Vaccine Efficacy, Impact, Hesitancy, and Acceptance: Trends for Public Health.

Vaccines are indispensable tools in the battle against infectious diseases and hold great potential in combating a myriad of other diseases [...].

Association of the Magnitude of Anti-SARS-CoV-2 Vaccine Side Effects with Sex, Allergy History, Chronic Diseases, Medication Intake, and SARS-CoV-2 Infection.

Vaccination provides the best protection against the increasing infections of SARS-CoV-2. The magnitude and type of anti-SARS-CoV-2 vaccine side effects (SEs) depend on parameters that are not fully understood. In this cross-sectional study, the associations between different anti-SARS-CoV-2 vaccine SEs and age, sex, the presence of chronic diseases, medication intake, history of allergies, and infections with SARS-CoV-2 were investigated. Our survey used the Google platform and had 866 participants, contacted through e-mails, social media and chain referral sampling (margin of error ≈ 4.38%, 99% confidence). More than 99% of the participants received the BNT162b2 and ChAdOx1-S vaccines. Being female, having chronic diseases, taking medicines routinely and the presence of a SARS-CoV-2 infection (p < 0.05) were associated with strong SEs after the BNT162b2 vaccine second dose. Having a history of allergies and a female sex (p < 0.01) were associated with strong SEs after the ChAdOx1-S vaccine second dose. Furthermore, the results reveal, for the first time, the associations between having a history of allergies, chronic diseases, medication usage, and SEs of a strong magnitude for the BNT162b2 and ChAdOx1-S vaccines. Additionally, this study supports the association of the female sex and infection with SARS-CoV-2 with an increased potential of developing stronger SEs with certain anti-SARS-CoV-2 vaccines.

Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs.

Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering (p < 0.01). IAPCs produced more PTN than MK (p < 0.01). NAS TLRs and iAPCs had differential abilities to induce the production of MK, which was induced in monocytes and pDCs by all NAS TLRs (p < 0.05) and in MDDCs by TLRs 7/8 (p < 0.05). TLR4 induced a stronger MK production than NAS TLRs (p ≤ 0.05). Monocytes produced higher levels of PTN after differentiation to macrophages and MDDCs (p < 0.05). The production of MK and PTN differs among iAPCs, with a higher production of PTN and a selective induction of MK production by NAS TLR. This highlights the potentially important role of iAPCs in angiogenesis, tumors, infections, and autoimmunity through the differential production of MK and PTN upon TLR triggering.

The Association of Human Leukocyte Antigens Complex with Type 1 Diabetes in the Omani Population.

Objectives: Identification of the high risk alleles, genotypes and haplotypes of the human leukocyte antigens (HLA) in different populations is beneficial for understanding their roles in type 1 diabetes (T1D) pathogenesis and intervention practices. This study aimed to identify T1D-associated HLA gene alleles in the Omani population. Methods: The present case-control study included 73 diabetic seropositive children (mean age 9.08 ± 3.27 years) attending the paediatric clinic at Sultan Qaboos University Hospital in Muscat, Oman, and 110 healthy controls. HLA-A, -B, -C, -DRB1 and -DQB1 genes were genotyped using a sequence-specific primer polymerase chain reaction (SSP-PCR). Results: Two HLA class I alleles (B*08, B*58) and three class II alleles (DQB1*02, DRB1*03 and DRB1*04) were associated with T1D susceptibility, while one class I (B*51) and three class II (DQB1*05, DQB1*06 and DRB1*16) alleles were associated with T1D protection. HLA-DRB1*03 and DQB1*02 alleles showed the strongest risk association among all alleles. Six DRB1 residues (E9, S11, S13, Y30, V70 and K71) were significantly associated with T1D susceptibility. Heterozygous genotypes, HLA-DRB1*03/*04 and DQB1*02/*03 were significantly associated with T1D susceptibility (P <0.0001, odds ratio [OR] = 63.21 and P = 0.02, OR = 3.63, respectively). Furthermore, a significant combined action of DRB1*03-DQB1*02 haplotype in T1D risk (P = 0.000176, OR = 15) and DRB1*16-DQB1*05 haplotype in protection (P = 0.0312, OR = 0.48) was detected. Conclusion: Known HLA class II gene alleles are associated with T1D in Omani children.

The Presence of Implicit Gender Bias in Colon and Rectal Surgery Residency Letters of Recommendation.

BACKGROUND: Selection for colorectal surgery residency relies on letters of recommendation for assessment of candidates' strengths and weaknesses. It is unclear whether this process incorporates implicit gender bias. OBJECTIVE: This study aimed to assess the presence of gender bias in letters of recommendation for colorectal surgery residency. DESIGN: Mixed methods assessment of the characteristics described within the blinded letters of the 2019 application cycle to a single academic residency. SETTINGS: Academic medical center. PATIENTS: Blinded letters from the 2019 colorectal surgery residency application cycle. INTERVENTIONS: Characteristics of the letters were qualitatively and quantitatively analyzed. MAIN OUTCOME MEASURES: Association of gender with the presence of descriptors within the letters. RESULTS: A total of 111 applicants, 409 letter writers, and 658 letters were analyzed. Forty-three percent of applicants were female. Female and male applicants had an equal mean number of positive (5.4 vs 5.8; p = 0.10) and negative (0.5 vs 0.4; p = 0.07) attributes represented. Female applicants were more likely to be described as having poor academic skills (6.0 vs 3.4%; p = 0.04) and possessing negative leadership qualities (5.2% vs 1.4%; p < 0.01) than male applicants. Male applicants were more likely to be described as kind (36.6% vs 28.3%; p = 0.03), curious (16.4% vs 9.2%; p = 0.01), possessing positive academic skills (33.7% vs 20.0%; p < 0.01), and possessing positive teaching skills (23.5% vs 17.0%; p = 0.04). LIMITATIONS: This study analyzed a single year of applications to an academic center and may not be generalizable. CONCLUSIONS: There are differences in the qualities used to describe female versus male applicants in colorectal surgery residency application letters of recommendation. Female applicants were more often described in negative academic terms and possessing negative leadership qualities. Males were more likely to be described as kind, curious, academically impressive, and possessing good teaching skills. The field may benefit from educational initiatives to reduce implicit gender bias in letters of recommendation. See Video Abstract at http://links.lww.com/DCR/C191 . LA PRESENCIA DE SESGO DE GNERO IMPLCITO EN LAS CARTAS DE RECOMENDACIN DE RESIDENCIA EN CIRUGA DE COLON Y RECTO: ANTECEDENTES:La selección para la residencia en cirugía colorrectal se basa en cartas de recomendación para la evaluación subjetiva de las fortalezas y debilidades de los candidatos. No está claro si este proceso incorpora un sesgo de género implícito.OBJETIVO:Evaluar la presencia de sesgo de género en las cartas de recomendación para la residencia en cirugía colorrectal.DISEÑO:Evaluación de métodos mixtos de las características descritas dentro de las cartas selladas del ciclo de solicitud de 2019 a una sola residencia académica.ENTORNO CLÍNICO:Centro médico académico.PACIENTES:Cartas selladas del ciclo de solicitud de residencia en cirugía colorrectal de 2019.INTERVENCIONES:Las características de las cartas se determinaron utilizando medidas cualitativas y cuantitativas.PRINCIPALES MEDIDAS DE VALORACIÓN:Asociación del género con la presencia de descriptores dentro de las cartas.RESULTADOS:Hubo 111 solicitantes, 409 escritores de cartas y se analizaron 658 cartas. El 43% de los solicitantes eran mujeres. Los solicitantes masculinos y femeninos tenían el mismo promedio de atributos positivos (5,4 frente a 5,8; p = 0,10) y negativos (0,5 frente a 0,4; p = 0,07) representados. Las solicitantes femeninas tenían más probabilidades de ser descritas como con deficientes habilidades académicas (6,0 frente a 3,4%, p = 0,04) y poseían cualidades de liderazgo negativas (5,2% frente a 1,4%; p < 0,01) en comparacion con los solicitantes masculinos. Los solicitantes masculinos tenían más probabilidades de ser descritos como amables (36,6 % frente a 28,3%; p = 0,03), curiosos (16,4% frente a 9,2%; p = 0,01), que poseían habilidades académicas positivas (33,7 % frente a 20,0%; p < 0,01), y habilidades docentes positivas (23,5% vs 17,0%; p = 0,04).LIMITACIONES:Este estudio analizó un solo año de solicitudes a un centro académico y puede no ser generalizable.CONCLUSIÓN:Existen diferencias en las cualidades utilizadas para describir a los solicitantes femeninos versus masculinos en las cartas de recomendación de solicitud de residencia en cirugía colorrectal. Las candidatas femeninas se describieron con mayor frecuencia en términos académicos negativos y poseían cualidades de liderazgo negativas. Los hombres eran más propensos a ser descritos como amables, curiosos, académicamente impresionantes y con buenas habilidades docentes. El campo puede beneficiarse de iniciativas educativas para reducir el sesgo de género implícito en las cartas de recomendación. Consulte Video Resumen en http://links.lww.com/DCR/C191 . (Traducción-Dr. Ingrid Melo ).

Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia.

Neonatal cerebral hypoxia-ischemia (HI) is the leading cause of death and disability in newborns with the only current treatment being hypothermia. An increased understanding of the pathways that facilitate tissue repair after HI may aid the development of better treatments. Here, we study the role of lactate receptor HCAR1 in tissue repair after neonatal HI in mice. We show that HCAR1 knockout mice have reduced tissue regeneration compared with wildtype mice. Furthermore, proliferation of neural progenitor cells and glial cells, as well as microglial activation was impaired. Transcriptome analysis showed a strong transcriptional response to HI in the subventricular zone of wildtype mice involving about 7300 genes. In contrast, the HCAR1 knockout mice showed a modest response, involving about 750 genes. Notably, fundamental processes in tissue repair such as cell cycle and innate immunity were dysregulated in HCAR1 knockout. Our data suggest that HCAR1 is a key transcriptional regulator of pathways that promote tissue regeneration after HI.

Hypoxic-ischaemic brain injury is the most common cause of disability in newborn babies. This happens when the blood supply to the brain is temporarily blocked during birth and cells do not receive the oxygen and nutrients they need to survive. Cooling the babies down after the hypoxic-ischemic attack (via a technique called hypothermic treatment) can to some extent reduce the damage caused by the injury. However, doctors still need new drugs that can protect the brain and improve its recovery after the injury has occurred. Research in mice suggests that a chemical called lactate might help the brain to recover. Lactate is produced by muscles during hard exercise to provide energy to cells when oxygen levels are low. Recent studies have shown that it can also act as a signalling molecule that binds to a receptor called HCAR1 (short for hydroxycarboxylic acid receptor) on the surface of cells. However, it is poorly understood what role HCAR1 plays in the brain and whether it helps the brain recover from a hypoxic-ischaemic injury. To investigate, Kennedy et al. compared newborn mice with and without the gene that codes for HCAR1 that had undergone a hypoxic-ischaemic brain injury. While HCAR1 did not protect the mice from the disease, it did help their brains to heal. Mice with the gene for HCAR1 partly recovered some of their damaged brain tissue six weeks after the injury. Their cells switched on thousands of genes involved in the immune system and cell cycle, resulting in new brain cells being formed that could repopulate the injured areas. In contrast, the brain tissue of mice lacking HCAR1 barely produced any new cells. These findings suggest that HCAR1 may help with brain recovery after hypoxia-ischemia in newborn mice. This could lead to the development of drugs that might reduce or repair brain damage in newborn babies. However, further studies are needed to investigate whether HCAR1 has the same effect in humans.

Iatrogenic Femoral Arteriovenous Fistula with Pseudoaneurysm Associated with Worsening Heart Failure Years after Percutaneous Impella Placement.

Iatrogenic arteriovenous fistulas (AVFs) and pseudoaneurysms (PSAs) are rare complications that may develop years after vascular access, and high-volume flow through these AVFs have been hypothesized to contribute to chronic heart failure. Formation of an AVF or PSA following Impella placement has rarely been described in the literature. Here, we describe a patient who had percutaneous placement of an Impella ventricular assist device through his right groin three years prior, now presenting with worsening heart failure and symptoms of volume overload. He was discovered to have a new, high-flow common femoral artery to femoral vein AVF with an associated PSA. The AVF and associated PSA were resected and repaired. This case study highlights a rare access-site complication from percutaneous Impella placement associated with worsening heart failure, strategies for preventing this complication during peripheral access, and the need to consider this differential in such a patient with a history of peripheral access who has an unexplained worsening of heart failure.

Human macrophages and monocyte-derived dendritic cells stimulate the proliferation of endothelial cells through midkine production.

The cytokine midkine (MK) is a growth factor that is involved in different physiological processes including tissue repair, inflammation, the development of different types of cancer and the proliferation of endothelial cells. The production of MK by primary human macrophages and monocyte-derived dendritic cells (MDDCs) was never described. We investigated whether MK is produced by primary human monocytes, macrophages and MDDCs and the capacity of macrophages and MDDCs to modulate the proliferation of endothelial cells through MK production. The TLR stimulation of human monocytes, macrophages and MDDCs induced an average of ≈200-fold increase in MK mRNA and the production of an average of 78.2, 62, 179 pg/ml MK by monocytes, macrophages and MDDCs respectively (p < 0.05). MK production was supported by its detection in CD11c+ cells, CLEC4C+ cells and CD68+ cells in biopsies of human tonsils showing reactive lymphoid follicular hyperplasia. JSH-23, which selectively inhibits NF-κB activity, decreased the TLR-induced production of MK in PMBCs, macrophages and MDDCs compared to the control (p < 0.05). The inhibition of MK production by macrophages and MDDCs using anti-MK siRNA decreased the capacity of their supernatants to stimulate the proliferation of endothelial cells (p = 0.01 and 0.04 respectively). This is the first study demonstrating that the cytokine MK is produced by primary human macrophages and MDDCs upon TLR triggering, and that these cells can stimulate endothelial cell proliferation through MK production. Our results also suggest that NF-κB plays a potential role in the production of MK in macrophages and MDDCs upon TLR stimulation. The production of MK by macrophages and MDDCs and the fact that these cells can enhance the proliferation of endothelial cells by producing MK are novel immunological phenomena that have potentially important therapeutic implications.

What Can an Aging Pouch Tell Us? Outcomes of Ileoanal Pouches Over 20 Years Old.

BACKGROUND: Little is known about the long-term functional outcomes of restorative proctocolectomy. OBJECTIVE: The aim of this study was to examine ileoanal pouch outcomes 20 and 30 years postoperatively. DESIGN: This is a retrospective case series. SETTING: This study was conducted at a tertiary care referral center. PATIENTS: Patients who underwent restorative proctocolectomy between 1980 and 1994 were identified. Those with ≥20 years of in-person follow-up were included. MAIN OUTCOMES MEASURES: Pouch function, pouchitis, anal stricture, and pouch failure rates were analyzed. RESULTS: A total of 203 patients had ≥20 years of follow-up. Of those, 71 had ≥30 years of follow-up. Initial diagnoses included ulcerative colitis (83%), indeterminate colitis (9%), familial adenomatous polyposis (4%), and Crohn's disease (3%). Twenty-one percent of those with ulcerative or indeterminate colitis later transitioned to Crohn's disease. Mean daily stool frequency was 7 (IQR 6-8), 38% experienced seepage, 31% had anal stenosis, 47% experienced pouchitis, and 18% had pouch failure. Over time, stool frequency increased in 41% of patients, stayed the same in 43%, and decreased in 16%. Patients older than 50 years at the time of construction had more daily bowel movements (median 8 vs 6; p = 0.02) and more seepage (77% vs 35%; p = 0.005) than those younger than 50 years. Patients with Crohn's disease had higher stool frequency (median 8 vs 6; p < 0.001) and higher rates of anal stenosis (44% vs 26%; p = 0.02), pouchitis (70% vs 40%; p < 0.001), and pouch failure (38% vs 12%; p < 0.001) compared to non-Crohn's patients. Patients with ≥30 years of follow-up had similar function as those with 20-30 years of follow-up. LIMITATIONS: This was a retrospective, single-institution study. Only 35% of pouches created during the study period had >20 years of follow-up. CONCLUSIONS: Most patients maintain reasonably good function and retain their pouches after 20 years. Over time, stool frequency and seepage increase. Older age and Crohn's disease are associated with worse outcomes. See Video Abstract at http://links.lww.com/DCR/B801. QU NOS DICE UN RESERVORIO A LARGO PLAZO RESULTADOS DE LOS RESERVORIOS ILEOANALES MAYORES DE AOS: ANTECEDENTES:se sabe poco sobre los resultados funcionales a largo plazo de la proctocolectomía restauradora.OBJETIVO:El objetivo de este estudio fue examinar los resultados del reservorio ileoanal 20 y 30 años después de la operación.DISEÑO:Serie de casos retrospectiva.ENTORNO CLÍNICO:Centro de referencia de atención terciariaPACIENTES:Se identificaron pacientes que se sometieron a proctocolectomía restauradora entre 1980 y 1994. Se incluyeron aquellos con ≥20 años de seguimiento en persona.PRINCIPALES MEDIDAS DE VALORACIÓN:Se analizaron la función, inflamación, tasas de falla del reservorio y estenosis anal.RESULTADOS:Un total de 203 pacientes tuvieron ≥20 años de seguimiento. De ellos, 71 tenían ≥30 años de seguimiento. Los diagnósticos iniciales incluyeron colitis ulcerosa (83%), colitis indeterminada (9%), poliposis adenomatosa familiar (4%) y enfermedad de Crohn (3%). El 21% de las personas con colitis ulcerosa o indeterminada pasaron posteriormente a la enfermedad de Crohn. La frecuencia promedio de las deposiciones diarias fue de 7 (rango intercuartil 6-8), el 38% experimentó filtración, el 31% tuvo estenosis anal, el 47% experimentó pouchitis y el 18% tuvo falla del reservorio. Con el tiempo, la frecuencia de las deposiciones aumentó en el 41% de los pacientes, se mantuvo igual en el 43% y disminuyó en el 16%. Los pacientes mayores de 50 años en el momento de la construcción tenían más evacuaciones intestinales diarias (media 8 vs 6, p = 0,02) y más filtraciones (77% vs 35%, p = 0,005) que los menores de 50 años. Los pacientes con enfermedad de Crohn tenían mayor frecuencia de deposiciones (media 8 vs 6, p < 0,001) y tasas más altas de estenosis anal (44% vs 26%, p = 0,02), inflamacion (70% vs 40%, p <0,001) y falla del reservorio (38% frente a 12%, p <0,001) en comparación con pacientes que tenian enfermedad de Crohn. Los pacientes con ≥30 años de seguimiento tuvieron una función similar a aquellos con 20-30 años de seguimiento.LIMITACIONES:Este fue un estudio retrospectivo de una sola institución. Solo el 35% de los reservorios creados durante el período de estudio tuvieron más de 20 años de seguimiento.CONCLUSIONES:La mayoría de los pacientes mantienen una función razonablemente buena y conservan el reservorio después de 20 años. Con el tiempo, la frecuencia de las deposiciones y la filtración aumentan. La vejez y la enfermedad de Crohn se asocian con peores resultados. Consulte Video Resumen en http://links.lww.com/DCR/B801. (Traducción - Dr. Ingrid Melo).

Effects of Bacterial Metabolites on the Immune System: Enemies and Friends.

Metabolites produced by bacteria can influence the immune system. These metabolites are produced by pathogenic bacteria as well as the friendly microbiota. This review sheds light on the major bacterial metabolites and their structures. It also describes the capacity of these molecules to stimulate and inhibit the immune responses in a way that affects their capacity to control different diseases.

Defining IL-6 levels in healthy individuals: A meta-analysis.

BACKGROUND: Interleukin-6 (IL-6) is produced by and impacts different cell types in human. IL-6 is associated with different diseases and viral infections, including COVID-19. To our knowledge, no normal values were reported for IL-6 in the blood of healthy individuals. We have reviewed and performed a meta-analysis on a total of 140 studies, including 12,421 values for IL-6 in the blood of healthy adult donors. Among these studies, 83 did not report a mean value and the standard deviation. Therefore, for the statistical analysis, we used the values reported in 57 studies, which included 3166 values for IL-6. RESULTS: The reported values for IL-6 in the blood of healthy donors varied between 0 and 43.5 pg/ml. The pooled estimate of IL-6 was 5.186 pg/ml (95% confidence interval [CI]: 4.631, 5.740). As the age increased by 1 year, IL-6 values increased by 0.05 pg/ml (95% CI: 0.02, 0.09; p < .01). Though the heterogenicity, as determined by I2 statistics, was high in our study, the differences in IL-6 values are still at the level of a few pg/ml, which might be related to the differences in the conditions that influence IL-6 production in the healthy population. CONCLUSIONS: This is the first meta-analysis reporting the levels of IL-6 in the blood of healthy donors based on a large number of studies and donors. Therefore the 95% CI values determined in our study could well serve as a reference range for quick decision-making in clinical interventions, particularly those aiming to inhibit IL-6, especially urgent interventions, for example, COVID-19.

Sleep deprivation alters neutrophil functions and levels of Th1-related chemokines and CD4+ T cells in the blood.

PURPOSE: The state of knowledge about the effect of sleep deprivation on the immune system is scarce and conflicting. It would therefore be useful to investigate the consequences of sleep deprivation on the immune system. We have studied the effect of sleep deprivation on the changes in neutrophil functions, and the ex vivo proliferative pattern of CD4+ T lymphocytes in relationship with blood cytokine and chemokine levels due to the crucial role of these cells in mounting potent immune responses. METHODS: Healthy volunteers were followed for 3 weeks. They had normal sleep in weeks 1 and 3 and they were sleep-deprived on week 2, sleeping < 6 h per 24 h, a pattern similar to sleep behaviors of many chronically sleep-deprived individuals. We assessed the levels of Th1/Th2 and inflammatory cytokines and chemokines, CD4+ T cells, and the NADPH oxidase activation and phagocytic functions in neutrophils. RESULTS: Our results suggest that sleep deprivation leads to a decreased neutrophil capacity to phagocytose bacteria and activate NADPH oxidase (p < 0.05). Sleep deprivation was associated with a potential increase in CXCL9 levels and decrease in CXCL10/CXCL9 and CCL5/CXCL9 ratios (p < 0.05). Furthermore, our results suggest that the decrease in CD4+ T cell due to sleep deprivation was not associated with changes in their proliferation as observed by Ki67 levels, but rather, it correlated with changes in CXCL10/CXCL9 ratio (p < 0.05). CONCLUSIONS: Sleep deprivation may lead to a decreased phagocytosis and NADPH oxidase activity in neutrophils and a decrease in the levels of CD4+ T cells which is related to changes in the Th1-related chemokine balance.

Genetic diversity and transmissibility of imported Plasmodium vivax in Qatar and three countries of origin.

Malaria control program in the Arabian Peninsula, backed by adequate logistical support, has interrupted transmission with exception of limited sites in Saudi Arabia and sporadic outbreaks in Oman. However, sustained influx of imported malaria represents a direct threat to the above success. Here we examined the extent of genetic diversity among imported P. vivax in Qatar, and its ability to produce gametocytes, compared to parasites in main sites of imported cases, the Indian subcontinent (india) and East Africa (Sudan and Ethiopia). High diversity was seen among imported P. vivax in Qatar, comparable to parasites in the Indian subcontinent and East Africa. Limited genetic differentiation was seen among imported P. vivax, which overlapped with parasites in India, but differentiated from that in Sudan and Ethiopia. Parasite density among imported cases, ranged widely between 26.25-7985934.1 Pv18S rRNA copies/µl blood, with a high prevalence of infections carried gametocytes detectable by qRT-PCR. Parasitaemia was a stronger predictor for P. vivax gametocytes density (r = 0.211, P = 0.04). The extensive diversity of imported P. vivax and its ability to produce gametocytes represent a major threat for re-introduction of malaria in Qatar. The genetic relatedness between P. vivax reported in Qatar and those in India suggest that elimination strategy should target flow and dispersal of imported malaria into the region.

Viruses Seen by Our Cells: The Role of Viral RNA Sensors.

The role of the innate immune response in detecting RNA viruses is crucial for the establishment of proper inflammatory and antiviral responses. Different receptors, known as pattern recognition receptors (PRRs), are present in the cytoplasm, endosomes, and on the cellular surface. These receptors have the capacity to sense the presence of viral nucleic acids as pathogen-associated molecular patterns (PAMPs). This recognition leads to the induction of type 1 interferons (IFNs) as well as inflammatory cytokines and chemokines. In this review, we provide an overview of the significant involvement of cellular RNA helicases and Toll-like receptors (TLRs) 3, 7, and 8 in antiviral immune defenses.

Heart Rate Variability in Extremely Preterm Infants Receiving Nasal CPAP and Non-Synchronized Noninvasive Ventilation Immediately After Extubation.

INTRODUCTION: There is a paucity of studies comparing the physiological effects of nasal CPAP or non-synchronized noninvasive ventilation (ns-NIV) during the postextubation phase in preterm infants. Heart rate variability (HRV) can identify system instability before clinical or laboratory signs of deterioration. Thus, we sought to investigate any differences in HRV between those modes. METHODS: 15 preterm infants with birthweight ≤1,250 g and undergoing their first extubation attempt were studied immediately after disconnection from mechanical ventilation. Electrocardiogram (ECG) recordings were obtained while on nasal CPAP and ns-NIV in a random order (30-60 min on each). Time and frequency domain analyses were used to calculate HRV from 5-min segments of ECG. RESULTS: 12 of 15 infants were analyzed (3 were excluded for low ECG quality): 7 successes and 5 failures. HRV parameters were higher during ns-NIV when compared to nasal CPAP, but differences were not statistically different. However, absolute and relative differences in HRV values (all time domain parameters) were significantly higher in infants who failed extubation during ns-NIV. CONCLUSIONS: Nasal CPAP or ns-NIV provided immediately postextubation did not affect HRV. Interestingly, in an exploratory analysis, changes in HRV did occur during ns-NIV in the subgroup of infants who failed extubation. Hence, changes in HRV as early as 2 h after extubation should be further explored in larger studies as a potential predictor of postextubation respiratory failure.

Altered blood cytokines, CD4 T cells, NK and neutrophils in patients with obstructive sleep apnea.

BACKGROUND: There are contradictory reports on the effects of obstructive sleep apnea (OSA) on the immune system. In order to clarify the effect of OSA on the different components of the immune system, we studied the association of OSA with changes in cytokine and chemokine levels, proliferative patterns of CD4 and CD8 T lymphocytes as well as NK cells ex vivo and neutrophil functions. METHODS: We investigated the association of OSA with potential alterations in 14 Th1/Th2 and inflammatory cytokines and chemokines, CD4 and CD8 T cells, NK cells, and the NADPH oxidase activation and phagocytic functions in neutrophils. RESULTS: Our results suggest that the increase in CD4 T cell frequency in OSA is associated with an increased expression of the nuclear protein Ki67 (p<0.05; power>0.8), and is correlated with the levels of IL-1ß (p<0.05; power>0.8). The levels of IL-1ß as well as IL-6 showed a potential increase, while the levels of IFN-γ (p<0.05; power>0.8) and the ratio IFN-γ/IL-4 in the blood were possibly decreased in OSA. Additionally, we observed a potential increase in the expression of Ki67 in CD8hi and CD8lo NK cells (p<0.05; power>0.8). Our results also suggest that neutrophils have a decreased capacity to phagocytose bacteria and activate NADPH oxidase in OSA patients (p<0.05; power>0.8). CONCLUSION: OSA may be associated with inflammatory and pro-Th2 immune responses, an increased proliferative potential of NK and CD4 T cells and a decreased capacity of neutrophils to phagocytose bacteria and produce ROS.

Increased CD86 but Not CD80 and PD-L1 Expression on Liver CD68+ Cells during Chronic HBV Infection.

BACKGROUND: The failure to establish potent anti-HBV T cell responses suggests the absence of an effective innate immune activation. Kupffer cells and liver-infiltrating monocytes/macrophages have an essential role in establishing anti-HBV responses. These cells express the costimulatory molecules CD80 and CD86. CD80 expression on antigen-presenting cells (APCs) induces Th1 cell differentiation, whereas CD86 expression drives the differentiation towards a Th2 profile. The relative expression of CD80, CD86 and PD-L1 on APCs, regulates T cell activation. Few studies investigated CD80 and CD86 expression on KCs and infiltrating monocytes/macrophages in HBV-infected liver and knowledge about the expression of PD-L1 on these cells is controversial. The expression of these molecules together in CD68+ cells has not been explored in HBV-infected livers. METHODS: Double staining immunohistochemistry was applied to liver biopsies of HBV-infected and control donors to explore CD80, CD86 and PD-L1 expression in the lobular and portal areas. RESULTS: Chronic HBV infection was associated with increased CD68+CD86+ cell count and percentage in the lobular areas, and no changes in the count and percentage of CD68+CD80+ and CD68+PD-L1+ cells, compared to the control group. While CD68+CD80+ cell count in portal areas correlated with the fibrosis score, CD68+CD80+ cell percentage in lobular areas correlated with the inflammation grade. CONCLUSION: The upregulation of CD86 but not CD80 and PD-L1 on CD68+ cells in HBV-infected livers, suggests that these cells do not support the induction of potent Th1. Moreover, the expression of CD80 on CD68+ cells correlates with liver inflammation and fibrosis.