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Background: China was the first country affected by the COVID-19 virus, and it is a very important case to study the effects of the virus and the consequent restrictions. However, national representative studies of how the COVID-19 pandemic affects mental health in China are still limited., Methods: Using two waves of the China Family Panel Studies, we follow the same individuals before and during the pandemic. We compare weighted means using 95% CIs to explore mental health deterioration, and we and perform several linear regressions with the Ordinaly Least Square (OLS) estimator to identify individuals most affected by the COVID-19 pandemic., Results: The prevalence of severe cases of depression, measured using an eight-item version of the common Centre for Epidemiologic Studies Depression Scale (CES-D), increased from 6.68% in 2018 to 7.86% in 2020; quantifiable as around a 18% increase. This deterioration is higher for individuals subject to strict lockdowns, about 0.4 symptoms more on average, and it is stronger among those who already reported symptoms of depression in the 2018 wave of data. Individuals with more open personalities tend to experience more severe deterioration: a 1 SD change in the openness trait corresponds to 0.05 more symptoms. On the other hand, more neurotic individuals seem less negatively affected., Conclusion: We find clear evidence of a moderate level of mental health deterioration between 2018 and 2020. These effects are larger for individuals subject to stricter lockdowns and for individuals with more open personalities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Bitter taste receptors are involved not only in taste perception but in various physiological functions as their anatomical location is not restricted to the gustatory system. We previously demonstrated expression and activity of the subtype hTAS2R46 in human airway smooth muscle and broncho-epithelial cells, and here we show its expression and functionality in human skeletal muscle cells. Three different cellular models were used: micro-dissected human skeletal tissues, human myoblasts/myotubes and human skeletal muscle cells differentiated from urine stem cells of healthy donors. We used qPCR, immunohistochemistry and immunofluorescence analysis to evaluate gene and protein hTAS2R46 expression. In order to explore receptor activity, cells were incubated with the specific bitter ligands absinthin and 3ß-hydroxydihydrocostunolide, and calcium oscillation and relaxation were evaluated by calcium imaging and collagen assay, respectively, after a cholinergic stimulus. We show, for the first time, experimentally the presence and functionality of a type 2 bitter receptor in human skeletal muscle cells. Given the tendentially protective role of the bitter receptors starting from the oral cavity and following also in the other ectopic sites, and given its expression already at the myoblast level, we hypothesize that the bitter receptor can play an important role in the development, maintenance and in the protection of muscle tissue functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Talmon, Massara, Quaregna, De Battisti, Boccafoschi, Lecchi, Puppo, Bettega Cajandab, Salamone, Bovio, Boldorini, Riva, Pollastro and Fresu.)

This article investigates the relationship between school openings and Covid-19 diffusion when school-age vaccination becomes available. The analysis relies on a unique geo-referenced high frequency database on age of vaccination, Covid-19 cases and hospitalization indicators from the Italian region of Sicily. The study focuses on the change of Covid-19 diffusion after school opening in a homogeneous geographical territory (i.e., with the same control measures and surveillance systems, centrally coordinated by the Regional Government). The identification of causal effects derives from a comparison of the change in cases before and after school opening in the school year 2020/21, when vaccination was not available, and in 2021/22, when the vaccination campaign targeted individuals of age 12-19 and above 19. Results indicate that, while school opening determined an increase in the growth rate of Covid-19 cases in 2020/2021, this effect has been substantially reduced by school-age vaccination in 2021/2022. In particular, we find that an increase of approximately 10% in the vaccination rate of school-age population reduces the growth rate of Covid-19 cases after school opening by approximately 1%., (© 2023 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Governments have implemented school closures and online learning as one of the main tools to reduce the spread of Covid-19. Despite the potential benefits in terms of containment of virus diffusion, the educational costs of these policies may be dramatic. This work identifies these costs, expressed as decrease in test scores, for the whole universe of Italian students attending the 5th, 8th and 13th grade of the school cycle during the 2021/22 school year. The analysis is based on a difference-in-difference model in relative time, where the control group is the closest generation before the Covid-19 pandemic. Results suggest a national average loss between 1.8-4.0% in Mathematics and Italian test scores. After collecting the precise number of school closure days for the universe of students in Sicily, this work also estimates that the average days of closure decrease the test score by 2.4%. In this context, parents appear to have a partial compensatory effect, but only when holding higher levels of education and when their children are attending low and middle schools. This is likely explained by the lower relevance of parental inputs and higher reliance on other inputs, such as peers, for the higher grades. Finally, the effects are also heterogeneous across class size, parents' country of birth and job conditions, pointing towards potential growing inequalities driven by the lack of frontal teaching., (© 2023 Elsevier B.V. All rights reserved.)

Microneedle (MN) patches are highly efficient and versatile tools for transdermal drug administration, in particular for pain-free, self-medication and rapid local applications. Diffraction ultraviolet (UV) light lithography offers an advanced method in fabricating poly(ethylene glycol)-based MNs with different shapes, by changing both the UV-light exposure time and photomask design. The exposure time interval is limited at obtaining conical structures with aspect ratio < 1:3, otherwise MNs exhibit reduced fracture load and poor indentation ability, not suitable for practical application. Therefore, this work is focused on a systematic analysis of the MN's base shapes effects on the structural characteristics, skin penetration and drug delivery. Analyzing four different base shapes (circle, triangle, square and star), it has been found that the number of vertices in the polygon base heavily affects these properties. The star-like MNs reveal the most efficient skin penetration ability (equal to 40 % of -their length), due to the edges action on the skin during the perforation. Furthermore, the quantification of the drug delivered by the MNs through ex-vivo porcine skin shows that the amounts of small molecules released over 24 h by star-like MNs coated by local anesthetic (Lidocaine) and an anti-inflammatory (Diclofenac epolamine) drugs are 1.5× and 2× higher than the circular-MNs, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Are schools triggering the diffusion of the Covid-19? This question is at the core of an extensive debate about the social and long-run costs of stopping the economic activity and human capital accumulation from reducing the contagion. In principle, many confounding factors, such as climate, health system treatment, and other forms of restrictions, may impede disentangling the link between schooling and Covid-19 cases when focusing on a country or regional-level data. This work sheds light on the potential impact of school opening on the upsurge of contagion by combining a weekly panel of geocoded Covid-19 cases in Sicilian census areas with a unique set of school data. The identification of the effect takes advantage of both a spatial and time-variation in school opening, stemming from the flexibility in opening dates determined by a Regional Decree, and by the occurrence of a national referendum, which pulled a set of poll-station schools towards opening earlier or later September 24th. The analysis finds that census areas where schools opened earlier observed a significant and positive increase in the growth rate of Covid-19 cases between 2.5-3.7%. This result is consistent across several specifications, including accounting for several determinants of school opening, such as the number of temporary teachers, Covid-19 cases in August, and pupils with special needs. Finally, the analysis finds lower effects in more densely populated areas, on younger population, and on smaller class size. The results imply that school reopening generated an increase of one third in cases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier B.V. All rights reserved.)

Healthcare workers have had the longest and most direct exposure to COVID-19 and consequently may suffer from poor mental health. We conducted one of the first repeated multi-country analysis of the mental wellbeing of medical doctors (n = 5,275) at two timepoints during the COVID-19 pandemic (June 2020 and November/December 2020) to understand the prevalence of anxiety and depression, as well as associated risk factors. Rates of anxiety and depression were highest in Italy (24.6% and 20.1%, June 2020), second highest in Catalonia (15.9% and 17.4%, June 2020), and lowest in the UK (11.7% and 13.7%, June 2020). Across all countries, higher risk of anxiety and depression symptoms were found among women, individuals below 60 years old, those feeling vulnerable/exposed at work, and those reporting normal/below-normal health. We did not find systematic differences in mental health measures between the two rounds of data collection, hence we cannot discard that the mental health repercussions of the pandemic are persistent., Competing Interests: The authors have declared that no competing interests exist.

Background: The present study analysed SARS-CoV-2 cases observed in Sicily and investigated social determinants that could have an impact on the virus spread., Methods: SARS-CoV-2 cases observed among Sicilian residents between the 1 February 2020 and 15 October 2020 have been included in the analyses. Age, sex, date of infection detection, residency, clinical outcomes, and exposure route have been evaluated. Each case has been linked to the census section of residency and its socio-demographic data., Results: A total of 10,114 patients (202.3 cases per 100,000 residents; 95% CI = 198.4-206.2) were analysed: 45.4% were asymptomatic and 3.62% were deceased during follow-up. Asymptomatic or mild cases were more frequent among young groups. A multivariable analysis found a reduced risk of SARS-CoV-2 cases was found in census sections with higher male prevalence (adj-OR = 0.99, 95% CI = 0.99-0.99; p < 0.001) and presence of immigrants (adj-OR = 0.89, 95% CI 0.86-0.92; p < 0.001). Proportion of residents aged <15 years, residents with a university degree, residents with secondary education, extra-urban mobility, presence of home for rent, and presence of more than five homes per building were found to increase the risk of SARS-CoV-2 incidence., Conclusion: Routinely collected socio-demographic data can be predictors of SARS-CoV-2 risk infection and they may have a role in mapping high risk micro-areas for virus transmission.

Microneedles (MNs) are an emerging technology in pharmaceutics and biomedicine, and are ready to be commercialized in the world market. However, solid microneedles only allow small doses and time-limited administration rates. Moreover, some well-known and already approved drugs need to be re-formulated when supplied by MNs. Instead, hollow microneedles (HMNs) allow for rapid, painless self-administrable microinjection of drugs in their standard formulation. Furthermore, body fluids can be easily extracted for analysis by a reverse use of HMNs, thus making them perfect for sensing issues and theranostics applications. The fabrication of HMNs usually requires several many-step processes, increasing the costs and consequently decreasing the commercial interest. Photolithography is a well-known fabrication technique in microelectronics and microfluidics that fabricates MNs. In this paper, authors show a proof of concept of a patented, easy and one-shot fabrication of two kinds of HMNs: (1) Symmetric HMNs with a "volcano" shape, made by using a photolithographic mask with an array of transparent symmetric rings; and (2) asymmetric HMNs with an oblique aperture, like standard hypodermic steel needles, made by using an array of transparent asymmetric rings, defined by two circles, which centers are slightly mismatched. Simulation of light propagation, fabrication process, and preliminary results on ink microinjection are presented.

Objective: The present Italian multicenter study aimed at investigating whether the course of primary headache disorders in children and adolescents was changed during the lockdown necessary to contain the COVID-19 emergency in Italy., Methods: During the lockdown, we submitted an online questionnaire to patients already diagnosed with primary headache disorders. Questions explored the course of headache, daily habits, psychological factors related to COVID-19, general mood and school stress. Answers were transformed into data for statistical analysis. Through a bivariate analysis, the main variables affecting the subjective trend of headache, and intensity and frequency of the attacks were selected. The significant variables were then used for the multivariate analysis., Results: We collected the answers of 707 patients. In the multivariate analysis, we found that reduction of school effort and anxiety was the main factor explaining the improvement in the subjective trend of headache and the intensity and frequency of the attacks ( p  < 0.001). The greater the severity of headache, the larger was the clinical improvement ( p  < 0.001). Disease duration was negatively associated with the improvement ( p  < 0.001). It is noteworthy that clinical improvement was independent of prophylaxis ( p  > 0.05), presence of chronic headache disorders ( p  > 0.05) and geographical area ( p  > 0.05)., Conclusions: Our study showed that lifestyle modification represents the main factor impacting the course of primary headache disorders in children and adolescents. In particular, reduction in school-related stress during the lockdown was the main factor explaining the general headache improvement in our population.

Transdermal drug delivery represents an appealing alternative to conventional drug administration systems. In fact, due to their high patient compliance, the development of dissolvable and biodegradable polymer microneedles has recently attracted great attention. Although stamp-based procedures guarantee high tip resolution and reproducibility, they have long processing times, low levels of system engineering, are a source of possible contaminants, and thermo-sensitive drugs cannot be used in conjunction with them. In this work, a novel stamp-based microneedle fabrication method is proposed. It provides a rapid room-temperature production of multi-compartmental biodegradable polymeric microneedles for controlled intradermal drug release. Solvent casting was carried out for only a few minutes and produced a short dissolvable tip made of polyvinylpyrrolidone (PVP). The rest of the stamp was then filled with degradable poly(lactide-co-glycolide) (PLGA) microparticles (μPs) quickly compacted with a vapor-assisted plasticization. The outcome was an array of microneedles with tunable release. The ability of the resulting microneedles to indent was assessed using pig cadaver skin. Controlled intradermal delivery was demonstrated by loading both the tip and the body of the microneedles with model therapeutics; POXA1b laccase from Pleurotus ostreatus is a commercial enzyme used for the whitening of skin spots. The action and indentation of the enzyme-loaded microneedle action were assessed in an in vitro skin model and this highlighted their ability to control the kinetic release of the encapsulated compound., (Copyright © 2019 Battisti, Vecchione, Casale, Pennacchio, Lettera, Jamaledin, Profeta, Di Natale, Imparato, Urciuolo and Netti.)

Deep Brain Stimulation (DBS) of the Subthalamic Nuclei (STN) is the most used surgical treatment to improve motor skills in patients with Parkinson's Disease (PD) who do not adequately respond to pharmacological treatment, or have related side effects. During surgery for the implantation of a DBS system, signals are obtained through microelectrodes recordings (MER) at different depths of the brain. These signals are analyzed by neurophysiologists to detect the entry and exit of the STN region, as well as the optimal depth for electrode implantation. In the present work, a classification model is developed and supervised by the K-nearest neighbour algorithm (KNN), which is automatically trained from the 18 temporal features of MER registers of 14 patients with PD in order to provide a clinical support tool during DBS surgery. We investigate the effect of different standardizations of the generated database, the optimal definition of KNN configuration parameters, and the selection of features that maximize KNN performance. The results indicated that KNN trained with data that was standardized per cerebral hemisphere and per patient presented the best performance, achieving an accuracy of 94.35% ( p < 0.001). By using feature selection algorithms, it was possible to achieve 93.5% in accuracy in selecting a subset of six features, improving computation time while processing in real time.

Purpose: The aim of this study was to analyze the effect of catheter displacement and anatomical variations of prostate and organs at risk on dose distribution in MRI-guided 19 Gy single fraction focal high-dose-rate brachytherapy (HDR-BT) of the prostate., Methods and Materials: Seventeen patients with localized prostate cancer were enrolled in a prospective trial investigating focal HDR-BT in a 1.5 T MRI-HDR-BT facility. The diagnostic MRI delineations were registered with intraoperative MR scan, and a single fraction of 19 Gy was applied to the visible tumor. Self-anchoring umbrella catheters were used for HDR-BT delivery. A 1.5 T MRI was performed directly after ultrasound (US)-guided catheter placement for treatment planning. After treatment and before removal of catheters, a posttreatment 1.5 T MRI was performed. Regions of interest were also delineated on the posttreatment MR images and the catheters of 17 patients were reconstructed. The dose plan was constructed for the posttreatment MRI scan to assess the influence of catheter migration and anatomical variation on the dose delivered to the target and the organs at risk. Also on the posttreatment MRI, the complete catheter reconstruction was reassessed, to correct for, for example, bending of the catheters. The displacement of catheters between the MRI scans was determined by comparing the catheter tip positions on the treatment planning and posttreatment 1.5 T MRI scans., Results: The displacements of 241 catheters were investigated. Average (range) displacements of the umbrella catheters are 0.6 (0-2.9) mm in the x-direction, 0.5 (0-2.1) mm in the y-direction, and 0.9 (0-5.5) mm in the z-direction. In 3 patients, the displacement was >4 mm and up to 5.5 mm. This occurred in respectively 1/13, 1/16, and 1/18 catheters in these patients. The dosimetric differences between the intraoperative treatment and the posttreatment plans were in most patients less than 1.5 Gy. In 4 patients, a dose difference in clinical target volume D95 of >2 Gy up to 5.8 Gy was reported. No discrimination can be made between dose differences due to catheter displacement and/or organ movement/anatomy changes., Conclusions: In general, catheter displacements were in the order of a mm and differences in dose to the clinical target volume and the organs at risk between the treatment and posttreatment plans smaller than 1.5 Gy. In some patients, dose differences up to 5.8 Gy were determined, due to either individual larger catheter displacement and/or anatomy changes. A longer followup is necessary to assess the clinical implications of individual large dose differences., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: The development of MR-guided high dose rate (HDR) brachytherapy is under investigation due to the excellent tumor and organs at risk visualization of MRI. However, MR-based localization of needles (including catheters or tubes) has inherently a low update rate and the required image interpretation can be hampered by signal voids arising from blood vessels or calcifications limiting the precision of the needle guidance and reconstruction. In this paper, a new needle tracking prototype is investigated using fiber Bragg gratings (FBG)-based sensing: this prototype involves a MR-compatible stylet composed of three optic fibers with nine sets of embedded FBG sensors each. This stylet can be inserted into brachytherapy needles and allows a fast measurement of the needle deflection. This study aims to assess the potential of FBG-based sensing for real-time needle (including catheter or tube) tracking during MR-guided intervention., Methods: First, the MR compatibility of FBG-based sensing and its accuracy was evaluated. Different known needle deflections were measured using FBG-based sensing during simultaneous MR-imaging. Then, a needle tracking procedure using FBG-based sensing was proposed. This procedure involved a MR-based calibration of the FBG-based system performed prior to the interventional procedure. The needle tracking system was assessed in an experiment with a moving phantom during MR imaging. The FBG-based system was quantified by comparing the gold-standard shapes, the shape manually segmented on MRI and the FBG-based measurements., Results: The evaluation of the MR compatibility of FBG-based sensing and its accuracy shows that the needle deflection could be measured with an accuracy of 0.27 mm on average. Besides, the FBG-based measurements were comparable to the uncertainty of MR-based measurements estimated at half the voxel size in the MR image. Finally, the mean(standard deviation) Euclidean distance between MR- and FBG-based needle position measurements was equal to 0.79 mm(0.37 mm). The update rate and latency of the FBG-based needle position measurement were 100 and 300 ms, respectively., Conclusions: The FBG-based needle tracking procedure proposed in this paper is able to determine the position of the complete needle, under MR-imaging, with better accuracy and precision, higher update rate, and lower latency compared to current MR-based needle localization methods. This system would be eligible for MR-guided brachytherapy, in particular, for an improved needle guidance and reconstruction.

The development of magnetic resonance (MR) guided high dose rate (HDR) brachytherapy for prostate cancer has gained increasing interest for delivering a high tumor dose safely in a single fraction. To support needle placement in the limited workspace inside the closed-bore MRI, a single-needle MR-compatible robot is currently under development at the University Medical Center Utrecht (UMCU). This robotic device taps the needle in a divergent way from a single rotation point into the prostate. With this setup, it is warranted to deliver the irradiation dose by successive insertions of the needle. Although robot-assisted needle placement is expected to be more accurate than manual template-guided insertion, needle positioning errors may occur and are likely to modify the pre-planned dose distribution.In this paper, we propose a dose plan adaptation strategy for HDR prostate brachytherapy with feedback on the needle position: a dose plan is made at the beginning of the interventional procedure and updated after each needle insertion in order to compensate for possible needle positioning errors. The introduced procedure can be used with the single needle MR-compatible robot developed at the UMCU. The proposed feedback strategy was tested by simulating complete HDR procedures with and without feedback on eight patients with different numbers of needle insertions (varying from 4 to 12). In of the cases tested, the number of clinically acceptable plans obtained at the end of the procedure was larger with feedback compared to the situation without feedback. Furthermore, the computation time of the feedback between each insertion was below 100 s which makes it eligible for intra-operative use.

Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm(3)to 23.3 cm(3)) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions.

The Doppler ultrasonography (DU) in cases of arteriovenous malformations (AVMs) is not widely use by dentists and there are a lack of information on the topic in the literature. AVM is common in the region of the head and neck and are commonly confused with hemangiomas (congenital). Appropriate classification is essential for therapeutic decision. The diferential diagnosis is based on clinical history, diascopy, and, if necessary, diagnostic imaging. This article present two cases of oral AVM in which DU was crucial in detecting a venous and/or arterial component in purplish lesions in the tongue and buccal mucosa, with positive diascopy. In our cases, after DU, we found a predominance of blood component within the lesion and therefore both patients were referred to the head and neck surgeon for surgical removal of the lesion. Only in the presence of a venous component does outpatient treatment become feasible. Given the predominance of the arterial component, outpatient procedures are contraindicated. Therefore DU is an important supplementary test, being of great importance in the clinical decision and treatment plan for oral AVMs and should become a routine part of the dentist front of vascular lesions of medium to large size.

Vascular access recirculation rate (AR) monitoring is fundamental to guarantee treatment adequacy and to detect access failure early. We have evaluated the GIT2 test to measure AR unaffected by cardio-pulmonary recirculation (CPR), based on a short glucose infusion in place of the bolus and on a two-operator sampling, differently from the classical glucose infusion test (GIT). The GIT2 test is based on four steps: 1) basal (B) glucose arterial sample; 2) 10% glucose infusion for 1 min, by infusion pump at 600 ml/hr; (or 20% at 300 ml/hr); 3) simultaneous sampling at arterial (A) and venous (V) ports, after 35-40 sec from starting the infusion, taking care to avoid blood pump stop during the test; 4) AR=100*((A-B)/(V-B)). In vitro tests by dialysis on a 40 L tank containing a urea solution, with AR volumetrically simulated at 0, 5, 10, 20%, and in vivo comparison of GIT, GIT2 with stop-flow (SF) urea method. Our results have shown in vitro an almost perfect correspondence of SF urea method and a better reliability of GIT2 than GIT. The methylene-blue test has shown that a single color bolus in V reaches the A port after variable time, depending on blood flow and AR, while the continuous infusion determines a steady gradient after about 30". In vivo tests (n=24) show good correspondence between GIT2 (4.37 +/- 3.36) and SF (4.51 +/- 3.62), while GIT data (1.01 +/- 0.51) are significantly underestimated. In conclusion, our preliminary results have evidenced a good reliability of the new test, the continuous infusion causing a steady gradient in V and A that more precisely reflects the AR rate.

Ecstasy ((+/-)3,4-methylenedioxymethamphetamine, MDMA) is a psychostimulant and a synthetic derivative of amphetamine that, according to its consumers, promotes the enhancement of sexual pleasure. This study sought to investigate the effects of ecstasy in the genital reflexes of paradoxical sleep deprived (PSD) male rats. Distinct groups of PSD rats were administered with saline or different doses of ecstasy. The incidence of genital reflexes was verified for 100 min. The four doses that were used induced genital reflexes in PSD animals and these significantly differed from their respective treated control groups. Under the influence of two intermediary doses (2.5 and 5mg/kg), all animals displayed erection and ejaculation. The frequency of genital reflexes was also significantly greater than in relation to the PSD-saline group. The comparison between cocaine and ecstasy in PSD rats revealed that ecstasy induced more erections and ejaculations than cocaine. Thus, the present results showed a great enhancement of the genital reflexes of PSD rats that might have occurred due to serotoninergic alterations induced by this illicit substance when associated to sleep deprivation.

Introduction: Abdominal scar recurrence of endometrial carcinoma after abdominal total hysterectomy is very rare. We report a case of a 65-year-old woman who had two recurrences in the abdominal incisional scar after total hysterectomy., Case Report: A 65-year-old woman underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy because of well-differentiated endometrial adenocarcinoma (Stage IIB). Thus, the patient was treated by external beam radiotherapy. She developed two recurrences in the abdominal incisional scar two and three years after total hysterectomy, respectively. Surgery plus chemotherapy and surgery plus hormonal therapy were used for treatment of the first and second scar recurrence, respectively., Conclusions: It is a very intriguing and controversial biologic question how neoplastic cells can implant and grow in an abdominal scar without other concomitant metastases. We report a review of the literature and the possible mechanism of recurrences in laparotomy wounds.

The angiogenic molecule placenta growth factor (PlGF) is a member of the cysteine-knot family of growth factors. In this study, a mature isoform of the human PlGF protein, PlGF-1, was crystallized as a homodimer in the crystallographic asymmetric unit, and its crystal structure was elucidated at 2.0 A resolution. The overall structure of PlGF-1 is similar to that of vascular endothelial growth factor (VEGF) with which it shares 42% amino acid sequence identity. Based on structural and biochemical data, we have mapped several important residues on the PlGF-1 molecule that are involved in recognition of the fms-like tyrosine kinase receptor (Flt-1, also known as VEGFR-1). We propose a model for the association of PlGF-1 and Flt-1 domain 2 with precise shape complementarity, consider the relevance of this assembly for PlGF-1 signal transduction, and provide a structural basis for altered specificity of this molecule.

In this paper we review current knowledge on placenta growth factor (PIGF) and summarise our data on its recombinant production in bacteria and its activity. PIGF and vascular endothelial growth factor (VEGF) are both angiogenic factors belonging to the platelet-derived growth factor (PDGF) family. PIGF is a dimeric glycoprotein which shares a number of biochemical and functional features with VEGF. The aminoacidic similarity between the two factors is high (about 50%) in the PDGF-like domain. By alternative splicing of the PIGF mRNA, three forms of PIGF protein are generated which are named PIGF-1, PIGF-2 and PIGF-3. We have focused our attention on form 1 of human PIGF (PIGF-1). A large quantity of active recombinant PIGF-1 has been obtained using a bacterial expression system. By optimising the fermentation and purification it was possible to produce about 140 mg/l of culture of active PIGF-1, which is potentially suitable for a pharmaceutical use. The angiogenic activity of two different batches of bacteria-derived PIGF-1 obtained in our laboratory was demonstrated in chick chorionallantoic membrane assays. Finally, in preliminary studies we have shown that bacteria-derived PIGF-1 has a protective effect against myocardial lesions induced by isoprenaline in rat and rabbit.

The placental-derived growth factor (PIGF) is a dimeric glycoprotein showing a high degree of sequence similarity to the vascular endothelial growth factor. Alternative splicing of the PIGF primary transcript gives rise to two forms, named PIGF-1 and PIGF-2, which differ only in the insertion of a highly basic 21-amino acid stretch at the carboxyl end. The presence of the PIGF mRNA in thyroid, placenta, lung, and goiter has indicated the tissues where this factor functions. However, the role of PIGF in vascular development has not yet been clearly established. In the present study, we described the purification of PIGF-1 from overexpressing eukaryotic cells and then measured the angiogenic activity of the purified PIGF-1 in vivo in the rabbit cornea and the chick chorioallantoic membrane assays. In both in vivo assays, PIGF-1 induced a strong neovascularization process that was blocked by affinity-purified anti-PIGF-1 antibody. In the avascular cornea, PIGF-1 induced angiogenesis in a dose-dependent manner and seemed to be at least as effective (if not more effective) than vascular endothelial growth factor and basic fibroblast growth factor under the same conditions and at the same concentration. PIGF-1 was shown to induce cell growth and migration of endothelial cells from bovine coronary postcapillary venules and from human umbilical veins. In these two in vitro assays, PIGF-1 seemed to have a comparable effect to that of vascular endothelial growth factor and basic fibroblast growth factor on the cultured microvascular endothelium (eg, capillary venule endothelial cells). In summary, this is the first study to demonstrate that PIGF-1 can induce angiogenesis in vivo and stimulate the migration and proliferation of endothelial cells in vitro.