Brain Magnetic Resonance Imaging Reveals Different Courses of Disease in Pediatric and Adult Cerebral Malaria.

BACKGROUND: Cerebral malaria is a common presentation of severe Plasmodium falciparum infection and remains an important cause of death in the tropics. Key aspects of its pathogenesis are still incompletely understood, but severe brain swelling identified by magnetic resonance imaging (MRI) was associated with a fatal outcome in African children. In contrast, neuroimaging investigations failed to identify cerebral features associated with fatality in Asian adults. METHODS: Quantitative MRI with brain volume assessment and apparent diffusion coefficient (ADC) histogram analyses were performed for the first time in 65 patients with cerebral malaria to compare disease signatures between children and adults from the same cohort, as well as between fatal and nonfatal cases. RESULTS: We found an age-dependent decrease in brain swelling during acute cerebral malaria, and brain volumes did not differ between fatal and nonfatal cases across both age groups. In nonfatal disease, reversible, hypoxia-induced cytotoxic edema occurred predominantly in the white matter in children, and in the basal ganglia in adults. In fatal cases, quantitative ADC histogram analyses also demonstrated different end-stage patterns between adults and children: Severe hypoxia, evidenced by global ADC decrease and elevated plasma levels of lipocalin-2 and microRNA-150, was associated with a fatal outcome in adults. In fatal pediatric disease, our results corroborate an increase in brain volume, leading to augmented cerebral pressure, brainstem herniation, and death. CONCLUSIONS: Our findings suggest distinct pathogenic patterns in pediatric and adult cerebral malaria with a stronger cytotoxic component in adults, supporting the development of age-specific adjunct therapies.

Household and individual level risk factors associated with declining malaria incidence in Meghalaya, India: implications for malaria elimination in low-endemic settings.

BACKGROUND: A detailed analysis of household and individual level Plasmodium infection patterns in two low-endemic districts of Meghalaya was undertaken to better understand the epidemiology of malaria in northeast India. METHODS: Socio-demographic and behavioural information from residents (aged 1-69 years) of households were collected through pre-tested, questionnaire conducted in 2018 and 2019. Blood samples collected from participants were tested for Plasmodium falciparum and/or Plasmodium vivax infection using rapid diagnostic test, microscopy and PCR. Plasma samples from a subset of participants were analysed for antibodies against thirteen P. falciparum and four P. vivax antigens. Associations between household and individual level risk factors, and Plasmodium infections were evaluated using multilevel logistic regression models. RESULTS: A total of 2753 individuals from 827 households were enrolled in 2018, and 834 individuals from 222 households were enrolled in 2019. Of them, 33 (1.2%) were positive by PCR for P. falciparum in 2018 and none were positive for P. vivax. In 2019, no PCR-positive individuals were detected. All, but one, infections were asymptomatic; all 33 infections were sub-microscopic. Reported history of malaria in the past 12 months (OR = 8.84) and history of travel in the past 14 days (OR = 10.06) were significantly associated with Plasmodium infection. A significant trend of increased seropositivity with age was noted for all 17 antigens. Although adults (≥ 18 years) consistently had the highest seropositivity rates, a sizeable proportion of under-five children were also found to be seropositive. Almost all individuals (99.4%) reported sleeping under an insecticide-treated bed-net, and household indoor residual spray coverage in the 12 months preceding the survey was low (23%). Most participants correctly identified common signs and symptoms of malaria, i.e., fever (96.4%), headache (71.2%), chills (83.2%) and body-ache (61.8%). Almost all participants (94.3%) used government-provided services for treatment of malaria. CONCLUSION: This study explored the epidemiology of malaria in two communities in Meghalaya, India, in the context of declining transmission. The presence of widespread asymptomatic infections and seropositivity among under-five children suggest that low-level Plasmodium transmission persists in this region. Implications of the study findings for malaria elimination efforts in low-transmission settings are discussed.

Spatial and temporal village-level prevalence of Plasmodium infection and associated risk factors in two districts of Meghalaya, India.

BACKGROUND: Despite declining incidence over the past decade, malaria remains an important health burden in India. This study aimed to assess the village-level temporal patterns of Plasmodium infection in two districts of the north-eastern state of Meghalaya and evaluate risk factors that might explain these patterns. METHODS: Primary Health Centre passive malaria case data from 2014 to 2018 were analysed to characterize village-specific annual incidence and temporal trends. Active malaria case detection was undertaken in 2018 and 2019 to detect Plasmodium infections using PCR. A questionnaire collected socio-demographic, environmental, and behavioural data, and households were spatially mapped via GPS. Adult mosquitoes were sampled at a subset of subjects' houses, and Anopheles were identified by PCR and sequencing. Risk factors for Plasmodium infection were evaluated using bivariate and multivariate logistic regression analysis, and spatial cluster analysis was undertaken. RESULTS: The annual malaria incidence from PHC-based passive surveillance datasets in 2014-2018 was heterogenous but declining across villages in both districts. Active surveillance in 2018 enrolled 1468 individuals from 468 households (West Jaintia Hills) and 1274 individuals from 359 households (West Khasi Hills). Plasmodium falciparum prevalence per 100 people varied from 0 to 4.1% in the nine villages of West Jaintia Hills, and from 0 to 10.6% in the 12 villages of West Khasi Hills. Significant clustering of P. falciparum infections [observed = 11, expected = 2.15, Relative Risk (RR) = 12.65; p < 0.001] was observed in West Khasi Hills. A total of 13 Anopheles species were found at 53 houses in five villages, with Anopheles jeyporiensis being the most abundant. Risk of infection increased with presence of mosquitoes and electricity in the households [Odds Ratio (OR) = 1.19 and 1.11], respectively. Households with reported animals had reduced infection risk (OR = 0.91). CONCLUSION: Malaria incidence during 2014-2018 declined in all study villages covered by the passive surveillance data, a period that includes the first widespread insecticide-treated net campaign. The survey data from 2018 revealed a significant association between Plasmodium infection and certain household characteristics. Since species of Plasmodium-competent mosquito vectors continue to be abundant, malaria resurgence remains a threat, and control efforts should continue.

Defining symptoms of malaria in India in an era of asymptomatic infections.

BACKGROUND: Malaria is a major public health problem in India. Data from surveys totaling 3031 participants at three sites revealed a high proportion of asymptomatic infections, complicating diagnosis. The aim of this study was to identify differences in complaints and symptoms between sites, and factors associated with asymptomatic Plasmodium infections. METHODS: Published data from community-based cross-sectional studies conducted between 2012 and 2015 in Nadiad (Gujarat), Chennai (Tamil Nadu), and Rourkela (Odisha) as part of the Center for the Study of Complex Malaria in India were analysed. Complaints and symptoms were systematically recorded, and Plasmodium infections confirmed using microscopy, rapid diagnostic tests (RDTs), and polymerase chain reaction (PCR). Multivariate analyses were conducted to determine the association between general symptoms and age, season, or gender, and factors associated with asymptomatic Plasmodium infections were assessed. RESULTS: Complaints of any illness were lowest in Chennai (17.7%), 30.6% in Rourkela and 42.7% in Nadiad. Complaints were more often reported for children; gender differences were noted in Rourkela only. In Nadiad, 7.0% of 796 participants were positive for malaria by PCR (32% Plasmodium falciparum); 78.6% had a history of fever or documented fever, 14.3% had other symptoms, and 7.1% were "truly asymptomatic". For Chennai this was 29.2%, 4.2% and 66.7% respectively, with a malaria prevalence of 2.6% by PCR of 928 participants (29% P. falciparum). In Rourkela, with 7.7% of 1307 participants positive for malaria by PCR (82% P. falciparum), the percentages were 35.6%, 24.8% and 39.6%, respectively. In Rourkela, asymptomatic infections were associated with young age and male gender (microscopy or RDT), and with rainy season (PCR). In the same site, participants with Plasmodium vivax were more likely to be asymptomatic (11/18 or 61.1%) than persons with P. falciparum mono-infections (27/78 or 34.6%); gametocytes for P. falciparum were evenly distributed between symptomatic and asymptomatic infections (2/53 vs. 2/49, respectively). The addition of the symptoms "headache", "aches" and "chills" to fever improved the case-definition of symptomatic malaria. CONCLUSION: There were considerable differences in complaints at the three sites in India. Malaria and asymptomatic infections differ by region, indicating that malaria elimination will require localized approaches.

What is the value of reactive case detection in malaria control? A case-study in India and a systematic review.

BACKGROUND: Reactive case detection (RCD) for malaria is a strategy to identify additional malaria infections in areas of low malaria transmission and can complement passive surveillance. This study describes experiences with RCD in two Indian sites, and aimed to synthesize experiences with RCD across endemic countries. METHODS: RCD programmes were piloted in two urban areas of India with a low prevalence of mainly Plasmodium vivax malaria in 2014. Cases were identified in a clinic by microscopy and contacts were screened within 2 weeks; PCR, in addition to microscopy, was used to detect Plasmodium parasites. A systematic review was conducted to identify RCD experiences in the literature. RESULTS: In Chennai, 868 contacts were enrolled for 18 index cases of clinical malaria; in Nadiad, 131 contacts were enrolled for 20 index cases. No new malaria infections were detected in Nadiad among contacts, and four new infections were detected in Chennai (three P. vivax and one Plasmodium falciparum), of which two were among household members of index cases. An additional five studies describing results from an RCD strategy were identified in the literature: four in Africa and one in Thailand. Including the results from India, the average number of contacts screened per index case in a total of seven studies ranged from four to 50, and 126 in a case study in Thailand with one index case. Malaria was detected in 0-45 % of the contacted persons. The average number of index cases needed to be traced to find one new case of malaria ranged from one to five, and could not be assessed in one study in India (no contacts positive for 20 cases). Sharing the household with an index case was associated with a five-fold increased risk of malaria compared to contacts from households without an index case (pooled risk ratio 5.29, 95 % CI 3.31-8.47, I(2) 0 %, four studies). CONCLUSIONS: RCD in areas of low malaria transmission is a labour-intensive strategy, and its benefit is not clear. Studies are needed to assess how RCD can be optimized or into alternatives where interventions are targeted to family members or hotspots.

Postsurgical volumetric airway changes in 2-jaw orthognathic surgery patients.

INTRODUCTION: Findings from early cephalometric studies on airway changes after 2-jaw orthognathic surgery have been challenged because the previous anteroposterior interpretation of airway changes can now be evaluated in 3 dimensions. The aims of this study were to use cone-beam computed tomography to quantify the nasopharynx, oropharynx, and total airway volume changes associated with skeletal movements of the maxilla and mandible in a sample of patients undergoing 2-jaw orthognathic surgery for correction of skeletal malocclusion. METHODS: Skeletal movements and airway volumes of 71 postpubertal patients (31 male, 40 female; mean age, 18.8 years) were measured. They were divided into 2 groups based on ANB angle, overjet, and occlusion (Class II: ANB, >2°; overjet, >1 mm; total, 35 subjects; and Class III: ANB, <1°; overjet, <1 mm; total, 36 subjects). Presurgical and postsurgical measurements were collected for horizontal, vertical, and transverse movements of the maxilla and the mandible, along with changes in the nasopharynx, oropharynx, and total airways. Associations between the directional movements of skeletal structures and the regional changes in airway volume were quantified. Changes in the most constricted area were also noted. RESULTS: Horizontal movements of D-point were significantly associated with increases in both total airway (403.6 ± 138.6 mm(3); P <0.01) and oropharynx (383.9 ± 127.9 mm(3); P <0.01) volumes. Vertical movements of the posterior nasal spine were significantly associated with decreases in total airway volume (-459.2 ± 219.9 mm(3); P = 0.04) and oropharynx volume (-639.7 ± 195.3 mm(3); P <0.01), increases in nasopharynx (187.2 ± 47.1 mm(3); P <0.01) volume, and decreases in the most constricted area (-10.63 ± 3.69 mm(2); P <0.01). In the Class III patients only, the vertical movement of D-point was significantly associated with decreases in both total airway (-724.0 ± 284.4 mm(3); P = 0.02) and oropharynx (-648.2 ± 270.4 mm(3); P = 0.02) volumes. A similar negative association was observed for the most constricted area for the vertical movement of D-point (-15.45 ± 4.91 mm(2); P <0.01). CONCLUSIONS: Optimal control of airway volume is through management of the mandible in the horizontal direction and the vertical movement of the posterior maxilla for all patients. The surgeon and the orthodontist should optimally plan these movements to control gains or losses in airway volume as a result of orthognathic surgery.

Comparative genomics of the neglected human malaria parasite Plasmodium vivax.

The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.

Pituitary carcinoma with endolymphatic sac metastasis.

Pituitary carcinoma is characterized by the presence of a metastatic lesion(s) in a location non-contiguous with the original pituitary tumor. The mechanism(s) of malignant transformation are not known. A 15 year-old male was diagnosed in 1982 with a pituitary macroadenoma and acromegaly (random GH 67 ng/ml and no suppression by oral glucose). His prolactin was normal between 18 and 23 ng/ml. Transcranial resection in July 1983 was followed by radiation therapy. The tumor was immunopositive for GH and prolactin. The proliferation MIB-1 index was 0-1%. With aqueous Octreotide 100 mcg 4× daily both GH and IGF-1 became normal. The patient was lost to follow-up and was treated by his local physician. In 2001, his IGF-1 level was 1271 ng/ml, and his random GH was 1.8-2.4 ng/ml by ILMA despite progressive increase in the dose of Sandostatin LAR to 140 mg/month in divided doses. Prolactin remained normal or minimally increased between 15 and 25 ng/ml. In 2009 he was diagnosed with the tumor in the location of left endolymphatic sac. Histological examination showed low grade pituitary carcinoma strongly immunopositive for prolactin but negative for GH. MIB-1 antibody labeled 0-5% cells. In 2012 endoscopic resection of the pituitary tumor remnant was attempted. Immunohistochemical stains were strongly immunopositive for both prolactin and GH, similar to his original pituitary tumor. The MIB-1 proliferation index was low from 0 to 1%. To our knowledge this is the first case of pituitary carcinoma in the endolymphatic sac region. The dichotomy between the cell population of the pituitary lesion (GH/prolactin producing) and the metastasis (purely prolactin-producing) may suggest that the metastatic pituitary lesion derived from a clone distinct from the original one.

Metal-free reductive cleavage of C-N and S-N bonds by photoactivated electron transfer from a neutral organic donor.

A photoactivated neutral organic super electron donor cleaves challenging arenesulfonamides derived from dialkylamines at room temperature. It also cleaves a) ArCNR and b) ArNC bonds. This study also highlights the assistance given to these cleavage reactions by the groups attached to N in (a) and to C in (b), by lowering LUMO energies and by stabilizing the products of fragmentation.

The Genome of Plasmodium gonderi: Insights into the Evolution of Human Malaria Parasites.

Plasmodium species causing malaria in humans are not monophyletic, sharing common ancestors with nonhuman primate parasites. Plasmodium gonderi is one of the few known Plasmodium species infecting African old-world monkeys that are not found in apes. This study reports a de novo assembled P. gonderi genome with complete chromosomes. The P. gonderi genome shares codon usage, syntenic blocks, and other characteristics with the human parasites Plasmodium ovale s.l. and Plasmodium malariae, also of African origin, and the human parasite Plasmodium vivax and species found in nonhuman primates from Southeast Asia. Using phylogenetically aware methods, newly identified syntenic blocks were found enriched with conserved metabolic genes. Regions outside those blocks harbored genes encoding proteins involved in the vertebrate host-Plasmodium relationship undergoing faster evolution. Such genome architecture may have facilitated colonizing vertebrate hosts. Phylogenomic analyses estimated the common ancestor between P. vivax and an African ape parasite P. vivax-like, within the Asian nonhuman primates parasites clade. Time estimates incorporating P. gonderi placed the P. vivax and P. vivax-like common ancestor in the late Pleistocene, a time of active migration of hominids between Africa and Asia. Thus, phylogenomic and time-tree analyses are consistent with an Asian origin for P. vivax and an introduction of P. vivax-like into Africa. Unlike other studies, time estimates for the clade with Plasmodium falciparum, the most lethal human malaria parasite, coincide with their host species radiation, African hominids. Overall, the newly assembled genome presented here has the quality to support comparative genomic investigations in Plasmodium.

An integrated self-optimizing programmable chemical synthesis and reaction engine.

Robotic platforms for chemistry are developing rapidly but most systems are not currently able to adapt to changing circumstances in real-time. We present a dynamically programmable system capable of making, optimizing, and discovering new molecules which utilizes seven sensors that continuously monitor the reaction. By developing a dynamic programming language, we demonstrate the 10-fold scale-up of a highly exothermic oxidation reaction, end point detection, as well as detecting critical hardware failures. We also show how the use of in-line spectroscopy such as HPLC, Raman, and NMR can be used for closed-loop optimization of reactions, exemplified using Van Leusen oxazole synthesis, a four-component Ugi condensation and manganese-catalysed epoxidation reactions, as well as two previously unreported reactions, discovered from a selected chemical space, providing up to 50% yield improvement over 25-50 iterations. Finally, we demonstrate an experimental pipeline to explore a trifluoromethylations reaction space, that discovers new molecules.

Overturning established chemoselectivities: selective reduction of arenes over malonates and cyanoacetates by photoactivated organic electron donors.

The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate-metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor 5 selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates.

Retinal NMDA receptor function and expression are altered in a mouse lacking D-amino acid oxidase.

D-serine is present in the vertebrate retina and serves as a coagonist for the N-methyl-D-aspartate (NMDA) receptors of ganglion cells. Although the enzyme D-amino acid oxidase (DAO) has been implicated as a pathway for d-serine degradation, its role in the retina has not been established. In this study, we investigated the role of DAO in regulating D-serine levels using a mutant mouse line deficient in DAO (ddY/DAO(-)) and compared these results with their wild-type counterparts (ddY/DAO(+)). Our results show that DAO is functionally present in the mouse retina and normally serves to reduce the background levels of D-serine. The enzymatic activity of DAO was restricted to the inner plexiform layer as determined by histochemical analysis. Using capillary electrophoresis, we showed that mutant mice had much higher levels of D-serine. Whole cell recordings from identified retinal ganglion cells demonstrated that DAO-deficient animals had light-evoked synaptic activity strongly biased toward a high NMDA-to-AMPA receptor ratio. In contrast, recordings from wild-type ganglion cells showed a more balanced ratio between the two receptor subclasses. Immunostaining for AMPA and NMDA receptors was carried out to compare the two receptor ratios by quantitative immunofluorescence. These studies revealed that the mutant mouse had a significantly higher representation of NMDA receptors compared with the wild-type controls. We conclude that 1) DAO is an important regulatory enzyme and normally functions to reduce D-serine levels in the retina, and 2) D-serine levels play a role in the expression of NMDA receptors and the NMDA-to-AMPA receptor ratio.

A comparison of particulate and Onyx embolization in preoperative devascularization of carotid body tumors.

INTRODUCTION: Preoperative embolization of a carotid body tumor (CBT) is a useful adjunct prior to surgical excision because it decreases operative blood loss and improves surgical outcomes. Traditionally, this is performed by transarterial particulate embolization (TAPE). More recently, direct percutaneous embolization (DPE) with Onyx is recognized as a promising technique for preoperative embolization. We compared these two techniques in patients treated for CBTs at our institution. METHODS: We retrospectively reviewed cases of preoperative devascularization of CBT from 1 January 1995 through 1 September 2012. Patient cases were placed into two groups: TAPE and DPE. Operative blood loss, operative length, angiographic devascularization, embolization procedure complications, operative transfusion requirements, postoperative hospital stay, intensive care unit (ICU) stay, and procedure-related mortalities were compared. RESULTS: A total of 17 patients underwent preoperative devascularization of their CBT with TAPE technique and ten patients using the DPE technique with Onyx. Average operative blood loss was significantly higher in the TAPE group (Mann-Whitney U test, p = 0.04). Operative time was also higher, although this difference was not significant. Two patients required intraoperative blood transfusions in the TAPE group while none required transfusions in the DPE group. There was no significant difference in ICU stay or length of hospitalization. One serious embolization procedure complication occurred in the TAPE group and none in the DPE group. CONCLUSION: Operative blood loss in the DPE group was significantly less than the TAPE group. Blood transfusion requirement, operative time, and complications were less in the DPE group, although they did not reach statistical significance.

A comparison of particulate and onyx embolization in preoperative devascularization of juvenile nasopharyngeal angiofibromas.

INTRODUCTION: Juvenile nasopharyngeal angiofibromas (JNAs) are hypervascular tumors that may benefit from preoperative devascularization to reduce intraoperative blood loss (IBL). The purpose of this study was to compare transarterial particulate embolization (TAPE) with the direct percutaneous embolization (DPE) technique using ethylene vinyl alcohol (Onyx, ev3, Irvine, CA) for the preoperative devascularization of a JNA. METHODS: We retrospectively reviewed 50 consecutive JNA resections since 1995 for which preoperative embolization was either transarterial with particulate material (n = 39) or DPE (n = 11) using only Onyx. The IBL, transfusion requirements, operative time, and length of hospital admission were compared between the two groups. RESULTS: The mean IBL was 1,348.7 ± 932.2 mL particulate group, 569.1 ± 700.7 mL Onyx group (one-tailed Student's t test p = 0.003). The mean unit of packed red blood cells was 1.56 ± 2.01 units particulate group, 0.45 ± 1.04 units Onyx group (p = 0.009). The relationship between embolization type and IBL remained significant or strongly correlated when accounting for the Fisch stage of the tumor (p = 0.010 and p = 0.056, respectively, by a multivariate least squares fit; alternately p = 0.0003 and p = 0.023, respectively, in the subset of patients with Fisch stage III tumors only). We also found that the proportion of resections for which an endoscopic approach could be used was significantly higher in the Onyx group than the particulate group (81.8 and 18.2 %; Pearson p = 0.0002), and this was also significant both in our multivariate nominal logistic fit (p < 0.001) and in the subset of patients with Fisch stage III tumors (p = 0.018). CONCLUSION: Pre-operative DPE with Onyx of a JNA when compared to TAPE significantly decreased IBL and RBC transfusion requirement during surgical resection. The proportion of surgical resections performed from an endoscopic approach was higher in the DPE Onyx group, which may have affected the results.

A strategy toward the synthesis of C13-oxidized cembrenolides.

An efficient strategy for the construction of C13-oxidized cembrenolides is reported. Central to this strategy is the installation of the C13 hydroxyl group prior to cembrane macrocyclization (via formation of the C1-C2 bond), allowing access to both C13 alcohol epimers. The orientation of the C13 alcohol was found to influence the cyclization mode of the cembranolide scaffold upon furan oxidation, leading to motifs reminiscent to bipinnatolide F, bielschowskysin, and verrillin.

Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli.

Extraintestinal pathogenic Escherichia coli (ExPEC) are a common cause of disease in both mammals and birds. A vaccine to prevent such infections would be desirable given the increasing antibiotic resistance of these bacteria. We have determined the genome sequence of ExPEC IHE3034 (ST95) isolated from a case of neonatal meningitis and compared this to available genome sequences of other ExPEC strains and a few nonpathogenic E. coli. We found 19 genomic islands present in the genome of IHE3034, which are absent in the nonpathogenic E. coli isolates. By using subtractive reverse vaccinology we identified 230 antigens present in ExPEC but absent (or present with low similarity) in nonpathogenic strains. Nine antigens were protective in a mouse challenge model. Some of them were also present in other pathogenic non-ExPEC strains, suggesting that a broadly protective E. coli vaccine may be possible. The gene encoding the most protective antigen was detected in most of the E. coli isolates, highly conserved in sequence and found to be exported by a type II secretion system which seems to be nonfunctional in nonpathogenic strains.

Predicting First-Time National Physical Therapy Examination Performance for Graduates of an Entry-Level Physical Therapist Education Program.

INTRODUCTION: The National Physical Therapy Examination (NPTE) is a standardized examination designed to assess competence after graduation from an entry-level physical therapist education program. REVIEW OF LITERATURE: Previous studies have identified applicant and student variables that are related to NPTE performance, with applicant variables reflecting performance before admission and student variables reflecting performance after admission. However, there are very few articles describing how these variables can be combined to predict NPTE performance. The purpose of this study was to develop, evaluate, and describe models to predict first-time NPTE scores and NPTE outcomes (pass vs fail), based on various applicant and student variables related to academic performance. SUBJECTS: Pre- and postadmission data and NPTE scores were recorded for 185 individuals who graduated from an entry-level physical therapist education program. METHODS: Multiple linear regression was used to develop a model to predict NPTE scores, and binary logistic regression was used to develop a model to predict NPTE outcomes (pass vs fail). RESULTS: A model including undergraduate prerequisite grade point average, grade point average in basic science courses taken during the program, and comprehensive examination scores combined to explain 30.9% of the variance in NPTE scores and accurately predicted NPTE outcomes (pass vs fail) 81.1% of the time. DISCUSSION: In general, our findings support the notion that prediction of NPTE performance should be based on a combination of applicant and student variables. The models described in this article could be used to identify students who may be likely to struggle on the NPTE, making it possible to provide additional support to these students. CONCLUSION: Various applicant and student variables related to academic performance can be combined to predict NPTE performance. The results of this study provide a framework for programs interested in applying models to predict NPTE performance.

Persistent Trichomonas vaginalis infections and the pseudocyst form.

Recent studies have proposed that Trichomonas vaginalis, the causative agent of trichomoniasis [the most common nonviral sexually transmitted infection (STI) in humans] can establish persistent infections in the vagina. T. vaginalis infections are often asymptomatic but can have adverse consequences such as increased risk of HIV-1 infection and cervical cancer. Despite this, it remains an understudied infection. A potential agent of persistent infections is the 'pseudocyst', a spherical form of T. vaginalis identified by several laboratories and linked to persistence in related species such as the avian parasite Trichomonas gallinae and cattle parasite Tritrichomonas foetus. Additional robust and reproducible research on pseudocysts and persistent T. vaginalis infections is required, which may ultimately shed light on how to better diagnose and treat trichomoniasis.

The effectiveness of malaria camps as part of the malaria control program in Odisha, India.

Durgama Anchalare Malaria Nirakaran (DAMaN) is a multi-component malaria intervention for hard-to-reach villages in Odisha, India. The main component, Malaria Camps (MCs), consists of mass screening, treatment, education, and intensified vector control. We evaluated MC effectiveness using a quasi-experimental cluster-assigned stepped-wedge study with a pretest-posttest control group in 15 villages: six immediate (Arm A), six delayed (Arm B), and three previous interventions (Arm C). The primary outcome was PCR+ Plasmodium infection prevalence. Across all arms, the odds of PCR+ malaria were 54% lower at the third follow-up compared to baseline. A time (i.e., visit) x study arm interaction revealed significantly lower odds of PCR+ malaria in Arm A versus B at the third follow-up. The cost per person ranged between US$3-8, the cost per tested US$4-7, and the cost per treated US$82-1,614, per camp round. These results suggest that the DAMaN intervention is a promising, financially feasible approach for malaria control.