Attitudes towards disclosure of familial genetic risk in a Mediterranean island population - A survey of the Maltese population.

Germline genetic testing has implications that extend beyond the individual patient to relatives, particularly for high-penetrance variants implicated in hereditary cancer or neurodegenerative syndromes. Many countries encourage patient-led communication to inform at-risk relatives, although the efficacy and uptake of this approach varies. Alternative scenarios envisage direct contact mediated by clinicians. The familial disclosure of sensitive genetic information is also determined by complex socio-ethnic factors. To date, no study has explored whether relatives would want to be informed of familial genetic risk and their preferences on different methods of communication in Malta. We thus used a published instrument that utilizes hypothetical scenario methodology to survey the attitudes of the Maltese population (n = 334) to receiving genetic information from family members. Two vignettes on Huntington's disease and colorectal cancer were presented. We also explored preferences towards the communication of genetic risk, confidentiality, and disclosure policies. Our preliminary results show that most respondents want to be informed of their increased risk by a family member or a clinician and would opt to receive confirmatory genetic testing. Most respondents preferred being informed of genetic risk by a close relative, but in the case of non-disclosure would want to be informed by a clinician. Most respondents expressed preference in favour of the introduction of registries, legislative change and sharing of contact details to address cases of nondisclosure. Our findings contribute further to evidence that supports, in selected hypothetical scenarios, an envisioned change in disclosure of genetic data policy by the public that is different from current practice to date.

Genotype-phenotype of autosomal dominant polycystic kidney disease in Malta.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple renal cysts causing kidney enlargement and end-stage renal disease (ESRD) in half the patients by 60 years of age. The aim of the study was to determine the genetic aetiology in Maltese patients clinically diagnosed with ADPKD and correlate the clinical features. METHODS: A total of 60 patients over 18 years of age clinically diagnosed with ADPKD were studied using a customized panel of genes that had sufficient evidence of disease diagnosis using next generation sequencing (NGS). The genes studied were PKD1, PKD2, GANAB, DNAJB11, PKHD1 and DZIP1L. Selected variants were confirmed by bidirectional Sanger sequencing with specifically designed primers. Cases where no clinically significant variant was identified by the customized gene panel were then studied by Whole Exome Sequencing (WES). Microsatellite analysis was performed to determine the origin of an identified recurrent variant in the PKD2 gene. Clinical features were studied for statistical correlation with genetic results. RESULTS: Genetic diagnosis was reached in 49 (82%) of cases studied. Pathogenic/likely pathogenic variants PKD1 and PKD2 gene were found in 25 and in 23 cases respectively. The relative proportion of genetically diagnosed PKD1:PKD2 cases was 42:38. A pathogenic variant in the GANAB gene was identified in 1 (2%) case. A potentially significant heterozygous likely pathogenic variant was identified in PKHD1 in 1 (2%) case. Potentially significant variants of uncertain significance were seen in 4 (7%) cases of the study cohort. No variants in DNAJB11 and DZIP1L were observed. Whole exome sequencing (WES) added the diagnostic yield by 10% over the gene panel analysis. Overall no clinically significant variant was detected in 6 (10%) cases of the study population by a customized gene panel and WES. One recurrent variant the PKD2 c.709+1G > A was observed in 19 (32%) cases. Microsatellite analysis showed that all variant cases shared the same haplotype indicating that their families may have originated from a common ancestor and confirmed it to be a founder variant in the Maltese population. The rate of decline in eGFR was steeper and progression to ESRD was earlier in cases with PKD1 variants when compared to cases with PKD2 variants. Cases segregating truncating variants in PKD1 showed a significantly earlier onset of ESRD and this was significantly worse in cases with frameshift variants. Overall extrarenal manifestations were commoner in cases segregating truncating variants in PKD1. CONCLUSIONS: This study helps to show that a customized gene panel is the first-line method of choice for studying patients with ADPKD followed by WES which increased the detection of variants present in the PKD1 pseudogene region. A founder variant in the PKD2 gene was identified in our Maltese cohort with ADPKD. Phenotype of patients with ADPKD is significantly related to the genotype confirming the important role of molecular investigations in the diagnosis and prognosis of polycystic kidney disease. Moreover, the findings also highlight the variability in the clinical phenotype and indicate that other factors including epigenetic and environmental maybe be important determinants in Autosomal Dominant Polycystic Kidney Disease.

[Dr Jean Languillon (1912-2003), a major unrecognized leprologist]. / Le Dr Jean Languillon (1912-2003), un léprologue majeur trop méconnu.

Languillon's contribution to the control of leprosy cannot be reduced to the manual of leprology which remains the reference for anyone working on this disease in sub-Saharan Africa. This would mean forgetting his works that established the immunological origin of leprosy and its cutaneous, adverse and neurological complications.Another major aspect, the importance of his contribution to the treatment of the disease, in particular through the development of polychimiotherapy (PCT), which has made Institut Marchoux in Bamako one of the five WHO's collaborating centers in the field of clinical research in leprosy.Languillon was also involved in a holistic approach of the disease by creating the first leprosy surgery unit and implementing physiotherapy, orthopedic care with appropriate equipment, and social rehabilitation… without forgetting preventive aspects of complications through the necessary regular administration of treatments, and control of patients spread over wide territories, by creating a corps of leprosy nurse monitors and leprosy specialists. These will provide essential support to the doctor most often in charge of a huge sector where the need of assistance was obvious.Languillon ended his African career by creating the ILAD, Institute of Applied Leprology in Dakar, which offers the full range of care, as he always advocated.Finally, he did not resist the call of Order of Malta which offered him to share his expertise in the different countries where the Order was involved.

Analysis of drying kinetic of brewer ́s spent grains: effect of the temperature on the physical properties and the content of bioactive compounds / Análisis de la cinética de secado del bagazo residual de malta: efecto de la temperatura sobre las propiedades físicas y el contenido de compuestos bioactivos

Background: Brewer ́s spent grain (BSG) is a biomass by-product generated in large volumes during industrial beer production. BSG has become a growing environmental problem, as most breweries discard it inappropriately, negatively impacting the environment. Alternatives for the exploitation of this by-product have consisted of elaborating food supplements for farm animals, obtaining biofuels, developing adsorbents, and obtaining substances for the food industry. However, the high moisture content in BSG (approximately 70%), poses a significant challenge in exploring various reuse alternatives. Therefore, the implementation of a pre-drying process becomes essential. Objective: This study aimed to analyze the BSG drying kinetics at different temperatures and the effect of the drying temperature on the physical properties and the content of bioactive compounds. Methods: BSG samples were dried at different temperatures (50, 60, 70, 80, 90, and 105°C) and analyzed for their moisture ratio, water activity, total polyphenol content (TPC), and DPPH (1,1-diphenyl-2-picrylhydrazil) radical scavenging activity. Also, four kinetics models were fitted to the drying data. Results:It was determined that the effective diffusivity was between 5.23x10

Antecedentes: El Bagazo residual de malta (BSG por sus siglas en inglés) es un subproducto biomásico generado en grandes volúmenes durante la producción industrial de cerveza. El BSG se ha convertido en un creciente problema para el medio ambiente, debido a que la mayoría de las cervecerías descartan inapropiadamente este residuo generando un impacto negativo al ambiente. Las alternativas para el aprovechamiento de este subproducto han consistido especialmente en la elaboración de suplementos alimenticios para animales de granja, obtención de biocombustibles, desarrollo de adsorbentes y obtención de productos para la industria alimentaria. Sin embargo, el alto contenido de humedad (~70%) del BSG representa un reto para el desarrollo de diferentes alternativas de reutilización, por lo que se hace necesario un proceso de secado previo. Objetivos: En este estudio se analizó la cinética de secado del BSG a diferentes temperaturas y el efecto de la temperatura de secado sobre sus propiedades físicas y contenido de compuestos bioactivos. Métodos: Las muestras de BSG fueron secadas a diferentes temperaturas (50, 60, 70, 80, 90 y 105°C) y analizadas en términos de razón de humedad, actividad acuosa, contenido de polifenoles totales (TPC) y actividad secuestradora del radical DPPH. Además, se ajustaron 4 modelos cinéticos a los datos de secado. Resultados: Se determinó que la difusividad efectiva del BSG varió entre 5.23x10

Patients' perspectives of the skills and competencies of therapy radiographers/radiation therapists (TRs/RTTs) in the UK, Portugal and Malta; a qualitative study from the SAFE Europe project.

INTRODUCTION: The role of the Therapy Radiographer/Radiation Therapist (TR/RTT) is to provide radiotherapy to patients with a cancer diagnosis. This includes, not only administration of treatment, but also management of side-effects and provision of support/care. Despite this role being consistent throughout Europe, there is currently no standardisation of education for TRs/RTTs. The SAFE EUROPE project aims to standardize TR/RTT education to enable 'safe and free exchange' of TRs/RTTs across Europe. Consequently, this study aims to explore patients' perspectives regarding the current skills and competencies of TRs/RTTs. METHODS: From May 2021 to February 2022, semi-structured interviews were conducted with patients who had recently received radiotherapy in the UK, Malta and Portugal. Ethical approval for this study was granted by the NHS Research Ethics Committee with additional local approvals obtained. RESULTS: Forty-eight participants from the UK (n = 18), Portugal (n = 19), and Malta (n = 11) completed interviews. Participants described high satisfaction with TRs'/RTTs' competence and skills in all three countries. The main theme arising from the analysis was the importance of trust building with TRs/RTTs. Six factors were identified as influencing levels of trust: communication; side-effect management; team consistency; relational skills; patient dignity; and competence. A small number of patients reported feeling rushed and not having their physical and emotional needs met by TRs/RTTs. CONCLUSION: This multicentre study demonstrated that patients perceive TRs/RTTs in the UK, Malta and Portugal as highly competent and skilled. Practical recommendations are provided to address identified deficits in practice, which can be addressed through adaptation of TR/RTT education/training and clinical practice. IMPLICATIONS FOR PRACTICE: Recommendations arising from this study are important to ensure that TRs/RTTs have transferable skills that provide consistently high quality care to patients throughout Europe.

Whole Genome Sequencing Unravels New Genetic Determinants of Early-Onset Familial Osteoporosis and Low BMD in Malta.

BACKGROUND: Osteoporosis is a skeletal disease with a strong genetic background. The study aimed to identify the genetic determinants of early-onset familial osteoporosis and low bone mineral density (BMD) in a two-generation Maltese family. METHODS: Fifteen relatives aged between 28-74 years were recruited. Whole genome sequencing was conducted on 12 relatives and shortlisted variants were genotyped in the Malta Osteoporotic Fracture Study (MOFS) for replication. RESULTS: Sequential variant filtering following a dominant inheritance pattern identified rare missense variants within SELP, TGF-ß2 and ADAMTS20, all of which were predicted to be likely pathogenic and participate in osteoimmunology. TGF-ß2 c.1136C>T was identified in five individuals from the MOFS in heterozygosity, four of whom had osteopenia/osteoporosis at the lumbar spine and hip, and/or had sustained a low-trauma fracture. Heterozygosity for the ADAMTS20 c.4090A>T was accompanied by lower total hip BMD (p = 0.018) and lower total serum calcium levels in MOFS (p < 0.01), recapitulating the findings from the family. Women carrying at least one copy of the alternative allele (TC/CC) for SELP c.2177T>C exhibited a tendency for lower lumbar spine BMD and/or wrist fracture history relative to women with TT genotype. CONCLUSIONS: Our findings suggest that the identified variants, alone or in combination, could be causal factors of familial osteoporosis and low BMD, requiring replication in larger collections.

Sexually transmitted infections epidemiology and risk assessment at the main correctional facility in Malta (2017-2019).

BACKGROUND: Inmates suffer from mental and physical ailments combined with substance misuse and addiction which are often underreported or disregarded by sufferers, for fear of being stigmatized. This vulnerable group has complex medical and psychosocial needs and hence gathering data is essential for a holistic approach to care. OBJECTIVES: Understanding the interplay between sexually transmitted (STIs) and blood borne infections, substance misuse and mental health is essential to enable targeted interventions and outreach programmes. The aim was to analyse the occurrence of STIs, hepatitis and tuberculosis in inmates at the main custodial facility in Malta; to assess risk behaviours and vulnerabilities through an outreach programme; to offer treatment and referral and to develop recommendations for screening of prison inmates. METHODS: A mixed methodology study was used which involved analysis of health data pooled from the Genitourinary Clinic (GUC) and Corradino Correctional Facility (CCF) in Malta. RESULTS: In the study period, 206 inmates were tested for STIs, 67.9% males, aged between 14 and 72. Only 27% were not sexually active in the 6 months prior to testing. Among those sexually active, 31% had had sex with casual partners and 43% had never used condoms for sexual intercourse. Seventy-five percent admitted to drug use. The most common STI diagnosed was HPV (16.5%), followed by syphilis (5.8%). Genital dermatoses were also frequent (9.2%). The prevalence of Hepatitis C was high (24.5%), in relation to intravenous drug use. CONCLUSION: The authors advocate for more collaboration between sexual health clinics and prisons to address educational interventions and STIs' testing. Cultural and linguistic barriers should be considered when devising national health strategies and screening recommendations in custodial settings. Adequate follow-up should extend into the community setting once inmates leave the prison to ensure a continuum of care.

Risk of Recurrent Stillbirth in Subsequent Pregnancies.

OBJECTIVE: To compare the prospective risk of stillbirth between women with and without a stillbirth in their first pregnancy. METHODS: We conducted a cohort study using perinatal data from Finland, Malta, and Scotland. Women who had at least two singleton deliveries were included. The exposed and unexposed cohorts comprised women with a stillbirth and live birth in their first pregnancy, respectively. The risk of stillbirth in any subsequent pregnancy was assessed using a Cox proportional hazards model. Time-to-event analyses were conducted to investigate whether first pregnancy outcome had an effect on time to or the number of pregnancies preceding subsequent stillbirth. RESULTS: The pooled data set included 1,064,564 women, 6,288 (0.59%) with a stillbirth and 1,058,276 with a live birth in a first pregnancy. Compared with women with a live birth, women with a stillbirth in the first pregnancy were more likely to have a subsequent stillbirth (adjusted hazard ratio [aHR] 2.25, 95% CI 1.86-2.72). For women with more than two pregnancies, the difference in risk of subsequent stillbirth between the two groups increased with the number of subsequent pregnancies. Maternal age younger than 25 years or 40 years and older, smoking, low socioeconomic status, not having a partner, pre-existing diabetes, preeclampsia, placental abruption, or delivery of a growth-restricted neonate in a first pregnancy were independently associated with subsequent stillbirth. Compared with women with a live birth in the first pregnancy, women with a stillbirth were more likely to have another pregnancy within 1 year. The absolute risk of stillbirth in a subsequent pregnancy for women with stillbirth and live birth in a first pregnancy were 2.5% and 0.5%, respectively. CONCLUSION: Compared with women with a live birth in a first pregnancy, women with a stillbirth have a higher risk of subsequent stillbirth irrespective of the number and sequence of the pregnancies. Despite high relative risk, the absolute risk of recurrence was low.

Testing Enhanced Active Choice to Optimize Acceptance and Participation in a Population-Based Colorectal Cancer Screening Program in Malta.

Opt-out strategies have been shown to improve participation in cancer screening; however, there are ethical concerns regarding the presumed consent. In this study, we tested an alternative opt-in strategy, called: "enhanced active choice," in which the response options summarize the consequences of the decision. The study was conducted as part of the Maltese colorectal cancer screening program, which offers men and women, aged 60-64, a "one-off" fecal immunochemical test (FIT). A total of 8349 individuals were randomly assigned to receive either an invitation letter that featured a standard opt-in strategy (control condition), or an alternative letter with a modified opt-in strategy (enhanced active choice condition). Our primary outcome was participation three months after the invitation was delivered. Additionally, we also compared the proportion who said they wanted to take part in screening. We used multivariable logistic regression for the analysis. Overall, 48.4% (N = 4042) accepted the invitation and 42.4% (N = 3542) did the screening test. While there were no statistically significant differences between the two conditions in terms of acceptance and participation, enhanced active choice did increase acceptance among men by 4.6 percentage points, which translated to a significant increase in participation of 3.4 percentage points. We conclude that enhanced active choice can improve male screening participation. Given the higher risk of CRC in men, as well as their lower participation screening, we believe this to be an important finding.

Secondhand smoke exposure in school children in Malta assessed through urinary biomarkers.

School children may be exposed to secondhand smoke (SHS) either at home, in transit or in social gatherings permitting smoking in their presence. Questionnaires about SHS often underestimate prevalence and extent of exposure. A more accurate tool is the use of biomarkers such as cotinine (COT) and trans-3'-hydrocycotinine (3HC) as biomarkers of SHS exposure, alongside 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a reduction product in the body of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), both potent carcinogens. We measured urinary COT, 3HC and total NNAL using sensitive and specific high-performance LC-MS/MS methods. The limit of quantification (LOQ) for each assay were 0.05 ng/mL, 0.1 ng/mL and 0.25 pg/mL respectively. The aim of this study was to evaluate the exposure to SHS of school children (9-11 years), from five public schools in the island of Malta, from questionnaire information about smoking at home and verify it by urinary biomarker data of COT, 3HC and NNAL. These biomarkers were measurable in 99.4%, 95.4% and 98.3% of the participating children respectively. From the children reporting smoking at home, 11% had a history of asthma and had COT, 3HC and NNAL geometric mean concentrations double compared to the non-asthmatic group. In has been confirmed that non-smokers exposed to SHS and THS have a higher NNAL/COT ratio than the group identified as smokers according to specific and defined COT threshold levels (despite the fact that a priori, the entire study group was composed of non-smokers). The implication of high measured levels of urinary NNAL in children should be of concern given its potency. A main effects multifactor ANOVA model was developed and the children's house and school locations and the smoking frequency were statistically significant to predict the levels of the three metabolites. For 3HC only, the status of the employment of the mother was also an important predictor.

Electrocardiographic abnormalities, preclinical carotid atherosclerosis and cardiovascular risk in an apparently healthy real-world population. Data from the "No Stroke, No Infarction" project of the Rotary International - district 2110 (Sicily and Malta).

BACKGROUND: Cardiovascular diseases (CVDs) represent important causes of morbidity and mortality. Our study aimed to evaluate cardiovascular risk using the EuroSCORE, ECG and carotid ultrasound for prevention purpose in a population of companions aged 50-70 years, asymptomatic and without CVD. METHODS: History of CVD, risk factors (RF), ECG and carotid ultrasound were evaluated. Intima-media thickness (IMT) was defined as wall thickness >0.9 mm, while focal thickening ≥1.5 mm protruding into the lumen as asymptomatic carotid plaque (ACP). RESULTS: Totally, 1860 subjects were screened. 393 (21.1%) had no RF, 780 (42%) hypertension, 571 (30.7%) hypercholesterolemia, 557 (29.9%) diabetes, 474 (25.5%) smoking, 648 (34.8%) overweight, 300 (16.1%) obesity and 184 (9.9%) metabolic syndrome. Carotid atherosclerosis was detected in 903 (48.5%) subjects, 821 (44.1%) had IMT and 547 (29.4%) ACP, and was significantly related to diabetes, hypertension and hypercholesterolemia. Atrial fibrillation was found in 29 subjects (1.6%) and Brugada pattern in one. Using EuroSCORE, 220 subjects resulted at low (11.8%), 1338 at moderate (71.9%), 292 at high (15.7%) and 10 at very-high risk (0.5%). Adding ACP, the percentages were: low 159 (8.54%), moderate 1020 (54.83%), high 663 (35.64%) and very-high risk 18 (0.96%). CONCLUSIONS: A total of 302 (16.2%) subjects were at least at high risk for CV events according to the EuroSCORE, increasing to 681 (36.61%; P<0.001) adding ACP. The combination of EuroSCORE with ECG may be a useful tool in primary prevention. Carotid ultrasound furtherly increases the power of stratification of asymptomatic patients suitable for pharmacological treatment.

The Impact of COVID-19 on Hospitalised COPD Exacerbations in Malta.

METHOD: Data was collected retrospectively from electronic hospital records during the periods 1st March until 10th May in 2019 and 2020. RESULTS: There was a marked decrease in AECOPD admissions in 2020, with a 54.2% drop in admissions (n = 119 in 2020 vs. n = 259 in 2019). There was no significant difference in patient demographics or medical comorbidities. In 2020, there was a significantly lower number of patients with AECOPD who received nebulised medications during admission (60.4% in 2020 vs. 84.9% in 2019; p ≤ 0.001). There were also significantly lower numbers of AECOPD patients admitted in 2020 who received controlled oxygen via venturi masks (69.0% in 2020 vs. 84.5% in 2019; p = 0.006). There was a significant increase in inpatient mortality in 2020 (19.3% [n = 23] and 8.4% [n = 22] for 2020 and 2019, respectively, p = 0.003). Year was found to be the best predictor of mortality outcome (p = 0.001). The lack of use of SABA pre-admission treatment (p = 0.002), active malignancy (p = 0.003), and increased length of hospital stay (p = 0.046) were also found to be predictors of mortality for AECOPD patients; however, these parameters were unchanged between 2019 and 2020 and therefore could not account for the increase in mortality. CONCLUSIONS: There was a decrease in the number of admissions with AECOPD in 2020 during the COVID-19 pandemic, when compared to 2019. The year 2020 proved to be a significant predictor for inpatient mortality, with a significant increase in mortality in 2020. The decrease in nebuliser and controlled oxygen treatment noted in the study period did not prove to be a significant predictor of mortality when corrected for other variables. Therefore, the difference in mortality cannot be explained with certainty in this retrospective cohort study.

Brachytrupes megacephalus Lefèbvre, 1827 (Orthoptera, Gryllidae) in the Maltese Islands: notes on biogeography, behaviour, and habitat of populations in the central Mediterranean area and the Maghreb.

Brachytrupes megacephalus (Lefebvre, 1827) is of significant biogeographic importance. It occurs in Sicily and on some of the circum-Sicilian and Pelagian islands, as well as in the Maltese Islands, Sardinia and the Maghreb (notably but not exclusively, in Algeria and Tunisia, where it maintains populations in both coastal and desert regions). Within European territory, it occurs solely in Italy and Malta, where it is protected under the EU Habitats Directive and the Bern Convention. In northern Africa, the species is regarded as a polyphagous pest, particularly in Saharan locations. The present work is based on field observations, mostly from the Maltese Islands, that span more than three decades; it provides insights on spatial distribution, population trends and behaviour. In examining the relationship between the species' frequency during its mating season and weather conditions, results suggest a weak yet statistically significant correlation between mating strategies and ambient meteorological conditions. Moreover, patch occupancy in spring and autumn varied considerably within a specified area of study, primarily due to competitive mating strategies employed in spring, with an occupancy ratio of approximately 1:6. To-date, the species is known from 13 locations, one in Gozo and 12 in Malta, of which some constitute the Ahrax promontory metapopulation. Connectivity between the Ahrax subpopulation cluster is discussed in the light of habitat and topographical characteristics. Contrasting findings on variances in behaviour between Maltese populations and other populations in Sicily and the Maghreb are discussed. Discernible behavioural disparities include the length of excavated tunnels during spring and summer/autumn seasons in the different geographical locations, attraction to artificial sources of light, and the degree of damage to crops across geographic regions.

Occupation and amyotrophic lateral sclerosis risk: a case-control study in the isolated island population of Malta.

Objective: Amyotrophic lateral sclerosis (ALS) is a mostly sporadic neurodegenerative disease. The role of environmental factors has been extensively investigated but associations remain controversial. Considering that a substantial proportion of adult life is spent at work, identifying occupations and work-related exposures is considered an effective way to detect factors that increase ALS risk. This process may be further facilitated in population isolates due to environmental and genetic homogeneity. Our study investigated occupations and occupational exposures potentially associated with ALS risk in the isolated island population of Malta, using a case-control study design. Methods: Patients with ALS and randomly identified matched controls (1:1) were recruited throughout a four-year window, from 2017 through 2020. Data on educational level, residence, main occupation, smoking, and alcohol history were collected. Results: We found that compared to controls (44.4%), a higher percentage (73.7%) of ALS patients reported a blue-collar job as their main occupation (OR 2.04, 95% CI 1.2-3.72; p = 0.0072). Through regression analysis, craft and related trades occupations such as carpentry and construction (ISCO-08 major group 7), were found to be positively associated with ALS, with patients in this occupational category found to be more prone to develop bulbar-onset ALS (p = 0.0297). Overall, patients with ALS reported a significantly higher exposure to work-related strenuous physical activity (OR 2.35, 95% CI 1.53-3.59; p = 0.0002). Conclusion: Our findings suggest that manual workers particularly those working in the carpentry and construction industries have an increased ALS risk, possibly due to a history of intense or sustained physical activity.

First Profile of Phenolic Compounds from Maltese Extra Virgin Olive Oils Using Liquid-Liquid Extraction and Liquid Chromatography-Mass Spectrometry.

This study presents the profile of phenolic extracts from different Extra Virgin Olive Oils (EVOOs) from Malta and is the first study that characterizes the phenolic profile of the Maltese EVOOs Bidni (B) and Malti (M) using liquid-liquid extraction (LLE) and Liquid Chromatography-Mass Spectrometry (LC-MS). The total phenolic content (TPC), ortho diphenolic content (TdPC) and flavonoid content (TFC) were determined using the Folin-Ciocalteau assay, the Arnow's assay and the Aluminium Chloride method respectively. Results show that the B variety had the highest TPC, TdPC and TFC. Using LC-MS analysis, over 30 phenolic compounds were identified belonging to different classes of phenolic compounds.

Essential oil compositions of Teucrium fruticans, T. scordium subsp. scordioides and T. siculum growing in Sicily and Malta.

In the present study, the chemical composition of the essential oils from the aerial parts of Teucrium fruticans L. collected in Sicily and Malta, Teucrium scordium subsp. scordioides (Schreb.) Arcang. and Teucrium siculum (Raf.) Guss., collected in Sicily, were evaluated by GC-MS. The main volatile components of both T. fruticans collections were germacrene D (29.4% and 50.0%), (E)-ß-caryophyllene (19.6% and 21.9%), and 1-octen-3-ol (19.7% and 7.4%); T. scordium subsp. scordioides essential oil was rich in caryophyllene oxide (25.8%), α-pinene (19.4%) and ß-pinene (8.5%); T. siculum essential oil was rich in (E)-ß-caryophyllene (30.9%), 1-octen-3-ol (9.0%), α-humulene (8.6%) and germacrene D (8.0%). The chemotaxonomic relationship with other members of the respective botanical sections was discussed.

Real-world safety and efficacy of nivolumab for ≥ 2nd line treatment of metastatic renal cell carcinoma: A retrospective cohort study in Croatia, Hungary, and Malta.

The objective of our study was to assess the real-world safety and efficacy of nivolumab in the second- or later-line treatment of metastatic renal cell carcinoma (mRCC). We conducted a multicenter, retrospective, observational study of real-world data from patients who were treated with nivolumab under a patient expanded access program from 2015 to 2017 in Croatia, Hungary, and Malta. The primary safety endpoint was the discontinuation of therapy because of adverse events. The primary efficacy endpoint was overall survival (OS). We collected data from 87 patients with a median (interquartile range (IQR)) age of 63 (57-68) years, and 21% were females. The median (IQR) follow-up was 11 (5-31) months. Treatment was discontinued because of toxicity in 4 (5%) patients. Four (5%) patients experienced treatment-related adverse events of grade 3 or 4. The OS was 18.0 (95% CI: 11.0 to 28.6) months, and the PFS was 8.5 (95% CI: 4.9 to 12.1) months. Our study indicated a good safety and efficacy profile of nivolumab in the second- or later-line treatment of mRCC patients in a real-world clinical practice environment, which is comparable with the findings of the registrational trial.