Microbiome and cancer: from mechanistic implications in disease progression and treatment to development of novel antitumoral strategies.

Cancer is a very aggressive disease and one of mankind's most important health problems, causing numerous deaths each year. Its etiology is complex, including genetic, gender-related, infectious diseases, dysbiosis, immunological imbalances, lifestyle, including dietary factors, pollution etc. Cancer patients also become immunosuppressed, frequently as side effects of chemotherapy and radiotherapy, and prone to infections, which further promote the proliferation of tumor cells. In recent decades, the role and importance of the microbiota in cancer has become a hot spot in human biology research, bringing together oncology and human microbiology. In addition to their roles in the etiology of different cancers, microorganisms interact with tumor cells and may be involved in modulating their response to treatment and in the toxicity of anti-tumor therapies. In this review, we present an update on the roles of microbiota in cancer with a focus on interference with anticancer treatments and anticancer potential.

Impact of the COVID-19 pandemic on the real-world diagnostic infrastructure for tuberculosis-An ESGMYC collaborative study.

We determined the impact of the COVID-19 pandemic on mycobacterial diagnostic services. 40 laboratories from 22 countries completed an online questionnaire covering the redeployment of the laboratory infrastructure and/or staff for SARS-CoV-2 testing, staff shortages and supply chain disruptions. 28 laboratories reported monthly numbers of samples processed for mycobacterial investigations and monthly numbers of M. tuberculosis complex (MTBC) PCRs performed between October 1st 2018 and October 31st 2020. More than half (23/40) of the participating TB laboratories reported having performed COVID-19 diagnostics in the early phase of the pandemic, in part with negative impact on the mycobacterial service activities. All participating laboratories reported shortages of consumables and laboratory equipment due to supply chain issues. Average monthly sample numbers decreased by 24% between January 2020 and October 2020 compared to pre-pandemic averages. At the end of the study period, most participating laboratories had not returned to pre-pandemic average MTBC PCR throughput.

The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been defined as the greatest global health and socioeconomic crisis of modern times. While most people recover after being infected with the virus, a significant proportion of them continue to experience health issues weeks, months and even years after acute infection with SARS-CoV-2. This persistence of clinical symptoms in infected individuals for at least three months after the onset of the disease or the emergence of new symptoms lasting more than two months, without any other explanation and alternative diagnosis have been named long COVID, long-haul COVID, post-COVID-19 conditions, chronic COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Long COVID has been characterized as a constellation of symptoms and disorders that vary widely in their manifestations. Further, the mechanisms underlying long COVID are not fully understood, which hamper efficient treatment options. This review describes predictors and the most common symptoms related to long COVID's effects on the central and peripheral nervous system and other organs and tissues. Furthermore, the transcriptional markers, molecular signaling pathways and risk factors for long COVID, such as sex, age, pre-existing condition, hospitalization during acute phase of COVID-19, vaccination, and lifestyle are presented. Finally, recommendations for patient rehabilitation and disease management, as well as alternative therapeutical approaches to long COVID sequelae are discussed. Understanding the complexity of this disease, its symptoms across multiple organ systems and overlapping pathologies and its possible mechanisms are paramount in developing diagnostic tools and treatments.

COVID-19 positive cases in a pediatric surgery department from Romania: Case series from 2 years of pandemics.

RATIONALE: The COVID-19 pandemic had a dramatic effect on various health systems in terms of admissions and outcomes, including pediatric surgery activity. The aim of this paper was to analyze the outcome of SARS-CoV-2-positive patients admitted to our department during the regional COVID-19 pandemic in North-Eastern Romania. We also evaluated the changes generated in our daily practice by the COVID-19 pandemic and the dynamic response to this major challenge. PATIENT CONCERNS: The patients presented with symptoms related to their primary diagnosis: local pain and deformity in case of fractures; pain, swelling, and erythema in case of abscess; pain and decreased range of motion (ROM) in case of intolerance to metal implants. Other specific concerns are mentioned on an individual basis. DIAGNOSES: Eighteen patients (of which 4 had acute appendicitis and were included in a previous article), representing 1.18% of the total number of admissions, tested positive for SARS-CoV-2. There were 4 patients with fractures, 3 patients with soft tissue abscess or cellulitis, 2 patients with intolerance to metal implants, 1 patient with facial burn, 1 patient with thumb laceration, 1 patient with liver trauma, 1 patient with undescende testis, and 1 patient with symptomatic inguinal hernia, respectively. Boys represented 11/ 14 (78.57%) of the cases. The mean age of the patients was 9 years 11 months. There were only mild COVID-19 cases. INTERVENTIONS: Surgery was performed in 13/ 14 (95.71%) of cases. The fractures were treated with open reduction internal fixation (ORIF); incision and drainage (I & D) were performed in case of soft tissue abscess; the metal implants were removed in case of local intolerance. Other conditions (burn, inguinal hernia, undescended testis, skin laceration) were treated specifically. Only 1 patient with liver laceration was treated conservatively under close hemodynamic monitoring. OUTCOMES: The mean length of stay (LoS) was 2.71 days. The infection with the SARS-CoV-2 virus had no deleterious effect on the surgical outcome among the 14 patients included in the study. There were no surgical complications during admission and no patient returned for late complications related to their primary disease or SARS-CoV-2 infection. LESSONS: The SARS-CoV-2 infection had no significant influence on the outcome of pediatric surgical cases included in the study. We noticed a significant (31.54%) decrease in the number of admissions compared to the previous 2-year interval before the COVID-19 pandemic. Fast and adequate adjustment of the daily activity imposed by the COVID-19 pandemic was feasible and may be used in the future should similar epidemiological emergencies occur.

Innovative Materials with Possible Applications in the Wound Dressings Field: Alginate-Based Films with Moringa oleifera Extract.

For a long time, biopolymers have proven their effectiveness in the development of materials with various applications, lately those intended for the biomedical and pharmaceutical industries, due to their high biocompatibility and non-toxic, non-allergenic, and non-immunogenic nature. The ability to incorporate various active substances in this matrix has yielded materials with characteristics that are far superior to those of classic, conventional ones. The beneficial effects of consuming Moringa oleifera have promoted the use of this plant, from Ayurvedic to classical medicine. The addition of such compounds in the materials intended for the treatment of surface wounds may represent the future of the development of innovative dressings. This study followed the development of materials based on sodium alginate and moringa powder or essential oil for use as dressings, pads, or sheets. Thus, three materials with the addition of 10-30% moringa powder and three materials with the addition of 10-30% essential oil were obtained. The data were compared with those of the control sample, with sodium alginate and plasticizer. The microtopography indicated that the materials have a homogeneous matrix that allows them to incorporate and maintain natural compounds with prolonged release. For example, the sample with 30% moringa essential oil kept its initial shape and did not disintegrate, although the swelling ratio value reached 4800% after 20 min. After testing the mechanical properties, the same sample had the best tensile strength (TS = 0.248 MPa) and elongation (31.41%), which is important for the flexibility of the dressing. The same sample exhibited a very high antioxidant capacity (60.78% inhibition). The materials obtained with moringa powder added presented good values of physical and mechanical properties, which supports their use as wound dressings for short-term application and the release of embedded compounds. According to the obtained results, all the biopolymeric materials with moringa added can be used as dressings for different wound types.

The Role of the Prognostic Inflammatory and Nutritional Index (PINI) in the Evolution of Patients with Chronic Kidney Disease and Other Pathologies.

BACKGROUND: Protein-energy loss and inflammation are the main risk factors in the occurrence of complications in hemodialysis patients. The Prognostic Inflammatory and Nutritional Index (PINI) is a simple, inexpensive test to identify the early onset of inflammation and malnutrition in hemodialysis patients, critically ill subjects and those with malignancies. METHODS: A systemic review of English literature was conducted on the topic published between 1985 and 2022. A focused and sensitive search strategy was applied to the PUBMED database to identify relevant scientific articles in English. Once articles were identified, a detailed quality and bias assessment was performed. Two independent researchers analyzed the detailed data extraction. RESULTS: PINI proved to be a sensitive, powerful, low-cost and simple test. PINI has been useful in assessing evolution and prognostics in clinical care, with values above one being associated with a high risk of mortality and morbidity. It is useful in cases with surgical and postoperative complications, long hospitalization, as well as increased associated expenses. CONCLUSIONS: This is the first review of the literature on the above-mentioned topic (PINI) and is a valuable candidate for validating prognosis in patients with different pathologies.

"Quo Vadis Diagnosis": Application of Informatics in Early Detection of Pneumothorax.

A pneumothorax is a condition that occurs in the lung region when air enters the pleural space-the area between the lung and chest wall-causing the lung to collapse and making it difficult to breathe. This can happen spontaneously or as a result of an injury. The symptoms of a pneumothorax may include chest pain, shortness of breath, and rapid breathing. Although chest X-rays are commonly used to detect a pneumothorax, locating the affected area visually in X-ray images can be time-consuming and prone to errors. Existing computer technology for detecting this disease from X-rays is limited by three major issues, including class disparity, which causes overfitting, difficulty in detecting dark portions of the images, and vanishing gradient. To address these issues, we propose an ensemble deep learning model called PneumoNet, which uses synthetic images from data augmentation to address the class disparity issue and a segmentation system to identify dark areas. Finally, the issue of the vanishing gradient, which becomes very small during back propagation, can be addressed by hyperparameter optimization techniques that prevent the model from slowly converging and poorly performing. Our model achieved an accuracy of 98.41% on the Society for Imaging Informatics in Medicine pneumothorax dataset, outperforming other deep learning models and reducing the computation complexities in detecting the disease.

Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection.

Mammalians sense antigenic messages from infectious agents that penetrate the respiratory and digestive epithelium, as well as signals from damaged host cells through membrane and cytosolic receptors. The transduction of these signals triggers a personalized response, depending on the nature of the stimulus and the host's genetics, physiological condition, and comorbidities. Interferons (IFNs) are the primary effectors of the innate immune response, and their synthesis is activated in most cells within a few hours after pathogen invasion. IFNs are primarily synthesized in infected cells, but their anti-infective effect is extended to the neighboring cells by autocrine and paracrine action. The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 2019 was a stark reminder of the potential threat posed by newly emerging viruses. This pandemic has also triggered an overwhelming influx of research studies aiming to unveil the mechanisms of protective versus pathogenic host immune responses induced by SARS-CoV-2. The purpose of this review is to describe the role of IFNs as vital players in the battle against SARS-CoV-2 infection. We will briefly characterize and classify IFNs, present the inductors of IFN synthesis, their sensors, and signaling pathways, and then discuss the role of IFNs in controlling the evolution of SARS-CoV-2 infection and its clinical outcome. Finally, we will present the perspectives and controversies regarding the prophylactic and therapeutic potential of IFNs in SARS-CoV-2 infection.

Spontaneous Pneumomediastinum in a 16-Year-Old Patient with SARS-CoV-2 Infection: A North-East Romanian Case.

Spontaneous pneumomediastinum (SPM) associated with SARS-CoV-2 infection is a rare condition but can represent a medical emergency. It is probably related to alveolar damage secondary to SARS-CoV-2 infection, which allows air to escape in the surrounding lung tissue. Cough and airways' barotrauma are also mentioned as contributing mechanisms. Treatment is generally conservative, but surgery may be required in severe cases. This paper presents the case of a 16-year-old girl with COVID-19-associated SPM who was treated conservatively in our department. The clinical course was favorable with resolution of respiratory symptoms and radiological (chest CT scan) image of pneumomediastinum. The patient was discharged 7 days after the confirmation of the initial SP diagnosis with appropriate treatment and recommendations for isolation. The sudden occurrence of chest pain and dyspnea should raise the suspicion of SPM in COVID-19 patients. Close surveillance and proper radiological monitoring are required in such cases. Treatment should be strictly individualized based on clinical course and radiological appearance.

Global Challenges to Public Health Care Systems during the COVID-19 Pandemic: A Review of Pandemic Measures and Problems.

Beginning in December 2019, the world faced a critical new public health stressor with the emergence of SARS-CoV-2. Its spread was extraordinarily rapid, and in a matter of weeks countries across the world were affected, notably in their ability to manage health care needs. While many sectors of public structures were impacted by the pandemic, it particularly highlighted shortcomings in medical care infrastructures around the world that underscored the need to reorganize medical systems, as they were vastly unprepared and ill-equipped to manage a pandemic and simultaneously provide general and specialized medical care. This paper presents modalities in approaches to the pandemic by various countries, and the triaged reorganization of medical sections not considered first-line in the pandemic that was in many cases transformed into wards for treating COVID-19 cases. As new viruses and structural variants emerge, it is important to find solutions to streamline medical care in hospitals, which includes the expansion of digital network medicine (i.e., telemedicine and mobile health apps) for patients to continue to receive appropriate care without risking exposure to contagions. Mobile health app development continues to evolve with specialized diagnostics capabilities via external attachments that can provide rapid information sharing between patients and care providers while eliminating the need for office visits. Telemedicine, still in the early stages of adoption, especially in the developing world, can ensure access to medical information and contact with care providers, with the potential to release emergency rooms from excessive cases, and offer multidisciplinary access for patients and care providers that can also be a means to avoid contact during a pandemic. As this pandemic illustrated, an overhaul to streamline health care is essential, and a move towards greater use of mobile health and telemedicine will greatly benefit public health to control the spread of new variants and future outbreaks.

Common themes in antimicrobial and anticancer drug resistance.

Antimicrobial and anticancer drug resistance represent two of the main global challenges for the public health, requiring immediate practical solutions. In line with this, we need a better understanding of the origins of drug resistance in prokaryotic and eukaryotic cells and the evolutionary processes leading to the occurrence of adaptive phenotypes in response to the selective pressure of therapeutic agents. The purpose of this paper is to present some of the analogies between the antimicrobial and anticancer drug resistance. Antimicrobial and anticancer drugs share common targets and mechanisms of action as well as similar mechanisms of resistance (e.g., increased drug efflux, drug inactivation, target alteration, persister cells' selection, protection of bacterial communities/malignant tissue by an extracellular matrix, etc.). Both individual and collective stress responses triggered by the chemotherapeutic agent involving complex intercellular communication processes, as well as with the surrounding microenvironment, will be considered. The common themes in antimicrobial and anticancer drug resistance recommend the utility of bacterial experimental models for unraveling the mechanisms that facilitate the evolution and adaptation of malignant cells to antineoplastic drugs.

microRNA-27b regulates hepatic lipase enzyme LIPC and reduces triglyceride degradation during hepatitis C virus infection.

miRNAs are short, noncoding RNAs that negatively and specifically regulate protein expression, the cumulative effects of which can result in broad changes to cell systems and architecture. The miRNA miR-27b is known to regulate lipid regulatory pathways in the human liver and is also induced by the hepatitis C virus (HCV). However, the functional targets of miR-27b are not well established. Herein, an activity-based protein profiling method using a serine hydrolase probe, coupled with stable isotope labeling and mass spectrometry identified direct and indirect targets of miR-27b. The hepatic lipase C (LIPC) stood out as both highly dependent on miR-27b and as a major modulator of lipid pathway misregulation. Modulation of miR-27b using both exogenous miRNA mimics and inhibitors demonstrated that transcription factors Jun, PPARα, and HNF4α, all of which also influence LIPC levels and activity, are regulated by miR-27b. LIPC was furthermore shown to affect the progress of the life cycle of HCV and to decrease levels of intracellular triglycerides, upon which HCV is known to depend. In summary, this work has demonstrated that miR-27b mediates HCV infection by downregulating LIPC, thereby reducing triglyceride degradation, which in turn increases cellular lipid levels.

Acute Appendicitis in COVID-19-Positive Children: Report of 4 Cases from an Endemic Area in Northeastern Romania.

Acute appendicitis (AA) is one of the most common surgical emergencies in children. Some reports have suggested that the COVID-19 pandemic was responsible for delays in the diagnostic and proper treatment of AA in pediatric patients. The aim of our study was to perform a retrospective study of cases of AA in children with SARS-CoV-2 infection treated in a highly endemic area for COVID-19 in Romania during a 2-year time interval. The SARS-CoV-2 infection had no unfavorable impact on children who presented with AA. Further data analysis should clarify the overall influence of COVID-19 on the management of surgical pediatric patients in such endemic areas.

Antiviral Immunity in SARS-CoV-2 Infection: From Protective to Deleterious Responses.

After two previous episodes, in 2002 and 2012, when two highly pathogenic coronaviruses (SARS, MERS) with a zoonotic origin emerged in humans and caused fatal respiratory illness, we are today experiencing the COVID-19 pandemic produced by SARS-CoV-2. The main question of the year 2021 is if naturally- or artificially-acquired active immunity will be effective against the evolving SARS-CoV-2 variants. This review starts with the presentation of the two compartments of antiviral immunity-humoral and cellular, innate and adaptive-underlining how the involved cellular and molecular actors are intrinsically connected in the development of the immune response in SARS-CoV-2 infection. Then, the SARS-CoV-2 immunopathology, as well as the derived diagnosis and therapeutic approaches, will be discussed.

Changes in Dietary Patterns and Clinical Health Outcomes in Different Countries during the SARS-CoV-2 Pandemic.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an excess in community mortality across the globe. We review recent evidence on the clinical pathology of COVID-19, comorbidity factors, immune response to SARS-CoV-2 infection, and factors influencing infection outcomes. The latter specifically includes diet and lifestyle factors during pandemic restrictions. We also cover the possibility of SARS-CoV-2 transmission through food products and the food chain, as well as virus persistence on different surfaces and in different environmental conditions, which were major public concerns during the initial days of the pandemic, but have since waned in public attention. We discuss useful measures to avoid the risk of SARS-CoV-2 spread through food, and approaches that may reduce the risk of contamination with the highly contagious virus. While hygienic protocols are required in food supply sectors, cleaning, disinfection, avoidance of cross-contamination across food categories, and foodstuffs at different stages of the manufacturing process are still particularly relevant because the virus persists at length on inert materials such as food packaging. Moreover, personal hygiene (frequent washing and disinfection), wearing gloves, and proper use of masks, clothes, and footwear dedicated to maintaining hygiene, provide on-site protections for food sector employees as well as supply chain intermediates and consumers. Finally, we emphasize the importance of following a healthy diet and maintaining a lifestyle that promotes physical well-being and supports healthy immune system function, especially when government movement restrictions ("lockdowns") are implemented.

Applications of Biopolymers for Drugs and Probiotics Delivery.

Research regarding the use of biopolymers has been of great interest to scientists, the medical community, and the industry especially in recent years. Initially used for food applications, the special properties extended their use to the pharmaceutical and medical industries. The practical applications of natural drug encapsulation materials have emerged as a result of the benefits of the use of biopolymers as edible coatings and films in the food industry. This review highlights the use of polysaccharides in the pharmaceutical industries and as encapsulation materials for controlled drug delivery systems including probiotics, focusing on their development, various applications, and benefits. The paper provides evidence in support of research studying the use of biopolymers in the development of new drug delivery systems, explores the challenges and limitations in integrating polymer-derived materials with product delivery optimization, and examines the host biological/metabolic parameters that can be used in the development of new applications.

Emergence of the First Strains of SARS-CoV-2 Lineage B.1.1.7 in Romania: Genomic Analysis.

BACKGROUND: The United Kingdom reported the emergence of a new and highly transmissible SARS-CoV-2 variant (B.1.1.7) that rapidly spread to other countries. The impact of this new mutation-which occurs in the S protein-on infectivity, virulence, and current vaccine effectiveness is still under evaluation. OBJECTIVE: The aim of this study is to sequence SARS-CoV-2 samples of cases in Romania to detect the B.1.1.7 variant and compare these samples with sequences submitted to GISAID. METHODS: SARS-CoV-2 samples were sequenced and amino acid substitution analysis was performed using the CoV-GLUE platform. RESULTS: We have identified the first cases of the B.1.1.7 variant in samples collected from Romanian patients, of which one was traced to the region of the United Kingdom where the new variant was originally sequenced. Mutations in nonstructural protein 3 (Nsp3; N844S and D455N) and ORF3a (L15F) were also detected, indicating common ancestry with UK strains as well as remote connections with strains from Nagasaki, Japan. CONCLUSIONS: These results indicate, for the first time, the presence and characteristics of the new variant B.1.1.7 in Romania and underscore the need for increased genomic sequencing in patients with confirmed COVID-19.

Profiling of MicroRNA Targets Using Activity-Based Protein Profiling: Linking Enzyme Activity to MicroRNA-185 Function.

MicroRNAs (miRNAs) act as cellular signal transducers through repression of protein translation. Elucidating targets using bioinformatics and traditional quantitation methods is often insufficient to uncover global miRNA function. Herein, alteration of protein function caused by miRNA-185 (miR-185), an immunometabolic miRNA, was determined using activity-based protein profiling, transcriptomics, and lipidomics. Fluorophosphonate-based activity-based protein profiling of miR-185-induced changes to human liver cells revealed that exclusively metabolic serine hydrolase enzymes were regulated in activity, some with roles in lipid and endocannabinoid metabolism. Lipidomic analysis linked enzymatic changes to levels of cellular lipid species, such as components of very-low-density lipoprotein particles. Additionally, inhibition of one miR-185 target, monoglyceride lipase, led to decreased hepatitis C virus levels in an infectious model. Overall, the approaches used here were able to identify key functional changes in serine hydrolases caused by miR-185 that are targetable pharmacologically, such that a small molecule inhibitor can recapitulate the miRNA phenotype.

Gut Dysbiosis and Clostridioides difficile Infection in Neonates and Adults.

In this review, we focus on gut microbiota profiles in infants and adults colonized (CDC) or infected (CDI) with Clostridioides difficile. After a short update on CDI epidemiology and pathology, we present the gut dysbiosis profiles associated with CDI in adults and infants, as well as the role of dysbiosis in C. difficile spores germination and multiplication. Both molecular and culturomic studies agree on a significant decrease of gut microbiota diversity and resilience in CDI, depletion of Firmicutes, Bacteroidetes, and Actinobacteria phyla and a high abundance of Proteobacteria, associated with low butyrogenic and high lactic acid-bacteria levels. In symptomatic cases, microbiota deviations are associated with high levels of inflammatory markers, such as calprotectin. In infants, colonization with Bifidobacteria that trigger a local anti-inflammatory response and abundance of Ruminococcus, together with lack of receptors for clostridial toxins and immunological factors (e.g., C. difficile toxins neutralizing antibodies) might explain the lack of clinical symptoms. Gut dysbiosis amelioration through administration of "biotics" or non-toxigenic C. difficile preparations and fecal microbiota transplantation proved to be very useful for the management of CDI.

Observation of intracellular protein localization area in a single neuron using gold nanoparticles with a scanning electron microscope.

The localization areas of intracellular proteins in rat cortical neurons were visualized using a scanning electron microscope (SEM) coupled with a focused ion beam (FIB) system. To obtain a clear contrast in the SEM images, gold nanoparticles (GNPs) were bound to specific intracellular proteins by antigen-antibody reactions. By obtaining a cross section of the desired location of the neurons by FIB milling under the SEM imaging condition, it was possible to observe the proteins inside the cells as clear bright spots. When a neuron was stained with anti-tau and anti-histone H1 antibodies, the bright spots were localized in the cross section of the axon and the nucleus, respectively. It was confirmed that targeted proteins in a single neuron on a substrate could be successfully identified. The development of FIB/SEM observation with immunological GNP staining will offer important information for the stable growth of neurons on various substrate structures, since the elongation and turning of axons on the substrates are activated by the redistribution of intracellular proteins.