Deciphering the Relationship between SARS-CoV-2 and Cancer.

Some viruses are known to be associated with the onset of specific cancers. These microorganisms, oncogenic viruses or oncoviruses, can convert normal cells into cancer cells by modulating the central metabolic pathways or hampering genomic integrity mechanisms, consequently inhibiting the apoptotic machinery and/or enhancing cell proliferation. Seven oncogenic viruses are known to promote tumorigenesis in humans: human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), Epstein-Barr virus (EBV), human T-cell leukemia virus 1 (HTLV-1), Kaposi sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCPyV). Recent research indicates that SARS-CoV-2 infection and COVID-19 progression may predispose recovered patients to cancer onset and accelerate cancer development. This hypothesis is based on the growing evidence regarding the ability of SARS-CoV-2 to modulate oncogenic pathways, promoting chronic low-grade inflammation and causing tissue damage. Herein, we summarize the main relationships known to date between virus infection and cancer, providing a summary of the proposed biochemical mechanisms behind the cellular transformation. Mechanistically, DNA viruses (such as HPV, HBV, EBV, and MCPyV) encode their virus oncogenes. In contrast, RNA viruses (like HCV, HTLV-1) may encode oncogenes or trigger host oncogenes through cis-/-trans activation leading to different types of cancer. As for SARS-CoV-2, its role as an oncogenic virus seems to occur through the inhibition of oncosuppressors or controlling the metabolic and autophagy pathways in the infected cells. However, these effects could be significant in particular scenarios like those linked to severe COVID-19 or long COVID. On the other hand, looking at the SARS-CoV-2─cancer relationship from an opposite perspective, oncolytic effects and anti-tumor immune response were triggered by SARS-CoV-2 infection in some cases. In summary, our work aims to recall comprehensive attention from the scientific community to elucidate the effects of SARS-CoV-2 and, more in general, ß-coronavirus infection on cancer susceptibility for cancer prevention or supporting therapeutic approaches.

Oxytocin-like signaling in ants influences metabolic gene expression and locomotor activity.

Ants are emerging model systems to study cellular signaling because distinct castes possess different physiologic phenotypes within the same colony. Here we studied the functionality of inotocin signaling, an insect ortholog of mammalian oxytocin (OT), which was recently discovered in ants. In Lasius ants, we determined that specialization within the colony, seasonal factors, and physiologic conditions down-regulated the expression of the OT-like signaling system. Given this natural variation, we interrogated its function using RNAi knockdowns. Next-generation RNA sequencing of OT-like precursor knock-down ants highlighted its role in the regulation of genes involved in metabolism. Knock-down ants exhibited higher walking activity and increased self-grooming in the brood chamber. We propose that OT-like signaling in ants is important for regulating metabolic processes and locomotion.-Liutkeviciute, Z., Gil-Mansilla, E., Eder, T., Casillas-Pérez, B., Di Giglio, M. G., Muratspahic, E., Grebien, F., Rattei, T., Muttenthaler, M., Cremer, S., Gruber, C. W. Oxytocin-like signaling in ants influences metabolic gene expression and locomotor activity.

Drivers, barriers, and response to care of Australian pregnant women seeking chiropractic care for low back and pelvic girdle pain: a qualitative case study.

BACKGROUND: Pregnancy-related low back and/or pelvic girdle pain is common, with a prevalence rate of up to 86% in pregnant women. Although 19.5% of Australian pregnant women visit a chiropractor for pelvic girdle pain, little is known about the experience of pregnant women who seek this care. The aim of this study was to describe and explore the experiences of Australian pregnant women who seek chiropractic care for their current pregnancy-related low back and/or pelvic girdle pain. METHODS: A qualitative case study approach with purposive sampling from 27 chiropractic practices was used. A grounded theory approach was informed by a constructivist and interpretivist stance, which provided understanding and meaning to the pregnant women's experiences. Online unstructured interviews were recorded, transcribed, and anonymised. A thematic analysis was subsequently conducted on the primary data. Codes and major themes were developed with the use of critical self- reflection (memos), survey finding triangulation and respondent validation. RESULTS: Sixteen potential respondents expressed interest in participating. After eligibility screening and data saturation, nine interviews were undertaken. Four key themes were identified: "Care drivers: what drives care seeking?", "Care barriers: what barriers are encountered?", "Chiropractic treatment: what does treatment consist of?" and "Response to care: what response was there to care?". CONCLUSION: Four key themes: care drivers, care barriers, chiropractic treatment, and response to care support an emergent substantive-level theory in women's care seeking experiences for pregnancy-related back pain and chiropractic care. This theory is that chiropractic care for pregnant women experiencing low back pain and pelvic girdle pain may improve pain and function, while reducing pregnancy-related biopsychosocial concerns. The findings may inform antenatal health providers and the chiropractic profession about pregnant women's experience seeking chiropractic care as well as directing future research.

Protocoled resuscitation and the prevention of acute kidney injury.

PURPOSE OF REVIEW: Acute kidney injury (AKI) occurrence in critically ill patients is common and is associated with a substantial increase in morbidity and mortality. The scope of this review is to summarize the most recent evidence-based knowledge for prevention of AKI. RECENT FINDINGS: Recent recommendations for prevention of AKI in ICU patients are all 'negative' and, similarly, the most recent and updated guidelines about major topic areas of interest for AKI, including definition and classification, prevention, and pharmacologic treatment, have failed to identify single evidence-based recommendations for prevention and treatment of AKI. Therefore, the evaluation and management of AKI should be guided by clinical algorithms aiming to protocolized hemodynamic optimization, metabolic control, monitoring of intra-abdominal hypertension, use of diuretics to control fluid overload, and careful management of nephrotoxic factors. SUMMARY: Key components of optimal AKI prevention include maintenance of renal perfusion and avoidance of precipitating factors. Adequate renal blood flow maintenance is the first strategy to employ not only to assure renal oxygenation, but also to prevent nephrotoxic drugs-associated AKI. Many potential therapies and interventions are on the horizon, but most of the future research will need to focus more on a step-wise, protocoled, kidney-oriented approach, than on single treatments.

Anti-Coronavirus Vaccines: Past Investigations on SARS-CoV-1 and MERS-CoV, the Approved Vaccines from BioNTech/Pfizer, Moderna, Oxford/AstraZeneca and others under Development Against SARSCoV- 2 Infection.

The aim of this review article is to summarize the knowledge available to date on prophylaxis achievements in the frame of the fight against Coronaviruses. This work will give an overview of what is reported in the recent literature on vaccines (under investigation or already developed like BNT162b2, mRNA-1273, and ChAdOx1-S) effective against the most pathogenic Coronaviruses (SARS-CoV-1, MERS-CoV-1, and SARS-CoV-2), with of course particular attention paid to those under development or already in use to combat the current COVID-19 (CoronaVIrus Disease 19) pandemic. Our main objective is to make a contribution to the comprehension, even at a molecular level, of what is currently ready for anti-SARS-CoV-2 prophylactic intervention, as well as to provide the reader with an overall picture of the most innovative approaches for the development of vaccines that could be of general utility in the fight against the most pathogenic Coronaviruses.

Haemodynamic goal-directed therapy and postoperative infections: earlier is better. A systematic review and meta-analysis.

INTRODUCTION: Infectious complications are the main causes of postoperative morbidity. The early timing of their promoting factors is the rationale for perioperative strategies attempting to reduce them. Our aim was to determine the effects of perioperative haemodynamic goal-directed therapy on postoperative infection rates. METHODS: We performed a systematic review and meta-analysis. MEDLINE, EMBASE, The Cochrane Library and the DARE databases were searched up to March 2011. Randomised, controlled trials of major surgery in adult patients managed with perioperative goal-directed therapy or according to routine haemodynamic practice were included. Primary outcome measure was specific type of infection. RESULTS: Twenty-six randomised, controlled trials with a combined total of 4,188 participants met our inclusion criteria. Perioperative goal-directed therapy significantly reduced surgical site infections (pooled OR 0.58, 95% CI 0.46 to 0.74; P < 0.0001), pneumonia (pooled OR 0.71, 95% CI 0.55 to 0.92; P = 0.009), and urinary tract infections (pooled OR 0.44, 95% CI 0.22 to 0.84; P = 0.02). A significant benefit was found regarding total infectious episodes (OR 0.40, 95% CI 0.28 to 0.58; P < 0.00001). CONCLUSIONS: Flow-directed haemodynamic therapy designed to optimise oxygen delivery protects surgical patients against postoperative hospital-acquired infections and must be strongly encouraged, particularly in the high-risk surgical population.

Preventing acute kidney injury after noncardiac surgery.

PURPOSE OF REVIEW: In surgical patients, outcome is strictly dependent on the occurrence of postoperative complications, and a postoperative failing kidney has a significant independent effect on outcome. Acute kidney injury (AKI) occurs in 1% of noncardiac surgical patients and is commonly associated with more serious complications. It is important to prevent AKI wherever possible. RECENT FINDINGS: The mainstay of postoperative AKI prevention is perioperative maintenance of blood volume with adequate cardiac output by hemodynamic monitoring and fluids/inotropes infusion. There is a growing interest for pharmacological and metabolic interventions. Most interventions, however, have been predominantly evaluated in cardiac surgery and no definite conclusion can be translated in other settings. Tight control of glycemia is still matter of debate and a role, if any, may be limited to cardiac surgical patients. SUMMARY: Adopting adequate nephroprotective strategies is favored by knowing the moment of the actual insult to the kidney. Nevertheless, in the literature too many areas of uncertainty still exist due to the lack of renal risk stratification, of adequately powered studies, of uniform AKI definition, and of appropriate sample composition. The only recommendation for renal protection still consists in maintaining an optimal blood volume and an adequate cardiac output.

SARS-CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and other Drugs for the Treatment of the New Coronavirus.

Here we report on the most recent updates on experimental drugs successfully employed in the treatment of the disease caused by SARS-CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease-19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir [which is widely used to treat Human Immunodeficiency Virus (HIV) infection] in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxychloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS-CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experimental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this virus. This also stresses the urgent need for the scientific community to devote its efforts to the development of other more specific antiviral strategies.

Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study.

OBJECTIVE: Postoperative acute deterioration in renal function, producing oliguria and/or increase in serum creatinine, is one of the most serious complication in surgical patients. Most cases are due to renal hypoperfusion as a consequence of systemic hypotension, hypovolemia, and cardiac dysfunction. Although some evidence suggests that perioperative monitoring and manipulation of oxygen delivery by volume expansion and inotropic drugs may decrease mortality in surgical patients, no study analyzed this approach on postoperative renal dysfunction. The objective of this investigation is to perform a meta-analysis on the effects of perioperative hemodynamic optimization on postoperative renal dysfunction. DATA SOURCES, STUDY SELECTION, DATA EXTRACTION: A systematic literature review, using MEDLINE, EMBASE, and The Cochrane Library databases through January 2008 was conducted and 20 studies met the inclusion criteria (4220 participants). Data synthesis was obtained by using odds ratio (OR) with 95% confidence interval (CI) by random-effects model. DATA SYNTHESIS: Postoperative acute renal injury was significantly reduced by perioperative hemodynamic optimization when compared with control group (OR 0.64; CI 0.50-0.83; p = 0.0007). Perioperative optimization was effective in reducing renal injury defined consistently with risk, injury, failure, and loss and end-stage kidney disease and Acute Kidney Injury Network classifications, and in studies defining renal dysfunction by serum creatinine and/or need of renal replacement therapy only (OR 0.66; CI 0.50-0.88; p = 0.004). The occurrence of renal dysfunction was reduced when treatment started both preoperatively and intraoperatively or postoperatively, was performed in high-risk patients, and was obtained by fluids and inotropes. Mortality was significantly reduced in treatment group (OR 0.50; CI 0.31-0.80; p = 0.004), but statistical heterogeneity was observed. CONCLUSIONS: Surgical patients receiving perioperative hemodynamic optimization are at decreased risk of renal impairment. Because of the impact of postoperative renal complications on adverse outcome, efforts should be aimed to identify patients and surgery that would most benefit from perioperative optimization.

Clinical guidelines for perioperative hemodynamic management of non cardiac surgical adult patients.

Perioperative hemodynamic management, through monitoring and intervention on physiological parameters to improve cardiac output and oxygen delivery (goal-directed therapy, GDT), may improve outcome. However, an Italian survey has revealed that hemodynamic protocols are applied by only 29.1% of anesthesiologists. Aim of this paper is to provide clinical guidelines for a rationale use of perioperative hemodynamic management in non cardiac surgical adult patients, oriented for Italy and updated with most recent studies. Guidelines were elaborated according to NICE (National Institute for Health and Care Excellence) and GRADE system (Grading of Recommendations of Assessment Development and Evaluations). Key questions were formulated according to PICO system (Population, Intervention, Comparators, Outcome). Guidelines and systematic reviews were identified on main research databases and strategy was updated to June 2018. There is not enough good quality evidence to support the adoption of a GDT protocol in order to reduce mortality, although it may be useful in high risk patients. Perioperative GDT protocol to guide fluid therapy is recommended to reduce morbidity. Continuous monitoring of arterial pressure may help to identify short periods of hemodynamic instability and hypotension. Fluid strategy should aim to a near zero balance in normovolemic patients at the beginning of surgery, and a slight positive fluid balance may be allowed to protect renal function. Drugs such as inotropes, vasocostrictors, and vasodilatator should be used only when fluids alone are not sufficient to optimize hemodynamics. Perioperative GDT protocols are associated with a reduction in costs, although no economic study has been performed in Italy.

Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide.

Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V1b receptors, but inhibited the human V1aR. Replacement of Arg8 of inotocin by D-Arg8 led to a potent, stable and competitive V1aR-antagonist ([D-Arg8]-inotocin) with a 3,000-fold binding selectivity for the human V1aR over the other three subtypes, OTR, V1bR and V2R. The Arg8/D-Arg8 ligand-pair was further investigated to gain novel insights into the oxytocin/vasopressin peptide-receptor interaction, which led to the identification of key residues of the receptors that are important for ligand functionality and selectivity. These observations could play an important role for development of oxytocin/vasopressin receptor modulators that would enable clear distinction of the physiological and pathological responses of the individual receptor subtypes.

HBV-DNA suppression and disease course in HBV cirrhosis patients on long-term lamivudine therapy.

In hepatitis B virus (HBV) cirrhosis patients on long-term lamivudine (LAM), the relationships between HBV suppression, development of viral resistance and disease outcome are unclear. We analysed the dynamic of serum HBV-DNA and its relationship with the clinical course of 59 patients (52 males, mean age 51.4 +/- 8.4 years, 12 HBeAg positive and 47 HBeAg negative, and 57 genotype D and two genotype A) with cirrhosis (45 in Child-Turcotte-Pugh class A) and high levels of serum HBV-DNA (median 14.7 x 10(7) genomes/ml) treated with LAM [median (range): 44 (15-78) months]. A total of 50 patient (84.7%) achieved a virological response (serum HBV-DNA negative by PCR) during the first 6 months of therapy, and nine (13.3%) achieved a reduction in viral load of > 3 log10. Mutations in the YMDD motif of HBV polymerase were documented in 26 patients [median (range) 18: (7-42) months]. At the time of the emergence of mutants, 22 patients had HBV-DNA < 10(5) genomes/ml and normal alanine aminotransferase (ALT) levels. The appearance of virological resistance was followed by an increase of HBV-DNA to > 10(5) genomes/ml and of ALT values in 19 out of 26 patients [median (range): 8 (3-19) months]. Event-free survival was significantly longer (P = 0.001) in patients who maintained virological suppression than in those who did not have a complete virological response or suffered a breakthrough. Patients with advanced cirrhosis were more likely to develop liver failure after the emergence of YMDD mutants. The risk of development of hepatocellular carcinoma in patients with compensated cirrhosis and YMDD mutations was maintained, regardless of HBV-DNA serum levels. Profound and maintained HBV-DNA suppression correlates with a better outcome. Early identification of LAM resistance mutations allows switching to other antivirals before liver decompensation or hepatocellular carcinoma development.

Cáncer de mama: epidemiología y supervivencia en un hospital bonaerense / Breast cancer: epidemiology and survival in a hospital bonaerense

Introducción El cáncer de mama continúa siendo causa importante de mortalidad en la población. El conocimiento de sus características epidemiológicas permite realizar mejoras en las estrategias de detección y tratamiento. En el hzga Manuel Belgrano esta situación aún es desconocida, por lo cual se hace imperioso conocerla para tomar conductas acertadas. Objetivos Estimar la supervivencia y características epidemiológicas de las pacientes atendidas con cáncer de mama en este hospital. Material y método Estudio epidemiológico, descriptivo, transversal con dos ramas: consulta por control clínico-imagenológico; y consulta por síntomas. Se enrolaron 172 pacientes. Resultados La edad media en la rama examen clínico-imagenológico es de 61,49 +/- 13,32 años, y en la rama de síntomas es de 62,07 +/- 14,58 años; no se encontraron diferencias significativas al ser comparadas: t=0,265, p=0,79. La supervivencia global y libre de enfermedad por estadios fue de 87,8%: en la rama de estadios precoces fue de 93,4% y en la de los tardíos de 66,7% , con diferencia estadística significativa (p=0,0001). La supervivencia global y libre de enfermedad por ramas de estudio fue de 87,79% y 87,8% respectivamente: para la rama sintomática, se encontró en una supervivencia global de 82,69 y una supervivencia libre de enfermedad de 82,7%; para la rama control clínico-imagenológico fue de 95,58% y 95,6% respectivamente, con diferencia estadística significativa (p=0,012). Conclusiones Las características epidemiológicas y tumorales son coincidentes con las de la población de otros estudios. Hubo mayores consultas en la rama sintomática, y la supervivencia fue menor en este grupo.

Introduction Breast cancer is still an important cause of mortality in the population. The knowledge of the epidemiological characteristics allows to improve detection and treatment strategies. In hzga Manuel Belgrano this situation is still in the dark, so it is imperative to make it known in order to take good decisions in the treatment of this pathology. Objectives To estimate survival and epidemiological characteristics of patients with breast cancer treated in this hospital. Materials and method An epidemiological, descriptive, cross-sectional study with two fold approach: clinic and imaging consultation, and by symptoms. 172 patients were enrolled in this study. Results Average age in the clinical and imaging approach is 61.49 +/- 13.32 years and in the consultation by symptoms was 62.07 +/- 14.58 years; no significant differences were found in comparison between the two methods available: t = 0.265, p = 0.79. The overall and free disease survival by stage is 87.8%. In the early stages approach was 93.4% and 66.7%, while late stages shown statistically significant difference with p=0.0001. The overall and free disease survival by approach of study was 87.79% and 87.8% respectively. In symptomatic consultations was found a free overall survival of 82.69 % and 82.7%. For clinical imaging control approach was 95.58% and 95.6% respectively, with significant statistical difference (p = 0.012). Conclusions The epidemiological and tumor characteristics agree with the population described in similar studies published at the time. There were further consultations in symptomatic approach, and survival was lower in this group.

HPV group- and type-specific concordance in HPV infected sexual couples.

The concordance of human papillomavirus (HPV) groups and types was evaluated in 45 sexual couples with both partners HPV infected, by analyzing cervical samples from women and three genital sites (penile brushing, urethral brushing, and semen) from men. When grouping HPV types, no significant HPV group sharing was found between partners, either considering samples from any male site (concordance: 55.5%; P = 0.11) or from each site (concordance by penile brushing, 37.8%; urethral brushing, 24.5%; semen, 22.3%; P > 0.05). Examining individual HPV types, using samples from any male site, concordance was found in 29 (64.4%; P = 0.036) couples; significant concordance was evident for 16 HPV genotypes, the most frequent being HPV-6, -66, -31, -51, and -53. Using samples from specific male sites, concordance was found by penile brushing in 24 (53.3%) couples, urethral brushing in 16 (35.5%), and semen in 7 (15.5%; P = 0.014). Among the 16 HPV types shared by examining samples from any male site, 9 (56.3%) were in common by penile brushing, 11 (68.7%) by urethral brushing, and 6 (37.5%; P = 0.48) by semen. Combined penile brushing and urethral brushing sampling identified all the 29 couples concordant by the three male sites; combined penile brushing and semen detected 26 (89.6%) concordant couples. The most adequate approach to the assessment of HPV concordance in sexual couples could be based on the analysis of individual HPV types and the sampling of men by penile brushing combined with urethral brushing. The high and significant degree of HPV type-specific concordance confirms HPV transmission between sexual partners.

Bacteriología comparativa de las amigdalitis agudas y crónicas en niños / Comparative bacteriology of acute and chronic tonsilitis in children

Se realiza un estudio bacteriológico del frotis amigdaliano de una muestra de 158 niños de 12 años o menos distribuidos en 4 grupos como sigue: Grupo A con 49 niños sanos; Grupo B con 52 niños con patología amigdaliana crónica sin enfermedad en el momento del estudio; Grupo C con 31 niños con patología amigdaliana aguda ocasional con enfermedad en el momento del estudio y Grupo D con 26 niños con patología amigdaliana crónica con enfermedad en el momento del estudio. Los resultados fueron sometidos a análisis estadístico. La presencia de Staphylococus aureus fue significamente mayor en los niños con amigdalitis aguda a repetición, estuvieran o no enfermos en el momento del estudio (grupos B y D) comparados con los niños sanos o con amigdalitis aguda ocasional (grupos A y C). Todos los demás gérmenes potencialmente patógenos encontrados no tenían relevancia estadísticamente significativa en la muestra analizada. Se concluyen los siguiente hexchos destacables: La Branhamella catarrhalis y el Streptococcus viridans son gérmenes presentes en todos los niños estudiados. En una patología amigdaliana aguda o crónica, la cantidad de microorganismos de la flora amigdaliana habitual está substancialmente aumentada en relación a la flora habitual de niños sanos de acuerdo a un recuento semicuantitativo en placa. El tratamiento habitual de una amigdalits con Penicilina, en cualquiera de sus formas, deberá considerar si se trata de una amigdalitis ocasional o bien de una amigdalitis crónica reagudizada, en el segundo caso deberá contemplarse la posibilidad de la existencia de un Staphylococcus aureus y asociar al tratamiento de un antibiótico antiestafilocócico, previo estudio bacteriológico. El hallazgo del Staphylococcus aureus en el cultivo del frotis amigdaliano de un niño con amigdalitis agudas a repetición, deberá ser considerado un eventual elemento de juicio más oara la calificación de cronicidad y ulterior decisión quirúrgica