Perceived health status and satisfaction with healthcare services of detained male individuals: a survey in Italy.

OBJECTIVES: This study investigated the perceived health status and satisfaction with prison healthcare services of detained male individuals in Italy. STUDY DESIGN: A cross-sectional study was performed between March and June 2021. METHODS: Of 800 male detained individuals who were invited to participate in the study, 632 returned the self-administered questionnaire, resulting in a response rate of 79%. RESULTS: Overall, 72.8% of participants reported that they were moderately or completely satisfied with their health status, and 27.2% stated that they were not at all satisfied. Moreover, 66.2% of participants reported that they had at least one health problem or disease, compared with 34% at the time of incarceration, with 35% reporting multiple health problems/diseases. In total, 10.1% of participants requested healthcare when a health problem occurred, and 12.4% were always satisfied with the healthcare that they received. Significant determinants of dissatisfaction with health status were older age, reported health problems/diseases, suicide attempts, emotional problems and no working activity in prison. Significant determinants of dissatisfaction with healthcare services were younger age, health problems at incarceration, suicide attempts and multiple experiences of incarceration. CONCLUSIONS: This study shows that detained male individuals have multiple and frequently unmet health needs. Some of the reported health problems or diseases were present at the time of incarceration, but these often worsened and/or increased during detention. This study highlights the need to promote evidence-based intervention to strengthen the role of healthcare services provided in prisons.

A qPCR Targeted Against the Viral Replication Origin Designed to Quantify Total Amount of Filamentous Phages and Phagemids.

Filamentous bacteriophages are widely used in phage display technology. The most common quantification method is lysis plaque formation test (PFT). This technique has several disadvantages, and only quantifies infective phages and is not effective when phagemids are used. We developed a qPCR method directed against the M13 replication origin, which detects between 3.3 × 103 and 3.3 × 108 viral genome copies with a linearity of R 2 = 0.9998. Using this method we were able to observe a difference of approximately ten more phages than with the PFT. This difference was not due to the presence of a free genome, which suggests the presence of non-infective particles. Using a DNaseI treatment, we observed the presence of 30% to 40% of unpackaged genome in recombinant phage modified in PIII or PVIII. The qPCR method with a DNase I treatment is an efficient method to quantify the total amount of filamentous phages.

Stratigraphic context and paleoenvironmental significance of minor taxa (Pisces, Reptilia, Aves, Rodentia) from the late Early Pleistocene paleoanthropological site of Buia (Eritrea).

The Buia Homo site, also known as Wadi Aalad, is an East African paleoanthropological site near the village of Buia that, due to its very rich yield from the late Early Pleistocene, has been intensively investigated since 1994. In this paper, which reports on the finds of the 2010-2011 excavations, we include new fossil evidence on previously identified taxa (i.e., reptiles), as well as the very first description of the small mammal, fish and bird remains discovered. In particular, this study documents the discovery of the first African fossil of the genus Burhinus (Aves, Charadriiformes) and of the first rodent from the site. This latter is identified as a thryonomyid rodent (cane rat), a relatively common taxon in African paleoanthropological faunal assemblages. On the whole, the new occurrences documented within the Buia vertebrate assemblage confirm the occurrence of taxa characterized by strong water dependence. The paleoenvironmental characteristics of the fauna are confirmed as fully compatible with the evidence obtained through sedimentology and facies analysis, documenting the sedimentary evolution of fluvio-deltaic and lacustrine systems.

Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification-an approach to classification of patients with t-MDS.

In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.

White matter lesions and vascular vertigo: clinical correlation and findings on cranial magnetic resonance imaging.

OBJECTIVE: Vestibular disorders and anxiety are closely related, probably because they share some neuronal pathways. Ageing and patient comorbidities are important facilitating factors, and multiple vascular risk factors could contribute to the onset of a vestibular syndrome called vascular vertigo. White matter lesions (WMLs) are often seen on magnetic resonance imaging (MRI) scans of elderly people and are related to various geriatric disorders, including dizziness. The cause of this correlation could be the disruption of neuronal networks that mediate higher vestibular cortical function. Numerous neuronal pathways link the vestibular network with limbic structures and the prefrontal cortex modulates anxiety through its connections to the amygdala. These could also explain nausea and sickness. The aim of the present work was to investigate the correlation between WML, vascular vertigo and cognitive functions. PATIENTS AND METHODS: Our team at the Poliambulanza Foundation Hospital of Brescia studied 90 patients (mean age 75 years) suffering from vascular vertigo with positive WML on MRI, by mapping the lesions and by grading anxiety and sickness symptoms. Furthermore, the same patients were treated with sulodexide (a glycosaminoglycan with antithrombotic activity) for 90 days (500 LSU/day for the first 45 days and 250 LSU/day for the following 45 days) to evaluate the efficacy on the vestibular symptoms. RESULTS: The results showed that the most frequent WML sites were frontal (n=34) and capsule (n=30) areas. Patients had a significant improvement on anxiety and sickness scores (p=0.0001 and p=0.02 respectively) after sulodexide treatment. CONCLUSIONS: In patients with vascular vertigo we confirmed the correlation between dizziness and anxiety and showed preliminary data regarding the efficacy of sulodexide in relieving in these patients anxiety and sickness.

Dual effect of parity on breast cancer risk.

This study examined whether breast cancer risk increased for a short period after childbirth, but decreased after a longer period of time. Data from an international case-control study on breast cancer conducted in the 1960s were used to study the modifying effect of age at enrolment on the relationship between parity and breast cancer risk, comparing first uniparous with nulliparous women, and then biparous versus uniparous women. The statistical analysis was performed by modelling through multiple logistic regression, adjusting for study site, age at menarche, menopausal status and obesity index. Comparing uniparous with nulliparous women, an early age at birth seems to be protective for all periods after birth, whereas a late age at birth imparts a higher risk than nulliparity in the period immediately after birth, which declines with the passage of time. The modification effect by age was not apparent when biparous women with different age at second birth were compared with uniparous women. The results support the hypothesis that pregnancy oestrogens impart a transient increase of maternal breast cancer risk when the full-term pregnancy occurs late in a woman's life.

6-Alkyl-N,N-disubstituted-2-pyridinamines as anticonvulsant agents.

The anticonvulsant effect of a series of 6-alkyl-N,N-disubstituted-2-pyridinamines is described. An investigation was carried out to optimize the anticonvulsant activity and reduce behavioral side effects in this series. Three compounds (7, 8, 10; Table I) were selected from initial screening for a more complete pharmacological evaluation. While each of these compounds was a potent anticonvulsant agent with ED50 values from 5 to 10 mg/kg, the activity was accompanied by significant behavioral side effects including decreased spontaneous locomotion, ataxia, and ptosis.

6-Alkoxy-N,N-disubstituted-2-pyridinamines as anticonvulsant agents.

The anticonvulsant effect of a series of 6-alkoxy-N,N-disubstituted-2-pyridinamines is described. An investigation was carried out to optimize the activity/side-effect ratio in this series of compounds. The most desirable profile was seen with 1-[6-(2-methylpropoxy)-2-pyridinyl]piperazine, 6, and this compound was selected for a more complete pharmacological evaluation. Overall, 6 has a pharmacological profile that is very similar to that of diphenylhydantoin (phenytoin). While nearly equipotent to phenytoin, animal studies suggest a fairly short duration of action. In addition, 6 exhibited some troublesome side effects including central nervous system depression and hypothermia.

3-Phenoxypyridine 1-oxides as anticonvulsant agents.

The anticonvulsant activity of a series of 3-phenoxypyridine 1-oxides is described. An investigation carried out to optimize the activity/side effect ratio provided 4-methyl-3-phenoxypyridine 1-oxide, 3, as the derivative of choice. Overall, 3 has a pharmacological profile that is very similar to phenytoin. It exhibited significant anticonvulsant activity at doses that did not produce ataxia or sedation but caused increased spontaneous behavioral activity not seen with most anticonvulsants. The short duration of pharmacological effect of 3 was attributed to metabolic hydroxylation at the C-4 pyridine methyl group; however, structural modifications designed to inhibit this metabolic pathway were unsuccessful.

N-phenyl-N'-pyridinylureas as anticonvulsant agents.

A series of N-phenyl-N'-pyridinylureas was examined for anticonvulsant activity. Extensive structure/activity investigations revealed optimal activity in the N-(2,6-disubstituted-phenyl)-N'-(4-pyridinyl)urea series, with 37 exhibiting the best overall anticonvulsant profile. Compound 37 was effective against seizures induced by maximal electroshock but did not protect mice from clonic seizures produced by the convulsant pentylenetetrazol. The overall pharmacological profile suggests that 37 would be of therapeutic use in the treatment of generalized tonic-clonic and partial seizures. Compound 37 was selected for Phase 1 clinical trials.

Amnesia-reversal activity of a series of cyclic imides.

A series of dihydro-1H-pyrrolizine-3,5(2H,6H)-diones were synthesized and evaluated for their ability to reverse electroconvulsive shock (ECS) induced amnesia in mice. Among the structure-activity relationships explored were the effects of ring size, the presence of heteroatoms (sulfur) in the ring system, and the introduction of alkyl substituents. The optimal ring size for the bicyclic system was 5.5 with dihydro-1H-pyrrolizine-3,5(2H,6H)-dione (3), although some activity was present in the corresponding 5.6 [hexahydro-3,5-indolizinedione (7)] and 6.6 [tetrahydro-2H-quinolizine-4,6(3H,7H)-dione (9)] analogues. Replacement of the C-1 carbon atom in compound 3 with a sulfur [dihydropyrrolo[2,1-b]thiazole-3,5(2H,6H)-dione (10)] abolished activity, and the introduction of methyl groups resulted in poorer biological profiles except when the substitution was made at the 7a position [dihydro-7a-methyl-1H-pyrrolizine-3,5(2H,6H)-dione (4)]. In several instances, hydrolysis of the parent bicyclic compound was carried out to furnish the corresponding lactam acids, which were further derivatized. Several exhibited interesting activity, especially the 5-oxo-2-pyrrolidinepropanoic acid derivatives such as 5-oxo-2-pyrrolidinepropanoic acid (12), 5-oxo-2-pyrrolidinepropanoic acid phenylmethyl ester (17), 5-oxo-2-pyrrolidinepropanoic acid (3-chlorophenyl)methyl ester (20), N-4-pyridyl-5-oxo-2-pyrrolidinepropanoic acid amide (25), and N-(2,6-dimethylphenyl)-5-oxo-2-pyrrolidinepropanoic acid amide (27). Compound 3 (CI-911; rolziracetam) was also observed to improve performance on a delayed-response task in aged rhesus monkeys and was selected for evaluation in cognitively impaired human subjects on the basis of its biological profile and a wide margin of safety in animals.

Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake.

The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of < 1 microM (including 5, Table I; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.

Design and synthesis of m1-selective muscarinic agonists: (R)-(-)-(Z)-1-Azabicyclo[2.2.1]heptan-3-one, O-(3-(3'-methoxyphenyl)-2-propynyl)oxime maleate (CI-1017), a functionally m1-selective muscarinic agonist.

The synthesis and SAR of a series of (Z)-(+/-)-1-azabicyclo[2.2. 1]heptan-3-one, O-(3-aryl-2-propynyl)oximes are described. The biochemistry and pharmacology of 24Z (PD 142505) and its enantiomers are highlighted. 24Z is functionally an m1-selective muscarinic agonist. Efficacy and m1 selectivity reside in the R enantiomer, (R)-24Z (CI-1017).

Hepatitis B and C virus infection in Crohn's disease.

Patients with Crohn's disease (CD) are at higher risk of hepatitis C (HCV) and B virus (HBV) infection, because of surgical and/or endoscopic procedures. However, the prevalence of HCV and HBV infection in CD is unknown. This issue may be relevant because of the growing use of immunomodulatory drugs in CD. The purpose of this study was to assess, in a multicenter study, the prevalence and risk factors of HCV and HBV infection in CD. The effect of immunomodulatory drugs for CD on the clinical course of hepatitis virus infections and of interferon-alpha (IFN-alpha) on the course of CD was examined in a small number of patients. Sera from 332 patients with CD and 374 control subjects (C) were tested for the following: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), HBcAb, HBeAg, HBeAb, anti-HCV, and HCV-RNA. An additional 162 patients with ulcerative colitis (UC) were tested as a disease control group. Risk factors were assessed by multivariate statistical analysis. Infection by either HCV or HBV was detected in 24.7% of patients with CD. In the age groups younger than 50 years, HCV prevalence was higher in CD than in C (p = 0.01). HCV infection in CD was associated with surgery (OR 1.71; 95% CI 1.00-2.93; p = 0.04), blood transfusions (OR 3.39; 95% CI 1.04-11.04; p = 0.04), and age (OR 2.3; 95% CI 1.61-3.56; p < 0.001). The event CD-related surgery appeared to be the main risk factor for HCV infection in CD. HCV prevalence was higher in CD (7.4%) than in UC (0.6%) (p = 0.001). HBcAb positivity was higher in CD (10.9%) and UC (11.5%) than in C (5.1%) (CD vs. C: p = 0.016; UC vs. C: p = 0.02), associated with age (OR 2.08; 95% CI 1.37-3.17; p = 0.001) and female gender (OR 2.68; 95% CI 1.37-3.17; p = 0.001) in CD and to UC duration (OR 1.20; 95% CI 1.06-1.36; p = 0.002). Immunomodulatory drugs did not influence the course of HBV or HCV infection in seven patients with CD, and IFN-alpha for chronic hepatitis C did not affect CD activity in six patients with CD. It is concluded that HBV prevalence is higher in CD than in C at all ages, whereas HCV prevalence is increased in young patients with CD, because of a greater need for surgery. The higher HCV (but not HBV) prevalence in CD than in UC suggests that the host immune response may influence the risk of HCV infection. Although a relatively high proportion of patients with CD showed HBV and/or HCV infections, this should not influence treatment strategies for CD.

Immunocytochemical localization of tryptamine in the rat brain.

Immunocytochemical localization of tryptamine in rat brain was performed at light and electron microscope level. The immunoreactive cells were present in the mesencephalon, pons and medulla, around the interpendicular nucleus in the reticular substantia nigra and in the giganto cellularis ventralis nucleus. Immunoreactive fibres were present in the dorsal region of the brain stem, and innervated the hippocampus, the ependymal epithelium and the corpus striatum. An ultrastructural study revealed that tryptamine was present only in neuronal perikaryon and processes.

Handedness, age at menarche, and age at menopause.

OBJECTIVE: To investigate the relation between handedness and age at menarche or age at menopause, as both handedness and reproductive variables have been suggested to be influenced by the intrauterine endocrine environment. METHODS: Self-reported information on handedness, age at menarche, age at menopause, and other demographic and reproductive variables was recorded for 10,328 women still menstruating or in natural menopause. These women had been selected as controls in a multicenter case-control study of breast cancer conducted in the 1960s. Left-handedness (including ambidexterity) was modeled as the outcome variable through multiple logistic regression. RESULTS: After adjusting for center, age, menopausal status, age at menopause, years of schooling, and parity, there was no significant relation of handedness to age at menarche (odds ratio for each year delayed 1.01, 95% confidence interval [CI] 0.97-1.06) or age at menopause (odds ratio 1.00, 95% CI 0.98-1.02). CONCLUSION: These findings lend no support to the hypothesis that intrauterine endocrine variables associated with handedness also are related to reproductive variables.

Cartilage synthesizes the serine protease inhibitor PAI-1: support for the involvement of serine proteases in cartilage remodeling.

The work described here demonstrates the synthesis by human articular cartilage of plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of the serine protease tissue plasminogen activator (tPA). We also present data demonstrating an increase in PAI-1 messenger ribonucleic acid (mRNA) in chondrocytes exposed to the cytokine interleukin-1 (IL-1). Interestingly, this elevation of steady-state mRNA levels does not appear to result in an increase in synthesis of PAI-1 protein. Northern blot analysis reveals that of the two mRNA species (3.4 kb, 2.4 kb) previously reported for PAI-1, only the larger species (3.4 kb) appears to be synthesized by chondrocytes. Our data demonstrate the IL-1-stimulated production by cartilage of tissue plasminogen activator. We also show evidence for the presence of plasminogen in cartilage. A scheme is presented indicating the probable importance of the serine proteases (tPA and plasminogen) and PAI-1 in cartilage degradation.

Prevalence of hospital-acquired infections in Italy.

A one-day prevalence survey was conducted in Calabria (Italy) to estimate the prevalence of hospital-acquired infections (HAI) and the effect of different variables on HAI in 888 patients present in a ward for at least 24 hours and not due for discharge or transfer on the day of the survey. The overall prevalence of HAI was 1.7% and urinary tract and surgical wounds were the most frequent sites (each four patients, 26.7%). In only eight (53.3%) of the fifteen HAI detected, had a microbiological examination been requested and the only two positive culture results involved Pseudomonas aeruginosa (surgical site) and Escherichia coli (urinary tract). Results of multiple logistic regression analysis indicated that HAI differed significantly in prevalence between age groups, ward, and was higher in patients with urinary catheters and in those receiving antibiotics.

Three-dimensional MR myelography of traumatic injuries of the brachial plexus.

PURPOSE: To determine the diagnostic accuracy of three-dimensional MR myelography in the evaluation of traumatic injuries of the brachial plexus. METHODS: Twenty patients with clinical and electromyographic evidence of traumatic brachial plexopathy were examined with three-dimensional MR myelography, conventional cervical myelography, and CT myelography 1 to 9 months after trauma. Three-dimensional MR myelography was performed on a 1.5-T MR unit with a constructive interference in steady state (CISS) technique. For each patient, maximum intensity myelographic projections and multiplanar reconstruction reformatted 1-mm axial sections were obtained from the same 3-D data set. Three-dimensional MR myelographic findings were compared with findings at cervical myelography and CT myelography. Surgical findings were available for comparison in 13 patients. RESULTS: Three-dimensional MR myelography enabled detection of meningoceles with avulsed or intact nerve roots, partial or complete radicular avulsions without disruption of the thecal sac, dural sleeve abnormalities, and dural scars. Assuming cervical myelography and CT myelography as the standards of reference, 3-D MR myelography showed 89% sensitivity, 95% specificity, and 92% diagnostic accuracy in the evaluation of nerve root integrity. CONCLUSION: Three-dimensional MR myelography can show the majority of traumatic lesions that involve the proximal portion of the brachial plexus in a single rapid examination. On the basis of our findings, we propose this technique as a screening examination for patients with traumatic brachial plexus palsy.

Synthesis and SAR of bulky 1-azabicyclo[2.2.1]-3-one oximes as muscarinic receptor subtype selective agonists.

The synthesis of a series of potent and efficacious 1-azabicyclo[2.2.1]heptan-3-one oxime muscarinic agonists is described. The oximes have extended appendages designed to span the cavity defined by the seven transmembrane helices of the muscarinic receptor. Some members of the series are selective for receptors of the m1 subtype. One such oxime, 31, shows affinity and functional selectivity for m1 over m2, m3, and m4 muscarinic receptor types.