Vibration Analysis at Castello Ursino Picture Gallery (Sicily, Italy) for the Implementation of Self-Generating AlN-MEMS Sensors.

This work explores the potential of self-powered MEMS devices for application in the preventive conservation of cultural heritage. The main objective is to evaluate the effectiveness of piezoelectric aluminum nitride MEMS (AlN-MEMS) for monitoring vibrations and to investigate its potential for harvesting energy from vibrations, including those induced by visitors. A preliminary laboratory comparison was conducted between AlN-MEMS and the commercial device Tromino®. The study was then extended to the Picture Gallery of Ursino Castle, where joint measurements with the two devices were carried out. The analysis focused on identifying natural frequencies and vibrational energy levels by key metrics, including spectral peaks and the Power Spectral Density (PSD). The results indicated that the response of the AlN-MEMS aligned well with the data collected by the commercial device, especially observing high vibrational energy around 100 Hz. Such results validate the potential of AlN-MEMS for effective vibration measurement and for converting kinetic energy into electrical power, thereby eliminating the need for external power sources. Additionally, the vibrational analysis highlighted specific locations, such as the measurement point Cu4, as exhibiting the highest vibrational energy levels. These points could be used for placing MEMS sensors to ensure efficient vibration monitoring and energy harvesting.

Prospective nonrandomized study to evaluate cone beam computed tomography for technical assessment of standard and complex endovascular aortic repair.

OBJECTIVE: The objective of this study was to analyze the utility of cone beam computed tomography (CBCT) for technical assessment of standard and complex endovascular aneurysm repair (EVAR). METHODS: Data of consecutive patients who underwent standard or complex EVAR in 2016 and 2017 at our institution were entered into a prospective database and analyzed retrospectively. There were 154 patients (126 male; mean age, 74 ± 8 years) enrolled in a prospective study between 2016 and 2017. A total of 170 aortic procedures were investigated, including 85 fenestrated-branched EVARs (F-BEVARs), 42 abdominal and thoracic EVARs, 32 EVARs with iliac branch devices, and 11 aorta-related interventions. Technical assessment was done using CBCT with and without contrast enhancement, digital subtraction angiography (DSA), and computed tomography angiography (CTA). Patients with stage 3B or stage 4 chronic kidney disease had CBCT without contrast enhancement. Radiation exposure (mean dose-area product), effective dose (ED), and amount of iodine contrast agent were analyzed. End points were presence of any endoleak, positive findings warranting possible intervention (stent kink or compression, type I or type III endoleak, dissection, thrombus), and need for secondary intervention. RESULTS: Radiation exposure and amount of iodine contrast agent were significantly higher (P < .05) for F-BEVAR compared with other aortic procedures (174±101 Gy∙cm2 vs 1135±113 Gy∙cm2 and 144±60 mL vs 122±49 mL). ED averaged 74±36 mSv for the aortic procedure, 18 ± 18 mSv for fluoroscopy, 7 ± 7 mSv for DSA acquisition, 15±7 mSv for CBCT, and 34±17 mSv for CTA imaging (P < .001). Endoleak detection was significantly higher (P < .001) with CBCT (53%) compared with DSA (14%) and CTA (46%). CBCT identified 52 positive findings in 43 patients (28%), higher for F-BEVAR compared with other aortic procedures (35% vs 16%; P = .01). Positive findings included stent compression or kink in 29 patients (17%), type I or type III endoleak in 16 patients (10%), and arterial dissection or thrombus in 7 patients (5%). Of these, 28 patients (18%) had positive findings that prompted an intraoperative (17%) or delayed intervention (1%). Another 15 patients (10%) with minor positive findings were observed with no clinical consequence. DSA alone would not have detected positive findings in 34 of 43 patients (79%), including 21 patients (49%) who needed secondary interventions. CTA diagnosed two (1%) additional endoleaks requiring intervention (one type IC, one type IIIC) that were not diagnosed by CBCT. Replacing DSA and CTA by CBCT would have resulted in 53% ± 13% reduction in amount of iodine contrast agent and 55% ± 12% reduction in ED (P < .05). CONCLUSIONS: CBCT reliably detected positive findings prompting immediate revisions in nearly one of five patients, with the highest rates among F-BEVAR patients. Detection of any endoleak was higher with CBCT compared with DSA or CTA, but most endoleaks were observed. DSA alone failed to detect positive findings warranting revisions.

Dietary approach to prevent obesity risk in Spina Bifida patients.

PURPOSE: The aim of this prospective, analytic study is to evaluate if dietary approach can improve the body mass index (BMI) in a total of N = 152 patients with SB. METHODS: BMI levels were evaluated stratifying patients by gender and age classes. Patients with BMI ≥ 25 have been randomized (1:1) in two groups: the "diet" group that received a dietary program and the "no diet" group that did not receive any program. Patients have been observed at the beginning of the study (T0), and again at the end of the study, 1 year later (T1). The main objective of the study was to evaluate BMI score in SB patients and how it could be influenced by dietary changes. RESULTS: A total of 36.8% patients were classified as overweight or obese. Females present a mean BMI level higher than male, and patients older than 20 years old present the highest mean BMI. The "diet" group BMI decreased from 29.7 (± 3.8) to 27.7 (± 3.7) during the year of program. The mean BMI in the "no diet" group decreased from 30.3 (± 4.6) to 29.2 (± 4.7). There was a statistically significant difference in BMI level between groups (p < 0.0005). There was a statistically significant effect of time on BMI levels for the "diet program" group (p = 0.001), and there was NOT a statistically significant effect of time on BMI levels for the "no diet group" (p = 0.053). CONCLUSIONS: Spina Bifida population has high risk of obesity which is related to other comorbidities such as diabetes and hypertension for example. Specific dietary program, since pediatric age, correlates with an improvement of quality of life, a reduction of BMI and of risk of related diseases with obesity. This study confirms that the transition to adulthood marks the beginning of the overweight status for many SB patients, but it also demonstrates that, following a dietary program, even disabled patients with limited training capabilities can achieve a BMI reduction.

Impact of onlay fusion and cone beam computed tomography on radiation exposure and technical assessment of fenestrated-branched endovascular aortic repair.

OBJECTIVE: The objective of this study was to analyze the impact of advanced imaging applications and cone beam computed tomography (CBCT) on radiation exposure of the patient and operator and detection of technical problems during fenestrated-branched endovascular aortic repair (F-BEVAR) for treatment of pararenal aneurysms and thoracoabdominal aortic aneurysms (TAAAs). METHODS: We reviewed the clinical data of 386 consecutives patients (289 male; mean age, 75 ± 8 years) treated by F-BEVAR for 196 pararenal aneurysms and 190 TAAAs (mean, 3.4 ± 0.9 targeted vessels/patient) between 2007 and 2017. Radiation exposure (cumulative air kerma) was analyzed in three fixed imaging systems used between 2007 and 2011 (system 1), 2012 and 2016 (system 2), and 2016 and 2017 (system 3). Onlay fusion and CBCT were available with systems 2 and 3, whereas digital zoom with fusion overlay was used with system 3. Operator effective dose was measured per month using a radiation dosimeter badge. Computed tomography angiography and CBCT were analyzed for findings requiring immediate revision or secondary interventions. End points were patient radiation exposure; operator effective dose; procedure technical success; and 30-day rates of mortality, major adverse events, and secondary interventions. RESULTS: F-BEVAR was performed using system 1 in 98 patients, system 2 in 198 patients, and system 3 in 90 patients. Use of onlay fusion/CBCT was 0% with system 1, 42% with system 2, and 98% with system 3. Procedures performed with onlay fusion/CBCT had significantly (P < .05) higher technical success (99.4% vs 98.8%) and lower contrast material volume (155 ± 58 mL vs 172 ± 80 mL), fluoroscopy time (83 ± 34 minutes vs 94 ± 49 minutes), and cumulative air kerma (2561 ± 1920 mGy vs 3767 ± 2307 mGy). Despite higher case volume and increasing complexity during the experience, operator effective dose decreased to 9 ± 4 × 10-2 mSv/case with system 3 compared with 26 ± 3 × 10-2 mSv/case with system 1 and 20 ± 2 × 10-2 mSv/case with system 2 (P = .001). Among 219 patients who had no CBCT, 18 (8%) had computed tomography angiography findings that prompted secondary interventions before dismissal. Conversely, among 167 patients who had CBCT, 14 patients (8%) had intraoperative CBCT findings requiring immediate revision, with no additional secondary interventions. Patients treated with onlay fusion/CBCT had significantly (P < .05) lower mortality (4% vs 1%), major adverse events (43% vs 19%), and secondary interventions (10% vs 4%) at 30 days. CONCLUSIONS: Radiation exposure and operator effective dose significantly decreased with evolution of F-BEVAR experience and use of advanced imaging applications such as onlay fusion and CBCT. CBCT allowed immediate assessment and identified intraoperative technical problems, leading to immediate revision and avoiding early secondary interventions.

Outcomes of upper extremity access during fenestrated-branched endovascular aortic repair.

OBJECTIVE: Upper extremity (UE) access is frequently used during fenestrated-branched endovascular aortic repair (F-BEVAR) to facilitate catheterization of downgoing vessels. Limitations include risk of cerebral embolization and of UE arterial or peripheral nerve injury. The aim of this study was to assess outcomes of F-BEVAR using UE access. METHODS: We reviewed the clinical data of 334 consecutive patients (74% males; mean age 75 ± 8 years) treated by F-BEVAR for thoracoabdominal aortic aneurysms or pararenal aortic aneurysms between 2007 and 2016. Patients who underwent F-BEVAR with an UE approach for catheterization of the renal and/or mesenteric arteries were included in the study. End points were technical success, mortality, and a composite of access-related complications including cerebral embolization (stroke/transient ischemic attack), peripheral nerve injury, and axillary-brachial arterial complications requiring intervention. RESULTS: There were 243 patients (73%) treated by F-BEVAR with UE access, including 147 patients (60%) with thoracoabdominal aortic aneurysms and 96 patients (40%) with pararenal aortic aneurysms. A total of 878 renal-mesenteric arteries were incorporated by fenestrations or branches with a mean of 3.6 ± 0.8 vessels per patient. All patients had surgical exposure of the brachial artery. The left side was selected in 228 (94%) and the right side in 15 (6%). The technical success of target vessel incorporation was achieved in 99% of patients (870 of 878). Arterial closure was performed using primary repair in 213 patients (88%) or bovine patch angioplasty in 29 (12%). Patch closure was required in 13% of patients (21 of 159) treated by 10- to 12F sheaths and 8% (7 of 83) of those who had 7- to 8F sheaths (P = .19). There were six deaths (2.5%) at 30 days or within the hospital stay, none owing to access-related complications. Major access-related complication occurred in eight patients (3%), with no difference between the 10- to 12F (6 of 159 [4%]) or 7- to 8F sheaths (2 of 83 [2%]; P = .45). Two patients (1%) had transient median nerve neuropraxia, which resolved within 1 year. One patient (0.5%) required surgical evacuation of an access site hematoma. There were no UE arterial pseudoaneurysms, occlusions, or distal embolizations. Five patients (2%) had strokes (three minor, two major), occurring more frequently with right side (2 of 15 [13%]) as compared with left-sided access (3 of 228 [1%]; P = .03). After a mean follow-up of 38 ± 15 months, there were no other access-related complications or reinterventions. CONCLUSIONS: UE arterial access with surgical exposure was associated with a low rate of complications in patients treated with F-BEVAR. Closure with patch angioplasty is frequently needed, but there were no arterial occlusions, pseudoaneurysms, or distal embolizations requiring secondary procedures.

Outcomes of an iliac branch endoprosthesis using an "up-and-over" technique for endovascular repair of failed bifurcated grafts.

OBJECTIVE: Type IB endoleak after endovascular aneurysm repair may be treated by an iliac branch endoprosthesis (IBE) through brachial access for internal iliac artery (IIA) stenting. The aim of this study was to evaluate outcomes of the IBE using an "up-and-over" transfemoral technique in patients with prior aortic repair compared with the standard technique in patients with de novo iliac aneurysms. METHODS: We reviewed the clinical data of patients treated for aortoiliac aneurysms using Gore IBE (W. L. Gore & Associates, Flagstaff, Ariz) between 2014 and 2017. The up-and-over technique was indicated in patients with type IB endoleak or common iliac aneurysms after prior aortic repair with bifurcated endografts or surgical grafts. End points were technical success, mortality, major adverse events, IIA patency, freedom from IIA branch instability (composite end point of any IIA branch-related complication leading to aneurysm rupture, death, occlusion, component separation, or reintervention to maintain branch patency or to treat a branch-related separation or endoleak), and freedom from secondary interventions or new-onset buttock claudication. RESULTS: There were 53 patients (51 male; 74 ± 8 years old) treated by 62 IBEs (9 bilateral). Standard technique was used in 36 patients (43 IBEs) and up-and-over technique in 17 (19 IBEs). Three patients had contralateral IIA embolization. Total procedure time, contrast material volume, and radiation dose averaged 168 ± 98 minutes, 140 ± 50 mL, and 1096 ± 1009 mGy, with no difference between techniques. Technical success was achieved in 98% of patients. Eleven patients had extension of IIA bridging stent into the posterior branch (eight standard, three up-and-over). Four patients (8%) had major adverse events due to estimated blood loss >1000 mL in all patients. There was no 30-day mortality after a median follow-up of 7 months (interquartile range, 3-12 months). There were two IIA stent occlusions (all standard), three iliac-related type I endoleaks (one standard, two up-and-over), and four secondary interventions (three standard, one up-and-over). At 1 year, patients treated by standard or up-and-over technique had similar primary patency (94% ± 4% vs 100%; P = .38) and secondary patency (97% ± 3% vs 100%; P = .54) and freedom from IIA branch instability (90% ± 6% vs 93% ± 7%; P = .48), secondary intervention (84% ± 8% vs 90% ± 9%; P = .63), and new-onset buttock claudication (90% ± 6% vs 100%; P = .35). CONCLUSIONS: Endovascular repair using IBE was associated with high technical success, no mortality, and low rate of complications using either the standard technique for de novo aneurysms or an up-and-over technique for patients with failed bifurcated endografts or grafts. The up-and-over technique should be considered a suitable alternative to brachial access in patients who require distal extension using IBEs.

Evolution from physician-modified to company-manufactured fenestrated-branched endografts to treat pararenal and thoracoabdominal aortic aneurysms.

OBJECTIVE: The purpose of this study was to review treatment trends and outcomes of patients who underwent fenestrated-branched endovascular aneurysm repair (F-BEVAR) of pararenal aneurysms (PRAs) or thoracoabdominal aortic aneurysms (TAAAs) using physician-modified endografts (PMEGs) or company-manufactured devices (CMDs). METHODS: We reviewed the clinical data of 316 consecutive patients (242 male patients; mean age, 75 ± 8 years) who underwent F-BEVAR between 2007 and 2016. F-BEVAR was performed under two prospective investigational device exemption protocols since 2013. End points were mortality, major adverse events (MAEs), patient survival, reintervention, branch instability, aneurysm-related mortality, renal function deterioration, and target vessel patency. RESULTS: There were 145 patients (46%) treated by PMEGs (84 PRAs, 26 extent IV and 35 extent I-III TAAAs) and 171 patients (54%) who had CMDs (88 PRAs, 42 extent IV and 41 extent I-III TAAAs). Choice of endograft evolved from PMEGs in 131 patients (83%) treated in the first half of experience to CMDs in 144 patients (91%) treated in the second half of experience (P < .001). Patients treated by PMEGs had significantly (P < .05) larger aneurysms, more chronic pulmonary and kidney disease, and higher comorbidity severity scores. A total of 1081 renal-mesenteric arteries were targeted in both groups. Technical success was lower for PMEGs (98% vs 99.5%; P = .02). Thirty-day mortality was 5.5% for PMEGs (PRAs, 1.2%; extent IV 3.8% and extent I-III, 17.1%) and 0% for CMDs (P = .0018). Patients treated by PMEGs had significantly more (P < .001) MAEs (48% vs 23%) and longer hospital stay (9 ± 10 days vs 6 ± 6 days; P = .001). Mean follow-up was significantly longer for patients treated by PMEGs (38 ± 26 months vs 14 ± 12 months; P < .001). At 3 years, patient survival (68% ± 4% vs 67% ± 8%; P = .11), freedom from reintervention (68% ± 4% vs 68% ± 8%; P = .17), primary (94% ± 2% vs 92% ± 2%; P = .64) and secondary target vessel patency (98% ± 1% vs 98% ± 1%; P = .89), and freedom from renal function deterioration (75% ± 4% vs 65% ± 6%; P = .24) were similar for patients treated by PMEGs or CMDs, respectively. CONCLUSIONS: Choice of F-BEVAR evolved from PMEGs to almost exclusively CMDs under physician-sponsored investigational device exemption protocols. PMEG patients had more comorbidities and larger aneurysms. CMDs were performed with higher technical success, no mortality, and fewer MAEs.

Cross-sectional associations between cutaneous viral infections and regulatory T lymphocytes in circulation.

BACKGROUND: Cutaneous viral infections and immune suppression are risk factors for some forms of nonmelanoma skin cancer; however, their interrelationship is poorly understood. OBJECTIVES: To examine cross-sectional associations between cutaneous viral infections and circulating forkhead-box P3 (FOXP3)-expressing T-regulatory (Treg) cells, suppressive cells that dampen effective antitumour immunity. MATERIALS AND METHODS: Blood, eyebrow hair (EBH) and skin swab (SSW) samples were collected from 352 patients 60 years and older undergoing skin screening, without prevalent skin cancer, while participating in an ongoing prospective cohort study of cutaneous viral infections and skin cancer. DNA corresponding to 98 cutaneous human papillomavirus (HPV) types and five human polyomaviruses (HPyV) was assessed in EBH and SSW. Distinct classes of circulating Treg-cell subpopulations were defined by flow cytometry including cutaneous lymphocyte antigen (CLA) and CCR4high Treg cells, both previously associated with cutaneous diseases. Age- and sex-adjusted associations between circulating T-cell populations and infection were estimated using logistic regression. RESULTS: Total Treg-cell proportion in peripheral blood was not associated with ß HPV or HPyV infection. However, the proportion of circulating CLA+ Treg cells was inversely associated with γ HPV EBH infection [odds ratio (OR) 0·54, 95% confidence interval (CI) 0·35-0·84]. Interestingly, circulating Treg cells expressing markers indicative of antigen activation (CD27- CD45RA- FOXP3+ CD4+ ) were also inversely associated with γ HPV infection in SSW (OR 0·55, 95% CI 0·30-0·99) and EBH (OR 0·56, 95% CI 0·36-0·86). CONCLUSIONS: Inverse associations between circulating Treg cells and γ HPV infection suggest that localized viral infection may promote immunosuppressive cell migration into skin.

Comparison of Perioperative Outcomes of Patients with Iliac Aneurysms Treated by Open Surgery or Endovascular Repair with Iliac Branch Endoprosthesis.

BACKGROUND: Treatment of common and internal iliac aneurysms is usually done by open surgery. A novel iliac branch endoprosthesis (IBE) is commercially available with encouraging initial results. Our objective is to compare perioperative outcomes of patients with iliac aneurysms treated by open surgery (OS) versus endovascular repair with IBE. METHODS: The study was a retrospective, single-center review of patients who were treated for aortoiliac or isolated common and/or internal iliac artery aneurysms from 2014 to 2017. Patients with connective tissue disorders, infected grafts, or thoracoabdominal aneurysms were excluded. Primary outcomes were perioperative mortality, length of hospital (LOS) and intensive care unit (ICU) stay, estimated blood loss, need for red blood cell transfusion (RBC), and perioperative reinterventions. RESULTS: Sixty-seven patients (96% male) were treated with OS (n = 25, mean age 68 ± 8 years) or IBE (n = 42, mean age 73 ± 8 years; P = 0.02) with 1 symptomatic patient in each group. Perioperative mortality occurred in 1 patient in the OS group (4%), with no mortality in the IBE group (P = 0.37) Total LOS and ICU stay was higher for OS compared to IBE (total stay 7.5 ± 3.4 vs. 1.7 ± 1.4 days for IBE, P < 0.0001 and ICU LOS 3.3 ± 2.1 vs. 0.1 ± 0.4 days, P < 0.0001). Estimated blood loss was higher for patients undergoing OS (4,732 ± 2,540 mL) compared to patients treated with IBE (263 ± 451 mL, P < 0.0001), resulting in higher RBC transfusion requirements (1.5 ± 2.4 vs. 0.2 ± 0.8 units, P = 0.001). Five patients in the OS group had early procedure-related reinterventions, while 2 patients in the IBE group required reintervention for access site complications (20% vs. 4.7%, P = 0.09). CONCLUSIONS: Endovascular repair of iliac aneurysms with IBE is feasible and is associated with lower blood loss, LOS and ICU stay, and had lower RBC transfusion requirements. Cost analysis and long-term follow-up will be needed to define the value of this modality for iliac artery aneurysm repair.

Distribution and factors associated with salivary secretory leukocyte protease inhibitor concentrations.

OBJECTIVES: This cross-sectional study examined the distribution and correlates of salivary secretory leukocyte protease inhibitor (SLPI) concentrations within a multinational cohort of men. METHODS: Extracellular SLPI was measured in oral gargle cell supernatants of 378 men from three countries using an ELISA-based assay. Risk factor data were collected by a questionnaire. Factors associated with SLPI were assessed using linear and logistic regression for continuous and categorical SLPI, respectively. RESULTS: Among men aged 18-73 years, the median SLPI concentration was 492.0 ng ml-1 (range: 2.3-1919.9). In multivariable modeling, men in Brazil and younger men (18-30 years) were more likely to have higher levels of SLPI [adjusted odds ratio (aOR) 3.84; 95% confidence interval (CI): 1.94-7.59, and aOR 3.84; 95% CI: 1.98-7.43, respectively]. Men with a self-reported sexually transmitted diseases diagnosis in the past 6 months were more likely to have higher SLPI levels (aOR 2.98; 95% CI: 1.1-7.83) and men reporting bleeding/swollen gums were less likely to have higher SLPI (aOR 0.34; 95% CI: 0.15-0.79). Similar results were observed for linear regression models. CONCLUSIONS: Secretory leukocyte protease inhibitor concentrations varied significantly by country and decreased with increasing age. The interaction between SLPI, modifiable factors, and oral infections that influence cancer risk warrants further investigation.

Impact of Consensus Guidelines by the Society of Surgical Oncology and the American Society for Radiation Oncology on Margins for Breast-Conserving Surgery in Stages 1 and 2 Invasive Breast Cancer.

BACKGROUND: This study aimed to evaluate the impact that the release of consensus guidelines for margins in breast-conserving surgery (BCS) had on re-excision rates. METHODS: A retrospective review examined a prospectively maintained database of patients who had operable invasive breast cancer treated with BCS at the authors' institution. The patients were divided into two groups: (1) those with a diagnosis determined from 1 July 2011 to 31 July 2013 (before release of the guidelines) and (2) those with a diagnosis determined from 1 February 2014 to 31 July 2014 (after release of the guidelines). The groups were evaluated with respect to patient and tumor characteristics, re-excision rates, and reasons for re-excision. RESULTS: A total of 846 cases of BCS were managed: 597 in group 1 and 249 in group 2. Re-excision rates were significantly reduced after release of the consensus guidelines (p = 0.03). Re-excisions were performed for 115 (19 %) of 597 patients in group 1 and 32 (13 %) of 249 patients in group 2. After release of the guidelines, re-excisions were performed for positive margins, as defined by the consensus statement, in 25 (78 %) of 32 cases. The two groups did not differ significantly in terms of age, tumor size, grade, nodal status, estrogen receptor status, progesterone receptor status, or human epidermal growth factor receptor 2 status. Group 1 had more tumors of mixed ductal and lobular histology than group 2, and group 2 had more lobular tumors than group 1 (p = 0.02). CONCLUSIONS: The consensus guidelines on margins for BCS were applied for 78 % of the patients who underwent re-excision and resulted in a significant reduction in re-excision rates.

Onabotulinumtoxin type A (Botox(®)) versus Incobotulinumtoxin type A (Xeomin(®)) in the treatment of focal idiopathic palmar hyperhidrosis: results of a comparative double-blind clinical trial.

Focal hyperhidrosis often has a substantial psychological and social impact on quality of life, since it interferes with daily activities. To date, for the treatment of focal hyperhidrosis, the botulinum toxin type A is an effective second line tool. The purpose of this study was to compare Onabotulinumtoxin A (Botox(®)) and Incobotulinumtoxin A (Xeomin(®)) administration in the treatment of palmar hyperhidrosis. In a double-blind clinical trial, 25 patients with moderate or severe palmar hyperhidrosis received in the same session intradermal injections of Onabotulinumtoxin A on one hand and Incobotulinumtoxin A on the other. Several measures of efficacy and safety were evaluated: disease severity improvement, sweat reduction, hand-grip strength decrease, pain/discomfort during the treatment, and patient's global satisfaction. All patients were responsive to the treatments (HDSS at T4 vs HDDs at T0; p < 0.0001), and no significant difference between Onabotulinumtoxin A and Incobotulinumtoxin A in terms of anhidrotic effect (Minor's test at T4; p = 0.51), long-term efficacy (Minor's test at T12; p = 0.76), (Minor's test at T24; p = 0.58), subjective pain related to the injections (p = 0.88), muscle strength reduction after treatment (p = 0.56), and global satisfaction with the treatment (p = 0.26). Onabotulinum toxin A and Incobotulinumtoxin A seem to be comparable in terms of anhidrotic effect (short-term results), duration of benefits (long-term efficacy), muscle strength reduction (safety), pain related to injections (tolerability), and treatment satisfaction expressed by patients.

Thermophilic two-phase anaerobic digestion of source-sorted organic fraction of municipal solid waste for bio-hythane production: effect of recirculation sludge on process stability and microbiology over a long-term pilot-scale experience.

A two-stage thermophilic anaerobic digestion process for the concurrent production of hydrogen and methane through the treatment of the source-sorted organic fraction of municipal solid waste was carried out over a long-term pilot scale experience. Two continuously stirred tank reactors were operated for about 1 year. The results showed that stable production of bio-hythane without inoculum treatment could be obtained. The pH of the dark fermentation reactor was maintained in the optimal range for hydrogen-producing bacteria activity through sludge recirculation from a methanogenic reactor. An average specific bio-hythane production of 0.65 m(3) per kg of volatile solids fed was achieved when the recirculation flow was controlled through an evaporation unit in order to avoid inhibition problems for both microbial communities. Microbial analysis indicated that dominant bacterial species in the dark fermentation reactor are related to the Lactobacillus family, while the population of the methanogenic reactor was mainly composed of Defluviitoga tunisiensis. The archaeal community of the methanogenic reactor shifted, moving from Methanothermobacter-like to Methanobacteriales and Methanosarcinales, the latter found also in the dark fermentation reactor when a considerable methane production was detected.

Analysis of polyphosphate in mammalian cells and tissues: methods, functions and challenges.

Polyphosphates play a crucial role in various biological processes, such as blood coagulation, energy homeostasis, and cellular stress response. However, their isolation, detection, and quantification present significant challenges. These difficulties arise primarily from their solubility, low concentration in mammals, and structural similarity to other ubiquitous biopolymers. This review provides an overview of the current understanding of polyphosphates in mammals, including their proposed functions and tissue distribution. It also examines key isolation techniques, such as chromatography and precipitation, alongside detection methods, such as colorimetric assays and enzymatic digestion. The strengths and limitations of these methods are discussed, as well as the challenges in preserving polyphosphate integrity. Recent advancements in isolation and detection are also highlighted, offering a comprehensive perspective essential for advancing polyphosphate research.

Membrane-permeable tenofovir-di- and monophosphate analogues.

The development of new antiviral agents such as nucleoside analogues or acyclic nucleotide analogues (ANPs) and prodrugs thereof is an ongoing task. We report on the synthesis of three types of lipophilic triphosphate analogues of (R)-PMPA and dialkylated diphosphate analogues of (R)-PMPA. A highly selective release of the different nucleotide analogues ((R)-PMPA-DP, (R)-PMPA-MP, and (R)-PMPA) from these compounds was achieved. All dialkylated (R)-PMPA-prodrugs proved to be very stable in PBS as well as in CEM/0 cell extracts and human plasma. In primer extension assays, both the monoalkylated and the dialkylated (R)-PMPA-DP derivatives acted as (R)-PMPA-DP as a substrate for HIV-RT. In contrast, no incorporation events were observed using human polymerase γ. The dialkylated (R)-PMPA-compounds exhibited significant anti-HIV efficacy in HIV-1/2 infected cells (CEM/0 and CEM/TK-). Remarkably, the dialkylated (R)-PMPA-MP derivative 9a showed a 326-fold improved activity as compared to (R)-PMPA in HIV-2 infected CEM/TK- cells as well as a very high SI of 14,000. We are convinced that this study may significantly contribute to advancing antiviral agents developed based on nucleotide analogues in the future.

Assessment of DNA methylation status in early stages of breast cancer development.

BACKGROUND: Molecular pathways determining the malignant potential of premalignant breast lesions remain unknown. In this study, alterations in DNA methylation levels were monitored during benign, premalignant and malignant stages of ductal breast cancer development. METHODS: To study epigenetic events during breast cancer development, four genomic biomarkers (Methylated-IN-Tumour (MINT)17, MINT31, RARß2 and RASSF1A) shown to represent DNA hypermethylation in tumours were selected. Laser capture microdissection was employed to isolate DNA from breast lesions, including normal breast epithelia (n=52), ductal hyperplasia (n=23), atypical ductal hyperplasia (n=31), ductal carcinoma in situ (DCIS, n=95) and AJCC stage I invasive ductal carcinoma (IDC, n=34). Methylation Index (MI) for each biomarker was calculated based on methylated and unmethylated copy numbers measured by Absolute Quantitative Assessment Of Methylated Alleles (AQAMA). Trends in MI by developmental stage were analysed. RESULTS: Methylation levels increased significantly during the progressive stages of breast cancer development; P-values are 0.0012, 0.0003, 0.012, <0.0001 and <0.0001 for MINT17, MINT31, RARß2, RASSF1A and combined biomarkers, respectively. In both DCIS and IDC, hypermethylation was associated with unfavourable characteristics. CONCLUSION: DNA hypermethylation of selected biomarkers occurs early in breast cancer development, and may present a predictor of malignant potential.

Analysis of overdispersed count data: application to the Human Papillomavirus Infection in Men (HIM) Study.

The Poisson model can be applied to the count of events occurring within a specific time period. The main feature of the Poisson model is the assumption that the mean and variance of the count data are equal. However, this equal mean-variance relationship rarely occurs in observational data. In most cases, the observed variance is larger than the assumed variance, which is called overdispersion. Further, when the observed data involve excessive zero counts, the problem of overdispersion results in underestimating the variance of the estimated parameter, and thus produces a misleading conclusion. We illustrated the use of four models for overdispersed count data that may be attributed to excessive zeros. These are Poisson, negative binomial, zero-inflated Poisson and zero-inflated negative binomial models. The example data in this article deal with the number of incidents involving human papillomavirus infection. The four models resulted in differing statistical inferences. The Poisson model, which is widely used in epidemiology research, underestimated the standard errors and overstated the significance of some covariates.

Design and validation of a multiplex specific primer-directed polymerase chain reaction assay for killer-cell immunoglobulin-like receptor genetic profiling.

Current methodologies for the analysis of the killer-cell immunoglobulin-like receptor (KIR) locus utilize specific primer-directed polymerase chain reaction (SSP-PCR), which require a wide range of DNA input, multiple reaction conditions, and up to 16 individual reactions. We have developed and validated a multiplex SSP-PCR method for the genetic analysis of the KIR locus. Design and optimization of four multiplex groups targeting 14 genes and their alleles on the KIR locus has been completed. Each multiplex group contains PCR products that differ in size by a minimum of 15 bp to allow sufficient fragment length resolution for size discrimination by gel electrophoresis. This assay allows for efficient genotyping of the KIR locus while requiring a minimum amount of DNA input, utilizing the simplicity of SSP-PCR.

Treatment of focal idiopathic hyperhidrosis with Botulinum Toxin Type A: clinical predictive factors of relapse-free survival.

BACKGROUND: No material about the identification of predictive clinical factors of therapeutic response to Botulinum Toxin Type A (BTX-A) in focal idiopathic hyperhidrosis has been found. OBJECTIVE: To evaluate if age, sex, extension rate of hyperhidrotic area, localization, disease-related impairment of life quality, number of previous local, non-invasive treatments different from BTX-A, and duration of disease, may affect the relapse-free survival (RFS) after a BTX-A treatment in palmar and axillary focal idiopathic hyperhidrosis. METHODS: Forty-one patients suffering from palmar hyperhidrosis, and 38 patients suffering from axillary hyperhidrosis received intradermal injections of BTX-A. All patients were clinically screened before and after treatment; they were followed for 15 months after it, according to Hyperhidrosis Disease Severity Scale (HDSS), Minor's test, and DLQI test, to state disease severity, and disease-related impairment of quality of life. RESULTS: The duration of therapeutic effect of BTX-A is not significantly influenced by age (P = 0.783), sex (P = 0.762), extension of hyperhidrotic area (P = 0.770), site of involvement (P = 0.402), disease-induced impairment of life quality (P = 0.745), number of previous therapies (P = 0.730), or site of involvement (P = 0.402). In palmar idiopathic hyperhidrosis, patients with a longer disease history show a shorter duration of RFS after a treatment with BTX-A (P = 0.01). CONCLUSIONS: Patients suffering from palmar hyperhidrosis have a longer lasting disease, and a length of disease more than 20 years in these patients influences the RFS after BTX-A treatment.

Two-phase thermophilic anaerobic digestion process for biohythane production treating biowaste: preliminary results.

This paper deals with the optimization of a two-phase anaerobic process treating biowaste for hydrogen and methane production. Neither physical nor chemical pre-treatments were used to optimize the process. The work was carried out at pilot scale, using two CSTRs (200 and 380 L working volume respectively) both maintained at thermophilic temperature (55 C) and fed semi-continuously with biowaste. The experiment was divided into three periods; during the first two periods the organic loading rate was maintained at 20 kg TVS/m3 d and the hydraulic retention time was changed from 6.6 to 3.3 days, while in the last period the digestate of the second reactor was recirculated to the first reactor in order to buffer the system and control pH at levels around 5. The HRT was maintained at 3.3 days and the OLR was decreased at 16.5 kg TVS/m3 d. The best yield was obtained in the last period where a specific hydrogen production of 50.9 L/kg VSfed was reached, with a H2 content in biogas from the first reactor of 36%. The methanogenic stage after the hydrogen conversion reached a specific biogas production of 0.62 m3/kg VSfed and an overall organic removal above 70%, without any stability problem. The overall biogas production was some 1.5 m3 per day with a gas composition of 10% H2 and 50% CH4.