Topical Analgesia with Lidocaine Plus Diclofenac Decreases Pain in Benign Anorectal Surgery: Randomized, Double-blind, and Controlled Clinical Trial

Objective: The aim of this study is to evaluate the efficacy and safety of a topical formulation containing lidocaine plus diclofenac (CLIFE1) compared to CLIFE2 (lidocaine), to decrease pain in benign anorectal surgery (BARS) to date not evaluated. Background: More than 50% of patients undergoing BARS, especially hemorrhoidectomy, suffer from moderate and severe postoperative pain. This remains an unresolved problem that could be addressed with the new CLIFE1 topical treatment. Methods: A multicenter, randomized double-blind, active-controlled parallel-group superiority trial, was conducted in two Spanish hospitals. Patients undergoing BARS (hemorrhoids, anal fistula and anal fissure) were randomized at the end of surgery at a 1:1 ratio to receive first dose either CLIFE1 (n=60) or CLIFE2 (n=60) anorectal topical treatment, and after every 12 hours for the first three postoperative days and once a day from the fourth to sixth. The primary outcome was average of pain decrease after topical treatment, measured with visual analogue scale (VAS) by the patients themselves, the evening in the surgery day and four times daily for the first three postoperative days. Results: The results of 120 patients included out of 150 selected undergoing BARS show a decrease in pain after CLIFE1 topical treatment (7.47±13.2) greater than with CLIFE2 (4.38±6.75), difference -3.21 (95% CI) -5.75; -0.676; p=0.008), decreasing significantly postoperative pain (≥ 9 mm, VAS) in 35% of patients undergoing benign anorectal surgery, compared to 18.33 % treated with lidocaine. Conclusions: The CLIFE1 topical treatment shows better analgesic efficacy than CLIFE2 in BARS

Dark Matter and Higgs Sector

The inert doublet model is an extension of the Standard Model of Elementary Particles that is defined by the only addition of a second Higgs doublet without couplings to quarks or leptons. This minimal framework has been studied for many reasons. In particular, it has been suggested that the new degrees of freedom contained in this doublet can account for the Dark Matter of the Universe.Comment: 6 pages, 3 figures,To appear in the Proceedings of the sixth International Workshop on the Dark Side of the Universe (DSU2010) Leon, Guanajuato, Mexico 1-6 June 201

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Twin pregnancy with complete hydatidiform mole and coexisting fetus following ovulation induction with a non-prescribed clomiphene citrate regimen: a case report

<p>Abstract</p> <p>Introduction</p> <p>Twin pregnancy with complete hydatidiform mole represents a very rare obstetric problem. Management of such cases is always problematic because the possibility of fetal survival should always be weighed against the risk of complications of molar pregnancy.</p> <p>Case presentation</p> <p>A 34-year-old Caucasian woman presented to our center with mild vaginal bleeding. Our patient was 16 weeks pregnant after a seven-year period of primary infertility. She became pregnant following a non-prescribed regimen of clomiphene citrate extending from the second day to the 13th day of her last cycle. A transabdominal ultrasound examination revealed a twin pregnancy with complete hydatidiform mole and a coexisting fetus. Serum β human chorionic gonadotropin was falsely low as identified by serial dilution of the sample (the 'hook effect'). Our patient refused termination of pregnancy and she was hospitalized for strict observation and follow-up. Unfortunately, she developed an attack of severe vaginal bleeding and a hysterotomy was performed. The fetus died shortly after birth.</p> <p>Conclusions</p> <p>Twin pregnancy with complete hydatidiform mole represents a matter of controversy. We suggest that conservation should always be considered whenever tertiary care services and strict observation are available.</p

Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation

Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection. pDC responsiveness to TLR7 and TLR9 stimulation was assessed in-vitro. Circulating pDC remained transcriptionally stable with gene expression altered for 8 genes (FDR < 0.07). There was no upregulation of co-stimulatory molecules CD86, CD80, CD40, and reduced surface expression of HLA-DR and CD123 (IL-3R-α). pDC loss from the circulation was associated with active caspase-3, suggesting pDC apoptosis during primary infection. pDC remained responsive to TLR stimulation, producing IFN-α and upregulating HLA-DR, CD86, CD123 at peak-infection. In clinical malaria, pDC retained HLA-DR but reduced CD123 expression compared to convalescence. These data demonstrate pDC retain function during a first blood-stage P. falciparum exposure despite sub-microscopic parasitaemia downregulating HLA-DR. The lack of evident pDC activation in both early infection and malaria suggests little response of circulating pDC to infection

Clinical significance of stromal apoptosis in colorectal cancer

BackgroundEpithelial and stromal cells play an important role in the development of colorectal cancer (CRC). We aimed to determine the prognostic significance of both epithelial and stromal cell apoptosis in CRC.MethodsTotal apoptosis was determined by caspase-3 activity measurements in protein homogenates of CRC specimens and adjacent normal mucosa of 211 CRC patients. Epithelial apoptosis was determined by an ELISA specific for a caspase-3-degraded cytokeratin 18 product, the M30 antigen. Stromal apoptosis was determined from the ratio between total and epithelial apoptosis.ResultsEpithelial and stromal apoptosis, as well as total apoptosis, were significantly higher in CRC compared with corresponding adjacent normal mucosa. Low total tumour apoptosis (&lt; or = median caspase-3 activity) was associated with a significantly worse disease recurrence (hazard ratio (HR), 95% confidence interval (95% CI): 1.77 (1.05-3.01)), independent of clinocopathological parameters. Epithelial apoptosis was not associated with clinical outcome. In contrast, low stromal apoptosis (&lt; or = median caspase-3/M30) was found to be an independent prognostic factor for overall survival, disease-free survival and disease recurrence, with HRs (95% CI) of 1.66 (1.17-2.35), 1.62 (1.15-2.29) and 1.69 (1.01-2.85), respectively.InterpretationStromal apoptosis, in contrast to epithelial apoptosis, is an important factor with respect to survival and disease-recurrence in CRC

The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice

BACKGROUND: Neutrophils have been shown to play a role in host defence against highly virulent and mouse-adapted strains of influenza virus, however it is not clear if an effective neutrophil response is an important factor moderating disease severity during infection with other virus strains. In this study, we have examined the role of neutrophils during infection of mice with influenza virus strain HKx31, a virus strain of the H3N2 subtype and of moderate virulence for mice, to determine the role of neutrophils in the early phase of infection and in clearance of influenza virus from the respiratory tract during the later phase of infection. METHODS: The anti-Gr-1 monoclonal antibody (mAb) RB6-8C5 was used to (i) identify neutrophils in the upper (nasal tissues) and lower (lung) respiratory tract of uninfected and influenza virus-infected mice, and (ii) deplete neutrophils prior to and during influenza virus infection of mice. RESULTS: Neutrophils were rapidly recruited to the upper and lower airways following influenza virus infection. We demonstrated that use of mAb RB6-8C5 to deplete C57BL/6 (B6) mice of neutrophils is complicated by the ability of this mAb to bind directly to virus-specific CD8+ T cells. Thus, we investigated the role of neutrophils in both the early and later phases of infection using CD8+ T cell-deficient B6.TAP-/- mice. Infection of B6.TAP-/- mice with a low dose of influenza virus did not induce clinical disease in control animals, however RB6-8C5 treatment led to profound weight loss, severe clinical disease and enhanced virus replication throughout the respiratory tract. CONCLUSION: Neutrophils play a critical role in limiting influenza virus replication during the early and later phases of infection. Furthermore, a virus strain of moderate virulence can induce severe clinical disease in the absence of an effective neutrophil response

Evaluation of IL-12 and CXCL-10 in patients with hepatitis C, non-alcoholic fatty liver disease and liver damage for alcohol consumption

Introduction and Objectives: To Compare serum levels of IL-12 and CXCL-10 in different etiologies of liver disease. Materials and methods: A cross-sectional and multicenter study was carried out, including subjects with alcoholism according to criteria WHO, without (OH) and with liver injury (cirrhosis, CiOH) and (Alcoholic Hepatitis, HA); non-alcoholic fatty liver (NAFLD) and chronic Hepatitis C (CHC), diagnosed by clinical, biochemical data. They were compared with subjects control (CT). For determination of IL-12 and CXCL-10 with Multiplex®-MERCK©. Statistical analysis by SPSS V.22 using U de Mann Whitney, p<0.05; values expressed as mean ± standard error. Results: Included 20 subjects with NAFLD, 78 CHC, 14 HA, 20 CiOH, 15 OH y 60 CT. IL-12 was found elevated in OH, HA, CHC vs. CT in OH vs. HCc y HGNA (p≤0.05). CXCL-10 was found elevated in CiOH, HA and CHC vs. CT(p≤0.050). Discussion: The IL-12 showed elevated levels in subjects with alcohol consumption and CHC vs. CT that activates other cell types involved in inflammation. CXCL-10 is induced by IFN-γ, was found elevated in CiOH, HA and CHC, exerting their biological effects through CXCR3, including activation of peripheral immune cells and apoptosis. The ratio of IL-12/CXCL-10 in OH increased 4.6 times, ratifying the participation in chronic and continual inflammatory response by alcohol consumption. Conclusions: IL-12 and CXCL-10 have an important role in alcohol-induced liver disease, confirming their contribution to inflammation, being evident CXCL-10 in advanced stages of the disease, by stimulating and favoring the migration of immune cells to the damage sites. Funding: This work was partially financed by CONACyT SALUD-2016-272579 and PAPIIT- UNAM TA200515. Declaration of interest: The authors declare no potential conflicts of interest