Dietary carbohydrate quality index and incidence of obesity-related cancers in the "Seguimiento Universidad De Navarra" (SUN) prospective cohort.

PURPOSE: The quality, rather than the quantity, of carbohydrate intake may play a major role in the etiology of obesity-related cancers (ORCs). We assessed the association between a previously defined carbohydrate quality index (CQI) and the risk of developing ORCs in the "Seguimiento Universidad de Navarra" (SUN) cohort. METHODS: A total of 18,446 Spanish university graduates [mean age 38 years (SD 12 years), 61% women, mean BMI 23.5 kg/m2 (SD 3.5 kg/m2)], with no personal history of cancer, were followed-up. Baseline CQI was assessed summing quintiles of four previously defined criteria: high dietary fiber intake, low glycemic index (GI), high whole-grain: total-grain carbohydrates ratio and high solid carbohydrates: total carbohydrates ratio. Participants were classified into tertiles of their total CQI. Incident ORCs were confirmed by an oncologist using medical records and by querying the National Death Index blindly to dietary exposures. RESULTS: During a median follow-up of 13.7 years, 269 incident cases of ORC were confirmed. A higher CQI was inversely associated with ORC incidence [multivariable-adjusted hazard ratio (HR) for the upper (T3) versus the lowest tertile (T1) of 0.68 (95% CI: 0.47-0.96), p for trend = 0.047]. Particularly, higher dietary fiber intake was inversely associated with ORC, HRT3 vs. T1=0.57 (95% CI 0.37-0.88 p for trend = 0.013). CONCLUSION: In this prospective Mediterranean cohort, an inverse association between a better global quality of carbohydrate intake and the risk of ORCs was found. Strategies for cancer prevention should promote a higher quality of carbohydrate intake.

Association between CACNG2 polymorphisms (rs4820242, rs2284015 and rs2284017) and chronic peripheral neuropathic pain risk in a Mexican population.

OBJECTIVE: In animal models and humans, mutations in voltage-dependent calcium channel gamma-2 subunit gene (CACNG2) have been associated with neuronal hyperexcitability, including neuropathic pain. The objective of this study was to determine the allelic and genotypic frequencies of CACNG2 polymorphisms (rs4820242, rs2284015 and rs2284017) and their association with the risk of chronic peripheral neuropathic pain (CPNP) in the Mexican population. PATIENTS AND METHODS: Single nucleotide polymorphisms (SNPs) were determined by real-time PCR, and allelic and genotypic frequencies were compared between healthy Mexican subjects and CPNP patients. The risk of association of CACNG2 SNPs with the presence of CPNP and its characteristics was evaluated. RESULTS: The allele G (OR 2.08, p = 0.01) of rs2284015 was observed as a risk factor for developing CPNP. The allele A of rs4820442 showed a risk of association with a history of surgery (OR 3.92, p = 0.04), radiculopathy (OR 4.29, p = 0.0001), bilateral presentation of pain (OR 3.15, p = 0.003), and neuropraxia (OR 0.36, p = 0.01). The allele C of rs2284015 was associated with an increased risk of burning and allodynia. In the analysis of the association of genotype frequencies and inheritance patterns, as well as in the analysis of interaction with sex, a modification of risk was observed. CONCLUSIONS: The allele G of rs2284015 and the AGC haplotype of CACNG2 rs4820242, rs2284015 and rs2284017, regardless of sex and etiology could contribute to the risk of CPNP. Certain alleles and genotypes could constitute severity markers in CPNP with sex-biased effects; however, further studies are required to confirm these observations.

Bezlotoxumab in the treatment of Clostridioides difficile infections: a real-life experience.

OBJECTIVE: Following the approval of bezlotoxumab in 2017, studies evaluating its effectiveness in prevention of Clostridioides difficile infection under "real-life" conditions are scarce. METHODS: We conducted a retrospective study developed in a large tertiary care hospital describing the use and outcomes of patients with Clostridioides difficile infection (CDI) treated with bezlotoxumab. RESULTS: A total of 16 patients were include, all of whom had an episode of CDI with high probability of recurrence and 14 of them had some kind of immunosuppression. Bezlotoxumab was effective in the prevention of CDI recurrence in 11 of the 14 cases in which follow up was possible, without significant side effects. CONCLUSIONS: Bezlotoxumab was well tolerated and the incidence of recurrent CDI in a high-risk population for recurrence was only 21.4%.

Increase in the frequency of catheter-related bloodstream infections during the COVID-19 pandemic: a plea for control.

BACKGROUND: The incidence of nosocomial infections including ventilator-associated pneumonia and bacteraemia has been described during the COVID-19 pandemic. However, information regarding the impact of COVID-19 on the incidence of catheter-related bloodstream infections (CR-BSIs) is very limited. AIM: To evaluate the impact of the COVID-19 pandemic in the evolution of CR-BSIs in a large hospital. METHODS: This was a retrospective study comparing the incidence, aetiology and outcome of CR-BSIs during the months of March to May 2019 (pre-pandemic) and 2020 (during the pandemic). FINDINGS: The number of patients with one or more CR-BSIs in 2019 and 2020 were 23 and 58, respectively (1.89 vs 5.53/1000 admissions); P<0.001. Median time from catheter implantation to demonstration of CR-BSI was 27.5 days (range 11.75-126.00 days) in the 2019 cases and 16.0 days (range 11.00-23.50 days) in the 2020 population (P=0.032). CONCLUSIONS: A dramatic increase of CR-BSIs was found during the COVID-19 pandemic. Reinforcement of classic and new preventive measures is necessary.

Unusual Near-Horizon Cosmic-Ray-like Events Observed by ANITA-IV.

ANITA's fourth long-duration balloon flight in 2016 detected 29 cosmic-ray (CR)-like events on a background of 0.37_{-0.17}^{+0.27} anthropogenic events. CRs are mainly seen in reflection off the Antarctic ice sheets, creating a phase-inverted waveform polarity. However, four of the below-horizon CR-like events show anomalous noninverted polarity, a p=5.3×10^{-4} chance if due to background. All anomalous events are from locations near the horizon; ANITA-IV observed no steeply upcoming anomalous events similar to the two such events seen in prior flights.

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019).

Small-cell lung cancer (SCLC) accounts for 15% of lung cancers. Only one-third of patients are diagnosed at limited stage. The median survival remains to be around 15-20 months without significative changes in the strategies of treatment for many years. In stage I and IIA, the standard treatment is the surgery followed by adjuvant therapy with platinum-etoposide. In stage IIB-IIIC, the recommended treatment is early concurrent chemotherapy with platinum-etoposide plus thoracic radiotherapy followed by prophylactic cranial irradiation in patients without progression. However, in the extensive stage, significant advances have been observed adding immunotherapy to platinum-etoposide chemotherapy to obtain a significant increase in overall survival, constituting the new recommended standard of care. In the second-line treatment, topotecan remains as the standard treatment. Reinduction with platinum-etoposide is the recommended regimen in patients with sensitive relapse (≥ 3 months) and new drugs such as lurbinectedin and immunotherapy are new treatment options. New biomarkers and new clinical trials designed according to the new classification of SCLC subtypes defined by distinct gene expression profiles are necessary.

Faecal microbiota transplantation for recurrent Clostridioides difficile infection: experience with lyophilized oral capsules.

BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective approach for refractory and recurrent Clostridioides difficile infection (CDI). Despite its excellent efficacy, FMT is not yet a routine procedure in most centres. There is very little experience with FMT based on lyophilized capsules, and data from European institutions are lacking. This article describes our experience with FMT to treat recurrent CDI using lyophilized oral capsules. METHODS: A prospectively recorded single-centre case series of patients with recurrent CDI who underwent FMT between January 2018 and May 2019 were analysed. The primary outcome was defined as resolution of CDI without recurrences over a two-month period. Overall resolution was defined as resolution of diarrhoea without recurrence of CDI within two months after a further cycle of FMT. The FMT process involved oral ingestion of four or five lyophilized capsules in a single dose. All stool donors were rigorously screened. FINDINGS: FMT was performed in 32 patients. Primary cure was achieved in 81.3% of patients, and the overall cure rate was 87.5%. FMT via lyophilized capsules was well tolerated. No FMT procedure-related adverse events and no further complications were observed for lyophilized-capsule FMT. CONCLUSIONS: This initial clinical experience suggests that FMT based on oral lyophilized preparations is a safe, well-tolerated, and highly effective treatment for recurrent CDI. Administration of oral lyophilized capsules seems feasible in hospital routine and will enable FMT to be more widely used.

Observation of an Unusual Upward-Going Cosmic-Ray-like Event in the Third Flight of ANITA.

We report on an upward traveling, radio-detected cosmic-ray-like impulsive event with characteristics closely matching an extensive air shower. This event, observed in the third flight of the Antarctic Impulsive Transient Antenna (ANITA), a NASA-sponsored long-duration balloon payload, is consistent with a similar event reported in a previous flight. These events could be produced by the atmospheric decay of an upward-propagating τ lepton produced by a ν_{τ} interaction, although their relatively steep arrival angles create tension with the standard model neutrino cross section. Each of the two events have a posteriori background estimates of ≲10^{-2} events. If these are generated by τ-lepton decay, then either the charged-current ν_{τ} cross section is suppressed at EeV energies, or the events arise at moments when the peak flux of a transient neutrino source was much larger than the typical expected cosmogenic background neutrinos.

Fecal microbiota transplantation for recurrent Clostridium difficile infection: Experience, protocol, and results.

OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI). Despite its excellent efficacy, it is still not a routine procedure in most European centers. FMT has not been widely used in Spain to date. We describe our experience with FMT, including a novel approach based on oral fecal capsules. METHODS: We analyzed a prospectively recorded case series of patients with R-CDI treated with FMT at a single center (June 2014-July 2017). Primary outcome was defined as resolution of CDI without recurrence in a two-month period. FMT was administered via colonoscopy, nasojejunal tube, or oral capsules. All stool donors were rigorously screened. RESULTS: FMT was performed in 13 patients with R-CDI. Median age was 75.0 years and 76.9% were females. Six FMT were performed via nasojejunal tube, 5 via oral capsules, and 2 by colonoscopy. There were no procedure-related adverse events, except for bacteremia in one patient. During follow-up, R- CDI was observed in one patient at one month after FMT. The primary resolution rate was 83.3% and the overall resolution rate was 91.7%. FMT by capsules achieved a 100% resolution rate, colonoscopy 100%, and nasojejunal tube 80.0%. CONCLUSIONS: In our cohort, FMT proved to be safe and effective, even in high risk patients. Oral administration in capsules also proved to be safe, well-tolerated, and highly effective for R-CDI. In our experience, the FMT capsule formulation seems feasible in the routine of a hospital. This administration method will allow FMT to be more widely used.

Fast update of undetected Mycobacterium chimaera infections to reveal unsuspected cases.

Mycobacterium chimaera is involved in a worldwide alert due to contaminated heater-cooler units. A real-time polymerase chain reaction (RT-PCR)-based procedure was implemented to survey undetected cases of M. chimaera infection. PCR was negative in the 59 prosthetic heart valves from patients with PCR-16SrRNA-negative infective endocarditis. PCR identified M. chimaera in one of 15 clinically significant retrospective Mycobacterium avium-Mycobacterium intracellulare complex isolates, which corresponded to a patient who had undergone heart valve replacement in a different institution. Whole-genome sequencing demonstrated that he was the first case in Spain with involvement of the strain responsible for the global outbreak. These results highlight the relevance of retrospective tracking for undetected M. chimaera infections.

Antitumor activity of lurbinectedin (PM01183) and doxorubicin in relapsed small-cell lung cancer: results from a phase I study.

BACKGROUND: Lurbinectedin (PM01183) has synergistic antitumor activity when combined with doxorubicin in mice with xenografted tumors. This phase I trial determined the recommended dose (RD) of doxorubicin (bolus) and PM01183 (1-h intravenous infusion) on day 1 every 3 weeks (q3wk), and obtained preliminary evidence of antitumor activity for this combination in small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with advanced solid tumors received doxorubicin and PM01183 following a standard dose escalation design and expansion at the RD. Twenty-seven patients had relapsed SCLC: 12 with sensitive disease (platinum-free interval ≥90 days) and 15 with resistant disease (platinum-free interval <90 days). RESULTS: Doxorubicin 50 mg/m2 and PM01183 4.0 mg flat dose was the RD. In relapsed SCLC, treatment tolerance at the RD was manageable. Transient and reversible myelosuppression (including neutropenia, thrombocytopenia, and febrile neutropenia) was the main toxicity, managed with dose adjustment and colony-stimulating factors. Fatigue (79%), nausea/vomiting (58%), decreased appetite (53%), mucositis (53%), alopecia (42%), diarrhea/constipation (42%), and asymptomatic creatinine (68%) and transaminase increases (alanine aminotransferase 42%; aspartate aminotransferase 32%) were common, and mostly mild or moderate. Complete (n = 2, 8%) and partial response (n = 13, 50%) occurred in relapsed SCLC, mostly at the RD. Response rates at second line were 91.7% in sensitive disease [median progression-free survival (PFS)=5.8 months] and 33.3% in resistant disease (median PFS = 3.5 months). At third line, response rate was 20.0% (median PFS = 1.2 months), all in resistant disease. CONCLUSION: Doxorubicin 50 mg/m2 and PM01183 4.0 mg flat dose on day 1 q3wk has shown remarkable activity, mainly in second line, with manageable tolerance in relapsed SCLC, leading to further evaluation of this combination within an ongoing phase III trial.

Sleeping Beauty? Developmental Timing, Sleep, and the Circadian Clock in Caenorhabditis elegans.

The genetics toolkit is pretty successful in drilling down into minutiae. The big challenge is to integrate the information from this specialty as well as those of biochemistry, physiology, behavior, and anatomy to explain how fundamental biological processes really work. Sleep, the circadian clock and development all qualify as overarching processes that encompass levels from molecule to behavior as part of their known mechanisms. They overlap each other, such that understanding the mechanisms of one can lead to insights into one of the others. In this essay, we consider how the experimental approaches and findings relating to Caenorhabditis elegans development and lethargus on one hand, and to the circadian clock and sleep in higher organisms on the other, could complement and enhance one another.

The antioxidant activity of soursop decreases the expression of a member of the NADPH oxidase family.

Cellular oxidative stress produced by an increase in free radicals is one of the factors that promote the development of chronic degenerative diseases; therefore, consuming natural antioxidants helps minimize their negative effects. This study evaluated the cytotoxicity of the soursop extract (Annona muricata), its cytoprotective capacity against oxidative stress induced by hydrogen peroxide, the inhibitory potential of reactive oxygen species (ROS), the molecular mechanism of its antioxidant action, and its capacity to repair cellular damage in the fibroblast cell line. The soursop extract proved not to be cytotoxic in fibroblast cultures and showed cytoprotective capacity against hydrogen peroxide-induced stress; in cell culture it reduced the generation of ROS significantly by inhibiting a sub-unit of the NADPH oxidase enzyme (p47phox). The soursop extract can prevent damage caused by cellular oxidants.

Chronic ethanol consumption in mice does not induce DNA damage in somatic or germ cells, evaluated by the bone marrow micronucleous assay and the dominant lethal mutation assay.

Although alcohol is known to be a carcinogen for humans, ethanol-genotoxicity studies are incomplete. Ethanol seems not to be a bacterial mutagen, but the results are conflicting in rodent assays. We investigate the genotoxicity in the bone marrow micronucleus (MN) test and in the dominant lethal mutation (DLM) assay using two long-term ethanol exposure protocols. In the MN test, mice consumed three doses (5, 10 and 15% v/v) for 32 weeks. MN induction was compared to two control groups of 5- and 38-week-old mice (the ages of the treated mice when the treatment was initiated and when they were killed, respectively). For the three groups treated with ethanol there was no significant increase in MN induction as compared to the first control group, but observed MN frequencies were significantly lower than in the 38-week-old control group. This suggests a protective effect against genotoxic damage caused by aging, probably due to ethanol action as a hydroxyl radical scavenger. In the DLM assay, male mice drank ethanol at 15% or 30% (v/v) for 20 weeks. In both groups the number of dead implants was similar to the control, but there was a significant reduction in total implants, indicating a pre-implantation loss.

Chronic ethanol consumption in mice does not induce DNA damage in somatic or germ cells, evaluated by the bone marrow micronucleous assay and the dominant lethal mutation assay

Although alcohol is known to be a carcinogen for humans, ethanol-genotoxicity studies are incomplete. Ethanol seems not to be a bacterial mutagen, but the results are conflicting in rodent assays. We investigate the genotoxicity in the bone marrow micronucleus (MN) test and in the dominant lethal mutation (DLM) assay using two long-term ethanol exposure protocols. In the MN test, mice consumed three doses (5, 10 and 15% v/v) for 32 weeks. MN induction was compared to two control groups of 5- and 38-week-old mice (the ages of the treated mice when the treatment was initiated and when they were killed, respectively). For the three groups treated with ethanol there was no significant increase in MN induction as compared to the first control group, but observed MN frequencies were significantly lower than in the 38-week-old control group. This suggests a protective effect against genotoxic damage caused by aging, probably due to ethanol action as a hydroxyl radical scavenger. In the DLM assay, male mice drank ethanol at 15% or 30% (v/v) for 20 weeks. In both groups the number of dead implants was similar to the control, but there was a significant reduction in total implants, indicating a pre-implantation loss.

Sensitive high performance liquid chromatographic assay for nitazoxanide metabolite in plasma.

A sensible and specific HPLC analytical method for the determination of tizoxanide (TZO), the active metabolite of nitazoxanide (NTZ) in rat plasma was developed and validated. Samples of 200 microL were efficiently deproteinized with acetonitrile. Assay was performed using a C18 CC with a ternary gradient elution of 50 mmol x L(-1) KH2PO4 : acetonitrile : methanol and UV/Vis detection at 416 nm. The analytical method was linear in a range of 10-1280 ng x mL(-1), precise (RSD % > 2.2), accurate (RE % < 7.8) and with high recovery (% > 95%). Stability studies showed that TZO was stable in plasma for short and long-time period (45 days) and proved to be suitable for pharmacokinetic studies of NTZ in rats. The method was also evaluated using human plasma samples and no statistical differences were found in the response-curve between rat and human samples.