Postnatal Unit Care and Safe Transition Home.

The United States has the highest maternal mortality rate among developed nations with 60% of deaths occurring during the postpartum period. This chapter presents the case study of Maya Howard. Maya represents of composite of qualitative research studies that reveals missteps, gaps, and oversights of Black mothers and birthing people during birth and the postpartum period. Using a Black feminist framework, the chapter offers solutions to improve postnatal unit care and the transition home, a critical step in improving care and saving lives for all mothers and birthing people.

Cholera in the Time of MINUSTAH: Experiences of Community Members Affected by Cholera in Haiti.

In 2010, Haiti experienced one of the deadliest cholera outbreaks of the 21st century. United Nations (UN) peacekeepers are widely believed to have introduced cholera, and the UN has formally apologized to Haitians and accepted responsibility. The current analysis examines how Haitian community members experienced the epidemic and documents their attitudes around accountability. Using SenseMaker, Haitian research assistants collected micronarratives surrounding 10 UN bases in Haiti. Seventy-seven cholera-focused micronarratives were selected for a qualitative thematic analysis. The five following major themes were identified: (1) Cholera cases and deaths; (2) Accessing care and services; (3) Protests and riots against the UN; (4) Compensation; and (5) Anti-colonialism. Findings highlight fear, frustration, anger, and the devastating impact that cholera had on families and communities, which was sometimes compounded by an inability to access life-saving medical care. Most participants believed that the UN should compensate cholera victims through direct financial assistance but there was significant misinformation about the UN's response. In conclusion, Haiti's cholera victims and their families deserve transparent communication and appropriate remedies from the UN. To rebuild trust in the UN and foreign aid, adequate remedies must be provided in consultation with victims.

"It's because We are 'Loose Girls' That's why We had Children with MINUSTAH Soldiers": A Qualitative Analysis of Stigma Experienced by Peacekeeper-Fathered Children and Their Mothers in Haiti.

Sexual abuse and exploitation (SEA) perpetrated by UN peacekeepers while on mission is a violation of human rights and undermines the goal of upholding human rights in countries that host peacekeeping missions. In addition to survivors, children fathered by peacekeepers are also victims of SEA that need protection. Stigma poses negative life course consequences for SEA survivors and their peacekeeper-fathered children. However, there is a considerable lack of empirical research concerning the stigma experiences of SEA survivors and their children in post-colonial contexts. The present study addresses this knowledge gap by drawing on The United Nations Stabilization Mission in Haiti as a case study to examine the lived experiences of stigma among SEA survivors and their resultant children. Using 18 qualitative semi-structured interviews conducted in 2017 with Haitian women raising peacekeeper-fathered children, we organized qualitative codes according to Link and Phelan's conceptual model of stigma. The stigmatization process was explored through the themes of labeling, stereotyping, separation, and status loss and discrimination, as described by Link and Phelan. In addition, we nuanced the lived experiences of stigma by discussing the buffering roles of familial acceptance, skin phenotype, and the Haitian context. The findings have implications for the UN. We advocate that stigma be recognized and acted upon as a fundamental protection concern for SEA survivors and their children. Accordingly, the UN has an obligation to provide stigma-related supports for victims and complainants as well as to facilitate long-term child support for the children left behind by peacekeepers.

Local induction of heat shock protein 70 (Hsp70) by proteasome inhibition confers chondroprotection during surgically induced osteoarthritis in the rat knee.

AIM: to determine if chondrocytic Hsp70 induction, via intra-articular injections of a reversible proteasome inhibitor (MG132), can protect articular chondrocytes from cellular death in experimental rat OA knee induced surgically by anterior cruciate ligament transection (ACLT). MATERIALS AND METHODS: ACLT was performed on D0. Histological lesions in naive (sham) controls (ACLT+saline) and treated (ACLT+MG132) rats were assessed according to Mankin's score. Repeated intra-articular injections (1.5 muM MG132 or saline were performed on D1, D7, D14 and D21. Rats were sacrificed sequentially on D7, D14 and D28. Detection of active caspase-3 and protein expression of Hsp70 was also determined on D7, D14 and D28 by immunostaining methods. RESULTS: MG132 significantly reduced OA lesions on D28 in the MG132 treated group. The expression of Hsp70 increased 11-fold in the MG132-treated group versus 2-3-fold in ACLT-control rats on D28. Concomitantly, cells expressing caspase-3 increased 4-fold in ACLT model and decreased 2-fold with MG132 treatment. CONCLUSIONS: Intra-articular induction of Hsp70 by MG132 could be a safe and interesting tool in chondrocytes protection from cellular injuries and thus might be a novel chondroprotective modality in rat OA.

In vivo rat knee cartilage volume measurement using quantitative high resolution MRI (7 T): feasibility and reproducibility.

OBJECTIVES: to assess reliability and reproducibility of quantitative MRI (7 T) in assessing rat femoro-tibial cartilage volume. METHODS: 5 healthy rat knees were scanned in vivo using a 7 T experimental imager. Sagittal high resolution 3D Gradient Echo with fat suppression sequences were performed with a dedicated home-made 2-elements array coil. 3D MRI sets were used to perform manual segmentation of the 3 cartilage compartments (femoral groove, medial and lateral tibial plateaus) by using a tactile screen. To evaluate inter- and intra-observer reproducibilities, the segmentation procedure was done blindly by two trained observers. One observer repeated the operation twice, with a period of 10 months between both readings. RESULTS: the mean duration to manually segment all the slices covering the cartilaginous joint was 4 hours. On the one hand, the inter-observer root mean square of coefficients of variation was 9.1%, 6.2%, 9.6% for the femoral, medial and lateral tibial compartments respectively. On the other hand, the intra-observer reproducibility was 2.1%, 3.2%, 2.5% for these cartilage compartments cited above. CONCLUSION: the image quality obtained at 7 Teslas with our dedicated coil allowed segmentation of the cartilage compartments with good reproducibility. This study demonstrated that MRI is a useful technology to provide a non-invasive and reliable assessment of rat knee cartilage volume.

Gene transfer with HSP 70 in rat chondrocytes confers cytoprotection in vitro and during experimental osteoarthritis.

Osteoarthritis is characterized by a gradual degradation of extracellular matrix, resulting from an excess of chondrocyte cell death, mainly due to an increase in apoptotis. Recent studies have revealed the essential role of HSP70 in protecting cells from stressful stimuli. Therefore, overexpressing HSP70 in chondrocytes could represent a good strategy to prevent extracellular matrix destruction. To this end, we have developed a vector carrying HSP70/GFP, and transduced chondrocytes were thus more resistant to cell death induced by mono-iodoacetate (MIA). To overcome the barrier-effect of matrix, we investigated the efficacy of plasmid delivery by electroporation (EP) in rat patellar cartilage. Two days after EP, 50% of patellar chondrocytes were HSP/GFP+. After 3 months, long-term expression of transgene was only depicted in the deep layer (20-30% positive cells). HSP70 overexpression inhibited the natural endochondral ossification in the deep layer, thus leading to a lesser decrease in chondrocyte distribution. Moreover, overexpression of HSP70, after a preventive EP transfer in rat patella, was sufficient to decrease the severity of osteoarthritis-induced lesions, as demonstrated histologically and biochemically. In conclusion, intracellular overexpression of HSP70, through EP delivery, could protect chondrocytes from cellular injuries and thus might be a novel chondroprotective modality in rat OA.

Direct gene transfer into rat articular cartilage by in vivo electroporation.

To establish a system for efficient direct in vivo gene targeting into rat joint, we have evaluated a strategy of gene transfer by means of the delivery of external electric pulses (EP) to the knee after intra-articular injection of a reporter gene (GFP). Rats were killed at various times after the electro gene-therapy to analyze GFP gene expression by immunohistochemistry. GFP staining was detected in the superficial, middle, and deep zones of the patellar cartilage at days 2 and 9, and thereafter only in the deep zone (months 1 and 2). The average percentage of GFP-positive cells was estimated at 30% both one and 2 months after the gene transfer. Moreover, no pathologic change caused by the EP was detected in the cartilage. The level and stability of the long-term GFP expression found in this study demonstrate the feasibility of a treatment of joint disorders (inflammatory or degenerative, focal or diffuse) using electric gene transfer.

Human Adenovirus Diversity in Water Samples Using a Next-Generation Amplicon Sequencing Approach.

This study aims to establish a straightforward and original workflow for high-throughput typing of human adenoviruses (HAdVs) in environmental samples. Occurrence of HAdVs in water is well documented worldwide, but data on diversity of HAdV types circulating in water are scarcely available. Here, the characterisation of viral particles was performed by determination of amplicon sequences using a next-generation sequencing (NGS) approach. Adenoviral DNA was either directly isolated from wastewater or river water concentrates or after a cell culture passage. Genome amplification targeted a hyper variable region of the hexon gene, allowing the discrimination of the 54 human adenoviral types described until now. After read generation on the benchtop MiSeq platform (Illumina), data were analysed using the Mothur software for identification of all HAdV species and types simultaneously present in a unique sample. NGS results showed a relatively wide HAdV diversity of up to six types in one sample, whereas Sanger sequencing always only retrieved the dominant one. Detected types included HAdV-1, HAdV-2, HAdV-3, HAdV-6, HAdV-12, HAdV-31, HAdV-40 and HAdV-41, HAdV-41 being the most abundant in tested samples. In addition, the influence of the cell line (A549 vs 293A cells) on the infectious HAdV typing results was clearly determined. The 293A appeared to be the most suitable cell line allowing the detection of a larger diversity of infectious HAdVs and reflecting a more realistic initial species distribution than using the A549 cells. These findings demonstrated the feasibility of amplicon sequencing NGS approach to identify viruses in complex environmental water samples.

In malignant cartilagenous tumors, immunohistochemical expression of procollagen PC1CP peptide is higher and that of PC2CP lower than in benign cartilaginous lesions.

Few studies on oncogenesis of chondrosarcoma (CS) are available in the literature. Our previously published experimental evidence suggests that while the C-propeptide of procollagen Iα1 (PC1CP), a component of cartilage, favors tumor progression, the C-propeptide of procollagen IIα1 (PC2CP) exerts antitumor properties. In this study, we analyzed expression of PC1CP and PC2CP by immunohistochemistry in a series of enchondromas and CS. Our retrospective series consisted of 88 cases, including 43 CSs, 34 enchondromas and 11 nontumor samples. Immunohistochemical staining for PC1CP and PC2CP was evaluated in the cytoplasm and in the extracellular matrix (ECM). Diffuse staining for PC1CP in ECM was significantly more frequent in tumor than in nontumor samples (32 % vs. 0 %; p = 0.03), and in CSs than in enchondromas (44 vs. 18 %; p = 0.02). ECM semiquantitative score was higher in tumors than in nontumor samples (p < 0.005) and higher in CSs than in enchondromas (p = 0.05). Staining for PC2CP in ECM was more frequently found in enchondromas than in CSs (59 vs. 33 %; p = 0.02). ECM semiquantitative score was higher in enchondromas than in CSs (p = 0.02). Diffuse staining for PC1CP in combination with absence of staining for PC2CP had 94 % specificity for CS but with a sensitivity of only 35 %. Expression of neither PC1CP nor PC2CP correlated with recurrence-free survival or occurrence of metastases. In conclusion, we show that the expression of PC1CP is higher and that of PC2CP lower in malignant cartilaginous tumors. These results support an oncogenic role of PC1CP and anti-oncogenic property of PC2CP in cartilaginous tumors.

Induction of heat shock protein 70 (Hsp70) by proteasome inhibitor MG 132 protects articular chondrocytes from cellular death in vitro and in vivo.

The aim of this work was to determine whether Hsp70 overexpression via proteasome inhibitor MG132 was able to protect chondrocytes towards mono-iodoacetate (MIA) cytotoxicity both in vitro and in vivo. In vitro, overexpression of Hsp70 via MG132 was significantly able to protect chondrocytes from MIA toxicity (MTT/LDH analyses). Hsp70 essentially mediated this chondroprotective effect as demonstrated by antisense strategy. In vivo, chondrocytic overexpression of Hsp70, after a preventive intra-articular injection of MG132 in rat knee, was sufficient to decrease the severity of OA-induced MIA lesions, as demonstrated histologically and biochemically. In conclusion, intracellular overexpression of Hsp70, through proteasome inhibition, could be an interesting tool in protecting chondrocytes from cellular injuries, either necrotic or apoptotic in nature, and thus might be a novel chondroprotective modality in rat experimental OA.

The biochemical content of articular cartilage: an original MRI approach.

The MR aspect of articular cartilage, that reflects the interactions between protons and macromolecular constituents, is affected by the intrinsic tissue structure (water content, the content of matrix constituents, collagen network organization), imager characteristics, and acquisition parameters. On the T1-weighted sequences, the bovine articular cartilage appears as an homogeneous tissue in high signal intensity, whatever the age of animals considered, whereas on the T2-weighted sequences, the articular bovine cartilage presents variations of its imaging pattern (laminar appearance) well correlated to the variations of its histological and biochemical structure. The T2 relaxation time measurement (T2 mapping), which reflects quantitatively the signal intensity variations observed on T2 weighted sequences, is a way to evaluate more precisely the modifications of cartilage structure during the aging and maturation processes (rat's study). This technique so far confined to experimental micro-imagers is now developed on clinical imagers. Consequently, it may permit to depict the early stages of osteoarthritic disease (OA) or to evaluate the chondroprotective effect of drugs.

Easy rider: monkeys learn to drive a wheelchair to navigate through a complex maze.

The neurological bases of spatial navigation are mainly investigated in rodents and seldom in primates. The few studies led on spatial navigation in both human and non-human primates are performed in virtual, not in real environments. This is mostly because of methodological difficulties inherent in conducting research on freely-moving monkeys in real world environments. There is some incertitude, however, regarding the extrapolation of rodent spatial navigation strategies to primates. Here we present an entirely new platform for investigating real spatial navigation in rhesus monkeys. We showed that monkeys can learn a pathway by using different strategies. In these experiments three monkeys learned to drive the wheelchair and to follow a specified route through a real maze. After learning the route, probe tests revealed that animals successively use three distinct navigation strategies based on i) the place of the reward, ii) the direction taken to obtain reward or iii) a cue indicating reward location. The strategy used depended of the options proposed and the duration of learning. This study reveals that monkeys, like rodents and humans, switch between different spatial navigation strategies with extended practice, implying well-conserved brain learning systems across different species. This new task with freely driving monkeys provides a good support for the electrophysiological and pharmacological investigation of spatial navigation in the real world by making possible electrophysiological and pharmacological investigations.

Where is my reward and how do I get it? Interaction between the hippocampus and the basal ganglia during spatial learning.

Spatial learning has been recognized over the years to be under the control of the hippocampus and related temporal lobe structures. Hippocampal damage often causes severe impairments in the ability to learn and remember a location in space defined by distal visual cues. Recent experimental evidence in rodents demonstrates, however, that other brain areas might also be involved in the acquisition of spatial information. Amongst these, the cortex--basal ganglia loop is known to be involved in reinforcement learning and has been identified as an important contributor to spatial learning. In particular, it has been shown that altered activity of the basal ganglia striatal complex can impair the ability to perform spatial learning tasks. Until recently, little was known about how the basal ganglia and the hippocampus interact and how their activities evolve during learning. The present review, focusing on rodent studies, provides a glimpse of the findings obtained over the past decade that support a dialog between these two structures during spatial learning. Based on these studies, we propose a new functional spatial decision network with three separate loops encompassing hippocampus and specific basal ganglia regions. Each of the three loops serves a different aspect of spatial decision making and all three are linked by their mutual connections and are under the control of the dopaminergic learning signal.

Matrilin-3 switches from anti- to pro-anabolic upon integration to the extracellular matrix.

The extracellular matrix (ECM) has long been viewed primarily as an organized network of solid-phase ligands for integrin receptors. During degenerative processes, such as osteoarthritis, the ECM undergoes deterioration, resulting in its remodeling and in the release of some of its components. Matrilin-3 (MATN3) is an almost cartilage specific, pericellular protein acting in the assembly of the ECM of chondrocytes. In the past, MATN3 was found required for cartilage homeostasis, but also involved in osteoarthritis-related pro-catabolic functions. Here, to better understand the pathological and physiological functions of MATN3, its concentration as a circulating protein in articular fluids of human osteoarthritic patients was determined and its functions as a recombinant protein produced in human cells were investigated with particular emphasis on the physical state under which it is presented to chondrocytes. MATN3 down-regulated cartilage extracellular matrix (ECM) synthesis and up-regulated catabolism when administered as a soluble protein. When artificially immobilized, however, MATN3 induced chondrocyte adhesion via a α5ß1 integrin-dependent mechanism, AKT activation and favored survival and ECM synthesis. Furthermore, MATN3 bound directly to isolated α5ß1 integrin in vitro. TGFß1 stimulation of chondrocytes allowed integration of exogenous MATN3 into their ECM and ECM-integrated MATN3 induced AKT phosphorylation and improved ECM synthesis and accumulation. In conclusion, the integration of MATN3 to the pericellular matrix of chondrocytes critically determines the direction toward which MATN3 regulates cartilage metabolism. These data explain how MATN3 plays either beneficial or detrimental functions in cartilage and highlight the important role played by the physical state of ECM molecules.

Ambivalent properties of hyaluronate and hylan during post-traumatic OA in the rat knee.

AIM: To determine whether viscosupplementation with intra-articular (i.a.) low- or high-molecular-weight hyaluronate (HA) injections influenced both chondral and synovial lesions in rats with surgically-induced OA knee. METHODS: On D0, rats underwent anterior cruciate ligament transection (ACLX) and were divided in 4 groups: sham group, ACLX-saline control group, ACLX-hyaluronate group, ACLX-hylan group. IA injections were performed on D7, D14 and D21. Histological grading of chondral and synovial lesions were performed on D28. Concomitant immunostainings of Caspase3a and Hsp70 were also performed. RESULTS: Articular damages were significantly reduced in both HAs-treated knee joints. In contrast, a significant increase of histological score of synovial inflammation was noted in both ACLX + HAs groups. Apoptotic events significantly decreased as anti-apoptotic Hsp70 expression increased significantly in both HAs groups. CONCLUSION: HAs may exert, independently of its molecular weight, ambivalent properties on articular structures, simultaneously exerting chondroprotective properties and promoting long-term subacute synovitis.

Activation of PPARs α, ß/δ, and γ Impairs TGF-ß1-Induced Collagens' Production and Modulates the TIMP-1/MMPs Balance in Three-Dimensional Cultured Chondrocytes.

Background and Purpose. We investigated the potency of Peroxisome Proliferators-Activated Receptors (PPARs) α, ß/δ, and γ agonists to modulate Transforming Growth Factor-ß1 (TGF-ß1-) induced collagen production or changes in Tissue Inhibitor of Matrix Metalloproteinase- (TIMP-) 1/Matrix Metalloproteinase (MMP) balance in rat chondrocytes embedded in alginate beads. Experimental Approach. Collagen production was evaluated by quantitative Sirius red staining, while TIMP-1 protein levels and global MMP (-1, -2, -3, -7, and -9) or specific MMP-13 activities were measured by ELISA and fluorigenic assays in culture media, respectively. Levels of mRNA for type II collagen, TIMP-1, and MMP-3 & 13 were quantified by real-time PCR. Key Results. TGF-ß1 increased collagen deposition and type II collagen mRNA levels, while inducing TIMP-1 mRNA and protein expression. In contrast, it decreased global MMP or specific MMP-13 activities, while decreasing MMP-3 or MMP-13 mRNA levels. PPAR agonists reduced most of the effects of TGF-ß1 on changes in collagen metabolism and TIMP-1/MMP balance in rat in a PPAR-dependent manner, excepted for Wy14643 on MMP activities. Conclusions and Implications. PPAR agonists reduce TGF-ß1-modulated ECM turnover and inhibit chondrocyte activities crucial for collagen biosynthesis, and display a different inhibitory profile depending on selectivity for PPAR isotypes.

C-propeptides of procollagens I alpha 1 and II that differentially accumulate in enchondromas versus chondrosarcomas regulate tumor cell survival and migration.

Chondrogenic tumors that exhibit benign or malignant behaviors synthesize variable amounts of cartilage-like extracellular matrix. To define the regulators of these phenotypes, we performed a proteomic comparison of multiple human chondrogenic tumors, which revealed differential accumulation of the C-propeptides of procollagens Ialpha1 and II (PC1CP and PC2CP) in malignant versus benign tumors, respectively. Expression patterns of PC1CP correlated with levels of tumor vascularization, whereas expression patterns of PC2CP suggested its susceptibility to immobilization within the extracellular matrix. Prompted by these observations, we investigated the functions of recombinant PC1CP and PC2CP in the extracellular matrix in soluble or immobilized states. Each induced beta1 integrin-mediated chondrocyte adhesion by distinct domains and efficacies, suggesting that they initiated distinct signaling pathways. Indeed, immobilized PC2CP, but not PC1CP, induced apoptosis of primary chondrocytes and EAhy926 endothelial cells. In contrast, soluble PC1CP, but not PC2CP, induced the migration of EAhy926 cells and increased vascular endothelial growth factor (VEGF) and CXCR4 expression in chondrocytes. Soluble PC2CP also increased VEGF expression, but along with a more pronounced effect on CXCR4 and matrix metalloproteinase 13 expression. Our findings suggest that PC1CP favors angiogenesis and tumor progression, but that PC2CP acts in a more complex manner, exerting antitumor and antiangiogenic properties through apoptosis induction when immobilized, but progression and metastasis when soluble. In summary, the relative levels of PC1CP and PC2CP and their interactions within the extracellular matrix contribute to tumor progression, angiogenesis, and metastasis in chondrogenic tumors.

Dose-response relationship for exercise on severity of experimental osteoarthritis in rats: a pilot study.

OBJECTIVE: To investigate the influence of a calibrated exercise on the progression of structural lesions in an experimental model of osteoarthritis (OA) in the rat, and to explore the effect of exercise on the level of chondrocyte caspase-dependent apoptosis and of Hsp70. METHODS: The OA model was induced by anterior cruciate ligament transection (ACLT). Rats were placed in 4 experimental groups: operated (ACLT) free moving rats, and 3 exercise groups (slight, moderate and intense) subjected to running training. Rats were killed 14 and 28 days after surgery. RESULTS: On D14 histological assessment demonstrated a beneficial influence of a slight and a moderate exercise vs control ACLT group. Hsp70 increased significantly in the moderate group vs controls. On D28, histological lesions strongly decreased in the slight and moderate exercise groups vs ACLT group, while an intense effort abolished this beneficial trend. Interestingly, the concomitant course of apoptotic events (caspase 3-positive cells) and the co-expression of Hsp70 in the various groups varied, when significant, in an inverse manner. In the intense group this overexpression was not noted, as a "burn out" appeared, thus leading to a loss of this protective effect. CONCLUSION: This study shows that a calibrated slight or moderate exercise exerts a beneficial influence on the severity of chondral lesions in ACLT rats. Conversely, a strong effort abolishes this chondroprotective effect. This effect could be related to a reduced level of chondrocyte apoptosis through anti-apoptotic capacities of stress-induced Hsp70 overexpression.