Impact of Covid-19 pandemic on injection-based practice: report from an Italian multicenter and multidisciplinary survey.

Background: There are no papers exploring the impact of COVID-19 pandemic on the injection-based practice in patients affected by different rheumatic diseases, including osteoarthritis. The aim was to investigate the impact of COVID-19 pandemic on injection-based practice trough the Italian country. Study design: A survey-based retrospective cross-sectional study. Methods: An Italian-language questionnaire was developed by a group of senior researchers and distributed by e-mail to some Rheumatology, Orthopedic and Rehabilitation Units from different geographic areas of Italy. The survey included information about the number of injections performed during COVID-19 pandemic (stratified by injected agents and injected joint), in comparison to the pre-pandemic period, and the possible reasons behind an eventual reduction. Responses were collected and descriptive analysis calculated. Results: Eleven centers of the National Health Service completed the survey. The activities of the injections services significantly decreased across the country with a percentage of reduction of 60% compared to the pre-pandemic period. A significant reduction of both intra-articular and peri-articular injections was registered. Among intra-articular. treatments, the most affected ones were the hyaluronic acid injections, when compared to corticosteroids. A significant decrease of the total amount of peri-articular injections was observed. The strict government restrictions and the fear of patients to become infected represented the most limiting factors. Conclusions: The reported decrease of the injection-based practice in our country during the COVID-19 pandemic highlights the detrimental effects of the COVID-19 pandemic on the management of chronic musculoskeletal diseases with possible negative consequences in terms of disability and quality of life.

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients.

BACKGROUND: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison's disease (AD). METHODS: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. RESULTS: The prevalence of APS-1 was 2.6 cases/million (range 0.5-17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. CONCLUSIONS: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.

Dysphagia in neurological diseases: a literature review.

Dysphagia is defined as an impairment of this complex and integrated sensorimotor system. It is estimated that 400,000 to 800,000 individuals worldwide develop neurogenic dysphagia per year. Neurogenic dysphagia is typically occurring in patients with neurological disease of different etiologies. A correct and early diagnosis and an appropriate management of dysphagia could be useful for improving patient's quality of life and may help to prevent or delay death. In the present review, we discuss thoroughly the anatomy and physiology of swallowing and also the pathophysiological mechanisms involved in impaired swallowing, as well as the diagnosis, management, and potential treatments of neurogenic dysphagia. Assessment of neurogenic dysphagia includes medical history, physical exam, and instrumental examinations (fiberoptic endoscopic evaluation of swallowing, videofluoroscopic swallowing study, electromyography). Pharmacological treatment of these problems includes oral anticholinergic drugs. Surgical myotomy of the cricopharyngeal muscle showed an important improvement of oropharyngeal dysphagia associated to upper esophageal sphincter hyperactivity. Chemical myotomy of the upper esophageal sphincter by local injections of botulinum toxin type A into the cricopharyngeal muscle has been proposed as an alternative less invasive and less unsafe than surgical myotomy.

Photoisomerizable Guanosine Derivative as a Probe for DNA Base-Pairing in Langmuir Monolayers.

Mixtures of azo-functionalized amphiphilic derivatives of guanosine and of amphiphilic derivatives of other DNA nucleobases were deposited at an air-water interface and repeatedly irradiated with light of 340 and 440 nm wavelengths. The consequent switching between cis and trans configurations of the azobenzene moiety caused changes in the surface pressure of the film, which were analyzed using a model based on the two-dimensional Van der Waals equation of state. For mixed films of guanosine and cytidine derivatives, the analysis revealed a significant modification of the strength of intermolecular interaction caused by the optical irradiation, while no such modifications were identified in mixed films involving other nucleobases. The difference is attributed to light-induced breaking of the hydrogen bonding that is established only between specific nucleobases. The results demonstrate that photosensitive nucleoside derivatives can be used as an efficient probe for base-pairing in Langmuir monolayers.

Prevalence of low back pain and its effect on health-related quality of life in 409 scholar adolescents from the Veneto region.

Low back pain (LBP) is a common condition with profound effects on well-being. We aimed to define the prevalence and the characteristics of LBP and to investigate its impact on the quality of life (QoL) of 409 students (265 females and 144 males), all high-school adolescents from the Veneto region. LBP was measured with a structured, self-report questionnaire, while the SF-36 questionnaire was used to measure physical and mental QoL. 253 students (61.3%) reported one or more episodes of LBP, with female predominance. Adolescents with LBP treated with drugs and rehabilitation cares have significantly poor belief in pain resolution (p=0.005), but more belief in a prevention program (p=0.006) than the others. After adjustment for sex, a significant association between the SF-36 dimension of vitality and the presence of LBP in males was observed. All SF-36 domains except mental health were significantly higher in females with LBP. Our study confirmed that LBP is frequent in Italian scholar adolescents and has an impact on QoL. Strategies for reducing the effects of LBP on QoL should be an important purpose for clinicians and health policy makers.

Whiplash-Associated Disorders : Clinical and medico-legal guidelines on the methods of ascertainment.

The manuscript presents the International Guidelines developed by the Working Group on Personal Injury and Damage under the patronage of the International Academy of Legal Medicine (IALM) regarding the Methods of Ascertainment of any suspected Whiplash-Associated Disorders (WAD).The document includes a detailed description of the logical and methodological steps of the ascertainment process as well as a synoptic diagram in the form of Flow Chart.

Dysphagia in the elderly: focus on rehabilitation strategies.

Prevalence of oropharyngeal dysphagia among the elderly is high, but underestimated and underdiagnosed. It may give raise to relevant complications impacting on morbidity, hospital length of stay and health care costs. Dysphagia evaluation and management is a multidisciplinary task; it includes a detailed history taking, clinical and instrumental exams, and identification of the risk of aspiration. Long-standing individual abilities and impairments determine the goals of an ad hoc rehabilitation program. Currently there are no standard algorithmic approaches for the management of dysphagia in the elderly. Education of health professionals on early diagnosis and improvement of therapeutic strategies are mainstays to allow maximal recovery potential in this population. This narrative review summarizes the current rehabilitation approaches for dysphagia in the elderly. The aim is to inform the treating health care professionals, whether caring physician, physical medicine doctor, speech/swallowing therapist or nurse, on the state-of-the-art and stimulate discussion in the scientific community.

Gonadal function in males with autoimmune Addison's disease and autoantibodies to steroidogenic enzymes.

Steroidogenic enzyme autoantibodies (SEAbs) are frequently present and are markers of autoimmune premature ovarian failure (POF) in females with autoimmune Addison's disease (AAD). The prevalence and significance of SEAbs in males with AAD have not yet been defined. We studied the prevalence of SEAbs in a large cohort of males with AAD and assessed the relationship between SEAbs positivity and testicular function. A total of 154 males with AAD (mean age 34 years) were studied. SEAbs included autoantibodies to steroid-producing cells (StCA), detected by immunofluorescence, and steroid 17α-hydroxylase (17α-OHAbs) and side chain cleavage enzyme (SCCAbs) measured by immunoprecipitation assays. Gonadal function was evaluated by measuring follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), sex hormone-binding globulin (SHGB), anti-müllerian hormone (AMH) and inhibin-B (I-B). Twenty-six males, 10 SEAbs((+)) and 16 SEAbs((-)), were followed-up for a mean period of 7·6 years to assess the behaviour of SEAbs and testicular function. SEAbs were found in 24·7% of males with AAD, with the highest frequency in patients with autoimmune polyendocrine syndrome type 1 (APS-1). The levels of reproductive hormones in 30 SEAbs((+)) males were in the normal range according to age and were not significantly different compared to 55 SEAbs((-)) males (P > 0·05). During follow-up, both SEAbs((+)) and SEAbs((-)) patients maintained normal testicular function. SEAbs were found with high frequency in males with AAD; however, they were not associated with testicular failure. This study suggests that the diagnostic value of SEAbs in males with AAD differs compared to females, and this may be related to the immunoprivileged status of the testis.

EEG Microstate as a Marker of Adolescent Idiopathic Scoliosis.

The pathophysiology of Adolescent Idiopathic Scoliosis (AIS) is not yet fully understood, but multifactorial hypotheses have been proposed that include defective central nervous system (CNS) control of posture, biomechanics, and body schema alterations. To deepen CNS control of posture in AIS, electroencephalographic (EEG) activity during a simple balance task in adolescents with and without AIS was parsed into EEG microstates. Microstates are quasi-stable spatial distributions of the electric potential of the brain that last tens of milliseconds. The spatial distribution of the EEG characterised by the orientation from left-frontal to right-posterior remains stable for a greater amount of time in AIS compared to controls. This spatial distribution of EEG, commonly named in the literature as class B, has been found to be correlated with the visual resting state network. Both vision and proprioception networks provide critical information in mapping the extrapersonal environment. This neurophysiological marker probably unveils an alteration in the postural control mechanism in AIS, suggesting a higher information processing load due to the increased postural demands caused by scoliosis.

Autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) in Sicily: confirmation that R203X is the peculiar AIRE gene mutation.

BACKGROUND: Autoimmune polyendocrinopathycandidiasis-ectodermal-dystrophy (APECED), also known as autoimmune polyendocrine syndrome type 1 (APS-1) (OMIM 240300), is a very rare disease. Accepted criteria for diagnosis require the presence of at least 2 of 3 major clinical features: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH), and Addison's disease (AD). AIM: We analyzed AIRE gene mutations and genotype-phenotype correlation in APECED patients originating from Sicily and in their relatives. SUBJECTS AND METHODS: In 4 patients, clinical evaluations, genetic analysis of AIRE, and APECED-related autoantibodies were performed. RESULTS: Two patients carried the mutation R203X in homozygosis on exon 5. One had the mutation R203X combined with R139X. The fourth had the R203X mutation in heterozygosis with R257X. Expression of the disease showed wide variability of clinical manifestations. Analysis of relatives allowed the identification of 10 heterozygotes for AIRE gene mutations. None of these subjects presented major findings of APECED. Three of the 4 patients were positive for autoantibodies to interferon-ω. CONCLUSIONS: In Sicily, R203X is confirmed to be the typical recessive and prevalent AIRE gene mutation on exon 5. Genotype-phenotype correlation failed to reveal a relationship between detected mutations and clinical expression. Mutations in heterozygosity in AIRE gene are not associated with major findings of APECED.

The value of intraoperative neurophysiological monitoring during positioning in pediatric scoliosis correction: A case report.

Introduction: Prone position during posterior spine surgery can represent a potentially risky procedure for the nervous system. Infrequent injuries due to prone positioning consist of subtle spinal cord infarction or myelopathy that can be promptly detected by intraoperative neurophysiological monitoring (IONM), if applied in this phase of surgery. Here, we report a case that stresses the value of IONM even in detecting spinal positioning-related neurological complications during kyphoscoliosis correction. Case presentation: A 3-year-old child with a severe thoracic kyphoscoliosis with the angle in the tract T5-T6 underwent an early treatment of scoliosis with growing rods. Before instrumentation or the reduction maneuver, lower limb somatosensory and motor responses disappeared. The patient was repositioned with neck and chest in a more protective position and neuromonitoring signals returned to baseline. The surgery could be completed and the patient had no postoperative neurologic or vascular deficits. Conclusion: Our findings suggest the importance of extending neuromonitoring in the early phases of anesthesia induction and patient positioning during corrective spinal deformity surgery.

Hyaluronan within fascia in the etiology of myofascial pain.

The layers of loose connective tissue within deep fasciae were studied with particular emphasis on the histochemical distribution of hyaluronan (HA). Samples of deep fascia together with the underlying muscles were taken from neck, abdomen and thigh from three fresh non-embalmed cadavers. Samples were stained with hematoxylin-eosin, Azan-Mallory, Alcian blue and a biotinylated HA-binding protein specific for HA. An ultrasound study was also performed on 22 voluntary subjects to analyze the thickness of these deep fasciae and their sublayers. The deep fascia presented a layer of HA between fascia and the muscle and within the loose connective tissue that divided different fibrous sublayers of the deep fascia. A layer of fibroblast-like cells that stained prominently with Alcian blue stain was observed. It was postulated that these are cells specialized for the biosynthesis of the HA-rich matrix. These cells we have termed "fasciacytes", and may represent a new class of cells not previously recognized. The ultrasound study highlighted a mean thickness of 1.88 mm of the fascia lata, 1.68 mm of the rectus sheath, and 1.73 mm of the sternocleidomastoid fascia. The HA within the deep fascia facilitates the free sliding of two adjacent fibrous fascial layers, thus promoting the normal function associated with the deep fascia. If the HA assumes a more packed conformation, or more generally, if the loose connective tissue inside the fascia alters its density, the behavior of the entire deep fascia and the underlying muscle would be compromised. This, we predict, may be the basis of the common phenomenon known as "myofascial pain."

From in vitro research to real life studies: an extensive narrative review of the effects of balneotherapy on human immune response.

PURPOSE: The biologic mechanisms by which balneotherapy (BT) alleviates symptoms of different diseases are still poorly understood. Recently, preclinical models and clinical trials have been developed to study the effects of BT on the immune system. This review summarizes the currently available evidence regarding the effects of spa therapy on the immune response, to confirm the role of BT in the enhancement of immune system and open interesting research fields. METHODS: PubMed and Google Scholar were searched from 1997 up to June 2020, with search criteria including terms related to BT and immune system. We selected only in vitro research, randomized controlled trials (RCTs) or clinical trials. RESULTS: In vitro studies on human and animal samples have demonstrated that thermal waters exert anti-inflammatory and immunomodulatory effects. In particular, H2S donors seem to counteract the inflammatory processes in psoriatic lesions, arthritic fibroblast-like synoviocytes and chondrocytes, and regulate important factors implicated in osteoarthritis pathogenesis and progression. RCTs and clinical trials revealed, after BT, a reduction in circulating levels of pro-inflammatory molecules, such as TNF-α, IL-1ß, and C-reactive protein, and an increase in anti-inflammatory molecules such as the IGF-1 growth factor especially in musculoskeletal diseases. CONCLUSION: Further preclinical studies and RCTs could help to exploit BT in real life for preventive and therapeutic treatments.

Glycaemic fall after a glucose load. A population-based study.

BACKGROUND AND AIMS: A blood glucose (BG) fall after an oral glucose load has never been described previously at a population level. This study was aimed at looking for a plasma glucose trend after an oral glucose load for possible blood glucose fall if any, and for its impact on coronary mortality at a population level. METHODS AND RESULTS: In subjects from an unselected general population, BG and insulin were detected before and 1 and 2h after a 75-g oral glucose load for insulin sensitivity and ß-cell function determination. Blood pressure, blood examinations and left ventricular mass were measured, and mortality was monitored for 18.8±7.7 years. According to discriminant analysis, the population was stratified into cluster 0 (1-h BG < fasting BG; n=497) and cluster 1 (1-h BG ≥ fasting BG; n=1733). To avoid any interference of age and sex, statistical analysis was limited to two age-gender-matched cohorts of 490 subjects from each cluster (n=940). Subjects in cluster 0 showed significantly higher insulin sensitivity and ß-cell function, lower visceral adiposity and lower blood pressure values. Adjusted coronary mortality was 8 times lower in cluster 0 than 1 (p<0.001). The relative risk of belonging to cluster 1 was 5.40 (95% CI 2.22-13.1). CONCLUSION: It seems that two clusters exist in the general population with respect to their response to an oral glucose load, independent of age and gender. Subjects who respond with a BG decrease could represent a privileged sub-population, where insulin sensitivity and ß-cell function are better, some risk factors are less prevalent, and coronary mortality is lower.

Dynamics of viral replication in infants with vertically acquired human immunodeficiency virus type 1 infection.

About one-third of vertically HIV-1 infected infants develop AIDS within the first months of life; the remainder show slower disease progression. We investigated the relationship between the pattern of HIV-1 replication early in life and disease outcome in eleven infected infants sequentially studied from birth. Viral load in cells and plasma was measured by highly sensitive competitive PCR-based methods. Although all infants showed an increase in the indices of viral replication within their first weeks of life, three distinct patterns emerged: (a) a rapid increase in plasma viral RNA and cell-associated proviral DNA during the first 4-6 wk, reaching high steady state levels (> 1,000 HIV-1 copies/10(5) PBMC and > 1,000,000 RNA copies/ml plasma) within 2-3 mo of age; (b) a similar initial rapid increase in viral load, followed by a 2.5-50-fold decline in viral levels; (c) a significantly lower (> 10-fold) viral increase during the first 4-6 wk of age. All infants displaying the first pattern developed early AIDS, while infants with slower clinical progression exhibited the second or third pattern. These findings demonstrate that the pattern of viral replication and clearance in the first 2-3 mo of life is strictly correlated with, and predictive of disease evolution in vertically infected infants.

TCR expression and clonality analysis in peripheral blood and lymph nodes of HIV-infected patients.

We compared the T cell receptor (TCR) V beta gene family repertoire in peripheral blood mononuclear cells (PBMC) and lymph node (LN) cells from 7 human immunodeficiency virus (HIV)-infected patients and 3 seronegative healthy controls. Virtually all the V beta family specificities were represented in patient PBMC and LN cells, and mean values for each specificity were comparable to figures in seronegative controls. In 4 patients, however, some V beta gene segment transcripts were overrepresented in the LN compartment, compared to the peripheral blood counterpart. To ascertain whether this phenomenon was due to polyclonal or oligoclonal expansion of T cells bearing the relevant V beta gene product, we sequenced the entire CDR3 region of a panel of 238 PCR clones corresponding to the V beta transcripts expanded in LN; as control, the same regions were cloned and sequenced in patient's PBMC, and in PBMC and LN cells from seronegative individuals. This analysis disclosed preferential usage of J beta 2 genes in PBMC and LN cells from both seropositive patients and controls, regardless of the V beta gene segment considered, thus indicating that this skewness in the V beta-J beta repertoire could be a consistent feature of at least a part of the V beta repertoire in different lymphoid compartments, regardless of the pathologic conditions. In addition, in LN from HIV seropositive patients we found the presence of recurrent TCR rearrangements, accounting for 8-23% of the generated clones, in each of the 4 V beta specificities analyzed; recurrent sequences were not found in PBMC from patients nor in PBMC and LN cells from seronegative controls. These findings suggest that antigen-driven oligoclonal T cell expansions may occur in vivo in lymphoid organs of HIV seropositive patients.

The self-assembly of lipophilic guanosine derivatives in solution and on solid surfaces

The self-assembly of lipophilic deoxyguanosine derivatives 1 and 2 has been studied in solution by NMR spectroscopy and ESI-MS (electrospray ionization mass spectrometry). NMR data show the existence of two types of self-assembled, ribbonlike structures (A and B), which are connected at the guanine moieties through two different H-bonded networks. The first species (A), which is stable in the solid state and characterised by cyclic NH(2)-O(6) and NH(1)-N(7) hydrogen bonds, is detected soon after dissolving the polycrystalline powder in rigorously anhydrous CDCl3. In solution it slowly undergoes a structural transition towards a thermodynamically stable ribbon characterised by NH(1)-O(6) and NH(2)-N(3) cyclic hydrogen bonds (B). On the other hand, at surfaces, self-assembled ribbon nanostructures have been grown from solutions of derivative 1 both on mica and at the graphite-solution interface. They have been investigated by means of tapping mode scanning force microscopy (SFM) and scanning tunnelling microscopy (STM), respectively. SFM revealed dry, micrometer-long nanoribbons with a molecular cross-section. while STM imaging at submolecular resolution indicates a molecular packing of type A, like the one detected in the solid state. This indicates that, upon adsorption at the solid-liquid interface, the guanosine moieties undergo a structural rearrangement from a B-type to an A-type ribbon.

Effects of aluminum lactate on murine neuroblastoma cells.

Aluminum is the most abundant metal and the third most common element in the earth's crust. It's toxicity has emerged as one of the most serious complications in the treatment of chronic renal failure. Aluminum lactate [Al(lac)3], at concentrations less than those affecting cell viability (< 5 mM) decreased the capability of mouse neuroblastoma cells to incorporate 14C-leucine and 3H-thymidine. This decreased capability to synthesize protein and DNA was accompanied by extension of neurites, increased capacity of the cells to take up silver stain, and decreased reactivity to antibodies against neurofilaments and to lectins that recognize cell surface carbohydrate residues. In conclusion, Allac3 should be considered as a marked cytostatic as well as a strong neuritogenic agent.

Columnar lyomesophases formed in hydrocarbon solvents by chiral lipophilic guanosine-alkali metal complexes.

The lipophilic guanosine derivative 1 acts as a self-assembled ionophore and, in the presence of alkali metal ions, forms chiral polymeric structures in organic solvents. These polymeric columnar aggregates are comprised of G-quartets held together by alkali metal ions which are located inside the tubular structure; the quartets are surrounded by hydrocarbon chains. In hydrocarbon solvents, these columnar aggregates form lyomesophases of the cholesteric and hexagonal type. Copyright 2000 Wiley-Liss, Inc.