Paradoxical effects of cigarette smoke and COPD on SARS-CoV-2 infection and disease.

BACKGROUND: How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial. We investigated the effects of COPD and CS on the expression of SARS-CoV-2 entry receptor ACE2 in vivo in COPD patients and controls and in CS-exposed mice, and the effects of CS on SARS-CoV-2 infection in human bronchial epithelial cells in vitro. METHODS: We quantified: (1) pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and/or TMPRSS2 mRNA levels by RT-qPCR in two independent human cohorts; and (2) pulmonary ACE2 protein levels by immunostaining and ELISA in C57BL/6 WT mice exposed to air or CS for up to 6 months. The effects of CS exposure on SARS-CoV-2 infection were evaluated after in vitro infection of Calu-3 cells and differentiated human bronchial epithelial cells (HBECs), respectively. RESULTS: ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus controls but similar in central airways. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice. CS treatment decreased viral replication in Calu-3 cells, as determined by immunofluorescence staining for replicative double-stranded RNA (dsRNA) and western blot for viral N protein. Acute CS exposure decreased in vitro SARS-CoV-2 replication in HBECs, as determined by plaque assay and RT-qPCR. CONCLUSIONS: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.

Strong Running Coupling from the Gauge Sector of Domain Wall Lattice QCD with Physical Quark Masses.

We report on the first computation of the strong running coupling at the physical point (physical pion mass) from the ghost-gluon vertex, computed from lattice simulations with three flavors of domain wall fermions. We find α_{MS[over ¯]}(m_{Z}^{2})=0.1172(11), in remarkably good agreement with the world-wide average. Our computational bridge to this value is the Taylor-scheme strong coupling, which has been revealed of great interest by itself because it can be directly related to the quark-gluon interaction kernel in continuum approaches to the QCD bound-state problem.

Position statement for the management of comorbidities in psoriasis.

BACKGROUND: The association between psoriasis and some diseases has become relevant in recent years. Providing appropriate management of psoriasis from an early stage requires prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat psoriasis potentially related to the onset of comorbidities. OBJECTIVE: To provide the dermatologist with an accurate and friendly tool for systematizing the diagnosis of psoriasis-associated comorbidities, which generally escapes the scope of the dermatology setting, and to facilitate decision-making about the referral and treatment of patients with comorbidities. METHODS: These position statement recommendations were developed by a working group composed of ten experts (four dermatologists, one cardiologist, one rheumatologist, one gastroenterologist, one nephrologist, one endocrinologist and one psychiatrist) and two health services researchers. The expert group selected the psoriasis comorbidities considered according to their relevance in the dermatology setting. The recommendations on diagnostic criteria are based on the current clinical practice guidelines for each of the comorbidities. The information regarding the repercussion of psoriasis medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. RESULTS: Recommendations were developed to detect and refer the following psoriasis comorbidities: psoriatic arthritis, cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), non-alcoholic fatty liver disease, inflammatory bowel disease, kidney disease and psychological disorders (anxiety and depression). In addition, alcohol consumption and tobacco consumption were included. The tables and figures are precise, easy-to-use tools to systematize the diagnosis of comorbidities in patients with psoriasis and facilitate the decision-making process regarding referral and treatment of patients with an associated disease. CONCLUSION: The application of these position statement recommendations will facilitate the dermatologist practice, and benefit psoriasis patients' health and quality of life.

Host defences against Giardia lamblia.

Giardia spp. is a protozoan parasite that inhabits the upper small intestine of mammals and other species and is the aetiological agent of giardiasis. It has been demonstrated that nitric oxide, mast cells and dendritic cells are the first line of defence against Giardia. IL-6 and IL-17 play an important role during infection. Several cytokines possess overlapping functions in regulating innate and adaptive immune responses. IgA and CD4(+) T cells are fundamental to the process of Giardia clearance. It has been suggested that CD4(+) T cells play a double role during the anti-Giardia immune response. First, they activate and stimulate the differentiation of B cells to generate Giardia-specific antibodies. Second, they act through a B-cell-independent mechanism that is probably mediated by Th17 cells. Several Giardia proteins that stimulate humoral and cellular immune responses have been described. Variant surface proteins, α-1 giardin, and cyst wall protein 2 can induce host protective responses to future Giardia challenges. The characterization and evaluation of the protective potential of the immunogenic proteins that are associated with Giardia will offer new insights into host-parasite interactions and may aid in the development of an effective vaccine against the parasite.

Work instability in rheumatoid arthritis patients from Argentina: prevalence and associated factors.

To determine the prevalence of and associated factors to work instability (WI) in rheumatoid arthritis (RA) Argentinean patients. Observational cross-sectional study that assessing employment status in currently working RA patients. They answered the validated version of RA work instability scale (RA-WIS). High-risk WI was considered when RA-WIS was ≥17. Factors associated with high-risk WI were examined by univariable and multivariable analysis. Four-hundred and fifty RA patients were enrolled; of these, 205 patients were currently employed, but only 172 have completed questionnaires required [RA-WIS and health assessment questionnaire (HAQ-A)]. Their mean age was 49.3 ± 10.8 years; 81.3 % were female; and their mean disease duration was 8.1 ± 7.2 years. Fifty-two percent of patients were doing manual work. The mean RA-WIS score was 11.4 ± 6.8, and 41 % of patients had a high-risk WI. High-risk WI was associated with radiographic erosions (p < 0.001) and HAQ-A >0.87 (p < 0.001) in the univariable analysis, whereas in the multivariable logistic regression analysis the variables associated with a high-risk WI were as follows: HAQ-A >0.87 [odds ratio (OR) 12.31; 95 % CI 5.38-28.18] and the presence of radiographic erosions (OR 4.848; 95 % CI 2.22-10.5). In this model, having a higher monthly income (OR 0.301; 95 % CI 0.096-0.943) and a better functional class (OR 0.151; 95 % CI 0.036-0.632) were protective. Forty-one percent of RA working patients had high-risk WI. The predictors of high RA-WIS were HAQ-A ≥0.87 and radiographic erosions, whereas having a better functional class and have higher incomes were protective.

Detection of hepatitis E virus genome in pig livers in Antioquia, Colombia.

Hepatitis E is a form of endemic acute hepatitis found in humans in many countries worldwide and is caused by the hepatitis E Virus (HEV). Detection of HEV in pigs indicates that they may be carriers, possibly through zoonosis. The prevalence of HEV in pigs in Colombia is unknown. Studies in the US found that 11% of pig livers sold in grocery stores are contaminated with HEV. It is also known that HEV can be inactivated when cooked, as it is labile to high temperatures. The aim of this study was to determine HEV contamination in pig livers sold in Medellín, Antioquia. A total of 150 livers from 5 slaughterhouses and 100 livers in grocery stores from different social strata of the city of Medellin analyzed to detect a segment of the HEV open reading frame-1 using reverse transcription-polymerase chain reaction. The results showed that 41.3% of pig livers from slaughterhouses and 25% of livers from grocery stores tested positive for HEV. Thus, the HEV genome is present in pig livers sold in Antioquia, revealing the presence of this virus in pigs from Colombia and the need subject entrails to proper cooking processes before consumption. Further research is required to determine the role of this virus in public health and pork production in Colombia.

Magnetic ordering in strong anisotropic ferromagnetic bilayers with dipolar and antiferromagnetic interlayer exchange interactions: Monte Carlo approach.

In this work, multilayer films consisting of two strong-anisotropic ferromagnetic layers antiferromagnetically coupled by a nonmagnetic spacer are studied by Monte Carlo simulations. The system is modeled by an Ising-based Hamiltonian that depends on both the intralayer exchange and dipolar constants and on the interlayer exchange constant (IEC). The ground state of the monolayers (null IEC) corresponds to alternate stripe domains with width h defined by the ratio between the exchange and dipolar constants (δ). The results show that IEC alters the energy balance that controls the stripe domain formation, leading to a ground state characterized by in-plane stripes out-plane antiferromagnetically coupled. When temperature increases two regimes are identified: an IEC-dominated regime where the orientational and positional orders are simultaneously lost in both layers, driving the system to the tetragonal liquid (TL) phase, and a dipolar-dominated one where signs of layers decoupling and the onset of positional disorder are observed. The last could be related with an intermediate nematic phase (NM). From the study of the nonequilibrium dynamics, the phase transitions to TL phase are characterized as continuous and those to the NM one as Kosterlitz-Thouless type. Also, for both layers the critical temperatures are the same and increase with IEC magnitude. Furthermore, the obtained critical exponents depend on the IEC values, which is indicative of a weak universality. For the dipolar-dominated regime, the decoupling between layers is also evidenced by the difference between their critical exponents.

Evaluation of aldosterone to direct renin ratio, low renin and related Phenotypes in Afro-Colombian patients with apparent treatment resistant hypertension.

Apparent resistant hypertension (aTRH) is a significant public health issue. Once low adherence to antihypertensive treatment has been ruled out and true resistant hypertension is diagnosed, aldosterone-direct-renin-ratio (ADRR) aids in the screening of an aldosterone-producing adenoma (APA) and primary aldosteronism (PA). Once PA and other secondary causes have been ruled out, the values of aldosterone and renin allow patients to be classified into phenotypes such as low renin hypertension (LRH), Liddle's-like (LLph), and primary hyperaldosteronism (PAph). These classifications could aid in the treatment decision-making process. However, optimal cut-off points for these classifications remain uncertain. This study aims to assess the prevalence of these phenotypes and the behavior of different cut-offs of the ADRR in an Afro-Colombian population with apparent resistant hypertension, as well to describe their sodium consumption. Afro-descendant individuals 18 years of age or older, diagnosed with resistant hypertension and attending to a primary care center in Colombia were recruited as volunteers. As part of the study, their plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured. The phenotypes were categorized into three groups based on multiple cut-off points from different authors: low renin and low aldosterone phenotype (LLph), low renin and high aldosterone phenotype (PAph), and high renin and high aldosterone phenotype, referred to as the renal phenotype (Rph). The prevalence of ADRR values exceeding the cut-off and phenotypes were calculated. A linear regression model was derived to assess the effect of sodium consumption with PAC, PRC and ADRR. A total of 88 patients with aTRH were included. Adherence to at least 3 antihypertensive medications was 62.5%. The median age was 56 years (IQR 48-60), 44% were female, and 20% had diabetes. The study found that the prevalence of ADRR values exceeding the cut-off ranged from 4.5 to 23%, while low-renin hypertension (LRH) varied from 15 to 74%, Rph was found in approximately 30 to 34% of patients, PAph in 30 to 51%, and the LLph in 15 to 41%, respectively, depending on the specific cut-off value by different authors. Notably, sodium consumption was associated with lower aldosterone (ß - 0.15, 95% CI [- 0.27, - 0.03]) and renin concentrations (ß - 0.75, 95% CI [- 1.5, - 0.02]), but ADRR showed no significant association with sodium consumption. There were no significant differences in prevalences between the groups taking < 3 vs ≥ 3 antihypertensive medications. Altered aldosterone-direct-renin-ratio, low renin hypertension, Liddle's-like, and primary hyperaldosteronism are prevalent phenotypes in patients within Afro-Colombian patients with apparent treatment-Resistant hypertension.

Association of socioeconomic factors with the receipt of neoadjuvant therapy for patients with non-small cell lung cancer.

BACKGROUND: Neoadjuvant therapy (NT) will be increasingly used for patients with non-small cell lung cancer (NSCLC), particularly given the recent approval of neoadjuvant chemoimmunotherapy. Several barriers may prevent the uptake of NT and should be identified and addressed. We queried the National Cancer Database (NCDB) to determine predictors of the use of NT. METHODS: Using the NCDB (2006-2019), we identified 80,707 patients who underwent surgery for clinical stage II and III NSCLC. Sociodemographic and clinical factors were reviewed, and univariable and multivariable analyses were performed to identify associations with the uptake of NT. In propensity score-matched groups, survival was determined using the Kaplan-Meier method. RESULTS: Among 80,707 eligible patients, 17,262 (21.4%) received NT. Clinical stage and node positivity were associated with receipt of NT. On multivariable analysis, factors associated with lower rates of NT included black race (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.67-0.90), Charlson Comorbidity Index ≥2 (OR, 0.75; 95% CI, 0.67-0.85), Medicaid/Medicare insurance (OR, 0.82; 95% CI, 0.75-0.90), lower income level (OR, 0.79; 95% CI, 0.71-0.87), and treatment at a community center (OR, 0.81; 95% CI, 0.67-0.96). In an exploratory analysis, those patients who received NT had longer 5-year overall survival compared with those who did not (48.3% vs 46.0%; P < .001). CONCLUSIONS: Rates of NT are relatively low for patients with clinical stage II/III NSCLC treated prior to recent chemoimmunotherapy trials. Socioeconomic barriers to the uptake of NT include race, insurance status, income, and area of residence. As NT becomes more widely offered, accessibility for vulnerable populations must be assured.

Quantitative proteomic mass spectrometry of protein kinases to determine dynamic heterogeneity of the human kinome.

The kinome is a dynamic system of kinases regulating signaling networks in cells and dysfunction of protein kinases contributes to many diseases. Regulation of the protein expression of kinases alters cellular responses to environmental changes and perturbations. We configured a library of 672 proteotypic peptides to quantify >300 kinases in a single LC-MS experiment using ten micrograms protein from human tissues including biopsies. This enables absolute quantitation of kinase protein abundance at attomole-femtomole expression levels, requiring no kinase enrichment and less than ten micrograms of starting protein from flash-frozen and formalin fixed paraffin embedded tissues. Breast cancer biopsies, organoids, and cell lines were analyzed using the SureQuant method, demonstrating the heterogeneity of kinase protein expression across and within breast cancer clinical subtypes. Kinome quantitation was coupled with nanoscale phosphoproteomics, providing a feasible method for novel clinical diagnosis and understanding of patient kinome responses to treatment.

Immunogenicity of pandemic influenza A H1N1/2009 adjuvanted vaccine in pediatric solid organ transplant recipients.

The aim of this study was to assess the immunogenicity of a vaccine against this virus in a prospective cohort of transplanted pediatric patients without previous influenza infection who received one dose of MF59®-adjuvanted pandemic H1N1/2009 vaccine. Seventeen patients who were being regularly followed up at the Outpatient Clinic of the Children's Transplant Unit (liver and kidney transplantation) in Hospital Universitari Vall d'Hebron (Barcelona) were included. Seroconversion was demonstrated in 15 of 17 (88.2%) vaccinated children. There were no rejection episodes or major adverse events. The MF59(®) -adjuvanted pandemic H1N1/2009 vaccine was safe and elicited an adequate response.

Intestinal perforation after pediatric liver transplantation: risk factors and management. / Perforación intestinal tras trasplante hepático pediátrico: factores de riesgo y manejo.

BACKGROUND: Intestinal perforation (IP) after pediatric liver transplant (PLT) is an uncommon complication with high mortality reported. The aim of this study is to identify the risk factors and management of this complication. MATERIALS AND METHODS: Retrospective study of IP after PLT from January 2014 to October 2020. RESULTS: Four intestinal perforations were indentificated in 102 PLT (3,9%). Three patients with BA and one neonate with hemochromatosis (HC) presented this complication. The mean weight of patients with IP was 6.3± 2.5kg (3.1-9) and 19.9 ± 15.4kg for the rest (p< 0.05). All IP with BA had a previous laparotomy. Two living donors and two left lateral reduced liver were implanted. The diagnosis of intestinal perforation was done on day 11 ± 3.3 (8-15 days). Diagnosis was suspected with clinical and biological signs of perforation, CT scan confirmed the diagnosis in patiens with BA and by direct visualization through the mesh for temporary closure in the patient with hemocromatosis. Urgent laparotomy was performed. We identified three colonic perforations, all of them in BA patients and all repaired with direct suture. The patient with HC presented multiple perforations secondary to necrotizing enterocolitis requiring an ileostomy and finally died due to multiorgan failure. CONCLUSION: Intestinal perforation after PLT is an infrequent complication. Age, weight, previous laparotomy and BA could be risk factors for IP in PLT. Urgent laparotomy after diagnosis should be performed in order to reduce mortality. Isolated IP with adequate treatment might not affect long term outcomes after pediatric liver transplantation.

INTRODUCCION: La perforación intestinal (PI) tras trasplante hepático pediátrico (THP) es una complicación poco frecuente, pero con una elevada mortalidad. El objetivo de este estudio es identificar los factores de riesgo y el manejo de esta complicación. MATERIAL Y METODOS: Estudio retrospectivo de la PI tras THP entre enero de 2014 y octubre de 2020. RESULTADOS: Se hallaron 4 perforaciones intestinales en 102 THP (3,9%). Presentaron esta complicación 3 pacientes con atresia biliar (AB) y un neonato con hemocromatosis (HC). El peso medio de los pacientes con PI era de 6,3 ± 2,5 kg (3.1-9) y de 19,9 ± 15,4 kg en el caso del resto (p<0,05). Todos los pacientes con PI y AB habían sido sometidos previamente a laparotomía. Se implantaron 2 hígados de donantes vivos y 2 hígados laterales reducidos izquierdos. El diagnóstico de perforación intestinal se efectúo en el día 11 ± 3,3 (8-15 días), sospechándose con signos clínicos y biológicos de perforación, y confirmándose mediante escáner en los pacientes con AB y mediante visualización directa a través de la malla para el cierre temporal en el paciente con hemocromatosis. Se llevó a cabo laparotomía de urgencia. Se identificaron 3 perforaciones de colon, todas ellas en pacientes con AB y reparadas con sutura directa. El paciente con HC presentaba múltiples perforaciones secundarias a enterocolitis necrotizante que precisaron ileostomía, falleciendo finalmente como consecuencia de un fallo multiorgánico. CONCLUSIONES: La perforación intestinal tras THP es una complicación poco frecuente. La edad, el peso, las laparotomías previas y la AB podrían ser factores de riesgo de PI en el THP. Para reducir la mortalidad, es conveniente practicar una laparotomía de urgencia tras el diagnóstico. Una PI aislada con un adecuado tratamiento puede no influir en los resultados a largo plazo tras un trasplante hepático pediátrico.

Assessment of beliefs and attitudes about electroconvulsive therapy posted on Twitter: An observational study.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective and safe medical procedure that mainly indicated for depression, but is also indicated for patients with other conditions. However, ECT is among the most stigmatized and controversial treatments in medicine. Our objective was to examine social media contents on Twitter related to ECT to identify and evaluate public views on the matter. METHODS: We collected Twitter posts in English and Spanish mentioning ECT between January 1, 2019 and October 31, 2020. Identified tweets were subject to a mixed method quantitative-qualitative content and sentiment analysis combining manual and semi-supervised natural language processing machine-learning analyses. Such analyses identified the distribution of tweets, their public interest (retweets and likes per tweet), and sentiment for the observed different categories of Twitter users and contents. RESULTS: "Healthcare providers" users produced more tweets (25%) than "people with lived experience" and their "relatives" (including family members and close friends or acquaintances) (10% combined), and were the main publishers of "medical" content (mostly related to ECT's main indications). However, more than half of the total tweets had "joke or trivializing" contents, and such had a higher like and retweet ratio. Among those tweets manifesting personal opinions on ECT, around 75% of them had a negative sentiment. CONCLUSIONS: Mixed method analysis of social media contents on Twitter offers a novel perspective to examine public opinion on ECT, and our results show attitudes more negative than those reflected in studies using surveys and other traditional methods.

Strong running coupling at τ and Z(0) mass scales from lattice QCD.

This Letter reports on the first computation, from data obtained in lattice QCD with u, d, s, and c quarks in the sea, of the running strong coupling via the ghost-gluon coupling renormalized in the momentum-subtraction Taylor scheme. We provide readers with estimates of α(MS[over ¯])(m(τ)(2)) and α(MS[over ¯])(m(Z)(2)) in very good agreement with experimental results. Including a dynamical c quark makes the needed running of α(MS[over ¯]) safer.

Influenza A H1N1/2009 infection in pediatric solid organ transplant recipients.

AIM AND METHOD: The aim of this study was to describe the clinical characteristics and outcome of pandemic influenza A H1N1/2009 (pH1N1) infection, in a retrospective cohort of pediatric patients with kidney and/or liver transplant and confirmed pH1N1 infection from June to December 2009, diagnosed in 2 Spanish teaching hospitals. RESULTS: Forty-nine patients were included. Pneumonia was diagnosed in 4 patients (8.2%), and 3 of them required respiratory support. There were no related deaths. CONCLUSION: Antiviral treatment within 48 h was associated with a lower likelihood of pneumonia (0/38, 0%) than treatment started after 48 h (4/11, 36.3%) (P < 0.01).

First Report of Curvularia lunata on Jatropha curcas in Mexico.

The Mexican nut or Jatropha curcas (Euphorbiaceae) is considered an alternative biodiesel source (2). This species is native to Mexico, but is widely distributed in Latin America, Africa, India, and Southeast Asia. Mexico has 6 million hectares with potential for cultivation of this crop (4). In Tamaulipas, Mexico, several adaptation trials have been conducted since 2008. In 2009, symptoms of Curvularia leaf spot were observed on basal leaves of 1-year-old J. curcas plants of the ecotype 'Yautepec' growing in El Mante, Tamaulipas. Spots with yellow borders originated on the edge of leaves, coalesced, and often resulted in approximately 20% leaf abscission on infected plants. Symptomatic leaves were sectioned into small pieces (0.5 cm) and gently washed with a 3:1 solution of 5% sodium hypochlorite to water and rinsed three times with sterilized distilled water. The leaf pieces were dried for 24 h on sterile filter paper, cultured on potato dextrose agar (PDA), and incubated at 27°C under continuous light for 7 days. Cultures produced pale brown conidia, relatively fusiform and cylindrical (25.6 ± 2.6 to 14.0 ± 1.6 µm) with a central cell that was slightly curved and larger and darker than the end cells. Conidia were loosely arranged on conidiophores sparsely distributed or in closer verticils (1). On the basis of the morphological characteristics, the fungus was identified as Curvularia lunata. A fraction of the mycelium grown on solid medium was inoculated into potato dextrose broth and grown for 72 h and DNA extraction was performed. PCR with primers designed for 26S and internal transcribed spacer (ITS) region were used to amplify and sequence 16S rRNA and the D2 region. This analysis resulted in 100% identity of the test isolate to GenBank Accession No. GQ328852.1 and the sequence of our isolate was submitted with Accession No. JF798505.1. Dried specimens were sent to the USA National Collection BPI. Koch's postulates were completed by testing for pathogenicity on 20 70-day-old Jatropha plants grown under greenhouse conditions. A conidial suspension (1 × 106 conidia ml-1) was prepared from monosporic cultures and hand sprayed onto test plants. Twenty plants were treated only with sterile water and used as controls. Symptoms appeared 2 weeks after inoculation, and 40 days later, all inoculated plants showed the same symptoms as those recorded in the field. Control plants did not show any disease symptoms. C. lunata was reisolated from 70% of the inoculated leaves. In Mexico, C. lunata was found on leaves of Quercus, Liquidambar, and Ananas, and was reported on cassava (Manihot esculentum), another member of the Euphorbiacea (3). To our knowledge, this is the first report of C. lunata on Jatropha in Mexico. References: (1) M. B. Ellis. Dematiaceous Hyphomycetes. CMI, Kew, Surrey, UK, 1971. (2) L. N. Lourenco et al. Crop Sci. 47:2228, 2007. (3) W. Msikita et al. Plant Dis. 91:1430, 2007. (4) C. A. Zamarripa et al. Biocombustibles: Perspectivas de producción de biodiesel a partir de Jatropha curcas L., en el trópico de Mexico. INIFAP-SAGARPA-MEXICO, 2009.

Similar programmed death ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer.

Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance in non-small cell lung cancer (NSCLC). Alveolar macrophage (AM)-derived PD-L1 binds to its receptor, PD-1, on surveilling lymphocytes, leading to lymphocyte exhaustion. Increased PD-L1 expression is associated with cigarette smoke (CS)-exposure. However, the PD-L1 role in CS-associated lung diseases associated with NSCLC, such as chronic obstructive pulmonary disease (COPD), is still unclear. In two different cohorts of ever smokers with COPD or NSCLC, and ever and never smoker controls, we evaluated PD-L1 expression: (1) via cutting-edge digital spatial proteomic and transcriptomic profiling (Geomx) of formalin-fixed paraffin-embedded (FFPE) lung tissue sections (n = 19); and (2) via triple immunofluorescence staining of bronchoalveolar lavage (BAL) AMs (n = 83). PD-L1 mRNA expression was also quantified in BAL AMs exposed to CS extract. PD-L1 expression was increased in the bronchiolar wall, parenchyma, and vascular wall from mild-moderate (GOLD 1-2) COPD patients compared to severe-very severe (GOLD 3-4) COPD patients and controls. Within all the COPD patients, PD-L1 protein expression was associated with upregulation of genes involved in tumor progression and downregulation of oncosuppressive genes, and strongly directly correlated with the FEV1% predicted, indicating higher PD-L1 expression in the milder vs. more severe COPD stages. In bronchioles, PD-L1 levels were strongly directly correlated with the number of functionally active AMs. In BAL, we confirmed that AMs from patients with both GOLD 1-2 COPD and NSCLC had the highest and similar, PD-L1 expression levels versus all the other groups, independently from active cigarette smoking. Intriguingly, AMs from patients with more severe COPD had reduced AM PD-L1 expression compared to patients with mild COPD. Acute CS extract stimulation increased PD-L1 mRNA expression only in never-and not in ever-smoker AMs. Lungs from patients with mild COPD and NSCLC are characterized by a similar strong PD-L1 expression signature in bronchioles and functionally active AMs compared to patients with severe COPD and controls. Active smoking does not affect PD-L1 levels. These observations represent a new resource in understanding the innate immune mechanisms underlying the link between COPD and lung cancer onset and progression and pave the way to future studies focused on the mechanisms by which CS promotes tumorigenesis and COPD.

Copulatory behaviour and the process of intromission in Anastrepha ludens (Diptera: Tephritidae).

Complex genitalia occur in many arthropods and in some species extreme female morphologies lead to serious mechanical difficulties for males. Tephritid flies offer examples of such complex genitalia. Because of their economic importance and the extensive use of sterile male releases for tephritid control in Texas and Mexico, studies have been done on various aspects of their basic reproductive biology, but the process of intromission has received little attention. The distiphallus of the male of Anastrepha ludens is complex. One membranous sac on the distiphallus is capable of rhythmic cycles of inflation and deflation. Inflations of the sac near the base of the distiphallus probably help propel the aedeagus deeper into the female along with stiffening of the basiphallus and may drive the genital rod (which does not transfer sperm) into the ventral receptacle. We were unable to establish an association between some of the behaviours displayed by males during mating and intromission process.

Thumb carpometacarpal arthroplasty and trapeziectomy using a tenodesis screw compared to ligament reconstruction.

This study aimed to compare the results of patients treated with a thumb carpometacarpal (CMC) suspension arthroplasty using an interference screw technique with patients that were treated by trapeziectomy and ligament reconstruction. A retrospective chart review was conducted of patients over 18 years old who required surgical treatment for thumb CMC joint arthritis treated by a single surgeon. Patients included in the study followed the same preoperative and postoperative protocol. Information related to functional outcomes was collected (pinch and grip strength, pain, Kapandji score, proximal migration of first metacarpal bone). One hundred and five patients were included, 77% were female, age at the time of the study was 62.7 years old; 74 (70%) patients were treated with the tenodesis screw (TS) technique and 31 (30%) with trapeziectomy and ligament reconstruction (TZLR). Patients were followed for a mean of 8.4 months. Postoperative pain was 1.2 in the TS group and 0.6 in the TZLR group; Kapandji score was 8.3 in the TS group and 9 in the TZLR group; in the TS group, the grip strength was 26.2kg and key pinch strength was 6.15kg; in the TZLR group, grip strength was 12.8kg and key pinch strength was 4.7kg. Proximal migration was 0.4cm in the TZLR group and 0.6cm in the TS group. The use of tenodesis screw and half of the flexor carpi radialis had minor advantages, such as increasing the grip and key pinch strength without differences relative the non-operated thumb, minimal migration of the first metacarpal bone compared with the other technique.

Exposure to 2.45 GHz radiofrequency modulates calcitonin-dependent activity and HSP-90 protein in parafollicular cells of rat thyroid gland.

In this study we analyzed the response of parafollicular cells in rat thyroid gland after exposure to radiofrequency at 2.45 GHz using a subthermal experimental diathermy model. Forty-two Sprague Dawley rats, divided into two groups of 21 rats each, were individually exposed at 0 (control), 3 or 12 W in a Gigahertz Transverse Electro-Magnetic (GTEM) chamber for 30 min. After radiation, we used simple or fluorescence immunohistochemistry to measure calcitonin cells or cellular stress levels, indicated by the presence hyperplasia of parafollicular cells, heat shock protein (HSP) 90. Immunomarking of calcitonin-positive cells was statistically significant higher in the thyroid tissue of rats exposed to 2.45 GHz radiofrequency and cell hyperplasia appeared 90 min after radiation at the SAR levels studied. At the same time, co-localized expression of HSP-90 and calcitonin in parafollicular cells was statistically significant attenuated 90 min after radiation and remained statistically significantly low 24 h after radiation, even though parafollicular cell levels normalized. These facts indicate that subthermal radiofrequency (RF) at 2.45 GHz constitutes a negative external stress stimulus that alters the activity and homeostasis of parafollicular cells in the rat thyroid gland. However, further research is needed to determine if there is toxic action in human C cells.