Evaluating the sociodemographic, anthropometric and lifestyle parameters, depression, quality of life, cognitive status, physical activity, and Mediterranean diet adherence of older adults in pre- and post-Covid-19 periods: a comparative cross-sectional study.

Ojective: Covid-19 pandemic has exerted deleterious effects on several aspect of mental health worldwide. The detrimental medical complications, the increased prevalence of morbidity and the rapid international spread of Covid-19 have resulted in urgent public health concerns and political measures across the world. This comparative, cross-sectional study aims to assess the changes that were established in sociodemographic, anthropometric and lifestyle parameters and several aspects of mental health of older adults due to Covid-19 pandemic by comparing the pre-Covid period with the post-Covid period. Methods: Qualified questionnaires were applied for assessing the prevalence of depression, quality of life, cognitive status, and Mediterranean Diet (MD) adherence, as well as sociodemographic, anthropometric and lifestyle parameters in 3388 older adults in the pre- and post-Covid period. Results: Covid-19 pandemic independently affected type of residence, smoking habits, BMI and WHR status, risk of depression, quality of life, cognitive status, physical activity levels, and MD adherence. Conclusions: Covid -19 pandemic has exerted persistent detrimental effects on daily quality of life and mental health of older adults in the post-Covid period. Future strategies and public policies should develop healthcare programs to provide psychological and nutritional counseling and support to older adults to minimize the detrimental effects of Covid pandemic.

Association of Mediterranean diet adherence with disease progression, quality of life and physical activity, sociodemographic and anthropometric parameters, and serum biomarkers in community-dwelling older adults with multiple sclerosis: a cross-sectional study.

BACKGROUND: Multiple sclerosis (MS) constitutes a chronic inflammatory and degenerative demyelinating disease, which can progressively lead to a broad range of sensorimotor, cognitive, visual, and autonomic function symptoms, independently of patient' age. However, the clinical studies that examine the role of dietary patterns against disease progression and symptomatology remain extremely scarce, especially concerning Mediterranean diet (MD) in the subgroup age of older adults with MS. AIMS: The present study aimed to investigate the potential impact of MD compliance in disease progression and symptoms severity as well as quality of life and physical activity of community-dwelling older adults with MS. METHODS: This is a cross-sectional conducted on 227 older adults with no history of other severe disease. Relevant questionnaires were applied to collect sociodemographic and anthropometric factors by face-to face interviews between patients and qualified personnel. Serum biomarkers were retrieved by patients' medical records. RESULTS: Higher MD compliance was independently associated with younger patients' age, lower risk of overweight/obesity and abdominal obesity, decreased disease progression and higher muscle mass, as well as greater physical activity, better quality of life, and adequate serum ferritin and albumin levels CONCLUSIONS: MD may exert beneficial effects in older adults with MS. Future strategies and policies are highly recommended to inform both the general population and the older patients with MS for the beneficial effects of MD in preventing MS and in improving or even slowing down the disease progression and symptoms severity of MS.

Associations between Mediterranean Diet Adherence, Quality of Life, and Mental Health in Patients with Multiple Sclerosis: A Cross-Sectional Study.

BACKGROUND: The Mediterranean diet (MD) is well-known as a diet which may exert a protective effect against neurodegenerative diseases, including multiple sclerosis (MS). To date, only a few clinical surveys have assessed the potential effects of the MD in patients with MS. The purpose of the present study is to evaluate the potential effects of MD compliance on disease disability, quality of life, physical activity, depressive symptomatology, and blood biochemical parameters related to nutritional status in MS patients, considering several socio-demographic, anthropometric, and lifestyle characteristics. METHODS: This is a cross-sectional study conducted on 558 adults with MS aged 18-64 years. Relevant questionnaires were utilized to evaluate socio-demographic and anthropometric parameters, disease disability (Expanded Disability Status Scale, EDSS), multidimensional health-related quality (MS Quality of Life-54, MSQOL-54), physical activity levels (International Physical Activity Questionnaire, IPAQ), depression (Beck Depression Inventory II, BDI-II), and MD adherence (MedDietScore), while several blood biochemical parameters were retrieved from the patients' medical records. RESULTS: Enhanced MD compliance was independently associated with a decreased frequency of overweight/obesity, as well as abdominal obesity, in patients suffering from MS. Elevated MD compliance was also independently associated with a decreased incidence of advanced disease disability, a higher prevalence of elevated physical activity, an improved quality of life, and lower depressive symptoms, as well as higher levels of certain blood biochemical parameters, which are effective indicators of iron deficiency and malnutrition. CONCLUSIONS: The present study found that higher MD adherence may slow down disease disability, promoting a better quality of life and mental health in adults with MS. Future prospective surveys are required to obtain conclusive results.

Nutritional interventional studies in patients with multiple sclerosis: a scoping review of the current clinical evidence.

A good nutritional status appears to slow down disease progression and ameliorate symptoms' intensity in patients with multiple sclerosis (MS). Up to date, there are several interventional studies, which have explored the potential beneficial effects of specific dietary patterns as well as specific bioactive nutrients against disease progression and symptomatology of MS patients. This is a thorough, scoping review, which aims to critically summarize and scrutinize the currently available clinical evidence of the potential beneficial effects of nutritional interventional studies against MS progression and symptomatology. This review was conducted to systematically map the research done in this area, as well as to identify gaps in knowledge. For this purpose, we thoroughly explored the most accurate scientific web databases, e.g., PubMed, Scopus, Web of Science, and Google Scholar to achieve the most relevant clinical human studies applying effective and characteristic keywords. There are currently several dietary patterns and specific bioactive nutrients that show promising results by slowing down disease progression and by improving MS symptoms. However, there are also certain conflicting results, while most of the existing studies enrolled a small number of MS patients. Nutritional interventions may exert substantial protective effects against MS progression and symptomatology. However, large, long-term, randomized, double-blind, controlled clinical trials with a prospective design are strongly recommended to delineate whether such nutritional intervention may attenuate disease progression, and improve symptomatology in MS patients.

Association of Higher Mediterranean Diet Adherence With Lower Prevalence of Disability and Symptom Severity, Depression, Anxiety, Stress, Sleep Quality, Cognitive Impairment, and Physical Inactivity in Older Adults With Multiple Sclerosis.

A good nutritional status and healthy diets may decelerate disease disability and symptom severity and quality of life of peoples with multiple sclerosis (MS). Mediterranean diet (MD) can prevent several chronic diseases, including neurodegenerative disease. This is an observational, cross-sectional study on 279 older adults with MS, aiming to investigate the effects of MD against several aspects of mental health. Qualified questionnaires were used to assess disability and symptom severity, depression, anxiety, stress, sleep quality, cognitive status, physical activity, and MD adherence. Multivariate analysis showed that enhanced MD adherence was independently associated with lower prevalence of disability and symptom severity (P = .0019), depression (P = .0201), anxiety (P = .0287), perceived stress (P = .0021), inadequate sleep quality (P = .0033), cognitive impairment (P = .0018) and physical inactivity (P = .0028). Adopting MD may ameliorate mental health disturbances in older adults with MS. Future public health policies should inform older adults with MS for the favorable impacts of MD in improving the mental health MS comorbidities.

Aetiology of Community-Acquired Pneumonia and the Role of Genetic Host Factors in Hospitalized Patients in Cyprus.

Community-acquired pneumonia (CAP) remains the leading cause of hospitalization among infectious disease in Europe, and a major cause of morbidity and mortality. In order to determine and characterize the aetiology of CAP in hospitalized adults in Cyprus, respiratory and blood samples were obtained from hospitalized patients with CAP, and analyzed using Multiplex Real-Time PCR/RT-PCR, and ID/AMR enrichment panel (RPIP) analysis. Probe-based allelic discrimination was used to investigate genetic host factors in patients. The aetiology could be established in 87% of patients. The most prevalent viral pathogens detected were influenza A, SARS-CoV-2, and human rhinovirus. The most common bacterial pathogens detected were Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. Antimicrobial resistance genes were identified in 23 patients. S. aureus was the most common AMR correlated strain in our study. A positive correlation was detected between bacterial infections and the NOS3 rs1799983 G allele and the FCGR2A rs1801274 G allele. A positive correlation was also detected between the TNF-α rs1800629 A allele and sepsis, while a negative correlation was detected with the ACE rs1799752 insertion genotype and the severity of pneumonia. In conclusion, the targeted NGS panel approach applied provides highly sensitive, comprehensive pathogen detection, in combination with antimicrobial resistance AMR insights that can guide treatment choices. In addition, several host factors have been identified that impact the disease progression and outcome.

AAV9-mediated SH3TC2 gene replacement therapy targeted to Schwann cells for the treatment of CMT4C.

Type 4C Charcot-Marie-Tooth (CMT4C) demyelinating neuropathy is caused by autosomal recessive SH3TC2 gene mutations. SH3TC2 is highly expressed in myelinating Schwann cells. CMT4C is a childhood-onset progressive disease without effective treatment. Here, we generated a gene therapy for CMT4C mediated by an adeno-associated viral 9 vector (AAV9) to deliver the human SH3TC2 gene in the Sh3tc2-/- mouse model of CMT4C. We used a minimal fragment of the myelin protein zero (Mpz) promoter (miniMpz), which was cloned and validated to achieve Schwann cell-targeted expression of SH3TC2. Following the demonstration of AAV9-miniMpz.SH3TC2myc vector efficacy to re-establish SH3TC2 expression in the peripheral nervous system, we performed an early as well as a delayed treatment trial in Sh3tc2-/- mice. We demonstrate both after early as well as following late treatment improvements in multiple motor performance tests and nerve conduction velocities. Moreover, treatment led to normalization of the organization of the nodes of Ranvier, which is typically deficient in CMT4C patients and Sh3tc2-/- mice, along with reduced ratios of demyelinated fibers, increased myelin thickness and reduced g-ratios at both time points of intervention. Taken together, our results provide a proof of concept for an effective and potentially translatable gene replacement therapy for CMT4C treatment.

Introduction, Spread and Impact of the SARS-CoV-2 Omicron Variants BA.1 and BA.2 in Cyprus.

The aim of this study was to investigate and obtain insights into the appearance, spread and impact of the Omicron variants and their sub-lineages in Cyprus by analyzing 611 high-coverage full-genome sequences for the period from November 2021 until April 2022. All viruses sequenced were identified to belong to either Delta (B.1.617.2) or Omicron (lineage BA.1 and BA.2, respectively), with a variety of different sub-lineages. A detailed analysis of the mutational profile is presented and discussed. The Omicron variant BA.1 was shortly followed by BA.2; despite emerging against a background of high vaccination (81% of adult population) and pre-existing natural immunity, they gave rise to the largest waves of infection, with daily numbers rising dramatically, highlighting their increased ability for immune evasion. Within a period of only five months, the percentage of the Cypriot population with a confirmed infection increased from ~15% of the total population to >57%. Despite unprecedented case numbers, a significant reduction in hospital burden and mortality was observed. Our findings highlight the role of the importation of new variants through travel and demonstrate the importance of genomic surveillance in determining viral genetic diversity and the timely identification of new variants for guiding public health intervention measures.

A translatable RNAi-driven gene therapy silences PMP22/Pmp22 genes and improves neuropathy in CMT1A mice.

Charcot-Marie-Tooth disease type 1A (CMT1A), the most common inherited demyelinating peripheral neuropathy, is caused by PMP22 gene duplication. Overexpression of WT PMP22 in Schwann cells destabilizes the myelin sheath, leading to demyelination and ultimately to secondary axonal loss and disability. No treatments currently exist that modify the disease course. The most direct route to CMT1A therapy will involve reducing PMP22 to normal levels. To accomplish this, we developed a gene therapy strategy to reduce PMP22 using artificial miRNAs targeting human PMP22 and mouse Pmp22 mRNAs. Our lead therapeutic miRNA, miR871, was packaged into an adeno-associated virus 9 (AAV9) vector and delivered by lumbar intrathecal injection into C61-het mice, a model of CMT1A. AAV9-miR871 efficiently transduced Schwann cells in C61-het peripheral nerves and reduced human and mouse PMP22 mRNA and protein levels. Treatment at early and late stages of the disease significantly improved multiple functional outcome measures and nerve conduction velocities. Furthermore, myelin pathology in lumbar roots and femoral motor nerves was ameliorated. The treated mice also showed reductions in circulating biomarkers of CMT1A. Taken together, our data demonstrate that AAV9-miR871-driven silencing of PMP22 rescues a CMT1A model and provides proof of principle for treating CMT1A using a translatable gene therapy approach.

Molecular epidemiology of SARS-CoV-2 in Cyprus.

Whole genome sequencing of viral specimens following molecular diagnosis is a powerful analytical tool of molecular epidemiology that can critically assist in resolving chains of transmission, identifying of new variants or assessing pathogen evolution and allows a real-time view into the dynamics of a pandemic. In Cyprus, the first two cases of COVID-19 were identified on March 9, 2020 and since then 33,567 confirmed cases and 230 deaths were documented. In this study, viral whole genome sequencing was performed on 133 SARS-CoV-2 positive samples collected between March 2020 and January 2021. Phylogenetic analysis was conducted to evaluate the genomic diversity of circulating SARS-CoV-2 lineages in Cyprus. 15 different lineages were identified that clustered into three groups associated with the spring, summer and autumn/winter wave of SARS-CoV-2 incidence in Cyprus, respectively. The majority of the Cypriot samples belonged to the B.1.258 lineage first detected in September that spread rapidly and largely dominated the autumn/winter wave with a peak prevalence of 86% during the months of November and December. The B.1.1.7 UK variant (VOC-202012/01) was identified for the first time at the end of December and spread rapidly reaching 37% prevalence within one month. Overall, we describe the changing pattern of circulating SARS-CoV-2 lineages in Cyprus since the beginning of the pandemic until the end of January 2021. These findings highlight the role of importation of new variants through travel towards the emergence of successive waves of incidence in Cyprus and demonstrate the importance of genomic surveillance in determining viral genetic diversity and the timely identification of new variants for guiding public health intervention measures.

Association of Epstein-Barr virus latently expressed genes with multiple sclerosis.

BACKGROUND: Despite mounting evidence supporting an etiologic role for Epstein-Barr virus (EBV) in multiple sclerosis (MS), the exact mechanisms through which the virus may contribute to disease development are still unknown. The aim of this study was to analyze seven highly polymorphic EBV latently expressed genes in individuals diagnosed with MS in comparison to healthy controls (HC), to investigate the possible association of EBV variants with an individual's risk towards MS. METHODS: B-lymphocytes were isolated from MS patients (n = 30) and HC (n = 33) for the isolation of EBV genomic DNA. Sanger sequencing was employed to analyze EBV latent gene regions. RESULTS: A total of 26 variants were detected in our cohort, 17 of which were significantly associated with the MS group while nine were significantly associated with HC. Following the designation of EBV alleles based on these variants, MS risk was found to be significantly associated with the presence of the EBNA3B2.1 allele (p = 0.0008) and LMP1.1 allele (p = 0.01), whereas the EBNA1.3 allele (p = 0.005), EBNA2.1 allele (p = 0.001) as well as the EBNA3B2.2 allele (p = 0.0003) appeared to provide a protective role. CONCLUSIONS: This study indicates a marked association between EBV genetic variants and MS, lending further support towards possible molecular mechanisms through which EBV may contribute to disease development.

AAV9-mediated Schwann cell-targeted gene therapy rescues a model of demyelinating neuropathy.

Mutations in the GJB1 gene, encoding the gap junction (GJ) protein connexin32 (Cx32), cause X-linked Charcot-Marie-Tooth disease (CMT1X), an inherited demyelinating neuropathy. We developed a gene therapy approach for CMT1X using an AAV9 vector to deliver the GJB1/Cx32 gene under the myelin protein zero (Mpz) promoter for targeted expression in Schwann cells. Lumbar intrathecal injection of the AAV9-Mpz.GJB1 resulted in widespread biodistribution in the peripheral nervous system including lumbar roots, sciatic and femoral nerves, as well as in Cx32 expression in the paranodal non-compact myelin areas of myelinated fibers. A pre-, as well as post-onset treatment trial in Gjb1-null mice, demonstrated improved motor performance and sciatic nerve conduction velocities along with improved myelination and reduced inflammation in peripheral nerve tissues. Blood biomarker levels were also significantly ameliorated in treated mice. This study provides evidence that a clinically translatable AAV9-mediated gene therapy approach targeting Schwann cells could potentially treat CMT1X.

Characterization of IgG Antibody Response against SARS-CoV-2 (COVID-19) in the Cypriot Population.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has hit its second year and continues to damage lives and livelihoods across the globe. There continues to be a global effort to present serological data on SARS-CoV-2 antibodies in different individuals. As such, this study aimed to characterize the seroprevalence of SARS-CoV-2 antibodies in the Cypriot population for the first time since the pandemic started. Our results show that a majority of people infected with SARS-CoV-2 developed IgG antibodies against the virus, whether anti-NP, anti-S1RBD, or both, at least 20 days after their infection. Additionally, the percentage of people with at least one antibody against SARS-CoV-2 in the group of volunteers deemed SARS-CoV-2 negative via RT-PCR or who remain untested/undetermined (14.43%) is comparable to other reported percentages worldwide, ranging anywhere from 0.2% to 24%. We postulate that these percentages reflect the underreporting of true infections in the population, and also show the steady increase of herd immunity. Additionally, we showed a significantly marked decrease in anti-NP IgG antibodies in contrast to relatively stable levels of anti-S1RBD IgG antibodies in previously infected individuals across time.

Mediterranean diet adherence is associated with better cognitive status and less depressive symptoms in a Greek elderly population.

PURPOSE: To evaluate the Mediterranean diet (MD) adherence of an elderly Greek population, and its association with the grade of cognitive decline and psychological status. METHODS: Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), and Mediterranean diet score (MedDietScore) questionnaires were used to assess the impact of MD adherence on cognitive abilities and psychological state of a Greek elderly population. PARTICIPANTS: 2092 men and women over 65 years old (mean age 74.97 ± 8.41 years) from seven different Greek cities RESULTS: 34.4% of the study population showed cognitive impairment, while 32.3% of the participants had depressive symptoms. More than half of the participants (52.1%) showed very low or low MD adherence. Higher MD adherence was significantly associated with better MMSE and GDS scores. Moreover, higher MD adherence was significantly associated with younger age, female gender, higher educational level, and better anthropometric parameters. MD adherence was independently associated with cognitive and psychological status, and gender after adjustment for potential confounders. CONCLUSION: Higher MD adherence is strongly associated with better cognitive status and less depressive symptomatology. Public health policies are recommended to focus on the promotion of the MD, as a crucial strategy to reduce the risk of cognitive impairment and depression.

Nutritional status is associated with the degree of cognitive impairment and depressive symptoms in a Greek elderly population.

Introduction: Cognitive impairment and malnutrition are two important public health issues in the elderly, which have been associated with their mental health.Aims: This study aims to evaluate the nutritional status of an elderly population in Greece, and its association with the grade of cognitive decline, anthropometric measures and psychological status.Materials and Methods: A total of 2092 elderly men and women were enrolled from seven Greek cities. Mini Nutritional Assessment (MNA), Mini Mental State Examination (MMSE) and Geriatric Depression Scale (GDS) questionnaires were used to assess the impact of nutritional status on cognitive abilities and psychological status of the participants.Results: Of the elderly, 35.0% were at risk of malnutrition and 11.3% were malnourished, while 34.4% of the participants had impaired cognitive function, and 32.3% showed depressive symptoms. Malnutrition was more frequently observed in participants presenting cognitive impairment, and depressive symptoms. In multiple regression analysis, nutritional status was independently associated with cognitive and psychological status.Conclusions: A high prevalence of malnutrition was recorded in this elderly population sample, which was directly associated with cognitive impairment and depression. Diagnostic tools such as MNA, MMSE, and GDS are strongly recommended to be applied as a routine clinical practice in the elderly to timely and effectively address these health problems.

Dietary Supplements on Controlling Multiple Sclerosis Symptoms and Relapses: Current Clinical Evidence and Future Perspectives.

Background: Multiple sclerosis (MS) constitutes a chronic progressive demyelinating disease which negatively affects the central nervous system. MS symptoms detrimentally affect the quality of life, as well as the life expectancy of MS patients. In this aspect, the present study aims to critically summarize and evaluate the currently available clinical studies focusing on the potential beneficial effects of dietary supplements on controlling MS symptomatology and relapse. Methods: PubMed database was comprehensively searched, using relative keywords to identify clinical trials that investigated the beneficial effects of dietary supplementation against MS symptomatology and progression. 40 clinical trials were found, which were divided into categories. Results: Nutritional status of MS patients, as well as supplementation have been suggested as potential factors affecting progression. Several substantial studies have documented a systematically high prevalence of vitamin A, B12 and D3 deficiency amongst MS patients. At present, clinical data have suggested that most of the dietary supplements under study may exert antioxidant and anti-inflammatory properties, improving depression symptomatology and quality of life overall. However, malnutrition risk in MS patients has not been adequately explored in order for more precise conclusions to be drawn. The supplements that may have a positive effect on MS are vitamins, fatty acids, antioxidants, phytochemicals and melatonin. Conclusions: Several dietary supplements may decrease inflammation and fatigue, also increasing also autoimmunity tolerance in MS patients, and thus improving quality of life and life expectancy. Currently, there is no effective clinical indication for applying dietary supplementation as complementary treatment against MS symptomatology.

Molecular epidemiology of enteroviruses in Cyprus 2008-2017.

Enteroviruses (EVs) are associated with a broad spectrum of disease manifestations, including aseptic meningitis, encephalitis, hand, foot and mouth disease, acute flaccid paralysis and acute flaccid myelitis with outbreaks being reported frequently world-wide. The aim of this study was the molecular characterization of all enteroviruses detected in Cyprus in the ten-year period from January 2008 and December 2017 as well as a description of the circulation patterns associated with the most frequently encountered genotypes. For this purpose, serum, cerebrospinal fluid, nasal swab, skin swab and/or stool samples from 2666 patients with a suspected EV infection were analysed between January 2008 and December 2017. Enteroviruses were detected in 295 (11.1%) patients, which were then investigated further for epidemiological analysis by VP1 genotyping. Overall, 24 different enterovirus types belonging to three different species were identified. The predominant species was EV-B (209/295, 71%), followed by species EV-A (77/295, 26.1%). Only one virus belonged to species EV-D, whereas EV-C enteroviruses were not identified at all. The most frequent genotypes identified were echovirus 30 (26.1%), echovirus 6 (14.2%) and coxsackievirus A6 (10.9%). While Echovirus 30 and echovirus 6 frequency was significantly higher in patients older than 3 years of age, the opposite was observed for CV-A16 and EV-A71, which dominated in young children less than 3 years. Importantly, for the current study period a significant increase of previously only sporadically observed EV-A types, such as EV-A71 and CV-A16 was noted. A phylogenetic analysis of EV-A71 showed that the majority of the EV-A71 strains from Cyprus belonged to sub-genogroup C1 and C2, with the exception of one C4 strain that was observed in 2011. The data presented provide a comprehensive picture of enteroviruses circulating in Cyprus over the last decade and will be helpful to clinicians and researchers involved in the treatment, prevention and control of enteroviral infections by helping interpret trends in enteroviral diseases by associating them with circulating serotypes, for studying the association of enteroviruses with clinical manifestations and develop strategies for designing future EV vaccines.

The Prevalence of Antibodies against Sandfly Fever Viruses and West Nile Virus in Cyprus.

BACKGROUND: Sandfly fever is an incapacitating disease caused by sandfly-borne Phleboviruses that can lead to meningitis, encephalitis or meningoencephalitis. West Nile virus (WNV), a mosquito-borne Flavivirus, can induce neuroinvasive disease manifested by meningitis, encephalitis or acute flaccid paralysis. Both vectors are endemic in Cyprus and very active during summer. The aims of this study were to determine first the prevalence of sandfly fever viruses (SFV) and WNV infections in Cyprus and second, to investigate their role in central nervous system (CNS) infections. METHODS: For the prevalence study, 327 sera collected in 2013 and 2014 were tested for anti-SFV and anti-WNV IgG using indirect immunofluorescence assay and ELISA, respectively. In order to investigate a possible role of SFV and WNV in CNS infections, 127 sera of patients presenting symptoms of SFV or WNV infections were screened for IgM specific to SFV and WNV. RESULTS: The overall anti-SFV IgG seroprevalence was 28% and was increasing with age (P< 0.01). The seroprevalence rate for anti-WNV IgG in Cyprus was 5%. Concerning the role of SFVs in CNS infections, anti-SFV IgM was detected in 8 out of 127 sera from selected patients presenting relevant symptoms of infections during vector's active period. In addition, anti-WNV IgM were detected in 17 out of the 127 patients with compatible symptoms. CONCLUSION: The findings confirm the presence of sandfly fever and WNV in Cyprus and should, therefore, be considered in the differential diagnosis of patients with febrile illness/meningitis.

Gene replacement therapy in a model of Charcot-Marie-Tooth 4C neuropathy.

Charcot-Marie-Tooth disease type 4C is the most common recessively inherited demyelinating neuropathy that results from loss of function mutations in the SH3TC2 gene. Sh3tc2-/- mice represent a well characterized disease model developing early onset progressive peripheral neuropathy with hypo- and demyelination, slowing of nerve conduction velocities and disturbed nodal architecture. The aim of this project was to develop a gene replacement therapy for treating Charcot-Marie-Tooth disease type 4C to rescue the phenotype of the Sh3tc2-/- mouse model. We generated a lentiviral vector LV-Mpz.SH3TC2.myc to drive expression of the human SH3TC2 cDNA under the control of the Mpz promoter specifically in myelinating Schwann cells. The vector was delivered into 3-week-old Sh3tc2-/- mice by lumbar intrathecal injection and gene expression was assessed 4-8 weeks after injection. Immunofluorescence analysis showed presence of myc-tagged human SH3TC2 in sciatic nerves and lumbar roots in the perinuclear cytoplasm of a subset of Schwann cells, in a dotted pattern co-localizing with physiologically interacting protein Rab11. Quantitative PCR analysis confirmed SH3TC2 mRNA expression in different peripheral nervous system tissues. A treatment trial was initiated in 3 weeks old randomized Sh3tc2-/- littermate mice which received either the full or mock (LV-Mpz.Egfp) vector. Behavioural analysis 8 weeks after injection showed improved motor performance in rotarod and foot grip tests in treated Sh3tc2-/- mice compared to mock vector-treated animals. Moreover, motor nerve conduction velocities were increased in treated Sh3tc2-/- mice. On a structural level, morphological analysis revealed significant improvement in g-ratios, myelin thickness, and ratios of demyelinated fibres in lumbar roots and sciatic nerves of treated Sh3tc2-/- mice. Finally, treated mice also showed improved nodal molecular architecture and reduction of blood neurofilament light levels, a clinically relevant biomarker for axonal injury/degeneration. This study provides a proof of principle for viral gene replacement therapy targeted to Schwann cells to treat Charcot-Marie-Tooth disease type 4C and potentially other similar demyelinating inherited neuropathies.

Wine: An Aspiring Agent in Promoting Longevity and Preventing Chronic Diseases.

INTRODUCTION: Moderate wine consumption is a characteristic of the Mediterranean diet. Studies around the world have shown a beneficial effect of moderate alcohol intake, especially wine, on health. This review aims to critically summarise the most recent studies that investigate the beneficial effects of moderate wine intake on human health. METHODS: The PubMed database was comprehensively searched to identify trials published from 2013 to 2018 that investigated the association between moderate wine consumption and health. RESULTS: The most recent studies confirm the valuable role of moderate wine consumption, especially red wine, in the prevention and treatment of chronic diseases such as cardiovascular disease, metabolic syndrome, cognitive decline, depression, and cancer. In the meantime, recent studies also highlight the beneficial role of red wine against oxidative stress and in favour of desirable gut bacteria. The beneficial role of red wine has been attributed to its phytochemical compounds, as highlighted by clinical trials, where the effect of red wine has been compared to white wine, non-alcoholic wine, other alcoholic drinks, and water. CONCLUSIONS: Moderate wine intake, at 1⁻2 glasses per day as part of the Mediterranean diet, has been positively associated with human health promotion, disease prevention, and disease prognosis.