Beta interferons as immunotherapy in multiple sclerosis: a new outlook on a classic drug during the COVID-19 pandemic.

Beta interferons (IFN-ß) are pleiotropic cytokines with antiviral properties. They play important roles in the pathogenesis of multiple sclerosis (MS), an incurable immune-mediated disorder of the central nervous system. The clinical expression of MS is heterogeneous, with relapses of neuroinflammation and with disability accrual in considerable part unrelated to the attacks. The injectable recombinant IFN-ß preparations are the first approved disease-modifying treatments for MS. They have moderate efficacy in reducing the frequency of relapses, but good long-term cost-efficacy and safety profiles, so are still widely used. They have some tolerability and adherence issues, partly mitigated in recent years by the introduction of a PEGylated formulation and use of 'smart' autoinjector devices. Their general impact on long-term disability is modest but could be further improved by developing accurate tools for identifying the patient profile of best responders to IFN-ß. Here, we present the IFN-ß-based immunomodulatory therapeutic approaches in MS, highlighting their place in the current coronavirus disease (COVID-19) pandemic. The potential role of IFN-ß in the treatment of COVID-19 is also briefly discussed.

Optimization of Patterned Surfaces for Improved Superhydrophobicity through Cost-Effective Large-Scale Computations.

The pattern design of superhydrophobic surfaces can be significantly aided by computations that predict the Cassie-Baxter (CB) to Wenzel (W) transition, which is responsible for the break-down of superhydrophobic behavior. We present a computational framework for the optimization of patterned surfaces based on the energy barriers of the CB-W transitions which comprises the following elements: (a) design of structured surface patterns, for example, arrays of pillars, with parameterized geometric features such as size, pitch, slope, and roundness. (b) Computation of the wetting states with a modified Young-Laplace equation that facilitates the introduction of solid/liquid interactions for complex surface patterns and has significantly lower computational cost than other commonly used methods, such as the volume-of-fluid, phase-field, and so forth. (c) Incorporation of the modified Young-Laplace in the simplified string method, allowing the calculation of the minimum energy paths of wetting transitions which, apart from the energy barriers, also reveal the transition mechanisms (CB failure modes). (d) Accommodation of large-scale problems with good parallel performance and scalability on multicore-distributed memory systems using fast iterative solvers and the Message Passing Interface communication protocol. We demonstrate the computational framework with a shape optimization study of inverted conical frustum pillars. The optimization objective function is the resistance to the CB-W transition, which is quantified by the energy barrier-a relatively large energy barrier suggests improved superhydrophobicity. We also report the parallel performance, in terms of parallel speedup for problems ranging from three hundred thousands to 12 million degrees of freedom, solved using up to 40 processing cores.

Wetting transitions on patterned surfaces with diffuse interaction potentials embedded in a Young-Laplace formulation.

The Minimum Energy Paths (MEPs) of wetting transitions on pillared surfaces are computed with the Young-Laplace equation, augmented with a pressure term that accounts for liquid-solid interactions. The interactions are smoothed over a short range from the solid phase, therefore facilitating the numerical solution of problems concerning wetting on complex surface patterns. The patterns may include abrupt geometric features, e.g., arrays of rectangular pillars, where the application of the unmodified Young-Laplace is not practical. The MEPs are obtained by coupling the augmented Young-Laplace with the modified string method from which the energy barriers of wetting transitions are eventually extracted. We demonstrate the method on a wetting transition that is associated with the breakdown of superhydrophobic behavior, i.e., the transition from the Cassie-Baxter state to the Wenzel state, taking place on a superhydrophobic pillared surface. The computed energy barriers quantify the resistance of the system to these transitions and therefore, they can be used to evaluate superhydrophobic performance or provide guidelines for optimal pattern design.

Reproducibility of vibration perception threshold values in children and adolescents with type 1 diabetes mellitus and associated factors.

AIMS: To define the reproducibility of vibration perception thresholds (VPTs) and the possible associated factors, as an early index of peripheral diabetic neuropathy (PDN) in type 1 diabetes mellitus (T1DM) children and adolescents. METHODS: A single examiner studied 118 T1DM subjects (aged 13.5±3.4 years) and 79 controls (aged 12.0±3.07 years). Glycaemic control was assessed with HbA1c levels. VPT was measured twice on upper and lower limbs, using a Biothesiometer. Concordance between the two VPT measurements was evaluated using the Cohen's Weighted Kappa statistic (Kappa=0.41-0.60→moderate concordance, Kappa=0.61-0.80→substantial concordance). RESULTS: T1DM children had significantly higher VPTs than controls at all sites (p=0.001), but with lower Kappa values (0.64-0.70). VPT values increased in parallel with HbA1c (a.<8%, b. 8-9.5%, c.>9.5%) and T1DM duration (a.<5 years, b.5.1-10, c.>10 years). However, Kappa values were lower in the groups with the poorest control (HbA1c>9.5%) (Kappa=0.54-0.76) or the longest T1DM duration (>10 years) (Kappa=0.49-0.71). Although VPTs increased with stature and male gender, no effect on VPT reproducibility was observed. However, obesity was associated with lower VPT values and poorer concordance. CONCLUSIONS: These findings suggest that the reproducibility of VPTs is lower in the high-risk patients for early subclinical PDN development, who need a regular follow-up.

The Problem Areas in Diabetes (PAID) scale: psychometric evaluation survey in a Greek sample with type 2 diabetes.

Several instruments have been developed for the assessment of emotional distress in patients with diabetes. The Problem Areas in Diabetes Scale (PAID) is a brief self-report scale that evaluates diabetes-related distress. There is a lack of validated instruments for the evaluation of psychological aspects in patients with diabetes in Greek language. The current study was conducted to translate and adapt the PAID scale in Greek language and to evaluate the psychometric properties in two different study populations of patients with diabetes. The aim of this study was to translate the Problem Areas in Diabetes (PAID) scale into Greek, adapt it culturally to Greece and determine its psychometric properties. The translation process included two forward translations, reconciliation, backward translation and pre-testing steps. The validation incorporated the exploration of internal consistency (Cronbach's alpha), test-retest reliability (interclass correlation coefficient), construct validity (exploratory factor analysis) and responsiveness (Spearman correlation coefficient). Participants included 101 consecutive patients from a rural primary healthcare centre and 101 patients from an urban hospital. All patients completed the PAID scale and the Short Form-36 (SF-36) version 2. Internal consistency considered good (Cronbach's alpha = 0.948). Interclass correlation coefficient was 0.942 (95% CI 0.915-0.961). Factor analysis yielded three factors: 'Diabetes-related emotional problems' (51.79% variance, Cronbach's alpha = 0.910), 'Food-related problems' (9.55% variance, Cronbach's alpha = 0.824) and 'Social support-related problems' (5.96% variance, Cronbach's alpha = 0.704). Screen plot test and conceptual congruency of items supported a three-factor solution. Total PAID showed a negative correlation with both SF-36 mental component summary (r = -0.733, P < 0.0001) and SF-36 physical component summary (r = -0.594, P < 0.0001). Our findings indicate that the Greek version of the PAID questionnaire is reliable and valid for patients with diabetes mellitus in Greece.

Cytopathologic interpretation of ascites due to malignancy.

The diagnosis of metastatic cancer in peritoneal fluid is of great importance for the patient and the attending physician. A cytopathologist's responsibility is twofold: (1) to accurately identify malignant cells; (2) to interpret tumor type and if possible the site of its origin even in the absence of complete clinical history of other clues. The difficulty in the diagnosis of metastatic neoplasms in peritoneal fluid is due to 2 factors: (1) abnormal mesothelial cells or macrophages may simulate cancer cells, or may conceal tumor cells; and (2) peritoneal fluid constitutes a natural and hitherto inadequately explored medium of cell culture, in which neoplastic cells may proliferate free of the boundaries imposed upon them by the framework of organs and tissues. Immunocytochemistry (ICC) and molecular techniques are essential to establish an accurate diagnosis. From a great many points of view malignant peritoneal fluid is suitable for continuous study of cancer cells, thus providing knowledge about biologic aspects of human solid tumors.

Gastric autoimmunity in children and adolescents with type 1 diabetes: a prospective study.

BACKGROUND/AIMS: Type 1 diabetes (T1DM) is associated with gastric autoimmunity, which is characterized by the presence of parietal cell antibodies (APCA). We investigated gastric autoimmunity prevalence in T1DM children, its manifestations, determinants and association with thyroid gland (anti-Tg, anti-TPO) and pancreatic ß-cell autoimmunity (anti-GAD) at baseline and 4 years later. METHODS: The initial cohort (D1) included 97 children with T1DM. At follow-up after 4 years (D2), 84.5% of participants were evaluated. We assessed APCA, anti-Tg, anti-TPO, and anti-GAD presence, as well as symptoms of gastritis. APCA-positive patients were evaluated with gastrin, B12, ferritin levels and were submitted to gastroscopy. RESULTS: Thyroid antibody positivity was increased among the APCA-positive patients. Four years later, among initially APCA-positive patients, 2/6 became APCA negative, while 4/6 developed high titers of APCA. On gastroscopy, 2 patients had chronic hypertrophic gastritis and one Helicobacter pylori gastritis. CONCLUSIONS: Gastric autoimmunity was associated with thyroid autoimmunity and anti-GAD persistence. After 4 years, the majority of APCA-positive patients developed high titers of APCA and mild symptoms of gastritis. Thus, patients with T1DM, and in particular those with thyroid and/or pancreatic autoimmunity, should have periodic autoantibody screening for the early diagnosis and follow-up of gastric autoimmunity.

A non-catecholamine-producing sympathetic paraganglioma of the spermatic cord: the importance of performing candidate gene mutation analysis.

BACKGROUND: Catecholamine-producing tumours are called pheochromocytomas when they are located in the adrenal gland and sympathetic paragangliomas when they are located elsewhere in the abdomen. Rarely these tumours do not produce catecholamines and even more rarely they arise in the spermatic cord. Over the past decade, systematic mutation analysis of apparently sporadic cases of pheochromocytomas and paragangliomas has elucidated the frequent presence of germ line mutations in one of five candidate genes, including RET, VHL, SDHB, SDHC, and SDHD. CLINICAL HISTORY AND METHODS: We describe a 45-year-old man with a non catecholamine-producing paraganglioma of the spermatic cord. We performed SDHB immunohistochemistry and performed mutation analysis of the SDHB, SDHC, and SDHD genes. RESULTS: There was no staining of tumour cells with SDHB immunohistochemistry, indicative of an SDH mutation. Mutation analysis demonstrated a germ line SDHD mutation (p.Val147Met). CONCLUSIONS: Systematic mutation analysis is required in paraganglioma patients for the detection of germ line mutations. This should be preceded by SDHB immunohistochemistry to limit the number of genes to be tested.

Treatment with thyroxine reduces thyroid volume in euthyroid children and adolescents with chronic autoimmune thyroiditis.

BACKGROUND/AIMS: Treatment with thyroxine in children with chronic autoimmune thyroiditis (AT) is controversial. The aim of this study is to investigate, by using thyroid ultrasonography, whether thyroxine influences thyroid volume in non-goitrous euthyroid children with AT. METHODS: We studied 50 euthyroid non-goitrous children and adolescents with AT for 2 years by thyroid function tests and ultrasonography; 25 were randomized to receive thyroxine and 25 did not receive treatment. Median (IQR) age was 12.1 (11.1-13.2) years. RESULTS: At baseline there was no difference in thyroid volume SDS between the two groups (treatment group 1.1 (0.7-1.5) and controls 0.9 (0.4-1.4), respectively). After 2 years the treatment group had lower thyroid volume SDS compared to the controls (0.6 (0.3-1.0) vs. 2.0 (1.1-2.3), p = 0.001). One child of the treatment group and 12 of the control group developed goiter. Two control children developed subclinical hypothyroidism. Within the treatment group, thyroid volume SDS was lower after 2 years of treatment (p = 0.002). Within the control group, thyroid volume SDS and TSH levels increased after 2 years of follow-up (p = 0.016, 1.9 (1.5-2.8) vs. 3.2 (2.4-4.4) mIU/ml, p = 0.006, respectively). CONCLUSIONS: Treatment with thyroxine reduces thyroid volume in non-goitrous euthyroid children with AT and may prevent goiter development.

Pyeloureteritis cystica.

Pyeloureteritis cystica is a rare situation of the renal pelvis and ureters, characterized by cystical formations of the epithelium. The etiology is unknown and there is no specific treatment. It is usually diagnosed accidently during imaging of the upper urinary tract for different reasons. We present a case of pyeloureteritis cystica.

Shockwave lithotripsy and endourological management of urinary calculi in children: a single-center 10-year experience.

PURPOSE: Shock wave lithotripsy (SWL) and endourological techniques revolutionized the management of pediatric urolithiasis. We sought to assess the impact of new technology and local practice in the treatment of pediatric urolithiasis during a 10-year period. MATERIALS AND METHODS: Between 1997 and 2006, 125 children (90 boys and 35 girls), aged 18 months to 15 years, were managed in our department for urolithiasis. Stone localization, stone composition, presence of anatomic abnormalities, and treatment modality were evaluated retrospectively. RESULTS: In 102 children, the stone was located in renal pelvis (0.5-45-mm diameter), in eight in the renal pelvis and one in the calyx; three had staghorn calculi; and 12 had ureteral stone (4-12-mm diameter). Ninety-three of 125 children underwent a total of 108 SWL sessions. Stone size ranged from 0.5 to 35 mm. The stone-free rates were 86%, 92%, and 96% after first, second, and third SWL session, respectively. Ureteroscopy was performed in 12/125 children, and 10/12 (83.5%) were rendered stone free. Nine of 125 children underwent percutaneous nephrolithotomy, and four of nine were stone free (44.5%), although five of the nine children (55.5%) required SWL for residual stone fragments. Open surgery was performed as initial procedure in 11 (9%) children. In 9 of 11 children, ureteropelvic junction obstruction was corrected simultaneously. Open surgery was followed by SWL in 3 of 11 patients. Two of three patients with staghorn calculi underwent nephrolithotomy and SWL and one of three with cysteinuria was managed with SWL. CONCLUSIONS: SWL and endourological techniques are safe and effective in managing urolithiasis in pediatric patients. These minimally invasive methods reduced dramatically the cases of open surgery, which should be undertaken mainly in coexisting anatomic abnormalities.

Mechanisms of equilibrium shape transitions of liquid droplets in electrowetting.

Liquid droplets bridging the gap between two dielectric-coated horizontal electrode plates suffer breakup instabilities when a voltage applied between the electrodes exceeds a threshold. Interestingly enough, broken liquid bridges (i.e. a pair of a sessile and a pendant drop) can spontaneously rejoin if the voltage is still applied to the electrodes. Here we study the electro-hydrostatics of the liquid bridges in the joined or broken state and we illuminate the mechanisms of the shape transitions that lead to bridge rupture or droplet joining. The governing equations of the capillary electro-hydrostatics form nonlinear and free boundary problems which are solved numerically by the Galerkin/finite element method. On one hand, we found that capillary bridges become unstable at a turning point bifurcation in their solution space. The solutions past the turning point are unstable and the instability signals the bridge rupture. On the other hand, the separate droplets approach each other as the applied voltage increases. However, solutions become unstable past a critical voltage at a turning point bifurcation and the droplets join. By studying the relative position of the turning points corresponding to bridge rupture and droplet joining, respectively, we define parameter regions where stable bridges or separate droplets or oscillations between them can be realized.

The effect of interleukin-6 on ciliary beat frequency in the human fallopian tube.

OBJECTIVE: To investigate the effect of interleukin-6 (IL-6) on ciliary activity within the human fallopian tube in vitro. DESIGN: An experimental laboratory-based study. SETTING: University teaching hospital. PATIENT(S): Fallopian tube specimens were obtained from eight women undergoing hysterectomy for fibroid uterus. MAIN OUTCOME MEASURE(S): Ciliary beat frequency (CBF) in the human fallopian tube. INTERVENTION(S): After baseline CBF measurements, increasing concentrations of IL-6 (10 pg/mL, 100 pg/mL, and 1000 pg/mL) were applied to fallopian tube mucosa explants and CBF measurements repeated. An anti-IL-6 monoclonal antibody was added and CBF measured once more. Negative and antibody-only control samples were used. RESULT(S): The CBF remained unchanged with the addition of IL-6 at concentrations of 10 pg/mL and 100 pg/mL but IL-6 at 1000 pg/mL significantly decreased CBF, an effect abolished by the addition of the specific antibody. CONCLUSION(S): These data suggest that IL-6 has an inhibitory effect on ciliary activity, suggesting a possible role for this cytokine in the subfertility process. This finding may be important in conditions where there are increased IL-6 levels in the peritoneal fluid, such as endometriosis and pelvic inflammatory disease.

Holmium laser lithothripsy of ureteral calculi: our initial experience.

AIM: To evaluate effectiveness and safety of intracorporeal holmium:YAG (Ho:YAG) laser lithotripsy of ureteral calculi. PATIENTS AND METHODS: Between October 2003 and September 2005, 45 patients (age range 27-74, mean age 51.5 years) with 49 ureteral stones (measuring 4-28 mm in size) were treated with Ho:YAG laser lithotripsy. The locations of the stones in the ureter were: 6 in the upper third, 7 in the middle third, and 36 in the lower third. Under general anaesthesia, we used semirigid 9- to 11-Fr ureteroscopes and a flexible 7.5-Fr ureteroscope. The Ho:YAG laser had a maximum power of 1.8 J at 8 Hz, and a 365-mum flexible quartz fibre was used. One month postoperatively the patients were followed up with imaging tests. RESULTS: Stone disintegration was feasible in all cases. The mean hospital stay was 2.8 days. One month postoperatively, stone-free status was revealed in 93.3% of the cases. Only minor complications were noted in 4 patients (8.8%). No long-term complications were recorded. CONCLUSION: Ho:YAG laser lithotripsy of ureteral calculi is a feasible, safe, and effective procedure.

Efficacy of captopril therapy in cystinuria lithiasis. A case report.

We present a 7-year old girl with severe urolithiasis due to cystinouria. Medical treatment after the surgical procedures was initiated with intensive hydration, urine alkalinisation and captopril. We discuss the therapeutic efficacy of captopril in resolving lithiasis as well as in preventing new stone formation.

Continent urinary diversion using Mainz II modified ureterosigmoidostomy.

OBJECTIVE: To assess the surgical technique of Mainz II urinary diversion and to discuss its simplicity, quickness of performance, short postoperative period, few postoperative complications, as well as its effectiveness allowing patients to have a very good quality of life. PATIENTS AND METHODS: Over the last six and a half years, 47 patients aged between 65 and 76 years (mean age 69.9 +/- 2.5 years) underwent radical cystectomy and Mainz II ureterosigmoidostomy for invasive bladder cancer. All patients were followed according to a standard protocol including assessment of continence, renal function and acid-base balance. RESULTS: Most of the patients retained normal renal function, complete continence and acid-base balance. There were no perioperative complications. In three patients there was urine leakage. Four patients presented with pyelonephritis and needed hospitalization. Mild hyperchloraemic acidosis was seen in nine patients. Most of them were pleased from their new quality of life. CONCLUSION: The modified Mainz II ureterosigmoidostomy is a simple, quick, easy and safe procedure to achieve urinary diversion in invasive bladder cancer resulting in a very good quality of life for patients without altering their appearance and making them capable of performing all kinds of work.