A cross-sectional study of ageing at the mouse neuromuscular junction and effects of an experimental therapeutic approach for dynapenia.

Despite prior efforts to understand and target dynapenia (age-induced loss of muscle strength), this condition remains a major challenge that reduces the quality of life in the aged population. We have focused on the neuromuscular junction (NMJ) where changes in structure and function have rarely been systematically studied as a dynamic and progressive process. Our cross-sectional study found neurotransmission at the male mouse NMJ to be biphasic, displaying an early increase followed by a later decrease, and this phenotype was associated with structural changes to the NMJ. A cross-sectional characterization showed that age-induced alterations fell into four age groups: young adult (3-6 months), adult (7-18 months), early aged (19-24 months), and later aged (25-30 months). We then utilized a small molecule therapeutic candidate, GV-58, applied acutely during the later aged stage to combat age-induced reductions in transmitter release by increasing calcium influx during an action potential, which resulted in a significant increase in transmitter release. This comprehensive study of neuromuscular ageing at the NMJ will enable future research to target critical time points for therapeutic intervention. KEY POINTS: Age-induced frailty and falls are the leading causes of injury-related death and are caused by an age-induced loss of muscle strength due to a combination of neurological and muscular changes. A cross-sectional approach was used to study age-induced changes to the neuromuscular junction in a mouse model, and physiological changes that were biphasic over the ageing time course were found. Changes in physiology at the neuromuscular junction were correlated with alterations in neuromuscular junction morphology. An acutely applied positive allosteric gating modifier of presynaptic voltage-gated calcium channels was tested as a candidate therapeutic strategy that could increase transmitter release at aged neuromuscular junctions. These results provide a detailed time course of age-induced changes at the neuromuscular junction in a mouse model and test a candidate therapeutic strategy for weakness.

Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6+B helper T cells in systemic lupus erythematosus.

Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4+CCR6+IL-7R+T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6+B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6+T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4+CCR6+T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4+CCR6+IL-7R+T cells were associated with the presence of pathogenic anti-dsDNA (double-stranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6+T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.

Successful Transplantation of Lungs From an Uncontrolled Donor After Circulatory Death Preserved In Situ by Alveolar Recruitment Maneuvers and Assessed by Ex Vivo Lung Perfusion.

We developed a protocol to procure lungs from uncontrolled donors after circulatory determination of death (NCT02061462). Subjects with cardiovascular collapse, treated on scene by a resuscitation team and transferred to the emergency room, are considered potential donors once declared dead. Exclusion criteria include unwitnessed collapse, no-flow period of >15 min and low flow >60 min. After death, lung preservation with recruitment maneuvers, continuous positive airway pressure, and protective mechanical ventilation is applied to the donor. After procurement, ex vivo lung perfusion (EVLP) is performed. From November 2014, 10 subjects were considered potential donors; one of these underwent the full process of procurement, EVLP, and transplantation. The donor was a 46-year-old male who died because of thoracic aortic dissection. Lungs were procured 4 h and 48 min after death, and deemed suitable for transplantation after EVLP. Lungs were then offered to a rapidly deteriorating recipient with cystic fibrosis (lung allocation score [LAS] 46) who consented to the transplant in this experimental setting. Six months after transplantation, the recipient is in good condition (forced expiratory volume in 1 s 85%) with no signs of rejection. This protocol allowed procurement of lungs from an uncontrolled donor after circulatory determination of death following an extended period of warm ischemia.

Particulate matter phagocytosis induces tissue factor in differentiating macrophages.

Airborne exposure to particulate matter with diameter < 10 mcM (PM10) has been linked to an increased risk of thromboembolic events, but the mechanisms are not completely understood. The aim of this study was to evaluate the effect of PM10 phagocytosis on the release of procoagulant molecules in human differentiating macrophages, and that of PM10 inhalation in an experimental model in rats. Human monocytes were separated from the peripheral blood by the lymphoprep method, differentiated in vitro and treated with standard PM10 or vehicle. Sprague-Dawley rats were instilled intratracheally with PM10 or vehicle alone. The outcome was expression of proinflammatory genes and of tissue factor (TF). In human differentiating macrophages, PM10 exposure upregulated inflammatory genes, but most consistently induced TF mRNA and protein levels, but not TF protein inhibitor, resulting in increased TF membrane expression and a procoagulant phenotype. Differentiation towards the anti-inflammatory M2 phenotype inhibited PM10 -mediated TF expression. TF induction required phagocytosis of PM10 , whereas phagocytosis of inert particles was less effective. PM10 phagocytosis was associated with a gene expression profile consistent with intracellular retention of iron, inducing oxidative stress. Both PM10 and iron activated the stress kinases ERK1/2 pathway, involved in the induction of TF expression. In rats, alveolar exposure to PM10 was associated with pulmonary recruitment of inflammatory cells and resulted in local, but not systemic, induction of TF expression, which was sufficient to increase circulating TF levels. In conclusion, TF induction by differentiating lung macrophages, activated following phagocytosis, contributes to the increased risk of thromboembolic complications associated with PM10 exposure.

MicroRNAs in myocardial ischemia: identifying new targets and tools for treating heart disease. New frontiers for miR-medicine.

MicroRNAs (miRNAs) are natural, single-stranded, small RNA molecules which subtly control gene expression. Several studies indicate that specific miRNAs can regulate heart function both in development and disease. Despite prevention programs and new therapeutic agents, cardiovascular disease remains the main cause of death in developed countries. The elevated number of heart failure episodes is mostly due to myocardial infarction (MI). An increasing number of studies have been carried out reporting changes in miRNAs gene expression and exploring their role in MI and heart failure. In this review, we furnish a critical analysis of where the frontier of knowledge has arrived in the fields of basic and translational research on miRNAs in cardiac ischemia. We first summarize the basal information on miRNA biology and regulation, especially concentrating on the feedback loops which control cardiac-enriched miRNAs. A focus on the role of miRNAs in the pathogenesis of myocardial ischemia and in the attenuation of injury is presented. Particular attention is given to cardiomyocyte death (apoptosis and necrosis), fibrosis, neovascularization, and heart failure. Then, we address the potential of miR-diagnosis (miRNAs as disease biomarkers) and miR-drugs (miRNAs as therapeutic targets) for cardiac ischemia and heart failure. Finally, we evaluate the use of miRNAs in the emerging field of regenerative medicine.

Brain-wide human oscillatory local field potential activity during visual working memory.

Oscillatory activity in the local field potential (LFP) is thought to be a marker of cognitive processes. To understand how it differentiates tasks and brain areas in humans, we recorded LFPs in 15 adults with intracranial depth electrodes, as they performed visual-spatial and shape working memory tasks. Stimulus appearance produced widespread, broad-band activation, including in occipital, parietal, temporal, insular, and prefrontal cortex, and the amygdala and hippocampus. Occipital cortex was characterized by most elevated power in the high-gamma (100-150 Hz) range during the visual stimulus presentation. The most consistent feature of the delay period was a systematic pattern of modulation in the beta frequency (16-40 Hz), which included a decrease in power of variable timing across areas, and rebound during the delay period. These results reveal the widespread nature of oscillatory activity across a broad brain network and region-specific signatures of oscillatory processes associated with visual working memory.

Recombinant AgB8/1 ELISA test vs. commercially available IgG ELISA test in the diagnosis of cystic echinococcosis.

The diagnosis and clinical management of cystic echinococcosis (CE) rely on imaging and serology, the latter still having a complementary role as its accuracy in assessing cyst viability is unsatisfactory. We used an experimental IgG ELISA test based on the recombinant antigen rEgAgB8/1 cloned from Echinococcus granulosus to differentiate active from inactive/cured CE infection, comparing its performance to that of a commercially available ELISA test used routinely in our hospital laboratory. Both tests were performed on sera from 88 patients with hepatic echinococcal cysts, grouped according to cyst stage based on ultrasonographical morphology, and on 17 patients surgically treated for echinococcosis and 18 patients with nonparasitic hepatic cysts included as controls. Tests' performances did not differ significantly, but the overall concordance between tests drastically dropped when groups were analysed separately. Further longitudinal studies should evaluate whether these discrepancies reflect the different ability of either test to predict the evolution of cysts over time. Although the recombinant-AgB8/1-based ELISA test seems to have no clinical advantage over the commercially available ELISA test in the assessment of hepatic CE cyst viability, the easiness of production and reproducibility of high-quality recombinant antigens makes rEgAgB8/1 a valid candidate for use in CE ELISA diagnostic tests.

Brain-wide human oscillatory LFP activity during visual working memory.

Oscillatory activity is thought to be a marker of cognitive processes, although its role and distribution across the brain during working memory has been a matter of debate. To understand how oscillatory activity differentiates tasks and brain areas in humans, we recorded local field potentials (LFPs) in 12 adults as they performed visual-spatial and shape-matching memory tasks. Tasks were designed to engage working memory processes at a range of delay intervals between stimulus delivery and response initiation. LFPs were recorded using intracranial depth electrodes implanted to localize seizures for management of intractable epilepsy. Task-related LFP power analyses revealed an extensive network of cortical regions that were activated during the presentation of visual stimuli and during their maintenance in working memory, including occipital, parietal, temporal, insular, and prefrontal cortical areas, and subcortical structures including the amygdala and hippocampus. Across most brain areas, the appearance of a stimulus produced broadband power increase, while gamma power was evident during the delay interval of the working memory task. Notable differences between areas included that occipital cortex was characterized by elevated power in the high gamma (100-150 Hz) range during the 500 ms of visual stimulus presentation, which was less pronounced or absent in other areas. A decrease in power centered in beta frequency (16-40 Hz) was also observed after the stimulus presentation, whose magnitude differed across areas. These results reveal the interplay of oscillatory activity across a broad network, and region-specific signatures of oscillatory processes associated with visual working memory.

A large outbreak of Opisthorchis felineus in Italy suggests that opisthorchiasis develops as a febrile eosinophilic syndrome with cholestasis rather than a hepatitis-like syndrome.

We describe the greatest Italian human acute opisthorchiasis outbreak acquired from eating raw tenches. Out of 52 people with suspected opisthorchiasis, 45 resulted in being infected. The most frequent symptoms and laboratory findings were fever, abdominal pain and eosinophilia. Seven tri-phasic computed tomography (CT) scans were done, showing multiple hypodense nodules with hyper-enhancement in the arterial phase. All patients took one day of praziquantel 25 mg/kg TID without failures. Reported symptoms suggested a febrile eosinophilic syndrome with cholestasis rather than a hepatitis-like syndrome. It seems common to find hepatic imaging alterations during acute opisthorchiasis: CT scan could be the most suitable imaging examination. Even if stool test remains the diagnostic gold standard, we found earlier positivity with the serum antibody test. Without previous freezing, the consumption of raw freshwater fish should be avoided.

Evidence of Air Trapping During Ex Vivo Lung Perfusion: A Swine Experimental Lung Imaging and Mechanics Study.

Ex vivo lung perfusion (EVLP) allows the ventilation and perfusion of lungs to evaluate their viability for transplantation. The aim of this study is to compare the mechanical, morphologic and functional properties of lungs during EVLP with values obtained in vivo to guide a safe mechanical ventilation strategy. Lungs from 5 healthy pigs were studied in vivo and during 4 hours of EVLP. Lung compliance, airway resistance, gas exchange, and hemodynamic parameters were collected at positive end-expiratory pressure (PEEP) of 5 cm H2O. Computed tomography was performed at PEEP 0, PEEP 5, and total lung capacity (TLC). Lung pressure-volume (PV) curves were performed from PEEP 0 to TLC. Lung compliance decreased during EVLP (53 ± 5 mL/cm H2O vs 29 ± 7 mL/cm H2O, P < .05), and the PV curve showed a lower inflection point. Gas content (528 ± 118 mL vs 892 ± 402 mL at PEEP 0) and airway resistance (25 ± 5 vs 44 ± 9 cmH2O/L∗s-1, P < .05) were higher during EVLP. Alveolar dead space (5% ± 2% vs 17% ± 6%, P < .05) and intrapulmonary shunt (9% ± 2% vs 28% ± 13%, P < .05) increased ex vivo compared to in vivo, while the partial pressure of oxygen to inspired oxygen fraction ratio (PO2/FiO2) did not differ (468 ± 52 mm Hg vs 536 ± 14 mm Hg). In conclusion, during EVLP lungs show signs of air trapping and bronchoconstriction, resulting in low compliance and increased alveolar dead space. Intrapulmonary shunt is high despite oxygenation levels acceptable for transplantation.

Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats.

Several studies indicate that adult stem cells may improve the recovery from acute tissue injury. It has been suggested that they may contribute to tissue regeneration by the release of paracrine factors promoting proliferation of tissue resident cells. However, the factors involved remain unknown. In the present study we found that microvesicles (MVs) derived from human liver stem cells (HLSC) induced in vitro proliferation and apoptosis resistance of human and rat hepatocytes. These effects required internalization of MVs in the hepatocytes by an alpha(4)-integrin-dependent mechanism. However, MVs pre-treated with RNase, even if internalized, were unable to induce hepatocyte proliferation and apoptosis resistance, suggesting an RNA-dependent effect. Microarray analysis and quantitative RT-PCR demonstrated that MVs were shuttling a specific subset of cellular mRNA, such as mRNA associated in the control of transcription, translation, proliferation and apoptosis. When administered in vivo, MVs accelerated the morphological and functional recovery of liver in a model of 70% hepatectomy in rats. This effect was associated with increase in hepatocyte proliferation and was abolished by RNase pre-treatment of MVs. Using human AGO2, as a reporter gene present in MVs, we found the expression of human AGO2 mRNA and protein in the liver of hepatectomized rats treated with MVs. These data suggested a translation of the MV shuttled mRNA into hepatocytes of treated rats. In conclusion, these results suggest that MVs derived from HLSC may activate a proliferative program in remnant hepatocytes after hepatectomy by a horizontal transfer of specific mRNA subsets.

Interleukin (IL)-6 gene expression in the central nervous system is necessary for fever response to lipopolysaccharide or IL-1 beta: a study on IL-6-deficient mice.

Interleukin (IL)-6, IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) are considered to act as endogenous pyrogens. Because of the complex pattern of cross-inductions between these cytokines, the relative role of the central and peripheral production of these cytokines in eliciting the fever response has not yet been clarified. The purpose of this study was to determine the role of IL-6 in the fever response by making use of mice carrying a null mutation in the IL-6 gene. The intraperitoneal injections of lipopolysaccharide (LPS) (50 micrograms/kg) and recombinant murine (rm) IL-1 beta (10 micrograms/kg), respectively, failed to evoke fever response in IL-6-deficient mice, whereas the same doses of LPS and rmIL-1 beta caused fever response in wild-type mice. The fever response could be induced in the IL-6-deficient mice by intracerebroventricular injection of recombinant human (rh) IL-6 (500 ng/mouse), whereas intracerebroventricular injection of rmIL-1 beta (100 ng/mouse) failed to produce fever response in the IL-6-deficient mice. These results suggest that central IL-6 is a necessary component of the fever response to both endogenous (IL-1 beta) and exogenous (LPS) pyrogens in mice and that IL-6 acts downstream from both peripheral and central IL-1 beta.

Thymidine kinase and uridine-cytidine kinase from Entamoeba histolytica: cloning, characterization, and search for specific inhibitors.

Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Although anti-amoebic drugs such as metronidazole, emetine, chloroquine and nitazoxanide are generally effective, there is always potential for development of drug resistance. In order to find novel targets to control E. histolytica proliferation we cloned, expressed and purified thymidine kinase (Eh-TK) and uridine-cytidine kinase (Eh-UCK) from E. histolytica. Eh-TK phosphorylates thymidine with a Km of 0.27 microm, whereas Eh-UCK phosphorylates uridine and cytidine with Km of 0.74 and 0.22 mM, respectively. For both enzymes, ATP acts as specific phosphate donor. In order to find alternative treatments of E. histolytica infection we tested numerous nucleoside analogues and related compounds as inhibitors and/or substrates of Eh-TK and Eh-UCK, and active compounds against E. histolytica in cell culture. Our results indicate that inhibitors or alternative substrates of the enzymes, although partially reducing protozoan proliferation, are reversible and not likely to become drugs against E. histolytica infections.

Preliminary Experience With Hypothermic Oxygenated Machine Perfusion in an Italian Liver Transplant Center.

BACKGROUND: Machine perfusion is increasingly utilized in liver transplantation to face the detrimental consequences of the use of extended-criteria donors. Hypothermic oxygenated machine perfusion (HOPE) appears to be more protective relative to static cold storage. Conversely, normothermic machine perfusion (NMP) allows a better graft evaluation. We describe a pilot prospective study on machine perfusion in selected grafts. METHODS: HOPE was executed for all the grafts procured from donors after cardiac death (DCDs) and for livers from donors after brain death (DBDs) requiring prolonged preservation time. NMP was used when a more precise evaluation was needed. Both HOPE and NMP were performed through the portal vein and hepatic artery. RESULTS: From July 2016 to November 2017, we performed 7 HOPE procedures: 5 for DCD and 2 for DBD grafts. Two livers presented with macrovesicular steatosis >30% (1 DCD and 1 DBD). HOPE lasted 240 minutes (180-320 min) with a total ischemia time of 575 minutes (410-810 min). Six grafts were successfully transplanted. One DCD graft required additional evaluation using NMP. The graft was then discarded due to extensive hepatocellular necrosis. In the post-transplant course, acute and chronic renal failure were the main complications affecting 3 and 2 recipients, respectively. In our series, steatosis was the main risk factor for kidney injury. Patient and graft survival rate was 100% and no ischemic cholangiopathies were observed after 270 days (106-582 days). CONCLUSIONS: Our study confirms HOPE safety and efficacy for DCD and DBD grafts. These data are particularly significant for DCD management in the Italian setting where the mandatory 20-minute hands-off interval before death declaration further prolongs warm ischemia time.

Switch in the expression of mGlu1 and mGlu5 metabotropic glutamate receptors in the cerebellum of mice developing experimental autoimmune encephalomyelitis and in autoptic cerebellar samples from patients with multiple sclerosis.

Recent evidence suggests that changes in the expression of membrane receptors/ion channels in cerebellar Purkinje cells contribute to the onset of cerebellar motor symptoms in patients with multiple sclerosis (MS). We examined the expression of group-I metabotropic glutamate receptors (mGlu1 and mGlu5 receptors) in the cerebellum of mice developing experimental autoimmune encephalomyelitis (EAE) and in autoptic cerebellar samples of MS patients. EAE was induced in mice by immunization with the 35-55 fragment of MOG (myelin oligodendrocyte glycoprotein). EAE mice showed a progressive loss of mGlu1a receptors in the cerebellum, associated with an increased expression of mGlu5 receptors. These changes were restricted to Purkinje cells and their dendritic arborization, as shown by immunohistochemistry. A reduced expression of mGlu1a receptors in cerebellar Purkinje cells was also found in 7 of 9 MS patients. In addition, a light/moderate to very strong mGlu5 receptor immunoreactivity was detected in Purkinje cells of 8 MS patients, but was always absent in non-MS control patients. In EAE mice, an acute treatment with the mGlu1 receptor enhancer, 9H-xanthene-9-carboxylic acid (4-trifluoromethyl-oxazol-2-yl)-amide (RO0711401), significantly improved motor coordination, whereas treatment with the mGlu5 receptor antagonists, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and 6-methyl-2-(phenylazo)-3-pyridinol (SIB-1757), had no effect. We conclude that mGlu1 receptor enhancers improve motor symptoms associated with EAE and might be helpful as symptomatic drugs in patients with MS.

Functionalization of a poly(D,L)lactic acid surface with galactose to improve human keratinocyte behavior for artificial epidermis.

The production of artificial epidermis using reabsorbable polymeric matrices is one of possible goals; one of most used strategies in this field is the polymer substrate functionalitation using specific growth factors, in order to accelerate and improve keratinocyte adhesion and proliferation. In this study films of poly(D,L)lactide (P(D,L)LA), have been functionalized with various concentrations of galactose (GAL, 1-5-10%, w/v) conjugated with poly-L-lysine (PLL) using 1-etil-3-(3-diaminopropil) carbodiimide (EDC) as a coupling agent. GAL is a disaccharide present in the extracellular matrix (ECM) and it is bind by Galectines, a family of cell receptors whose activation regulate the cell-matrix interaction and cell growth and apoptosis. One of these receptors, Galectin-7 (Gal-7), is selectively expressed by human keratinocytes. Spontaneously immortalized human keratinocytes (HaCaT) that express high level of Gal-7 were allowed to adhere for 4 h in serum free condition on control P(D,L)LA (PLA), and on PLA-GAL and cell proliferation; the production of matrix metalloproteinases (MMP-2, MMP-9, and MMP-28), involved in cellular migration and tissue homeostasis have been analyzed after 24 h. The presence of GAL onto the polymer surface increased both cell adhesion, spreading and proliferation along with MMP-9 and MMP-28 production, suggesting that polymer functionalization using GAL could be an useful tool for the production of an artificial epidermis.

Properties of zinc releasing surfaces for clinical applications.

Two series of glasses of general formula (2-p) SiO2.1.1Na2O.CaO.pP2O5.xZnO (p=0.10, 0.20; x=0.0, 0.16, 0.35, and 0.78) have been analyzed for physico-chemical surface features before and after contact with simulated body fluid, morphological characteristics, and osteoblast-like cells behavior when cultured on them. The resulted good cell adhesion and growth, along with nonsignificant changes of the focal contacts, allow the authors to indicate HZ5 and HP5Z5 glasses as the ones having optimal ratio of Zn/P to maintain acceptable cell behavior, comparable to the bioactive glass (Bioglass) used as a control; results are also rationalized by means of three-dimensional models derived by molecular dynamic simulations, with decomposition and conversion rates optimized with respect to the parent Hench's Bioglass.

Fever: links with an ancient receptor.

Recent advances have provided evidence that prostaglandin E2 mediates the generation of fever in response to interleukin-1 or lipopolysaccharide and have reinforced the similarities of signaling downstream of these two pyrogens.

Genetic identification of neurons controlling a sexually dimorphic behaviour.

In the fruit fly Drosophila melanogaster, locomotor activity is sexually dimorphic: female flies constantly modulate their activity pattern whereas males show a steadier, stereotyped walking pace [1]. Here, we mapped the area of the brain controlling this behavioural dimorphism. Adult male Drosophila expressing a dominant feminising transgene in a small cluster of neurons in the pars intercerebralis exhibited a female-like pattern of locomotor activity. Genetic ablation of these neurons prevented the feminisation of the locomotor activity of transgenic males. The results suggest that this cluster of neurons modulates sex-specific activity, but is not involved in initiating fly locomotion. Nor does it control male courtship behaviour, because feminisation of courtship was not correlated with the feminisation of locomotor activity.

[Low incidence of hip fractures among the elderly in Guadeloupe: a spared Caribbean island population]. / Faible incidence des fractures de l'extrémité supérieure du fémur chez les patients de plus de 60 ans dans les îles de Guadeloupe.

PURPOSE OF THE STUDY: The purpose of this study was to determine the incidence of hip fractures among the elderly population in Guadeloupe, a French Caribbean archipelago with 440,000 inhabitants who present two rarely associated characteristics: 90% of the population is of African descent and life expectancy is similar to that of European populations. MATERIAL AND METHODS: Using the recent census report, we established that in 2002, 61,000 persons aged 60 years or more (27,000 men and 34,000 women) lived in Guadeloupe. All new cases of hip fracture among the population aged 60 years or more were recorded in 2002, 2003, and 2004 in the seven islands that compose Guadeloupe. For each case, we noted patient age and gender, type of hip fracture, and treatment administered. We excluded open and pathologic fractures. Overall and age-specific incidence of hip fractures were determined and compared with rates reported for other countries. RESULTS: Three hundred and two new cases of hip fracture were recorded from 2002 to 2005 in 211 women (70%) and 91 men (30%). The age of patients was 82 years on average (range 60-102). There were 134 neck fractures and 168 intertrochanteric fractures which were treated by osteosynthesis for 193 and arthroplasty for 108. Only one orthopedic treatment was noted. The incidence of hip fracture for people aged over 60 years was 16.9/10,000; for the population aged 65 years or more, it was 22.2/10,000. DISCUSSION: Osteoporotic fracture is a pandemic problem. Incidence is increasing worldwide. Our findings demonstrate that Guadeloupeans are spared from this pathology. This population offers an interesting field for research into the causal mechanisms of osteoporotic fractures and potential means of prevention or screening. CONCLUSION: The incidence of hip fractures among the elderly population in Guadeloupe is the lowest recorded in the world. We suggest that an environmental and genetic study in this spared population could provide interesting insight into the cause of hip fractures and appropriate means of prevention and screening among the elderly. The geographic and environmental characteristics of Guadeloupe make this area a unique zone of research and should enable new insight into the genetic and environmental factors involved in hip fractures.