Emergence and evolution of the Omicron SARS-CoV-2 variant in the island of Martinique.

INTRODUCTION: We aimed to describe the epidemiological situation during the Omicron variant circulation in light of genomic surveillance data in Martinique, a territory with low vaccination rates. PATIENTS AND METHODS: We exploited COVID-19 national databases of virological tests, for the collection of hospital data and for the sequencing data from December 13, 2021 to July 11, 2022. RESULTS: Three prevailing sub-lineages of Omicron have been identified in Martinique (BA.1, BA.2, BA.5) during this period causing three distinct waves characterized by an increase in virological indicators compared to previous waves, with moderate severity in the first and last waves, caused by BA.1 and BA.5, respectively. CONCLUSION: The SARS-CoV-2 outbreak is still progressing in Martinique. Genomic surveillance system in this overseas territory must be continued for rapid detection of emerging variants/sub-lineages.

Cognitive Function and Amyloid Marker in Frail Older Adults: The COGFRAIL Cohort Study.

BACKGROUND: Frailty and cognitive impairment are common manifestations of the ageing process and are closely related. But the mechanisms linking aging, physical frailty, and cognitive disorders, are complex and remain unclear. OBJECTIVES: We aim to explore the role of cerebral amyloid pathology, but also a range of nutritional, physical, biological or brain-aging marker in the development of cognitive frailty. METHOD: COGFRAIL study is a monocentric prospective study of frail older patients with an objective cognitive impairment (Clinical Dementia Rating Scale global score at 0.5 or 1). Three-hundred-and-twenty-one patients are followed up every 6 months, for 2 years. Clinical assessment at baseline and during follow-up included frailty, physical, mood, sensory, nutritional, and cognitive assessment (with a set of neuropsychological tests). Cerebral amyloid pathology is measured by amyloid Positron Emission Tomography (PET) or amyloid-ß-1-42 level in cerebrospinal fluid. Brain magnetic resonance imaging, measurement of body composition using Dual X Ray Absorptiometry and blood sampling are performed. The main outcome of the study is to assess the prevalence of positive cerebral amyloid status according to amyloid PET or amyloid-ß-1-42 level CSF. Secondary outcomes included biological, nutritional, MRI imaging, cognitive, clinical, physical and body composition markers to better understand the mechanisms of cognitive frailty. PERSPECTIVE: COGFRAIL study will give the opportunity to better understand the link between Gerosciences, frailty, cognitive impairment, and Alzheimer's disease, and to better characterize the physical and cognitive trajectories of frail older adults according to their amyloid status. Understanding the relationship between physical frailty and cognitive impairment is a prerequisite for the development of new interventions that could prevent and treat both conditions.

[Barriers and enablers to pharmacist-led medication review in community pharmacy: A prospective study in Grand Est, France]. / Freins et leviers à la réalisation des bilans partagés de médication en officine : retour sur une expérimentation dans la région Grand Est.

Since 2018, French community pharmacists are involved in pharmaceutical care program performing medication review (MR). Near graduated pharmacy students from two faculties of pharmacy were assigned to implement and perform 3 MR in order to identify enablers and barriers of the implementation of MR by community pharmacists. Among 179 MR performed by 117 pharmacists during 5 months, they reported 3 main barriers: the time spending to initiate and perform all steps in MR (lack of time), patients recruiting, and compensation by health care system. Communications initiatives to patients and health professionals in primary care could facilitate patient MR adhesion. Simplification of administrative approach and optimization of software will be welcome and useful in order to reinforced MR implementation and leading.

Age effects on the neural processing of object-context associations in briefly flashed natural scenes.

In daily life, fast visual recognition of surrounding objects is facilitated through context-based expectations. However the ability to rapidly and accurately recognize unexpected stimuli in a given environment is also crucial and this ability is impaired with age. The present fMRI study aimed at comparing in young and older adults the neural correlates of fast object processing. Patterns of cerebral activity were investigated in response to briefly-presented (100 ms) congruent and incongruent natural scenes. Participants were slower and less accurate when categorizing objects in incongruent relative to congruent contexts. This behavioral cost was notably more pronounced in the older group. Height and multivariate patterns of fMRI activity in context-selective regions were equivalent in both age groups, suggesting preserved processing of coarse scene features in older participants. Incongruent scenes elicited additional activity in the parahippocampal gyrus that possibly reflected simultaneous activation of rarely co-occurring neural representations. Contextual effects were observed in object-selective cortex for the young group only, and may be driven by detection of mismatch between actually perceived and previously-experienced associations. In the older group exclusively, increased bilateral prefrontal and left fusiform activity in response to incongruent scenes was observed. However this supplemental activity was not found to efficiently contribute to improve task performance in difficult visual conditions. Altogether these results suggest age-related changes in the interaction between object- and context-processing pathways, that may subserve impairment in fast identification of unexpected objects in natural scenes.

[Outcomes after a 2-year pharmaceutical care program for patients taking vitamin K antagonist therapy? Community pharmacist's perception]. / Quel bilan à deux ans de la mise en place de l'accompagnement des patients traités par anti-vitamines K ? Le point de vue du pharmacien d'officine.

OBJECTIVES: Since 2013 French community pharmacist are involved in pharmaceutical care program (PCP) for patients treated with vitamin K antagonist (VKA). While PCPs are now extending to other patient populations, we aimed to evaluate pharmacists' perception after 2-years implementation and leading of PCP. METHODS: A prospective investigational survey from 1st August to 31st December, 2015 from 400 community pharmacies in Champagne-Ardenne Region. Survey focuses on 3 points: first about implementation and leading of PCP; secondly about patient's population description; finally on the global perception by CP about new tasks. RESULTS: Among n=47, 72% of pharmacists performed VKA PCP. Almost all received appropriate training (96%). Remuneration appears to be insufficient given the time spent for 73%. Ninety-five percent met patient's refusal mainly because of interest lacking or time lacking (54% and 22%, respectively). Pharmacists reported 3 main lacks of knowledges of patients: drugs, which increase drug-drug interaction risk (28%), VKA overdose effects (27%) and VKA-food interactions (23%). Overall view of pharmacist for PCP appears to be positive (81%) in part because of improvement of pharmacist-patient relationship perception for 66%. CONCLUSIONS: Community pharmacists' perception for PCP for patients treated by VKA is broadly positive. However, organizational or economic constraints can lead to a decreasing adherence by pharmacists to PCPs. A global issue about amount of compensation and communications campaigns to patients and others health professionals will be useful in order to reinforced PCP implementation and leading taxonomy.

Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer's disease dementia.

The development of tau-specific positron emission tomography (PET) tracers allows imaging in vivo the regional load of tau pathology in Alzheimer's disease (AD) and other tauopathies. Eighteen patients with baseline investigations enroled in a 17-month follow-up study, including 16 with AD (10 had mild cognitive impairment and a positive amyloid PET scan, that is, prodromal AD, and six had AD dementia) and two with corticobasal syndrome. All patients underwent PET scans with [18F]THK5317 (tau deposition) and [18F]FDG (glucose metabolism) at baseline and follow-up, neuropsychological assessment at baseline and follow-up and a scan with [11C]PIB (amyloid-ß deposition) at baseline only. At a group level, patients with AD (prodromal or dementia) showed unchanged [18F]THK5317 retention over time, in contrast to significant decreases in [18F]FDG uptake in temporoparietal areas. The pattern of changes in [18F]THK5317 retention was heterogeneous across all patients, with qualitative differences both between the two AD groups (prodromal and dementia) and among individual patients. High [18F]THK5317 retention was significantly associated over time with low episodic memory encoding scores, while low [18F]FDG uptake was significantly associated over time with both low global cognition and episodic memory encoding scores. Both patients with corticobasal syndrome had a negative [11C]PIB scan, high [18F]THK5317 retention with a different regional distribution from that in AD, and a homogeneous pattern of increased [18F]THK5317 retention in the basal ganglia over time. These findings highlight the heterogeneous propagation of tau pathology among patients with symptomatic AD, in contrast to the homogeneous changes seen in glucose metabolism, which better tracked clinical progression.

Bioinspired Nanofeatured Substrates: Suitable Environment for Bone Regeneration.

Bone mimicking coatings provide a complex microenvironment in which material, through its inherent properties (such as nanostructure and composition), affects the commitment of stem cells into bone lineage and the production of bone tissue regulating factors required for bone healing and regeneration. Herein, a bioactive mineral/biopolymer composite made of calcium phosphate/chitosan and hyaluronic acid (CaP-CHI-HA) was elaborated using a versatile simultaneous spray coating of interacting species. The resulting CaP-CHI-HA coating was mainly constituted of bioactive, carbonated and crystalline hydroxyapatite with 277 ± 98 nm of roughness, 1 µm of thickness, and 2.3 ± 1 GPa of stiffness. After five days of culture, CaP-CHI-HA suggested a synergistic effect of intrinsic biophysical features and biopolymers on stem cell mechanobiology and nuclear organization, leading to the expression of an early osteoblast-like phenotype and the production of bone tissue regulating factors such as osteoprotegerin and vascular endothelial growth factor. More interestingly, amalgamation with biopolymers conferred to the mineral a bacterial antiadhesive property. These significant data shed light on the potential regenerative application of CaP-CHI-HA bioinspired coating in providing a suitable environment for stem cell bone regeneration and an ideal strategy to prevent implant-associated infections.

General practitioners adherence to recommendations from geriatric assessments made during teleconsultations for the elderly living in nursing homes.

OBJECTIVES: To determine the factors associated with general practitioners adherence to recommendations from geriatric assessments made during teleconsultations for the elderly living in nursing homes. STUDY DESIGN: Prospective cohort study in three nursing homes in Vendee, France, with access to teleconsultations from Challans Hospital. Teleconsultations with geriatric assessment for which recommendations were made by a geriatrician (n=69). MAIN OUTCOME MEASUREMENTS: Participants were separated into two groups based on the evidence of general practitioners adherence to recommendations 30 days after teleconsultation. Their adherence has been defined by the application by themselves supporting the elderly of prescription or organization of all recommendations made by the geriatrician during the teleconsultation. The type of recommendations was pharmacological and non-pharmacological treatments, and expert medical advice. The recorded data included the main reason of teleconsultation's request, age, sex, dementia diagnosis, multimorbidities scale, body mass index, Activities of Daily Living Scale, 4-items Geriatric Depression Scale, existence of a fall, and the Neuropsychiatric Inventory. Logistic regressions were performed to examine the factors associated with general practitioners adherence to recommendations from the geriatric assessment. RESULTS: General practitioners adherence to recommendations was made for 58 teleconsultations (86.3%). A fully adjusted logistic regression showed that general practitioners adherence to recommendations was associated with risk of depressive syndrome (OR=8.00, P=0.040) and expert medical advice's recommendations (OR=17.97, P=0.040). CONCLUSIONS: General practitioners adherence to recommendations from the geriatric assessment made during teleconsultations for elderly living in nursing homes is associated with the risk of depressive syndrome's existence and the expert medical advice recommendations.

Comparison between PET template-based method and MRI-based method for cortical quantification of florbetapir (AV-45) uptake in vivo.

PURPOSE: Florbetapir (AV-45) has been shown to be a reliable tool for assessing in vivo amyloid load in patients with Alzheimer's disease from the early stages. However, nonspecific white matter binding has been reported in healthy subjects as well as in patients with Alzheimer's disease. To avoid this issue, cortical quantification might increase the reliability of AV-45 PET analyses. In this study, we compared two quantification methods for AV-45 binding, a classical method relying on PET template registration (route 1), and a MRI-based method (route 2) for cortical quantification. METHODS: We recruited 22 patients at the prodromal stage of Alzheimer's disease and 17 matched controls. AV-45 binding was assessed using both methods, and target-to-cerebellum mean global standard uptake values (SUVr) were obtained for each of them, together with SUVr in specific regions of interest. Quantification using the two routes was compared between the clinical groups (intragroup comparison), and between groups for each route (intergroup comparison). Discriminant analysis was performed. RESULTS: In the intragroup comparison, differences in uptake values were observed between route 1 and route 2 in both groups. In the intergroup comparison, AV-45 uptake was higher in patients than controls in all regions of interest using both methods, but the effect size of this difference was larger using route 2. In the discriminant analysis, route 2 showed a higher specificity (94.1 % versus 70.6 %), despite a lower sensitivity (77.3 % versus 86.4 %), and D-prime values were higher for route 2. CONCLUSION: These findings suggest that, although both quantification methods enabled patients at early stages of Alzheimer's disease to be well discriminated from controls, PET template-based quantification seems adequate for clinical use, while the MRI-based cortical quantification method led to greater intergroup differences and may be more suitable for use in current clinical research.

Object recognition in congruent and incongruent natural scenes: a life-span study.

Efficient processing of our complex visual environment is essential and many daily visual tasks rely on accurate and fast object recognition. It is therefore important to evaluate how object recognition performance evolves during the course of adulthood. Surprisingly, this ability has not yet been investigated in the aged population, although several neuroimaging studies have reported altered activity in high-level visual ventral regions when elderly subjects process natural stimuli. In the present study, color photographs of various objects embedded in contextual scenes were used to assess object categorization performance in 97 participants aged from 20 to 91. Objects were either animals or pieces of furniture, embedded in either congruent or incongruent contexts. In every age group, subjects showed reduced categorization performance, both in terms of accuracy and speed, when objects were seen in incongruent vs. congruent contexts. In subjects over 60 years old, object categorization was greatly slowed down when compared to young and middle-aged subjects. Moreover, subjects over 75 years old evidenced a significant decrease in categorization accuracy when objects were seen in incongruent contexts. This indicates that incongruence of the scene may be particularly disturbing in late adulthood, therefore impairing object recognition. Our results suggest that daily visual processing of complex natural environments may be less efficient with age, which might impact performance in everyday visual tasks.

[Discovery and follow-up of a lead-poisoning outbreak in a shantytown of Le Port, Reunion Island]. / Investigation et gestion d'un foyer de saturnisme infantile dans un quartier de la commune du Port, Île de la Réunion.

BACKGROUND: A national survey conducted in 2008-2009 by the French Institute for Public Health Surveillance for detection of lead impact in childhood identified a high blood lead level in a young boy living in the town of "Le Port", Reunion Island. Previously, cases of lead-poisoning on the island had been exceptional; only a dozen cases were reported in the 1980s in adults, related to the use of lead-containing instruments for food preparations. METHODS: The family of the index case was invited to participate in screening tests and an environmental investigation was conducted using a standardized questionnaire. Screening was then broadened to the neighborhood of the index case and samples of soil outside the home and in the immediate vicinity were taken. The environmental survey was then extended with soil samples taken from the entire geographical area. Information was then provided to local inhabitants (87 families and 287 people) in order to encourage lead blood testing for all children under six years and all pregnant women living in the area. RESULTS: The index case lived in the neighborhood of "The Oasis", a shantytown of Le Port. The results of soil analysis revealed heterogeneous pollution of superficial soils by lead throughout the area of the shantytown, the highest level recorded (5200mg/kg) reached more than 300 times the background level of the natural soils of the island. The screening identified 76 cases of childhood lead-poisoning (blood lead level greater or equal to 100µg/L) among 148 samples (51%). All cases of blood poisoning involved children under the age of 15 years. The median age of children with a positive test was 5.6 years; the median blood lead level was 196µg/L [102-392µg/L]. CONCLUSION: The main hypothesis to explain the contamination of the soil in the area of the shantytown is the presence of waste deposits (car batteries) and diffuse activities of metal recovery. The authorities managed to remove all the families from the environmental exposure to lead by rapidly ensuring rehousing outside the contaminated area.

[Early diagnosis of Alzheimer's disease]. / Diagnostic précoce de la maladie d'Alzheimer.

INTRODUCTION: Diagnosis of Alzheimer's disease (AD) remains difficult to establish, and can only be considered as certain thanks to anatomopathological evidence, or genetic mutations. Current diagnostic criteria rely on innovative imaging and biological tools, in order to detect pathological cues from very early stages, and with best sensibility and sensitivity. STATE OF ART: Advances in neuro-imaging enabled the development of different tools to help establishing the diagnosis, such as cerebral atrophy assessment on magnetic resonance imaging (MRI), and cerebral metabolism study on positron emission tomography (PET). Besides, the increasing use of in vivo biological markers, combined to clinical criteria, enables to discriminate patients from healthy controls at even earlier stages. This includes studies on tau and beta-amyloid proteins concentrations in the cerebrosinal fluid, and amyloid-specific radioligands uptake. Familial forms of Alzheimer represent a great model for studying early or even pre-symptomatic AD, as genetic analyses constitute a diagnosis of certainty, even though they usually evolve earlier and faster. PERSPECTIVES, CONCLUSION: Diagnostic tools are more and more numerous and performant. According to patients' clinical heterogeneity, it appears essential to associate different method to investigate, in order to make a diagnosis as early and as reliable as possible.

[Acute axonal polyneuropathy and Gougerot-Sjögren syndrome]. / Polyneuropathie axonale aiguë et syndrome de Gougerot-Sjögren.

INTRODUCTION: Gougerot-Sjögren syndrome (GSS) is an autoimmune disease characterized by a lymphocytic infiltration and destruction of saliva and lachrymal glands. About 20% of patients develop a neurological involvement. CASE REPORT: A 29-year-old woman was admitted with a dysautonomic and sensorial neuropathy. Clinical manifestations (dry syndrome and positive Schirmer's test), blood (anti-SSA and anti-SSB antibodies) and histological (chronic sialadenitis) tests linked this neuropathy to a primary GSS. The characteristics of this case were acute onset (within a few days), severe clinical presentation (continued confinement to bed and malnutrition) and non-responsiveness to all treatments (intravenous immunoglobulins, corticosteroids, plasmapheresis, rituximab). CONCLUSION: This case illustrates various clinical signs and inconstant responsiveness to treatment of neuropathy associated with primary GSS.

Long-term endometrial and breast safety of a specific, standardized soy extract.

OBJECTIVE: To assess the effects of an oral soy isoflavone extract (Phytosoya) on endometrium and breast in postmenopausal women treated for 3 years. METHODS: A total of 395 postmenopausal women were included in this international prospective, open-label study. The number of patients who completed the 3-year study was 197. The women were treated for 3 years with a specific, standardized soy isoflavone extract (total 70 mg/day). Endometrial biopsy, transvaginal ultrasonography and mammography were performed before and after 3 years of treatment. RESULTS: No case of hyperplasia/cancer was diagnosed among the 192 interpretable biopsies at 3 years. Only one case of simple hyperplasia was diagnosed among 197 post-baseline interpretable biopsies. The endometrial safety of this extract has been demonstrated (point estimate 0.5%). There was no statistically significant change in endometrial thickness after 3 years (98.4% inactive or atrophic and 0.3% proliferative endometrium at 1 year). Mammography results showed no notable change from baseline. No patient in any set developed an ACR classification of 4 or 5 after 3 years of treatment. The global safety was rated as either 'excellent' or 'good' by 99.1% of investigators and 99.0% of patients after 3 years of treatment. The adverse events were as follows: eight patients had metrorrhagia and seven patients had at least one breast adverse event: three patients had 'breast pain', two patients reported 'breast tenderness' and two patients had 'hypertrophic breast' (most of them were possibly treatment-related). CONCLUSIONS: As no case of hyperplasia was diagnosed among the 301 interpretable biopsies at 1 year and there was only one case of simple hyperplasia in the 197 post-baseline biopsies at 3 years, the endometrial safety of this extract has been demonstrated. Furthermore, as demonstrated by the lack of change in endometrial thickness associated with the histologic results, we suggest that this extract does not exert a mitogenic effect on the endometrium. These results suggest that daily administration of 70 mg of a specific, standardized isoflavone extract for 3 years could be a safe treatment for both endometrium and breast.

Estrous cycle effects on behavior of C57BL/6J and BALB/cByJ female mice: implications for phenotyping strategies.

Systematic behavioral phenotyping of genetically modified mice is a powerful method with which to identify the molecular factors implicated in control of animal behavior, with potential relevance for research into neuropsychiatric disorders. A number of such disorders display sex differences, yet the use of female mice in phenotyping strategies has been a rare practice because of the potential variability related to the estrous cycle. We have now investigated the behavioral effects of the estrous cycle in a battery of behavioral tests in C57BL/6J and BALB/cByJ inbred strains of mice. Whereas the performance of BALB/cByJ female mice varied significantly depending on the phase of the estrous cycle in the open field, tail flick and tail suspension tests, the behavior of C57BL/6J females, with the exception of the tail suspension performance, remained stable across all four phases of the estrous cycle in all of the tests including open field, rotarod, startle reflex and pre-pulse inhibition, tail flick and hot plate. We also found that irrespective of the estrous cycle, the behavior of C57BL/6J females was different from that of BALB/cByJ groups in all of the behavioral paradigms. Such strain differences were previously reported in male comparisons, suggesting that the same inter-group differences can be revealed by studying female or male mice. In addition, strain differences were evident even for behaviors that were susceptible to estrous cycle modulations, although their detection might necessitate the constitution of large experimental groups.

Auditory and visual prepulse inhibition in mice: parametric analysis and strain comparisons.

Prepulse inhibition (PPI) is a multimodal phenomenon where the prepulse and the startling stimulus can be presented in either the same or the different sensory modalities. The aim of the present study was to characterize intramodal and cross-modal PPI in mice. We first examined the effects of varying prepulse intensity and prepulse duration on auditory and visual PPI in three inbred mouse strains C57BL/6J, 129S2 and BALB/cByJ mice. Increasing the intensity (5-15 dB above the background) and the duration (1-25 milliseconds) of the acoustic prepulse increased auditory PPI, and maximum level of inhibition was reached with each prepulse intensity at specific prepulse duration (between 5 and 15 milliseconds). Varying the intensity (30-300 lux) and the duration (1-25 milliseconds) of the light flashes had similar impact on visual PPI level (optimal durations between 1 and 10 milliseconds). There were also marked strain differences in PPI performances, with 129S2 and BALB/cByJ mice displaying the highest and the lowest scores of auditory PPI, respectively. In contrast, opposite strain ranking was obtained for visual PPI. The temporal expression of PPI was then studied in the same mouse strains using a wide range of interstimulus intervals (2-2000 milliseconds between the prepulse offset and the pulse onset). The time-course of the auditory and the visual PPI were relatively comparable (bell-shaped curve) with optimal lead-times between 10 and 100 milliseconds, but the shape of the temporal function varied between the mouse strains depending on the prepulse modality. These findings demonstrate that PPI has many physiological and genetic determinants that vary greatly across temporal and intensity domain, as well as stimulus modality.

Induction of the skin endogenous protective mitochondrial MnSOD by Vitreoscilla filiformis extract.

Vitreoscilla filiformis (Vf), a filamentous bacteria living in fresh water is thought to contribute to the observed beneficial effects of Spa water on skin. An active fraction obtained from a Vf biomass was evaluated for its ability to modulate mRNA expression in cultured skin cells. cDNA array analysis was conducted first using a customized membrane including 1176 selected and fully identified genes involved in skin physiology and homeostasis then the newly developed full genome U133 plus 2.0 GeneChip from Affymetrix. The mitochondrial protective manganese superoxide dismutase (MnSOD/SOD-2) was identified as a preferentially induced mRNA target in both normal human dermal fibroblasts and keratinocytes. Induction at the transcriptional level in both cell types was confirmed using quantitative real time/polymerase chain reaction and a kinetic analysis revealed a maximal increase in mRNA expression 20 h after stimulation with Vf extract (Vfe). Using immunofluorescent (fluorescent cell sorter) analysis, an induction of MnSOD protein in both normal human dermal skin fibroblasts (x1.6; P < 0.01) and epidermal keratinocytes (x1.4; P < 0.01) was confirmed. As MnSOD is a major inducible free-radical scavenger in skin, these results suggest that the Vfe could induce skin cells to produce their own endogenous protective defences in vivo against both exogenous environmental stressors such as UV irradiation or microflora as well as to combat endogenous sources of deleterious free radicals involved in skin ageing. Finally, in order to confirm the in vivo potential of this original extract in human, we evaluated its protective activity vs. placebo on the generation of sunburn cells in epidermis under UVB stress. As expected from in vitro profiling, Vfe was indeed found to significantly inhibit the appearance of sunburn cells in UVB-exposed areas, a signature of skin alteration which has been suggested to be linked to a defect in MnSOD protective activity. Altogether, those data suggest that the combination of a suitable protective UV filter together with this bioactive Vfe might improve skin protection through complementary pathways.

Macro- and microanatomical characterization of the cat brachial plexus.

The anatomy of the cat brachial plexus is poorly documented despite its importance for reparative surgery. The present work aims to study the anatomy of the brachial plexus of 20 European cats and to analyze the radicular constituents of 10 of them using histological techniques. The plexus radicular constitution is very homogeneous and is mainly composed of the ventral rami (also called ventral branches) arising from C6, C7, C8 and T1 spinal nerves. The fascicular and axonal structure is more variable. C8 is the ventral ramus that contains the largest number of axons (16,673 +/- 3,307), and is composed of 6.7 +/- 3.5 fascicles. The radial nerve is the peripheral nerve that contains the largest number of axons (11,245 +/- 2,217), and is composed of 7.3 +/- 3.8 fascicles. The number of nervous fibers does not differ proportionally to the weight of the cat, or between the right or the left side. Our data could help neurotization and entubulation repair after brachial plexus injury.

Nitric oxide prevents gamma-radiation-induced cell cycle arrest by impairing p53 function in MCF-7 cells.

We previously reported that nitric oxide (NO) released from S-nitrosoglutathione induces conformational change of the p53 tumor-suppressor protein that impairs its DNA-binding activity in vitro. We now demonstrate that MCF-7 cells preincubated in the presence of 0.5-1 mM S-nitrosoglutathione for 4 h before gamma-irradiation failed to arrest in the G1 phase of the cell cycle, whereas those gamma-irradiated without S-nitrosoglutathione exhibited a normal cell cycle arrest. The S-nitrosoglutathione-treated cells did not express the p53 target gene p21(waf-1) after gamma-irradiation, although p21(waf-1) was strongly expressed in cells irradiated in the absence of S-nitrosoglutathione. These results strongly suggest that NO impairs the function of p53 possibly via conformational change and/or amino acid modifications. On the other hand, cells incubated for 16 h in the presence of 1 mM S-nitrosoglutathione underwent apoptosis with accumulation of the pro-apoptotic protein Bax. This Bax accumulation, however, was shown to occur via a p53-independent pathway.