Box and block test, hand grip strength and nine-hole peg test: correlations between three upper limb objective measures in multiple sclerosis.

BACKGROUND AND PURPOSE: Limited data are available in the literature for upper limb impairment in multiple sclerosis (MS). This study aimed to report the distribution of values of hand grip strength (HGS), of the box and block test (BBT) and of the nine-hole peg test (9HPT) correlated with demographic and clinical data in subjects with MS. METHODS: This study involved five Italian neurological centres. The inclusion criteria were age ≥ 18, MS diagnosis, stable disease phase, right-hand dominance. All subjects underwent HGS, BBT and 9-HPT evaluation. RESULTS: In all, 202 subjects with MS were enrolled: 137 females; mean age 48.4 years; mean Expanded Disability Status Scale (EDSS) 4.17; mean disease duration 14.12 years; disease course 129 relapsing-remitting, 21 primary progressive and 52 secondary progressive MS subjects; mean right HGS 25.3 kg, left 23.2 kg; mean right BBT 45.7 blocks, left 44.9 blocks; mean right 9-HPT 30.7 s, left 33.4 s. All results were statistically significantly different compared to healthy controls. HGS, BBT and 9-HPT were associated with age, EDSS and disease duration, whilst disease course correlated with BBT and 9-HPT. The BBT and 9-HPT scores significantly differed according to level of disability (EDSS ≤3.0, 3.5-5.5, ≥6.0). CONCLUSION: Hand grip strength and BBT value distribution in a large MS population is reported. Correlations between HGS, BBT and 9-HPT were generally low.

Impact of Nutritional Stress on Honeybee Gut Microbiota, Immunity, and Nosema ceranae Infection.

Honeybees are important pollinators, having an essential role in the ecology of natural and agricultural environments. Honeybee colony losses episodes reported worldwide and have been associated with different pests and pathogens, pesticide exposure, and nutritional stress. This nutritional stress is related to the increase in monoculture areas which leads to a reduction of pollen availability and diversity. In this study, we examined whether nutritional stress affects honeybee gut microbiota, bee immunity, and infection by Nosema ceranae, under laboratory conditions. Consumption of Eucalyptus grandis pollen was used as a nutritionally poor-quality diet to study nutritional stress, in contraposition to the consumption of polyfloral pollen. Honeybees feed with Eucalyptus grandis pollen showed a lower abundance of Lactobacillus mellifer and Lactobacillus apis (Firm-4 and Firm-5, respectively) and Bifidobacterium spp. and a higher abundance of Bartonella apis, than honeybees fed with polyfloral pollen. Besides the impact of nutritional stress on honeybee microbiota, it also decreased the expression levels of vitellogenin and genes associated to immunity (glucose oxidase, hymenoptaecin and lysozyme). Finally, Eucalyptus grandis pollen favored the multiplication of Nosema ceranae. These results show that nutritional stress impacts the honeybee gut microbiota, having consequences on honeybee immunity and pathogen development. Those results may be useful to understand the influence of modern agriculture on honeybee health.

Efficacy of focal muscular vibration in the treatment of upper limb spasticity in subjects with stroke outcomes: randomized controlled trial.

Focal muscular vibration (FMV) is a non-invasive technique that showed positive effects on spasticity of the upper limb in stroke subjects but different protocols have been proposed so the studies are not comparable and, to date, it is not clear which muscles should be treated, agonist, or antagonist muscles to obtain the better result on spasticity. The objective of this study is to evaluate the effects on spasticity of FMV on the upper limb flexor spastic muscles compared to the effects of FMV on the upper limb extensor muscles in subacute stroke patients. We treated 28 subacute stroke patients (mean age 64.28±13.79) randomized into two groups: Group A and Group B. Group A was treated by applying FMV to the flexor muscles of the upper limb, while Group B was treated by applying FMV to the extensor muscles of the upper limb. The effects on spasticity were assessed by Modified Ashworth Scale (primary outcome) and the upper limb motor function by instrumental robotic outcomes; moreover, muscle strength and pain were evaluated using Motricity Index and Numerical Rating Scale, respectively (secondary outcomes). Patients were subjected to FMV for three consecutive days and were evaluated three times: before treatment (T0), after a week (T1) and after a month (T2) from the end of treatment. Within group, analysis showed statistically significant changes over time of the MAS at the three joints (shoulder, elbow and wrist) in both groups, but post-hoc analysis showed that, only in Group A, MAS was significantly lower at T2, when compared with T0 at the shoulder and elbow. NRS, significantly changed over time only in the Group B. Motricity Index, did not change over time neither in the Group A, nor in the Group B. No statistically significant differences were detected in the between group analysis. Regarding the instrumental robotic outcomes, we detected a statistically significant reduction of the time required to complete the task (Duration) in both group a T2. In conclusion, this study highlighted how the same treatment protocol can determine an improvement in muscle tone and in the Duration to perform a task, regardless of the muscles treated, while the pain improves if we treat the agonist muscles.

Worldwide HLA-E nucleotide and haplotype variability reveals a conserved gene for coding and 3' untranslated regions.

The human leukocyte antigen-E (HLA-E) locus is a human major histocompatibility complex (MHC) gene associated with immune-modulation and suppression of the immune response by the interaction with specific natural killer (NK) and T cell receptors (TCRs). It is considered one of the most conserved genes of the human MHC; however, this low nucleotide variability seems to be a consequence of the scarce number of studies focusing on this subject. In this manuscript we assessed the nucleotide variability at the HLA-E coding and 3' untranslated regions (3'UTRs) in Brazil and in the populations from the 1000Genomes Consortium. Twenty-eight variable sites arranged into 33 haplotypes were detected and most of these haplotypes (98.2%) are encoding one of the two HLA-E molecules found worldwide, E*01:01 and E*01:03. Moreover, three worldwide spread haplotypes, associated with the coding alleles E*01:01:01, E*01:03:01 and E*01:03:02, account for 85% of all HLA-E haplotypes, suggesting that they arose early before human speciation. In addition, the low nucleotide diversity found for the HLA-E coding and 3'UTR in worldwide populations suggests that the HLA-E gene is in fact a conserved gene, which might be a consequence of its key role in the modulation of the immune system.

A nonsynonymous mutation at HLA-E defines the new E*01:06 allele in Brazilian individuals.

We report a novel nonclassical class I HLA-E*01:06 allele observed in Brazilian individuals.

Supplementation of honey bee production colonies with a native beneficial microbe mixture.

Honey bee colonies form a complex superorganism, with individual and social immune defences that control overall colony health. Sometimes these defences are not enough to overcome infections by parasites and pathogens. For that reason, several studies have been conducted to evaluate different strategies to improve honey bee health. A novel alternative that is being studied is the use of beneficial microbes. In a previous study, we isolated and characterised bacterial strains from the native gut microbiota of honey bees. Four Apilactobacillus kunkeei strains were mixed and administered in laboratory models to evaluate their potential beneficial effect on larvae and adult bees. This beneficial microbe mixture was safe; it did not affect the expression of immune-related genes, and it was able to decrease the mortality caused by Paenibacillus larvae infection in larvae and reduced the Nosema ceranae spore number in infected adult honey bees. In the present study, we aimed to delve into the impact of the administration of this beneficial microbe mixture on honey bee colonies, under field conditions. The mixture was administered in sugar syrup using lyophilised bacterial cells or fresh cultures, by aspersion or sprayed and feeder, once a week for three consecutive weeks, in autumn or spring 2015, 2017 and 2019. Colony strength parameters were estimated before the administration, and one and three months later. Simultaneously different samples were collected to evaluate the infection levels of parasites and pathogens. The results showed that administering the beneficial microbe mixture decreased or stabilised the infection by N. ceranae or Varroa destructor in some trials but not in others. However, it failed to improve the colony's strength parameters or honey production. Therefore, field studies can be a game-changer when beneficial microbes for honey bees are tested, and meticulous studies should be performed to test their effectiveness.

Robotic-assisted rehabilitation for balance in stroke patients (ROAR-S): effects of cognitive, motor and functional outcomes.

OBJECTIVE: Due to the aging population, the incidence of stroke is steadily increasing. In patients with stroke outcomes, sensory, motor and cognitive problems limit the performance of activities of daily living. The development of new technologies in rehabilitation is improving the quality and efficiency of functional recovery. Hunova robotic platform (Movendo Technology, srl, Genoa, Italy) is a robotic device for functional assessment and rehabilitation of balance. The purpose of this study is to evaluate the effects of rehabilitation with Hunova on cognitive function and balance in older adults with stroke. PATIENTS AND METHODS: This is a randomized, controlled, single-blind study. Twenty-four older adults with stroke outcomes were randomized into the Hunova group (HuG), which performed a specific rehabilitation program for balance using Hunova for 12 sessions in addition to conventional rehabilitation, and the control group (CoG), which performed only conventional rehabilitation. All patients underwent a clinical cognitive, balance, quality of life and fatigue assessment, and an instrumental balance assessment with Hunova at the beginning and end of treatment. RESULTS: Statistical analysis showed significant improvements in most clinical scales in both groups. Comparing the groups, HuG showed greater improvements in executive functions, speed of information processing, attention and discrimination of multiple stimuli, static and dynamic balance and autonomy in daily activities, standing postural sway, and trunk control in static and dynamic conditions. CONCLUSIONS: Data analysis showed that elderly with stroke who underwent balance technology treatment with Hunova in combination with conventional treatment had a greater improvement in cognitive functions, balance and reduced risk of falling.

A novel HLA-E allele, E*01:03:05, identified in two Brazilian individuals.

Here, we report a novel non-classical class I HLA-E allele found in the Brazilian population.

Non-classical HLA-E gene variability in Brazilians: a nearly invariable locus surrounded by the most variable genes in the human genome.

The non-classical human leukocyte antigen (HLA) class I genes present a very low rate of variation. So far, only 10 HLA-E alleles encoding three proteins have been described, but only two are frequently found in worldwide populations. Because of its historical background, Brazilians are very suitable for population genetic studies. Therefore, 104 bone marrow donors from Brazil were evaluated for HLA-E exons 1-4. Seven variation sites were found, including two known single nucleotide polymorphisms (SNPs) at positions +424 and +756 and five new SNPs at positions +170 (intron 1), +1294 (intron 3), +1625, +1645 and +1857 (exon 4). Haplotyping analysis did show eight haplotypes, three of them known as E*01:01:01, E*01:03:01 and E*01:03:02:01 and five HLA-E new alleles that carry the new variation sites. The HLA-E*01:01:01 allele was the predominant haplotype (62.50%), followed by E*01:03:02:01 (24.52%). Selective neutrality tests have disclosed an interesting pattern of selective pressures in which balancing selection is probably shaping allele frequency distributions at an SNP at exon 3 (codon 107), sequence diversity at exon 4 and the non-coding regions is facing significant purifying pressure. Even in an admixed population such as the Brazilian one, the HLA-E locus is very conserved, presenting few polymorphic SNPs in the coding region.

Identification of two new HLA-G alleles, G*01:01:03:03 and G*01:01:21, in Brazilian individuals.

Here we report two new non-classical class I HLA-G alleles found in the Brazilian population.

Stimulatory effect of SOM230 on human and rat adrenal corticosteroid secretion in vitro.

SOM230 (pasireotide, Signifor), a recently developed somatostatin analog, has been tested in ACTH-secreting pituitary tumors with promising results. No study has yet evaluated whether this analog also directly affects adrenal steroid production. The aim of the current study was to evaluate whether SOM230 modulates corticosteroid secretion by normal adrenals in vitro. Primary cultures from normal human and rat adrenals were incubated with 10-100 nM SOM230 with and without 10nM ACTH. Dose-response studies with 1 nM-1 µM SOM230 were performed on rat adrenals. Cortisol/corticosterone levels in medium were measured after 4 and 24h. SOM230 (10nM) significantly increased corticosteroid levels after 24h incubation in both human (36.4 ± 0.43 ng/well vs 27.7 ± 3.17 ng/well, p<0.05) and rat (16.2 ± 1.16 ng/well vs 11.6 ± 0.92 ng/well p<0.05) adrenals; lesser effects were observed with 100 nM SOM (33.4 ± 2.59 ng/well vs 27.7 ± 3.17 ng/well p<0.05; 13.4 ± 0.82 ng/well vs 11.6 ± 0.92 ng/well, N.S. vs baseline secretion for human and rat adrenals, respectively). Dose-response curves confirmed maximal effect at 10nM SOM230. The corticosteroid secretory response to ACTH was unaffected by SOM230 co-incubation. In conclusion, SOM230 exerts a moderate stimulatory effect on adrenal corticosteroid secretion in vitro. This argues against a direct adrenal involvement in the clinical efficacy of SOM230 in patients with ACTH-secreting pituitary tumors and widens the known range of action of SOM230.

Prehabilitation and heart failure: main outcomes in the COVID-19 era.

OBJECTIVE: The advent of the SARS-CoV-2 pandemic has resulted in an increase in sedentary behavior, with consequences on cardiopulmonary capacity, especially in the elderly population. Prehabilitation is a strategy usually used before a surgical procedure to improve functional capacity; however, it can be used for non-surgical patients and not in the acute phase of disease. The purpose of this study is to evaluate the effectiveness of a prehabilitation program, using telerehabilitation, in frail elderly patients with chronic heart failure. PATIENTS AND METHODS: This is a randomized, controlled, single-blind study. Fifteen patients with chronic heart failure were randomized into three groups: two active groups (telerehabilitation and in-person) and the control group. Patients in the active groups underwent a rehabilitation program divided into two 4-week periods, for 45-60 minutes per day, 2 days per week. RESULTS: In the Study Group, the quality of life significantly improved (EQoL-5D), and between the two groups a statistically significant difference in the motor dimension of SF-36 was identified. CONCLUSIONS: The telerehabilitation prehabilitation program for patients with chronic heart failure was confirmed to be effective and not inferior to a prehabilitation program performed in-person, avoiding the worsening of some domains of quality of life and motor performance, and leading to the improvement of others.

Fast screening of depression in cancer patients: the effectiveness of the HADS.

In oncology clinics, there is an increasing need for fast and accurate screening scales and procedures in order to evaluate cancer patients for depression. The present study investigated the comparative effectiveness in recognising depressed patients of the Hospital Anxiety and Depression Scale (HADS), a self-report screening scale, and the Montgomery-Asberg Depression Rating Scale (MADRS), a semi-structured clinician-rated scale, in 151 patients affected by mixed cancer pathologies. With the MADRS, 73.5% of the patients were identified as depressed, whereas the HADS identified 36.4% and 58.3% as depressed, using the cut-offs of 11 and 8 respectively. The results suggest moderate agreement between the MADRS and the HADS when a cut-off of 8 is used (K-test: 0.44), while using a HADS cut-off of 11 gave a significantly higher underestimation of depressed patients (K-test: 0.29). In conclusion, the results suggest that the HADS can be useful as a sufficiently accurate first-step screening tool for depression in mixed oncology settings.

Prehabilitation and heart failure: perspective in primary outcomes, a randomized controlled trial.

OBJECTIVE: Prehabilitation, intended as a multidisciplinary approach where physical training is combined with educational and counselling training, in cardiology could optimizing care, and has been shown to be able to reduce morbidity and mortality in several diseases. The present study aims to assess the effectiveness of a prehabilitation program in elderly patients (over 65) with chronic heart failure and to evaluate functional and quality indices of life. PATIENTS AND METHODS: This is randomized, single blind controlled trial. Fourteen older adult patients diagnosed with chronic heart failure were enrolled. Patients were randomly assigned into the study or the control group. Patients in the study group underwent physical training organized into 10 twice-weekly meetings, nutritional and lifestyle counseling. RESULTS: In the Study Group, the quality of life improved significantly (EQoL-5D), and between the two groups there is a statistically significant difference in the motor dimension of SF-36. CONCLUSIONS: Because of our preliminary results, prehabilitation program should be included among the management strategies of in elderly patients with chronic heart failure to better manage their disease and to improve their Quality of Life.

LABEC, the INFN ion beam laboratory of nuclear techniques for environment and cultural heritage.

The LABEC laboratory, the INFN ion beam laboratory of nuclear techniques for environment and cultural heritage, located in the Scientific and Technological Campus of the University of Florence in Sesto Fiorentino, started its operational activities in 2004, after INFN decided in 2001 to provide our applied nuclear physics group with a large laboratory dedicated to applications of accelerator-related analytical techniques, based on a new 3 MV Tandetron accelerator. The new accelerator greatly improved the performance of existing Ion Beam Analysis (IBA) applications (for which we were using since the 1980s an old single-ended Van de Graaff accelerator) and in addition allowed to start a novel activity of Accelerator Mass Spectrometry (AMS), in particular for 14C dating. Switching between IBA and AMS operation became very easy and fast, which allowed us high flexibility in programming the activities, mainly focused on studies of cultural heritage and atmospheric aerosol composition, but including also applications to biology, geology, material science and forensics, ion implantation, tests of radiation damage to components, detector performance tests and low-energy nuclear physics. This paper describes the facilities presently available in the LABEC laboratory, their technical features and some success stories of recent applications.

Evaluation of computational methods for the reconstruction of HLA haplotypes.

Human leukocyte antigen (HLA) haplotypes are frequently evaluated for population history inferences and association studies. However, the available typing techniques for the main HLA loci usually do not allow the determination of the allele phase and the constitution of a haplotype, which may be obtained by a very time-consuming and expensive family-based segregation study. Without the family-based study, computational inference by probabilistic models is necessary to obtain haplotypes. Several authors have used the expectation-maximization (EM) algorithm to determine HLA haplotypes, but high levels of erroneous inferences are expected because of the genetic distance among the main HLA loci and the presence of several recombination hotspots. In order to evaluate the efficiency of computational inference methods, 763 unrelated individuals stratified into three different datasets had their haplotypes manually defined in a family-based study of HLA-A, -B, -DRB1 and -DQB1 segregation, and these haplotypes were compared with the data obtained by the following three methods: the Expectation-Maximization (EM) and Excoffier-Laval-Balding (ELB) algorithms using the arlequin 3.11 software, and the PHASE method. When comparing the methods, we observed that all algorithms showed a poor performance for haplotype reconstruction with distant loci, estimating incorrect haplotypes for 38%-57% of the samples considering all algorithms and datasets. We suggest that computational haplotype inferences involving low-resolution HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1 haplotypes should be considered with caution.

High prevalence of neuropathies in patients with end-stage liver disease.

OBJECTIVES: Peripheral neuropathy has been reported in association with end-stage liver disease, but there is only a limited number of reports on the incidence and features of these neuropathies. MATERIALS AND METHODS: In this study, 83 patients awaiting liver transplantation were evaluated for the presence of peripheral and autonomic neuropathy. RESULTS: Sixty-five percent of the patients had evidence of neuropathy, in agreement with peripheral NCS or cardiovascular autonomic function test. The neuropathy was more frequent in patients with advanced hepatic failure, evaluated with the MELD score. The most frequent abnormalities in nerve conduction studies were sensory-motor neuropathies and sensory neuropathies, with a length-dependent pattern. CONCLUSION: Peripheral neuropathy and autonomic neuropathy are common in patients with end-stage liver disease with different etiology and correlate with the severity of the liver disease.

Effect of chronotype on motor skills specific to soccer in adolescent players.

Circadian rhythms influence daily behavior, psychological and physiological functions, as well as physical performance. Three chronotypes are distinguished according to the preferences people typically display for activity at certain times of day: Morning, Neither, and Evening types (M-, N- and E-types). The chronotype changes with age: eveningness tends to be stronger in youth and morningness in older age. The progressive shift toward eveningness during adolescence creates misalignment with morning society schedules and can lead to a deterioration in intellectual and physical performance. Soccer is one of the world's most popular sports practiced by adolescents and soccer workouts are usually held after school in the afternoon or evening. Performance in soccer is related to a host of factors, including physiological variables and motor skills that have a circadian variation. The aim of this study was to determine the effect of chronotype on motor skills specific to soccer, specifically whether agility, aerobic endurance, and explosive power differ among the three chronotypes in relation to the time of day. For this study 141 adolescent soccer players filled in the Morningness-Eveningness Questionnaire (MEQ) for the assessment of chronotype. A subsample of 75 subjects, subdivided in M-types (n= 25), E-types (n= 25), and N-types (n= 25), performed three tests (Sargent Jump Test - SJT, Illinois Agility Test - IAT, and 6-Minutes Run Test - 6MRT) at a morning and an evening training session (9:00 am and 6:00 pm). Mixed ANOVA was used to test the interactions between chronotypes, physical performance, and time. On all tests, better performance during the morning than the evening session was observed for the M-types (p< .05), whereas the E-types performed better in the evening than in the morning session (p< .05), and no differences in test performance were detected for the N-types. These findings underline the importance of a correct chronobiological approach to sports training. Scheduling training sessions according to an athlete's circadian preferences could be a valid strategy to enhance performance.

Rest-activity rhythm in breast cancer survivors: an update based on non-parametric indices.

Recently we evaluated by actigraphy the rest-activity circadian rhythm (RAR) in breast cancer (BC) survivors at 5 years from primary diagnosis, as well as in a control group with similar age and body mass index (BMI). RAR, analyzed by Cosinor method, resulted significantly different in BC survivors compared to healthy subjects: BC survivors showed lower values of MESOR and Amplitude (A), while acrophase (φ) was similar in the two groups. Now, using non-parametric methods we have detected Interdaily Stability (IS), Intradaily Variability (IV), nocturnal activity (L5), and daily activity (M10) on the same sample of previous study: 15 BC survivors at 5 years from the primary diagnosis (mean age = 56.7 ± 6.6 yrs; mean BMI = 24.5 ± 3.8 Kg/m2) and 13 healthy controls (mean age = 54.4 ± 7.2 yrs; mean BMI = 25.2 ± 2.8 Kg/m2). The non-parametric indices showed that in BC-group IV was significantly higher than in Ctrl-group (0.86 vs. 0.65 a.u. in BC and Ctrl, respectively; p <.01), while L5 (11.27 vs. 34.41 a.c. in BC and Ctrl, respectively; p <.0001) and M10 (326.82 vs. 428.07 a.c. in BC and Ctrl, respectively; p <.01) were significantly lower compared to Ctrl-group. The data suggest that BC patients need constant clinical assessment of RAR characteristics along the years following the primary diagnosis. The analysis of RAR in all its components, parametric and non-parametric, is important to detect alterations in the sleep-wake cycle and can be useful for developing new strategies for health protection, such as structured and tailored physical activity programs, to improve circadian activity level in order to raise the quality of life in BC survivors.

Neuro-psychiatric therapy during chronic subthalamic stimulation in Parkinson's disease.

BACKGROUND: Neuro-psychiatric (NP) disturbances are highly prevalent in patients with Parkinson's disease (PD) and contribute to worsen quality of life. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is commonly utilized as surgical treatment for advanced PD with motor complications. The effectiveness of the procedure on motor symptoms is well established whereas the effects of STN-DBS on NP symptoms are less clear. The aim of our study was to analyze the postoperative pharmacological therapy for NP symptoms in a group of STN-DBS treated PD patients. Such therapy provides indirect information about the evolution of underlying NP disturbances during the follow-up in this group of PD patients. METHODS: NP therapy (benzodiazepines, antidepressants, antipsychotics) was assessed in 48 consecutive PD patients treated by STN-DBS, preoperatively and postoperatively after 4 months, 1 year and 3 years. Motor symptoms were evaluated by the Unified PD Rating Scale (UPDRS) and levodopa equivalence daily dose (LEDD) was calculated. Cognitive, mood and anxiety assessments were performed with appropriate rating scales. RESULTS: The number of patients treated with antidepressant drugs gradually increased during the follow-up. The use of antipsychotic drugs was stable until 1 year, with a subsequent increase at 3 years. Benzodiazepines were given to fewer patients immediately after surgery. CONCLUSIONS: Pharmacological treatment supplies further information about NP symptoms in the follow-up of PD patients undergoing STN stimulation.