Shrouded in history: Unveiling the ways of life of an early Muslim population in Santarém, Portugal (8th- 10th century AD).

In around 716 AD, the city of Santarém, Portugal, was conquered by the Berber and Arab armies that swept the Iberian Peninsula and went on to rule the region until the 12th century. Archaeological excavations in 2007/08 discovered an Islamic necropolis (Avenida 5 de Outubro #2-8) that appears to contain the remains of an early Muslim population in Santarém (8th- 10th century). In this study, skeletal material from 58 adult individuals was analysed for stable carbon (δ13Ccol; δ13Cap), nitrogen (δ15N) and sulphur (δ34S) isotope ratios in bones, and stable oxygen (δ18O), carbon (δ13Cen) and radiogenic strontium (87Sr/86Sr) isotopes in tooth enamel. The results of this study revealed a dietary pattern of predominantly C3-plant and domestic C3-fed herbivore consumption during adulthood (δ13Ccol and δ15N, respectively) but a higher proportion of C4-plant input during childhood (δ13Cen) for some individuals-interpreted as possible childhood consumption of millet porridge, a common practice in North Africa-in those with unorthodox burial types (Groups 1 and 2) that was not practiced in the individuals with canonical burials (Group 3). In this first mobility study of a medieval Muslim population in Portugal, δ18ODW values revealed greater heterogeneity in Groups 1 and 2, consistent with diverse origins, some in more humid regions than Santarém when compared to regional precipitation δ18O data, contrasting the more homogenous Group 3, consistent with the local precipitation δ18O range. Ancient DNA analysis conducted on three individuals revealed maternal (mtDNA) and paternal (Y-chromosome) lineages compatible with a North African origin for (at least) some of the individuals. Additionally, mobility of females in this population was higher than males, potentially resulting from a patrilocal social system, practiced in Berber and Arab communities. These results serve to offer a more detailed insight into the ancestry and cultural practices of early Muslim populations in Iberia.

Repetitive mRNA vaccination is required to improve the quality of broad-spectrum anti-SARS-CoV-2 antibodies in the absence of CXCL13.

Since the initial spread of severe acute respiratory syndrome coronavirus 2 infection, several viral variants have emerged and represent a major challenge for immune control, particularly in the context of vaccination. We evaluated the quantity, quality, and persistence of immunoglobulin G (IgG) and IgA in individuals who received two or three doses of messenger RNA (mRNA) vaccines, compared with previously infected vaccinated individuals. We show that three doses of mRNA vaccine were required to match the humoral responses of preinfected vaccinees. Given the importance of antibody-dependent cell-mediated immunity against viral infections, we also measured the capacity of IgG to recognize spike variants expressed on the cell surface and found that cross-reactivity was also strongly improved by repeated vaccination. Last, we report low levels of CXCL13, a surrogate marker of germinal center activation and formation, in vaccinees both after two and three doses compared with preinfected individuals, providing a potential explanation for the short duration and low quality of Ig induced.

Development of a personalized shared decision-making tool for knee osteoarthritis and user-testing with African American and Latina women.

Background: Patients with chronic knee pain are often unaware of treatment options and likely outcomes-information that is critical to decision-making. A consistent framework for communicating patient-personalized information enables clinicians to provide consistent, targeted, and relevant information. Our objective was to user-test a shared decision-making (SDM) tool for chronic knee pain. Methods: A cross-functional team developed a Markov-based health economics model and tested the model outputs with patient panels, patient and clinician focus groups, and clinical specialists. The resulting SDM tool was user-tested in a parallel-designed, randomized controlled study with 52 African American and 52 Latina women from geographically representative areas of the US. Participants were randomized to counseling with or without the SDM tool. Feedback was collected at intervention and at 1 month after intervention and analyzed with Student's t-tests and Chi-squared analyses (alpha = 0.05). Results: Qualitative results indicated patients understood the material, rated the overall experience highly, and were likely to recommend the physician. The SDM group reported high satisfaction with the tool. A greater proportion of the SDM group (56%) reported increased physical activity over baseline at 1 month compared with the control group (33%) (P = 0.0005). New use of medications for knee pain (58% SDM; 49% control) did not differ significantly between groups (P = 0.15). Conclusion: Use of this innovative SDM tool was associated with high satisfaction and a significant increase in self-reported physical activity level at 1 month. The SDM tool may elicit behavioral changes to promote musculoskeletal health.

Apolipoprotein E, a Crucial Cellular Protein in the Lifecycle of Hepatitis Viruses.

Apolipoprotein E (ApoE) is a multifunctional protein expressed in several tissues, including those of the liver. This lipoprotein component is responsible for maintaining lipid content homeostasis at the plasma and tissue levels by transporting lipids between the liver and peripheral tissues. The ability of ApoE to interact with host-cell surface receptors and its involvement in several cellular pathways raised questions about the hijacking of ApoE by hepatotropic viruses. Hepatitis C virus (HCV) was the first hepatitis virus reported to be dependent on ApoE for the completion of its lifecycle, with ApoE being part of the viral particle, mediating its entry into host cells and contributing to viral morphogenesis. Recent studies of the hepatitis B virus (HBV) lifecycle have revealed that this virus and its subviral envelope particles also incorporate ApoE. ApoE favors HBV entry and is crucial for the morphogenesis of infectious particles, through its interaction with HBV envelope glycoproteins. This review summarizes the data highlighting the crucial role of ApoE in the lifecycles of HBV and HCV and discusses its potential role in the lifecycle of other hepatotropic viruses.

Differentiated Cells in Prolonged Hypoxia Produce Highly Infectious Native-Like Hepatitis C Virus Particles.

BACKGROUND AND AIMS: Standard hepatitis C virus (HCV) cell-culture models present an altered lipid metabolism and thus produce lipid-poor lipoviral particles (LVPs). These models are thereby weakly adapted to explore the complete natural viral life cycle. APPROACH AND RESULTS: To overcome these limitations, we used an HCV cell-culture model based on both cellular differentiation and sustained hypoxia to better mimic the host-cell environment. The long-term exposure of Huh7.5 cells to DMSO and hypoxia (1% O2 ) significantly enhanced the expression of major differentiation markers and the cellular hypoxia adaptive response by contrast with undifferentiated and normoxic (21% O2 ) standard conditions. Because hepatocyte-like differentiation and hypoxia are key regulators of intracellular lipid metabolism, we characterized the distribution of lipid droplets (LDs) and demonstrated that experimental cells significantly accumulate larger and more numerous LDs relative to standard cell-culture conditions. An immunocapture (IC) and transmission electron microscopy (TEM) method showed that differentiated and hypoxic Huh7.5 cells produced lipoproteins significantly larger than those produced by standard Huh7.5 cell cultures. The experimental cell culture model is permissive to HCV-Japanese fulminant hepatitis (JFH1) infection and produces very-low-buoyant-density LVPs that are 6-fold more infectious than LVPs formed by standard JFH1-infected Huh7.5 cells. Finally, the IC-TEM approach and antibody-neutralization experiments revealed that LVPs were highly lipidated, had a global ultrastructure and a conformation of the envelope glycoprotein complex E1E2 close to that of the ones circulating in infected individuals. CONCLUSIONS: This relevant HCV cell culture model thus mimics the complete native intracellular HCV life cycle and, by extension, can be proposed as a model of choice for studies of other hepatotropic viruses.

Potential Role of Cost and Quality of Life in Treatment Decisions for Arthritis-Related Knee Pain in African American and Latina Women.

OBJECTIVE: The present study was undertaken to investigate whether Latina and African American women with arthritis-related knee pain and primary care providers who treat them believe their treatment decisions would benefit from having more information about the impact of treatment on their quality of life, medical care costs, and work productivity. METHODS: We conducted 4 focus groups of Latina and African American women over age 45 years who had knee pain. We also conducted 2 focus groups with primary care providers who treated Latina and African American women for knee pain. The participants were recruited from the community. They were asked their opinions about a decision tool that presented information on a range of treatment options and their impacts on quality of life, medical care costs, and work productivity. They were asked whether providing this information would help them make better treatment decisions. We analyzed the focus group transcripts using ATLAS.ti. RESULTS: We found that minority women and primary care providers endorsed the use of a decision-making tool that provided information of the impact of treatment on quality of life, medical care costs, and work productivity. Providers felt that patients would benefit from having the additional information but were concerned about its complexity and some patients' ability to comprehend the information. CONCLUSION: Latina and African American women could make more informed treatment decisions for their knee pain using a decision-making tool that provides them with significant information about how various treatment options may impact their quality of life, medical care costs, and workforce productivity.

Effect of different healing stages on stable isotope ratios in skeletal lesions.

INTRODUCTION: Physiological stress is one of the various factors that can have an impact on stable isotope ratios. However, its effect on bone collagen stable isotope ratios is still not fully understood. This study aims to build on previous research on how different disease stages may affect bone collagen stable isotope ratios. MATERIALS AND METHODS: Carbon (δ13 C) and nitrogen (δ15 N) isotope ratios were assessed in 33 skeletons that retained evidence of infectious disease and healed fractures. Samples were taken from active lesions (long bones n = 14; ribs n = 4), healed lesions (long bones n = 10; ribs n = 9), or a fracture callus (long bones n = 9; ribs n = 3). Results were compared to stable isotope ratios calculated for regions on these bones that did not retain evidence of disease or fracture. RESULTS: Long bones with active lesions had a significantly higher average δ15 N (δ15 N = 11.1 ± 0.9‰) compared to those without lesions (δ15 N = 10.7 ± 0.7‰; p = .02), while fracture calluses showed the largest range for both δ15 N and δ13 C. There were no significant differences in stable isotope ratios when compared between nonlesion and lesion sites in the ribs. DISCUSSION: The increase in δ15 N seen in active lesions, when compared with δ15 N from nonlesion regions on the same long bone, may be a consequence of altered protein metabolism. The high variability of δ15 N and δ13 C in fractures may be related to different healing stages of the calluses. This study suggests that stable isotope data can contribute information about diseases in the past, as well as an individual's response to diseases in the absence of modern medicine and antibiotics.

Endoplasmic Reticulum Detergent-Resistant Membranes Accommodate Hepatitis C Virus Proteins for Viral Assembly.

During Hepatitis C virus (HCV) morphogenesis, the non-structural protein 2 (NS2) brings the envelope proteins 1 and 2 (E1, E2), NS3, and NS5A together to form a complex at the endoplasmic reticulum (ER) membrane, initiating HCV assembly. The nature of the interactions in this complex is unclear, but replication complex and structural proteins have been shown to be associated with cellular membrane structures called detergent-resistant membranes (DRMs). We investigated the role of DRMs in NS2 complex formation, using a lysis buffer combining Triton and n-octyl glucoside, which solubilized both cell membranes and DRMs. When this lysis buffer was used on HCV-infected cells and the resulting lysates were subjected to flotation gradient centrifugation, all viral proteins and DRM-resident proteins were found in soluble protein fractions. Immunoprecipitation assays demonstrated direct protein-protein interactions between NS2 and E2 and E1 proteins, and an association of NS2 with NS3 through DRMs. The well-folded E1E2 complex and NS5A were not associated, instead interacting separately with the NS2-E1-E2-NS3 complex through less stable DRMs. Core was also associated with NS2 and the E1E2 complex through these unstable DRMs. We suggest that DRMs carrying this NS2-E1-E2-NS3-4A-NS5A-core complex may play a central role in HCV assembly initiation, potentially as an assembly platform.

A Fresh Perspective on a Familiar Problem: Examining Disparities in Knee Osteoarthritis Using a Markov Model.

BACKGROUND: Disparities in the presentation of knee osteoarthritis (OA) and in the utilization of treatment across sex, racial, and ethnic groups in the United States are well documented. OBJECTIVES: We used a Markov model to calculate lifetime costs of knee OA treatment. We then used the model results to compute costs of disparities in treatment by race, ethnicity, sex, and socioeconomic status. RESEARCH DESIGN: We used the literature to construct a Markov Model of knee OA and publicly available data to create the model parameters and patient populations of interest. An expert panel of physicians, who treated a large number of patients with knee OA, constructed treatment pathways. Direct costs were based on the literature and indirect costs were derived from the Medical Expenditure Panel Survey. RESULTS: We found that failing to obtain effective treatment increased costs and limited benefits for all groups. Delaying treatment imposed a greater cost across all groups and decreased benefits. Lost income because of lower labor market productivity comprised a substantial proportion of the lifetime costs of knee OA. Population simulations demonstrated that as the diversity of the US population increases, the societal costs of racial and ethnic disparities in treatment utilization for knee OA will increase. CONCLUSIONS: Our results show that disparities in treatment of knee OA are costly. All stakeholders involved in treatment decisions for knee OA patients should consider costs associated with delaying and forgoing treatment, especially for disadvantaged populations. Such decisions may lead to higher costs and worse health outcomes.

Association between the growth arrest-specific 6 (Gas6) gene polymorphism c.834 + 7G>A and preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a hypertensive disease of pregnancy complicating 2-8% of all pregnancies. The exact pathophysiology still remains unknown. Growth arrest-specific 6 (Gas6) is a member of the vitamin K-dependent protein family and it has been suggested as a novel atherothrombotic risk factor with anti-angiogenic and pro-atherogenic properties. The goal of the our study was to investigate the relationships between the c.834 + 7G > A polymorphism of GAS6, plasma Gas6 levels and PE. METHODS: A total of 150 women, including 82 preeclamptic pregnant women and 68 normotensive pregnant (NP) women, were recruited in the current study. Blood samples were taken from all participants. Plasma Gas6 levels measured by an enzyme-linked immunosorbent assay. GAS6 polymorphism was determined using a PCR-RFLP method. RESULTS: The plasma Gas6 levels of preeclamptic patients were significantly lower than those of NP women (8.65 ± 3.70 ng/ml and 10.89 ± 4.23 ng/ml respectively, p < 0.001). The GG genotype was the most prevalent, and the risk of PE was 3.5-fold higher in pregnant women with GG genotype compared to woman with AA genotype (p < 0.01). The A allele was less frequent in preeclamptic patients than in control subjects (OR = 2.118, 95% CI = 1.330-3.371, p < 0.001). CONCLUSIONS: Our results suggest that GAS6 c.834 + 7G > A polymorphism may have a pivotal role in the pathogenesis of PE suggesting that the A allele has a protective role for PE.

Ovarian stem cells: From basic to clinical applications.

The field of reproductive biology has undergone significant developments in the last decade. The notion that there is a fixed reserve pool of oocytes before birth was established by Zuckerman in 1951. However, in 2004, an article published in nature challenged this central dogma of mammalian reproductive biology. Tilly's group reported the existence of ovarian germline stem cells (GSCs) in postnatal ovaries of mice and suggested that the bone marrow could be an extragonadal source of ovarian GSCs. These findings were strongly criticized; however, several independent groups have since successfully isolated and characterized ovarian GSCs in postnatal mice. The ovarian GSCs are located in the ovarian surface epithelium and express markers of undifferentiated GSCs. When transplanted into mouse ovaries, mouse ovarian GSCs could differentiate and produce embryos and offspring. Similarly, in a recent study, ovarian GSCs were found to be present in the ovaries of women of reproductive age. Conversely, there is increasing evidence that stem cells responsible for maintaining a healthy state in normal tissue may be a source of some cancers, including ovarian cancer. Cancer stem cells (CSCs) have been found in many tissues, including ovaries. Some researchers have suggested that ovarian cancer may be a result of the transformation and dysfunction of ovarian GSCs with self-renewal properties. Drug resistant and metastasis-generating CSCs are responsible for many important problems affecting ovarian cancer patients. Therefore, the identification of CSCs will provide opportunities for the development of new therapeutic strategies for treatments for infertility and ovarian cancer. In this article, we summarize the current understanding of ovarian GSCs in adult mammals, and we also discuss whether there is a relationship between GSCs and CSCs.

Tracking a tuberculosis outbreak over 21 years: strain-specific single-nucleotide polymorphism typing combined with targeted whole-genome sequencing.

BACKGROUND: Whole-genome sequencing (WGS) is increasingly used in molecular-epidemiological investigations of bacterial pathogens, despite cost- and time-intensive analyses. We combined strain-specific single-nucleotide polymorphism (SNP) typing and targeted WGS to investigate a tuberculosis cluster spanning 21 years in Bern, Switzerland. METHODS: On the basis of genome sequences of 3 historical outbreak Mycobacterium tuberculosis isolates, we developed a strain-specific SNP-typing assay to identify further cases. We screened 1642 patient isolates and performed WGS on all identified cluster isolates. We extracted SNPs to construct genomic networks. Clinical and social data were retrospectively collected. RESULTS: We identified 68 patients associated with the outbreak strain. Most received a tuberculosis diagnosis in 1991-1995, but cases were observed until 2011. Two thirds were homeless and/or substance abusers. Targeted WGS revealed 133 variable SNP positions among outbreak isolates. Genomic network analyses suggested a single origin of the outbreak, with subsequent division into 3 subclusters. Isolates from patients with confirmed epidemiological links differed by 0-11 SNPs. CONCLUSIONS: Strain-specific SNP genotyping allowed rapid and inexpensive identification of M. tuberculosis outbreak isolates in a population-based strain collection. Subsequent targeted WGS provided detailed insights into transmission dynamics. This combined approach could be applied to track bacterial pathogens in real time and at high resolution.

Lombards on the move--an integrative study of the migration period cemetery at Szólád, Hungary.

In 2005 to 2007 45 skeletons of adults and subadults were excavated at the Lombard period cemetery at Szólád (6th century A.D.), Hungary. Embedded into the well-recorded historical context, the article presents the results obtained by an integrative investigation including anthropological, molecular genetic and isotopic (δ(15)N, δ(13)C, (87)Sr/(86)Sr) analyses. Skeletal stress markers as well as traces of interpersonal violence were found to occur frequently. The mitochondrial DNA profiles revealed a heterogeneous spectrum of lineages that belong to the haplogroups H, U, J, HV, T2, I, and K, which are common in present-day Europe and in the Near East, while N1a and N1b are today quite rare. Evidence of possible direct maternal kinship was identified in only three pairs of individuals. According to enamel strontium isotope ratios, at least 31% of the individuals died at a location other than their birthplace and/or had moved during childhood. Based on the peculiar 87 Sr/86 Sr ratio distribution between females, males, and subadults in comparison to local vegetation and soil samples, we propose a three-phase model of group movement. An initial patrilocal group with narrower male but wider female Sr isotope distribution settled at Szólád, whilst the majority of subadults represented in the cemetery yielded a distinct Sr isotope signature. Owing to the virtual absence of Szólád-born adults in the cemetery, we may conclude that the settlement was abandoned after approx. one generation. Population heterogeneity is furthermore supported by the carbon and nitrogen isotope data. They indicate that a group of high-ranking men had access to larger shares of animal-derived food whilst a few individuals consumed remarkable amounts of millet. The inferred dynamics of the burial community are in agreement with hypotheses of a highly mobile lifestyle during the Migration Period and a short-term occupation of Pannonia by Lombard settlers as conveyed by written sources.

Musculoskeletal healthcare disparities: influence of patient sex, race, and ethnicity on utilization of total joint arthroplasty.

Total joint arthroplasty is an effective treatment of musculoskeletal diseases including osteoarthritis, rheumatoid arthritis, trauma, and other diseases of the major joints. Based on data obtained from the National Inpatient Survey from 2000 through 2010, substantial differences in the rates of utilization of total hip, knee, and shoulder arthroplasty were detected with respect to race, ethnicity, and gender/sex. The results of this study support the likelihood that it is the interaction between multiple factors (patient, physician, and system/institutional) that contributes to musculoskeletal health disparities. Our study shows that disparities in the utilization of total joint arthroplasty that were evident in 2000 continue to exist. Additional studies evaluating innovative approaches to reducing musculoskeletal disparities relating to total joint arthroplasty are needed.

Promoting Effects of Heparin on ex vivo Expansion of Megakaryocytopoiesis from Human Cord Blood CD34+ Cells.

INTRODUCTION: Transfusion of ex vivo expanded megakaryocytes (MKs) has been proposed to sustain platelet recovery after cord blood (CB) hematopoietic stem cell transplantation. In this study, we investigated the effects of heparin on ex vivo colony forming unit-megakaryocytes (CFU-MKs) and MKs expansion from CB CD34+ cells. METHODS: CB CD34+ cells were stimulated by a combination of thrombopoietin (TPO), stem cell factor (SCF), Flt3-Ligand (FL), IL-6, and IL-11 supplemented with autologous serum and heparin during 14 days. Expanded cells were analyzed by flow cytometry and cultured in a CFU-MK assay. RESULTS: Compared to control cultures, the 5-factor combination with heparin induced significantly (p ≤ 0.05) higher numbers of: CFU-MKs and CD41+ cells on days 7 and 14; CD41+ cells displaying hyperploidy levels (≥8N) on day 14; platelets on day 14. The culture-derived platelets were activated upon collagen stimulation. CONCLUSION: Heparin can significantly enhance the stimulating effects of a combination of TPO, SCF, FL, IL-6, and IL-11 supplemented with autologous serum on CFU-MK, MK, and platelet production from CB CD34+ cells. This expansion system could represent a promising method to generate CFU-MKs and MKs cells for transfusion to sustain platelet reconstitution following CB transplantation.

Pro-inflammatory cytokine and caspase-1 responses to pattern recognition receptor activation of neutrophils and dendritic cells in Behcet's disease.

OBJECTIVE: Activated innate immunity is implicated in the pathogenesis of Behcet's disease (BD). To clarify the mechanisms of innate immune responses, we investigated inflammasome activation in dendritic cells (DCs) and neutrophils, following stimulation with two different pattern recognition receptors (PRRs) RIG-1-like (RLR) and NOD-like (NLR) in patients with BD. METHODS: Sixteen active BD patients with mucocutaneous lesions and 17 healthy controls (HCs) were included in this study. DCs were generated from monocytes. DCs and isolated neutrophils were activated by RLR and NLR ligands. Caspase-1 activation and expression of p38 and RIP2 were determined by flow cytometry. Levels of IL-1ß, IL-6, TNF-α, IFN-α and IL-18 in culture supernatants were measured by ELISA. RESULTS: Activation of caspase-1 following intracellular PRR stimulation was found to be of similar levels in DCs and neutrophils of BD patients compared with HCs. However, activation of DCs from BD patients to NOD2 stimulus measured by the expression of RIP2 and p38 as well as IL-18 levels was found to be slightly defective (P < 0.05). In neutrophil cultures, IL-6 levels were lower in response to all stimuli in patients with BD compared with HCs (P < 0.01). CONCLUSION: Inflammasome formation following stimulation with NOD1/NOD2 and RIG measured by caspase-1 activation, cytokine levels and expression of RIP2 and p38 seems to be functionally normal in DCs and neutrophils of BD patients, although slightly defective responses in some pathways and cytokine levels were observed. These results may suggest that caspase-1-independent pathways such as toll-like receptors may be more prominent in BD pathogenesis.

Bioavailable 87Sr/86Sr in different environmental samples--effects of anthropogenic contamination and implications for isoscapes in past migration studies.

(87)Sr/(86)Sr reference maps (isoscapes) are a key tool for investigating past human and animal migrations. However, there is little understanding of which biosphere samples are best proxies for local bioavailable Sr when dealing with movements of past populations. In this study, biological and geological samples (ground vegetation, tree leaves, rock leachates, water, soil extracts, as well as modern and archeological animal teeth and snail shells) were collected in the vicinity of two early medieval cemeteries ("Thuringians", 5-6th century AD) in central Germany, in order to characterize (87)Sr/(86)Sr of the local biosphere. Animal tooth enamel is not appropriate in this specific context to provide a reliable (87)Sr/(86)Sr baseline for investigating past human migration. Archeological faunal teeth data (pig, sheep/goat, and cattle) indicates a different feeding area compared to that of the human population and modern deer teeth (87)Sr/(86)Sr suggest the influence of chemical fertilizers. Soil leachates do not yield consistent (87)Sr/(86)Sr, and (87)Sr/(86)Sr of snail shells are biased towards values for soil carbonates. In contrast, water and vegetation samples seem to provide the most accurate estimates of bioavailable (87)Sr/(86)Sr to generate Sr isoscapes in the study area. Long-term environmental archives of bioavailable (87)Sr/(86)Sr such as freshwater bivalve shells and tree cores were examined in order to track potential historic anthropogenic contamination of the water and the vegetation. The data obtained from the archeological bivalve shells show that the modern rivers yield (87)Sr/(86)Sr ratios which are similar to those of the past. However, the tree cores registered decreasing (87)Sr/(86)Sr values over time towards present day likely mirroring anthropogenic activities such as forest liming, coal mining and/or soil acidification. The comparison of (87)Sr/(86)Sr of the Thuringian skeletons excavated in the same area also shows that the vegetation samples are very likely anthropogenically influenced to some extent, affecting especially (87)Sr/(86)Sr of the shallow rooted plants.

Influence of Leishmania (Viannia) species on the response to antimonial treatment in patients with American tegumentary leishmaniasis.

BACKGROUND: Pentavalent antimonials (SbV) are the first-line chemotherapy for American tegumentary leishmaniasis (ATL). There are, however, reports of the occurrence of treatment failure with these drugs. Few studies in Latin America have compared the response to SbV treatment in ATL caused by different Leishmania species. METHODS: Clinical parameters and response to SbV chemotherapy were studied in 103 patients with cutaneous leishmaniasis (CL) in Peru. Leishmania isolates were collected before treatment and typed by multilocus polymerase-chain-reaction restriction fragment-length polymorphism analysis. RESULTS: The 103 isolates were identified as L. (Viannia) peruviana (47.6%), L. (V.) guyanensis (23.3%), L. (V.) braziliensis (22.3%), L. (V.) lainsoni (4.9%), L. (Leishmania) mexicana (1%), and a putative hybrid, L. (V.) braziliensis/L. (V.) peruviana (1%). L. (V.) guyanensis was most abundant in central Peru. Of patients infected with the 3 former species, 21 (21.9%) did not respond to SbV chemotherapy. The proportions of treatment failure (after 12 months of follow-up) were 30.4%, 24.5%, and 8.3% in patients infected with L. (V.) braziliensis, L. (V.) peruviana, and L. (V.) guyanensis, respectively. Infection with L. (V.) guyanensis was associated with significantly less treatment failure than L. (V.) braziliensis, as determined by multiple logistic regression analysis (odds ratio, 0.07 [95% confidence interval, 0.007-0.8]; P=.03). CONCLUSIONS: Leishmania species can influence SbV treatment outcome in patients with CL. Therefore, parasite identification is of utmost clinical importance, because it should lead to a species-oriented treatment.

Roles of platelet factor 4 in hematopoiesis and angiogenesis.

Platelet factor 4 (PF4) has been recognized as a physiological inhibitor of megakaryocytopoiesis and angiogenesis for two decades. Structure-function studies have shown that the DLQ determinant in position 54-56 is necessary for megakaryocytic inhibition whereas mutations of these residues into ELR sequence and more importantly, into DLR sequence, induce a stronger inhibitory activity of peptide p47-70 on angiogenesis. The alpha-helix region of peptides may participate in the fixation of the effector to its cellular receptor and the other important structural domains would activate the receptor. In vivo, PF4 and its related peptides can protect hematopoiesis from chemotherapy by enhancing cell viability and suppress tumor growth through anti-angiogenic pathway. Several PF4 fragments and modified molecules exhibit antiangiogenesis properties and may become an alternative for further therapeutic angiogenesis.