Ventilator-associated pneumonia by Weeksella virosa: case report.

BACKGROUND: Weeksella virosa pneumonia is an infection that has been described as a healthcare-associated infection. This is a rare gram-negative anaerobic bacterium associated with the use of mechanical ventilation for a long period of time and is more frequent in immunosuppressed patients. This is the first case reported in the state of Veracruz and the second in Mexico. CASE PRESENTATION: We present the case of a 64-year-old female from Veracruz, Mexico who developed an infectious process in the right pelvic limb after a transcatheter aortic valve replacement procedure and subsequently developed sudden cardiorespiratory arrest requiring mechanical ventilation, with subsequent imaging studies demonstrating a pneumonic process associated with a nosocomial infection. DISCUSSION AND CONCLUSIONS: We should take into consideration that this pathogen affects not only adults with multiple comorbidities but also children with renal, hepatic, or oncological pathologies, as well as immunocompromised patients, who should be considered high-risk populations for W. virosa infection.

Rationale for Hepatitis C Virus Treatment During Hematopoietic Stem Cell Transplant in the Era of Novel Direct-Acting Antivirals.

BACKGROUND AND AIMS: Untreated hepatitis C (HCV) infection in patients undergoing hematopoietic stem cell transplantation (HSCT) can lead to worse outcomes. Traditionally, HSCT patients infected with HCV would wait until after immune reconstitution to receive HCV therapy, as the oncologic urgency of transplant would not allow time for a full preceding treatment course of HCV therapy. However, in the era of newer direct-acting antivirals (DAAs), we propose that concomitant treatment of HCV while undergoing HSCT is safe and feasible, while keeping in mind potential drug-drug interactions. METHODS: A literature review was performed to summarize the available data on the impact of HCV on patients undergoing HSCT. Drug-drug interactions for DAA's and pertinent HSCT drugs were evaluated using Lexicomp online® and http://hep-druginteractions.org . RESULTS: During HSCT, HCV appears to be a conditional risk factor for sinusoidal obstruction syndrome and a potential risk factor for graft versus host disease, both of which are associated with increased mortality. HCV reactivation and exacerbation may impact the use of chemotherapeutics, but available studies haven't shown impact specifically on HSCT. Limited case reports exist but demonstrate safe and effective use DAAs during HSCT. These, along with a drug-drug interaction review demonstrate agents such as sofosbuvir/velpatasvir and glecaprevir/pibrentasvir are promising DAAs for use in HSCT. CONCLUSION: HCV infection may worsen outcomes for patients undergoing HSCT. Concomitant treatment of HCV during HSCT using newer DAAs appears feasible and may improve patient morbidity and mortality, however large-scale studies are needed to further support this practice.

Tumor Regression Grade and Overall Survival following Gastrectomy with Preoperative Therapy for Gastric Cancer.

BACKGROUND: Pre-/perioperative chemotherapy is well-established for management of locoregional gastric cancer (LRGC). The American Joint Committee on Cancer advocates histopathologic assessment of tumor regression grade (TRG) but does not endorse a specific schema. We sought to examine the prognostic value of the recently revised National Comprehensive Cancer Network (NCCN) definition of TRG specifying TRG0 as no disease in primary tumor or lymph nodes. PATIENTS AND METHODS: Patients with clinical-stage T2+/N+/M0 LRGC receiving preoperative chemotherapy and curative-intent gastrectomy were identified (2000-2020). TRG using the current NCCN definition was retrospectively assigned. Factors associated with TRG were examined using ordinal logistic regression and overall survival (OS) was assessed using the Kaplan-Meier method and Cox regression. RESULTS: Among 117 patients, the most common chemotherapy regimen was epirubicin, cisplatin, plus fluorouracil or capecitabine (ECF/ECX) (n = 48, 41%), followed by folinic acid, fluorouracil, and oxaliplatin (FOLFOX) (n = 30, 26%), and fluorouracil, leucovorin, oxaliplatin, plus docetaxel (FLOT) (n = 13, 11%). TRG3 was the most common histopathologic response (n = 68, 58%), followed by TRG2 (n = 25, 21%), TRG1 (n = 18, 15%), and, lastly, TRG0 (n = 6, 5.1%). The only preoperative factor independently associated with lower TRG was gastroesophageal junction tumor location (OR 0.24, p = 0.012). Higher TRG was independently associated with worse OS in a stepwise fashion (HR 1.49, p = 0.026). Posttreatment pathologic lymph node status was the strongest prognostic factor (HR 1.93, p = 0.026). Independent prognostic value of TRG and ypT stage could not be shown due to substantial overlap. CONCLUSIONS: TRG using the contemporary NCCN definition is associated with OS in LRGC. TRG0 is uncommon but with excellent prognosis. ypN status is the strongest prognostic factor and the revised NCCN definition acknowledging this is appropriate.

Malignant colon polyps: predicting lymph node metastasis following endoscopic excision.

AIM: The risk of lymph node metastasis (LNM) of malignant colon polyps (MCPs) is partly estimated by histologic features of the sampled polyp. However, the routinely available histologic data is limited to tumor grade and status of lymphovascular invasion (LVI). METHODS: The NCDB for colon cancer 2004-2018 was utilized. Patients with pT1Nx adenocarcinoma arising in a polyp and undergoing partial colectomy with ≥ 12 retrieved nodes were selected. NCDB 2004-2017 was used as a training cohort to develop two scoring systems based on a multivariable regression for predictors of LNM including clinical characteristics, grade, and LVI: a nomogram scoring system (NSS) and a simplified scoring system (SSS). These models were internally validated using NCDB 2018 to calculate precision metrics for each model. RESULTS: Six thousand sixty-nine patients were selected in the training cohort. 64.5% of MCPs were in the sigmoid, and LNM rate was 11.2%. Multivariable regression identified younger age, females, hindgut location, higher grade, and LVI as significant predictors of LNM. LNM risk was 1.2% when all unfavorable predictors were absent and exceeded 10% when NSS > 70 or SSS ≥ 3. In the 2018 validation cohort, 723 patients were scored per NSS and SSS, and the negative predictive value for both was 96%. CONCLUSION: Estimating LNM risk in MCPs by applying clinical characteristics along with limited histologic data can help inform decision-making when considering formal oncologic resection. The NSS and SSS demonstrated comparable predictability of LNM among pT1Nx MCPs. The models require external validation and may be strengthened by incorporating additional endoscopic and pathologic characteristics.

A microRNA Signature Identifies Patients at Risk of Barrett Esophagus Progression to Dysplasia and Cancer.

BACKGROUND: Progression of Barrett esophagus (BE) to esophageal adenocarcinoma occurs among a minority of BE patients. To date, BE behavior cannot be predicted on the basis of histologic features. AIMS: We compared BE samples that did not develop dysplasia or carcinoma upon follow-up of ≥ 7 years (BE nonprogressed [BEN]) with BE samples that developed carcinoma upon follow-up of 3 to 4 years (BE progressed [BEP]). METHODS: The NanoString nCounter miRNA assay was used to profile 24 biopsy samples of BE, including 13 BENs and 11 BEPs. Fifteen samples were randomly selected for miRNA prediction model training; nine were randomly selected for miRNA validation. RESULTS: Unpaired t tests with Welch's correction were performed on 800 measured miRNAs to identify the most differentially expressed miRNAs for cases of BEN and BEP. The top 12 miRNAs (P < .003) were selected for principal component analyses: miR-1278, miR-1301, miR-1304-5p, miR-517b-3p, miR-584-5p, miR-599, miR-103a-3p, miR-1197, miR-1256, miR-509-3-5p, miR-544b, miR-802. The 12-miRNA signature was first self-validated on the training dataset, resulting in 7 out of the 7 BEP samples being classified as BEP (100% sensitivity) and 7 out of the 8 BEN samples being classified as BEN (87.5% specificity). Upon validation, 4 out of the 4 BEP samples were classified as BEP (100% sensitivity) and 4 out of the 5 BEN samples were classified as BEN (80% specificity). Twenty-four samples were evaluated, and 22 cases were correctly classified. Overall accuracy was 91.67%. CONCLUSION: Using miRNA profiling, we have identified a 12-miRNA signature able to reliably differentiate cases of BEN from BEP.

The Electromagnetic Vacuum Field as an Essential Hidden Ingredient of the Quantum-Mechanical Ontology.

This paper provides elements in support of the random zero-point radiation field (zpf) as an essential ontological ingredient needed to explain distinctive properties of quantum-mechanical systems. We show that when an otherwise classical particle is connected to the zpf, a drastic, qualitative change in the dynamics takes place, leading eventually to the quantum dynamics. In particular, we demonstrate that in parallel with the evolution of the canonical variables of the particle into quantum operators satisfying the basic commutator x^,p^=iℏ, also the field canonical variables are transformed, giving rise to the corresponding creation and annihilation operators a^†,a^, satisfying a^,a^†=1. This allows for an explanation of quantum features such as quantum fluctuations, stationary states and transitions, and establishes a natural contact with (nonrelativistic) quantum electrodynamics.

Ultradoping Boron on Si(100) via Solvothermal Chemistry*.

Ultradoping introduces unprecedented dopant levels into Si, which transforms its electronic behavior and enables its use as a next-generation electronic material. Commercialization of ultradoping is currently limited by gas-phase ultra-high vacuum requirements. Solvothermal chemistry is amenable to scale-up. However, an integral part of ultradoping is a direct chemical bond between dopants and Si, and solvothermal dopant-Si surface reactions are not well-developed. This work provides the first quantified demonstration of achieving ultradoping concentrations of boron (∼1e14 cm2 ) by using a solvothermal process. Surface characterizations indicate the catalyst cross-reacted, which led to multiple surface products and caused ambiguity in experimental confirmation of direct surface attachment. Density functional theory computations elucidate that the reaction results in direct B-Si surface bonds. This proof-of-principle work lays groundwork for emerging solvothermal ultradoping processes.

New sulfonamides containing organometallic-acylhydrazones: synthesis, characterisation and biological evaluation as inhibitors of human carbonic anhydrases.

A series of organometallic acylhydrazones was prepared, incorporating Re(CO)3, Mn(CO)3 and ferrocenyl moieties, which were subsequently reacted with amino-sulfonamides in order to obtain carbonic anhydrase (CA, EC 4.2.1.1) inhibitors possessing organometallic moieties in their molecules. The new derivatives were investigated as inhibitors of four human (h) CA isoforms with pharmaceutical applications, such as the cytosolic hCA I, II and VII and the mitochondrial hCA VA. An interesting inhibitory profile against these isoforms was obtained, with some of these metal complexes acting as subnanomolar or low nanomolar inhibitors. They were also thoroughly characterised from the chemical point of view, making them of interest for further developments in the field of metal complexes of sulfonamides with CA inhibitory action.

Snake Venom Hemotoxic Enzymes: Biochemical Comparison between Crotalus Species from Central Mexico.

Snakebite envenoming is a serious medical problem in different areas of the world. In Latin America, the major prevalence is due to snakes of the family Viperidae, where rattlesnakes (Crotalus) are included. They produce hemotoxic venom which causes bleeding, tissue degradation and necrosis. Each venom has several enzymatic activities, producing different effects in the envenoming, doing its clinical effects difficult to study. Comparison between venom molecules is also difficult when different techniques are used, and therefore, their identification/characterization using the same methodology is necessary. In this work, a general biochemical characterization in snake venom of serine proteases (SVSP), phospholipases A2 (PLA2), metalloproteases (SVMP) and hyaluronidases (SVH) of Crotalus aquilus (Ca), Crotalus polystictus (Cp) and Crotalus molossus nigrescens (Cmn) was done. Differences in protein pattern, enzyme content and enzymatic activities were observed. All the venoms showed high PLA2 activity, high molecular weight SVSP, and a wide variety of SVMP and SVH forms. Ca and Cp showed the highest enzymatic activities of SVMP and SVSP trypsin-like and chymotrypsin-like, whereas Cmn showed the highest SVH and similar PLA2 activity with Ca. All the venoms showed peptides with similar molecular weight to crotamine-like myotoxins. No previous biochemical characterization of C. aquilus has been reported and there are no previous analyses that include these four protein families in these Crotalus venoms.

In Situ Infrared Absorption Study of Plasma-Enhanced Atomic Layer Deposition of Silicon Nitride.

Despite the success of plasma-enhanced atomic layer deposition (PEALD) in depositing quality silicon nitride films, a fundamental understanding of the growth mechanism has been difficult to obtain because of lack of in situ characterization to probe the surface reactions noninvasively and the complexity of reactions induced/enhanced by the plasma. These challenges have hindered the direct observation of intermediate species formed during the reactions. We address this challenge by examining the interaction of Ar plasma using atomically flat, monohydride-terminated Si(111) as a well-defined model surface and focusing on the initial PEALD with aminosilanes. In situ infrared and X-ray photoelectron spectroscopy reveals that an Ar plasma induces desorption of H atoms from H-Si(111) surfaces, leaving Si dangling bonds, and that the reaction of di-sec-butylaminosilane (DSBAS) with Ar plasma-treated surfaces requires the presence of both active sites (Si dangling bonds) and Si-H; there is no reaction on fully H-terminated or activated surfaces. By contrast, high-quality hydrofluoric acid-etched Si3N4 surfaces readily react with DSBAS, resulting in the formation of O-SiH3. However, the presence of back-bonded oxygen in O-SiH3 inhibits H desorption by Ar or N2 plasma, presumably because of stabilization of H against ion-induced desorption. Consequently, there is no reaction of adsorbed aminosilanes even after extensive Ar or N2 plasma treatments; a thermal process is necessary to partially remove H, thereby promoting the formation of active sites. These observations are consistent with a mechanism requiring the presence of both undercoordinated nitrogen and/or dangling bonds and unreacted surface hydrogen. Because active sites are involved, the PEALD process is found to be sensitive to the duration of the plasma exposure treatment and the purge time, during which passivation of these sites can occur.

Steering and switching of soliton-like beams via interaction in a nanocolloid with positive polarizability.

We unveil different regimes for the interaction between two orthogonally polarized soliton-like beams in a colloidal suspension of nanoparticles with positive polarizability. The interaction is always attractive. However, it noticeably changes as a function of the angle and the power distribution between the input beams. For small angles, both interacting solitons fuse into a single entity, whose propagation direction can be continuously steered. As the interaction angle increases, the resulting self-collimated beam can be practically switched between two positions when the power imbalance between the beams is changed. For interaction angles larger than ∼10°, the result is no longer a single emerging soliton when the input power is balanced between the two beams.

The Role of Diagnosis and Treatment of Underlying Liver Disease for the Prognosis of Primary Liver Cancer.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Underlying chronic liver disease has been associated with an increased risk of developing HCC. This study is a review of the current literature regarding the diagnosis, prognostic significance, and role of treating underlying liver disease in patients who are at risk of primary liver cancer. Relevant peer review of the English literature between 1980 and 2017 within PubMed and the Cochrane library was conducted for scientific content on current advances in managing chronic liver diseases and the development of hepatocellular carcinoma. Hepatitis C virus, hepatitis B virus (HBV), nonalcoholic steatohepatitis, autoimmune hepatitis, hereditary hemochromatosis, Wilson disease, primary biliary cirrhosis, α 1-antitrypsin deficiency, and certain drugs lead to an increased risk of developing HCC. Patients with underlying liver disease have an increased incidence of HCC. Hepatitis C virus, HBV, and hemochromatosis can directly lead to HCC without the presence of cirrhosis, while HCC related to other underlying liver diseases occurs in patients with cirrhosis. Treating the underlying liver disease and reducing the progression to cirrhosis should lead to a decreased incidence of HCC.

Advances in the Endoscopic Diagnosis of Barrett Esophagus.

BACKGROUND: Barrett esophagus (BE) continues to be a major risk factor for developing esophageal adenocarcinoma. METHODS: We review the risk factors, diagnosis, and management of BE, with an emphasis on the most current endoscopic diagnostic modalities for BE. RESULTS: Novel diagnostic modalities have emerged to address the inadequacies of standard, untargeted biopsies, such as dye-based and virtual chromoendoscopy, endoscopic mucosal resection, molecular biomarkers, optical coherence tomography, confocal laser endomicroscopy, volumetric laser endomicroscopy, and endocytoscopy. Treatment of BE depends on the presence of intramucosal cancer or dysplasia, particularly high-grade dysplasia with or without visible mucosal lesions. CONCLUSIONS: Recent advances in endoscopic diagnostic tools demonstrate promising results and help to mitigate the shortcomings of the Seattle protocol. Future research as well as refining these tools may help aid them in replacing standard untargeted biopsies.

[Prognostic variability in atypical meningioma with complete resection. Proposed treatment algorithm]. / Variabilidad pronóstica del meningioma atípico con resección completa. Propuesta de algoritmo de tratamiento.

OBJECTIVE: The authors attempt to show how the current prognostic factors that try to assess the risk of recurrence of atypical meningiomas are insufficient to predict the future of this disease. MATERIALS AND METHOD: Using data obtained from hospital databases, a sample of 27 patients was obtained with pathological diagnosis of atypical meningioma, and who had a minimum follow-up time of 6months after diagnosis. Later prognostic factors (age <50years, male gender, bone involvement, peri-lesional swelling, tumour volume, location, Ki67/MIB-1) were evaluated after the stratification of patients undergoing complete resection in recurrencies and non-recurrencies. Univariate analysis was performed using Mann-Whitney test, χ(2) homogeneity test/Fisher exact test. Finally, multivariate analysis was performed using binary logistic regression to obtain the values for R(2) Nagelkerke and the Hosmer-Lemeshow to evaluate the goodness of fit. RESULTS: The uni- and multivariate analysis showed no statistically significant differences between recurrent and non-recurrent subgroups of patients undergoing complete resection. It is noted in the results that for each year of age above 50 years, the risk of recurrence is decreased by 5.8%. CONCLUSIONS: Although current prognostic factors may show an increased risk of recurrence once patients are stratified by the two most important factors (pathology and extent of resection), those factors are insufficient to predict the ultimate outcome of patients affected by this pathology.

Long-term outcome of patients undergoing liver transplantation for mixed hepatocellular carcinoma and cholangiocarcinoma: an analysis of the UNOS database.

BACKGROUND: Mixed hepatocellular and cholangiocarcinoma (HCC-CC) have been associated with a poor prognosis after liver transplantation (LT). We aimed to evaluate long-term outcomes in patients undergoing LT for HCC-CC versus patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC). METHODS: Retrospective analysis of the United Network for Organ Sharing (UNOS) database from 1994-2013. Overall survival (OS) in patients with HCC-CC, HCC, and CC, were compared. RESULTS: We identified 4049 patients transplanted for primary malignancy (94 HCC-CC; 3515 HCC; 440 CC). Mean age of patients with HCC-CC was 57 ± 10 years, and 77% were male. MELD score did not differ among the groups (p = 0.637). Hepatitis C virus was the most common secondary diagnosis within the HCC-CC (44%) and HCC (36%) cohorts, with primary sclerosing cholangitis in the CC (16%) cohort. OS rates at 1, 3 and 5 years for HCC-CC (82%, 47%, 40%) were similar to CC (79%, 58%, 47%), but significantly worse than HCC (86%, 72%, and 62% p = 0.002). DISCUSSION: Patients undergoing LT for HCC had significantly better survival compared to those transplanted for HCC-CC and CC. LT for mixed HCC-CC confers a survival rate similar to selected patients with CC. Efforts should be made to identify HCC-CC patients preoperatively.

Pan-American mDNA haplogroups in Chilean patients with Leber's hereditary optic neuropathy.

PURPOSE: The clinical impact of mDNA mutations on the development of Leber hereditary optic neuropathy (LHON) may be modulated by mitochondrial haplogroups, which vary across populations. The aim of this research was to determine the clinical spectrum and molecular characteristics, including the haplogroup, of 15 South American families with LHON. METHODS: This study was a prospective, observational study conducted between March 2006 and August 2012. All patients were referred to the Clinical Hospital of the University of Chile, where the clinical study was conducted. Molecular studies were conducted at the Biomedical Sciences Institute (ICBM) of the University of Chile. Fifteen index cases were identified with molecular analysis after initial neuroophthalmic examination at different centers throughout Chile. Clinical features of patients with LHON and maternal relatives of the 15 families (75 individuals: 26 affected and 49 healthy carriers) were evaluated. The primary mDNA mutations (m.3460G>A, m.11778G>A, or m.14484T>C) were determined with restriction fragment length polymorphism analysis in all individuals. Mitochondrial haplogroups were determined with direct sequencing of two hypervariable regions (HV1 and HV2) and compared with reference sequences. RESULTS: The m.11778G>A mutation was found in 59 subjects (78.7%), the m.14484T>C mutation was found in 12 subjects (16.0%), and the m.3460G>A mutation was found in four (5.3%) subjects. The average age of onset of symptoms in affected subjects was 22.2 years old (range 3 to 53 years); 21 (80.7%) were male, and five (19.3%) were female. Twelve families (80%) had Amerindian haplogroups: One family had the A2 haplogroup, four families had the B2i2 haplogroup, six families had the C1b haplogroup, and one family had the D1g haplogroup. CONCLUSIONS: In this limited sample size, the Amerindian haplogroup A2 was associated with delayed onset of disease in this population. Patients with haplogroup C retained better vision than the patients with other haplogroups in this population. Disease in subjects with haplogroup D appeared to be underrepresented compared to the population at large.

Mitochondrial Dynamics, Diabetes, and Cardiovascular Disease.

Mitochondria undergo repeated cycles of fusion and fission that regulate their size and shape by a process known as mitochondrial dynamics. Numerous studies have revealed the importance of this process in maintaining mitochondrial health and cellular homeostasis, particularly in highly metabolically active tissues such as skeletal muscle and the heart. Here, we review the literature on the relationship between mitochondrial dynamics and the pathophysiology of type 2 diabetes and cardiovascular disease (CVD). Importantly, we emphasize divergent outcomes resulting from downregulating distinct mitochondrial dynamics proteins in various tissues. This review underscores compensatory mechanisms and adaptive pathways that offset potentially detrimental effects, resulting instead in improved metabolic health. Finally, we offer a perspective on potential therapeutic implications of modulating mitochondrial dynamics proteins for treatment of diabetes and CVD.

Towards Sustainable Temperature Sensor Production through CO2-Derived Polycarbonate-Based Composites.

The steep increase in carbon dioxide (CO2) emissions has created great concern due to its role in the greenhouse effect and global warming. One approach to mitigate CO2 levels involves its application in specific technologies. In this context, CO2 can be used for a more sustainable synthesis of polycarbonates (CO2-PCs). In this research, CO2-PC films and composites with multiwalled carbon nanotubes (MWCNTs, ranging from 0.2 to 7.0 wt.%) have been prepared to achieve more sustainable multifunctional sensing devices. The inclusion of the carbonaceous fillers allows for the electrical conductivity to be enhanced, reaching the percolation threshold (Pc) at 0.1 wt.% MWCNTs and a maximum electrical conductivity of 0.107 S·m-1 for the composite containing 1.5 wt.% MWCNTs. The composite containing 3.0 wt.% MWCNTs was also studied, showing a stable and linear response under temperature variations from 40 to 100 °C and from 30 to 45 °C, with a sensitivity of 1.3 × 10-4 °C-1. Thus, this investigation demonstrates the possibility of employing CO2-derived PC/MWCNT composites as thermoresistive sensing materials, allowing for the transition towards sustainable polymer-based electronics.