Does fecal calprotectin increase may be linked to lactose intolerance in patients with irritable bowel syndrome?

BACKGROUND: Irritable bowel syndrome (IBS) is a multifactorial condition without any specific investigation. Fecal calprotectin (FC) may be elevated in IBS without any explanation. In addition, some patients with IBS have symptoms related to lactose intolerance. Our main aim was to investigate whether an increase in FC could be related to lactose intolerance in patients with IBS. METHODS: In this retrospective single-center study, all patients with IBS who have underwent a FC test and a lactose respiratory test within a period of less than 6 months were eligible. A FC greater than or equal to 50 µg/g was considered abnormal. RESULTS: Severnty-six patients (48 females), mean age 38±15 years were included. Symptoms were respectively: bloating in 57%, diarrhea in 76% and abdominal pain in 46% of cases. Among the 76 patients: 22 (29%) had FC≥50 µg/g and 9/22 (41%) had a positive lactose test. No significant relationship could be identified between the increase in FC and the lactose test positivity. The value of the FC was also not related to the subtype of IBS or the positivity of the glucose test. CONCLUSIONS: In our study, the increase in FC was not significantly related to the presence of lactose intolerance. Nevertheless, our work, despite its originality, is limited by its retrospective nature and small number of patients. Future studies including larger numbers of patients may identify the causes of elevated FC in patients with IBS to individualize different subgroups of patients to best adapt therapeutic management.

Neuromuscular Control of Vertical Jumps in Female Adolescents.

BACKGROUND: Poor landing mechanics are considered deficits in neuromuscular control and risk factors for lower extremity injury. The Landing Error Scoring System (LESS) has been used to assess the neuromuscular control of landing mechanics for the first landing in a drop vertical jump (DVJ) task. However, the second DVJ landing may provide different results, warranting assessment. HYPOTHESES: (1) LESS scores will differ between first and second DVJ landings across all female participants with (2) greater intraparticipant variability among the second landing compared with the first landing scores. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 13 gymnasts and 31 softball players (N = 44) performed 3 DVJ trials. The mean ± SD age of 44 female athletes was 16.46 ± 2.59 years. The LESS was scored using 2-dimensional video of each trial. RESULTS: There was a significant difference between the first and second DVJ landings (P < 0.01). All participants demonstrated higher LESS scores (worse landing mechanics) during the second DVJ landing (10.10 ± 2.25) than the first landing (6.97 ± 2.72). CONCLUSION: The initial landing in a DVJ has been the focus of neuromuscular control studies using the LESS. This study found worse neuromuscular control during the second DVJ landing, which highlights the importance of evaluating landing mechanics beyond the initial landing. CLINICAL RELEVANCE: LESS analysis of both DVJ landings might improve neuromuscular control screening in female athletes and augment lower extremity and anterior cruciate ligament injury prevention programs.

Broadly neutralizing antibodies with few somatic mutations and hepatitis C virus clearance.

Here, we report the isolation of broadly neutralizing mAbs (bNAbs) from persons with broadly neutralizing serum who spontaneously cleared hepatitis C virus (HCV) infection. We found that bNAbs from two donors bound the same epitope and were encoded by the same germline heavy chain variable gene segment. Remarkably, these bNAbs were encoded by antibody variable genes with sparse somatic mutations. For one of the most potent bNAbs, these somatic mutations were critical for antibody neutralizing breadth and for binding to autologous envelope variants circulating late in infection. However, somatic mutations were not necessary for binding of the bNAb unmutated ancestor to envelope proteins of early autologous transmitted/founder viruses. This study identifies a public B cell clonotype favoring early recognition of a conserved HCV epitope, proving that anti-HCV bNAbs can achieve substantial neutralizing breadth with relatively few somatic mutations, and identifies HCV envelope variants that favored selection and maturation of an anti-HCV bNAb in vivo. These data provide insight into the molecular mechanisms of immune-mediated clearance of HCV infection and present a roadmap to guide development of a vaccine capable of stimulating anti-HCV bNAbs with a physiologic number of somatic mutations characteristic of vaccine responses.

Extra-epitopic hepatitis C virus polymorphisms confer resistance to broadly neutralizing antibodies by modulating binding to scavenger receptor B1.

Broadly-neutralizing monoclonal antibodies (bNAbs) may guide vaccine development for highly variable viruses including hepatitis C virus (HCV), since they target conserved viral epitopes that could serve as vaccine antigens. However, HCV resistance to bNAbs could reduce the efficacy of a vaccine. HC33.4 and AR4A are two of the most potent anti-HCV human bNAbs characterized to date, binding to highly conserved epitopes near the amino- and carboxy-terminus of HCV envelope (E2) protein, respectively. Given their distinct epitopes, it was surprising that these bNAbs showed similar neutralization profiles across a panel of natural HCV isolates, suggesting that some viral polymorphisms may confer resistance to both bNAbs. To investigate this resistance, we developed a large, diverse panel of natural HCV envelope variants and a novel computational method to identify bNAb resistance polymorphisms in envelope proteins (E1 and E2). By measuring neutralization of a panel of HCV pseudoparticles by 10 µg/mL of each bNAb, we identified E1E2 variants with resistance to one or both bNAbs, despite 100% conservation of the AR4A binding epitope across the panel. We discovered polymorphisms outside of either binding epitope that modulate resistance to both bNAbs by altering E2 binding to the HCV co-receptor, scavenger receptor B1 (SR-B1). This study is focused on a mode of neutralization escape not addressed by conventional analysis of epitope conservation, highlighting the contribution of extra-epitopic polymorphisms to bNAb resistance and presenting a novel mechanism by which HCV might persist even in the face of an antibody response targeting multiple conserved epitopes.

Prenatal Nicotine Exposure Impairs Executive Control Signals in Medial Prefrontal Cortex.

Prenatal nicotine exposure (PNE) is linked to numerous psychiatric disorders including attention deficit hyperactivity disorder (ADHD). Current literature suggests that core deficits observed in ADHD reflect abnormal inhibitory control governed by the prefrontal cortex. Yet, it is unclear how neural activity in the medial prefrontal cortex (mPFC) is modulated during tasks that assess response inhibition or if these neural correlates, along with behavior, are affected by PNE. To address this issue, we recorded from single mPFC neurons in control and PNE rats as they performed a stop-signal task. We found that PNE rats were faster for all trial-types, made more premature responses, and were less likely to inhibit behavior on 'STOP' trials during which rats had to inhibit an already initiated response. Activity in mPFC was modulated by response direction and was positively correlated with accuracy and movement time in control but not PNE rats. Although the number of single neurons correlated with response direction was significantly reduced by PNE, neural activity observed on general STOP trials was largely unaffected. However, dramatic behavioral deficits on STOP trials immediately following non-conflicting (GO) trials in the PNE group appear to be mediated by the loss of conflict monitoring signals in mPFC. We conclude that prenatal nicotine exposure makes rats impulsive and disrupts firing of mPFC neurons that carry signals related to response direction and conflict monitoring.

Reactivation Kinetics of HIV-1 and Susceptibility of Reactivated Latently Infected CD4+ T Cells to HIV-1-Specific CD8+ T Cells.

UNLABELLED: The "shock and kill" model of human immunodeficiency virus type 1 (HIV-1) eradication involves the induction of transcription of HIV-1 genes in latently infected CD4(+) T cells, followed by the elimination of these infected CD4(+) T cells by CD8(+) T cells or other effector cells. CD8(+) T cells may also be needed to control the spread of new infection if residual infected cells are present at the time combination antiretroviral therapy (cART) is discontinued. In order to determine the time frame needed for CD8(+) T cells to effectively prevent the spread of HIV-1 infection, we examined the kinetics of HIV transcription and virus release in latently infected cells reactivated ex vivo. Isolated resting, primary CD4(+) T cells from HIV-positive (HIV+) subjects on suppressive regimens were found to upregulate cell-associated HIV-1 mRNA within 1 h of stimulation and produce extracellular virus as early as 6 h poststimulation. In spite of the rapid kinetics of virus production, we show that CD8(+) T cells from 2 out of 4 viremic controllers were capable of effectively eliminating reactivated autologous CD4(+) cells that upregulate cell-associated HIV-1 mRNA. The results have implications for devising strategies to prevent rebound viremia due to reactivation of rare latently infected cells that persist after potentially curative therapy. IMPORTANCE: A prominent HIV-1 cure strategy termed "shock and kill" involves the induction of HIV-1 transcription in latently infected CD4(+) T cells with the goal of elimination of these cells by either the cytotoxic T lymphocyte response or other immune cell subsets. However, the cytotoxic T cell response may also be required after curative treatment if residual latently infected cells remain. The kinetics of HIV-1 reactivation indicate rapid upregulation of cell-associated HIV-1 mRNA and a 5-h window between transcription and virus release. Thus, HIV-specific CD8(+) T cell responses likely have a very short time frame to eliminate residual latently infected CD4(+) T cells that become reactivated after discontinuation of antiretroviral therapy following potentially curative treatment strategies.

Salmonella enterica serovar Typhimurium-infected pigs with different shedding levels exhibit distinct clinical, peripheral cytokine and transcriptomic immune response phenotypes.

Foodborne salmonellosis costs the US $2.7 billion/year, including $100.0 million in annual losses to pork producers. Pigs colonized with Salmonella are usually asymptomatic with varied severity and duration of fecal shedding. Thus, understanding the responses that result in less shedding may provide a mechanism for control. Fifty-four pigs were inoculated with Salmonella enterica serovar Typhimurium (ST) and clinical signs, fecal ST shedding, growth performance, peripheral cytokines and whole blood gene expression were measured. Persistently shedding (PS) pigs had longer pyrexia and elevated serum IL-1ß, TNF-α and IFN-γ compared with low shedding (LS) pigs, while LS pigs had brief pyrexia, less shedding that decreased more rapidly and greater serum CXCL8 than PS pigs. The PS pigs up-regulated genes involved with the STAT1, IFNB1 and IFN-γ networks on d 2, while up-regulation of genes involved in immune response regulation were only detected in LS pigs. This is the first study to examine host responses to ST infection at a clinical, performance, cytokine and transcriptomic level. The results indicated that pigs with different shedding outcomes developed distinct immune responses within the first 2 d of ST infection, and elucidated alternative mechanisms that could be targeted to reduce Salmonella shedding and spread.

Dynamic anal endosonography and MRI defecography in diagnosis of pelvic floor disorders: comparison with conventional defecography.

BACKGROUND: Pelvic floor disorders are frequent, especially in women. Surgeons need more information on the accuracy of available diagnostic techniques to make therapeutic decisions. OBJECTIVE: This study aimed to compare the accuracy of dynamic anorectal endosonography and dynamic MRI defecography with conventional defecography as the criterion standard in the diagnosis of pelvic floor disorders. DESIGN: We used a prospective crossover design in which patients underwent each procedure in random order within the same month. SETTING: Investigations were conducted at a regional referral center in Marseille, France. PATIENTS: Women with dyschezia who were undergoing diagnostic evaluation were eligible. INTERVENTION: Dynamic anorectal endosonography, dynamic MRI, and conventional defecography were performed in all patients by 3 blinded operators. MAIN OUTCOME MEASURE: The accuracy of dynamic anorectal endosonography and dynamic MRI in the diagnosis of pelvic floor disorders was assessed by calculating sensitivity, specificity, positive and negative predictive values, correlation coefficients, concordance rates, and the Cohen κ statistic, with conventional defecography used as the criterion standard. RESULTS: The study comprised 56 women with a mean age of 50.7 (SD, 12.5) years. No significant differences were observed between dynamic anorectal endosonography and dynamic MRI in the number of patients with rectocele (P = .49), perineal descent (P = .11 when dynamic anorectal endosonography measured descent of the puborectalis muscle; P = .27 for bladder descent), or enterocele (P = .78); no differences were found between these techniques in sensitivity, specificity, or positive and negative predictive values. Diagnostic concordance with conventional defecography as the standard did not differ significantly between dynamic MRI and dynamic anorectal endosonography: Concordance rates for dynamic anorectal endosonography were 75% for rectocele, 64% for perineal descent, and 91% for enterocele (no rectal intussusception was found with dynamic anorectal endosonography); concordance rates for dynamic MRI were 82% for rectocele, 57% for perineal descent, 93% for enterocele, and 55% for rectal intussusception. Significantly more internal anal sphincter defects were found with dynamic anorectal endosonography than with dynamic MRI defecography: 21 patients (37.5%) vs 12 patients (21.4%); P = .02. Patient tolerance was significantly better for dynamic anorectal endosonography than for dynamic MRI (P = .002) or conventional defecography (P = .005). Most patients said they would choose dynamic anorectal endosonography (72.1%) rather than dynamic MRI (25.6%) or conventional defecography (2.3%) if follow-up were necessary (P < .001). CONCLUSION: Dynamic anorectal endosonography and dynamic MRI defecography show equivalent diagnostic performance in assessing pelvic floor disorders. However, because of its better tolerance and availability, dynamic anorectal endosonography may be preferable as the initial imaging procedure after clinical examination in the evaluation of pelvic floor disorders.

A complex forefoot malunion in a patient with Werner's syndrome: a case report.

Lower extremity surgical procedures in patients with Werner's syndrome are uncommon, and for this reason they are rarely reported in the literature. In this report, we present the case of a 39-year-old man with a history of Werner's syndrome, and a malunited right hallux varus and first ray insufficiency after previous bunionectomy performed 4 years earlier. Further reconstructive surgery involved forefoot osteotomy and arthrodesis with internal fixation, and the patient ultimately healed the soft tissues and bones, despite delayed wound healing.

Phenotypic variation of Pseudomonas brassicacearum as a plant root-colonization strategy.

Pseudomonas brassicacearum was isolated as a major root-colonizing population from Arabidopsis thaliana. The strain NFM421 of P. brassicacearum undergoes phenotypic variation during A. thaliana and Brassica napus root colonization in vitro as well as in soil, resulting in different colony appearance on agar surfaces. Bacteria forming translucent colonies (phase II cells) essentially were localized at the surface of young roots and root tips, whereas wild-type cells (phase I cells) were localized at the basal part of roots. The ability of phase II cells to spread and colonize new sites on root surface correlates with over-production of flagellin as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of surface proteins and microsequencing. Moreover, phase II cells showed a higher ability to swim and to swarm on semisolid agar medium. Phase I and phase II cells of P. brassicacearum NFM421 were tagged genetically with green fluorescent protein and red fluorescent protein. Confocal scanning laser microscopy was used to localize phase II cells on secondary roots and root tips of A. thaliana, whereas phase I cells essentially were localized at the basal part of roots. These experiments were conducted in vitro and in soil. Phenotypic variation on plant roots is likely to be a colonization strategy that may explain the high colonization power of P. brassicacearum.