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BACKGROUND: Ceftolozane/tazobactam (C-T) is a novel beta-lactam/beta-lactamase inhibitor combination approved for the treatment of various infections caused by difficult-to-treat Pseudomonas aeruginosa. In critically ill patients, C-T may exhibit significant pharmacokinetic variability, both between individuals and within individuals, warranting therapeutic drug monitoring for clinical purposes. We aim to develop and validate a novel and sensitive analytical method for concurrently determining C and T in human plasma microsamples (3 µL). METHODS: The method was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with positive electrospray ionization and multiple reaction monitoring (MRM) detection modes, employing specific mass transitions for both drugs. Sample preparation was simple, and the chromatographic run lasted only 4 minutes. Validation was conducted according to European Medicines Agency (EMA) guidelines, encompassing specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, and drug stability. The validated method was applied to measure C and T in 32 plasma samples collected from critically ill patients with multidrug-resistant, gram-negative, bacterial infections. RESULTS: The method ensured accurate (BIAS% 2.1-9.6 for C and -2.2 to 15.2 for T) and precise intraday CV% for C: 6.7-5.5; for T: 1.3-8.9; interday CV% for C 6.0-10.8; for T 4.1-10.2) measurements of C-T over a wide concentration range (0.2-200.0 mg/L for C and 0.1-100.0 mg/L for T). Overall, the recovery at quality control concentration levels was high for both C and T (mean values: 90-91 for C and 89-92 for T). Analyte stability was satisfactory in both human plasma and extracts under various storage conditions. The clinical applicability of the assay was confirmed by the reliably quantifying C and T in clinical plasma samples. CONCLUSIONS: The developed and validated LC-MS/MS method is sensitive and suitable for monitoring C and T in human plasma microsamples.
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INTRODUCTION: Sleep problems commonly occur in Parkinson's disease (PD) and significantly affect patients' quality of life. A possible effect on subjective sleep disturbances of monoamine oxidase-B inhibitors (MAOB-Is) has been described. METHODS: This prospective, observational, single-centre study involved 45 fluctuating PD patients complaining sleep problems as documented by the PD Sleep Scale -2nd version (PDSS-2 ≥18) starting rasagiline 1 mg/daily or safinamide 100 mg/daily, according to common clinical practice, and maintaining antiparkinsonian therapy unchanged. Polysomnography (PSG), sleep questionnaires (PDSS-2, Epworth Sleepiness Scale - ESS), and motor function were evaluated at baseline (T0) and after 4 months of treatment (T1). RESULTS: Safinamide was prescribed in thirty patients and rasagiline in fifteen patients. Both drugs induced a significant improvement in Movement Disorder Society Unified PD Rating Scale III scores. Patients treated with rasagiline showed a significant increase in stage 1 (N1) Non-REM sleep compared to T0, with no significant effects on sleep scales. Patients treated with safinamide showed a significant increase in stage 3 of Non-REM sleep and sleep efficiency and a reduction in the rate of periodic limb movements, matching a significant reduction in PDSS-2 and ESS scales compared to T0. CONCLUSION: This study showed that safinamide, in addition to having a significant effect on PD motor symptoms, like the other MAOB-Is, may exert a specific beneficial effect on subjective and objective sleep, probably driven by its dual mechanism of action, which involves both dopaminergic and glutamatergic neurotransmission.
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Early-onset Parkinson's disease (EOPD) occurs during the fertile life, when circulating neuroactive sex hormones might enhance the sexual dimorphism of the disease. Here, we aimed to examine how sex hormones can contribute to sex differences in EOPD patients. A cohort of 34 EOPD patients, 20 males and 14 females, underwent comprehensive clinical evaluation of motor and non-motor disturbances. Blood levels of estradiol, total testosterone, follicle-stimulating hormone, and luteinizing hormone were measured in all patients and correlated to clinical features. We found that female patients exhibited greater non-motor symptoms and a relatively higher rate of dystonia than males. In females, lower estradiol levels accounted for higher MDS-UPDRS-II and III scores and more frequent motor complications, while lower testosterone levels were associated with a major occurrence of dystonia. In male patients, no significant correlations emerged. In conclusion, this study highlighted the relevance of sex hormone levels in the sexual dimorphism and unique phenotype of EOPD.
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Autonomic symptoms in Parkinson's disease result from variable involvement of the central and peripheral systems, but many aspects remain unclear. The analysis of functional connectivity has shown promising results in assessing the pathophysiology of Parkinson's disease. This study aims to investigate the association between autonomic symptoms and cortical functional connectivity in early Parkinson's disease patients using high-density EEG. 53 early Parkinson's disease patients (F/M 18/35) and 49 controls (F/M 20/29) were included. Autonomic symptoms were evaluated using the Scales for Outcomes in Parkinson's disease-Autonomic Dysfunction score. Data were recorded with a 64-channel EEG system. We analyzed cortical functional connectivity, based on weighted phase-lag index, in θ-α-ß-low-γ bands. A network-based statistic was used to perform linear regression between Scales for Outcomes in Parkinson's disease-Autonomic Dysfunction score and functional connectivity in Parkinson's disease patients. We observed a positive relation between the Scales for Outcomes in Parkinson's disease-Autonomic Dysfunction score and α-functional connectivity (network τ = 2.8, P = 0.038). Regions with higher degrees were insula and limbic lobe. Moreover, we found positive correlations between the mean connectivity of this network and the gastrointestinal, cardiovascular, and thermoregulatory domains of Scales for Outcomes in Parkinson's disease-Autonomic Dysfunction. Our results revealed abnormal functional connectivity in specific areas in Parkinson's disease patients with greater autonomic symptoms. Insula and limbic areas play a significant role in the regulation of the autonomic system. Increased functional connectivity in these regions might represent the central compensatory mechanism of peripheral autonomic dysfunction in Parkinson's disease.
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Autonomic Nervous System Diseases , Electroencephalography , Parkinson Disease , Humans , Parkinson Disease/physiopathology , Parkinson Disease/diagnostic imaging , Parkinson Disease/complications , Female , Male , Middle Aged , Aged , Autonomic Nervous System Diseases/physiopathology , Autonomic Nervous System Diseases/etiology , Insular Cortex/diagnostic imaging , Insular Cortex/physiopathology , Limbic System/physiopathology , Limbic System/diagnostic imaging , Neural Pathways/physiopathology , Neural Pathways/diagnostic imagingABSTRACT
Lifestyle factors, such as diet and sleep quality, are receiving increasing interest as accessible therapeutic approaches to migraine. The Mediterranean diet (MD) has shown clear benefits in cardiovascular and metabolic diseases, as well as in sleep patterns. Here, our objective was to identify the impact of adherence to the MD and other lifestyle factors on the clinical burden of migraine. For this purpose, we enrolled 170 migraine patients and 100 controls, assessing the clinical disability of headache using standardized clinical scales (HIT-6 and MIDAS) in the migraineur cohort and lifestyle patterns in both groups through the PREDIMED score for MD adherence, the IPAQ scale for physical activity, and BMI. Subjects were also screened for sleep-wake disturbances based on the Pittsburgh Sleep Quality Index (PSQI). We found that migraine patients had lower adherence to the MD compared to the controls and that the HIT-6 scale had a significant negative relationship with MD adherence in patients with high-frequency episodic and chronic migraine. Additionally, in the same migraine patients, the presence of sleep-wake disturbances was correlated with greater migraine disability as assessed by the MIDAS score. In conclusion, this study found that among different lifestyle factors, poor adherence to the MD and the presence of sleep-wake disturbances were closely associated with migraine disability and chronification.
Subject(s)
Diet, Mediterranean , Migraine Disorders , Sleep Wake Disorders , Humans , Migraine Disorders/diet therapy , Diet, Mediterranean/statistics & numerical data , Female , Male , Italy/epidemiology , Sleep Wake Disorders/epidemiology , Adult , Middle Aged , Patient Compliance/statistics & numerical data , Life Style , Sleep Quality , Case-Control StudiesABSTRACT
OBJECTIVE: In this pilot prospective cohort study, we aimed to evaluate, using high-density electroencephalography (HD-EEG), the longitudinal changes in functional connectivity (FC) in patients with chronic migraine (CM) treated with onabotulinumtoxinA (OBTA). BACKGROUND: OBTA is a treatment for CM. Several studies have shown the modulatory action of OBTA on the central nervous system; however, research on migraine is limited. METHODS: This study was conducted at the Neurology Unit of "Policlinico Tor Vergata," Rome, Italy, and included 12 adult patients with CM treated with OBTA and 15 healthy controls (HC). Patients underwent clinical scales at enrollment (T0) and 3 months (T1) from the start of treatment. HD-EEG was recorded using a 64-channel system in patients with CM at T0 and T1. A source reconstruction method was used to identify brain activity. FC in δ-θ-α-ß-low-γ bands was analyzed using the weighted phase-lag index. FC changes between HCs and CM at T0 and T1 were assessed using cross-validation methods to estimate the results' reliability. RESULTS: Compared to HCs at T0, patients with CM showed hyperconnected networks in δ (p = 0.046, area under the receiver operating characteristic curve [AUC: 0.76-0.98], Cohen's κ [0.65-0.93]) and ß (p = 0.031, AUC [0.68-0.95], Cohen's κ [0.51-0.84]), mainly involving orbitofrontal, occipital, temporal pole and orbitofrontal, superior temporal, occipital, cingulate areas, and hypoconnected networks in α band (p = 0.029, AUC [0.80-0.99], Cohen's κ [0.42-0.77]), predominantly involving cingulate, temporal pole, and precuneus. Patients with CM at T1, compared to T0, showed hypoconnected networks in δ band (p = 0.032, AUC [0.73-0.99], Cohen's κ [0.53-0.90]) and hyperconnected networks in α band (p = 0.048, AUC [0.58-0.93], Cohen's κ [0.37-0.78]), involving the sensorimotor, orbitofrontal, cingulate, and temporal cortex. CONCLUSION: These preliminary results showed that patients with CM presented disrupted EEG-FC compared to controls restored by a single session of OBTA treatment, suggesting a primary central modulatory action of OBTA.
Subject(s)
Botulinum Toxins, Type A , Electroencephalography , Migraine Disorders , Humans , Botulinum Toxins, Type A/pharmacology , Botulinum Toxins, Type A/administration & dosage , Pilot Projects , Migraine Disorders/drug therapy , Migraine Disorders/physiopathology , Female , Male , Adult , Electroencephalography/drug effects , Middle Aged , Chronic Disease , Prospective Studies , Neuromuscular Agents/pharmacology , Neuromuscular Agents/administration & dosage , Brain/drug effects , Brain/physiopathology , Brain/diagnostic imagingABSTRACT
The aim of this study was to develop and validate a fast and sensitive bioanalytical method for the accurate quantification of fosfomycin concentrations in human prostatic tissue. The sample preparation method only required milligrams of tissue sample. Each sample was mixed with two times its weight of water and homogenized. A methanol solution that was three times the volume of the internal standard (fosfomycin-13C3) was added, followed by vortex mixing and centrifugation. After its extraction from the homogenized prostatic tissue, fosfomycin was quantified by means of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) triple quadrupole system operating in negative electrospray ionization and multiple reaction monitoring detection mode. The analytical procedure was successfully validated in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, and stability, according to EMA guidelines. The validation results, relative to three QC levels, were 9.9% for both the within-day and inter-day accuracy (BIAS%); 9.8% for within-day precision; and 9.9 for between-day precision. A marked matrix effect was observed in the measurements but was corrected by normalization with the internal standard. The average total recovery was high (approximatively 97% at the three control levels). The dynamic range of the method was 0.1-20 µg/g (R2 of 0.999). Negligible carry-over was observed after the injection of highly concentrated samples. F in the sample homogenate extracts was stable at 10 °C and 4 °C for at least 24 h. In the tissue sample freeze-thaw experiments, a significant decrease in F concentrations was observed after only two cycles from -80 °C to room temperature. The novel method was successfully applied to measure fosfomycin in prostatic tissue samples collected from 105 patients undergoing prostatectomy.
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BACKGROUND: Sensorial non-motor symptoms (NMSs) in Parkinson's disease (PD) still lack appropriate investigation in clinical practice. This study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient's quality of life (QoL). METHODS: We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. Demographic and clinical data were collected. Patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed Non-Motor Symptoms Scale (NMSS) and Parkinson's Disease Questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis. RESULTS: 60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25 dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS. CONCLUSION: This study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. Our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL.
Subject(s)
Parkinson Disease , Quality of Life , Humans , Parkinson Disease/complications , Parkinson Disease/physiopathology , Male , Female , Aged , Middle Aged , Audiometry, Pure-Tone , Hearing Loss/physiopathology , Hearing Loss/etiology , Cost of Illness , Surveys and Questionnaires , Otoacoustic Emissions, Spontaneous/physiology , Severity of Illness IndexABSTRACT
INTRODUCTION: In this work, we describe a new case of association between SCA2 and MND. CASE REPORT: A 58-year-old man who was diagnosed with spinocerebellar ataxia type 2 presented dysphagia and a significant decline in his ability to walk, with a reduction in autonomy and the need to use a wheelchair. We performed electromyography and electroneurography of the four limbs and of the cranial district and motor-evoked potentials to study upper and lower motor neurons. Referring to the revised El Escorial criteria of 2015, ALS diagnosis was made. DISCUSSION: Considering different cases described in literature over the years, SCA2 could represent an important risk factor for developing ALS. In particular, the presence of alleles of ATXN2 with 27 and 28 CAG repeats seems to slightly decrease the risk of developing the disease, which would instead be progressively increased by the presence of alleles with 29, 30, 31, 32, and 33 repeats. The exact physiopathological mechanism by which the mutation increases the risk of developing the disease is currently unknown. Transcriptomic studies on mouse models have demonstrated the involvement of several pathways, including the innate immunity regulation by STING and the biosynthesis of fatty acid and cholesterol by SREBP. CONCLUSION: CAG repeat expansions in the ATXN2 gene have been associated with variable neurological presentations, which include SCA2, ALS, Parkinsonism, or a combination of them. Further research is needed to understand the relationship between SCA2 and ALS better and explore molecular underlying mechanisms.
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Amyotrophic Lateral Sclerosis , Ataxin-2 , Spinocerebellar Ataxias , Humans , Male , Middle Aged , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/diagnosis , Amyotrophic Lateral Sclerosis/complications , Spinocerebellar Ataxias/genetics , Spinocerebellar Ataxias/complications , Spinocerebellar Ataxias/physiopathology , Ataxin-2/genetics , Trinucleotide Repeat Expansion/geneticsABSTRACT
Despite the availability of new classes of glucose-lowering drugs that improve glycaemic levels and minimise long-term complications, at least 20-25% of people with type 2 diabetes require insulin therapy. Moreover, a substantial proportion of these individuals do not achieve adequate metabolic control following insulin initiation. This is due to several factors: therapeutic inertia, fear of hypoglycaemia and/or weight gain, poor communication, complexity of insulin titration, and the number of injections needed, with the associated reduced adherence to insulin therapy. Once-weekly insulins provide a unique opportunity to simplify basal insulin therapy and to allow good glycaemic control with a low risk of hypoglycaemia. Several approaches to developing a stable and effective once-weekly insulin have been proposed, but, to date, insulin icodec and basal insulin Fc (insulin efsitora alfa) are the only two formulations for which clinical studies have been reported. The results of Phase I and II studies emphasise both efficacy (in term of glucose levels) and potential risks and adverse events. Phase III studies involving insulin icodec are reassuring regarding the risk of hypoglycaemia compared with daily basal insulin analogues. Despite some concerns raised in ongoing clinical trials, the available data suggest that weekly insulins may also be an option for individuals with type 1 diabetes, especially when adherence is suboptimal. For the first time there is an opportunity to make an important breakthrough in basal insulin therapy, particularly in people with type 2 diabetes, and to improve not only the quality of life of people with diabetes, but also the practice of diabetologists.
Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Insulin , Humans , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/administration & dosage , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Insulin/therapeutic use , Insulin/administration & dosage , Drug Administration Schedule , Blood Glucose/drug effects , Blood Glucose/metabolism , Hypoglycemia/prevention & control , Hypoglycemia/chemically induced , Insulin, Long-Acting/therapeutic use , Insulin, Long-Acting/administration & dosageABSTRACT
AIMS: Several studies showed that Assisted Reproductive Technology (ART) could affect gestational diabetes mellitus (GDM) onset. The aim of this study was to estimate the prevalence of GDM risk factors in a cohort of women with singleton pregnancy obtained by ART and complicated by GDM. Maternal and neonatal outcomes were explored. METHODS: We retrospectively collected data of pregnancies of women with singleton pregnancy obtained by ART and complicated by GDM consecutively cared for at a specialized center for diabetes and pregnancy care. Prevalence and combination of GDM risk factors, their combinations and maternal-fetal outcomes were estimated. RESULTS: Overall, our cohort included 50 women (mean age of 40.4 ± 4.7 years, mean pre-pregnancy BMI 26.3 ± 6.2 kg/m2). The most frequent GDM traditional risk factors were age ≥ 35 years (94 %), family history of diabetes (44 %), overweight (29 %) and obesity (19 %). Combining risk factors, 5 groups were identified with 1, 2, 3, 4, or 5 risk factors with a prevalence respectively of 28 %, 46 %, 20 %, 4 %, and 2 %. Examining features of the above groups, pre-pregnancy weight (p < 0.0001) and pre-pregnancy BMI (p < 0.0001) statistically significant differed in the 5 groups, increasing with higher numbers of risk factors. Regarding neonatal outcomes only neonatal hypoglycemia (p = 0.03) differed significantly among the groups, with higher percentages in women with higher numbers of combined risk factors. CONCLUSION: Prevalence of GDM traditional risk factors in singleton ART pregnancies complicated by GDM is considerable. Such pregnancies need appropriate clinical attention because of the risk of adverse outcomes.
Subject(s)
Diabetes, Gestational , Pregnancy , Infant, Newborn , Female , Humans , Adult , Middle Aged , Diabetes, Gestational/epidemiology , Diabetes, Gestational/etiology , Retrospective Studies , Prevalence , Risk Factors , Registries , Pregnancy Outcome/epidemiologyABSTRACT
Parkinson's disease (PD) symptomatology differs between females and males, yet the contribution of sex on sleep problems needs further analysis. Here, we aimed to investigate sex-specific patterns in the relationship between sleep problems, assessed using the Parkinson's disease sleep scale (PDSS-2), non motor symptoms (NMS), measured by the NMS scale (NMSS), and health-related quality of life (HR-QoL), evaluated by the Parkinson's disease questionnaire (PDQ-39), in a large cohort of PD patients. One-hundred-fifty-four PD patients were included in the study. Female PD patients (n = 62) exhibited a higher prevalence of sleep problems than males (n = 92), with nocturnal motor-related sleep issues being the most frequent. Sleep disturbances differently correlated with a range of NMS between the two sexes. In females, sleep problems mostly correlated with pain; on the other hand, sleep disturbances were linked to a frailer phenotype characterized by global dysautonomia, perception disturbances, and impaired cognitive function in males. Whether female PD patients experienced a lower HR-QoL than males, sleep disturbances were associated with a worse HR-QoL in both sexes. In conclusion, sleep problems in PD differently burden the two sexes, suggesting possible different etiopathogenesis, diagnostic investigations, and possibly tailored approaches.
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Menopause increases the risk for Parkinson's disease (PD), although the underlying biological mechanisms have not been established in patients. Here, we aimed to understand the basis of menopause-related vulnerability to PD. Main motor and non-motor scores, blood levels of estradiol, testosterone, follicle-stimulating hormone, and luteinizing hormone, CSF levels of total α-synuclein, amyloid-ß-42, amyloid-ß-40, total tau, and phosphorylated-181-tau were examined in 45 women with postmenopausal-onset PD and 40 age-matched controls. PD patients had higher testosterone and lower estradiol levels than controls, and the residual estradiol production was associated with milder motor disturbances and lower dopaminergic requirements. In PD but not in controls, follicle-stimulating hormone levels correlated with worse cognitive scores and CSF markers of amyloidopathy and neuronal loss. In conclusion, menopause-related hormonal changes might differentially contribute to clinical-pathological trajectories of PD, accounting for the peculiar vulnerability to the disease.
Subject(s)
Parkinson Disease , Postmenopause , tau Proteins , Humans , Female , Parkinson Disease/blood , Parkinson Disease/cerebrospinal fluid , Postmenopause/blood , Middle Aged , Aged , tau Proteins/cerebrospinal fluid , tau Proteins/blood , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Peptides/blood , Estradiol/blood , alpha-Synuclein/blood , alpha-Synuclein/cerebrospinal fluid , Follicle Stimulating Hormone/blood , Follicle Stimulating Hormone/cerebrospinal fluid , Testosterone/blood , Testosterone/cerebrospinal fluid , Peptide Fragments/cerebrospinal fluid , Peptide Fragments/blood , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Luteinizing Hormone/blood , Luteinizing Hormone/cerebrospinal fluidABSTRACT
Background: Calabria, the southernmost tip of the Italian Peninsula, is a biogeographically very interesting region for lichenologists, characterised by the abundance of oceanic and suboceanic species with subtropical affinities, but also by the presence of the southernmost outposts of several boreal species on the highest peaks. The lichen biota of Calabria, which began to be intensively studied only from the 1980s, hosts more than 1000 infrageneric taxa. The lichen herbarium of the Botanical Garden of the University of Calabria (CLU) is the most relevant lichen collection from this region. It was established in 1985 and it presently includes 16926 specimens, most of which were collected in Calabria, although there are also several specimens from other parts of Italy and from abroad. New information: This dataset contains 16926 records of lichens for a total of 1316 species. Of the 15219 georeferenced specimens, 10254 were collected in Calabria, while 4965 in other administrative regions of Italy. The dataset is available through GBIF, as well as in ITALIC, the Information System of Italian Lichens.
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The Dolichens project provides the first dynamic inventory of the lichens of the Dolomites (Eastern Alps, Italy). Occurrence records were retrieved from published and grey literature, reviewed herbaria, unpublished records collected by the authors, and new sampling campaigns, covering a period from 1820 to 2022. Currently, the dataset contains 56,251 records, referring to 1,719 infrageneric taxa, reported from 1820 to 2022, from hilly to nival belts, and corresponding to about half of the species known for the whole Alpine chain. Amongst them, 98% are georeferenced, although most of them were georeferenced a posteriori. The dataset is available through the Global Biodiversity Information Facility (GBIF; https://www.gbif.org/es/dataset/cea3ee2c-1ff1-4f8e-bb37-a99600cb4134) and through the Dolichens website (https://italic.units.it/dolichens/). We expect that this open floristic inventory will contribute to tracking the lichen diversity of the Dolomites over the past 200 years, and providing the basis for future taxonomic, biogeographical, and ecological studies.
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Vaccines have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality, yet emerging variants challenge their effectiveness. The prevailing approach to updating vaccines targets the antibody response, operating under the presumption that it is the primary defense mechanism following vaccination or infection. This perspective, however, can overlook the role of T cells, particularly when antibody levels are low or absent. Here we show, through studies in mouse models lacking antibodies but maintaining functional B cells and lymphoid organs, that immunity conferred by prior infection or mRNA vaccination can protect against SARS-CoV-2 challenge independently of antibodies. Our findings, using three distinct models inclusive of a novel human/mouse ACE2 hybrid, highlight that CD8+ T cells are essential for combating severe infections, whereas CD4+ T cells contribute to managing milder cases, with interferon-γ having an important function in this antibody-independent defense. These findings highlight the importance of T cell responses in vaccine development, urging a broader perspective on protective immunity beyond just antibodies.
Subject(s)
COVID-19 , Vaccines , Humans , Animals , Mice , SARS-CoV-2 , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , Antibodies , Vaccination , Antibodies, Viral , Antibodies, NeutralizingABSTRACT
Intermittently Scanned Continuous Glucose Monitoring (isCGM) devices are increasingly being used in patients with type 2 diabetes mellitus (T2DM) on insulin therapy for their benefits regarding disease management. Evidence of isCGM use in patients with T2DM on basal or non-insulin therapy is lacking. This study aimed at assessing the efficacy and safety of isCGM in this population. This was an observational, retrospective, real-world study enrolling patients with T2DM who were starting the use of isCGM. Data from medical records (i.e., demographics, clinical characteristics, laboratory assessments, and isCGM metrics) were collected over three time periods (baseline, 3 and 6 months). The endpoints were glycated haemoglobin (HbA1c) changes and changes in isCGM metrics as defined by the International Consensus from baseline to 3 months and 6 months. Overall, 132 patients were included (69.5% male; mean age 68.2 ± 11.0 years; mean disease duration 19.0 ± 9.4 years; 79.7% on basal insulin ±non-insulin therapy; mean baseline HbA1c 8.1% ± 1.3%). The estimated mean change in HbA1c was statistically significant at three (-0.4 ± 1.0%; p = 0.003) and six months (-0.6 ± 1.3%; p < 0.0001). In conclusion, isCGM proved to be effective and safe in improving glycaemic control in patients with T2DM on basal insulin or non-insulin therapy.
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REM sleep behavior disorder (RBD) is a frequent non-motor symptom of Parkinson's disease (PD), and the timing of its presentation might have a role in the underlying neurodegenerative process. Here, we aimed to define the potential impact of probable RBD (pRBD) on PD motor progression.We conducted a longitudinal retrospective study on 66 PD patients followed up at the University Hospital of Rome Tor Vergata. Patients were divided into three groups: with post-motor pRBD (pRBDpost, n = 25), without pRBD (pRBDwo, n = 20), and with pre-motor pRBD (pRBDpre, n = 21). Hoehn and Yahr (H&Y) scores, Unified PD Rating Scale (UPDRS) motor scores, and levodopa equivalent daily dose were collected at two follow-up visits conducted in a 5-year interval (T0 and T1). pRBDpost patients had a greater rate of motor progression in terms of the H&Y scale compared to pRBDpre and pRBDwo patients, without the influence of anti-parkinsonian treatment.These preliminary findings suggest that the post-motor occurrence of pRBD can be associated with an acceleration in PD motor progression.
Subject(s)
Parkinson Disease , REM Sleep Behavior Disorder , Humans , Parkinson Disease/complications , Parkinson Disease/drug therapy , Parkinson Disease/epidemiology , Retrospective Studies , REM Sleep Behavior Disorder/diagnosis , REM Sleep Behavior Disorder/etiology , Levodopa , Longitudinal StudiesABSTRACT
INTRODUCTION: As the most common cause of autosomal recessive early onset Parkinson's disease (EOPD), parkin type Parkinson's disease (PRKN-PD) may affect female patients in childbearing age. Accordingly, issues related to fertility must be adequately addressed. Here, we landscaped fertile life factors and pregnancy course of a PRKN-PD cohort, including both novel cases directly observed at our center and published ones. METHODS: Six patients with confirmed PRKN-PD were examined by a structured interview on reproductive factors and associated modifications of PD disturbances, including one case followed up throughout pregnancy which was described in greater detail. Six studies reporting fertile life factors of nine PRKN-PD patients were reviewed collecting homogeneous data on fertile life and pregnancy course. RESULTS: PRKN-PD female patients experienced motor fluctuations with the menstrual cycle, pregnancy, and puerperium, which suggests a role for sex hormones in PD clinical burden. In some cases, abortion and miscarriages occurred during the organogenesis phase in patients receiving oral antiparkinsonian therapy; however, levodopa/benserazide monotherapy resulted to be the safest choice in pregnancy. CONCLUSION: Collectively these data disclose the importance of pre-conception counseling in childbearing age PRKN-PD patients and EOPD in general.