Effects of Terpenes on the Osteoarthritis Cytokine Profile by Modulation of IL-6: Double Face versus Dark Knight?

BACKGROUND: Hemp seed oil and terpenes are emerging as a dietary supplement and complementary therapy for patients suffering from knee osteoarthritis (KOA). However, the mechanisms and effects induced by these molecules on inflammatory cytokines are not yet fully understood. The aim of this study was to evaluate the changes in the cytokine IL-1ß, IL-1α, IL-2, IL-6, and TNF-α levels from two oral hemp seed oil-based dietary supplements, of which only one included the addition of terpenes, in a population of KOA patients. METHODS: Sera from venous blood samples were collected from thirty-eight patients who were divided into two subgroups. The control group underwent a 45-day treatment with a dietary supplement containing only hemp seed oil, while the treatment group assumed a hemp seed oil and terpene-based dietary supplement for the same number of days. A Bio-Plex Human Cytokine assay was performed by a customized human cytokine five-plex panel for IL-1ß, IL-1α, IL-2, IL-6, and TNF-α. Patients were evaluated before the beginning of the treatment (T0) and soon after it (T1). RESULTS: No measurable levels of IL-2 and TNF-α were found in any of the subjects. Low levels of IL-1ß were found, which were significantly decreased in the treatment group. No change in IL-1α levels was observed, while treated patients had a significant increase in IL-6 levels. CONCLUSIONS: Hemp seed oil and terpene treatment modified the IL-1ß and IL-6 levels, counteracting KOA inflammation in this way. In this study, IL-6 revealed its new and alternative action, since it is traditionally known as a pro-inflammatory factor, but it recently has been found to have anti-inflammatory activity in the muscle-derived form, which is the one it assumes as a myokine when activated by terpenes.

A Gel-Based Proteomic Analysis Reveals Synovial α-Enolase and Fibrinogen ß-Chain Dysregulation in Knee Osteoarthritis: A Controlled Trial.

BACKGROUND: The identification of synovial fluid (SF) biomarkers that could anticipate the diagnosis of osteoarthritis (OA) is gaining increasing importance in orthopaedic clinical practice. This controlled trial aims to assess the differences between the SF proteome of patients affected by severe OA undergoing Total Knee Replacement (TKR) compared to control subjects (i.e., subjects younger than 35, undergoing knee arthroscopy for acute meniscus injury). METHODS: The synovial samples were collected from patients with Kellgren Lawrence grade 3 and 4 knee osteoarthritis undergoing THR (study group) and young patients with meniscal tears and no OA signs undergoing arthroscopic surgery (control group). The samples were processed and analyzed following the protocol defined in our previous study. All of the patients underwent clinical evaluation using the International Knee Documentation Committee (IKDC) subjective knee evaluation (main outcome), Knee Society Clinical Rating System (KSS), Knee injury and Osteoarthritis Outcome Score (KOOS), and Visual Analogue Scale (VAS) for pain. The drugs' assumptions and comorbidities were recorded. All patients underwent preoperative serial blood tests, including complete blood count and C-Reactive Protein (CRP). RESULTS: The synovial samples' analysis showed a significantly different fibrinogen beta chain (FBG) and alpha-enolase 1 (ENO1) concentration in OA compared to the control samples. A significant correlation between clinical scores, FBG, and ENO1 concentration was observed in osteoarthritic patients. CONCLUSIONS: Synovial fluid FBG and ENO1 concentrations are significantly different in patients affected by knee OA compared with non-OA subjects.

A Multi-Institutional Informed Consent Proposal as a Prevention Tool for Combined Oral Contraceptive Intake and Thrombotic Risk.

Combined oral contraceptives (COC), are among the most widely used contraceptive methods in the world today. Despite the different changes in terms of estrogen/progestogen combinations and dosages, the thromboembolic risk for a woman who takes combined oral contraceptives persists to date. METHODS: The review of relevant literature and international guidelines on prescription of combined oral contraceptives made it possible to create a proposal for informed consent to be used for prescribing. RESULTS: The several sections of our consent proposal were designed according to a rationale in order to cover all the aspects presented by worldwide guidelines: how to take, adverse effects, advertisements, extra-contraceptive benefits and effects, a checklist for condition at risk of thromboembolism, the signature of the woman. CONCLUSIONS: An informed consent to standardize combined oral contraceptives prescription can improve women's eligibility, mitigate thromboembolic risk, and assure legal protection to healthcare providers. In this systematic review in particular, we refer to the Italian medical-legal scenario, to which our group of researchers belongs. However, the model proposed was designed in the respect of main healthcare organization guidelines, and it could be easily used by any center in the world.

Is the Non-Coding RNA miR-195 a Biodynamic Marker in the Pathogenesis of Head and Neck Squamous Cell Carcinoma? A Prognostic Meta-Analysis.

Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of neoplasms whose histological derivation comes from the mucous membranes lining the epithelium: the oral cavity, the larynx, the hypopharynx, the nasopharynx, and the oropharynx. The etiopathogenetic mechanisms involving tumor genesis including the alteration of cell proliferation, apoptosis, invasion, migration, and death may involve alterations in the expression of microRNA (miR). To date there have been no systematic reviews with meta-analysis conducted specifically on the role of miR-195 in HNSCC; therefore, our hypothesis was to evaluate if the aberrant expression of miR-195 in HNSCC tissues may represent a prognostic biomarker of survival through the hazard ratio (HR) and relative risk (RR) analysis. The systematic review was designed according to the PRISMA indications; in total, three electronic databases were consulted (PubMed, Scopus, Cochrane Central Trial) including Google Scholar and the gray literature, and a combination of keywords was used such as miR-195 AND HNSCC, microRNA AND HNSCC and miR-195. The meta-analysis and trial sequential analysis were performed using RevMan 5.41 software and TSA software (Cochrane Collaboration, Copenhagen, Denmark). This search identified 1592 articles and, at the end of the selection process, three articles were included. The results of the meta-analysis reported an aggregated risk ratio for overall survival (OS) between the expression of miR-195 at the highest and lowest of 0.36 and 6, respectively, 95% CI: [0.25, 0.51]. Heterogeneity was evaluated through Chi2 = 0.05 df = 2 (p = 0.98) and the Higgins index I2 = 0%. The test for the overall effect was Z = 5.77 (p < 0.00001). The forest plot was in favor of higher OS in patients with high miR-195 expression.

"GONE WITH THE WIND": The Transitory Effects of COVID-19 on the Gynecological System.

The coronavirus disease no longer seems to represent an insurmountable global problem. This is thanks to the advent of coronavirus vaccines, which have alleviated the most serious symptoms associated with this disease. On the other hand, there are still many extrapulmonary symptoms of COVID-19, and among these also those of a gynecological nature. At the moment, there are several questions in this field, one above all concerns the causal link between COVID-19, vaccines and gynecological alterations. Furthermore, another important aspect is represented by the clinical impact of post-COVID-19 gynecological alterations on the female population which, to date, would seem to be mainly due to their duration, even if the extent of these symptoms is still poorly understood. Furthermore, it is not possible to foresee eventual long-term aggravations, or more serious symptoms caused by other viral variants that may arrive in the future. In this review, we focus on this theme and attempt to reorganize the different pieces of a puzzle which, to date, does not seem to have shown us its complete picture.

Inflammation as Prognostic Hallmark of Clinical Outcome in Patients with SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often characterized by a life-threatening interstitial pneumonia requiring hospitalization. The aim of this retrospective cohort study is to identify hallmarks of in-hospital mortality in patients affected by Coronavirus Disease 19 (COVID-19). A total of 150 patients admitted for COVID-19 from March to June 2021 to "F. Perinei" Murgia Hospital in Altamura, Italy, were divided into survivors (n = 100) and non-survivors groups (n = 50). Blood counts, inflammation-related biomarkers and lymphocyte subsets were analyzed into two groups in the first 24 h after admission and compared by Student's t-test. A multivariable logistic analysis was performed to identify independent risk factors associated with in-hospital mortality. Total lymphocyte count and CD3+ and CD4+ CD8+ T lymphocyte subsets were significantly lower in non-survivors. Serum levels of interleukin-6 (IL-6), lactate dehydrogenase (LDH), C-reactive protein (CRP) and procalcitonin (PCT) were significantly higher in non-survivors. Age > 65 years and presence of comorbidities were identified as independent risk factors associated with in-hospital mortality, while IL-6 and LDH showed a borderline significance. According to our results, markers of inflammation and lymphocytopenia predict in-hospital mortality in COVID-19.

Hemp Seed Oil in Association with ß-Caryophyllene, Myrcene and Ginger Extract as a Nutraceutical Integration in Knee Osteoarthritis: A Double-Blind Prospective Case-Control Study.

Background and Objectives: Nutraceuticals are gaining more and more importance as a knee osteoarthritis (KOA) complementary treatment. Among nutraceuticals, hemp seed oil and terpenes are proving to be very useful as therapeutic support for many chronic diseases, but there are still few studies regarding their effectiveness for treating KOA, both in combination and separately. The aim of this study is thus to compare the effect of two dietary supplements, both containing hemp seed oil, but of which only one also contains terpenes, in relieving pain and improving joint function in patients suffering from KOA. Materials and Methods: Thirty-eight patients were recruited and divided into two groups. The control group underwent a 45 day treatment with a hemp seed oil-based dietary supplement, while the treatment group assumed a hemp seed oil and terpenes dietary supplement for the same period. Patients were evaluated at the enrollment (T0) and at the end of treatment (T1). Outcome measures were: Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), Short-Form-12 (SF-12), Knee Injury Osteoarthritis Outcome Score (KOOS), and Oxford Knee Score (OKS). Results: All outcome measures improved at T1 in both groups, but NRS, KOOS and OKS had a greater significant improvement in the treatment group only. Conclusions: Hemp seed oil and terpenes resulted a more effective integrative treatment option in KOA, improving joint pain and function and representing a good complementary option for patients suffering from osteoarthritis.

Turner Syndrome Mosaicism 45,X/46,XY with Genital Ambiguity and Duchenne Muscular Dystrophy: Translational Approach of a Rare Italian Case.

Turner syndrome (gonadal dysgenesis with short stature and sterility) is characterized by chromosomal karyotype 45,X in 50% of cases or by mosaicism (45,X/46,XX and 45,X/46,XY) in 30-40% or X structural defects (deletions, long arm isochromosome, ring chromosome). When mosaic Turner syndrome (TS) occurs with a Y chromosome, there may be ambiguous genitalia. Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disease with an X-Linked recessive pattern of inheritance that predominantly affects males, while females are usually asymptomatic. DMD has also been observed in groups of females affected by TS, not homozygous for the mutation. Here, we report a case of an Indian neonate born with ambiguous genitalia diagnosed prenatally by ultrasound who had a karyotype of 45,X/46,XY and who also had Duchenne muscular dystrophy caused by a de novo mutation in the DMD gene. Physical examination was normal without the typical dysmorphic features of TS with the exception of the genitourinary system showing ambiguous genitalia. Gender was assigned as female. At the age of three years, she had increasing difficulty walking, running, jumping and climbing stairs, proximal upper and lower extremity muscle weakness and a positive Gowers' sign. In addition, the serum creatine kinase (CK) value was over 30X the upper limit of normal. This study shows that DMD can occur in females with TS having 45,X/46,XY mosaicism and that this coexistence should be considered in women affected by TS who start to develop potential typical symptoms such as motor or developmental delay.

The Usefulness of Synovial Fluid Proteome Analysis in Orthopaedics: Focus on Osteoarthritis and Periprosthetic Joint Infections.

Synovial fluid (SF) is a viscous and mucinous substance produced by the synovium, a specialized connective tissue that lines diarthrodial joints. SF represents a source of disease-related proteins that could be used as potential biomarkers in several articular diseases. Based on these findings the study of SF has been gaining increasing importance, in recent years. This review aims to summarize the usefulness of synovial fluid in orthopaedics research and clinical practice, mainly focusing on osteoarthritis (OA) and periprosthetic joint infections (PJIs). Proteomics of the SF has shown the up-regulation of several components of the classic complement pathway in OA samples, including C1, C2, C3, C4A, C4B, C5, and C4 C4BPA, thus depicting that complement is involved in the pathogenesis of OA. Moreover, proteomics has demonstrated that some pro-inflammatory cytokines, namely IL-6, IL-8, and IL-18, have a role in OA. Several SF proteins have been studied to improve the diagnosis of PJIs, including alpha-defensin (Alpha-D), leukocyte esterase (LE), c-reactive protein (CRP), interleukin-6 (IL-6), calprotectin and presepsin. The limits and potentials of these SF biomarkers will be discussed.

Lactobacillus crispatus M247 oral administration: Is it really an effective strategy in the management of papillomavirus-infected women?

BACKGROUND: Recent studies have shown the importance of the microbiota in women's health. Indeed, the persistence of Human Papilloma Virus (HPV)-related lesions in patients with dysbiosis can be the antechamber to cervical cancer. The aim of this study was to evaluate whether long term administration of oral Lactobacillus crispatus can restore eubiosis in women with HPV infections and hence achieve viral clearance. METHODS: In total, 160 women affected by HPV infections were enrolled at the Department of Gynecological Obstetrics of "San Paolo" Hospital, Italy between February 2021 and February 2022. The women were randomly assigned to two groups, one in treatment with oral Lactobacillus crispatus M247 (group 1, n = 80) versus the control group, that hence only in follow-up (Group 2, n = 80). RESULTS: After a median follow-up of 12 months (range 10-30 months), the likelihood of resolving HPV-related cytological anomalies was higher in patients in treatment with the long term oral probiotic (group 1) versus the group that perfom only follow-up (group 2) (60.5% vs. 41.3%, p = 0.05). Total HPV clearance was shown in 9.3% of patients undergoing only follow-up compared to 15.3% of patients in the group taking long term oral Lactobacillus crispatus M247 (p = 0.34). However, the percentage of HPV-negative patients, assessed with the HPV-DNA test, documented at the end of the study period was not significantly different from the control group. CONCLUSIONS: Despite the limitations of our analysis, we found a higher percentage of clearance of PAP-smear abnormalities in patients who took long term oral Lactobacillus crispatus M247 than in the control group. Larger studies are warranted, but we believe that future research should be aimed in this direction. Trial registration This study is retrospectively registered.

SARS-CoV-2 Vaccines and Adverse Effects in Gynecology and Obstetrics: The First Italian Retrospective Study.

The most common effects reported by the Italian Medicine Agency following administration of SARS-CoV-2 vaccine are myalgia, soreness to the arm of inoculation, fever, and asthenia. To date, there are no specific and official reports registered by the Italian Medicine Agency on possible alterations of the menstrual cycle, or of the female reproductive system, following the vaccine. Actually, clinical experience showed a spread of transient adverse drug reactions of the menstrual cycle, following the administration of all COVID-19 vaccine types, both mRNA and Adenovirus vectored ones. In this work, we conducted the first retrospective study on Italian patients vaccinated for SARS-CoV-2 in the period between April 2021 and April 2022, to report the onset of menstrual changes after the vaccine in order to understand: etiology, duration of possible adverse effects, and the extent of the phenomenon. We recruited 100 women aged 18-45, vaccinated for SARS-CoV-2, who were asked to complete a questionnaire consisting of 12 multiple choice questions about the effects of the vaccine on the reproductive system. Thirty-seven of them received three doses of the vaccine, while the remaining 63 received two doses. Symptoms such as delayed menstruation and abnormal uterine bleeding (metrorrhagia, menometrorrhagia, and menorrhagia) were generally reported within the first three weeks of vaccination, especially after the second dose, with a percentage of 23% and 77%, respectively. These preliminary data suggest that this problem may be broader and deserving of further investigation in the future.

Update on COVID-19 and Effectiveness of a Vaccination Campaign in a Global Context.

The COVID-19 pandemic caused by SARS-CoV-2 remains a significant issue for global health, the economy, and society. When SARS-CoV-2 began to spread, the most recent serious infectious disease of this century around the world, with its high morbidity and mortality rates, it is understandable why such infections have generally been spread in the past, mainly from international travel movements. This perspective review aimed to provide an update for clinicians on the recent developments related to the microbiological perspectives in pandemics, diagnostics, prevention (such as the spread of a virus), vaccination campaigns, treatment options, and health consequences for COVID-19 based on the current literature. In this way, the authors attempt to raise awareness on the transversal nature of these challenges by identifying the main risk/vulnerability factors that the scientific community must face including our current knowledge on the virus capacity of the mechanism of entry into the cells, the current classifications of viral variants, the knowledge of the mathematical model on the spread of viruses (the possible routes of transmission), and the effectiveness of vaccination campaigns in a global context of pandemic, particularly from COVID-19, with a look at new or future vaccines.

Communications Is Time for Care: An Italian Monocentric Survey on Human Papillomavirus (HPV) Risk Information as Part of Cervical Cancer Screening.

Human papilloma virus (HPV) infection could be considered a social disease, both for its high incidence, especially in younger subjects, and for the risk of neoplastic evolution linked to viral infection. Therefore, the National Health System, in collaboration with the state, must help women to understand the oncological risk of HPV and suitable methods of prevention. We conducted an Italian monocentric survey on HPV risk information as part of cervical cancer screening. An anonymous questionnaire was administered to 200 women with high-risk positive HPV and low-grade cervical lesions during second-level cervical cancer screening at the Gynecology and Obstetrics Unit of the "San Paolo" Hospital. From this survey, the need to improve communication for patients has emerged, as currently it is not exhaustive. In response to this need, organizational changes have been implemented to centralize the moment of counseling in the second levels of screening and to improve the training of health workers in level I as well as family doctors. In addition, psychological support was also proposed to patients who requested it, as was the dissemination of material such as that produced by GISCI (Italian Cervico-Carcinoma Screening Group) and updated in May 2018, which provides 100 answers to questions on HPV in order to achieve effective and comprehensive communication. This investigation requires further development, and the expansion of this investigation to the multicenter level is already underway. Therefore, this survey will represent a cornerstone for further discussion on the topic considering the necessity of appropriate communication in the oncological context.

Does miR-197 Represent a Valid Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma (HNSCC)? A Systematic Review and Trial Sequential Analysis.

(1) Background: Between tumors of the head and neck region, the squamous cell variant (HNSCC) is the most common and represents one of the main neoplasms affecting humans. At the base of carcinogenesis processes, there are genetic alterations whose regulation can be influenced by changes in the expression of microRNA (miR). Consequently, despite recent studies indicating miR-197 as a potential prognostic biomarker of survival for many varieties of cancer, there are currently no systematic reviews and trial sequential/bioinformatics/meta-analysis regarding the role of miR-197 in HNSCC. Our hypothesis was that with the existing literature, it is possible to clarify whether the different expressions of miR-197 in neoplastic tissues can represent a prognostic biomarker of survival in head and neck tumors. (2) Methods: The systematic review was reported following the indications of PRISMA and by consulting six electronic databases (including one register). Moreover, this review was carried out using the Kaplan-Meier plotter database portal, and hazard ratio (HR) data were extracted. Finally, a trial sequential analysis (TSA) was conducted to test the robustness of the proposed meta-analysis. (3) Results: This search identified 1119 articles and outcomes of the meta-analysis, reporting an aggregate HR for overall survival (OS) between the highest and lowest miR-197 expression of 1.01, 95% CI: [1.00, 1.02]. (4) Conclusions: We can state that, from the literature data included in the present meta-analysis, and from the TSA and bioinformatics analysis data, miR-197 does not currently represent a valid prognostic biomarker for HNSCC, although the data provided by the Kaplan-Meier plotter suggest that miR-197 can serve as a putative biomarker in short-term (5 years) survival.

Effects of Oral Supplementation with Myo-Inositol and D-Chiro-Inositol on Ovarian Functions in Female Long-Term Survivors of Lymphoma: Results from a Prospective Case-Control Analysis.

The progressive improvement of lymphoma treatment has led to an important prolongation of patient survival and life expectancy. The principal international scientific societies of oncology now therefore recommend that long-term survivors of lymphoma join fertility programs. Specifically, fertile-age patients should be assisted by a multidisciplinary team, including specialists dedicated to fertility preservation in oncology, in order to support the completion of their reproductive project. In the general population, the use of Myo-Inositol and D-Chiro-Inositol (MI/DCI) has been demonstrated to be an effective choice to treat ovarian dysfunctions, with a consequent improvement in reproductive outcomes, so it may represent an adjuvant strategy for this purpose. We therefore conducted a pilot prospective case-control study to evaluate the potentialities of this nutritional supplement, with the aim of optimizing reproductive function in female long-term survivors of lymphoma. One group underwent oral supplementation with MI 1200 mg and DCI 135 mg per day for 12 months, compared with controls who underwent no treatment in the same period. After 12 months, FSH, LH, and progesterone levels, as well as oligomenorrhea and antral follicle count (AFC), were significantly improved in the MI/DCI group. In addition, a significantly higher mean value in FSH and LH and a significantly lower mean AFC value in the right ovary were observed in controls compared to the MI/DCI group. Despite the need for further investigation, MI/DCI could be considered a potential adjuvant strategy to restore ovarian function in female long-term survivors of lymphoma.

Antibiotic Abuse and Antimicrobial Resistance in Hospital Environment: A Retrospective Observational Comparative Study.

Background and Objectives: Antimicrobial resistance represents a serious problem, and it may be life-threatening in the case of severe hospital-acquired infections (HAI). Antibiotic abuse and multidrug resistance (MDR) have significantly increased this burden in the last decades. The aim of this study was to investigate the distribution and susceptibility rates of five selected bacterial species (E. coli, K. pneumoniae, P. aeruginosa, S. aureus and E. faecium) in two healthcare settings located in the Apulia region (Italy). Materials and Methods: Setting n.1 was a university hospital and setting n.2 was a research institute working on oncological patients. All the enrolled patients were diagnosed for bacterial HAI. The observation period was between August and September 2021. Clinical samples were obtained from several biological sources, in different hospital wards. Bacterial identification and susceptibility were tested by using the software VITEC 2 Single system. Results: In this study, a higher incidence of multi-drug-resistant K. pneumoniae was reported (42,2% in setting n.1 and 50% in setting n.2), with respect to the Italian 2019 statistics report (30.3%). All the isolates of E. faecium and S. aureus were susceptible to linezolid. All the bacterial isolates of P. aeruginosa and most of K. pneumoniae were susceptible to ceftazidime-avibactam. Amikacin and nitrofurantoin represented a good option for treating E. coli infections. Multidrug-resistant (MDR) P. aeruginosa, methicillin-resistant S. aureus (MRSA) and vancomycin-resistantE. faecium (VRE) had a lower incidence in the clinical setting, with respect to E. coli and K. pneumoniae. Conclusions: The data obtained in this study can support clinicians towards a rational and safe use of antibiotics for treating the infections caused by these resistant strains, to enhance the overall efficacy of the current antibiotic protocols used in the main healthcare environments.

The Thousand Faces of Malignant Melanoma: A Systematic Review of the Primary Malignant Melanoma of the Esophagus.

Primary Malignant Melanoma of the Esophagus (PMME) is an extremely rare cancer of the esophagus, accounting for 0.1−0.8% of all oro-esophageal cancers and <0.05% of all melanoma subtypes, with an estimated incidence of 0.0036 cases per million/year. We conduct a careful analysis of the literature starting from 1906 to the beginning of 2022, searching the PubMed, Science.gov, Scopus and Web of Science (WoS) databases. A total of 457 records were initially identified in the literature search, of which 17 were duplicates. After screening for eligibility and inclusion criteria, 303 publications were ultimately included, related to 347 patients with PMME. PMME represents a very rare entity whose very existence has been the subject of debate for a long time. Over time, an increasing number of cases have been reported in the literature, leading to an increase in knowledge and laying the foundations for a discussion on the treatment of this pathology, which still remains largely represented by surgery. In recent times, the possibility of discovering greater mutations in gene hotspots has made it possible to develop new therapeutic strategies of which nivolumab is an example. Future studies with large case series, with clinicopathological and molecular data, will be necessary to improve the outcome of patients with PMME.

Nutrition as Personalized Medicine against SARS-CoV-2 Infections: Clinical and Oncological Options with a Specific Female Groups Overview.

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is acknowledged that vulnerable people can suffer from mortal complications of COVID-19. Therefore, strengthening the immune system particularly in the most fragile people could help to protect them from infection. First, general nutritional status and food consumption patterns of everyone affect the effectiveness of each immune system. The effects of nutrition could impact the level of intestinal and genital microbiota, the adaptive immune system, and the innate immune system. Indeed, immune system cells and mediators, which are crucial to inflammatory reaction, are in the structures of fats, carbohydrates, and proteins and are activated through vitamins (vit) and minerals. Therefore, the association of malnutrition and infection could damage the immune response, reducing the immune cells and amplifying inflammatory mediators. Both amount and type of dietary fat impact on cytokine biology, that consequently assumes a crucial role in inflammatory disease. This review explores the power of nutrition in the immune response against COVID-19 infection, since a specific diet could modify the cytokine storm during the infection phase. This can be of vital importance in the most vulnerable subjects such as pregnant women or cancer patients to whom we have deemed it necessary to dedicate personalized indications.

Testicular Immunity and Its Connection with the Microbiota. Physiological and Clinical Implications in the Light of Personalized Medicine.

Reproduction is a complex process, which is based on the cooperation between the endocrine-immune system and the microbiota. Testicular immunity is characterized by the so-called immune privilege, a mechanism that avoids autoimmune attacks against proteins expressed by spermatozoa. Testicular microbiota is connected with the gut microbiota, the most prevalent site of commensals inthe body. Both microbiotas take part inthe development of the immune system and protection againstpathogen invasion. Dysbiosis is caused by concurrent pathologies, such as obesity, diabetes, infections and trauma. The substitution of beneficial bacteria with pathogens may lead to destruction of spermatozoa directly or indirectly and, ultimately, to male infertility. Novel therapeutic interventions, i.e., nutritional interventions and supplementation of natural products, such as, probiotics, prebiotics, antioxidants and polyphenols, may lead to the restoration of the otherwise-impaired male reproductive potential, even if experimental and clinical results are not always concordant. In this review, the structure and immune function of the testis will be described with special reference to the blood-testisbarrier. The regulatory role of both the gut and testicular microbiota will be illustrated in health and disease, also emphasizing therapeutic attempts with natural products for the correction of male infertility, in the era of personalized medicine.

Potential Role of miR-196a and miR-196b as Prognostic Biomarkers of Survival in Head and Neck Squamous Cell Carcinoma: A Systematic Review, Meta-Analysis and Trial Sequential Analysis.

The etiopathogenetic mechanisms involving tumor genesis, including alteration of cell proliferation, apoptosis, invasion, migration, and death, may lead to alterations in microRNAs (miR) expression. The hypothesis is that with the presence in the literature of recent studies conducted on miR-196a and miR-196b, it is possible to clearly determine, by aggregating the results, whether miR-196 upregulation in head and neck squamous cell carcinoma (HNSCC) tissues can represent a prognostic biomarker of survival through hazard ratio (HR) analysis. The systematic review was conducted following the indications of the PRISMA, and four electronic databases were used (Science Direct, SCOPUS, PubMed, and Cochrane Central), with the addition of gray literature. Combinations of keywords were used, such as miR-196, miR-196 AND HNSCC, microRNA AND HNSCC, LSCC AND miR-196, OSCC AND miR-196, OPSCC AND miR-196, HSCC AND miR-196. The meta-analysis and trial sequential analysis (TSA) were performed using RevMan 5.41 software and Stata 13 (StataCorp, College Station, TX, USA) with the implementation of the R 4.2 software. This search identified 1593 reports and, at the end of the selection, five articles were inserted. The results of the meta-analysis report an aggregate HR for overall survival (OS), between the highest and lowest miR-196 expression of 1.67, 95% CI: [1.16, 2.49]. In this meta-analysis, we found that the forest plot is in favor of higher OS in HNSCC patients, compared with the control, with low miR-196 expression, correlating this data with a favorable prognosis, which indicated the potential role of this miRNA in strengthening the therapy sensitiveness of the HNSCC patients. Consequently, the present systematic review places itself, together with other systematic reviews on this topic, in a key role to the finding of Phase 3 clinical trials studies, in search for a prognostic model of miR-196 for HNSCC. In conclusion, with the limitations of the meta-analysis, it can be argued that miRs of the miR-196 family could be independent prognostic biomarkers of survival for HNSCC.