Exploring factors shaping antibiotic resistance patterns in Streptococcus pneumoniae during the 2020 COVID-19 pandemic.

Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.

The interactions of SARS-CoV-2 with cocirculating pathogens: Epidemiological implications and current knowledge gaps.

Despite the availability of effective vaccines, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that cocirculation with other pathogens and resulting multiepidemics (of, for example, COVID-19 and influenza) may become increasingly frequent. To better forecast and control the risk of such multiepidemics, it is essential to elucidate the potential interactions of SARS-CoV-2 with other pathogens; these interactions, however, remain poorly defined. Here, we aimed to review the current body of evidence about SARS-CoV-2 interactions. Our review is structured in four parts. To study pathogen interactions in a systematic and comprehensive way, we first developed a general framework to capture their major components: sign (either negative for antagonistic interactions or positive for synergistic interactions), strength (i.e., magnitude of the interaction), symmetry (describing whether the interaction depends on the order of infection of interacting pathogens), duration (describing whether the interaction is short-lived or long-lived), and mechanism (e.g., whether interaction modifies susceptibility to infection, transmissibility of infection, or severity of disease). Second, we reviewed the experimental evidence from animal models about SARS-CoV-2 interactions. Of the 14 studies identified, 11 focused on the outcomes of coinfection with nonattenuated influenza A viruses (IAVs), and 3 with other pathogens. The 11 studies on IAV used different designs and animal models (ferrets, hamsters, and mice) but generally demonstrated that coinfection increased disease severity compared with either monoinfection. By contrast, the effect of coinfection on the viral load of either virus was variable and inconsistent across studies. Third, we reviewed the epidemiological evidence about SARS-CoV-2 interactions in human populations. Although numerous studies were identified, only a few were specifically designed to infer interaction, and many were prone to multiple biases, including confounding. Nevertheless, their results suggested that influenza and pneumococcal conjugate vaccinations were associated with a reduced risk of SARS-CoV-2 infection. Finally, fourth, we formulated simple transmission models of SARS-CoV-2 cocirculation with an epidemic viral pathogen or an endemic bacterial pathogen, showing how they can naturally incorporate the proposed framework. More generally, we argue that such models, when designed with an integrative and multidisciplinary perspective, will be invaluable tools to resolve the substantial uncertainties that remain about SARS-CoV-2 interactions.

The environmentally friendly approaches based on the heterojunction interface of the LaFeO3/Fe2O3@g-C3N4 composite for the disposable and laboratory sensing of triclosan.

Triclosan (TCS) is a polychlorinated phenoxy phenol (PCPPs) used as a disinfectant and a broad-spectrum antibacterial and antifungal agent in personal hygiene products. TCS easily forms diphenyl ethers and dioxins, which are persistent organic pollutants. This work used a double approach for the TSC sensing: a) screen-printed (SPE) electrochemical platform for on-site application, modified with lanthanum iron oxide and graphitic carbon nitride composite (LaFeO3/Fe2O3@g-C3N4/SPE); and b) carbon paste electrode (CPE), modified with the same material and used in laboratory conditions. Linear range from 0.1 µM to 10 µM, the limit of detection (LOD) of 29 nM and the limit of quantification (LOQ) of 91 nM were obtained for CP electrode in BRBS pH 8. SPE showed the best analytical parameters in BRBS at pH 3, with a linear range from 0.3 µM to 7 µM, LOD of 0.09 µM and LOQ of 0.28 µM. Furthermore, the influence of potential interferents was investigated and proven to be negligible. Determination of TSC was performed to estimate the environmental impact of this compound as well as the practical usefulness of the proposed sensor in the real sample analysis, confirmed with a HPLC analysis.

Vascular comorbidities in patients with multiple sclerosis and their impact on physical disability.

Aim Given the impact of vascular comorbidities (VC) on the diagnosis, treatment, and outcome of multiple sclerosis (MS), we examined the incidence and correlation of VC and risk factors for vascular disease in people with MS (PwMS) compared to the general population, and the impact on the physical disability of patients. Methods Cross-sectional study involved 100 patients with MS and 50 healthy people from the general population, matched by sex and age. The values of demographic, biochemical, and anthropometric parameters, the presence of VC and risk factors for vascular diseases in both groups, and clinical parameters in PwMS were analysed. Statistical analysis included methods of descriptive statistics, χ2 test, Student's t-test, analysis of variance, correlation and regression analysis. Results Groups differed by a higher frequency of transient ischemic attack in the control group (p=0.024), and the treatment of hypertension (p=0.038) and smoking frequency (p=0.044) in the MS group. Normal triglycerides levels were statistically significantly more prevalent in the MS group (p=0.000). Total body weight and BMI were statistically significantly higher in the control group (p=0.000). The increase in Expanded Disability Status Scale (EDSS) score was associated with higher levels of total (p=0.001) and low-density lipoprotein (LDL) cholesterol (p=0.003), and activated partial thromboplastin time APTT (p=0.002). Conclusion In PwMS it is necessary to pay attention to the higher frequency of smoking than in general population, and the impact of total cholesterol, LDL and APTT levels as significant parameters that affect physical disability.

Influence of Gender, Body Mass Index, and Age on the Pharmacokinetics of Itraconazole in Healthy Subjects: Non-Compartmental Versus Compartmental Analysis.

Itraconazole is a triazole antifungal agent with highly variable pharmacokinetics, with not yet fully identified factors as the source of this variability. Our study aimed to examine the influence of body mass index, gender, and age on the first dose pharmacokinetics of itraconazole in healthy subjects, using pharmacokinetic modeling, non-compartmental versus compartmental ones. A total of 114 itraconazole and hydroxy-itraconazole sets of plasma concentrations of healthy subjects of both genders, determined using a validated liquid chromatographic method with mass spectrometric detection (LC-MS), were obtained for pharmacokinetic analyses performed by the computer program Kinetica 5®. Genetic polymorphism in CYP3A4, CYP3A5, CYP1A1, CYP2C9, and CYP2C19 was analyzed using PCR-based methods. Multiple linear regression analysis indicated that gender had a significant effect on AUC as the most important pharmacokinetics endpoint, whereas body mass index and age did not show such an influence. Therefore, further analysis considered gender and indicated that both geometric mean values of itraconazole and hydroxy-itraconazole plasma concentrations in men were prominently higher than those in women. A significant reduction of the geometric mean values of Cmax and AUC and increment of Vd in females compared with males were obtained. Analyzed genotypes and gender differences in drug pharmacokinetics could not be related. Non-compartmental and one-compartmental models complemented each other, whereas the application of the two-compartmental model showed a significant correlation with the analysis of one compartment. They indicated a significant influence of gender on itraconazole pharmacokinetics after administration of the single oral dose of the drug, given under fed conditions. Women were less exposed to itraconazole and hydroxy-itraconazole than men due to poorer absorption of itraconazole, its more intense pre-systemic metabolism, and higher distribution of both drug and its metabolite.

Symptomatic and neurotrophic effects of GABAA receptor positive allosteric modulation in a mouse model of chronic stress.

Chronic stress is a risk factor for Major Depressive Disorder (MDD), and in rodents, it recapitulates human behavioral, cellular and molecular changes. In MDD and after chronic stress, neuronal dysfunctions and deficits in GABAergic signaling are observed and responsible for symptom severity. GABA signals predominantly through GABAA receptors (GABAA-R) composed of various subunit types that relate to downstream outcomes. Activity at α2-GABAA-Rs contributes to anxiolytic properties, α5-GABAA-Rs to cognitive functions, and α1-GABAA-Rs to sedation. Therefore, a therapy aiming at increasing α2- and α5-GABAA-Rs activity, but devoid of α1-GABAA-R activity, has potential to address several symptomologies of depression while avoiding side-effects. This study investigated the activity profiles and behavioral efficacy of two enantiomers of each other (GL-II-73 and GL-I-54), separately and as a racemic mixture (GL-RM), and potential disease-modifying effects on neuronal morphology. Results confirm GL-I-54 and GL-II-73 exert positive allosteric modulation at the α2-, α3-, α5-GABAA-Rs and α5-containing GABAA-Rs, respectively, and separately reduces immobility in the forced swim test and improves stress-induced spatial working memory deficits. Using unpredictable chronic mild stress (UCMS), we show that acute and chronic administration of GL-RM provide pro-cognitive effects, with mild efficacy on mood symptoms, although at lower doses avoiding sedation. Morphology studies showed reversal of spine density loss caused by UCMS after chronic GL-RM treatment at apical and basal dendrites of the PFC and CA1. Together, these results support using a racemic mixture with combined α2-, α3-, α5-GABAA-R profile to reverse chronic stress-induced mood symptoms, cognitive deficits, and with anti-stress neurotrophic effects.

Modelling imperfect knowledge via location semantics for realistic privacy risks estimation in trajectory data.

Mobility patterns of vehicles and people provide powerful data sources for location-based services such as fleet optimization and traffic flow analysis. Location-based service providers must balance the value they extract from trajectory data with protecting the privacy of the individuals behind those trajectories. Reaching this goal requires measuring accurately the values of utility and privacy. Current measurement approaches assume adversaries with perfect knowledge, thus overestimate the privacy risk. To address this issue, we introduce a model of an adversary with imperfect knowledge about the target. The model is based on equivalence areas, spatio-temporal regions with a semantic meaning, e.g. the target's home, whose size and accuracy determine the skill of the adversary. We then derive the standard privacy metrics of k-anonymity, l-diversity and t-closeness from the definition of equivalence areas. These metrics can be computed on any dataset, irrespective of whether and what kind of anonymization has been applied to it. This work is of high relevance to all service providers acting as processors of trajectory data who want to manage privacy risks and optimize the privacy vs. utility trade-off of their services.

The Impact of Cocirculating Pathogens on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/Coronavirus Disease 2019 Surveillance: How Concurrent Epidemics May Introduce Bias and Decrease the Observed SARS-CoV-2 Percentage Positivity.

BACKGROUND: Circulation of seasonal non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) respiratory viruses with syndromic overlap during the coronavirus disease 2019 (COVID-19) pandemic may alter the quality of COVID-19 surveillance, with possible consequences for real-time analysis and delay in implementation of control measures. METHODS: Using a multipathogen susceptible-exposed-infectious-recovered (SEIR) transmission model formalizing cocirculation of SARS-CoV-2 and another respiratory virus, we assessed how an outbreak of secondary virus may affect 2 COVID-19 surveillance indicators: testing demand and positivity. Using simulation, we assessed to what extent the use of multiplex polymerase chain reaction tests on a subsample of symptomatic individuals can help correct the observed SARS-CoV-2 percentage positivity and improve surveillance quality. RESULTS: We find that a non-SARS-CoV-2 epidemic strongly increases SARS-CoV-2 daily testing demand and artificially reduces the observed SARS-CoV-2 percentage positivity for the duration of the outbreak. We estimate that performing 1 multiplex test for every 1000 COVID-19 tests on symptomatic individuals could be sufficient to maintain surveillance of other respiratory viruses in the population and correct the observed SARS-CoV-2 percentage positivity. CONCLUSIONS: This study showed that cocirculating respiratory viruses can distort SARS-CoV-2 surveillance. Correction of the positivity rate can be achieved by using multiplex polymerase chain reaction tests, and a low number of samples is sufficient to avoid bias in SARS-CoV-2 surveillance.

Longitudinal study of neuropathic pain in patients with Guillain-Barré syndrome.

OBJECTIVE: The aim of this study was to analyze neuropathic pain (NeP) and its therapy in patients with Guillain-Barré syndrome (GBS) during a 6-month follow-up period. METHOD: This longitudinal multicenter study included 69 newly diagnosed adult GBS patients. NeP diagnosis was based on the criteria of Finnerup and confirmed by the PainDETECT Questionnaire (PD-Q). Severity of GBS was assessed by GBS disability scale (GDS). Patients were assessed: on day 14 (D14), day 28 (D28), month 3 (M3), and month 6 (M6) from the disease onset. RESULTS: At D14, pain was present in 85.5% of patients, while 26.4% had NeP. At M6, 72.5% of patients had pain, 20.0% of them NeP. In acute GBS, pain intensity was higher in patients with NeP compared to those with non-NeP (p < 0.01). Pain intensity in patients with NeP did not change during time, but it decreased in patients with non-NeP at M6 (p < 0.05). Around 20% of GBS patients were on specific NeP medication throughout the observed period. One quarter of patients with NeP were not on specific NeP drug in the acute phase. Up to one third of patients with NeP were on NeP medication but still had significant NeP. Pooled PD-Q score was in correlation with pooled GDS score (rho = + 0.43, p < 0.01). CONCLUSIONS: NeP is a common and potentially severe symptom in GBS that may persist for months. It is important to recognize NeP, start specific treatment on time, in adequate doses, and for prolonged period of time.

Six-month prospective study of quality of life in Guillain-Barre syndrome.

OBJECTIVE: Guillain-Barre syndrome (GBS) is an acute disease of the peripheral nerves and their roots. Quality of life (QoL) in the first year after acute episode of GBS is still underresearched area. The aim of our study was to investigate QoL in GBS patients during a 6-month follow-up period. METHODS: Multicentric, prospective study included 74 adult patients with GBS (54% males). GBS disability scale (GDS) was used to assess functional disability (severe disability GDS > 2), and Individualized Neuromuscular Quality of Life Questionnaire (INQoL) to asses QoL. Patients were tested on day 14, day 28, month 3, and month 6 from symptom onset. RESULTS: Disability as measured by GDS improved during time (P < .01). INQoL scores also improved during time (P < .01) but were not able to differentiate between day 14 and day 28, and some scores also did not make difference between month 3 and 6 (pain, social relations, emotions and total INQoL score; P > .05). Pooled GDS scores correlated with pooled INQoL scores, especially with independence, activities, and weakness subscores (P < .01). Multiple linear regression analysis showed that GDS at day 14 (ß = .52, P < .01) and fatigue score at day 14 (ß = .41, P < .01) were independent predictors of the worse GDS at month 6 (adjusted R2  = .34, P < .01 for overall model). CONCLUSIONS: During a 6-month follow-up period of GBS patients, we observed a gradual recovery of patients' disability and QoL. Our study confirms the importance of patient-reported outcomes and their ability to capture some important issues that are omitted by classic ability measures such as GDS.

Recurrent Guillain-Barré Syndrome - Case Series.

Recurrent Guillain-Barré syndrome (RGBS) episodes appear in up to 6% of Guillain-Barré syndrome (GBS) patients. The purpose of this study was to identify patients with previous episodes of GBS and to assess their clinical features in a large cohort of adult GBS patients. GBS patients hospitalized at tertiary centers in three Balkan countries were included in the study (n = 404). We identified 13 (3.2%) patients with recurrent GBS (RGBS). The male to female ratio was 3: 1. All RGBS patients had two episodes of the disease. The most common GBS subtype in both episodes of the disease was acute inflammatory demyelinating polyradiculoneuropathy (AIDP) (77%, first episode; 85%, second episode). Around 23% of patients presented with a different variant during the second GBS attack. Disability seems to be equally severe at both episodes (P > 0.05). Recurrent GBS was registered in 3% of our GBS patients. The majority of them were younger males. Different GBS subtypes were found to recur.

Rate dynamics of ectotherm responses to thermal stress.

Critical thermal limits (CTLs) show much variation associated with the experimental rate of temperature change used in their estimation. Understanding the full range of variation in rate effects on CTLs and their underlying basis is thus essential if methodological noise is not to overwhelm or bias the ecological signal. We consider the effects of rate variation from multiple intraspecific assessments and provide a comprehensive empirical analysis of the rate effects on both the critical thermal maximum (CTmax) and critical thermal minimum (CTmin) for 47 species of ectotherms, exploring which of the available theoretical models best explains this variation. We find substantial interspecific variation in rate effects, which takes four different forms (increase, decline, no change, mixed), with phylogenetic signal in effects on CTmax, but not CTmin. Exponential and zero exponential failure rate models best explain the rate effects on CTmax. The majority of the empirical rate variation in CTmin could not be explained by the failure rate models. Our work demonstrates that rate effects cannot be ignored in comparative analyses, and suggests that incorporation of the failure rate models into such analyses is a useful further avenue for exploration of the fundamental basis and implications of such variation.

Metamizole Utilization and Expenditure During 6-Year Period: Serbia vs. Croatia.

Background: Metamizole is a medication with analgesic, antipyretic, spasmolytic, and weak anti-inflammatory effects. The aim of our study was to evaluate a six-year trend in the utilization and expenditure of metamizole in comparison to other group of licensed non-opioid analgesics in Serbia and Croatia, in order to rationalize its use and prescribing in these countries. Methods: The data of metamizole vs. all other non-opioid analgesics utilization and expenditure in Serbia and Croatia was analyzed according to the WHO methodology and expressed as defined daily doses per 1,000 inhabitants per day (DDD/1,000 inhabitants/per day) and total costs, respectively, during the 6-year period from 2010 to 2015. Results: In the observed period, utilization of metamizole was 3.31 fold higher in Serbia than in Croatia (median in Serbia was 2.238 vs. 0.675 in Croatia DDD/1,000 inhabitants/per day/per year). Expenditure of metamizole in the same period was 5.29-fold higher in Serbia than in Croatia (median in Serbia was 1,738,192.51 €/per year vs. 328,355.03 €/per year in Croatia). Conclusion: Utilization and expenditure of non-opioid analgesics, including metamizole, in Serbia was significantly higher comparing with Croatia.Further research is needed to determine whether the current analgesic consumption in Serbia meets the needs of the patient. The benefits of metamizole should be weighed against the risk of metamizole-induced adverse effects. Until then, its prescribing should be based on indications and the appropriate duration of therapy.

The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in Rats.

Amifostine is well known cytoprotector which is efficient when administered before a wide range of antineoplastic agents. The aim of our study was to investigate amifostine effects on doxorubicin-induced toxic changes in rats. Amifostine (75 mg/kg ip) was given 30 min before each dose of doxorubicin (cumulatively 20 mg/kg ip, for 28 days). The animals' whole-body, liver, and kidney weight, serum biochemical examination, as well as microscopic examination of bone marrow, peripheral blood, liver, and kidney, were done on day 56 of the study. Hepatic and renal alterations were carefully quantified by semiquantitative grading scales-hepatic and renal damage score, respectively. In amifostine-pretreated rats, the number of peripheral blood leukocytes was significantly higher in comparison to doxorubicin-only treated group, preferentially protecting neutrophils. In the same group of rats, hepatic and renal alterations associated with polymorphonuclear cell infiltrates were significantly less severe than those observed in animals receiving only doxorubicin. Our results showed that amifostine successfully protected rats against multiple-dose doxorubicin-induced toxicity by complex, and still not fully elucidated mechanisms of action.

Frequency and features of the central poststroke pain.

BACKGROUND: Central poststroke pain (CPSP) is often unrecognized in clinical practice, it may aggravate the rehabilitation process and reduce quality of life. AIM: To determine the frequency and features of CPSP, as well as to make possible associations of CPSP with sociodemographic and clinical features of subjects with stroke. METHOD: In a two-year period 602 patients with previous stroke were consecutively tested. We used three questionnaires for the diagnosis of neuropathic pain (Pain Detect Questionnaire - PD-Q, The Leeds Assessment of Neuropathic Symptoms and Signs - LANSS and Douleur neuropatathique en 4 questions - DN4). RESULTS: CPSP was present in 12% of our patients with stroke, and usually occurred in the first several months after stroke. It was associated with cortical and thalamic localization of stroke, higher level of functional disability, as well as with younger age. The most important features that distinguish CPSP from other types of pain were presence of allodynia and pricking hypoesthesia, while other neuropathic sensations were common in stroke subjects both with and without CPSP. CONCLUSION: Younger subjects with cortical/thalamic stroke and higher level of disability should be thoroughly examined for the presence of neuropatic pain, since this may highly influence therapeutic strategy and quality of life in these subjects.

Bioequivalence study of two formulations of itraconazole 100 mg capsules in healthy volunteers under fed conditions: a randomized, three-period, reference-replicated, crossover study.

BACKGROUND: The aim of the study was to evaluate the bioequivalence of two itraconazole 100 mg capsule formulations. RESEARCH DESIGN AND METHODS: The single-center, open-label, randomized, three-period, three-sequence, reference-replicated, cross-over study included 38 healthy subjects under fed conditions. In each study period (separated by a 14-day washout), a single oral dose of the test (T) or reference (R) product was administered. Blood samples were collected at pre-dose and up to 72.0 h after administration. The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxy itraconazole, were AUC0-72h, AUC0-∝, Cmax, Tmax, T1/2 and Kel. RESULTS: The 90% CI for the test/reference geometric means ratio for the parent compound, itraconazole, was in the range from 85.29% to 116.07% for AUC0-72h. Since the coefficient of variation (CV) for the reference product was 44.95% for Cmax, the 90% CI for this parameter for itraconazole was 93.49-133.78%, which was within the proposed limits of the EMA for bioequivalence of 72.15-138.59%. During the study, 4 subjects encountered a total of 14 mild adverse events. CONCLUSIONS: The use of the reference-scaling approach with 3-period design (TRR, RTR, and RRT) was an efficient way to demonstrate that two commercially available oral itraconazole formulations met the predetermined bioequivalence criteria.

Employment status of patients with chronic inflammatory demyelinating polyradiculoneuropathy.

It has been previously shown that patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who are unemployed or retired have worse quality of life. The aim of this study was to assess predictors of early retirement in CIDP. One hundred five patients with CIDP were included. Following measures were used: questionnaire on employment status, Medical Research Council Sum Score, INCAT disability score, Beck Depression Inventory, and Krupp's Fatigue Severity Scale. At the moment of testing, 2% of patients were students, 15% were employed, 9% were unemployed due to CIDP, 9% were unemployed but not due to CIDP, 28% were retired early due to disability caused by CIDP, and finally 37% were in old-age pension. Mean age when patients retired due to CIDP was 50 ± 8 years. Mean time from CIDP onset to retirement was 2.7 ± 2.3 years. Older age at onset, lower education, and more severe weakness at the time of diagnosis were significant predictors of early retirement due to CIDP. Retired patients were 12 times more likely to suffer from depression, compared to employed patients (OR = 12.2, 95% CI = 1.41-100, P < 0.01), and eight times more likely to have fatigue (OR = 8.2, 95% CI = 1.89-35.82, P < 0.01). Older patients with lower education and more severe weakness at the time of diagnosis were most likely retired due to CIDP. Early retirement was associated with depression and fatigue. Therefore, maintaining employment should be an important aim in the management of CIDP patients.

Three-Year Follow-Up Study in Patients with Guillain-Barré Syndrome.

A majority of patients with Guillain-Barré syndrome (GBS) have tendency of a good recovery. Our aim was to evaluate the outcome of the disease 1 and 3 years after GBS symptom onset. METHODS: During 2014, GBS was diagnosed in 82 patients in seven tertiary healthcare centers. Neurological follow-up was conducted in 57 (70%) patients after 1 year, and in 54 (66%) after 3 years. Functional disability was estimated according to the GBS disability scale (GDS), with a score of 0-3 indicating mild disability and a score of 4-6 indicating severe disability during acute phase, whereas a score >1 indicated poor recovery on follow-ups. Visual analog scale was used to assess sensory symptoms and musculoskelatal pain, and Krupp's Fatigue Severity Scale was used to asses fatigue. RESULTS: Poor functional outcome was found in 39% of GBS patients at year 1 and 30% at year 3. Paresthesias/dysesthesias were detected in 60% of patients after 1 year and 43% after 3 years. Musculoskeletal pain was present in 40% of patients at year 1 and 33% at year 3. Significant fatigue after 1 year was found in 21% of subjects and after 3 years in 7%. Parameters associated with poor functional outcome after 1 year were age >55 years (p=0.05), severe disability at admission (p1 indique une récupération difficile au moment des suivis. L'échelle visuelle analogue (EVA) a aussi été utilisée pour évaluer leurs symptômes sensoriels et leurs douleurs musculo-squelettiques. Enfin, l'échelle de gravité de la fatigue de Krupp a été utilisée pour évaluer leur degré de fatigue. Résultats: La première année, on a observé une piètre amélioration des capacités fonctionnelles chez 39% des patients atteints du SGB; pour la troisième année, cette proportion était de 30%. Au bout d'un an, on a aussi détecté la présence de paresthésie/dysesthésie chez 60% des patients; pour la troisième année, cette proportion était de 43%. Des douleurs musculo-squelettiques ont été rapportées chez 40% des patients après un an; deux ans plus tard, ce pourcentage chutait à 33%. Enfin, un état de fatigue important a été noté chez 21% des patients au bout d'un an; ce pourcentage n'était plus que de 7% au bout de trois ans. Les paramètres associés à une piètre amélioration des capacités fonctionnelles au bout d'un an étaient l'âge (>55 ans; p=0,05) ainsi qu'une incapacité sévère au moment de leur admission (p<0,05) et de leur congé (p<0,01). Au bout de trois ans, une piètre amélioration des capacités fonctionnelles était associée au sexe masculin (p<0,05) et à une incapacité sévère au moment d'obtenir un congé (p=0,06). CONCLUSIONS: Un an et trois ans après l'apparition des premiers symptômes du SGB, un nombre important de patients donnaient à voir des séquelles neurologiques, ce qui incluait une forme ou une autre d'incapacité fonctionnelle, des symptômes sensoriels, des douleurs et un état de fatigue.

Neuromuscular disease-specific questionnaire to assess quality of life in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

To date, generic questionnaires have been used to investigate quality of life (QoL) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients. Although these measures are very useful, they are not usually precise enough to measure all specific characteristics of the disease. Our aim was to investigate QoL using the neuromuscular disease-specific questionnaire (individualized neuromuscular quality of life, INQoL) in a large cohort of patients with CIDP. Our study comprised 106 patients diagnosed with CIDP. INQoL questionnaire, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, Visual Analogue Pain Scale, Beck Depression Inventory, and Krupp's Fatigue Severity Scale were used in our study. Physical domains of INQoL were more affected than mental, and the overall score was 57 ± 25. Significant predictors of higher INQoL score in our patients with CIDP were severe fatigue (ß = 0.35, p < 0.01), higher INCAT disability score at time of testing (ß = 0.29, p < 0.01), and being unemployed/retired (ß = 0.22, p < 0.05). QoL was reduced in our cohort of CIDP patients, which was more pronounced in physical segments. Patients with fatigue, more severe disability, and unemployed/retired need special attention of neurologists because they could be at greater risk to have worse QoL.

Developmental plasticity and stability in the tracheal networks supplying Drosophila flight muscle in response to rearing oxygen level.

While it is clear that the insect tracheal system can respond in a compensatory manner to both hypoxia and hyperoxia, there is substantial variation in how different parts of the system respond. However, the response of tracheal structures, from the tracheoles to the largest tracheal trunks, have not been studied within one species. In this study, we examined the effect of larval/pupal rearing in hypoxia, normoxia, and hyperoxia (10, 21 or 40kPa oxygen) on body size and the tracheal supply to the flight muscles of Drosophila melanogaster, using synchrotron radiation micro-computed tomography (SR-µCT) to assess flight muscle volumes and the major tracheal trunks, and confocal microscopy to assess the tracheoles. Hypoxic rearing decreased thorax length whereas hyperoxic-rearing decreased flight muscle volumes, suggestive of negative effects of both extremes. Tomography at the broad organismal scale revealed no evidence for enlargement of the major tracheae in response to lower rearing oxygen levels, although tracheal size scaled with muscle volume. However, using confocal imaging, we found a strong inverse relationship between tracheole density within the flight muscles and rearing oxygen level, and shorter tracheolar branch lengths in hypoxic-reared animals. Although prior studies of larger tracheae in other insects indicate that axial diffusing capacity should be constant with sequential generations of branching, this pattern was not found in the fine tracheolar networks, perhaps due to the increasing importance of radial diffusion in this regime. Overall, D. melanogaster responded to rearing oxygen level with compensatory morphological changes in the small tracheae and tracheoles, but retained stability in most of the other structural components of the tracheal supply to the flight muscles.