Retrospective study in clinical governance and financing system impacts of the COVID-19 pandemic in the hand surgery and microsurgery HUB center.

INTRODUCTION: The authors presented a retrospective study in the surgical activity of the HUB center for Hand Surgery and Microsurgery in Emilia-Romagna comparing the data between March and April 2020, in the peak of Covid pandemic, with the same period in 2019. MATERIALS AND METHODS: During the two months period of March-April 2020 versus 2019 the authors analyzed the surgical procedures performed in elective and emergency surgery with hospitalization and Day or Outpatient surgery regime. Surgical treatments with no hospitalization were planned in the Day-Surgery Service. The financing system impacts were analyzed according to the Diagnosis Related Groups (DRG), the costs accounting method mostly used in European countries. RESULTS: An overall reduction of 68.5% was recorded in surgical procedures, with a more relevant reduction of 92.3% in elective surgery and a significantly less relevant reduction of 37.2% in urgent one. Replantation did not present a reduction in number of cases, while cutting lesions of tendons at the hand and fingers increased such as the bone and ligament injuries during domestic accidents. The negative impact in the financial system recorded a reduction of 32.5%. DISCUSSION: The epidemiology of hand trauma looks not only at the artisanal and industrial injuries, but also mostly at the accidents in daily life activities. The data of the study evidenced the significantly increase in the injuries occurring in the domestic environment. Elective surgery was canceled. The 86% of surgical procedures performed were urgent ones and the 72.8% of these were possible in Day and Outpatient surgery with significantly reduction in hospitalization. All procedures followed a rigid process for patient and healthcare workers with regard for personal protection and safety. Telemedicine was arranged in emergencies, and economic damage was analyzed also in the following rebound effect during summer period. CONCLUSIONS: The significantly less reduction recorded in urgent surgery vs the more relevant reduction in elective one showed how the hand injuries remained a major issue also during the lockdown. The data highlighted the relevant role of the organizational aspects of the surgical procedures and planning in hand trauma. Despite the financial impact of the elective surgery, the presence of a functional and skill Emergency Service and Day-Surgery Service resulted fundamental in the efficacy and efficiency of the patient management and in containment of economic damage. The telemedicine was significantly limited by liability and risk management issues.

Combined Methodologies for Determining In Vitro Bioavailability of Drugs and Prediction of In Vivo Bioequivalence From Pharmaceutical Oral Formulations.

With the aim of developing an in vitro model for the bioavailability (BA) prediction of drugs, we focused on the study of levonorgestrel (LVN) released by 1.5 mg generic and brand-name tablets. The developed method consisted in combining a standard dissolution test with an optimized parallel artificial membrane permeability assay (PAMPA) to gain insights into both drug release and gastrointestinal absorption. Interestingly, the obtained results revealed that the tablet standard dissolution test, combined with an optimized PAMPA, highlighted a significant decrease in the release (15 ± 0.01 µg min-1 vs 30 ± 0.01 µg min-1) and absorption (19 ± 7 × 10-6 ± 7 cm/s Pe vs 41 ± 15 × 10-6 cm/s Pe) profiles of a generic LVN tablet when compared to the brand-name formulation, explaining unbalanced in vivo bioequivalence (BE). By using this new approach, we could determine the actual LVN drug concentration dissolved in the medium, which theoretically can permeate the gastrointestinal (GI) barrier. In fact, insoluble LVN/excipient aggregates were found in the dissolution media giving rise to non-superimposable dissolution profiles between generic and brand-name LVN tablets. Hence, the results obtained by combining the dissolution test and PAMPA method provided important insights confirming that the combined methods can be useful in revealing crucial issues in the prediction of in vivo BE of drugs.

Paleogenomics illuminates the evolutionary history of the extinct Holocene "horned" crocodile of Madagascar, Voay robustus.

Ancient DNA is transforming our ability to reconstruct historical patterns and mechanisms shaping modern diversity and distributions. In particular, molecular data from extinct Holocene island faunas have revealed surprising biogeographic scenarios. Here, we recovered partial mitochondrial (mt) genomes for 1300-1400 year old specimens (n = 2) of the extinct "horned" crocodile, Voay robustus, collected from Holocene deposits in southwestern Madagascar. Phylogenetic analyses of partial mt genomes and tip-dated timetrees based on molecular, fossil, and stratigraphic data favor a sister group relationship between Voay and Crocodylus (true crocodiles). These well supported trees conflict with recent morphological systematic work that has consistently placed Voay within Osteolaeminae (dwarf crocodiles and kin) and provide evidence for likely homoplasy in crocodylian cranial anatomy and snout shape. The close relationship between Voay and Crocodylus lends additional context for understanding the biogeographic origins of these genera and refines competing hypotheses for the recent extinction of Voay from Madagascar.

Development of an UHPLC-diode arrays detector (DAD) method for the analysis of polydatin in human plasma.

A new chromatographic method by Ultra High Performance Liquid Chromatographic (UHPLC) technology, has been developed and validated for the determination of polydatin and resveratrol, as potential metabolite, in human plasma. After the optimization of the chromatographic conditions, the method has been validated on spiked human plasma samples. The optimized extraction allowed to obtain analytes recovery up to 98.48 ± 4.03 %. Then, the isocratic elution in reversed phase mode, provides the separation of polydatin and resveratrol in less than 10.0 min. Chromatographic analysis was performed on a C18, 10 cm x 3.0 mm, 2.7 µm stationary phase, by using triethanolamine phosphate solution (0.1 M, pH = 3.7) and ACN 85:15 (v/v) as mobile phase at a flow rate of 0.5 mL/min. The UV detector was set at 306 nm for the analysis of both polydatin and resveratrol. The limit of detection (LoD) and the limit of quantification (LoQ) for polydatin in plasma samples were found to be 7.82 ± 0.38 nM and 26.06 ± 1.28 nM respectively. The method was found to be accurate and precise with a coefficient for intra- and inter-day variation below 5 %. All the reported data demonstrate how the developed method is rapid and sensitive. Moreover, results of the analysis of plasma samples, obtained from orally treated volunteers with nutritional supplements containing polydatin, have shown the method to be suitable for the pharmacokinetic characterization of polydatin and resveratrol, as metabolite, in humans.

Environmental nanoparticles are significantly over-expressed in acute myeloid leukemia.

The increase in the incidence of acute myeloid leukemia (AML) may suggest a possible environmental etiology. PM2.5 was declared by IARC a Class I carcinogen. No report has focused on particulate environmental pollution together with AML. The study investigated the presence and composition of particulate matter in blood with a Scanning Electron Microscope coupled with an Energy Dispersive Spectroscope, a sensor capable of identifying the composition of foreign bodies. 38 peripheral blood samples, 19 AML cases and 19 healthy controls, were analyzed. A significant overload of particulate matter-derived nanoparticles linked or aggregated to blood components was found in AML patients, while almost absent in matched healthy controls. Two-tailed Student's t-test, MANOVA and Principal Component Analysis indicated that the total numbers of aggregates and particles were statistically different between cases and controls (MANOVA, P<0.001 and P=0.009 respectively). The particles detected showed to contain highly-reactive, non-biocompatible and non-biodegradable metals; in particular, micro- and nano-sized particles grouped in organic/inorganic clusters, with statistically higher frequency of a subgroup of elements in AML samples. The demonstration, for the first time, of an overload of nanoparticles linked to blood components in AML patients could be the basis for a possible, novel pathogenetic mechanism for AML development.

The evolution of cranial form and function in theropod dinosaurs: insights from geometric morphometrics.

Theropod dinosaurs, an iconic clade of fossil species including Tyrannosaurus and Velociraptor, developed a great diversity of body size, skull form and feeding habits over their 160+ million year evolutionary history. Here, we utilize geometric morphometrics to study broad patterns in theropod skull shape variation and compare the distribution of taxa in cranial morphospace (form) to both phylogeny and quantitative metrics of biting behaviour (function). We find that theropod skulls primarily differ in relative anteroposterior length and snout depth and to a lesser extent in orbit size and depth of the cheek region, and oviraptorosaurs deviate most strongly from the "typical" and ancestral theropod morphologies. Noncarnivorous taxa generally fall out in distinct regions of morphospace and exhibit greater overall disparity than carnivorous taxa, whereas large-bodied carnivores independently converge on the same region of morphospace. The distribution of taxa in morphospace is strongly correlated with phylogeny but only weakly correlated with functional biting behaviour. These results imply that phylogeny, not biting function, was the major determinant of theropod skull shape.

The gender gap in stroke: a meta-analysis.

UNLABELLED: Several studies have indicated that gender differences might exist in stroke. OBJECTIVES AND METHODS: Our goal was to perform a comprehensive meta-analysis in order to evaluate and quantify stroke gender disparities through a systematic search of relevant articles published up to October 2009 and addressing gender related differences in ischemic stroke risk factors, stroke subtype and severity, diagnostic tests, and acute phase and secondary prevention treatments. RESULTS: Forty-five articles were included in the analysis, representing a total of 673,935 patients. Women were globally older than men (+5.2 years) and suffered more hypertension (P = 0.017) and atrial fibrillation (P < 0.001), although they were less likely to drink alcohol (P < 0.001), smoke cigarettes (P < 0.001), present hyperlipidemia (P = 0.033) or diabetes (P = 0.003) than men. Baseline stroke severity was not different between genders. Women suffered more cardioembolic strokes, while men had more atherothrombotic strokes. Moreover, women were less likely to receive stroke-related treatments, such as antiplatelets (P < 0.001), statins (P < 0.001), and tPA (P < 0.001) than men. Although meta-regression did not identify age or stroke etiology as sources of heterogeneity, caution should be taken as that analysis was possible only for gender differences in secondary prevention with antiplatelets because of limited data for other end points. CONCLUSIONS: Gender differences have been identified on the risk factors profile and diagnostic and therapeutic management of patients with ischemic stroke. Active measures should thus be taken to avoid bias in clinical practice.

Update on the Serum Biomarkers and Genetic Factors Associated with Safety and Efficacy of rt-PA Treatment in Acute Stroke Patients.

An accurate understanding of the mechanisms underlying an individual's response to rt-PA treatment is critical to improve stroke patients' management. We thus reviewed the literature in order to identify biochemical and genetic factors that have been associated with safety and efficacy of rt-PA administration after stroke.

Concentration and surface of absorption: concepts and applications to gastrointestinal patches delivery.

Gastrointestinal patches represent a novel multiparticulate drug delivery system able to increase the intestinal absorption of drugs with poor bioavailability. The number of patches to administer is a critical issue since it is related to the surface and drug concentration at the absorption site. The objective of this article is to evaluate the effect of the number of administered patches on the final absorption of leuprolide, a peptide chosen as model drug, assuming complete adhesion of all the devices to the intestinal membrane. The same dose of leuprolide was encapsulated into 2, 4 and 6 patches; the resulting intestinal absorption profiles were measured with the Ussing chamber ex vivo experimental setup and compared between them. The results showed that varying the number of patches, the final absorption does not present statistically significant changes, indicating that changes in concentration are balanced by change in absorption surface. These experimental findings can also be explained considering the equation that links the drug flow to surface and concentration at the absorption site, showing that the drug flow is related only to the geometry of each individual patch.

No evidence of APP point mutation and locus duplication in individuals with cerebral amyloid angiopathy.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is a well-established cause of lobar intracerebral hemorrhage (ICH). Familial forms of CAA are because of mutations in the gene encoding the beta-amyloid precursor protein (APP) and duplications of this gene can cause early-onset Alzheimer's disease associated with CAA. However, the contribution of APP genetic variants in the development of sporadic CAA remains unknown. METHODS: The presence of genetic variants in the APP was examined in 78 patients with CAA-related ICH by sequencing exons 16 and 17 coding the ß-amyloid protein and analyzing the presence of possible duplications of APP by microsatellite analysis and quantitative PCR. RESULTS: We did not identify any pathogenic mutation or chromosomal duplication of APP. CONCLUSIONS: Our results suggest that APP genetic variants, point mutations and locus duplication, are not a common cause of CAA-related ICH in the Spanish population.

Osteopontin predicts long-term functional outcome among ischemic stroke patients.

Osteopontin (OPN) is a multifunctional protein which has shown neuroprotective properties in animal models of cerebral ischemia. Nevertheless, its role in acute human stroke has not yet been established. Therefore, we aimed to determine human serum OPN level during acute ischemic stroke and its relationship with patient outcome. We measured OPN levels in 178 consecutive patients with a middle cerebral artery (MCA) occlusion who received fibrinolytic therapy and in 40 control subjects. OPN level was determined by an enzyme-linked immunosorbent assay (ELISA). Bad functional outcome was defined by modified Rankin Scale (mRS) score >2 at 3 months after stroke onset. A logistic regression analysis was performed to determine factors that could be independently associated with poor prognosis. OPN levels among stroke patients did not differ from the controls' OPN levels (16.65 vs. 17.83 ng/mL, p = 0.404). Interestingly, OPN level was increased among those patients who showed worse prognosis at 3 months (19.96 vs. 15.48 ng/mL, p = 0.040). In a logistic regression model, an OPN level >27.22 ng/mL was found to be an independent factor for a bad outcome (OR 5.01, 95% CI 1.60-15.72, p = 0.006) after adjusting for potential confounders. Those patients showing higher OPN levels before tPA administration displayed a worse prognosis compared to those with lower OPN levels. Further research is necessary to elucidate the role of OPN in ischemic stroke pathophysiology and validate OPN as a useful tool to predict long-term stroke outcome.

Leukoaraiosis is associated with genes regulating blood-brain barrier homeostasis in ischaemic stroke patients.

BACKGROUND: The biologic agents causing leukoaraiosis are unknown. Our aim was to study the genetic basis of leukoaraiosis. METHODS: We analyzed 212 single nucleotide polymorphisms (SNPs) in 142 patients with ischaemic stroke, generating a total of 30,104 genotypes. Seventy-nine subjects (55.6%) presented leukoaraiosis measured by the Fazekas scale and 69 (48.6%) by ARWMC scale. We analyzed the presence of synergic associations between SNPs using the hfcc software. Finally, functional studies were performed in 56 subjects. The Ingenuity Pathways software (ipa) was used to examine the role of the identified genes. RESULTS: Six SNPs were associated with leukoaraiosis using both measuring scales. After logistic regression adjusted for leukoaraiosis risk factors, the rs2252070 of MMP13 (OR = 4.9, 95%CI: 1.34-17.9, P = 0.016), rs662 of PON1 (OR = 0.37, 95%CI: 0.15-0.87, P = 0.024) and rs1800779 of NOS3 (OR = 3.9, 95%CI: 1.38-11.38, P = 0.01) were independently associated with leukoaraiosis under a dominant/recessive model and the rs2290608 of IL5RA (OR = 0.46, 95%CI: 0.25-0.85, P = 0.013) and rs669 of A2M (OR = 2.5, 95%CI: 1.36-4.83, P = 0.004) under an additive model. Computational analysis showed a synergic association of rs10497212-AA of ITGB6 and rs2290608-GG of IL5RA with leukoaraiosis using both scales. (i) ARWMC (P = 1.3 × 10(-4) ) and (ii) Fazekas (P = 4.5 × 10(-5) ). Functional studies showed that the rs669 SNP was associated with plasma levels of A2M (P = 0.012) and A2M levels with leukoaraiosis in Fazekas scale (P = 0.02). ipa analysis revealed that the genes associated with leukoaraiosis were involved in blood-brain barrier (BBB) homeostasis. CONCLUSIONS: Amongst patients with ischaemic stroke, several genes associated with BBB homeostasis could be involved with a higher risk of leukoaraiosis.

The I/D polymorphism of the ACE1 gene is not associated with ischaemic stroke in Spanish individuals.

BACKGROUND: The angiotensin-converting enzyme 1 (ACE1) gene has been extensively studied in stroke, yet generating conflicting results. The goal of our study was thus to clarify the influence of the ACE1 on the risk of suffering an ischaemic stroke (IS). METHODS: We genotyped the rs4341 (in linkage disequilibrium with the I/D polymorphism) of the ACE1 gene in 531 patients with IS and 549 healthy controls, and the rs1799752 (I/D polymorphism) in a subset of 68 patients with IS and 27 controls. We also performed functional studies by measuring serum ACE protein levels and enzymatic activity in 27 controls, 68 patients with IS at baseline and 35 patients with IS 24 h after onset of stroke symptoms. RESULTS: There was no association of the ACE1 variant with IS, although it affected ACE protein levels (P = 0.001). Indeed, patients with IS showed lower ACE levels than controls in the acute phase (115.9 } 38.9 vs. 174.1 } 56.1 ng/ml, P < 0.001), but not in the chronic phase (168.2 } 51.2, P = 0.673), and ACE protein levels did not differ between IS etiologies. Similar results were found for ACE activity. CONCLUSIONS: The D allele of the ACE1 I/D and ACE protein levels was not associated with a higher risk of IS in Spanish individuals.

PAI-1 4G/5G polymorphism is associated with brain vessel reocclusion after successful fibrinolytic therapy in ischemic stroke patients.

BACKGROUND: Despite t-PA proven benefits related to vessel reopening, up to 13% of stroke patients suffer reocclusions after t-PA. We aimed to analyze whether a functional polymorphism in a fibrinolysis inhibitor gene [plasminogen activator inhibitor-1 (PAI-1)] might be associated with reocclusion rates after stroke thrombolytic therapy. METHODS: 165 patients with ischemic stroke who received t-PA < 3 h were studied. Reocclusion and recanalization was diagnosed by transcranial Doppler. PAI-1 4G/5G polymorphism determination was performed by sequencing. PAI-1 mRNA was studied by real-time PCR analysis. National institutes of health stroke scale (NIHSS) was serially measured since patients arrival to assess the neurological outcome, and modified ranking scale (mRS) at 3rd month was used to evaluate functional outcome following stroke. RESULTS: PAI-1 4G/4G patients had higher reocclusion rates (4G/4G = 12.5% versus other genotypes = 2.7%, p = 0.025). . In a logistic regression, the 4G/4G genotype was the only factor associated with reocclusion (OR = 15.16 95%, CI = 1.4-163.4, p = 0.025). 4G/4G genotype was also associated with poor functional outcome at 3rd month (4G/4G = 4 versus others genotypes = 3, p = 0.017) and with mRNA levels at 12 h post stroke symptoms onset (4G/4G patients = 2.01% versus other genotypes = 0.68%, p = 0.034). CONCLUSIONS: PAI-1 4G/4G genotype is associated with reocclusion rates and poor functional outcome among stroke patients treated with t-PA.

Retrieval analysis of clinical explanted vena cava filters.

Vena cava filters are the most commonly used mechanical devices to prevent pulmonary embolism. A retrievable permanent filter has been available since 1999. That has allowed the direct study of thrombi captured in humans and the punctual interaction of blood and device at long and short term. Through traditional histologic methods, captured thrombi and the tissues formed around the filter were observed. An innovative environmental scanning electron microscopy technique allowed detection of micro- and nanosized foreign bodies inside thrombi and tissues, and chemical analysis could be carried out by means of energy dispersive spectroscopy. All specimens contained different quantities of foreign debris ranging from few tens of microns to 50 nanometers; their chemistry was not homogeneous when patients were compared, and also differed considerably within the same filter. The constant presence of debris deeply embedded in all thrombi observed may mean that they are the cause that triggered the formation of those thrombi as a result of the interaction between foreign bodies and blood components.

Raman scattering study of GaN nanostructures obtained by bottom-up and top-down approaches.

GaN nanocolumnar structures were grown by plasma-assisted molecular beam epitaxy (PAMBE) and also fabricated by electron cyclotron resonance reactive ion etching (ECR-RIE) of a compact GaN film parallel to the [111] direction of the Si(111) substrates. Scanning electron microscopy shows that the nanocolumns fabricated by PAMBE have a length of about 300-500 nm with diameters ranging from 20 to 150 nm while nanowhiskers formed by RIE have diameters of 40-80 nm and a height between 1.4 and 1.7 µm. A comparative study of the vibrational spectrum (including optical and interface phonons) of the nanostructures using conventional macro-Raman and micro-Raman scattering as well as surface-enhanced Raman scattering is presented.