A Multidomain Adhesion Protein Family Expressed in Plasmodium falciparum Is Essential for Transmission to the Mosquito

The recent sequencing of several apicomplexan genomes has provided the opportunity to characterize novel antigens essential for the parasite life cycle that might lead to the development of new diagnostic and therapeutic markers. Here we have screened the Plasmodium falciparum genome sequence for genes encoding extracellular multidomain putative adhesive proteins. Three of these identified genes, named PfCCp1, PfCCp2, and PfCCp3, have multiple adhesive modules including a common Limulus coagulation factor C domain also found in two additional Plasmodium genes. Orthologues were identified in the Cryptosporidium parvum genome sequence, indicating an evolutionary conserved function. Transcript and protein expression analysis shows sexual stage–specific expression of PfCCp1, PfCCp2, and PfCCp3, and cellular localization studies revealed plasma membrane–associated expression in mature gametocytes. During gametogenesis, PfCCps are released and localize surrounding complexes of newly emerged microgametes and macrogametes. PfCCp expression markedly decreased after formation of zygotes. To begin to address PfCCp function, the PfCCp2 and PfCCp3 gene loci were disrupted by homologous recombination, resulting in parasites capable of forming oocyst sporozoites but blocked in the salivary gland transition. Our results describe members of a conserved apicomplexan protein family expressed in sexual stage Plasmodium parasites that may represent candidates for subunits of a transmission-blocking vaccine

Consideration of within-patient diversity highlights transmission pathways and antimicrobial resistance gene variability in vancomycin-resistant Enterococcus faecium

BackgroundWGS is increasingly being applied to healthcare-associated vancomycin-resistant Enterococcus faecium (VREfm) outbreaks. Within-patient diversity could complicate transmission resolution if single colonies are sequenced from identified cases.ObjectivesDetermine the impact of within-patient diversity on transmission resolution of VREfm.Materials and methodsFourteen colonies were collected from VREfm positive rectal screens, single colonies were collected from clinical samples and Illumina WGS was performed. Two isolates were selected for Oxford Nanopore sequencing and hybrid genome assembly to generate lineage-specific reference genomes. Mapping to closely related references was used to identify genetic variations and closely related genomes. A transmission network was inferred for the entire genome set using Phyloscanner.Results and discussionIn total, 229 isolates from 11 patients were sequenced. Carriage of two or three sequence types was detected in 27% of patients. Presence of antimicrobial resistance genes and plasmids was variable within genomes from the same patient and sequence type. We identified two dominant sequence types (ST80 and ST1424), with two putative transmission clusters of two patients within ST80, and a single cluster of six patients within ST1424. We found transmission resolution was impaired using fewer than 14 colonies.ConclusionsPatients can carry multiple sequence types of VREfm, and even within related lineages the presence of mobile genetic elements and antimicrobial resistance genes can vary. VREfm within-patient diversity could be considered in future to aid accurate resolution of transmission networks

Sex-Based Differences in Outcomes After Hip Arthroscopic Surgery for Femoroacetabular Impingement: A Systematic Review

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: While sex-based differences in outcomes after hip arthroscopic surgery for femoroacetabular impingement syndrome (FAIS) are often recorded, no studies have been dedicated to analyzing the literature as a whole. Purpose: To investigate whether sex is a predictor of outcomes in studies evaluating hip arthroscopic surgery for FAIS. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched the PubMed, Embase, Cochrane, Ovid, and PubMed Central databases for English-language studies that evaluated sex-specific outcomes in human populations. The search terms used were as follows: (“Hip Arthroscopy”) AND (“Femoroacetabular Impingement” OR “FAI”) AND (“Sex” OR “Gender” OR “Male” OR “Female”). Studies with evidence levels 2 through 4 were included. The studies were then screened, followed by data extraction. Modified Harris Hip Score (mHHS) outcomes and return-to-sport (RTS) rates were recorded. These were analyzed using random-effects meta-analysis. Heterogeneity was calculated using the I2 statistic. Results: Of 256 full-text articles screened, 48 articles were included in this analysis; of these, 14 studies (29%) concluded that female sex was a negative predictor of postoperative outcomes, while 6 studies (13%) found female sex to be positive predictor. The remaining 28 studies (58%) found no sex-based differences in postoperative outcomes. Of 7 studies (416 male and 519 female) included in the mHHS analysis, 2 studies concluded that male patients had significantly higher postoperative mHHS scores. Of 6 studies (502 male and 396 female) included in the RTS analysis, 1 study concluded that male patients had a significantly higher RTS rate. Conclusion: Almost one-third of the included studies determined that female sex was a negative predictor of postoperative outcomes, 13% found female sex to be a positive predictor, and 58% found no sex-based differences. Our study illustrates an insufficiency of high-level evidence supporting sex-specific differences in outcomes after hip arthroscopic surgery, but findings indicated that the postoperative mHHS score and RTS rate may be influenced by sex

Circulating Soluble Endoglin Levels in Pregnant Women in Cameroon and Malawi—Associations with Placental Malaria and Fetal Growth Restriction

Placental infections with Plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (LBW). The mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. Soluble endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune system and influences angiogenesis. We hypothesized that sEng may play a role in development of LBW associated with placental malaria (PM). Plasma levels of sEng were measured in women (i) followed prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case-control study at delivery in Malawi (n = 479). The relationships between sEng levels and gravidity, peripheral and placental parasitemia, gestational age, and adverse outcomes of PM including maternal anemia and LBW were determined. In the longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one malaria infection during pregnancy. In Malawi we enrolled two aparasitemic gravidity-matched controls for every case with PM. sEng levels varied over the course of gestation and were significantly higher in early and late gestation as compared to delivery (P<0.006 and P<0.0001, respectively). Circulating sEng levels were higher in primigravidae than multigravidae from both Cameroon and Malawi, irrespective of malarial infection status (p<0.046 and p<0.001, respectively). Peripheral parasitemia in Cameroonian women and PM in Malawian women were each associated with elevated sEng levels following correction for gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased sEng was also associated with the delivery of LBW infants in primigravid Malawian women (p = 0.017); the association was with fetal growth restriction (p = 0.003) but not pre-term delivery (p = 0.286). Increased circulating maternal sEng levels are associated with P. falciparum infection in pregnancy and with fetal growth restriction in primigravidae with PM

Impact of differing methodologies for serum miRNA-371a-3p assessment in stage I testicular germ cell cancer recurrence.

INTRODUCTION Current evidence shows that serum miR-371a-3p can identify disease recurrence in testicular germ cell tumour (TGCT) patients and correlates with tumour load. Despite convincing evidence showing the advantages of including miR-371a-3p testing to complement and overcome the classical serum tumour markers limitations, the successful introduction of a serum miRNA based test into clinical practice has been impeded by a lack of consensus regarding optimal methodologies and lack of a universal protocol and thresholds. Herein, we investigate two quantitative real-time PCR (qRT-PCR) based pipelines in detecting disease recurrence in stage I TGCT patients under active surveillance, and compare the sensitivity and specificity for each method. METHODS Sequential serum samples collected from 33 stage I TGCT patients undergoing active surveillance were analysed for miR-371a-3p via qRT-PCR with and without an amplification step included. RESULTS Using a pre-amplified protocol, all known recurrences were detected via elevated miR-371a-3p expression, while without pre-amplification, we failed to detect recurrence in 3/10 known recurrence patients. For pre-amplified analysis, sensitivity and specificity was 90% and 94.4% respectively. Without amplification, sensitivity dropped to 60%, but exhibited 100% specificity. DISCUSSION We conclude that incorporating pre-amplification increases sensitivity of miR-371a-3p detection, but produces more false positive results. The ideal protocol for quantification of miR-371a-3p still needs to be determined. TGCT patients undergoing active surveillance may benefit from serum miR-371a-3p quantification with earlier detection of recurrences compared to current standard methods. However, larger cross-institutional studies where samples are processed and data is analysed in a standardised manner are required prior to its routine clinical implementation

Treatment Outcomes for Men with Clinical Stage II Nonseminomatous Germ Cell Tumours Treated with Primary Retroperitoneal Lymph Node Dissection: A Systematic Review

CONTEXT Guidelines recommend primary retroperitoneal lymph node dissection (RPLND) as a treatment option for tumour marker-negative stage II nonseminomatous germ cell tumour (NSGCT). OBJECTIVE To review the literature on oncological outcomes for men with stage II NSGCT treated with RPLND. EVIDENCE ACQUISITION A systematic review of studies describing clinicopathological outcomes following primary RPLND in stage II NSGCT was conducted in the MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews databases according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. Baseline data, perioperative and postoperative parameters, and oncological outcomes were collected. EVIDENCE SYNTHESIS In total, 12 of 4387 studies were included, from which we collected data for 835 men. Among men with clinical stage II NSGCT, pathological stage II was confirmed in 615 of 790 patients (78%). Most studies administered adjuvant chemotherapy in cases with large lymph nodes, multiple affected lymph nodes, or persistently elevated tumour markers. Recurrence was observed in 12-40% of patients without adjuvant chemotherapy and 0-4% of patients who received adjuvant chemotherapy. CONCLUSIONS The literature describing RPLND in clinical stage II NSGCT is heterogeneous and no meta-analysis was possible, but RPLND can provide accurate staging and may be curative in selected patients. PATIENT SUMMARY We reviewed the literature to summarise results after surgical removal of enlarged lymph nodes in the back of the abdomen in men with testis cancer. This procedure provides accurate information on how far the cancer has spread and may provide a cure in selected patients