Search

Purpose: Hashimoto thyroiditis and Graves’s disease are two related autoimmune disorders, representing the leading causes of hypothyroidism and hyperthyroidism. Autoimmune hypothyroidism is generally irreversible but very rarely, some patients would shift to hyperthyroidism. The aim of the study was to seek for possible clinical predictors of the transition from hypo to hyperthyroidism in patients with Hashimoto thyroiditis and to outline their clinical phenotype. Methods: Twelve patients with overt autoimmune hypothyroidism who had at least one transition from hypothyroidism to autoimmune hyperthyroidism were compared with 294 consecutive patients with autoimmune hypothyroidism and 69 consecutive patients with autoimmune hyperthyroidism that accessed the outpatient clinic over six months. Demographic, hormonal data and autoantibodies titers were compared. Results: Prevalence of smoking habit was significantly higher in switchers compared to controls. Switchers showed a significantly higher prevalence of personal and familial history of non-thyroidal autoimmune disorders. TSH levels were significantly lower in the switcher group during the hypothyroid phase and levothyroxine dose required was lower. TSH concentrations were significantly lower while free fT4 and free fT3 values were higher in GD patients compared to switchers during the hyperthyroid phase despite comparable TRAb levels. Prevalence and type of hyperthyroid symptoms and orbitopathy were similar between switchers and GD group. Mean dose of anti-thyroid drugs was significantly higher in GD patients compared to switchers. No differences were observed in the remission rate from hyperthyroidism between the two groups, despite switchers showed a significantly lower time-to-remission. Conclusions: Conversion of Hashimoto Thyroiditis towards Graves’ disease is a rare phenomenon which can occur almost at any time after the development of autoimmune hypothyroidism. Our findings suggest active surveillance of hypothyroid patients who require frequent reduction of levothyroxine during follow up and testing for TSHR antibodies in these patients.

Elizabeth Otto, Haunted Bauhaus: Occult Spirituality, Gender Fluidity, Queer Identities, and Radical Politics, (Cambridge, MA: MIT Press, 2019). Recto, 2019. 280 pp./$34.95 (hb). In Hans Richter's 1928 experimental film Vormittagsspuk [...]

Objective: To present the changes in 5-year relative survival of patients with breast and colorectal cancer in a northern Italian province in the 2000–2012 period. Changes are presented in relation to stage, period, and age in the screening population.Methods: A total of 5073 breast cancer and 4093 colorectal cancer cases were registered. Breast cancer was divided into 5 age groups: <45, 45–49, 50–69, 70–74 (the target screening population is ages 45–74), and >74 years. Colorectal cancers were classified into 3 age groups: <50, 50–69 (screening target population), and >69 years. Survival was analysed by stage, period, and screening program.Results: Five-year breast cancer relative survival was 92.9% overall, with 100%, 91.9%, 78.8%, 34.2%, and 76.4% for stages I, II, III, IV, and unknown, respectively. Survival increased from 89.7%, 91.8%, and 93.4%, respectively, in the periods 2000–2005, 2006–2009, and 2010–2012. Breast cancer survival was stable in early stages (although already high); a slight improvement was seen for stages III and IV. Five-year colorectal cancer relative survival was 63.6% overall, with 93.3%, 78.6%, 69.8%, 13.2%, and 55.8% for stages I, II, III, IV, and unknown, respectively. No improvement in survival was seen in the periods analysed, although the introduction of screening in 2005 did lead to a sharp decrease in incidence and mortality.Conclusions: For breast cancer, extending the screening target age led to an improvement in survival; for colorectal cancer, the best impact was on incidence and mortality rate.

•Analysis of the experiment on variable pricing techniques in San Francisco (USA).•Guidance for an application of the performance-based pricing schemes in Italy.•Simulation of the method in Brescia (IT), showing the potential of this technique.•Variable-priced schemes can regenerate city centres by freeing spaces.•Demonstration of possibility of applying this technique in Italy.

With the aim of identifying novel antagonists selective for the EphA receptor family, a combined experimental and computational approach was taken to investigate the molecular basis of the recognition between a prototypical Eph–ephrin antagonist (UniPR1447) and two representative receptors of the EphA and EphB subfamilies, namely, EphA2 and EphB2 receptors. The conformational free-energy surface (FES) of the binding state of UniPR1447 within the ligand binding domain of EphA2 and EphB2, reconstructed from molecular dynamics (MD) simulations performed on the microsecond time scale, was exploited to drive the design and synthesis of a novel antagonist selective for EphA2 over the EphB2 receptor. The availability of compounds with this pharmacological profile will help discriminate the importance of these two receptors in the insurgence and progression of cancer.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic disorder of the kidney and accounts for over 95% of all cystic diseases involving loss of kidney function. The diagnosis of ADPKD is confirmed by mutational analysis of PKD1 and PKD2 genes, which is complex, because of the significant allelic heterogeneity and the presence of six pseudogenes presenting highly homologous sequences with an extended region of the PKD1 gene (exons 1–33). The aim of this study was to develop a rapid and reliable method for the molecular diagnosis of ADPKD using the technology of Next Generation Sequencing (NGS), that could be used for a diagnostic purpose. We first validated the test on two cohorts of ADPKD patients previously characterized by traditional Sanger sequencing method; then we analyzed a cohort of 58 patients not characterized and we achieved a mutation detection rate of 84.7%.

The evolutionary process which academic and research libraries are facing in recent years is strictly connected with the market-driven world of higher education, an increasingly competitive environment. Research libraries, facing challenge of the definition of a new role, must demonstrate that they are a strategic asset for the University goals. The study offers, using selected international universities comparisons, a tool to identify the strategic alignment between the library's role and the emergent needs of the academy and the institutional context. [ABSTRACT FROM AUTHOR]

This clinical report describes the successful implant-supported prosthetic rehabilitation of a patient who underwent subtotal bilateral maxillectomy for an oral squamous cell carcinoma with a consequent wide defect interesting the whole hard palate and most of the soft palate, causing a large opening that directly connects the oral cavity to the nasal fossa bilaterally. The innovative aspect of this case is represented by the realization of an obturator prosthesis supported by just 3 zygoma implants.

Facial fractures are one of the most common orofacial injury sustained during participation in sporting events.

The objective of this clinical trial was the analysis of 2 methods for engineering of autologous bone grafts for maxillary sinus augmentation with secondary implant placement. Group 1 (8 patients, 12 sinuses): cells of mandibular periosteum were cultured in a good manufacturing practice laboratory (2 weeks) with autologous serum and then transferred onto a collagen matrix. After another week, these composites were transplanted into the sinuses. In group 2A (2 patients, 3 sinuses), cells of maxillary bone were cultivated with autologous serum for 2 weeks, seeded onto natural bone mineral (NBM, diameter [Ø] = 8 mm) blocks, and cultivated for another 1.5 months. These composites were transplanted into the sinuses. Group 2B (control, 3 patients, 5 sinuses) received NBM blocks alone. In the course of implant placement 6 (group 1) and 8 (group 2) months later, core biopsy were taken. Clinical follow-up period was 1 to 2.5 years in group 1 and approximately 7 years in groups 2A and 2B. New vital bone was found in all cases at median densities of 38% (n = 12) in group 1, 32% in group 2A (n = 3), and 25% in group 2B (n = 5). Differences between group 1 and 2B as well as 2A and 2B were statistically significant ( p = 0.025). No adverse effects were seen. All methods described were capable of creating new bone tissue with sufficient stability for successful implant placement.

The neurotoxicity of the AMPAkainate receptor agonist kainate was investigated in motor and cortical neurones from mice over-expressing the wild-type and G93A mutant form of CuZn superoxide dismutase (SOD1) human gene, a mouse model of familial amyotrophic lateral sclerosis. G93A mutant motor neurones were more vulnerable and wild-type SOD1 motor neurones were more resistant to kainate toxicity than were controls. Voltage-gated Nachannels blockage prevented G93A mutant SOD1 motor neurone death. Cortical cultures exhibited fewer differences in their vulnerability to kainate toxicity. These results demonstrate that SOD1 over-expression selectively affects the sensitivity to kainate excitotoxicity of motor neurones but not neocortical neurones, and that wild-type SOD1 expression increases the resistance to excitotoxicity of motor neurones.

Giuliani, D. and F. Ferrari. Involvement of dopamine receptors in the antipsychotic profile of (−) eticlopride. Physiol Behav 61(4) 563–567, 1997.—The present study was performed to assess the effects exerted by the dopamine (DA) D2/D3antagonist (−) eticlopride on rodent behavioral models considered to be predictive of antipsychotic activity, namely, antagonism toward DA agonist-induced stereotyped behavior (SB), and ketamine- and cocaine-induced hypermotility. (−) Eticlopride (10–50 μg/kg) dose-dependently inhibited SB elicited by SND 919 (10 mg/kg), CQP 201–403 (0.5 mg/kg), and 7-OH-DPAT (5 mg/kg); moreover, it significantly counteracted the hypermotility induced in rats and mice by ketamine (5 and 10 mg/kg). When (−) eticlopride was injected before cocaine (15 mg/kg) either acutely or subchronically administered in male rats, it also potently antagonized the hypermotility typically induced by the drug. These results are discussed in the light of putative D2/D3receptor involvement, and are considered as predictive of antipsychotic potential.

A number of animal behavioural models were used to study the activity of imidazole (IMID) on the central nervous system. IMID antagonized in a dose-related fashion penile erections (PE) as well as stretching and yawning (SY) elicited in male rats by B-HT 920, an a2 and dopamine (DA) autoreceptor agonist. Inhibition of B-HT 920-induced PE and SY was also exhibited by haloperidol, a DA receptor blocker, and yohimbine, but not by prazosin, a2 and a1 receptor antagonists respectively. Moreover IMID behaved similarly to yohimbine in: 1) counteracting clonidine-induced hypothermia in mice; 2) antagonizing sedation and sleep induced by clonidine and B-HT 920 in chicks, while haloperidol was ineffective.

Lisuride increased the incidence of stretching and yawning (SY) as well as of penile erection (PE) and elicited stereotyped behavior (SB), aggressive behavior and mounting in male rats, depending on the dose used. SY was prevented by two dopaminergic antagonists, haloperidol and sulpiride, but not by methysergide, a serotoninergic antagonist, while PE was antagonized by all three drugs. With regard to SB, aggressive behavior and mounting, all three were suppressed by haloperidol; sulpiride, while partially antagonizing aggressiveness, failed to affect SB and mounting; methysergide did not significantly influence any of the three. This suggests that lisuride principally affects the dopaminergic system. Although further detailed studies are required to elucidate which type of the complex population of DA-receptors is involved in each kind of behavior, we suggest that SY at least is due to the activation by lisuride of presynaptic DA-receptors.

The influence of lisuride on naloxone-induced withdrawal signs (wet shakes, escape attempts) was studied in morphine-dependent rats. Lisuride, injected IP at doses of 12.5 and 25 µg/kg, inhibited wet shakes while not significantly altering escape attempts induced by naloxone (4 mg/kg IP). At higher doses (50 and 100 µg/kg IP), lisuride's inhibitory effect on wet shakes persisted while escape attempts were actually potentiated with respect to control withdrawal rats. Increases in aggressive behavior were seen at all doses, and were dose-related. Haloperidol (0.3 mg/kg IP), administered 40 min before lisuride, did not modify the antagonistic effect on wet shakes, unlike sulpiride (40 mg/kg IP 30 min before lisuride), but at the same time blocked the increase in escape attempts and aggressiveness induced by lisuride. We suggest that lisuride modulates withdrawal signs by stimulation of dopamine receptors in the CNS. The effect of the dopamine mimetic N-n-propylnorapomorphine (NPA) on the same variables is reported as well as the influence of haloperidol on NPA, and a comparison between the effects of the two drugs is made.

The effects of the selective D2 DA receptor antagonist, (-)eticlopride, a drug belonging to the benzamide class, were investigated on the D2 DA agonist SND 919- and CQP 201–403-induced stereotyped behaviour and on CQP 201–403-induced shaking, in rats, and on isolation-induced aggression, in mice. (-)Eticlopride was also tested over a wide dose range (52–1200 μg kg−1, s.c.) for sedative and cataleptic activity, in rats. For comparison, some experiments were performed with (-)sulpiride (10 and 40 mg kg−1, s.c.) The data obtained show that (-)eticlopride differs from (-)sulpiride and potentially modifies animal behaviour, whether spontaneous or induced; moreover, they suggest a potential clinical use for this neuroleptic in the management of psychotic states.

Cimetidine injected IP 15 min before (±) N-n-propylnorapomorphine (NPA) antagonized in dose-dependent fashion the penile erections (PE) and stretching and yawning (SY) induced by this typical dopaminergic agonist in male rats. Ranitidine, which acts on H2 histamine receptors in much the same way as cimetidine despite its lack of an imidazole ring, failed to produce the same effect. On the other hand, imidazole itself was similar to cimetidine in antagonizing PE and SY induced by (±) NPA, whether injected IP or ICV. Neither imidazole nor cimetidine antagonized the stereotyped behaviour (SB) induced by (±) NPA. Indeed, imidazole reduced the latency of this response. A mechanism which may underly these effects is discussed, as well as the possible preclinical use of this test in animals.

Copy number variations (CNVs) are deletions or duplications in a gene segment that commonly occur in normal individuals. CNVs can be benign or pathogenic and have been used as a diagnostic aid for identification of a variety of genetic diseases. Structural variations such as CNVs may contribute more to genomic differences between individuals than single-nucleotide polymorphisms. There is no known cause for as many 60 of stillbirths. Genetic karyotyping methods have identified cytogenetic abnormalities in only a small percentage (5–13) of all stillbirths. The contribution of genomic defects to stillbirth is likely underrepresented with use of conventional cytogenetics due to low resolution and other inherent limitations of these methods. Array-based copy number analysis increases test resolution by orders of magnitude compared with cytogenetic methods and has replaced karyotyping as the first-line diagnostic test in pediatric genetic analyses.

Naloxone at a dose of 2 mg·kg−1, which per se did not significantly alter the copulatory pattern of sexually active adult male rats, did significantly reduce the intromission frequency as well as latency to ejaculation when administered before a low and inactive dose of N-n-propylnorapomorphine (0.5 μg·kg−1).

Background: Hereditary Hemochromatosis, once considered a monogenic disorder, is now seen as a polygenic disease, with clinical phenotype also influenced by several environmental factors. Besides the classic HFE gene, other genes involved in modulation of iron homeostasis and clinical phenotype include those coding for hemojuvelin and hepcidin (both responsible for Juvenile Hemochromatosis), ferroportin, and, possibly, H-ferritin.