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Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, miserable, potentially severe, and often dose-limiting side effect of several first and second-line anti-cancer agents with little in the way of effective, acceptable treatment. Although mechanisms of damage differ, manual therapy (therapeutic massage) has effectively reduced symptoms and improved quality of life in patients with diabetic peripheral neuropathy.Methods: Here, we describe application of manual therapy (techniques of effleurage and petrissage) to the extremities in a patient with grade 2 CIPN subsequent to prior treatment with docetaxel and cisplatin for stage III esophageal adenocarcinoma. Superficial cutaneous temperature was monitored using infrared thermistry as proxy for microvascular blood flow.Results: By the end of the course of manual therapy without any change in medications, CIPN symptoms were greatly reduced to grade 1, with corresponding improvement in quality of life. Improvements in superficial temperature were observed in fingers and toes.Conclusions: Manual therapy was associated with almost complete resolution of the tingling and numbness and pain of CIPN in this patient. Concurrently increased superficial temperature suggests improvements in CIPN symptoms may have involved changes in blood circulation. To our knowledge, this is the first report of using manual therapy for amelioration of CIPN. [ABSTRACT FROM AUTHOR]

Authors report clinical outcomes of patients treated with robotic stereotactic body radiotherapy (SBRT) for primary, recurrent and metastatic lung lesions.

Although Plasmodium vivax is responsible for the majority of malaria infections outside Africa, little is known about its evolution and pathway to humans. Its closest genetic relative, P. vivax-like, was discovered in African great apes and is hypothesized to have given rise to P. vivax in humans. To unravel the evolutionary history and adaptation of P. vivax to different host environments, we generated using long- and short-read sequence technologies 2 new P. vivax-like reference genomes and 9 additional P. vivax-like genotypes. Analyses show that the genomes of P. vivax and P. vivax-like are highly similar and colinear within the core regions. Phylogenetic analyses clearly show that P. vivax-like parasites form a genetically distinct clade from P. vivax. Concerning the relative divergence dating, we show that the evolution of P. vivax in humans did not occur at the same time as the other agents of human malaria, thus suggesting that the transfer of Plasmodium parasites to humans happened several times independently over the history of the Homo genus. We further identify several key genes that exhibit signatures of positive selection exclusively in the human P. vivax parasites. Two of these genes have been identified to also be under positive selection in the other main human malaria agent, P. falciparum, thus suggesting their key role in the evolution of the ability of these parasites to infect humans or their anthropophilic vectors. Finally, we demonstrate that some gene families important for red blood cell (RBC) invasion (a key step of the life cycle of these parasites) have undergone lineage-specific evolution in the human parasite (e.g., reticulocyte-binding proteins [RBPs]).

Enteroviruses (EVs) belong to the family Picornaviridae and are responsible for mild to severe diseases in mammals including humans and non-human primates (NHP). Simian EVs were first discovered in the 1950s in the Old World Monkeys and recently in wild chimpanzee, gorilla and mandrill in Cameroon. In the present study, we screened by PCR EVs in 600 fecal samples of wild apes and monkeys that were collected at four sites in Gabon. A total of 32 samples were positive for EVs (25 from mandrills, 7 from chimpanzees, none from gorillas). The phylogenetic analysis of VP1 and VP2 genes showed that EVs identified in chimpanzees were members of two human EV species, EV-A and EV-B, and those identified in mandrills were members of the human species EV-B and the simian species EV-J. The identification of two novel enterovirus types, EV-B112 in a chimpanzee and EV-B113 in a mandrill, suggests these NHPs could be potential sources of new EV types. The identification of EV-B107 and EV90 that were previously found in humans indicates cross-species transfers. Also the identification of chimpanzee-derived EV110 in a mandrill demonstrated a wide host range of this EV. Further research of EVs in NHPs would help understanding emergence of new types or variants, and evaluating the real risk of cross-species transmission for humans as well for NHPs populations.

Avoiding biological contaminants is a well-known manifestation of the adaptive system of disgust. In theory, animals evolved with such a system to prevent pathogen and parasite infection. Bodily products are human-universal disgust elicitors, but whether they also elicit avoidance behaviour in non-human primates has yet to be tested. Here, we report experimental evidence that potential exposure to biological contaminants (faeces, blood, semen), as perceived via multiple sensory modalities (visual, olfactory, tactile), might influence feeding decisions in chimpanzees (Pan troglodytes troglodytes)—our closest phylogenetic relatives. Although somewhat mixed, our results do show increased latencies to feed, tendencies to maintain greater distances from contaminants and/or outright refusals to consume food in test versus control conditions. Overall, these findings are consistent with the parasite avoidance theory of disgust, although the presence of biological contaminants did not preclude feeding entirely. The avoidance behaviours observed hint at the origins of disgust in humans, and further comparative research is now needed.

Dans le cadre du respect des normes éthiques internationales, le Centre International de Recherches Médicales de Franceville (CIRMF) a décidé il y a plusieurs années d’améliorer les conditions de vie de ses grands singes, gorilles et chimpanzés, en les plaçant dans des sanctuaires au Gabon. Les gorilles ont déjà tous rejoint le Projet Gorille Fernan Vaz (Ogooué Maritime). Les chimpanzés iront dans un sanctuaire dans la région de Gamba (Ogooué Maritime). Une ONG de droit gabonais, indépendante du CIRMF, est en cours de création et les chimpanzés du CIRMF lui seront confiés. Cette ONG se chargera de toute la gestion du projet sur le long terme. L’impact d’un tel projet doit largement dépasser l’objectif de l’amélioration des conditions de vie des chimpanzés. Son développement doit se faire de manière transversale, c’est-à-dire qu’il doit permettre la mise en place d’activités annexes comme le tourisme de vision et l’agriculture dont la production servira à nourrir les chimpanzés, mais également à approvisionner les marchés locaux en fruits et légumes. Les communautés locales sont, en effet, d’autant plus réceptives aux exigences de conservation qu’elles peuvent bénéficier d’une partie des revenus tirés du tourisme et de l’agriculture et c’est donc ce modèle de gestion intégrée où la communauté prend part au projet qui nous donne un gage de succès et de pérennité. Le tourisme de vision s’intègre parfaitement dans cette région du Gabon connue sous le nom de Complexe d’Aires Protégées de Gamba (CAPG) puisqu’elle se situe entre deux parcs nationaux : le parc national de Loango, le joyau des parcs nationaux du Gabon et celui de Moukalaba Doudou, dont la richesse écosystémique présente également un intérêt touristique évident. Non loin de Gamba se situe également la lagune du Fernan Vaz et c’est cet ensemble qui permet d’inscrire notre futur projet dans un circuit touristique cohérent. L’impact du projet agricole sur l’environnement doit être minime et l’approche classique de l’agriculture locale qui consiste à défricher la forêt et brûler les terres pour cultiver doit être évitée. C’est pourquoi nous planifions de développer, en partenariat avec l’Institut Gabonais d’Appui au Développement (IGAD), un projet d’agroécologie de manière à optimiser et pérenniser l’utilisation des terres exploitées. Les défis à relever pour ce projet d’agroécologie sont doubles. Ils tiennent d’abord au fait que ce projet sera implanté dans une région majoritairement sablonneuse où les sols sont pauvres et où des connaissances spécifiques d’agronomie doivent permettre de limiter l’utilisation d’intrants phytosanitaires. D’autre part, la région de Gamba est fortement pourvue en éléphants. Il s’agira alors d’être capable d’éviter les destructions des plantations par ces pachydermes. Montrer qu’il est possible de gérer le conflit hommes/éléphants par la protection efficace des plantations avec des mesures novatrices et la mutualisation des moyens constituera une solution encourageante pour tous les paysans de la sous-région d’Afrique Centrale et un signal très fort pour le milieu de la conservation. En définitive, la valeur intrinsèque de ce projet réside non seulement dans l’amélioration des conditions de vie des chimpanzés du CIRMF, mais également dans la création d’emplois locaux, dans le renforcement de l’offre touristique, dans l’initiation d’un projet agricole dans une région jusque-là peu tournée vers la culture vivrière, et dans l’apport de solutions novatrices pour l’exploitation des terres et la gestion du conflit hommes/éléphants. Nous espérons que cette approche holistique entrainera une adhésion forte de la population locale dont le libre arbitre permettra certainement d’avoir une visibilité sur le long terme dans la gouvernance de ce projet.Je souhaite remercier l’ensemble des personnes qui ont contribué ou qui participent à ce projet et plus particulièrement Anaïs Herbert, Sébastien Koumba de l’Institut Gabonais d’Appui au Développement (IGAD), Debby Cox de Jane Goodall Institute (JGI), Pierre Brice Maganga de World Wide Fund (WWF), Lee Ann Rottman de Tampa’s Lowry Park Zoo, Angélique Todd et Dr Aurélie Flore Koumba Pambo de l’Agence Nationale des Parcs Nationaux (ANPN) et Laura Darby de Great Apes Survival Partnership (GRASP).

De par leur diversité communautaire (hommes, primates non humains (PNH), rongeurs), les conditions de contact et de promiscuité entre PNH et soigneurs, le Centre de Primatologie du CIRMF (CDP), le Parc de Bakoumba et le Projet Protection Gorille (PPG) au Gabon représentent une situation exceptionnelle pour l'étude de transmission inter espèces entre les PNH et l'homme. En réunissant ces conditions de contacts répétés entre hôtes de sensibilités différentes, ces sites constituent un modèle pour d'une part mieux comprendre les interactions entre les communautés d'agents infectieux, les communautés d'hôtes et le risque en termes de santé animale et humaine, et d'autre part, pour développer une approche pouvant être transposée à d'autres écosystèmes plus complexes. La principale question de recherche est d'identifier si les soigneurs et les PNH cohabitant dans les sanctuaires et aires de conservations échangent des agents infectieux. Si oui, quels sont, parmi nos modèles parasites, ceux qui sont les plus concernés par ces échanges et les plus impliqués en termes de risque pour la santé humaine et la conservation des espèces. En combinant des études épidémiologiques sur le terrain à la fois chez l'homme et l'animal, le séquençage et des analyses phylogénétiques ainsi que la modélisation statistique, notre travail abordera les questions suivantes sur différents agents infectieux (bactéries, virus, protozoaires) : (i) Quels sont les agents infectieux qui circulent dans les différentes espèces et quels sont leur prévalence respective et les facteurs de risque individuels dans les populations ? (ii) Existe-t-il des interactions entre les différents agents infectieux infectant un même hôte ? (iii) Les agents infectieux qui circulent dans la communauté sont-ils spécialistes d'une espèce hôte ou au contraire généralistes ? (iv) Enfin, cette cohabitation favorise-t-elle la transmission inter espèce ? Si oui, quels sont les facteurs écologiques et adaptatifs qui favorisent ces transmissions ?

The difficulty involved in following mandrills in the wild means that very little is known about social structure in this species. Most studies initially considered mandrill groups to be an aggregation of one-male/multifemale units, with males occupying central positions in a structure similar to those observed in the majority of baboon species. However, a recent study hypothesized that mandrills form stable groups with only two or three permanent males, and that females occupy more central positions than males within these groups. We used social network analysis methods to examine how a semi-free ranging group of 19 mandrills is structured. We recorded all dyads of individuals that were in contact as a measure of association. The betweenness and the eigenvector centrality for each individual were calculated and correlated to kinship, age and dominance. Finally, we performed a resilience analysis by simulating the removal of individuals displaying the highest betweenness and eigenvector centrality values. We found that related dyads were more frequently associated than unrelated dyads. Moreover, our results showed that the cumulative distribution of individual betweenness and eigenvector centrality followed a power function, which is characteristic of scale-free networks. This property showed that some group members, mostly females, occupied a highly central position. Finally, the resilience analysis showed that the removal of the two most central females split the network into small subgroups and increased the network diameter. Critically, this study confirms that females appear to occupy more central positions than males in mandrill groups. Consequently, these females appear to be crucial for group cohesion and probably play a pivotal role in this species.

BACKGROUND: Toxoplasma gondii is found worldwide, but distribution of its genotypes as well as clinical expression of human toxoplasmosis varies across the continents. Several studies in Europe, North America and South America argued for a role of genotypes in the clinical expression of human toxoplasmosis. Genetic data concerning T. gondii isolates from Africa are scarce and not sufficient to investigate the population structure, a fundamental analysis for a better understanding of distribution, circulation, and transmission. METHODOLOGY/PRINCIPAL FINDINGS: Seropositive animals originating from urban and rural areas in Gabon were analyzed for T. gondii isolation and genotyping. Sixty-eight isolates, including one mixed infection (69 strains), were obtained by bioassay in mice. Genotyping was performed using length polymorphism of 13 microsatellite markers located on 10 different chromosomes. Results were analyzed in terms of population structure by Bayesian statistical modeling, Neighbor-joining trees reconstruction based on genetic distances, F(ST) and linkage disequilibrium. A moderate genetic diversity was detected. Three haplogroups and one single genotype clustered 27 genotypes. The majority of strains belonged to one haplogroup corresponding to the worldwide Type III. The remaining strains were distributed into two haplogroups (Africa 1 and 3) and one single genotype. Mouse virulence at isolation was significantly different between haplogroups. Africa 1 haplogroup was the most virulent. CONCLUSION: Africa 1 and 3 haplogroups were proposed as being new major haplogroups of T. gondii circulating in Africa. A possible link with strains circulating in South and Central America is discussed. Analysis of population structure demonstrated a local spread within a rural area and strain circulation between the main cities of the country. This circulation, favored by human activity could lead to genetic exchanges. For the first time, key epidemiological questions were addressed for the West African T. gondii population, using the high discriminatory power of microsatellite markers, thus creating a basis for further epidemiological and clinical investigations.

The majority of microplastics (MPs) found in the environment originate from plastic fragmentation occurring in the environment and are influenced by environmental factors such as UV irradiation and biotic interactions. However, the effects of river drying on plastic fragmentation remain unknown, despite the global prevalence of watercourses experiencing flow intermittence. This study investigates, through laboratory experiments, the coupled effects of drying duration and UV irradiation on PVC film fragmentation induced by artificial mechanical abrasion. This study shows that PVC film fragmentation increases with drying duration through an increase in the abundance and size of formed MPs as well as mass loss from the initial plastic item, with significant differences for drying durations >50% of the experiment duration. The average abundance of formed MPs in treatments exposed to severe drying duration was almost two times higher than in treatments nonexposed to drying. Based on these results, we developed as a proof of concept an Intermittence-Based Plastic Fragmentation Index that may provide insights into plastic fragmentation occurring in river catchments experiencing large hydrological variability. The present study suggests that flow intermittence occurring in rivers and streams can lead to increasing plastic fragmentation, unraveling new insights into plastic pollution in freshwater systems.

Alzheimer's Disease (AD) biomarker measurement is key to aid in the diagnosis and prognosis of the disease. In the research setting, participant recruitment and retention and optimization of sample use, is one of the main challenges that observational studies face. Thus, obtaining accurate established biomarker measurements for stratification and maximizing use of the precious samples is key. Accurate technologies are currently available for established biomarkers, mainly immunoassays and immunoprecipitation liquid chromatography-mass spectrometry (IP-MS), and some of them are already being used in clinical settings. Although some immunoassays- and IP-MS based platforms provide multiplexing for several different coding proteins there is not a current platform that can measure all the stablished and emerging biomarkers in one run. The NUcleic acid Linked Immuno-Sandwich Assay (NULISA ™ ) is a mid-throughput platform with antibody-based measurements with a sequencing output that requires 15μL of sample volume to measure more than 100 analytes, including those typically assayed for AD. Here we benchmarked and compared the AD-relevant biomarkers including in the NULISA against validated assays, in both CSF and plasma. Overall, we have found that CSF measures of Aß42/40, NfL, GFAP, and p-tau217 are highly correlated and have similar predictive performance when measured by immunoassay, mass-spectrometry or NULISA. In plasma, p-tau217 shows a performance similar to that reported with other technologies when predicting amyloidosis. Other established and exploratory biomarkers (total tau, p-tau181, NRGN, YKL40, sTREM2, VILIP1 among other) show a wide range of correlation values depending on the fluid and the platform. Our results indicate that the multiplexed immunoassay platform produces reliable results for established biomarkers in CSF that are useful in research settings, with the advantage of measuring additional novel biomarkers using minimal sample volume., Competing Interests: RB has received funding from NIH, Alzheimer’s Association, Biogen, AbbVie, Bristol Meyer Squibbs, Novartis, and EISAI. RB has equity and is on the scientific advisory board of C2N Diagnostics. SES has served on advisory boards and consulted on biomarker testing for Eisai, and she has received speaker fees from Eli Lilly. DMH has equity and is on the scientific advisory board of C2N Diagnostics. DMH is on the scientific advisory board of Denali, Genentech, and Cajal Neuroscience and consults for Asteroid. TLSB received research funding from Siemens and is an investigator on clinical trials and studies of AD with partial support from Eisai, Lilly, Roche, Janssen, and Biogen. TLSB is a consultant to Eisai. CC has received research support from: GSK and Eisai. CC is a member of the advisory board of Circular Genomics and owns stocks. CC is a member of the advisory board of ADmit. The other authors report no conflict of interest. The funders of the study had no role in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

Objective: To determine the influence of screw direction on complications following transcondylar screw placement for the treatment of canine humeral intracondylar fissures (HIFs)., Study Design: Equivalence, parallel group, randomized clinical trial., Sample Population: Fifty-two client owned dogs (73 elbows)., Methods: Transcondylar screw placement was randomized to either a medial or lateral approach. The primary outcome was the incidence of postoperative complications., Results: There were 37 cases in the lateral approach group and 36 cases in the medial approach group. There was a significantly greater proportion of postoperative complications following placement of transcondylar screws from a lateral to medial direction (p = .001). There were seven cases with complications (19%) in the medial approach group versus 23 cases with complications (62%) in the lateral approach group. The majority of complications were seromas (n = 13) and surgical site infections (n = 16) with 4 complications requiring further surgery. Implant area moment of inertia (AMI), normalized to bodyweight, was lower in dogs with a major complication (p = .037)., Conclusion: Transcondylar screws placed from lateral to medial for canine HIFs had a greater proportion of postoperative complications in this randomized clinical trial design. Implants with a lower AMI, relative to bodyweight, were more likely to lead to major complications., Clinical Significance: We recommend placing transcondylar screws from medial to lateral for canine HIFs to reduce the risk of postoperative complications. Relatively small diameter implants had an increased risk of major complications., (© 2023 American College of Veterinary Surgeons.)

Introduction: Current approaches for treating sporadic Alzheimer's disease (sAD) focus on removal of amyloid beta 1-42 (Aβ 1-42 ) or phosphorylated tau, but additional strategies are needed to reduce neuropathology at earlier stages prior to neuronal damage. Longstanding data show that calcium dysregulation is a key etiological factor in sAD, and the cortical neurons most vulnerable to tau pathology show magnified calcium signaling, for example in dorsolateral prefrontal cortex (dlPFC) and entorhinal cortex (ERC). In primate dlPFC and ERC, type 3 metabotropic glutamate receptors (mGluR3s) are predominately post-synaptic, on spines, where they regulate cAMP-calcium signaling, a process eroded by inflammatory glutamate carboxypeptidase II (GCPII) actions. The current study tested whether enhancing mGluR3 regulation of calcium via chronic inhibition of GCPII would reduce tau hyperphosphorylation in aged macaques with naturally-occurring tau pathology., Methods: Aged rhesus macaques were treated daily with the GCPII inhibitor, 2-MPPA (2-3-mercaptopropyl-penanedioic acid (2-MPPA)),Aged rhesus macaques were treated daily with the GCPII inhibitor, 2-MPPA (2-3-mercaptopropyl-penanedioic acid (2-MPPA))., Results: Aged macaques that received 2-MPPA had significantly lower pT217Tau levels in dlPFC and ERC, and had lowered plasma pT217Tau levels from baseline. pT217Tau levels correlated significantly with GCPII activity in dlPFC. Both 2-MPPA- and vehicle-treated monkeys showed cognitive improvement; 2-MPPA had no apparent side effects. Exploratory CSF analyses indicated reduced pS202Tau with 2-MPPA administration, confirmed in dlPFC samples., Discussion: These data provide proof-of-concept support that GCPII inhibition can reduce tau hyperphosphorylation in the primate cortices most vulnerable in sAD. GCPII inhibition may be particularly helpful in reducing the risk of sAD caused by inflammation. These data in nonhuman primates should encourage future research on this promising mechanism., Highlights: Inflammation is a key driver of sporadic Alzheimer's disease.GCPII inflammatory signaling in brain decreases mGluR3 regulation of calcium.Chronic inhibition of GCPII inflammatory signaling reduced pT217Tau in aged monkeys.GCPII inhibition is a novel strategy to help prevent tau pathology at early stages., Competing Interests: The authors have no financial conflicts of interest to disclose., (© 2023 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: Assess the feasibility of a randomized controlled trial (RCT) exploring the use of medical imaging as a therapeutic education (TPE) intervention in external radiation therapy., Materials and Methods: Experimental feasibility trial of "RCT" type carried out in a single-center, between November 2019 and March 2020, following adult patients treated by thoracic radiotherapy. In addition to the information usually given, the experimental group benefited from an intervention consisting in the visualization of their own medical images using the open-source software "Stone of Orthanc"., Results: Forty-nine patients were recruited with a refusal rate of 8.16% (4/49). 20 patients were withdrawn from the study for health reasons (COVID), 10 for medical reasons. All the remaining 15 participants completed the process. Although not significant, the experimental group showed a median gain in the perception of knowledge compared to the control group (+ 1.9 (1.6 - 2.2)) vs (+ 1.4 (1.4 - 1.8)), as well as a decrease in scores related to anxiety (- 3.0 (-4.5 - (-2.0)) vs - 1.0 (-5.0 - 0.0)) and emotional distress ((- 5.0 (- 7.5 - (- 3.5)) vs (- 2.0 (- 5.0 - (- 1.0)) A significant reduction (p=0.043) is observed for the depression score ((- 2.0 (-3.0 - (-1.5)) vs (0.0 (0.0 - 0.0))., Conclusion: This study demonstrates the feasibility of the project, with promising preliminary results. Some adaptations in order to conduct a larger-scale RCT are highlighted., (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: Hyperphosphorylation of tau leads to conformational changes that destabilize microtubules and hinder axonal transport in Alzheimer's disease (AD). However, it remains unknown whether white matter (WM) decline due to AD is associated with specific Tau phosphorylation site(s)., Methods: In autosomal dominant AD (ADAD) mutation carriers (MC) and non-carriers (NC) we compared cerebrospinal fluid (CSF) phosphorylation at tau sites (pT217, pT181, pS202, and pT205) and total tau with WM measures, as derived from diffusion tensor imaging (DTI), and cognition. A WM composite metric, derived from a principal component analysis, was used to identify spatial decline seen in ADAD., Results: The WM composite explained over 70% of the variance in MC. WM regions that strongly contributed to the spatial topography were located in callosal and cingulate regions. Loss of integrity within the WM composite was strongly associated with AD progression in MC as defined by the estimated years to onset (EYO) and cognitive decline. A linear regression demonstrated that amyloid, gray matter atrophy and phosphorylation at CSF tau site pT205 each uniquely explained a reduction in the WM composite within MC that was independent of vascular changes (white matter hyperintensities), and age. Hyperphosphorylation of CSF tau at other sites and total tau did not significantly predict WM composite loss., Conclusions: We identified a site-specific relationship between CSF phosphorylated tau and WM decline within MC. The presence of both amyloid deposition and Tau phosphorylation at pT205 were associated with WM composite loss. These findings highlight a primary AD-specific mechanism for WM dysfunction that is tightly coupled to symptom manifestation and cognitive decline., (Copyright © 2022. Published by Elsevier Inc.)

Early discussion on palliative care with patients with advanced, progressive or terminal disease is difficult regardless patient's life expectancy. In Belgium, a Royal Decree sets the criteria to identify patients with palliative needs. For that purpose, the Palliative Care Indicators Tool (PICT) is proposed. This 3-step identification tool designed for physicians begins with the so-called surprise question, «Would you be surprised if your patient died in the next 6 to 12 months?». The second and third steps examine the fragility and incurability criteria, respectively. The surprise question intends to encourage the clinician to trust his/her intuition and to promote a reflection on patient's needs. The PICT facilitates communication between caregivers. Also, it makes possible early thinking about advanced care planning. Hence, it allows patients to receive palliative care in due time. In this paper, after reviewing the background of the surprise question, we shall examine the benefits and limitations of the surprise question.

Progress of medical knowledge pushed the limits of medicine. This raises major ethical issues. The Belgian lawmaker, concerned to ensure the observance of Human Rights, attempted to regulate some of these issues. It remains essential to listen to the patient and to respect his/her will. Likewise, defining therapeutic goals based on patient's values and priorities is crucial until the end of patient's life.

Background: This practical guideline is based on the current scientific ESPEN guidelines on nutrition in cancer patients., Methods: ESPEN guidelines have been shortened and transformed into flow charts for easier use in clinical practice. The practical guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with cancer., Results: A total of 43 recommendations are presented with short commentaries for the nutritional and metabolic management of patients with neoplastic diseases. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in cancer patients., Conclusion: This practical guideline gives guidance to health care providers involved in the management of cancer patients to offer optimal nutritional care., Competing Interests: Conflicts of interest No conflict of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of this study is to describe the presentation, surgical management and perioperative outcome of cats with acetabular fractures., Methods: Case records and radiographs of cats with acetabular fractures were reviewed from presentation to the end of follow-up. Surgical technique, complications, radiographic reduction and the presence of neurological deficits were recorded., Results: Sixteen cats with 17 acetabular fractures met the inclusion criteria. All fractures were associated with concurrent orthopaedic injuries. All cats were either moderately or severely lame on presentation. Five fractures were stabilised using screws, wire, pins and polymethylmethacrylate, nine were repaired using a straight dynamic compression plate and three were repaired using a locking plate. Two of seven cats that were neurologically normal prior to surgery developed transient neuropraxia following surgery. There were three major complications and no minor complications. At the end of follow-up 3/16 cats had full function, whereas 13/16 had acceptable function., Conclusions and Relevance: All cats undergoing surgical stabilisation of acetabular fractures returned to full or acceptable function by the end of the follow-up period and there was a low number of intraoperative and short-term complications. Neurological deficits were common preoperatively, but the majority of these deficits had resolved by follow-up.

Matthew, a category 4 hurricane, struck Haiti on October 4, 2016, causing widespread flooding and damage to buildings and crops, and resulted in many deaths. The damage caused by Matthew raised concerns of increased cholera transmission particularly in Sud and Grand'Anse departments, regions which were hit most heavily by the storm. To evaluate the change in reported cholera cases following Hurricane Matthew on reported cholera cases, we used interrupted time series regression models of daily reported cholera cases, controlling for the impact of both rainfall, following a 4-week lag, and seasonality, from 2013 through 2016. Our results indicate a significant increase in reported cholera cases after Matthew, suggesting that the storm resulted in an immediate surge in suspect cases, and a decline in reported cholera cases in the 46-day post-storm period, after controlling for rainfall and seasonality. Regression models stratified by the department indicate that the impact of the hurricane was regional, with larger surges in the two most highly storm-affected departments: Sud and Grand'Anse. These models were able to provide input to the Ministry of Health in Haiti on the national and regional impact of Hurricane Matthew and, with further development, could provide the flexibility of use in other emergency situations. This article highlights the need for continued cholera prevention and control efforts, particularly in the wake of natural disasters such as hurricanes, and the continued need for intensive cholera surveillance nationally.

Haiti's health system has faced many challenges over the years, with competing health priorities in the context of chronic financial and human resource limitations. As a result, the existing notifiable disease surveillance system was unable to provide the most basic epidemiologic data for public health decision-making and action. In the wake of the January 2010 earthquake, the Haitian Ministry of Public Health and Population collaborated with the U.S. Centers for Disease Control and Prevention, the Pan American Health Organization, and other local and international partners to implement a functional national surveillance system. More than 7 years later, it is important to take the opportunity to reflect on progress made on surveillance and response in Haiti, including disease detection, reporting, outbreak investigation, and response. The national epidemiologic surveillance network that started with 51 sites in 2010 has been expanded to 357 sites as of December 2015. Disease outbreaks identified via the surveillance system, or other surveillance approaches, are investigated by epidemiologists trained by the Ministry of Health's Field Epidemiology Training Program. Other related surveillance modules have been developed on the same model and electronic platform, allowing the country to document the impact of interventions, track progress, and monitor health problems. Sustainability remains the greatest challenge since most of the funding for surveillance come from external sources.

Cancers are among the leading causes of morbidity and mortality worldwide, and the number of new cases is expected to rise significantly over the next decades. At the same time, all types of cancer treatment, such as surgery, radiation therapy, and pharmacological therapies are improving in sophistication, precision and in the power to target specific characteristics of individual cancers. Thus, while many cancers may still not be cured they may be converted to chronic diseases. All of these treatments, however, are impeded or precluded by the frequent development of malnutrition and metabolic derangements in cancer patients, induced by the tumor or by its treatment. These evidence-based guidelines were developed to translate current best evidence and expert opinion into recommendations for multi-disciplinary teams responsible for identification, prevention, and treatment of reversible elements of malnutrition in adult cancer patients. The guidelines were commissioned and financially supported by ESPEN and by the European Partnership for Action Against Cancer (EPAAC), an EU level initiative. Members of the guideline group were selected by ESPEN to include a range of professions and fields of expertise. We searched for meta-analyses, systematic reviews and comparative studies based on clinical questions according to the PICO format. The evidence was evaluated and merged to develop clinical recommendations using the GRADE method. Due to the deficits in the available evidence, relevant still open questions were listed and should be addressed by future studies. Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. They may be driven by inadequate food intake, decreased physical activity and catabolic metabolic derangements. To screen for, prevent, assess in detail, monitor and treat malnutrition standard operating procedures, responsibilities and a quality control process should be established at each institution involved in treating cancer patients. All cancer patients should be screened regularly for the risk or the presence of malnutrition. In all patients - with the exception of end of life care - energy and substrate requirements should be met by offering in a step-wise manner nutritional interventions from counseling to parenteral nutrition. However, benefits and risks of nutritional interventions have to be balanced with special consideration in patients with advanced disease. Nutritional care should always be accompanied by exercise training. To counter malnutrition in patients with advanced cancer there are few pharmacological agents and pharmaconutrients with only limited effects. Cancer survivors should engage in regular physical activity and adopt a prudent diet., (Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd.. All rights reserved.)

Alzheimer's disease (AD) is the most common form of dementia in humans, and a major public health concern with 35 million of patients worldwide. Cerebrospinal fluid (CSF) biomarkers being early diagnostic indicators of AD, it is essential to use the most efficient analytical methods to detect and quantify them accurately. These biomarkers, and more specifically amyloid-β (Aβ) peptides, are measured in routine clinical practice using immunoassays. However, there are several limits to this immunodetection in terms of specificity and multiplexing of the multiple isoforms of the Aβ peptides. To overcome these issues, the quantification of these analytes by mass spectrometry (MS) represents an interesting alternative, and several assays have been described over the past years. This article reviews the different Aβ peptides quantitative MS-based approaches published so far, compares their pre-analytical phase, and the different quantitative strategies implemented that might be suitable for clinical applications.

Tau protein concentration in cerebrospinal fluid (CSF) is currently used as a sensitive and specific biomarker for Alzheimer's disease. Its detection currently relies on ELISA but the perspective of using mass spectrometry (MS) to detect its different proteoforms represents an interesting alternative. This is however an analytical challenge because of its low concentration in the CSF, a biological fluid collected in small volume by lumbar puncture, and with a high structural heterogeneity. To overcome these issues, instead of using immunocapture as previously done, we rather relied on an original two steps pre-fractionation technique of CSF: perchloric acid (PCA) followed by micro solid phase extraction (μSPE). We could then measure seven tau trypsic peptides by Multiple Reaction Monitoring (MRM) on a triple quadrupole mass spectrometer. Quantification was performed using isotopically labeled (15)N- recombinant tau protein as internal standard and validated using CSF pools with low, medium, or high tau concentrations (HTCs). Repeatability, intermediate precision, linearity, limit of quantification (LOQ), and recovery were calculated for the different peptides. This new MRM assay, which allowed for the first time CSF tau protein quantification without immunocapture, has important potential application to follow tau metabolism in both diagnostic and therapeutic research.

Purpose: The assessment of nutritional problems is vital to support patients undergoing radiotherapy. Poor nutritional status may occur as a result of preexisting problems, older age, the cancer itself, or treatment side effects. Malnutrition impairs the outcome of the disease and affects patients. This prospective study aimed at developing two simple tools to screen malnutrition before radiotherapy and to assess, prior to treatment, the risk of malnutrition after radiotherapy., Methods: Forty-seven lung cancer patients treated with curative intent were evaluated before radiotherapy and after completion of the treatment. To assess patient's malnutrition, two well-known screening tools (PG-SGA and NRS-2002) were used, complemented by patient-specific characteristics, yielding a 59-item questionnaire. Malnutrition status was defined using Thoresen's criteria. The two screening tools derived by multivariate analyses were validated by comparing anthropometric, biological, and nutritional variables between patients at risk of malnutrition and those who are not., Results: Malnutrition detection prior to radiotherapy was based on the equation "MDS = 5.88 - 0.20 × BMI + 0.05 × (percent weight loss over past 6 months)," while malnutrition prediction after radiotherapy was given by "MPS = 3.67 + 0.98 × (age ≥70) - 0.12 × BMI + 1.20 × edema." Agreement between observed and estimated outcomes was quite high for the two scores (kappa coefficient 0.80 and 0.85, respectively)., Conclusions: The two assessment tools were found parsimonious and easy to use. Further studies are needed to validate them in larger lung cancer groups and in other cancer populations.

Glioblastoma is a primary brain tumor that occurs most often in elderly patients. Despite improved management, the prognosis of this cancer remains poor. This review describes the multidisciplinary management of the patient with glioblastoma. It includes surgery, radiation therapy and chemotherapy.

Objectives: to evaluate in vitro the strength of different compositions of beta-tricalcium phosphate (β-TCP) wedges in comparison with titanium foam and cages. To study the response to cyclic loading of the strongest β-TCP wedge, titanium foam and titanium cage., Methods: Compression test: Twenty-five tibiae were prepared for tibial tuberosity advancement using the modified Maquet technique. Five groups were defined depending on the material used to maintain the tibial tuberosity: Group 1=titanium cage; Group 2=wedges of porous titanium foam with 50% porosity (OrthoFoam®); Group 3=blocks of biphasic synthetic bone (60% hydroxyapatite [HAP] and 40% β-TCP, porosity 80%); Group 4=blocks of biphasic synthetic bone (60% HAP and 40% β-TCP, porosity 70%) and Group 5=blocks of biphasic synthetic bone (65% HAP and 35% β-TCP, porosity 60%). Loads to failure were calculated for each implant. Cyclic study: Five additional tibiaes of group 1, 2 and 5 were fatigue tested from 100 to 500 N at a rate of 4 Hz for 200,000 cycles or until failure., Results: Compression test: For the five groups, the mean load at failure was 1895 N, 1917 N, 178 N, 562 N and 1370 N respectively. Cyclical study: All samples in the three groups tested withstood 200,000 cycles without failure., Clinical Significance: The ideal implant to maintain tibial tuberosity advancement after the modified Maquet technique would be absorbable and allow osteoconduction and osteoinduction. As such, β-TCP wedges have many advantages and our study shows that they can withstand loads in the patellar tendon up to 500 N over 200,000 cycles in vitro and deserve more investigation.

Non-small cell lung cancer (NSCLC) is common. Approximately one out of every five patients with NSCLC has locally advanced disease that is surgically unresectable. For these patients, the disease has a poor prognosis characterized by a high rate of local disease progression or recurrence despite attempts at chemo- and radiation therapy. The purpose of this review is to describe the heterogeneity of this group of patients, to clarify the terms of the combination of chemotherapy and radiotherapy and to clarify the efficacy of modern radiotherapy techniques to increase local control.

Nowadays, the cancer patient has access to a highly technical, more and more targeted and increasingly individualized medicine. And the human being in that matter ? Numerous tools have been developed to help physicians and caregivers to reconcile contemporary medicine and the rights of the patient. Among these are multidisciplinary oncology meetings and treatment guidelines published by national and international scientific societies. The patients care must be cross-disciplinary and evidence-based. This shared decision-making process should at the end be in accordance with the wishes of the patient. This approach should allow him/her to maintain autonomy and be the main actor in the decision-making process.

Background: Since the beginning of the cholera epidemic in Haiti, attack rates have varied drastically with alternating peak and lull phases, which were partly associated with the fluctuating dry, rainy and cyclonic seasons. According to a study conducted in 2012, the toxigenic V. cholerae O1 strain responsible for the outbreak did not settle at a significant level in the Haitian aquatic environment. Therefore, we hypothesize that some areas of lingering cholera transmission during the dry season could play an important role in the re-emergence of outbreaks during the rainy season. Our objective was therefore to describe the dynamics of cholera and assess the fight against the disease during the dry season., Methods: A field study was conducted from February 19 to March 29, 2013. After identifying the affected communes by analyzing the national cholera database, we visited corresponding health facilities to identify patient origins. We then conducted a field assessment of these foci to confirm the presence of cholera, assess factors associated with transmission and examine the activities implemented to control the epidemic since the beginning of the current dry season., Results: We found that the great majority of Haitian communes (109/140) presented no sign of cholera transmission in February and March 2013. Suspected cases were concentrated in a small number of urban and rural areas, almost all of which were located in the northern half of the country and often in inland locales. In these areas, community health activities appeared insufficient and were often inappropriately targeted. Out of 49 analyzed foci, only 10 had benefited from at least one intervention involving the distribution of water treatment products together with an awareness campaign since December 2012., Conclusion: Cholera continues to affect Haiti as observed in early 2013; however, activities implemented to interrupt cholera transmission appear insufficient and poorly suited. This deficiency in the fight against cholera, especially at a period when transmission is weak, may explain the persistence of cholera even in the absence of significant aquatic reservoirs in Haiti.

Objectives: This in vitro study evaluated three modified techniques of tibial tuberosity advancement (TTA). Loads to failure were calculated for each technique., Methods: A 9 mm TTA procedure was performed in the tibiae of dogs weighing between 32 and 38 kg. In group 1 (n = 12), the distal part of the tibial crest was left attached to the tibia by the cranial cortex, and a figure-of-eight wire was added for stabilisation. In group 2 (n = 12), the tibial crest was left attached but no additional device was used for stabilisation. In group 3 (n = 12), the tibial crest was completely separated from the tibia and fixed by a figure-of-eight wire so that, in this group, only the wire opposed avulsion of the tibial crest. Unidirectional axial force was applied via the patella to determine the maximal load to failure of the model., Results: There was no significant difference between group 1 and group 2. These two groups both had a significantly stronger construct than that of group 3., Clinical Significance: We described modifications to the TTA procedure without plate fixation that warrant clinical investigation. When the crest is broken during its advancement, the tension sustained by the repair is significantly weaker from a biomechanical point of view and the use of such a repair clinically is not recommended by the authors.

There is a never ending discussion on the need for radiotherapy after conservative breast surgery for DCIS (Ductal Carcinoma In Situ). It is true that adjuvant irradiation does not yield any difference in overall survival in the published randomized trials. However, postoperative irradiation after breast conserving surgery (BCS) has been shown to significantly reduce ipsilateral breast event (IBE), whether this is a DCIS recurrence or a recurrence with an invasive component. The real question is to define if there is a subgroup of patients for whom radiotherapy can be withheld without taking any significant local risk. Nowadays, we are not able to define such a subgroup as the possible selection criteria to avoid radiotherapy have never been validated within a well designed prospective randomized trial. Therefore, we think that there is no available evidence to avoid radiotherapy after BCS for DCIS. However, radiotherapy is not indicated after mastectomy.

Unlabelled: From 1972 to 1985, 260 cases of anal canal epidermoid carcinoma were irradiated. Eighteen cases treated for palliation were excluded from the study; 242 (93%) were treated with curative intent. The sex ratio was 1/5.5; mean age was 66 years., Histology: 60.3% were well differentiated epidermoid carcinoma; 31.0% moderately differentiated and 8.7%, cloacogenic cases. Staging: T1: 11.5%; T2: 16.1%; T3a: 17%; T3b: 33.5%; and T4: 21.9%. Abnormal inguinal nodes were present in 15.3% of cases. Crude overall survival (Kaplan-Meier) for the 242 cases is 86.4% at 1 year, 63.9% at 3 years, 51.2% at 5 years, and 30.8% at 10 years. Radiation therapy was the sole treatment for 193 cases. No chemotherapy was given. Patients were irradiated by external beam. They received a first course of X rays (mostly 18 MV, some 6 MV) 40 to 45 Gy (box technique) over 4 to 5 weeks in the pelvis. Age and size of tumor were considered when deciding on the target volume. After a rest period of 4 to 6 weeks, a second course of 15 to 20 Gy in 2 weeks was given through a perineal field by electron-beam of suitable energy. The mean total dose was 60.56 Gy and median was 62.5 Gy; the mean overall treatment duration was 85.3 days (median 82 days) and the mean Time Dose Factor including decay factor was 98.96. In this group, 5-year determinate survival was: T1-T2, 84.5%; T3a, 74.8%; T3b, 64.9%; T4, 58.9%. In 147/193 patients (76.2%) local control was achieved. The overall anal conservation rate was 62.6%. In 106 cases (55%), the anus had maintained normal function. The 5-year survival rate by N was 73.3% in the absence of inguinal nodes (169 cases) and 36.1% if such nodes were present. There was no significant difference in survival rate according to histological type. In the second group, receiving radiation therapy plus surgery, 33/49 cases (T3b-T4) were irradiated before surgery (median dose 40.5 Gy). Post operative radiation therapy was administered in 16 cases (T3b-T4) (median dose 49.6 Gy). The 5-year determinate survival is 53.2% for T3b and 79% for T4. According to the log-rank test, there was no significant difference between survival with radiation therapy alone and radiation therapy plus surgery. Multivariate analysis of the whole group indicated that T stage is the only predictive variable.(ABSTRACT TRUNCATED AT 400 WORDS)