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STUDY QUESTION Are chromosome abnormalities detected at Day 3 post-fertilization predominantly retained in structures of the blastocyst other than the inner cell mass (ICM), where chromosomally normal cells are preferentially retained? SUMMARY ANSWER In human embryos, aneuploid cells are sequestered away from the ICM, partly to the trophectoderm (TE) but more significantly to the blastocoel fluid within the blastocoel cavity (Bc) and to peripheral cells (PCs) surrounding the blastocyst during Day 3 to Day 5 progression. WHAT IS KNOWN ALREADY A commonly held dogma in all diploid eukaryotes is that two gametes, each with ‘n’ chromosomes (23 in humans), fuse to form a ‘2n’ zygote (46 in humans); a state that remains in perpetuity for all somatic cell divisions. Human embryos, however, display high levels of chromosomal aneuploidy in early stages that reportedly declines from Day 3 (cleavage stage) to Day 5 (blastocyst) post-fertilization. While this observation may be partly because of aneuploid embryonic arrest before blastulation, it could also be due to embryo ‘normalization’ to a euploid state during blastulation. If and how this normalization occurs requires further investigation. STUDY DESIGN, SIZE, DURATION A total of 964 cleavage-stage (Day 3) embryos underwent single-cell biopsy and diagnosis for chromosome constitution. All were maintained in culture, assessing blastulation rate, both for those assessed euploid and aneuploid. Pregnancy rate was assessed for those determined euploid, blastulated and subsequently transferred. For those determined aneuploid and blastulated (174 embryos), ICM (all 174 embryos), TE (all 174), Bc (47 embryos) and PC (38 embryos) were analyzed for chromosome constitution. Specifically, concordance with the original Day 3 diagnosis and determination if any ‘normalized’ to euploid karyotypes within all four structures was assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients (144 couples) were undergoing routine preimplantation genetic testing for aneuploidy in three IVF clinical settings. Cleavage-stage biopsy preceded chromosome analysis by next-generation sequencing. All patients provided informed consent. Additional molecular testing was carried out on blastocyst embryos and was analyzed for up to four embryonic structures (ICM, TE, Bc and PC). MAIN RESULTS AND THE ROLE OF CHANCE Of 463/964 embryos (48%) diagnosed as euploid at Day 3, 70% blastulated (leading to a 59% pregnancy rate) and 30% degenerated. Conversely, of the 501 (52%) diagnosed as aneuploid, 65% degenerated and 35% (174) blastulated, a highly significant difference (P < 0.0001). Of the 174 that blastulated, the ratio of ‘(semi)concordant-aneuploid’ versus ‘normalized-euploid’ versus ‘other-aneuploid’ embryos was, respectively, 39%/57%/3% in the ICM; 49%/48%/3% in the TE; 78%/21%/0% in the PC; and 83%/10%/5% in the Bc. The TE karyotype therefore has a positive predictive value of 86.7% in determining that of the ICM, albeit with marginally higher aneuploid rates of abnormalities (P = .071). Levels of abnormality in Bc/PC were significantly higher (P < 0.0001) versus the ploidy of the ICM and TE and nearly all chromosome abnormalities were (at least partially) concordant with Day 3 diagnoses. LIMITATIONS, REASONS FOR CAUTION The results only pertain to human IVF embryos so extrapolation to the in vivo situation and to other species is not certain. We acknowledge (rather than lineage-specific survival, as we suggest here) the possibility of other mechanisms, such as lineage-specific movement of cells, during blastulation. Ethical considerations, however, make investigating this mechanism difficult on human embryos. WIDER IMPLICATIONS OF THE FINDINGS Mosaic human cleavage-stage embryos can differentiate into a euploid ICM where euploid cell populations predominate. Sequestering of aneuploid cells/nuclei to structures no longer involved in fetal development has important implications for preimplantation and prenatal genetic testing. These results also challenge previous fundamental understandings of mitotic fidelity in early human development and indicate a complex and fluid nature of the human embryonic genome. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by Organon Pharmaceuticals and Merck Serono by grants to W.G.K. W.G.K. is also an employee of AdvaGenix, who could, potentially, indirectly benefit financially from publication of this manuscript. R.C.M. is supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM133747. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. D.K.G. provides paid consultancy services for Care Fertility. TRIAL REGISTRATION NUMBER N/A.

New facilities such as the National Ignition Facility and the Linac Coherent Light Source have pushed the frontiers of high energy-density matter. These facilities offer unprecedented opportunities for exploring extreme states of matter, ranging from cryogenic solid-state systems to hot, dense plasmas, with applications to inertial-confinement fusion and astrophysics. However, significant gaps in our understanding of material properties in these rapidly evolving systems still persist. In particular, non-equilibrium transport properties of strongly-coupled Coulomb systems remain an open question. Here, we study ion-ion temperature relaxation in a binary mixture, exploiting a recently-developed dual-species ultracold neutral plasma. We compare measured relaxation rates with atomistic simulations and a range of popular theories. Our work validates the assumptions and capabilities of the simulations and invalidates theoretical models in this regime. This work illustrates an approach for precision determinations of detailed material properties in Coulomb mixtures across a wide range of conditions., Most plasmas are created in a nonequilibrium state and understanding the non-trivial pathway to equilibrium is critical for predicting their time-evolving properties. Here the authors discuss the ion-ion temperature relaxation in a dual-species ultracold neutral plasma.

In strongly magnetized neutral plasmas, electron motion is reduced perpendicular to the magnetic field direction. This changes dynamical plasma properties such as temperature equilibration, spatial density evolution, electron pressure, and thermal and electrical conductivity. In this paper we report measurements of free plasma expansion in the presence of a strong magnetic field. We image laser-induced fluorescence from an ultracold neutral Ca^{+} plasma to map the plasma size as a function of time for a range of magnetic field strengths. The asymptotic expansion velocity perpendicular to the magnetic field direction falls rapidly with increasing magnetic field strength. We observe that the initially Gaussian spatial distribution remains Gaussian throughout the expansion in both the parallel and perpendicular directions. We compare these observations with a diffusion model and with a self-similar expansion model and show that neither of these models reproduces the observed behavior over the entire range of magnetic fields used in this study. Modeling the expansion of a magnetized ultracold plasma poses a nontrivial theoretical challenge.

Background and purpose Heterozygous mutations in the STUB1 gene have recently been associated with an autosomal dominant form of spinocerebellar ataxia (SCA) associated with cerebellar cognitive-affective syndrome (CCAS), named SCA48. Methods Molecular screening was performed in a cohort of 235 unrelated patients with adult-onset, autosomal dominant (17) or sporadic (218) cerebellar ataxia, negative for pathological trinucleotide expansions in the common SCAs, FRDA and FXTAS loci, by using targeted multigene panels or whole-exome sequencing. Bioinformatics analyses, detailed neurological phenotyping and family segregation studies corroborated the pathogenicity of the novel STUB1 mutations. Clinico-diagnostic findings were reviewed to define the phenotypic spectrum. Results Eight heterozygous STUB1 mutations were identified, six of which were novel in 11 patients from eight index families, giving an estimated overall frequency of 3.4% (8/235) for SCA48 in our study cohort, rising to 23.5% (4/17) when considering only familial cases. All our SCA48 patients had cerebellar ataxia and dysarthria associated with cerebellar atrophy on brain magnetic resonance imaging; of note, many cases were also associated with parkinsonism, chorea and dystonia. CCAS also occurred frequently, whereas definite signs of pyramidal tract dysfunction and peripheral nervous system involvement were absent. One SCA48 patient presented with hypogonadism, associated with other autoimmune endocrine dysfunctions. Conclusions Our results support SCA48 as a significant cause of adult-onset SCA. Besides CCAS, our SCA48 patients often showed movement disorders and other clinical manifestations previously described in SCAR16, linked to biallelic variants in the same gene, thus suggesting a continuous clinical spectrum and significant overlap amongst recessive and dominantly inherited mutations in STUB1.

This paper looks at patients with a diagnosis of tubulointerstitial nephritis and uveitis (TINU) presenting to the Northern Ireland regional adult and paediatric uveitis service in the Belfast Health and Social Care Trust. The demographic distribution, treatment required and the visual and renal outcomes of these patients are documented.Data were collected retrospectively on 24 patients with TINU using the Northern Ireland Electronic Care Record, central pathology records alongside the adult and paediatric uveitis databases from 2011 to 2021. Patients were categorised into two groups using the Mandeville classification system. Standard Uveitis Nomenclature (SUN) was used to classify the uveitis.The population prevalence is at least 12.6 cases per million based on a population of 1.9 million. Nineteen of 24 cases were definite TINU and five of 24 probable. Seventeen out of 24 had biopsy-positive TIN, all of which met all of the Mandeville clinical diagnostic features required for a definite diagnosis. All but one presented with acute bilateral anterior uveitis. The paediatric cases ranged from age 12 to 18 at age of onset with a mean age of 14. Of the 18 adult onset cases, the age ranged from 20 to 76 years. The mean age of onset for the adult cases was 53 years. Of these patients 71% were female; 42% required second-line immunosuppression for ocular disease. Visual acuity was maintained. Follow-up time ranged from 3 months to 16 years. No patient developed long-term renal impairment.TINU is a cause of uveitis in both the paediatric and adult populations. In Northern Ireland average age with TINU was older than much of the published literature. Long-term immunosuppression for uveitis may be required as ongoing ocular, rather than renal inflammation seemed to require treatment.

Progressive supranuclear palsy (PSP) is a neurodegenerative disease of the central nervous system, presenting with different clinical phenotypes, all involving the extrapyramidal system. Orthostatic hypotension (OH) is a common symptom of cardiovascular autonomic dysfunction. OH is defined as a fall in systolic blood pressure of at least 20 mmHg and/or a fall in diastolic blood pressure of at least 10 mmHg on standing or head-up tilt. In this pilot study, we tested the feasibility and efficacy of the ERIGO® device in managing OH non-responsive to conventional treatments in a sample of patients with PSP. OH was chosen as the primary outcome, as the symptom is a serious complication in neurodegenerative disorders, challenging the rehabilitation treatment. Six patients received intensive training using ERIGO®, a robot- assisted tilt table with an integrated leg movement system that allows progressive verticalization of the patient, and application of functional electrical stimulation. In all the participants, OH improved after the training with the device, suggesting that robotic verticalization may be a feasible and effective tool in improving blood pressure stability in patients with PSP. Further studies in larger samples, also including patients with other neurodegenerative disorders associated with OH, are needed to confirm these promising results.

BACKGROUND: The Lung Volume Reduction Coil Treatment in Patients With Emphysema (RENEW) trial reported improvements in quality of life, pulmonary function, and exercise performance following endobronchial coil treatment.OBJECTIVES: The purpose of this post hoc analysis was to identify baseline predictors, including quantitative CT measures, that identify patients most likely to significantly benefit from endobronchial coil therapy.METHODS: Quantitative CT analysis by an independent radiology laboratory and a qualitative evaluation by five blinded experts of the baseline thoracic CT imaging were performed. Univariate and multivariate logistic regression analyses were performed to elucidate characteristics associated with clinical response.RESULTS: In total, 125 patients underwent coil treatment and had evaluable 12-month follow-up results. Of these, 78 patients received treatment of lobes with the highest emphysematous destruction determined by quantitative CT analysis (quantitative visual match [QVM]+), and 47 received treatment in at least one lobe that was not the most destroyed (QVM-). From the 78 patients with QVM+ treatment, a subgroup of 50 patients (64%) was identified with baseline residual volume > 200% predicted, emphysema score > 20% low attenuation area, and absence of airway disease. In this subgroup, greater lobar residual volume reduction in the treated lobes was achieved, which was associated with significant mean +/- SE improvement in FEV1 (15.2 +/- 3.1%), St. George's Respiratory Questionnaire (-12 +/- 2 points), and residual volume (-0.57 +/- 0.13 L).DISCUSSION: This post hoc analysis found that both significant hyperinflation (residual volume >= 200% predicted) and CT analysis are critical for patient selection and treatment planning for endobronchial coil therapy. Quantitative CT analysis is important to identify optimal lobar treatment and to exclude patients with insufficient emphysema (

Aim: To evaluate the resistance to load of maxillary molars restored with composite overlays manufactured with three different techniques, namely the traditional indirect technique, a chairside semi-direct technique, and a CAD/CAM technique. Methods: Sample size was calculated considering the results obtained in preliminary experimental studies (α=0.05; β=0.20; δ =500.0; σ =300.0). Eighteen sound maxillary molars of comparable size were selected from a pool of freshly extracted teeth and received a standardized preparation for a full-coverage overlay with two proximal boxes. The prepared teeth were randomly divided into three experimental groups of 8 elements each: traditional indirect technique with polyvinyl siloxane impression and stratification on a stone model; chairside semi-direct technique with alginate impression and stratification on a silicon model; CAD/CAM technique with digital impression and production with the Cerec 3 system. All tested materials were resin-based composites of the same brand (Voco). For the CAD/CAM production process, a custom-designed phantom model was used. The cementation protocol was the same for all groups and involved the use of sandblasting, self-etch adhesive procedures with selective enamel etching, and dual cure resin cement. All the restored teeth underwent thermomechanical aging (1,250,000 cycles, 1Hz, 5-55°C); afterwards, they were axially loaded to fracture with a universal testing machine with a round-head stainless steel stylus. The type of fracture was registered. The groups were compared in terms of maximum load to fracture with a one-way analysis of variance and Scheffè post-hoc test (p

Non-invasive and simple to measure biomarkers are still an unmet need for myotonic dystrophy type 1 (DM1). Indeed, muscle biopsies can be extremely informative, but their invasive nature limits their application. Extracellular microRNAs are emerging humoral biomarkers and preliminary studies identified a group of miRNAs that are deregulated in the plasma or serum of small groups of DM1 patients. Here we adopted very stringent selection and normalization criteria to validate or disprove these miRNAs in 103 DM1 patients and 111 matched controls. We confirmed that 8 miRNAs out of 12 were significantly deregulated in DM1 patients: miR-1, miR-27b, miR-133a, miR-133b, miR-206, miR-140-3p, miR-454 and miR-574. The levels of these miRNAs, alone or in combination, discriminated DM1 from controls significantly, and correlated with both skeletal muscle strength and creatine kinase values. Interestingly, miR-133b levels were significantly higher in DM1 female patients. Finally, the identified miRNAs were also deregulated in the plasma of a small group (n = 30) of DM2 patients. In conclusion, this study proposes that miRNAs might be useful as DM1 humoral biomarkers.

Purpose: To determine the incidence of blindness secondary to idiopathic intracranial hypertension (IIH) in the United Kingdom. Methods: New cases of blindness occurring secondary to IIH were identified prospectively through the British Ophthalmological Surveillance Unit (BOSU) from October 2005 to November 2006. Only idiopathic cases of intracranial hypertension and those meeting the World Health Organisation`s definition of blindness were included. Cases that were already blind or had already been blind registered before the study period were excluded. Results: There were 24 new cases of registerable blindness secondary to IIH reported during the 12 month period. Questionnaires were completed for 19 cases. Of these 19 cases, 3 were not truly idiopathic and 3 cases did not fulfil the strict criteria for blindness. One case was a duplicate report. There were 12 definite cases of blindness secondary to IIH giving a UK incidence of blindness secondary to IIH of 0.6-2% (assuming a UK population of 63.2 million and an incidence of IIH of 1-3/100,000). If the 5 cases reported as blind but without a completed questionnaire are assumed to be true cases then the incidence of blindness would be 1-3%. Conclusions: The results of this study suggest that approximately 1-2% of new cases of IIH are likely to become blind in a given year. This contrasts with rates of between 4-10% reported previously in hospital-based studies, but may be a more accurate figure for the population as a whole. Under-ascertainment and improving standards of care may also have contributed to the lower figure than previously reported.

While previous studies have shown that CD4+ T cells expressing CCR6 and CD161 are depleted from blood during HIV infection, the mechanisms underlying their loss remain unclear. In this study, we investigated how the homeostasis of CCR6+ and CD161+ CD4+ T cells contributes to SIV disease progression and the mechanisms responsible for their loss from circulation. By comparing SIV infection in rhesus macaques (RMs) and natural host sooty mangabeys (SMs), we found that the loss of CCR6+ and CD161+ CD4+ T cells from circulation is a distinguishing feature of progressive SIV infection in RMs. Furthermore, while viral infection critically contributes to the loss of CD161+CCR6-CD4+ T cells, a redistribution of CCR6+CD161− and CCR6+CD161+CD4+ T cells from the blood to the rectal mucosa is a chief mechanism for their loss during SIV infection. Finally, we provide evidence that the accumulation of CCR6+CD4+ T cells in the mucosa is damaging to the host by demonstrating their reduction from this site following initiation of antiretroviral therapy in SIV-infected RMs and their lack of accumulation in SIV-infected SMs. These data emphasize the importance of maintaining CCR6+ and CD161+ CD4+ T cell homeostasis, particularly in the mucosa, to prevent disease progression during pathogenic HIV/SIV infection.

DJ-1 mutations are associated to early-onset Parkinson's disease and accounts for about 1-2% of the genetic forms. The protein is involved in many biological processes and its role in mitochondrial regulation is gaining great interest, even if its function in mitochondria is still unclear. We describe a 47-year-old woman affected by a multisystem disorder characterized by progressive, early-onset parkinsonism plus distal spinal amyotrophy, cataracts and sensory-neural deafness associated with a novel homozygous c.461CA [p.T154K] mutation in DJ-1. Patient's cultured fibroblasts showed low ATP synthesis, high ROS levels and reduced amount of some subunits of mitochondrial complex I; biomarkers of oxidative stress also resulted abnormal in patient's blood. The clinical pattern of multisystem involvement and the biochemical findings in our patient highlight the role for DJ-1 in modulating mitochondrial response against oxidative stress.

Standard of Care (SOC) vs. Study Driven (SD) Bronchoscopies. (DOCX 16 kb)

Syndesmosis ankle sprains should not be overlooked because of the significant morbidity associated with a missed injury.

The aims of this study were to: Investigate retinal changes associated with type 2 membranoproliferative glomerulonephritis (type 2 MPGN). Assess whether there was a relationship between the severity of the kidney disease and ophthalmoscopically visible fundal changes. Find out if renal transplantation was linked with visual deterioration. Decide if patients with type 2 MPGN need to be referred for ophthalmological assessment.The patients were identified from pathology department records as having renal biopsy proven type 2 MPGN from January 1981 to October 2003. Patients were invited to attend for ophthalmic assessment.A total of 26 biopsy proven cases of type 2 MPGN were identified. One patient lost vision from a possible occult choroidal neovascular membrane. The extent of ocular involvement did not consistently appear to be related to the severity of the renal involvement, although there was a relationship between the presence of ocular lesions and the duration of the disease. The longer the disease was present the more likely the patients were to have ophthalmoscopically visible fundal changes. Renal transplantation did not appear to have a detrimental effect on vision with the possible exception of one patient.Referral of type 2 MPGN patients by the renal physician for an initial ophthalmological assessment may be beneficial so that symptoms of choroidal neovascularization can be explained and patients advised to seek urgent help if distortion of central vision occurs. Renal transplantation does not appear to be a risk factor for the development of choroidal neovascular membranes.

Ninety-nine Italian elite athletes (61 M, 38 F, mean age +/- SE: 24.1 +/- 0.6 yr, age range: 17-47 yr) of different disciplines volunteered to participate in this investigation. Basal GH concentrations were significantly higher (p0.0001) in females (6.2 +/- 1.1 ng/ml) vs males (1.9 +/- 0.5 ng/ml). Basal GH values were negatively correlated with age and body mass index (BMI); no significant correlation was found between GH and IGF-I levels. Among female athletes, 8/38 had basal GH values higher than 10 ng/ml [2/8 athletes were taking oral contraceptives (OC)], while among males 6/61 had values higher than 5 ng/ml. In females, training sessions significantly increased (p0.0001) basal GH concentrations (peak GH: 18.5 +/- 1.9 ng/ml), while in males GH responses were lower than in females (11.8 +/- 1.4 ng/ml, vs F: p0.005). Six out of 38 female and 6/61 male athletes were considered GH hypo-responders (i.e. negative difference between peak GH and basal GH values), the large majority of them being subjects with elevated basal GH concentrations. In responsive athletes, peak GH values occurred immediately at the end of the training session both in males and in females; GH concentrations rapidly declined during recovery. No significant correlations were found between peak GH and age, body weight and BMI in either gender. GH responses were directly related (p0.001) to the intensity of the workload during the sessions. In conclusion, the present study demonstrates that: 1) some elite athletes had increased GH concentrations before training, which were however associated with normal IGF-I levels; 2) GH peaks after a discipline-specific training session were significantly higher in females than in males performing the same discipline, gender-related differences disappearing when post-exercise total GH outputs (area under the curve) were compared; 3) peak GH values were directly correlated with training workload; 4) GH concentrations rapidly declined during recovery, values at the end of the post-training GH sampling being generally lower than those found in basal condition.

Si esaminano i principali elementi che caratterizzano la mobilità degli studenti nell'indagine del profilo dei laureati 2009.

A 14-yr-old White male was referred to the Urology Unit of the G. Gaslini Institute because of a post-traumatic urethral stenosis (arising from a bicycle accident) that, during the previous 18 months, had required repeated endoscopic urethral dilation manoeuvres at the patient's local hospital. Apart from the urethral stenosis, the patient had been in excellent health until 2 months before admission, when slowly progressive exertional dyspnoea, associated with nonproductive cough and right-sided posterior chest pain, developed. On admission, the patient appeared in good clinical condition. Decreased percussion and auscultatory sounds were noted over the middle and lower portions of the right hemithorax. A summary of the results of the blood tests performed on admission is shown in table 1⇓. View this table: Table 1 Results of blood tests performed on admission Chest radiography (fig. 1⇓) and high-resolution computed tomography (HRCT) (fig. 2⇓) were performed. Fig. 1.— Chest radiograph. Fig. 2.— High-resolution computed tomography of the chest at two different window settings: a) “parenchymal”; and b) “soft tissue”. Thoracocentesis was performed and 500 mL haemorrhagic pleural fluid aspirated. Pleural fluid analysis did not show any cytological changes suggesting malignancies, amylase levels were within the normal range and microbiological evaluation results were negative for bacteria, fungi, mycoplasmata, mycobacteria and viruses. Plasma d‐dimer levels were slightly elevated but ultrasonography of the deep venous system did not show signs of thrombosis in the legs, penis or pelvis. Echocardiographic evaluation did not demonstrate any right ventricular dysfunction. Ultrasonographic examinations showed that there were no abnormalities of the abdominal organs and no peritoneal effusion and ruled out the presence of testicular or thyroid tumours. Fibreoptic bronchoscopy was then performed and did not reveal any airway abnormalities. Bronchoalveolar lavage analysis was nondiagnostic (no siderocytes suggestive of pulmonary haemorrhage, acid-fast bacilli, bacteria, viruses, fungi or malignant cells were identified in the epithelial lining fluid or lavage fluid …

Treatment of acrolein diethyl acetal sulfide 8 with methanesulfenyl bromide at low temperature results in an efficient thiirane ring opening to a halo disulfide 9. The bromine in this halo disulfide is easily substituted by silver acetate, sodium azide, sodium iodide, and silver nitrate. Treatment of 9 with tetrabutylammonium acetate yields a novel dehydrohalogenation product 12. Silica gel converts bromide 9 into a disulfide-substituted version of acrolein 15. The orthogonal-protected version of 2-thioglyceraldehyde 13 can be deprotected to a useful form of this aldehyde.

With the aim of quantifying the use of oral anticoagulant (OA) therapy in clinical practice, we surveyed 150 consecutive patients admitted with a diagnosis of atrial fibrillation (AF). Each patient was administered a questionnaire relating to the classic vascular risk factors and to the antithrombotic treatment received at home. The diagnosis of AF was formulated at the time of admission in 45 cases. Of the 105 cases with a previous diagnosis, OA therapy was relatively or absolutely contraindicated in 21 patients (20%), whereas the other 84 (80%) were ideal candidates for the treatment. Of these, 20 (24%) were actually receiving OA, 16 (19%) were on platelet anti-aggregants (PA), and 48 (57%) were receiving no antithrombotic treatment at all. Even lower percentages of OA use were found in the patients with a previous (20%) or recent (16%) history of cerebral ischemia. Upon discharge, of the 115 patients without contraindications to OA (84 with previously known and 31 with newly diagnosed AF), 50% were receiving OA and 20% PA. The results of this survey show that OA therapy is little used in the Valle d'Aosta Region for the prevention of ischemic stroke in AF patients at high risk for cerebral ischemia. The lack of knowledge among the general population, the difficulty of initiating the therapy in patients such as ours with severe comorbidities, and the absence of disorganization of centers for OA monitoring may be the main reasons underlying this low level of use. Population screening or a sensitization campaign could increase the identification of subjects at risk, whereas better organization of coagulation monitoring centers could encourage OA use in subjects at high risk for cerebral ischemia.

An outbreak of Salmonella enterica serotype Typhimurium belonging to phage type (PT) 193 occurred in autumn 1995 and involved 83 individuals in a large area of Northern Italy (Lombardy Region). Epidemiological and microbiological investigations of strains isolated from clinical and food specimens revealed that the vehicle was a batch of salami, produced on 4 September 1995 by a local firm. The outbreak was contained when the batch was withdrawn from sale. Insufficient ripening of the salami had allowed the salmonella to survive, emphasizing the need to define criteria for the ripening process of foods such as salami.

A linear low-density polyethylene was gamma irradiated in presence of carbon dioxide under supercritical conditions. As already reported, this process can be an interesting way to graft carboxylated functions to the polyethylene chains. In this work a detailed analytical investigation of the carboxylation products grafted on LLDPE are presented. Derivatization procedures with sulfur tetrafluoride and nitrogen monoxide, in order to selectively convert the carboxylated functions into groups more easily identified and quantified by FTIR, were performed. The chemical nature of the grafted groups is very similar to that obtained through gamma irradiation in air; furthermore, a significant degree of crosslinking is observed.

A small supernumerary chromosome was observed in two Prader-Willi syndrome (PWS) patients. The clinical diagnosis of PWS was confirmed by the ascertainment of the deletion of region 15q11-13 in one case and uniparental disomy (UPD) of the same region in the other. The markers were negative for dystamycinA/DAPI banding, did not contain NOR-positive satellites, and had an appearance consistent with a very small ring chromosome. Fluorescent in situ hybridization (FISH) analysis with the “all human centromere” probe indicated the presence of centromeric sequences in both markers. Chromosomal in situ suppression hybridization with chromosome specific libraries demonstrated that the small markers in the deleted and UPD patient originated from chromosome 15 and X, respectively. To the best of our knowledge these are the only PWS patients reported with a supernumerary marker chromosome other than inv dup(15) characterized by FISH. Am. J. Med. Genet. 68:99–104, 1997 © 1997 Wiley-Liss, Inc.

A complete survey of the immunofluorescence distribution of the cytoskeletal protein vinculin in the normal skeletal muscle and peripheral nerve of humans and of different rodent species was performed. Our results enable us to localize vinculin in different types of adhesion plaques such as sarcolemmal costameres and neuromuscular and myotendinous junctions, but also in a fine intermyofibrillar lattice, possibly associated with intermediate filaments and/or with the triads. Moreover, we describe the presence of vinculin in junctional domains of several, previously unrecognized, specialized cells such as: the outer sheath of the muscle spindle capsule, the multilayered flat cells of the perineurium, the smooth muscle cells of epineurial blood vessels, and the endothelial cells in the endoneurium. These data call for a major role of vinculin in mechanisms of adhesion between cells, between cell and substrate and between intermyofibrillar components in the neuromuscular system. Such knowledge provides an anatomical background for studies on the possible pathological effects induced by an impairment in vinculin function. © John Wiley & Sons, Inc.

Purpose Investigation of cataract frequencies, yellow discoloration and light scattering profiles in the lenses of a subset of nuns from the Irish Nun Eye Study (INES) correlated to age and outdoor activity. Methods After obtaining informed consent, the anterior eye segment of 144 retired nuns from contemplative and missionary convents in Northern Ireland and the Republic of Ireland were monitored with a Scheimpflug camera (Pentacam HR®, Oculus, Wetzlar, Germany). Images of the cornea and lens were recorded automatically in 25 meridians in mydriasis, using the recording algorithm of the camera. In addition retro-images of the lenses were recorded using the Neitz Cataract screener and lens discoloration was recorded using a manual slitlamp and the LOCS III grading system. Image analysis was performed using special analytical software (BIOM®) and cataract classification was done using the Bonn cataract classification system. Results Age-related light scattering increase is most pronounced in the anterior deep cortex and the anterior nuclear shell of the lenses and is generally lowest in the posterior nuclear shell. Cortical cataracts were the most frequent type in this study, the highest frequency found in the lower nasal quadrant followed by the lower temporal quadrant. Pure subcapsular cataracts have not been found in this study. The increase in yellow discoloration correlated to the increase in nuclear light scattering. Nuns with cortical cataracts had less discoloration, but were also younger. Conclusion The frequency of nuclear cataracts was lower in the INES cohort was lower, but the amount of cortical cataracts was similar to other studies like Beaver Dam Eye Study. The increases in nuclear light scattering and discoloration correlated with age and exposure index. The data from the INES study support the hypothesis that light protection has a positive effect on the frequencies of nuclear and subcapsular cataracts as well as on lens discoloration. The Pentacam HR® provided better documentation of lens transmission characteristics than the Neitz cataract scanner.

Purpose To report our experience with the intravitreal fluocinolone acetonide implant (Retisert TM) in treating patients with severe chronic non-infectious posterior uveitis. Methods Retrospective review of case notes of patients with severe posterior uveitis who had Retisert TM implants over a 6-year period. 12 eyes of 9 patients were identified. Indications for implantation included need for repeated sub-tenon triamcinolone injections, non-responsiveness, poor tolerance to systemic medication or unilateral disease. Results The follow-up time ranged from 9 to 76 months (mean - 35.4). 3 patients received implants in both eyes. In 3 patients who were followed up for longer than 36 months, a second implant was inserted. Snellen visual acuity improved in all eyes, average gain being 3.5 lines (range 1-6). There was improved control of the intraocular inflammation in all patients. All patients have been able to either stop or reduce systemic immunosuppressant therapy within 6- 12 months of the procedure. Six (40%) eyes developed raised IOP with 4 requiring trabeculectomy. Five patients required cataract surgery. One patient developed a peripheral retinal tear with localised detachment, which was treated successfully with vision returning to 6/6. Conclusion RetisertTM is very effective in severe non-infectious posterior uveitis and may be the ideal option in those intolerant or unresponsive to topical and systemic immunosuppression. It can also be used in bilateral disease. The significant complications are acceleration of cataract and raised IOP. However, these need to be considered against the benefits of better control of inflammation and reduced systemic immunosuppression.

Treatment of acrolein diethyl acetal sulfide 8 with methanesulfenyl bromide at low temperature results in an efficient thiirane ring opening to a halo disulfide 9. The bromine in this halo disulfide is easily substituted by silver acetate, sodium azide, sodium iodide, and silver nitrate. Treatment of 9 with tetrabutylammonium acetate yields a novel dehydrohalogenation product 12. Silica gel converts bromide 9 into a disulfide-substituted version of acrolein 15. The orthogonal-protected version of 2-thioglyceraldehyde 13 can be deprotected to a useful form of this aldehyde.