Elastic Instability behind Brittle Fracture.

We argue that nucleation of brittle cracks in initially flawless soft elastic solids is preceded by a nonlinear elastic instability, which cannot be captured without accounting for geometrically precise description of finite elastic deformation. As a prototypical problem we consider a homogeneous elastic body subjected to tension and assume that it is weakened by the presence of a free surface which then serves as a location of cracks nucleation. We show that in this maximally simplified setting, brittle fracture emerges from a symmetry breaking elastic instability activated by softening and involving large elastic rotations. The implied bifurcation of the homogeneous elastic equilibrium is highly unconventional for nonlinear elasticity as it exhibits strong sensitivity to geometry, reminiscent of the transition to turbulence in fluids. We trace the postbifurcational development of this instability beyond the limits of applicability of scale-free continuum elasticity and use a phase-field approach to capture the scale dependent subcontinuum strain localization, signaling the formation of actual cracks.

ACROMORFO study: gait analysis in a cohort of acromegalic patients.

PURPOSE: In acromegaly, skeletal complications resulted to be associated with low quality of life (QoL) and high risk of falls. The aim of the present study was to perform a quantitative assessment of movement through gait analysis technique in patients with acromegaly. STUDY POPULATION: Thirty-three acromegalic patients [9 with active disease (AD), 14 with controlled disease (CD) and 10 with disease remission (RD)] and 20 healthy subjects were enrolled for the study. MEASUREMENTS: Kinetic and kinematic data were collected with 3D-gait analysis. Kinematic data were processed to compute the Gait Profile Score (GPS), a parameter that summarizes the overall deviation of kinematic gait data relative to unaffected population. RESULTS: The acromegalic group showed longer stance phase duration (p < 0.0001) compared to controls. The GPS and several gait variable scores resulted to be statistically higher in the acromegalic group compared to healthy controls. GPS values were significantly higher in AD compared to CD (p < 0.05) and RD groups (p = 0.001). The AD group presented significantly higher values in terms of hip rotation and ankle dorsiflexion compared to CD and RD groups and with regard to the foot progression compared to RD. Interestingly, patients with RD exhibited a more physiological gait pattern. CONCLUSION: Acromegalic patients showed quantitative alterations of gait pattern, suggesting instability and increased risk of falls. Arthropathy, along with its associated abnormal joint loading, proprioceptive impairment and hyperkyphosis could be contributing factors. Disease control and remission appear to improve postural balance. A better knowledge on walking performance in acromegaly would help to develop specific rehabilitation programmes to reduce falls' risk and improve QoL.

Visual lung ultrasound protocol (VLUP) in acute respiratory failure: description and application in clinical cases.

Lung ultrasound (LUS) is widely used as a diagnostic and monitoring tool in critically ill patients. Lung ultrasound score (LUSS) based on the examination of twelve thoracic regions has been extensively validated for pulmonary assessment. However, it has revealed significant limitations: when applied to heterogeneous lung diseases with intermediate LUSS pattern (LUSS 1 and 2), for instance, intra-observer consistency is relatively low. In addition, LUSS is time-consuming and a more rapid overview of the extent of lung pathology and residual lung aeration is often required, especially in emergency setting. We propose a Visual Lung Ultrasound Protocol (VLUP) as a rapid monitoring tool for patients with acute respiratory failure. It consists of a probe sliding along the mid-clavicular, mid-axillary and scapular lines in transversal scan. VLUP allows a visualization of a large portion of the antero-lateral and/or posterior pleural surface. Serial assessments of two clinical cases are recorded and visually compared, enabling rapid understanding of lung damage and its evolution over time. VLUP allows a semi-quantitative and qualitative point-of-care assessment of lung injury. Through this standardized approach it is possible to accurately compare subsequent scans and to monitor the evolution of regional parenchymal damage. VLUP enables a quick estimation of the quantitative-LUSS (qLUSS) as the percentage of pleura occupied by artifacts, more suitable than LUSS in inhomogeneous diseases. VLUP is designed as a standardized, point-of-care lung aeration assessment and monitoring tool. The purpose of the paper is to illustrate this new technique and to describe its applications.

Long-term effects of somatostatin analogues in rat GH-secreting pituitary tumor cell lines.

PURPOSE: First-generation somatostatin analogs, octreotide (OCT) and lanreotide, are the cornerstone for the medical treatment of growth hormone (GH)-secreting pituitary tumors. A new multireceptor analog, such as pasireotide (PAS), showed better activity than OCT in long-term treatment of patients with acromegaly, but modulation of intracellular key processes is still unclear in vitro. In this study, we evaluated the antitumor activity of OCT and PAS in two GH-secreting pituitary tumor cell lines, GH3 and GH4C1, after a long-term incubation. METHODS: The effects of PAS and OCT on the cell viability, cell cycle, apoptosis, GH secretion, and tumor-induced angiogenesis have been evaluated through a colorimetric method (MTS Assay), DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, ELISA assay and zebrafish platform, respectively. RESULTS: PAS showed a more potent antitumor activity compared to OCT in GH3 cell line exerted through inhibition of cell viability, perturbation of cell cycle progression, and induction of apoptosis after 6 days of incubation. A concomitant decrease in GH secretion has been observed after 2 days of incubation only with PAS. No effect on tumor-induced angiogenesis has been reported after treatment with OCT or PAS in zebrafish/tumor xenograft model. CONCLUSION: Long-term incubation with PAS showed a more potent antitumor activity than that reported after OCT in GH3 cells, mainly modulated by a cell cycle perturbation and a relevant induction in apoptosis.

From mothership to drip-and-ship: Effects of staff shortages at a comprehensive stroke center.

BACKGROUND: Mechanical thrombectomy (MT) has been shown to be effective in the acute phase of ischemic stroke. Current data suggests that the drip-and-ship and mothership telestroke models are equally effective for its administration. We describe the consequences of changing the telestroke model due to staff shortages in a comprehensive stroke center (Besançon), which was replaced by a more distant one (Dijon). METHODS: We conducted a retrospective analysis of all patients referred for MT from January 2015 to December 2018. We analyzed the time between symptom onset and arrival in the angiography suite. We also calculated number of thrombectomies divided by number of days on call, and rate of thrombectomies relative to the number of strokes in each group. RESULTS: In Besançon, 205 patients underwent an MT procedure, versus 43 patients in Dijon. A further four patients were transferred to Dijon but not treated. The time from symptom onset to arrival in the angiography suite was longer for Dijon; 334min versus 281min for Besançon (p<0.001). The percentage of thrombectomies performed per day on call was higher for Besançon: 18.6% versus 13.2% in Dijon (p=0.026). CONCLUSIONS: Over the study period, the time from symptom onset to angiography suite was longer for patients who were transferred to Dijon. The period in which the Besançon hospital experienced the greatest lack of personnel corresponded to a decrease in the number of MTs performed.

Safeguard pressure assisted device for local femoral hemostasis in neuroendovascular procedures: A single center study of 879 patients.

BACKGROUND: Various vascular closure devices (VCDs) are available for local hemostasis after percutaneous transfemoral approach for neuroendovascular procedures but they have been associated with an increased complication rate and limitations to a re-puncture of the artery. We evaluated the safety and efficacy of Safeguard® 24 cm pressure assisted device (Merit Medical, West Jordan, UT, USA) and the associated complications. METHODS: From September 2016 to December 2019, 879 patients underwent neuroendovascular procedures via transfemoral approach using an introducer sheath ranging from 4 to 6-French and they were included in a prospective database. We registered the demographic characteristics and procedural factors. We evaluated the device failure and associated complications. RESULTS: The Safeguard® was successful in 862 cases (98.1 %) with post-procedural local bleeding in 17 patients (1.9%). On univariate analysis, an association with local bleeding was observed with age >60 years (Odds ratio [OR] = 3.2, P = 0.04) and the use of an introducer sheath >4 F ([OR] = 3.1, P = 0.007). Female gender, antithrombotic medication and type of procedure (diagnostic or interventional) were not associated with local bleeding. On binary logistic regression analysis, there was association only for age >60 years ([OR] = 3, P = 0.04). CONCLUSION: The Safeguard® 24 cm is safe and efficient. It is simple to use and it can be applied independently from vessel anatomic characteristics. It should though be used with caution in case of a femoral introducer sheath larger than 4 Fr and patients older than 60 years.

Comparing the efficacy of initial percutaneous transhepatic biliary drainage and endoscopic retrograde cholangiopancreatography with stenting for relief of biliary obstruction in unresectable cholangiocarcinoma.

BACKGROUND: In patients with cholangiocarcinoma (CC), management of biliary obstruction commonly involves either up-front percutaneous transhepatic biliary drainage (PTBD) or initial endoscopic retrograde cholangiopancreatography (ERCP) with stent placement. The objective of the study was to compare the efficacy and of initial ERCP with stent placement with efficacy of initial PTBD in management of biliary obstruction in CC. METHODS: A single-center database of patients with unresectable CC treated between 2006 and 2017 was queried for patients with biliary obstruction who underwent either PTBD or ERCP. Groups were compared with respect to patient, tumor, procedure, and outcome variables. RESULTS: Of 87 patients with unresectable CC and biliary obstruction, 69 (79%) underwent initial ERCP while 18 (21%) underwent initial PTBD. Groups did not differ significantly with respect to age, gender, or tumor location. Initial procedure success did not differ between the groups (94% ERCP vs 89% PTBD, p = 0.339). Total number of procedures did not differ significantly between the two groups (ERCP median = 2 vs. PTC median = 2.5, p = 0.83). 21% of patients required ERCP after PTBD compared to 25% of patients requiring PTBD after ERCP (p = 1.00). Procedure success rate (97% ERCP vs. 93% PTBD, p = 0.27) and rates of cholangitis (22% ERCP vs. 17% PTBD, p = 0.58) were similar between the groups. Number of hospitalizations since initial intervention did not differ significantly between the two groups (ERCP median = 1 vs. PTC median = 3.5, p = 0.052). CONCLUSIONS: In patients with CC and biliary obstruction, initial ERCP with stent placement and initial PTBD both represent safe and effective methods of biliary decompression. Initial ERCP and stenting should be considered for relief of biliary obstruction in such patients in centers with advanced endoscopic capabilities.

Arthropathy in acromegaly: a questionnaire-based estimation of motor disability and its relation with quality of life and work productivity.

PURPOSE: Arthropathy is a common and disabling complication of acromegaly. Since in this condition radiological findings rarely correspond to functional impairment, we elected to quantify in a large cohort of acromegalic patients: the degree of motor disability compared with data from general population, the impact of joint involvement on quality of life and work productivity, and to look for associated factors. METHODS: In 211 acromegalic patients, 131 with controlled disease and 80 with active disease, eight validated scales were used to evaluate the (i) prevalence and distribution of arthropathy, (ii) degree of motor disability and joint symptoms (VAS, AIMS symptoms and WOMAC), (iii) quality of life (AcroQoL and PASQ) and work capability (WPAI:GH) as consequences of joint complications. RESULTS: Using the WOMAC questionnaire, for which population based normative values are available, a significantly higher prevalence and severity of motor disability was detected in acromegalics compared to the general population from literature. The results provided by the different questionnaires turned out to be highly concordant. All measures of motor disability correlated both with impaired quality of life and motor disability and were worse in females and in patients with higher BMI. CONCLUSIONS: The questionnaires VAS, AIMS symptoms, and WOMAC (this latter both as a whole and with its functionality subscale), with their scores, proved to be the most adequate tools to evaluate motor disability and its consequences on both quality of life and work productivity in acromegaly. Female gender and higher BMI are associated with worse articular symptoms.

The Frailty Index in centenarians and their offspring.

Frailty has been indicated as a way for capturing biological aging of the individual and Frailty Index (FI) may serve for this purpose. This study designed the FI in a cohort of centenarians, their offspring and control subjects sex- and age-matched with offspring. The FI mean value was 0.47 (SD 0.13) in centenarians, 0.15 (SD 0.12) in their offspring, and 0.22 (SD 0.14) in controls (p < 0.001). The difference between offspring and controls was statistically significant (p = 0.003). The correlation between FI and age was significant in offspring (r = 0.46, p < 0.001), close to significance in controls (r = 0.25, p = 0.08) and not significant in centenarians. Our study confirms that FI is a marker of biological age useful to discriminate different degrees of frailty even at extremely advanced age.

A comparison study of cleanup techniques for oil spill treatment using magnetic nanomaterials.

Magnetic nanoparticles have been successfully used to recovery oil from oil spilled on water. Two different methods, floating and vortex, were employed to promote the interaction of four oil samples with different API (e.g., 10, 20, 28 and 45) spilled on seawater and deionized water with three magnetic materials, namely: magnetite nanoparticles (N); magnetic nanocomposites of yeast biomass provided by ethanol industry (Y); and magnetic nanocomposites of cork powder (C). The magnetic nanomaterials exposed to oil on water were taking out by a neodymium magnet, and the oil recoveries were determined by gravimetric analysis before and after lyophilization. The lyophilization was determinant to guarantee the accuracy of the experiments, and without this step, the masses of oil recovered would be overestimated due to the drag of water during the oil and magnetic material removal process. Three main factors, API, contact method and magnetic material, and two interactions (i.e., API × contact method, and contact method × magnetic material) presented a statistically significant effect on oil recovery. It was observed that oil recovery increases as API decreases, and it was possible to establish a model to predict the amount of recovered oil according to this effect. Higher oil recoveries were also obtained by magnetic nanocomposites of yeast biomass (Y), regardless of the contact method and type of water, recoveries of 23% and 100% for 45 and 10 API, respectively, employing around 20 mg of Y on 300 mg of spilled oil. These percentages correspond to 0.29 ±â€¯0.01 kg/kg and 15.98 kg/kg of recovering oil by the magnetic procedure. The increase of mass of magnetic material improved the recovery of oils with higher APIs. The reusability of the spent materials presents potential for its application in oil spill cleaning technologies.

Dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists are effective in inhibiting proliferation of progenitor/stem-like cells isolated from nonfunctioning pituitary tumors.

The role of progenitor/stem cells in pituitary tumorigenesis, resistance to pharmacological treatments and tumor recurrence is still unclear. This study investigated the presence of progenitor/stem cells in non-functioning pituitary tumors (NFPTs) and tested the efficacy of dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists to inhibit in vitro proliferation. They found that 70% of 46 NFPTs formed spheres co-expressing stem cell markers, transcription factors (DAX1, SF1, ERG1) and gonadotropins. Analysis of tumor behavior showed that spheres formation was associated with tumor invasiveness (OR = 3,96; IC: 1.05-14.88, p = 0.036). The in vitro reduction of cell proliferation by DRD2 and SSTR2 agonists (31 ± 17% and 35 ± 13% inhibition, respectively, p < 0.01 vs. basal) occurring in about a half of NFPTs cells was conserved in the corresponding spheres. Accordingly, these drugs increased cyclin-dependent kinase inhibitor p27 and decreased cyclin D3 expression in spheres. In conclusion, they provided further evidence for the existence of cells with a progenitor/stem cells-like phenotype in the majority of NFPTs, particularly in those with invasive behavior, and demonstrated that the antiproliferative effects of dopaminergic and somatostatinergic drugs were maintained in progenitor/stem-like cells.

Safety and efficacy of direct-acting antivirals for the treatment of chronic hepatitis C in a real-world population aged 65 years and older.

The availability of direct-acting antiviral agents (DAA) regimens has expanded the pool of patients eligible for treatment. However, data on the virologic response and tolerability of DAAs in elderly patients are lacking. We evaluated the efficacy and safety of DAAs in patients with advanced fibrosis/cirrhosis in real-life practice with the focus on those aged ≥65 years. Between January and December 2015, all consecutive patients with HCV-related advanced fibrosis/cirrhosis treated with DAA at eleven tertiary referral centres in Emilia Romagna (Italy) were enrolled. Regimen choice was based on viral genotype and stage of disease, according to guidelines. The primary end point was sustained virologic response 12 weeks after the end of treatment (SVR12). Overall, 282 of 556 (50.7%) patients evaluated were elderly, most of them with cirrhosis. Antiviral therapy was stopped prematurely in four (1.4%) patients. Two patients, both with cirrhosis, died during treatment due to worsening of liver/renal function. SVR12 was achieved by 94.7% and was comparable to that obtained in patients aged <65 (P=.074). Similar data were also reported in subgroup of patients aged ≥75 years. All patients with advanced fibrosis achieved virologic response. SVR12 was 80.8% in Child-Pugh-Turcotte (CTP)-B cirrhosis and 95.4% in CTP-A (P=.013). According to genotype, the SVR12 was achieved in 172 of 181 (95%) with genotype 1b cirrhosis and in 44 of 48 (91.7%) with genotype 2 cirrhosis. In conclusions, in a real-world setting, DAAs are safe and effective in elderly patients with HCV-related advanced fibrosis/cirrhosis, but SVR12 is lower with worsening CTP class.

Antitumor activity of interferon-ß1a in hormone refractory prostate cancer with neuroendocrine differentiation.

PURPOSE: Type I interferons (IFN-α and IFN-ß) are a class of cytokines that exert several biological activities, such as modulation of cell proliferation and differentiation and of the immune system. Although these cytokines interact with a common receptor complex, IFN-ß showed a more potent antitumor activity than IFN-α in several tumor models. New recombinant human IFN-ß products, such as IFN-ß1a and IFN-ß1b, have been produced in order to improve the stability and bioavailability of natural IFN-ß. In this report, we analyzed the effects of recombinant IFN-ß1a on the cell proliferation of two human androgen-resistant prostate cancer cell lines with neuroendocrine differentiation (DU-145, PC-3) and related mechanisms of action. METHODS: The effects of IFN-ß1a on the cell growth proliferation, cell cycle, and apoptosis have been evaluated in DU-145 and PC-3 cells through MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. Moreover, the expression of neuron-specific enolase (NSE), cleaved caspase-3, caspase-8, and PARP was evaluated through Western blotting. RESULTS: IFN-ß1a showed a significant anti-proliferative activity in both androgen-resistant cell lines. This effect was related to cell cycle perturbation and induction in apoptosis, as shown by flow cytometric analysis, the activation of caspase-3 and caspase-8 and PARP cleavage during incubation with IFN-ß1a. Moreover, this cytokine reduced the expression of NSE in both cell lines. CONCLUSIONS: Recombinant IFN-ß1a (Rebif) showed a potent in vitro anti-proliferative activity in androgen-resistant prostate cancer cells, and it could represent a promising tool for the treatment of this tumor.

[Facelift under local anesthaesia in outpatient surgery]. / Le lifting du visage sous anesthésie locale en ambulatoire.

Facelift under local anesthesia: the author recounts his experience and methodology developed to operate facelift under local anesthesia in order to reduce operative morbidity and be able to operate persons who do not desire general anesthesia. The technique is based on the knowledge of the sensitive anatomy of the face as well as the practice of sensitive conduction blocks at the level of the face allowing to decrease the doses of local anesthetics.

Methane intestinal production and poor metabolic control in type I diabetes complicated by autonomic neuropathy.

AIM: At the state of art it's unknown the correlation between diabetes and lower gastrointestinal disorders. Some studies show a significantly higher prevalence of small intestinal bacterial overgrowth in patients with type I diabetes in particular complicated by autonomic neuropathy. No data exists about gastrointestinal methane production in patients with diabetes and autonomic diabetic neuropathy. The aim of this paper was to evaluate the correlation of small intestinal bacterial overgrowth and gastrointestinal methane production with metabolic control and daily insulin requirements in patients with type 1 diabetes and. autonomic diabetic neuropathy. METHODS: Thirty subjects with type 1 diabetes and autonomic diabetic neuropathy were underwent hydrogen and methane lactulose breath test (LBT) to evaluate the presence of small intestinal bacterial overgrowth (double peak of hydrogen) and methane production. The metabolic control was evaluated through the glycated hemoglobin and the daily insulin requirement (calculated as ratio between total insulin units in a day and body weight). Methane producers were treated with metronidazole (500 mg bid for 10 days) and perform a LBT 8 weeks after the end of therapy RESULTS: Eight over thirty patients (26.6%) met the diagnostic criteria for small intestinal bacterial overgrowth. 11/30 patients (36%) were methane-producers (mean baseline value 16.37 ± 13.01 ppm; mean peak 26.62 ± 11.41 ppm); interestingly this subset of patients showed a worse glycemic control (mean HbA1c 8.16 ± 0.9% vs. 7.49 ± 0.8%, P<0.05). After metronidazole therapy 7/11 (63.3%) reduced CH4 production and they showed a mean HbA1c significantly lower than corresponding value before antibiotic therapy (7.63 ± 0.7% vs. 8.25 ± 0.8%). CONCLUSION: Our study showed for the first time a possible role of CH4 production in metabolic control. In particular, the most interesting data is that an increased values of HbA1c seems to be related to a gut CH4 production as confirmed by its significant improvement after eradication therapy. We are not yet able to determine whether poor glycemic control is the cause or the consequence of the selection of methanogenic flora.

Rifaximin treatment for small intestinal bacterial overgrowth in children with irritable bowel syndrome.

OBJECTIVES: Aims of the study were to assess the effects of rifaximin treatment on small intestinal bacterial overgrowth (SIBO) prevalence and gastrointestinal symptoms. STUDY DESIGN: Fifty (50) irritable bowel syndrome (IBS) children were consecutively enrolled. All subjects underwent lactulose hydrogen/methane breath test (LBT) to assess SIBO before and one month after the treatment with rifaximin 600 mg daily for one week. All IBS patients filled out a Visual Analogic Scale (VAS) to assess and score gastrointestinal symptoms (abdominal pain, constipation, diarrhoea, bloating, flatulence) at baseline and one month after treatment. RESULTS: The prevalence of abnormal LBT in patients with IBS was 66% (33/50). LBT normalization rate was 64% (21/33). Compliance was excellent, and no relevant side-effects were observed during treatment. VAS score was significantly higher in IBS patients with abnormal LBT than SIBO negatives, and strongly improved after successful treatment. CONCLUSIONS: Rifaximin was effective and safe in SIBO treatment and IBS symptoms improvement in childhood. Double blind placebo-controlled interventional studies are warranted to verify the real impact of SIBO on gastrointestinal symptoms in children with IBS.

Minimally Invasive Treatment in Benign Prostatic Hyperplasia (BPH).

Review efficacy and safety of minimally-invasive treatments for Low Urinary Tract Symptoms (LUTS) in patients affected by Benign Prostate Hyperplasia (BPH). We performed a systematic review of the literature from 1993 to 2022 leveraging original research articles, reviews, and case-studies published in peer-reviewed journals and stored in public repositories. Prostate artery embolization (PAE), transurethral needle ablation (TUNA), transurethral microwave thermotherapy (TUMT), high intensity focused ultrasound (HIFU), laser treatments and Cryoablation are valid and safe alternatives to the gold standard (surgery) in the treatment of LUTS in patients affected by BPH, with fewer undesired effects being reported.

Everolimus is an active agent in medullary thyroid cancer: a clinical and in vitro study.

Everolimus, an mTOR inhibitor, which has been demonstrated to induce anti-tumour effects in different types of neuroendocrine tumours, has never been evaluated in patients with medullary thyroid cancer (MTC). The aim of this study was to evaluate the in vitro and in vivo effects of everolimus in combination with octreotide in MTC. Two patients with progressive metastatic MTC and high calcitonin levels were treated with everolimus 5-10 mg/day. Both patients were under treatment with octreotide LAR at the study entry. An in vitro study was also performed to assess everolimus effects on MTC cell lines (TT and MZ-CRC-1 cells). A tumour response was observed in both patients. Serum calcitonin decreased by 86% in patient 1 and by 42% in patient 2. In TT and MZ-CRC-1 cells, everolimus induced a significant dose-dependent inhibition in cell proliferation. This effect seems to be related to a cell cycle arrest in G(0) /G(1) phase in both cell lines and to the induction of cellular senescence in TT cells. Everolimus in combination with octreotide may be active as anti-tumour therapy in patients with progressive metastatic MTC, suggesting to further evaluate this agent in MTC patients in a large prospective study.