Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative Multiplexed Imaging Analysis Reveals a Strong Association between Immunogen-Specific B Cell Responses and Tonsillar Germinal Center Immune Dynamics in Children after Influenza Vaccination

Generation of Ag-specific humoral responses requires the orchestrated development and function of highly specialized immune cells in secondary lymphoid organs. We used a multiparametric approach combining flow cytometry, confocal microscopy, and histocytometry to analyze, for the first time to our knowledge in children, tonsils from seasonal influenza–vaccinated children. We used these novel imaging assays to address the mucosal immune dynamics in tonsils investigating the spatial positioning, frequency, and phenotype of immune cells after vaccination. Vaccination was associated with a significantly higher frequency of follicular helper CD4 T cells compared with the unvaccinated control group. The imaging analysis revealed that potential suppressor (FOXP3hi) CD4 T cells are mainly located in extrafollicular areas. Furthermore, a significantly reduced frequency of both follicular and extrafollicular FOXP3hi CD4 T cells was found in the vaccine group compared with the control group. Levels of circulating CXCL13 were higher in those vaccinated compared with controls, mirroring an increased germinal center reactivity in the tonsils. Notably, a strong correlation was found between the frequency of tonsillar T follicular helper cells and tonsillar Ag-specific Ab-secreting cells. These data demonstrate that influenza vaccination promotes the prevalence of relevant immune cells in tonsillar follicles and support the use of tonsils as lymphoid sites for the study of germinal center reactions after vaccination in children.
Conservative management of preterm premature rupture of membranes beyond 32 weeks’ gestation: Is it worthwhile?

Abstract We aimed to investigate whether conservative management of preterm premature rupture of membranes (PPROM) at 32–34 weeks’ gestation improves outcome. In this retrospective analysis of singleton pregnancies, the study group included patients with PPROM at 28–34 weeks’ gestation and the control group included patients presented with spontaneous preterm delivery at 28–34 weeks’ gestation. Both groups were subdivided according to gestational age – early (28–31 weeks’ gestation) versus late (32–34 weeks’ gestation). Adverse neonatal outcome included neonatal death, intraventricular haemorrhage grade 3/4, respiratory distress syndrome, periventricular leucomalacia and neonatal sepsis. The study and control groups included 94 and 86 women, respectively. The study group had a lower incidence of adverse neonatal outcome at the earlier weeks (28–31), compared with the control group at the same gestational age. In contrast, at 32–34 weeks’ gestation no difference in the risk for adverse neonatal outcome was noticed. Additionally, within the study group, chorioamnionitis rate was significantly higher among those who delivered at 32–34 weeks’ gestation (p < 0.01). No advantage for conservative management of PPROM was demonstrated beyond 31 weeks’ gestation. Moreover, conservative management of PPROM at 32–34 weeks’ gestation may expose both mother and neonate to infectious morbidity.
Cervical ectopic pregnancy treated with systemic methotrexate and following successful term pregnancy: case report.

Introduction Implantation of the zygote outside the uterine cavity occurs in 2% of all pregnancies. Cervical ectopic pregnancy characterised by implantation of fertilised ovum in the cervical mucosa represents less than 1% of all ectopic pregnancies, with an estimated incidence of one in 2500 to one in 12,000 pregnancies (Cepni et al. 2004). The most common predisposing factors are the previous dilatation and curettage, previous caesarean delivery, assisted reproduction technologies (ART), Asherman’s syndrome, therapeutic abortion or ectopic pregnancies. The ultrasound imaging of cervical ectopic pregnancy shows round gestational sac (GS) located below the level of internal ostium of uterus, empty uterine cavity and peritrophoblastic Doppler colour flow. There are no specific guidelines about the treatment of cervical pregnancy and only case reports are reported. The early diagnosis in asymptomatic cases has provided the feasibility for a conservative management of cervical pregnancy. Medical treatment with methotrexate (MTX) can be administered by systemic or local route under ultrasound guidance (Vela and Tulandi 2007). A non-conservative therapy such as hysterectomy is used when conservative strategies failed or in case of massive haemorrhage and haemodynamic instability in order to preserve woman’s life. We present a case of cervical pregnancy at 7 weeks’ gestation resolved by two intra-muscular injection of MTX without any additional surgical modality. Case presentation A 38-year-old nulliparous woman became pregnant by intra-cytoplasmic sperm injection (ICSI). She did not undergo any previous cervical or intra-uterine procedure. After the stimulation with clomiphene citrate she underwent an ICSI with single embryo transfer. Beta-human chorionic gonadotropin (BHCG) values were 153 mIU/ ml 15 days after the transfer, 2885 mIU/ml after 20 days and 9595 mIU/ml after 23 days. She was admitted to our Department at 7 weeks of pregnancy for severe pelvic pain without vaginal bleeding. Ultrasounds showed that the GS was implanted in the cervix 18 mm away from the inner uterine orifice. Trophoblast seemed to be well-vascularised and to invade myometrium in the anterior-right wall of the cervix (Figure 1). The patient was hospitalised and we administered an intra-muscular injection of MTX (50 mg/mq) at day 1. At day 7, we repeated a second dose of MTX because the BHCG levels had not declined to 15% from the initial value. Neither ultrasound-guided curettage nor evacuation were required. No side effects or toxicity occurred after treatment. We measured weekly BHCG levels and performed ultrasound monitoring until BHCG was undetectable 30 days after the first administration Ultrasound findings of ectopic pregnancy disappeared after 40 days. Nine months later patient underwent an ICSI obtainiga singleton successful term pregnancy delivered by a scheduled caesarean section at 39 weeks’ gestation for breech presentation. No maternal or neonatal complication occurred.
Different Selected Mechanisms Attenuated the Inhibitory Interaction of KIR2DL1 with C2+ HLA-C in Two Indigenous Human Populations in Southern Africa

The functions of human NK cells in defense against pathogens and placental development during reproduction are modulated by interactions of killer cell Ig-like receptors (KIRs) with HLA-A, -B and -C class I ligands. Both receptors and ligands are highly polymorphic and exhibit extensive differences between human populations. Indigenous to southern Africa are the KhoeSan, the most ancient group of modern human populations, who have highest genomic diversity worldwide. We studied two KhoeSan populations, the Nama pastoralists and the ≠Khomani San hunter-gatherers. Comprehensive next-generation sequence analysis of HLA-A, -B, and -C and all KIR genes identified 248 different KIR and 137 HLA class I, which assort into ∼200 haplotypes for each gene family. All 74 Nama and 78 ≠Khomani San studied have different genotypes. Numerous novel KIR alleles were identified, including three arising by intergenic recombination. On average, KhoeSan individuals have seven to eight pairs of interacting KIR and HLA class I ligands, the highest diversity and divergence of polymorphic NK cell receptors and ligands observed to date. In this context of high genetic diversity, both the Nama and the ≠Khomani San have an unusually conserved, centromeric KIR haplotype that has arisen to high frequency and is different in the two KhoeSan populations. Distinguishing these haplotypes are independent mutations in KIR2DL1, which both prevent KIR2DL1 from functioning as an inhibitory receptor for C2+ HLA-C. The relatively high frequency of C2+ HLA-C in the Nama and the ≠Khomani San appears to have led to natural selection against strong inhibitory C2-specific KIR.
INCIDENCE OF NON-CANDIDA ALBICANS IN PATIENTS WITH URINARY TRACT INFECTION WITH SPECIAL REFERENCE TO SPECIATION AND ANTIFUNGAL SUSCEPTIBILITY

BACKGROUND AND OBJECTIVES: Fungal urinary tract infections have become frequent, as a result of increased use of broad spectrum antibiotics, corticosteroids, immunosuppressive drugs and bladder catheters in acute care settings. The associated risk factors which are seen in cases of candiduria are: antibiotic therapy, female gender, urinary catheterization, surgical procedure and extended hospitalization. Candiduria has become a potential source of morbidity and mortality if untreated. We undertook a prospective study to note the incidence of non-Candida albicans in patients with urinary tract infection with special reference to speciation, antifungal susceptibility and the associated risk factors. METHODS: Candida species isolated from urine samples of patients with urinary tract infection were subjected to speciation using standard yeast identification protocol and CHROM agar. Antifungal Susceptibility testing was done by the disc diffusion method to amphotericin B and fluconazole. Clinical details and risk factors of the patients were noted down. RESULTS: Among the 60 culture positive cases, six Candida species which were isolated are : C.tropicalis (66.66%), C.albicans (13.33%), C.parapsilosis (8.33%), C.glabrata (6.66%), C.kefyr (3.33%) and C.guilliermondii (1.66%) The susceptibility pattern showed, that of the 60 isolates, 40% were resistant to fluconazole. No resistance was seen to amphotericin B. CONCLUSION: Isolation of non-Candida albicans species was more than Candida albicans. Candida tropicalis was the predominant isolate. The following risk factors were noted: 43.33 % of the patients had diabetes mellitus, 30%had history of prolonged antibiotics (cephalosporin and aminoglycosides), 16.66% had underlying renal pathology, 3.33% had post -renal transplant status, 1.66% were on steroids, 1.66%had pregnancy and 3.33% had no identifiable risk factors.20% patients had an indwelling catheter in them. The antifungal resistance was more in the non-Candida albicans species than in Candida albicans. Hence there is a need for speciation, susceptibility testing of Candida species.
miR-340 Alleviates Psoriasis in Mice through Direct Targeting of IL-17A

Th17 cell is a well-known lineage of CD4+ effector Th cells that selectively produce IL-17A and play critical roles during the pathogenesis of autoimmune disease. A microRNA (miRNA) is a small noncoding RNA molecule that functions in posttranscriptional regulation of gene expression. Recently, an increasing number of studies have demonstrated that multiple miRNAs are dysregulated in patients with various autoimmune diseases and mediate autoimmune disease pathologic condition at least in part through the regulation of Th17 response. However, among the few miRNAs identified so far that play possible roles in the differentiation of Th17 cells, they all regulate the Th17 response through targeting negative or positive regulators of Th17 differentiation. In the current study, we sought to identify new miRNAs that can directly regulate the expression of IL-17A, the most important cytokine produced by Th17 cells. Our results showed that the 3′ untranslated region of mouse IL-17A can act as a negative regulatory element to downregulate gene expression. Further study revealed that miR-340 can specifically bind to the 3′ untranslated region of mouse IL-17A and downregulate the expression of endogenous IL-17A. More importantly, we demonstrated that treatment with miR-340 alleviates the clinical severity of imiquimod-induced psoriasis in mice through the downregulation of IL-17A. These data indicate that miR-340 may be a useful therapeutic target for the treatment of psoriasis and other IL-17A–mediated autoimmune diseases.
Innate Lymphoid Cells Have Decreased HLA-DR Expression but Retain Their Responsiveness to TLR Ligands during Sepsis

Sepsis, one of the leading causes of death in intensive care units, is caused by a dysregulated host response to infection that leads to life-threatening organ dysfunction. The proinflammatory and anti-inflammatory responses activated by the infecting microorganism become systemic, and the sustained anti-inflammatory response induces a state of immunosuppression that is characterized by decreased expression of HLA-DR on monocytes, T cell apoptosis, and reduced production of TNF-α by monocytes and macrophages in response to TLR ligands. Innate lymphoid cells (ILCs) are lymphocytes that lack Ag-specific receptors and lineage-specific markers; they express HLA-DR and are activated by cytokines and by direct recognition of microbial molecules. In this study, we evaluated if ILCs are affected by the anti-inflammatory response during sepsis. We found that the number of peripheral blood ILCs was decreased in septic patients compared with healthy volunteers; this decrease was caused by a reduction in ILC1 and ILC3 and is associated with apoptosis, because ILCs from septic patients expressed active caspase 3. ILCs from septic patients had decreased HLA-DR expression but increased expression of the activating receptors NKp46 and NKp44; they also showed a sustained expression of CD127 (IL-7R α-chain) and retained their capacity to produce TNF-α in response to TLR ligands. These results indicate that during sepsis, ILCs have decreased HLA-DR expression and die via apoptosis, similar to monocytes and T cells, respectively. However, other effector functions of ILCs (activation through NKp46 and NKp44, TNF-α production) may remain unaffected by the immunosuppressive environment prevailing in septic patients.
Plasma Soluble Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis

Rationale: The receptor for advanced glycation end products (RAGE) is underexpressed in idiopathic pulmonary fibrosis (IPF) lung, but the role of RAGE in human lung fibrosis remains uncertain. Objectives: To examine (1) the association between IPF risk and variation at rs2070600, a functional missense variant in AGER (the gene that codes for RAGE), and (2) the associations between plasma‐soluble RAGE (sRAGE) levels with disease severity and time to death or lung transplant in IPF. Methods: We genotyped the rs2070600 single‐nucleotide polymorphism in 108 adults with IPF and 324 race‐/ethnicity‐matched control subjects. We measured plasma sRAGE by ELISA in 103 adults with IPF. We used generalized linear and additive models as well as Cox models to control for potential confounders. We repeated our analyses in 168 (genetic analyses) and 177 (sRAGE analyses) adults with other forms of interstitial lung disease (ILD). Results: There was no association between rs2070600 variation among adults with IPF (P = 0.31). Plasma sRAGE levels were lower among adults with IPF and other forms of ILD than in control subjects (P < 0.001). The rs2070600 allele A was associated with a 49% lower sRAGE level (95% confidence interval [CI], 11 to 71%; P = 0.02) among adults with IPF. In adjusted analyses, lower sRAGE levels were associated with greater disease severity (14% sRAGE decrement per 10% FVC decrement; 95% CI, 5 to 22%) and a higher rate of death or lung transplant at 1 year (adjusted hazard ratio, 1.9 per logarithmic unit of sRAGE decrement; 95% CI, 1.2‐3.3) in IPF. Similar findings were observed in a heterogeneous group of adults with other forms of ILD. Conclusions: Lower plasma sRAGE levels may be a biological measure of disease severity in IPF. Variation at the rs2070600 single‐nucleotide polymorphism was not associated with IPF risk.
Does the number of tissue fragments removed from the cervix with excisional treatment for CIN pathology affect the completeness of excision and cytology recurrence at follow-up? An observational cohort study

The objective of our study was to determine whether removing multiple pieces of cervical tissue during large loop excision of the transformation zone (LLETZ) reduced the margin positivity of excision and cytology recurrence rates at follow-up. We conducted an observational cohort study and identified 462 women having had a single LLETZ treatment for cervical intraepithelial neoplasia (CIN) over a two-year period. Women with previous cervical treatment, cervical cancer on the excised tissue or missing follow-up data were excluded. Multiple regression analysis showed that removal of cervical tissue in multiple pieces did not offer any benefit in removing more disease and less recurrence rates. When multiple pieces were taken there was a four-fold increased risk for inconclusive excision margins as reported by the histopathologist. Removal of multiple pieces led to significantly more tissue being removed which may expose the patient to an increased risk of preterm delivery in a future pregnancy.
Readmission to the Intensive Care Unit: Incidence, Risk Factors, Resource Use, and Outcomes. A Retrospective Cohort Study

&NA; Rationale: Readmission to the intensive care unit (ICU) is associated with poor clinical outcomes, increased length of ICU and hospital stay, and higher costs. Nevertheless, knowledge of epidemiology of ICU readmissions, risk factors, and attributable outcomes is restricted to developed countries. Objectives: To determine the effect of ICU readmissions on in‐hospital mortality, determine incidence of ICU readmissions, identify predictors of ICU readmissions and hospital mortality, and compare resource use and outcomes between readmitted and nonreadmitted patients in a developing country. Methods: This retrospective single‐center cohort study was conducted in a 40‐bed, open medical‐surgical ICU of a private, tertiary care hospital in São Paulo, Brazil. The Local Ethics Committee at Hospital Israelita Albert Einstein approved the study protocol, and the need for informed consent was waived. All consecutive adult (≥18 yr) patients admitted to the ICU between June 1, 2013 and July 1, 2015 were enrolled in this study. Results: Comparisons were made between patients readmitted and not readmitted to the ICU. Logistic regression analyses were performed to identify predictors of ICU readmissions and hospital mortality. Out of 5,779 patients admitted to the ICU, 576 (10%) were readmitted to the ICU during the same hospitalization. Compared with nonreadmitted patients, patients readmitted to the ICU were more often men (349 of 576 patients [60.6%] vs. 2,919 of 5,203 patients [56.1%]; P = 0.042), showed a higher (median [interquartile range]) severity of illness (Simplified Acute Physiology III score) at index ICU admission (50 [41‐61] vs. 42 [32‐54], respectively, for readmitted and nonreadmitted patients; P < 0.001), and were more frequently admitted due to medical reasons (425 of 576 [73.8%] vs. 2,998 of 5,203 [57.6%], respectively, for readmitted and nonreadmitted patients; P < 0.001). Simplified Acute Physiology III score (P < 0.001), ICU admission from the ward (odds ratio [OR], 1.907; 95% confidence interval [CI], 1.463‐2.487; P < 0.001), vasopressors need during index ICU stay (OR, 1.391; 95% CI, 1.130‐1.713; P = 0.002), and length of ICU stay (P = 0.001) were independent predictors of ICU readmission. After adjusting for severity of illness, ICU readmission (OR, 4.103; 95% CI, 3.226‐5.518; P < 0.001), admission source, presence of cancer, use of vasopressors, mechanical ventilation or renal replacement therapy, length of ICU stay, and nighttime ICU discharge were associated with increased risk of in‐hospital death. Conclusions: Readmissions to the ICU were frequent and strongly related to poor outcomes. The degree to which ICU readmissions are preventable as well as the main causes of preventable ICU readmissions need to be further determined.
Pulse Pressure Not Mean Pressure Determines Cardiovascular Risk in Older Hypertensive Patients

Background: Current guidelines for the management of hypertension rest almost completely on the measurement of systolic and diastolic blood pressure. However, the arterial blood pressure wave is more correctly described as consisting of a pulsatile (pulse pressure) and a steady (mean pressure) component. Objective: To explore the independent roles of pulse pressure and mean pressure as determinants of cardiovascular prognosis in older hypertensive patients. Methods: This meta-analysis, based on individual patient data, pooled the results of the European Working Party on High Blood Pressure in the Elderly trial (n = 840), the Systolic Hypertension in Europe Trial (n = 4695), and the Systolic Hypertension in China Trial (n = 2394). The relative hazard rates associated with pulse pressure and mean pressure were calculated using Cox regression analysis, with stratification for the 3 trials and with adjustments for sex, age, previous cardiovascular complications, smoking, and treatment group. Results: A 10-mm Hg wider pulse pressure increased the risk of major cardiovascular complications; after controlling for mean pressure and the other covariates, the increase in risk ranged from approximately 13% for all coronary end points (P = .02) to nearly 20% for cardiovascular mortality (P = .001). In a similar analysis, mean pressure predicted the incidence of cardiovascular complications but only after removal of pulse pressure as an explanatory variable from the model. Furthermore, the probability of a major cardiovascular end point increased with higher systolic blood pressure; at any given level of systolic blood pressure, it also increased with lower diastolic blood pressure, suggesting that the wider pulse pressure was driving the risk of major complications. Conclusions: In older hypertensive patients, pulse pressure not mean pressure is the major determinant of cardiovascular risk. The implications of these findings for the management of hypertensive patients should be further investigated in randomized controlled outcome trials in which the pulsatile component of blood pressure is differently affected by antihypertensive drug treatment. Arch Intern Med. 2000;160:1085-1089
Parental Beliefs About Cause and Course of their Child's Autism and Outcomes of their Beliefs: A Review of the Literature

Background: This article provides a review of the literature on beliefs that parents of children with autism hold, with a focus on their beliefs on the cause and course of the disorder. Research on the outcomes of their beliefs also was reviewed. Methods: Medline, PsychInfo, Nursing@Ovid and PubMed were searched from 1995 through 2009 using the keywords autism, autistic disorder, beliefs, culture, parents, attitudes, and perceptions. Additional articles were identified through Google Scholar and from references in related articles. Thirteen articles were retrieved and reviewed. Results: It was found in the review that parents hold a wide variety of beliefs about the cause of their child's autism, including genetic factors, events surrounding the child's birth, and environmental influences in the early childhood period. Some parents continue to attribute their child's autism to immunizations, although more recent studies suggest the frequency may be decreasing. Some parents are pessimistic about their child's future while others are hopeful that new strategies will be developed. Some trust that society will become more accepting of their child's idiosyncrasies. Parents' beliefs about the cause of their child's autism have been found to have an impact on decisions regarding future health care, family planning, and maternal mental health. The link between parental beliefs and their choices for interventions has not yet been empirically explored. Conclusions: Research on the impact of cultural beliefs specific to autism is very limited, although studies focusing on other developmental disorders suggest that it is influential. The importance of exploring parental beliefs during the process of treatment planning is discussed.