The role of Serratia marcescens porins in antibiotic resistance

The outer membrane permeability of Serratia marcescens was studied by comparing porin-deficient mutants with their parental strains. Omp1-deficient strains were selected by moxalactam resistance, whereas mutants lacking the Omp2 porin were obtained by experimental infection with the SMP2 phage, whose primary receptor is the Omp2 porin. The role of porins was demonstrated in quinolone accumulation assays, where semiquantitative differences in accumulation were observed. Permeability coefficients to cephaloridine of Omp1 mutants were determined and compared with those of the parental strain. The clinical isolates S. marcescens HCPR1 and 866 showed 30- to 200-fold reduced permeability coefficients when Omp1 porin was absent.     

Hypergonadotrophinaemia with reduced uterine and ovarian size in women born small-for-gestational-age

BACKGROUND: Fetal growth restraint has been associated with FSH hypersecretion in early infancy and in early post-menarche, and with reduced uterine and ovarian size in adolescence. It is unknown whether these reproductive anomalies persist, respectively, into late infancy and into the reproductive age range. METHODS: We report follow-up findings in two age groups of girls. A cohort of infants [n=26; n=10 born appropriate-for-gestational-age (AGA) and n=16 born small-for-gestational-age (SGA)], who had been studied at the age of approximately 4 months, was assessed again at the age of 12 months. A cohort of teenagers (n=28), who had been studied at the age of approximately 14 years, was assessed again at the age of approximately 18 years; this group was complemented by a transversal cohort of similar age (n=19) for a total of 47 young women (n=27 AGA; n=20 SGA). In infants, only serum FSH was measured; adolescents underwent endocrine-metabolic screening, ultrasound assessment of uterine-ovarian size, and evaluation of body composition by dual X-ray absorptiometry. RESULTS: Serum FSH levels were higher in SGA than AGA infant girls at 4 and 12 months, and higher in SGA than AGA adolescents at 14 and 18 years (all P<0.01). Longitudinal ultrasound assessments disclosed a late-adolescent increment of uterine size that was less obvious in SGA than AGA girls. In contrast, ovarian volume remained stable in both subgroups. Compilation of longitudinal and transversal results at 18 years of age corroborated the persistent reduction in the uterine size of SGA girls (by approximately 20%; P<0.005) and in their ovarian volume (by approximately 40%; P<0.0001); moreover, SGA girls displayed not only a persistent elevation of FSH (by approximately 50%; P<0.001), but also a rise of LH and fasting insulin, as well as an excess of abdominal fat (all P<0.01). CONCLUSIONS: The gynaecology of young women born SGA was found to be characterized by hypergonadotrophinaemia and by a reduced uterine and ovarian size.     

Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia.

PURPOSE: To investigate whether allogeneic stem-cell transplantation (allo-SCT) may overcome the negative impact of unmutated VH genes in the outcome of patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: We analyzed the outcome of patients who underwent SCT according to their VH mutational status. RESULTS: Thirty-four patients (14 allo-SCT and 20 autologous SCT [auto-SCT]) presented unmutated VH genes and 16 patients presented mutated VH genes (nine allo-SCT and seven auto-SCT). Tumoral burden pre-SCT was significantly higher in the allo-SCT patients independent of the VH mutational status. The risk of relapse was significantly higher after auto-SCT (5-year risk, 61%; 95% CI, 44% to 84%) than after allo-SCT (5-year risk 12%, 95% CI, 3% to 44%; P < .05). In the unmutated group, 13 of 20 auto-SCT and two of 14 allo-SCT patients experienced disease progression, with a risk of relapse at 5 years of 66% (95% CI, 48% to 93%) v 17% (95% CI, 5% to 60%), respectively (P = .01). CONCLUSION: These results show that allo-SCT may overcome the unfavorable effect of unmutated VH genes in patients with CLL.     

Psychological Pathways to Paranoia and Psychotic-Like Experiences in Daily-Life: The Mediating Role of Distinct Affective Disturbances

Background and HypothesisInfluential models of psychosis indicate that the impact of putative causal factors on positive symptoms might be explained partly through affective disturbances. We aimed to investigate whether pathways from stress and self-esteem to positive symptoms, as well as reversal pathways from symptoms to stress and self-esteem, were mediated through specific affective disturbances across the extended psychosis phenotype.Study DesignUsing experience sampling methodology, 178 participants (65 high-schizotypy, 74 at-risk mental state, and 39 first-episode psychosis) were assessed on levels of momentary stress, self-esteem, anxiety, sadness, psychotic-like experiences (PLE), and paranoia. Multilevel mediation models were fit to examine indirect effects of each of these pathways. Considering evidence of mediation, each indirect pathway will be combined in a single model to explore their relative contributions.Study ResultsAnxiety, sadness, and self-esteem mediated the pathways from stress to PLE and paranoia in daily-life. In the pathway to paranoia, sadness, and self-esteem showed larger contributions than anxiety. Pathways from self-esteem to PLE and paranoia were mediated by anxiety and sadness, the later showing a larger contribution. Pathways from symptoms to stress, but not from symptoms to self-esteem, were differently explained by emotional states; sadness lost its mediating effect and anxiety was the most important mediator. Few differences across groups were found.ConclusionsThis study lends support to psychological models of psychosis that highlight the relevance of affective disturbances in the risk and expression of psychosis. Furthermore, specific influences of different negative emotional states were identified, which could enhance psychological treatments.     

HIV screening and linkage to care in a health department in Valencia,Spain: Lessons learned from a healthcare quality improvement project

Spain’s rate of new human immunodeficiency virus (HIV) diagnoses exceeds that of the European Economic Area average (8.6 vs 5.6:100,000 in 2018). The country has failed to meet the first of United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets for HIV control by 2020, with 87.0% of people living with HIV knowing their status, and late presentation rates of 47.6% and 51.5% country-wide and in the Valencian autonomous community, respectively. Advancing screening and linkage to care (SLTC) practices is necessary to effectively control the epidemic. The Valencia Viral Screening (CRIVALVIR) project adopted the TEST model for opportunistic and systematic HIV SLTC in individuals aged 18 to 80 who required blood work for any purpose, as of February 2019. SLTC was integrated into routine clinical workflow across primary care centers serving a population of 360,000 people in Valencia, Spain. Our project successfully upscaled total HIV testing by 194% to over 32,000 patients tested in 14 months. We found an overall prevalence of 0.13% (0.08–0.21) among those screened per protocol (n = 13,061), with foreign-born citizens presenting a 12.5 times significantly higher likelihood of acquiring HIV (95% confidence interval 4.63–33.96, P < .0001). We improved late presentation by 18.2 percentage points and prevented an estimated 58 to 70 new secondary infections. HIV screening of the general population in primary care is an effective strategy for achieving timely diagnosis and preventing new infections. Opportunistic, systematic, opt-out approaches are essential to control the HIV epidemic.     

Feeding Jejunostomy after esophagectomy cannot be routinely recommended. Analysis of nutritional benefits and catheter-related complications

Background

Patients undergoing esophagectomy for cancer usually deal with malnourishment which increases postoperative morbimortality. The objective of this paper is to analyze the nutritional benefits of feeding jejunostomy (FJ) for early postoperative enteral nutrition (EN) and directly-related complications.

Thyroid disease in primary Sjögren syndrome. Study in a series of 160 patients

We studied 160 consecutive patients (147 female and 13 male) with primary Sj?gren syndrome (SS) to determine the prevalence and clinical significance of thyroid disease in a large series of patients with primary SS from our unit and to compare the prevalence and significance with those in 75 individuals without SS from a primary care center. Serum levels of thyroid hormones (free thyroxine, triiodothyronine, and thyroid-stimulating hormone) and autoantibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) were measured in all SS patients and in 75 control patients. Fifty-eight (36%) of the 160 patients with primary SS had evidence of thyroid disease. Autoimmune thyroid disease (ATD) was diagnosed in 32 (20%) patients and nonautoimmune thyroid disease (NATD) in 26 (16%). No significant differences were found when these prevalences were compared with those in control patients. On the other hand, comparing those patients with altered hormonal profiles, patients with NATD showed mainly hyperthyroidism (10/17, 59% versus 2/20, 10% in patients with ATD, p = 0.001). Finally, when clinical and immunologic manifestations of SS were analyzed in patients with and without thyroid disease, respectively, we found that patients with thyroid disease had a higher prevalence of female gender (98% versus 88%, p = 0.03), antiparietal cell autoantibodies (33% versus 12%, p = 0.002), TgAb (30% versus 5%, p < 0.001), and TPOAb (40% versus 5%, p < 0.001). In conclusion, thyroid disease occurred in more than one-third of patients with primary SS; the main cause was ATD, which was present in 20% of the patients studied. We note that no significant differences were observed when the prevalence of thyroid disease (either ATD or NATD) was compared with that in a control group of similar age and gender. Our results indicate that middle-aged women (with or without SS) should be screened periodically for thyroid function.