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Abstract Background With the development of medical technology, many countries around the world have been implementing ethical guidelines and laws regarding Medically Assisted Reproduction (MAR). A physician's reproductive decisions are not solely based on technical criteria but are also influenced by society values. Therefore, the aim of this study was to analyze the factors prioritized by MAR professionals when deciding on whether to accept to perform assisted reproduction and to show any existing cultural differences. Methods Cross-sectional study involving 224 healthcare professionals working with assisted reproduction in Brazil, Italy, Germany and Greece. Instrument used for data collection: a questionnaire, followed by the description of four special MAR cases (a single woman, a lesbian couple, an HIV discordant couple and gender selection) which included case-specific questions regarding the professionals' decision on whether to perform the requested procedure as well as the following factors: socio-demographic variables, moral and legal values as well as the technical aspects which influence decision-making. Results Only the case involving a single woman who wishes to have a child (without the intention of having a partner in the future) demonstrated significant differences. Therefore, the study was driven towards the results of this case specifically. The analyses we performed demonstrated that professionals holding a Master's Degree, those younger in age, female professionals, those having worked for less time in reproduction, those in private clinics and Brazilian health professionals all had a greater tendency to perform the procedure in that case. A multivariate analysis demonstrated that the reasons for the professional's decision to perform the procedure were the woman's right to gestate and the duty of MAR professionals to help her. The professionals who decided not to perform the procedure identified the woman's marital status and the child's right to a father as the reason to withhold treatment. Conclusion The study indicates differences among countries in the evaluation of the single woman case. It also discloses the undervaluation of bioethics committees and the need for a greater participation of healthcare professionals in debates on assisted reproduction laws.

Abstract A 10‐year‐old mixed breed male cat presented with clinical signs related to chronic orthopaedic pain. Upon physical examination, pain was noted, based on the feline Musculoskeletal Pain Index (FMPI). An analgesic treatment with a full spectrum cannabis oil (1.8% CBD and 0.8% THC) was proposed for 30 days (0,5 mg/kg based on CBD). The FMPI scale score decreased more than 50%. This case reported a satisfactory outcome for the patient and the owner, although this medication could increase ALT. Given the paucity of literature published to date on the treatment of veterinary species with cannabis‐based medications, further clinical and pharmacokinetic studies are necessary to study the safety and efficacy of its use.

Abstract Background For many women finding the right contraceptive method can be challenging and consistent and correct use over a lifetime is difficult. Even remembering to take a birth control pill every day can be a challenge. The primary objective of this study was to evaluate women's experience with a weekly ethinylestradiol/norelgestromin contraceptive patch (EE/NGMN patch), given new technologies recently developed in hormonal contraception to increase women's options in avoiding daily dosing. Methods In 24 Italian sites, 207 women received the EE/NGMN patch for up to 6 cycles. At study end, overall satisfaction and preference, as well as compliance, efficacy and safety, were evaluated. Results 175 women (84.5%) completed the study. The overall satisfaction rate was 88%; convenience and once-a-week frequency of the patch were especially appreciated. At baseline, 82 women (39.4%) were using a contraceptive method, mainly oral contraceptives and barrier methods, but only 45.1% were very satisfied/satisfied; after 6 months with the patch, 86.3% of this subset was very satisfied/satisfied. Considering the method used in the 3 months before the study entry, 78.1% strongly preferred/preferred the patch, for convenience (53.9%), ease of use/simplicity (28.9%), fewer (9.2%) and less severe (2.6%) side effects. Compliance was very high: 1034/1110 cycles (93.2%) were completed with perfect compliance and the mean subject's compliance score was 90%. One on-therapy pregnancy occurred. The patch was safe and well tolerated: adverse events frequency was low, with predominantly single reports of each event. Most of them started and subsided during cycle 1. Conclusion This study demonstrated that the EE/NGMN patch is associated with high satisfaction levels and excellent compliance. At study end, the majority of women indicated that they would continue using the patch.

Abstract Background As weight gain is one of the most frequently cited reasons for not using and for discontinuing hormonal contraceptives, in an open-label, single-arm, multicentre clinical study we evaluated the effect of the ethinylestradiol/norelgestromin contraceptive patch (EVRA, Janssen-Cilag International, Belgium) on body composition using bioelectrical impedance analysis (BIA). Methods Body weight and impedance vector components (resistance (R) and reactance (Xc), at 50 kHz frequency, Akern-RJL Systems analyzer) were recorded before entry, after 1, 3 and 6 months in 182 Italian healthy women aged 29 yr (18 to 45), and with BMI 21.8 kg/m2 (16 to 31). Total body water (TBW) was estimated with a BIA regression equation. Vector BIA was performed with the RXc mean graph method and the Hotelling's T2 test for paired and unpaired data. Results After 6 months body weight increased by 0.64 kg (1.1%) and TBW increased by 0.51 L (1.7%). The pattern of impedance vector displacement indicated a small increase in soft tissue hydration (interstitial gel fluid). Body composition changes did not significantly differ among groups of previous contraceptive methods. Arterial blood pressure did not significantly change over time. Conclusion After 6 months of treatment with the ethinylestradiol/norelgestromin contraceptive patch we found a minimal, clinically not relevant, increase in body weight less than 1 kg that could be attributed to an adaptive interstitial gel hydration. This fluctuation is physiological as confirmed by the lack of any effect on blood pressure. This could be useful in increasing women's choice, acceptability and compliance of the ethinylestradiol/norelgestromin contraceptive patch.

Abstract Background The production of vinyl chloride (VC) and polyvinyl chloride (PVC) involves the use of various chemicals, some known to be toxic and potentially or definitely carcinogenic. The related potential risk often has not been properly investigated. Updated cancer mortality among different subgroups of workers employed in a VC-PVC production plant located in Porto Marghera (Italy) was re-analyzed using an internal reference group of workers with low (or null) exposure to VC. Methods Mortality of 1658 male workers was analyzed by Poisson regression. Relative risks (RRs) and 95% confidence intervals (CIs) for blue collar workers and their specific subgroups of PVC baggers, PVC compound, autoclave and other blue collar workers were calculated using technicians and clerks as an internal reference group. The follow-up covered the period 1972–1999. Results Significantly increased mortality rates were observed for all causes of death among the whole blue collar workforce (RR = 1.55; 95% CI = 1.03–2.35; 229 deaths), PVC baggers (1.72; 95% CI = 1.04–2.83; 49 deaths) and PVC compound workers (1.71; 95% CI = 1.09–2.67; 72 deaths). Liver cancer, including angiosarcoma, was increased among autoclave workers (9.57; 95% CI = 3.71–24.68; 7 deaths) and cardiovascular diseases among PVC baggers (2.25; 95% CI = 1.08–4.70; 12 deaths). Hemolymphopoietic system tumors, leukemias and lymphomas prevalently, were found only among exposed workers, with 4, 4 and 6 deaths observed among PVC baggers, PVC compound and other blue collar workers, respectively. An excess of lung cancer was found among PVC baggers. Conclusion This cohort analysis, based on internal comparison, confirmed previously reported specific risk excesses for liver tumors and liver cirrhosis among autoclave workers and for lung cancer among PVC baggers, and revealed PVC compound workers as a possible new at risk group for all causes, all tumors and for liver and lung tumors. In conclusion, RRs for all causes of death and all tumors were increased among all blue collar workers.

Abstract Background Birth defects are a leading cause of neonatal and infant mortality in Italy, however little is known of the etiology of most defects. Improvements in diagnosis have revealed increasing numbers of clinically insignificant defects, while improvements in treatment have increased the survival of those with more serious and complex defects. For etiological studies, prevention, and management, it is important to have population-based monitoring which provides reliable data on the prevalence at birth of such defects. Methods We recently initiated population-based birth defect monitoring in the Provinces of Mantova, Sondrio and Varese of the Region of Lombardy, northern Italy, and report data for the first year of operation (1999). The registry uses all-electronic source files (hospital discharge files, death certificates, regional health files, and pathology reports) and a proven case-generation methodology, which is described. The data were checked manually by consulting clinical records in hospitals. Completeness was checked against birth certificates by capture-recapture. Data on cases were coded according to the four-digit malformation codes of the International Classification of Diseases, Ninth Revision (ICD-9). We present data only on selected defects. Results We found 246 selected birth defects in 12,008 live births in 1999, 148 among boys and 98 among girls. Congenital heart defects (particularly septal defects) were the most common (90.8/10,000), followed by defects of the genitourinary tract (34.1/10, 000) (particularly hypospadias in boys), digestive system (23.3/10,000) and central nervous system (14.9/10,000), orofacial clefts (10.8/10,000) and Down syndrome (8.3/10,000). Completeness was satisfactory: analysis of birth certificates resulted in the addition of two birth defect cases to the registry. Conclusion This is the first population-based analysis on selected major birth defects in the Region. The high birth prevalences for septal heart defect and hypospadias are probably due to the inclusion of minor defects and lack of coding standardization; the latter problem also seems important for other defects. However the data produced are useful for estimating the demands made on the health system by babies with birth defects.

Abstract Background Automated procedures are increasingly used in cancer registration, and it is important that the data produced are systematically checked for consistency and accuracy. We evaluated an automated procedure for cancer registration adopted by the Lombardy Cancer Registry in 1997, comparing automatically-generated diagnostic codes with those produced manually over one year (1997). Methods The automatically generated cancer cases were produced by Open Registry algorithms. For manual registration, trained staff consulted clinical records, pathology reports and death certificates. The social security code, present and checked in both databases in all cases, was used to match the files in the automatic and manual databases. The cancer cases generated by the two methods were compared by manual revision. Results The automated procedure generated 5027 cases: 2959 (59%) were accepted automatically and 2068 (41%) were flagged for manual checking. Among the cases accepted automatically, discrepancies in data items (surname, first name, sex and date of birth) constituted 8.5% of cases, and discrepancies in the first three digits of the ICD-9 code constituted 1.6%. Among flagged cases, cancers of female genital tract, hematopoietic system, metastatic and ill-defined sites, and oropharynx predominated. The usual reasons were use of specific vs. generic codes, presence of multiple primaries, and use of extranodal vs. nodal codes for lymphomas. The percentage of automatically accepted cases ranged from 83% for breast and thyroid cancers to 13% for metastatic and ill-defined cancer sites. Conclusion Since 59% of cases were accepted automatically and contained relatively few, mostly trivial discrepancies, the automatic procedure is efficient for routine case generation effectively cutting the workload required for routine case checking by this amount. Among cases not accepted automatically, discrepancies were mainly due to variations in coding practice.

Abstract Patients with acute pancreatitis (AP) often require ICU admission, especially when signs of multiorgan failure are present, a condition that defines AP as severe. This disease is characterized by a massive pancreatic release of pro-inflammatory cytokines that causes a systemic inflammatory response syndrome and a profound intravascular fluid loss. This leads to a mixed hypovolemic and distributive shock and ultimately to multiorgan failure. Aggressive fluid resuscitation is traditionally considered the mainstay treatment of AP. In fact, all available guidelines underline the importance of fluid therapy, particularly in the first 24–48 h after disease onset. However, there is currently no consensus neither about the type, nor about the optimal fluid rate, total volume, or goal of fluid administration. In general, a starting fluid rate of 5–10 ml/kg/h of Ringer’s lactate solution for the first 24 h has been recommended. Fluid administration should be aggressive in the first hours, and continued only for the appropriate time frame, being usually discontinued, or significantly reduced after the first 24–48 h after admission. Close clinical and hemodynamic monitoring along with the definition of clear resuscitation goals are fundamental. Generally accepted targets are urinary output, reversal of tachycardia and hypotension, and improvement of laboratory markers. However, the usefulness of different endpoints to guide fluid therapy is highly debated. The importance of close monitoring of fluid infusion and balance is acknowledged by most available guidelines to avoid the deleterious effect of fluid overload. Fluid therapy should be carefully tailored in patients with severe AP, as for other conditions frequently managed in the ICU requiring large fluid amounts, such as septic shock and burn injury. A combination of both noninvasive clinical and invasive hemodynamic parameters, and laboratory markers should guide clinicians in the early phase of severe AP to meet organ perfusion requirements with the proper administration of fluids while avoiding fluid overload. In this narrative review the most recent evidence about fluid therapy in severe AP is discussed and an operative algorithm for fluid administration based on an individualized approach is proposed.

BackgroundThere are only two countries in the world (the United States and New Zealand) that allow the pharmaceutical branch to advertise prescription medication directly to consumers. There is pressure on governments to allow direct-to-consumer advertising (DTCA) for prescription drugs elsewhere too. One argument the industry uses frequently is the claim that exposure to DCTA, through various methods and occasions, is supposed to improve customers’ knowledge of a disease and treatment. This argument has been part of the health care community’s wider discussion of whether DTCA of prescription drugs benefits the population’s general interest or is only an attempt to increase the sales of the pharmaceutical branch. Belief in true learning by DTCA is rooted in concepts of empowered consumers and their autonomous and empowered decision-making. ObjectiveIn this study, we tested the hypotheses that contact with DTCA increases recipients’ literacy/knowledge, especially regarding the side effects of treatment (hypothesis 1), and empowerment (hypothesis 2). We further hypothesized that DTCA exposure would not increase depression knowledge (ie, about treatments, symptoms, and prevalence) (hypothesis 3). MethodsA snowball sample of 180 participants was randomly split into three experimental groups receiving (1) a traditional information sheet, (2) a DTCA video clip for an antidepressant prescription drug, or (3) both. The video was original material from the United States translated into Italian for the experiment. Dependent variables were measures of depression knowledge (regarding treatments, symptoms and prevalence, and antidepressant side effects), depression literacy, and empowerment. ResultsNone of the experimental groups differed significantly from the others in the empowerment measure (hypothesis 2 not confirmed). Partial confirmation of hypothesis 1 was obtained. Lower values on the depression literacy scale were obtained when participants had been given the video compared to the sheet condition. However, the general depression knowledge and its subscale on side effects reached higher scores when participants were exposed to the DTCA, alone or in combination with the information sheet. Finally, participants showed lower scores on knowledge about treatment and symptoms or prevalence after watching the video compared to the sheet condition (hypothesis 3 confirmed). Symptoms and prevalence knowledge increased only when the video was presented in combination with the sheet. ConclusionsThere is no evidence for an increase in empowerment following DTCA exposure. An increase in knowledge of the side effects of the medication was observed in the group exposed to the DTCA video. This was the only result that confirmed the hypothesis of the beneficial effect of DTCA videos on knowledge. Written information proved to be the most suitable way to convey knowledge on treatments and symptoms prevalence. Our findings support the necessity of studying health literacy and patient empowerment together and the consequences of such an increase in knowledge in terms of help-seeking behavior.

The use of cannabinoids in both veterinary and human medicine is controversial for legal and ethical reasons. Nonetheless, the availability and therapeutic use of naturally occurring or synthetic phytocannabinoids, such as Δ9-tetrahydrocannabidiol and cannabidiol, have been the focus of attention in studies regarding their medical uses. This review aims to examine the role of cannabinoids in pain modulation by analyzing scientific findings regarding the signaling pathways of the endocannabinoid system and discussing the analgesic effects of synthetic cannabinoids compared to cannabinoid extracts and the extent and involvement of their receptors. In animals, studies have shown the analgesic properties of these substances and the role of the cannabinoid binding −1 (CB1) and cannabinoid binding −2 (CB2) receptors in the endocannabinoid system to modulate acute, chronic and neuropathic pain. This system consists of three main components: endogenous ligands (anandamide and 2-arachidonoylglycerol), G protein-coupled receptors and enzymes that degrade and recycle the ligands. Evidence suggests that their interaction with CB1 receptors inhibits signaling in pain pathways and causes psychoactive effects. On the other hand, CB2 receptors are associated with anti-inflammatory and analgesic reactions and effects on the immune system. Cannabis extracts and their synthetic derivatives are an effective therapeutic tool that contributes to compassionate pain care and participates in its multimodal management. However, the endocannabinoid system interacts with different endogenous ligands and neurotransmitters, thus offering other therapeutic possibilities in dogs and cats, such is the case of those patients who suffer from seizures or epilepsy, contact and atopic dermatitis, degenerative myelopathies, asthma, diabetes and glaucoma, among other inflammatory diseases. Moreover, these compounds have been shown to possess antineoplastic, appetite-stimulating, and antiemetic properties. Ultimately, the study of the endocannabinoid system, its ligands, receptors, mechanism of action, and signaling, has contributed to the development of research that shows that hemp-derived and their synthetic derivatives are an effective therapeutic alternative in the multimodal management of pain in dogs and cats due to their ability to prevent peripheral and central sensitization.

Through the use of bulk measurements in metabolic organs, the circadian clock was shown to play roles in organismal energy homeostasis. However, the relationship between metabolic and circadian oscillations has not been studied in vivo at a single-cell level. Also, it is unknown whether the circadian clock controls metabolism in stem cells. We used a sensitive, noninvasive method to detect metabolic oscillations and circadian phase within epidermal stem cells in live mice at the single-cell level. We observe a higher NADH/NAD+ ratio, reflecting an increased glycolysis/oxidative phosphorylation ratio during the night compared to the day. Furthermore, we demonstrate that single-cell metabolic heterogeneity within the basal cell layer correlates with the circadian clock and that diurnal fluctuations in NADH/NAD+ ratio are Bmal1 dependent. Our data show that, in proliferating stem cells, the circadian clock coordinates activities of oxidative phosphorylation and glycolysis with DNA synthesis, perhaps as a protective mechanism against genotoxicity.

We have developed a two-photon fluorescence microscope capable of imaging up to 4mm in turbid media with micron resolution. The key feature of this instrument is the innovative detector, capable of collecting emission photons from a wider surface area of the sample than detectors in traditional two-photon microscopes. This detection scheme is extremely efficient in the collection of emitted photons scattered by turbid media which allows eight fold increase in the imaging depth when compared with conventional two-photon microscopes. Furthermore, this system also has in-depth fluorescence lifetime imaging microscopy (FLIM) imaging capability which increases image contrast. The detection scheme captures emission light in a transmission configuration, making it extremely efficient for the detection of second harmonic generation (SHG) signals, which is generally forward propagating. Here we present imaging experiments of tissue phantoms and in vivo and ex vivo biological tissue performed with this microscope.

We describe a novel two-photon fluorescence microscopy system capable of producing high-quality second harmonic generation (SHG) images in thick turbid media by using an innovative detection system. This novel detection system is capable of detecting photons from a very large surface area. This system has proven effective in providing images of thick turbid samples, both biological and artificial. Due to its transmission detection geometry, the system is particularly suitable for detecting SHG signals, which are generally forward directed. In this article, we present comparative data acquired simultaneously on the same sample with the forward and epidetection schemes.

The term frailty in the era of coronavirus disease 2019 (COVID-19) has a manifold implication. The vast majority of the countries worldwide being hit by the pandemic have shown the frailty of their health and social care systems. Although the surprise factor could somehow justify the unpreparedness experienced during the first wave, the second wave still led to significant difficulties almost everywhere. Looking at Italy's situation, it is evident how the stress test applied by COVID-19 on the system has threatened its stability, getting it closer to collapsing many times. It is true that Italy, in particular the Northern regions, has been the epicenter of COVID-19 in Europe in a time when information about the severe acute respiratory syndrome coronavirus 2 was still lacking and confusing. Nevertheless, what happened has demonstrated significant issues in the structure, priorities, and organization of the system. It has exemplified the obsolete approach adopted in clinical practice, particularly when applied to frail older persons. The COVID-19 pandemic has made emerging the need for a substantial reshaping of our healthcare system. The hospital-centered model has dramatically failed. To adequately face the new challenges brought by the increasing complexity of our aging society, it is critical to move the barycenter of action toward the community/primary care, promoting the integration of services and centralization of clinical/administrative data. It is vital to train healthcare professionals in the identification and basic principles of geriatric conditions, clarifying the role that geriatricians play. In the present article, some cornerstone concepts of geriatric medicine (i.e., definition of geriatrics, multidisciplinarity, integrated care, and development of clinical databases for filling the evidence-based medicine gaps) are presented, explaining the challenges they have faced during the COVID-19 pandemic and possible solutions for implementing improvements in the future.

We constructed an advanced detection system for two-photon fluorescence microscopy that allows us to image in biological tissue and tissue phantoms up to the depth of a few mm with micron resolution. The innovation lies in the detection system which is much more sensitive to low level fluorescence signals than the fluorescence detection configuration used in conventional two-photon fluorescence microscopes. A wide area photocathode photomultiplier tube (PMT) was used to detect fluorescence photons directly from a wide (1 inch diameter) area of the turbid sample, as opposed to the photon collection by the microscope objective which can only collect light from a relatively small area of the sample. The optical path between the sample and the photocathode is refractive index matched to curtail losses at the boundaries due to reflections. The system has been successfully employed in the imaging of tissue phantoms simulating brain optical properties and in biological tissues, such as murine small intestine, colon, tumors, and other samples. The system has in-depth fluorescence lifetime imaging (FLIM) capabilities and is also highly suitable for SHG signal detection, such as collagen fibers and muscles, due to the intrinsically forward-directed propagation of SHG photons. © 2013 SPIE.

We constructed an advanced detection system for two-photon fluorescence microscopy that allows us to image in biological tissue and tissue phantoms up to the depth of a few mm with micron resolution. The innovation lies in the detection system which is much more sensitive to low level fluorescence signals than the fluorescence detection configuration used in conventional two-photon fluorescence microscopes. A wide area photocathode photomultiplier tube (PMT) was used to detect fluorescence photons directly from a wide (1 inch diameter) area of the turbid sample, as opposed to the photon collection by the microscope objective which can only collect light from a relatively small area of the sample. The optical path between the sample and the photocathode is refractive index matched to curtail losses at the boundaries due to reflections. The system has been successfully employed in the imaging of tissue phantoms simulating brain optical properties and in biological tissues, such as murine small intestine, colon, tumors, and other samples. The system has in-depth fluorescence lifetime imaging (FLIM) capabilities and is also highly suitable for SHG signal detection, such as collagen fibers and muscles, due to the intrinsically forward-directed propagation of SHG photons. © 2013 SPIE.

Abstract.We describe a novel technical approach with enhanced fluorescence detection capabilities in two-photon microscopy that achieves deep tissue imaging, while maintaining micron resolution. Compared to conventional two-photon microscopy, greater imaging depth is achieved by more efficient harvesting of fluorescence photons propagating in multiple-scattering media. The system maintains the conventional two-photon microscopy scheme for excitation. However, for fluorescence collection the detection system harvests fluorescence photons directly from a wide area of the turbid sample. The detection scheme relies on a wide area detector, minimal optical components and an emission path bathed in a refractive-index-matching fluid that minimizes emission photon losses. This detection scheme proved to be very efficient, allowing us to obtain high resolution images at depths up to 3 mm. This technique was applied to in vivo imaging of the murine small intestine (SI) and colon. The challenge is to image normal and diseased tissue in the whole live animal, while maintaining high resolution imaging at millimeter depth. In Lgr5-GFP mice, we have been successful in imaging Lgr5-eGFP positive stem cells, present in SI and colon crypt bases.

Recently we described a novel technical approach with enhanced fluorescence detection capabilities in two-photon microscopy that achieves deep tissue imaging, while maintaining micron resolution. This technique was applied to in vivo imaging of murine small intestine and colon. Individuals with Inflammatory Bowel Disease (IBD), commonly presenting as Crohn's disease or Ulcerative Colitis, are at increased risk for developing colorectal cancer. We have developed a Giα2 gene knock out mouse IBD model that develops colitis and colon cancer. The challenge is to study the disease in the whole animal, while maintaining high resolution imaging at millimeter depth. In the Giα2-/- mice, we have been successful in imaging Lgr5-GFP positive stem cell reporters that are found in crypts of niche structures, as well as deeper structures, in the small intestine and colon at depths greater than 1mm. In parallel with these in vivo deep tissue imaging experiments, we have also pursued autofluorescence FLIM imaging of the colon and small intestine-at more shallow depths (roughly 160μm)- on commercial two photon microscopes with excellent structural correlation (in overlapping tissue regions) between the different technologies. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

Recently we described a novel technical approach with enhanced fluorescence detection capabilities in two-photon microscopy that achieves deep tissue imaging, while maintaining micron resolution. This technique was applied to in vivo imaging of murine small intestine and colon. Individuals with Inflammatory Bowel Disease (IBD), commonly presenting as Crohn's disease or Ulcerative Colitis, are at increased risk for developing colorectal cancer. We have developed a Giα2 gene knock out mouse IBD model that develops colitis and colon cancer. The challenge is to study the disease in the whole animal, while maintaining high resolution imaging at millimeter depth. In the Giα2-/- mice, we have been successful in imaging Lgr5-GFP positive stem cell reporters that are found in crypts of niche structures, as well as deeper structures, in the small intestine and colon at depths greater than 1mm. In parallel with these in vivo deep tissue imaging experiments, we have also pursued autofluorescence FLIM imaging of the colon and small intestine-at more shallow depths (roughly 160μm)- on commercial two photon microscopes with excellent structural correlation (in overlapping tissue regions) between the different technologies. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

The depth of two-photon fluorescence imaging in turbid media can be significantly enhanced by the use of the here described fluorescence detection method that allows to efficiently collect scattered fluorescence photons from a wide area of the turbid sample. By using this detector we were able to perform imaging of turbid samples, simulating brain tissue, at depths up to 3 mm, where the two-photon induced fluorescence signal is too weak to be detected by means used in conventional two-photon microscopy.

Electroejaculation (EE) is stressful and probably painful; thus the administration of anaesthesia is recommended to decrease those negative effects. However, anaesthesia has a direct risk of provoking death, but sedation is less risky than anaesthesia. At the same time, α2-adrenergic agonists may improve semen quality. Therefore, the aim of the present study was to compare the physiological and behavioural responses indicative of stress and possibly pain, and the semen quality in electroejaculated untreated, anaesthetised or sedated goat bucks. Semen was collected from eight bucks using three different procedures in all them (EE in untreated bucks, EE under sedation or EE under general anaesthesia). The number of vocalizations during EE and the behavioural pattern before and after procedures were recorded. Pain visual analogue scale (VAS) score was also determined during EE. Rectal temperature, heart rate, serum cortisol concentration, biochemical and haematological parameters were measured before and after each procedure, and sperm characteristics were determined. Bucks vocalised more often when untreated than sedated or anaesthetised (P

Diesel exhaust is hazardous to human health. In time, this has led the EU to impose on manufacturers lower and lower emission standards. These limits are very challenging in particular for nitrogen oxides (NOx) emitted by diesel-fueled vehicles. For the town of Milan (Italy), we used a complex modeling system that takes into account the NOx emissions from vehicular traffic and other urban sources, as well as their dispersion and chemical transformations in the atmosphere related to meteorological parameters. The traffic emissions in the Milan urban area were estimated using the geometric and structural characteristics of the road network, whereas the traffic flows were provided by the Environment and Territory Mobility Agency. Car emissions were estimated by the official European method COPERT 5. The nitrogen dioxide (NO2) concentrations were estimated under two scenarios: the actual scenario with real emissions and the Diesel Emission Standards Compliance (DESC) scenario. Using a recent meta-analysis, limited to European studies, we evaluated the relationship between NO2 concentrations and natural mortality. For the actual scenario, the NO2 annual concentration mean was 44.3 µg/m3, whereas under the DESC hypothetical scenario, this would have been of 37.7 µg/m3. This “extra” exposure of 6.6 µg/m3 of NO2 leads to a yearly excess of 574 “natural” deaths. Diesel emissions are very difficult to limit and are harmful for exposed people. This suggests that specific policies, including traffic limitations, need to be developed and enforced in urban environments.

Bertrand's paradox (Bertrand 1889 "Calcul des Probabilites" (Paris: Gauthier-Villars)) can be considered as a cautionary memento, to practitioners and students of probability calculus alike, of the possible ambiguous meaning of the term "at random" when the sample space of events is continuous. It deals with the existence of different possible answers to the following question: what is the probability that a chord, drawn at random in a circle of radius "R", is longer than the side R[square root]3 of an inscribed equilateral triangle? Physics can help to remove the ambiguity by identifying an actual experiment, whose outcome is obviously unique and prescribes the physical variables to which the term "random" can be correctly applied. In this paper, after briefly describing Bertrand's paradox, we associate it with an experiment, which is basically a variation of the famous Buffon's needle experiment (Buffon 1733 "Histoire de l'Acad. Roy. des. Sciences" pp 43-5; Buffon 1777 "Histoire naturelle, generale et particuliere" Supplement 4 46) for estimating the value of [pi]. Its outcome is compared with the analytic predictions of probability calculus, that is with the probability distribution of variables whose uniform distribution can be considered a sound implementation of complete randomness. (Contains 6 figures.)

A polioencefalomalacia (PEM) é uma doença neurológica que acomete ruminantes e pode ser desencadeada por diversos fatores, dentre eles o consumo excessivo de enxofre. Este trabalho teve como objetivo verificar a relação entre dietas ricas em enxofre, altos níveis de gás sulfídrico ruminal e a ocorrência de polioencefalomalácia em ovinos. Foram utilizados 18 ovinos, divididos em três grupos (G1, G2 e G3) que receberam diferentes níveis de enxofre na dieta; 0,2%, 0,9% e 1,2%, respectivamente. Exames físicos (frequência cardíaca, frequência respiratória, temperatura retal e motricidade ruminal) e complementares (concentração de sulfeto de hidrogênio ruminal, hemogasometria venosa, pH do fluído ruminal, concentração de cobre sérico e hepático, tomografia computadorizada, necropsia e histopatologia) foram realizados. A temperatura retal, a hemogasometria venosa e o pH do fluido ruminal permaneceram dentro dos valores de referência para a espécie. A motricidade ruminal estava diminuída nos grupos G2 e G3 em comparação com o G1 (controle). Quanto maior a ingestão de enxofre, menores foram os níveis de cobre sérico e hepático. Valores elevados de sulfeto de hidrogênio ruminal foram detectados nos grupos G2 e G3. Nenhum animal apresentou sinais clínicos de PEM. Nos exames de tomografia computadorizada, necropsia e exame histopatológico do sistema nervoso central (SNC), não foram observadas alterações compatíveis com PEM. É provável que algum outro fator esteja associado ao excesso de enxofre na dieta para o desenvolvimento de PEM em ovinos.

Objective. To investigate compliance, satisfaction, and preference in women using a transdermal contraceptive patch. Methods. Women (18–46 years) from eight European countries used contraceptive patches (norelgestromin 6 mg, ethinylestradiol 600 μg) for six, 4-week treatment cycles. Compliance, satisfaction, and preference were assessed after 3 and 6 cycles and study completion using self-report methods. Results. Of the 778 participants, 36.8% (n = 287) used no contraception at baseline. The most common methods were oral contraceptives (67.9%, n = 334) and barrier methods (21.5%, n = 106). Of oral contraception users, 63.5% (n = 212) were satisfied or very satisfied with their previous method, but compliance was poor with 77.8% (n = 260) reporting missed doses. After 3 and 6 cycles, >80% of all included women were satisfied or very satisfied with the patch. At study completion, most participants (73.7%) reported a preference for the patch compared to their previous method. Of 4107 cycles, 3718 (90.5%) were completed with perfect compliance. Two pregnancies occurred during this study, representing a Pearl Index of 0.63. No new safety issues were identified and the patch was well tolerated. Conclusion. Women were highly satisfied with transdermal contraception and preferred this form of family planning over their previous method. Transdermal contraception represents a valuable addition to contraceptive options with potential to offer high compliance and efficacy.

The announcement of “Artificial Life” by the Craig Venter group, and the media stir that arose from the news, provoked thoughts about the current technologies in contemporary science and the cultural tension of such projections on the media. The increasingly blurred boundaries between specialist and generalist media, while promising a wider appreciation of scientific discovery, potentially allow unrealistic, ideological claims to dictate scientific research. This is particularly evident in biology, where the pervading paradigm is still dominated by a physically naïve reductionism in which the only relevant causative layer is the molecular one. The reductionist hypothesis is that everything one observes is the result of an underlying molecular mechanism almost independent of the context in which it operates. Molecular mechanisms are often necessarily studied in isolation and therefore operate in unnatural conditions. The mechanistic view of biological regulation implies that we think of genes as intelligent agents. Here we try to critically analyze the motivations behind the spread of such unrealistic simplifications.