Nurses' preferences regarding MenACWY conjugate vaccines attributes: a discrete choice experiment in Spain.

OBJECTIVES: Immunisation against preventable diseases as meningitis is crucial from a public health perspective to face challenges posed by these infections. Nurses hold a great responsibility for these programs, which highlights the importance of understanding their preferences and needs to improve the success of campaigns. This study aimed to investigate nurses' preferences regarding Meningococcus A, C, W, and Y (MenACWY) conjugate vaccines commercialised in Spain. STUDY DESIGN: A national-level discrete choice experiment (DCE) was conducted. METHODS: A literature review and a focus group informed the DCE design. Six attributes were included: pharmaceutical form, coadministration evidence, shelf-life, package contents, single-doses per package, and package volume. Conditional logit models quantified preferences and relative importance (RI). RESULTS: Thirty experienced primary care nurses participated in this study. Evidence of coadministration with other vaccines was the most important attribute (RI = 43.78%), followed by package size (RI = 22.17%), pharmaceutical form (RI = 19.07%), and package content (RI = 11.80%). There was a preference for evidence of coadministration with routine vaccines (odds ratio [OR] = 2.579, 95% confidence interval [95%CI] = 2.210-3.002), smaller volumes (OR = 1.494, 95%CI = 1.264-1.767), liquid formulations (OR = 1.283, 95%CI = 1.108-1.486) and package contents including only vial/s (OR = 1.283, 95%CI = 1.108-1.486). No statistical evidence was found for the remaining attributes. CONCLUSIONS: Evidence of coadministration with routine vaccines, easy-to-store packages, and fully liquid formulations were drivers of nurses' preferences regarding MenACWY conjugate vaccines. These findings provide valuable insights for decision-makers to optimize current campaigns.

Surgical management of complex perianal fistula revisited in a systematic review: a critical view of available scientific evidence.

BACKGROUND: Treating complex perianal fistulas in Crohn's disease patients remains a challenge. Classical surgical treatments for Crohn's disease fistulas have been extrapolated from cryptoglandular fistulas treatment, which have different etiology, and this might interfere with its effectiveness, in addition, they increase fecal incontinence risk. Recently, new surgical techniques with support from biological approaches, like stem cells, have been developed to preserve the function of the sphincter. We have performed a systematic literature review to compare the results of these different techniques in the treatment of Crohn's or Cryptoglandular fistula. METHODS: PubMed, EMBASE, Database of Abstracts of Reviews of Effectiveness, Cochrane Central Register of Controlled Trials were searched systematically for relevant articles. We included randomized controlled trials and observational studies that referred to humans, were written in English, included adults 18+ years old, and were published during the 10-year period from 2/01/2010 to 2/29/2020. Evidence level was assigned as designated by the Scottish Intercollegiate Guidelines Network. RESULTS: Of the 577 citations screened, a total of 79 were ultimately included in our review. In Crohn's disease patients, classical techniques such as primarily seton, Ligation of Intersphincteric Fistula Tracks, or lay open, healing rates were approximately 50-60%, while in cryptoglandular fistula were around, 70-80% for setons or flaps. In Crohn's disease patients, new surgical techniques using derivatives of adipose tissue reported healing rates exceeding 70%, stem cells-treated patients achieved higher combined remission versus controls (56.3% vs 38.6%, p = 0.010), mesenchymal cells reported a healing rate of 80% at week 12. In patients with cryptoglandular fistulas, a healing rate of 70% using derivatives of adipose tissue or platelets was achieved, and a healing rate of 80% was achieved using laser technology. Fecal incontinence was improved after the use of autologous platelet growth factors and Nitinol Clips. CONCLUSION: New surgical techniques showed better healing rates in Crohn's disease patients than classical techniques, which have better results in cryptoglandular fistula than in Crohn's disease. Healing rates for complex cryptoglandular fistulas were similar between the classic and new techniques, being the new techniques less invasive; the incontinence rate improved with the current techniques.

Type 2 diabetes progression: A regulatory network approach.

In order to elucidate central elements underlying type 2 diabetes, we constructed a regulatory network model involving 37 components (molecules, receptors, processes, etc.) associated to signaling pathways of pancreatic beta-cells. In a first approximation, the network topology was described by Boolean rules whose interacting dynamics predicted stationary patterns broadly classified as health, metabolic syndrome, and diabetes stages. A subsequent approximation based on a continuous logic analysis allowed us to characterize the progression of the disease as transitions between these states associated to alterations of cell homeostasis due to exhaustion or exacerbation of specific regulatory signals. The method allowed the identification of key transcription factors involved in metabolic stress as essential for the progression of the disease. Integration of the present analysis with existent mathematical models designed to yield accurate account of experimental data in human or animal essays leads to reliable predictions for beta-cell mass, insulinemia, glycemia, and glycosylated hemoglobin in diabetic fatty rats.

Nanoparticulated Systems Based on Natural Polymers Loaded with Miconazole Nitrate and Lidocaine for the Treatment of Topical Candidiasis.

People with weakened immune systems are at risk of developing candidiasis which is a fungal infection caused by several species of Candida genus. In this work, polymeric nanoparticles containing miconazole nitrate and the anesthetic lidocaine clorhydrate were developed. Miconazole was chosen as a typical drug to treat buccopharyngeal candidiasis whereas lidocaine may be useful in the management of the pain burning, and pruritus caused by the infection. Nanoparticles were synthesized using chitosan and gelatin at different ratios ranging from 10:90 to 90:10. The nano-systems presented nanometric size (between 80 and 300 nm in water; with polydispersion index ranging from 0.120 to 0.596), and positive Z potential (between 20.11 and 37.12 mV). The determined encapsulation efficiency ranges from 65 to 99% or 34 to 91% for miconazole nitrate and lidocaine clorhydrate, respectively. X-ray diffraction and DSC analysis suggested that both drugs were in amorphous state in the nanoparticles. Finally, the systems fitted best the Korsmeyer-Peppas model showing that the release from the nanoparticles was through diffusion allowing a sustained release of both drugs and prolonged the activity of miconazole nitrate over time against Candida albicans for at least 24 h.

First Result on the Neutrinoless Double-ß Decay of

We report the result of the search for neutrinoless double beta decay of ^{82}Se obtained with CUPID-0, the first large array of scintillating Zn^{82}Se cryogenic calorimeters implementing particle identification. We observe no signal in a 1.83 kg yr ^{82}Se exposure, and we set the most stringent lower limit on the 0νßß ^{82}Se half-life T_{1/2}^{0ν}>2.4×10^{24} yr (90% credible interval), which corresponds to an effective Majorana neutrino mass m_{ßß}<(376-770) meV depending on the nuclear matrix element calculations. The heat-light readout provides a powerful tool for the rejection of α particles and allows us to suppress the background in the region of interest down to (3.6_{-1.4}^{+1.9})×10^{-3} counts/(keV kg yr), an unprecedented level for this technique.

[Cocaine induced midline destructive lesions. Report of one case]. / Lesiones destructivas de la línea media facial secundarias al consumo de cocaína. Caso clínico.

Vasculitic midline destructive lesions can be a complication of cocaine use. We report a 44-year-old man who presented with a two months history of left facial pain associated with ipsilateral facial paralysis and a cheek phlegmon. Magnetic resonance imaging showed broad soft tissue destruction linked to important cranial nerve involvement. Antibiotic and antifungal therapy was started and multiple surgical debridement procedures were performed, with no clinical improvement. Microbiological analysis was negative. Finally, thanks to the histologic findings corresponding to vasculitis and granuloma formation and the history of cocaine abuse, a cocaine induced midline destructive lesion was diagnosed.

Development and Evaluation of Buccal Films Based on Chitosan for the Potential Treatment of Oral Candidiasis.

In this work, chitosan films were prepared by a casting/solvent evaporation methodology using pectin or hydroxypropylmethyl cellulose to form polymeric matrices. Miconazole nitrate, as a model drug, was loaded into such formulations. These polymeric films were characterized in terms of mechanical properties, adhesiveness, and swelling as well as drug release. Besides, the morphology of raw materials and films was investigated by scanning electron microscopy; interactions between polymers were analyzed by infrared spectroscopy and drug crystallinity studied by differential scanning calorimetry and X-ray diffraction. In addition, antifungal activity against cultures of the five most important fungal opportunistic pathogens belonging to Candida genus was investigated. Chitosan:hydroxypropylmethyl cellulose films were found to be the most appropriate formulations in terms of folding endurance, mechanical properties, and adhesiveness. Also, an improvement in the dissolution rate of miconazole nitrate from the films up to 90% compared to the non-loaded drug was observed. The in vitro antifungal activity showed a significant activity of the model drug when it is loaded into chitosan films. These findings suggest that chitosan-based films are a promising approach to deliver miconazole nitrate for the treatment of candidiasis.

[Lupus enteritis as initial manifestation of systemic lupus erythematosus. Report of one case]. / Enteritis lúpica como manifestación inicial de lupus eritematoso sistémico. Caso clínico.

Although gastrointestinal symptoms are not rare in Systemic lupus erythematosus, enteritis is an atypical manifestation of the disease. We report a 54 year-old woman who presented acute symptoms of diarrhea, fever and abdominal pain, receiving empiric antibiotic therapy for bacterial enteritis with no response. Computed tomography showed diffuse small intestine inflammation and serositis. Antinuclear antibodies, anti-Ro and anti-La were positive on blood tests. A lupic enteropathy was diagnosed and steroid treatment was initiated, with subsequent clinical improvement.

Antimicrobial susceptibility and typing of Neisseria gonorrhoeae strains from Southern Spain, 2012-2014.

BACKGROUND: Gonorrhoea remains an important health problem worldwide. The latest European guidelines have recommended the introduction of dual antimicrobial therapy due to the increase in its resistance to antimicrobial agents. METHODS: In the present study, the susceptibility to some antibiotics was evaluated, and the typing of Neisseria gonorrhoeae strains was also performed. All Neisseria gonorrhoeae (NG) strains isolated from January 2012 to October 2014 were included in this work. Gonococcal isolates were tested for susceptibility according to the recommendations of both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). A total of 65 isolates were typed by the NG multi-antigen sequence types (NG-MAST) technique. RESULTS: The most frequent types found were ST 1407, ST 5405, ST 2992, and ST 5120. If CLSI and EUCAST criteria were applied, an ST 9807 type was found non-susceptible to ceftriaxone and cefixime (MIC 0.5µg/mL). When only EUCAST breakpoints were taken into account, three strains were also resistant to cefixime (MIC 0.25µg/mL) and two isolates were resistant to ceftriaxone (MIC 0.19 and 0.25µg/mL, respectively). The majority of strains were resistant to ciprofloxacin, and all Neisseria gonorrhoeae strains were susceptible to spectinomycin; twenty-five percent of isolates were resistant to azithromycin. CONCLUSIONS: The implementation of antimicrobial surveillance programs at regional level should be part of an overall gonococcal infection control strategy. Efforts should be made to perform antimicrobial susceptibility, a "cured test" in all gonorrhoea cases, and identify treatment failures to verify emerging resistance. Some types have been associated with decreased susceptibility to cephalosporins, making molecular typing a useful tool to predict antimicrobial resistance.

MUC1/SEC and MUC1/Y overexpression is associated with inflammation in Sjögren's syndrome.

OBJECTIVES: To evaluate the expression and localization of MUC1/SEC and MUC1/Y isoforms in labial salivary glands (LSG) from Sjögren's syndrome patients (SS patients), as well as their in vitro expression induced by cytokines. SUBJECTS AND METHODS: Labial salivary gland from 27 primary SS patients and 22 non-SS sicca subjects were studied. Relative MUC1/SEC and MUC1/Y mRNA levels were determined by qPCR and protein levels by Western blotting. Induction of mucin mRNAs was assayed in vitro. Immunohistochemistry was used for localization. RESULTS: Relative MUC1/SEC and MUC1/Y mRNA and protein levels were significantly higher in LSG from SS patients. These mRNAs were induced by cytokines. MUC1/SEC and MUC1/Y were detected in acini apical region of control LSGs, and significant cytoplasmic accumulation was observed in acini of SS patients. MUC1/Y localized in acinar nuclei and cytoplasm of inflammatory cells of LSG from SS patients. A strong positive correlation was observed between cellular MUC1/SEC levels and glandular function determined by scintigraphy. CONCLUSIONS: We show for the first time that MUC1/SEC and MUC1/Y are expressed in LSG of both SS patients and non-SS sicca subjects. The observed overexpression and aberrant localization of MUC1/SEC and MUC1/Y and their induction by pro-inflammatory cytokines may favor the perpetuation of the inflammatory environment that disrupts the salivary glandular homeostasis in SS patients.

Strongyloidiasis in immigrants in Southern Spain.

OBJECTIVE: To analyse clinical and epidemiological characteristics of immigrant patients diagnosed with strongyloidiasis in our area. METHODS: An analyse was performed on patients with strongyloidiasis seen in the Tropical Medicine Unit of the "Hospital de Poniente" in Almeria (Spain), from April 2004 to May 2012. RESULTS: A total of 320 patients were diagnosed with Strongyloides stercoralis infection, and 284 out of 314 patients (90.4%) had a positive specific serology. Forty-two percent of the patients reported symptoms and 45% had eosinophilia. The serological results were monitored in some of the patients, confirming a loss of antibodies in all 20 patients studied. CONCLUSIONS: Strongyloidiasis is a parasitic disease increasingly diagnosed in developed countries due to increased migratory flows from endemic areas. Often being asymptomatic, its diagnosis and treatment may prevent fatal outcomes, especially in immunocompromised patients.

"Very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study.

OBJECTIVE: To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. BACKGROUND: Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. METHODS: Multicenter, retrospective, matched cohort 1:2 study. STUDY GROUP: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months. RESULTS: The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). CONCLUSIONS: Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

Does the use of the revised psychosocial assessment tool (PATrev) result in improved quality of life and reduced psychosocial risk in Canadian families with a child newly diagnosed with cancer?

OBJECTIVES: Early psychosocial screening may guide interventions and ameliorate the adverse psychosocial effects of childhood cancer. The revised psychosocial assessment tool provides risk information - Universal (typical distress), Targeted (additional specific distress), and Clinical (severe distress) - about the child with cancer and his or her family. This pilot study investigated the benefits of providing a summary of family psychosocial risk information to the medical team treating the newly diagnosed child (Experimental Group, EG). METHOD: We conducted a pilot randomized control trial with a sample of 67 parents, comparing the EG to the control group (CG) on parental perception of family psychosocial difficulties (revised psychosocial assessment tool risk levels), child behavior (behavior assessment scale for children-2), pediatric quality of life (PedsQL), and parental anxiety (state-anxiety scale of the state-trait anxiety inventory ), 2-4 weeks after diagnosis (Time 1) and 6 months later (Time 2). RESULTS: Compared to the CG, participants in the EG had significantly reduced targeted and clinical risk (p < 0.001), and improved pain related PedsQL at Time 2 (p < 0.05). Scores for PedsQL total and nearly all subscales improved over time in both groups (p < 0.05 to p < 0.001). No changes in behavior scores were noted. CONCLUSION: Preliminary findings suggest that providing a summary of the Psychosocial Assessment Tool to the treating team shortly after diagnosis may help reduce family wide psychosocial risk 6 months later and improve quality of life related to pain for children who are undergoing treatment for cancer.

External validity and reliability of the Psychosocial Assessment Tool (PAT) among Canadian parents of children newly diagnosed with cancer.

BACKGROUND: The Psychosocial Screening Tool (PAT) was developed and validated with a sample of caregivers of children newly diagnosed with cancer in the United States. This study aimed to assess cultural adaptation (Phase 1) and validity and reliability of the revised PAT (PATrev) with a Canadian sample (Phase 2). PROCEDURE: In Phase 1, a convenience sample of seven parents of children who were treated for cancer and six pediatric oncology healthcare experts participated. In Phase 2, 67 parents of children newly diagnosed with cancer from 4 Canadian pediatric cancer centers participated. To assess reliability and validity of the PATrev, parents completed behavioral (BASC-2) and quality of life (PedsQL) instruments about the child and an anxiety inventory (STAI) about themselves. RESULTS: The PAT required minor changes to be culturally adapted for the Canadian population. The PATrev had strong inter-rater (0.77) test-retest (0.75), and internal consistency reliability (0.85), as well as moderate to strong validity comparing PATrev child's problems and PedsQL total (-0.49), PedsQL anxiety (-0.47), BASC-2 internalizing (0.64), behavioral (0.63), and adaptive scores (-0.56). PATrev discriminative validity was confirmed with BASC-2 scores (AUR scores of 0.70-0.74). PATrev parental stressors were strongly correlated to STAI scores (0.53). Finally, agreement between PATrev child's problems and parental anxiety scores was moderate (0.47). CONCLUSION: This study supports the original PAT, demonstrates PATrev is a reliable and valid psychosocial screening tool, and provides unique evidence regarding early psychosocial risk in the family, which have important implications for guiding psychosocial practice.

Exploring fermentation with lactic acid bacteria as a pretreatment for enhancing antioxidant potential in broccoli stem powders.

Fruit and vegetable industries face a major environmental challenge with food loss and waste. Broccoli stems, comprising 38% of the plant's total weight, are usually discarded by the industry producing fourth-range and ready-to-use products, despite being rich in antioxidants, vitamins, fiber, carotenoids, phenolic compounds, and glucosinolates. Addressing the challenge of reducing waste in this sector includes the production of stable and nutrient-concentrated powders, which can be consumed directly or used as ingredients in functional food formulation. This study investigated fermentation with lactic acid bacteria (Limosilactobacillus reuteri, Lactiplantibacillus plantarum, and Lactobacillus salivarius) as a pretreatment for enhancing antioxidant and probiotic potential in broccoli stem powders. Results showed maximum counts 24 h after inoculation, and no effect of the previous disruption intensity on microbial growth was observed. Fermenting broccoli stems for 24 h with the three microbial strains led to a significant increase in total phenols and flavonoids but to a general reduction in the samples' capacity to scavenge DPPH and ABTS free radicals. Overall, ground broccoli stems exhibited the most favorable antioxidant properties following the 24 h fermentation step. The subsequent freeze-drying and final grinding had minimal impact on the microbial population but significantly enhanced the extractability of the antioxidant compounds. This study offers a valuable reference for researchers and stakeholders exploring the development of new products and innovations from vegetable waste.

Sjögren's syndrome and the epithelial target: a comprehensive review.

The most difficult component in our understanding of human autoimmunity remains a rigorous dissection of etiological events. Indeed, the vast literature on autoimmune diseases focuses on the inflammatory response, with the hope of developing drugs that reduce inflammation. However, there is increasing recognition that understanding the immunobiology of target tissues will also have direct relevance to disease natural history, including breach of tolerance. Sjögren's syndrome is essentially an epitheliitis and there are major changes to normal architectural salivary organization. We propose that loss of homeostasis is the initial event that precipitates inflammation and that such inflammatory response includes not only the adaptive response, but also an intense innate immune/bystander response. To understand these events this review focuses on the architecture, phenotype, function and epithelial cell organization. We further submit that there are several critical issues that must be defined to fully understand epithelial cell immunobiology in Sjögren's syndrome, including defining epithelial cell polarity, cell-cell and cell to extracellular matrix interactions and a variety of chemical and mechanical signals. We also argue that disruption of tight junctions induces disorganization of the apical pole of salivary acinar cells in Sjögren's syndrome. In addition, there will be a critical role of inflammatory cytokines in the apico-basal relocation of tight junction proteins. Further, the altered disorganization and relocation of proteins that participate in secretory granule formation are also dysregulated in Sjögren's syndrome and will contribute to abnormalities of mucins within the extracellular matrix. Our ability to understand Sjögren's syndrome and develop viable therapeutic options will depend on defining these events of epithelial cell biology.