments in LX-2 cells (immortalized human hepatic stellate cells [HSCs], the principal effectors of hepatic fibrogenesis), which were activated by succinate and exhibited elevated expression of α-smooth muscle actin, collagen type 1, and pro-inflammatory cytokines and increased cell proliferation. In vivo, we examined the effects and mechanisms of gemigliptin on a high-fat, high-cholesterol–induced mouse model of nonalcoholic steatohepatitis (NASH). @*Results@#Gemigliptin decreased the expression of fibrogenesis markers and reduced the abnormal proliferation of HSCs. In addition, gemigliptin reduced the succinate-induced production of mitochondrial reactive oxygen species (ROS), intracellular ROS, and mitochondrial fission in HSCs. Furthermore, in the mouse model of NASH-induced liver fibrosis, gemigliptin alleviated both liver fibrosis and mitochondrial dysfunction. @*Conclusion@#Gemigliptin protected against HSC activation and liver fibrosis by alleviating mitochondrial dysfunction and ROS production, indicating its potential as a strategy for preventing the development of liver disease.

The kinetic profile of clinical and laboratory findings and treatment outcome of patients with toxocariasis.

OBJECTIVES: Human toxocariasis is a widespread zoonosis for which a chemotherapy decision and therapy effectiveness are difficult to determine. We aimed to investigate the kinetic profile of clinical and laboratory findings and treatment outcome of patients with toxocariasis in Vietnam. METHODS: The prospective study was conducted between October 2017 and June 2019. The diagnosis of toxocariasis was established based on clinical, laboratory (eosinophilia, raised IgE concentration) and serological (positive Toxocara IgG ELISA) evaluation as well as the exclusion of another helminthic co-infection. The patients were followed up after seven days, then one, three and six months after chemotherapy by thiabendazole. RESULTS: The study involved 80 patients with a mean age of 41.6 ± 15.2 years of whom 58.8% were female. At three and six months after chemotherapy, most patients demonstrated resolution of clinical signs and symptoms, eosinophil count and IgE concentration but not in the proportion of IgG seropositivity. Skin lesions and eosinophilia resolved earlier than the other symptoms (one month after treatment). About four-fifths of the patients were "cured" after three and six months of follow-up; 33.8% showed side effects to thiabendazole therapy but no severe events were reported. The most common adverse reaction was neurologic symptoms followed by gastrointestinal or skin manifestations which lasted as long as 4 days. CONCLUSIONS: In toxocariasis patients, cutaneous manifestations and eosinophilia resolve more rapidly than other clinical and laboratory findings while IgG titre has a very slow kinetic after therapy. Thiabendazole seems to be a potential alternative for the treatment of human toxocariasis.

Genetic landscape of recessive diseases in the Vietnamese population from large-scale clinical exome sequencing.

Accurate profiling of population-specific recessive diseases is essential for the design of cost-effective carrier screening programs. However, minority populations and ethnic groups, including Vietnamese, are still underrepresented in existing genetic studies. Here, we reported the first comprehensive study of recessive diseases in the Vietnamese population. Clinical exome sequencing data of 4503 disease-associated genes obtained from a cohort of 985 Vietnamese individuals was analyzed to identify pathogenic variants, associated diseases and their carrier frequencies in the population. A total of 118 recessive diseases associated with 164 pathogenic or likely pathogenic variants were identified, among which 28 diseases had carrier frequencies of at least 1% (1 in 100 individuals). Three diseases were prevalent in the Vietnamese population with carrier frequencies of 2-12 times higher than in the world populations, including beta-thalassemia (1 in 23), citrin deficiency (1 in 31), and phenylketonuria (1 in 40). Seven novel pathogenic and two likely pathogenic variants associated with nine recessive diseases were discovered. The comprehensive profile of recessive diseases identified in this study enables the design of cost-effective carrier screening programs specific to the Vietnamese population.

T cell immune discriminants of HIV reservoir size in a pediatric cohort of perinatally infected individuals.

The size of the latent HIV reservoir is associated with the timing of therapeutic interventions and overall health of the immune system. Here, we demonstrate that T cell phenotypic signatures associate with viral reservoir size in a cohort of HIV vertically infected children and young adults under durable viral control, and who initiated anti-retroviral therapy (ART) <2 years old. Flow cytometry was used to measure expression of immune activation (IA), immune checkpoint (ICP) markers, and intracellular cytokine production after stimulation with GAG peptides in CD4 and CD8 T cells from cross-sectional peripheral blood samples. We also evaluated the expression of 96 genes in sort-purified total CD4 and CD8 T cells along with HIV-specific CD4 and CD8 T cells using a multiplexed RT-PCR approach. As a measure of HIV reservoir, total HIV-DNA quantification by real-time PCR was performed. Poisson regression modeling for predicting reservoir size using phenotypic markers revealed a signature that featured frequencies of PD-1+CD4 T cells, TIGIT+CD4 T cells and HIV-specific (CD40L+) CD4 T cells as important predictors and it also shows that time of ART initiation strongly affects their association with HIV-DNA. Further, gene expression analysis showed that the frequencies of PD-1+CD4 T cells associated with a CD4 T cell molecular profile skewed toward an exhausted Th1 profile. Our data provide a link between immune checkpoint molecules and HIV persistence in a pediatric cohort as has been demonstrated in adults. Frequencies of PD-1+ and TIGIT+CD4 T cells along with the frequency of HIV-specific CD4 T cells could be associated with the mechanism of viral persistence and may provide insight into potential targets for therapeutic intervention.

Clinical and Laboratory Findings among Patients with Toxocariasis in Medic Medical Center, Ho Chi Minh City, Vietnam in 2017-2019.

BACKGROUND: Human toxocariasis is prevalent in many countries but this disease has been rarely reported from Vietnam. We aimed to investigate the clinical and laboratory findings and assess possible association between these findings in patients with toxocariasis in Vietnam. METHODS: A prospectively study, between October 2017 and June 2019 was performed involving 120 toxocariasis patients at Medic Medical Center, Ho Chi Minh City, Vietnam. The diagnosis of toxocariasis was established based on clinical, laboratory (eosinophilia, raised IgE concentration) and serological (positive Toxocara IgG ELISA test) evaluation as well as the exclusion of other helminthic coinfection. RESULTS: The most frequently reported manifestation was of skin (n = 93, 77.5%), including urticarial (n= 69, 57.5%) followed by neurologic, gastrointestinal and pulmonary signs/symptoms. Hepatic involvement occurred in 8.3% of the patients. No significant relationship between clinical findings and laboratory parameters was found except the higher values of eosinophil count and IgE concentration among patients with liver involvement. There was a significant relationship between eosinophil count and IgE concentration (r=0.389, P<0.001). Serological findings did not show a correlation with clinical and other laboratory findings. CONCLUSION: Our data revealed a wide range of clinical symptoms/signs and a high incidence of skin manifestations in patients with toxocariasis. Eosinophil count and IgE concentration are valuable markers for the evaluation of the disease.

Impact of Early Antiretroviral Therapy Initiation on HIV-Specific CD4 and CD8 T Cell Function in Perinatally Infected Children.

Early initiation of antiretroviral therapy (ART) in vertically HIV-infected children limits the size of the virus reservoir, but whether the time of treatment initiation (TI) can durably impact host immune responses associated with HIV infection is still unknown. This study was conducted in PBMC of 20 HIV-infected virally suppressed children on ART (mean age 9.4 y), classified as early treated (ET; age at ART initiation ≤0.5 y, n = 14) or late treated (LT; age at ART initiation 1-10 y, n = 6). Frequencies and functions of Ag-specific CD4 (CD40L+) and CD8 (CD69+) T cells were evaluated by intracellular IL-2, IFN-γ, and TNF-α production with IL-21 in CD4 or CD107a, granzyme B and perforin in CD8 T cells following stimulation with HIV gp140 protein (ENV) or GAG peptides by multiparameter flow cytometry. ET showed a higher proportion of cytokine-producing ENV- and GAG-specific CD4 and CD8 T cells compared with LT. In particular, ET were enriched in polyfunctional T cells. RNA sequencing analysis showed upregulation of immune activation pathways in LT compared with ET. Our results suggest that timing of TI in HIV-infected children has a long-term and measurable impact on the quality of the HIV-specific T cell immune responses and transcriptional profiles of PBMC, reinforcing the importance of early TI.

Rectification Using Different Types of Cameras Attached to a Vehicle.

The rectification process is a compulsory step in stereo matching computation. To obtain depth information, stereo camera systems are often installed in vehicles for outdoor and street-related applications, including vehicle and pedestrian detection, lane detection, and traffic sign recognition. In this paper, we propose a rectification method that uses currently available front- and rear-view vehicle cameras to produce rectified stereo images. The proposed method can be employed with different types of cameras that have varying focal lengths. In addition, this method tolerates the problem of camera alignment variation from normal stereo camera systems. To achieve this, a compensation method for different focal lengths and the estimation of image relationships are introduced. The experimental results demonstrate that the proposed method can operate robustly and accurately with different kinds of stereo images and significantly outperforms a state-of-the-art rectification method.

The effects of AICAR and rapamycin on mitochondrial function in immortalized mitochondrial DNA mutator murine embryonic fibroblasts.

Mitochondrial DNA mutations accumulate with age and may play a role in stem cell aging as suggested by the premature aging phenotype of mitochondrial DNA polymerase gamma (POLG) exonuclease-deficient mice. Therefore, E1A immortalized murine embryonic fibroblasts (MEFs) from POLG exonuclease-deficient and wild-type (WT) mice were constructed. Surprisingly, when some E1A immortalized MEF lines were cultured in pyruvate-containing media they slowly became addicted to the pyruvate. The POLG exonuclease-deficient MEFs were more sensitive to several mitochondrial inhibitors and showed increased reactive oxygen species (ROS) production under standard conditions. When cultured in pyruvate-containing media, POLG exonuclease-deficient MEFs showed decreased oxygen consumption compared to controls. Increased AMP-activated protein kinase (AMPK) signaling and decreased mammalian target of rapamycin (mTOR) signaling delayed aging and influenced mitochondrial function. Therefore, the effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMPK activator, or rapamycin, an mTOR inhibitor, on measures of mitochondrial function were determined. Rapamycin treatment transiently increased respiration only in WT MEFs and, under most conditions, increased ATP levels. Short term AICAR treatment transiently increased ROS production and, under most conditions, decreased ATP levels. Chronic AICAR treatment decreased respiration and ROS production in WT MEFs. These results demonstrate the context-dependent effects of AICAR and rapamycin on mitochondrial function.

Individual Amino Acid Supplementation Can Improve Energy Metabolism and Decrease ROS Production in Neuronal Cells Overexpressing Alpha-Synuclein.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein accumulation and loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Increased levels of alpha-synuclein have been shown to result in loss of mitochondrial electron transport chain complex I activity leading to increased reactive oxygen species (ROS) production. WT alpha-synuclein was stably overexpressed in human BE(2)-M17 neuroblastoma cells resulting in increased levels of an alpha-synuclein multimer, but no increase in alpha-synuclein monomer levels. Oxygen consumption was decreased by alpha-synuclein overexpression, but ATP levels did not decrease and ROS levels did not increase. Treatment with ferrous sulfate, a ROS generator, resulted in decreased oxygen consumption in both control and alpha-synuclein overexpressing cells. However, this treatment only decreased ATP levels and increased ROS production in the cells overexpressing alpha-synuclein. Similarly, paraquat, another ROS generator, decreased ATP levels in the alpha-synuclein overexpressing cells, but not in the control cells, further demonstrating how alpha-synuclein sensitized the cells to oxidative insult. Proteomic analysis yielded molecular insights into the cellular adaptations to alpha-synuclein overexpression, such as the increased abundance of many mitochondrial proteins. Many amino acids and citric acid cycle intermediates and their ester forms were individually supplemented to the cells with L-serine, L-proline, L-aspartate, or L-glutamine decreasing ROS production in oxidatively stressed alpha-synuclein overexpressing cells, while diethyl oxaloacetate or L-valine supplementation increased ATP levels. These results suggest that dietary supplementation with individual metabolites could yield bioenergetic improvements in PD patients to delay loss of dopaminergic neurons.

Robust Matching Cost Function for Stereo Correspondence Using Matching by Tone Mapping and Adaptive Orthogonal Integral Image.

Real-world stereo images are inevitably affected by radiometric differences, including variations in exposure, vignetting, lighting, and noise. Stereo images with severe radiometric distortion can have large radiometric differences and include locally nonlinear changes. In this paper, we first introduce an adaptive orthogonal integral image, which is an improved version of an orthogonal integral image. After that, based on matching by tone mapping and the adaptive orthogonal integral image, we propose a robust and accurate matching cost function that can tolerate locally nonlinear intensity distortion. By using the adaptive orthogonal integral image, the proposed matching cost function can adaptively construct different support regions of arbitrary shapes and sizes for different pixels in the reference image, so it can operate robustly within object boundaries. Furthermore, we develop techniques to automatically estimate the values of the parameters of our proposed function. We conduct experiments using the proposed matching cost function and compare it with functions employing the census transform, supporting local binary pattern, and adaptive normalized cross correlation, as well as a mutual information-based matching cost function using different stereo data sets. By using the adaptive orthogonal integral image, the proposed matching cost function reduces the error from 21.51% to 15.73% in the Middlebury data set, and from 15.9% to 10.85% in the Kitti data set, as compared with using the orthogonal integral image. The experimental results indicate that the proposed matching cost function is superior to the state-of-the-art matching cost functions under radiometric variation.