Development of Artificial Intelligence-Teaching Assistant System for Undergraduate Nursing Students: A Field-Testing Study.

Keeping students engaged and motivated during online or class discussion may be challenging. Artificial intelligence has potential to facilitate active learning by enhancing student engagement, motivation, and learning outcomes. The purpose of this study was to develop, test usability of, and explore undergraduate nursing students' perceptions toward the Artificial Intelligence-Teaching Assistant System. The system was developed based on three main components: machine tutor intelligence, a graphical user interface, and a communication connector. They were included in the system to support contextual machine tutoring. A field-testing study design, a mixed-method approach, was utilized with questionnaires and focus group interview. Twenty-one undergraduate nursing students participated in this study, and they interacted with the system for 2 hours following the required activity checklist. The students completed the validated usability questionnaires and then participated in the focus group interview. Descriptive statistics were used to analyze quantitative data, and thematic analysis was used to analyze qualitative data from the focus group interviews. The results showed that the Artificial Intelligence-Teaching Assistant System was user-friendly. Four main themes emerged, namely, functionality, feasibility, artificial unintelligence, and suggested learning modality. However, Artificial Intelligence-Teaching Assistant System functions, user interface, and content can be improved before full implementation.

Reduced Peak Bone Mass in Young Adults With Low Motor Competence.

Although suboptimal bone health has been reported in children and adolescents with low motor competence (LMC), it is not known whether such deficits are present at the time of peak bone mass. We examined the impact of LMC on bone mineral density (BMD) in 1043 participants (484 females) from the Raine Cohort Study. Participants had motor competence assessed using the McCarron Assessment of Neuromuscular Development at 10, 14, and 17 years, and a whole-body dual-energy X-ray absorptiometry (DXA) scan at 20 years. Bone loading from physical activity was estimated from the International Physical Activity Questionnaire at the age of 17 years. The association between LMC and BMD was determined using general linear models that controlled for sex, age, body mass index, vitamin D status, and prior bone loading. Results indicated LMC status (present in 29.6% males and 21.9% females) was associated with a 1.8% to 2.6% decrease in BMD at all load-bearing bone sites. Assessment by sex showed that the association was mainly in males. Osteogenic potential of physical activity was associated with increased BMD dependent on sex and LMC status, with males with LMC showing a reduced effect from increasing bone loading. As such, although engagement in osteogenic physical activity is associated with BMD, other factors involved in physical activity, eg, diversity, movement quality, may also contribute to BMD differences based upon LMC status. The finding of lower peak bone mass for individuals with LMC may reflect a higher risk of osteoporosis, especially for males; however, further research is required. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Utilizing educational technology in enhancing undergraduate nursing students' engagement and motivation: A scoping review.

BACKGROUND: Modern educational technology (Edtech) combines technological tools with educational theories. Over the years, Edtech has been adopted in nursing education to address student needs and expectations, institutional resources, community stakeholder expectations, and healthcare trends. However, regardless of the technologies used, keeping students engaged in learning is still challenging. As intrinsic motivation is significantly related to academic achievement, ensuring student engagement and motivation for learning becomes crucial. AIMS: This scoping review aims to explore the types and features of modern Edtech that have impacted on undergraduate nursing students' engagement and motivation. DESIGN: This scoping review is based on the five-stage approach following Arksey and O'Malley's framework, and the Engagement theory framework for technology-based teaching and learning. METHODS: A systemic search was conducted across 10 electronic databases (PubMed, EMBASE, CINAHL, PsycINFO, ProQuest, Web of Science, Cochrane, Engineering Village, and IEEE Explore). The titles, abstracts, and full texts were screened and reviewed based on the inclusion criteria of undergraduate nursing students, using innovative Edtech, and outcomes of engagement and motivation. Studies published in non-peer reviewed journals, or not in English were excluded. Study characteristics were summarized and quantified. Descriptions of educational technology characteristics from selected studies were coded and categorized as follows: "Facilitating collaboration", "Stimulating problem-solving", and "Pursuing authentic focus". RESULTS: Majority of the studies utilised gamification over other types of Edtech such as virtual reality or smart glasses, successfully engaging and motivating students through the features of collaboration, competition, and challenge. Despite the high technology aspect of the interventions used, the human presence as an authentic focus was perceived to be important in engaging students in learning experience. Moreover, attaining meaningful achievements also improves engagement and motivation. CONCLUSIONS: Edtech can promote positive engagement and motivation of undergraduate nursing students. Educators should emphasize an authentic focus in students' learning experience with Edtech.

Association of developmental coordination disorder and low motor competence with impaired bone health: A systematic review.

AIMS: Individuals with developmental coordination disorder (DCD) and low motor competence (LMC) may be at increased risk of low bone health due to their lifetime physical activity patterns. Impaired bone health increases an individual's risk of osteoporosis and fracture; therefore, it is necessary to determine whether a bone health detriment is present in this group. Accordingly, this systematic review explores the association between DCD/LMC and bone health. METHODS AND PROCEDURES: Studies were included with assessment of bone health in a DCD/LMC population. Study bias was assessed using the JBI critical appraisal checklist. Due to heterogeneity, meta-analysis was not possible and narrative synthesis was performed with effect size and direction assessed via harvest plots. OUTCOMES AND RESULTS: A total of 16 (15 paediatric/adolescent) studies were included. Deficits in bone measures were reported for the DCD/LMC group and were more frequent in weight-bearing sites. Critical appraisal indicated very low confidence in the results, with issues relating to indirectness and imprecision relating to comorbidities. CONCLUSIONS AND IMPLICATIONS: Individuals with DCD or LMC are at increased risk of bone health deficits. Bone impairment locations indicate insufficient loading via physical activity as a potential cause of bone deficits. Results indicate a potential for earlier osteoporosis onset.

Biofluid markers of blood-brain barrier disruption and neurodegeneration in Lewy body spectrum diseases: A systematic review and meta-analysis.

BACKGROUND: Mixed evidence supports blood-brain barrier (BBB) dysfunction in Lewy body spectrum diseases. METHODS: We compare biofluid markers in people with idiopathic Parkinson's disease (PD) and people with PD dementia (PDD) and/or dementia with Lewy bodies (DLB), compared with healthy controls (HC). Seven databases were searched up to May 10, 2021. Outcomes included cerebrospinal fluid to blood albumin ratio (Qalb), and concentrations of 7 blood protein markers that also reflect BBB disruption and/or neurodegenerative co-pathology. We further explore differences between PD patients with and without evidence of dementia. Random-effects models were used to obtain standardized mean differences (SMD) with 95% confidence interval. RESULTS: Of 13,949 unique records, 51 studies were meta-analyzed. Compared to HC, Qalb was higher in PD (NPD/NHC = 224/563; SMD = 0.960 [0.227-1.694], p = 0.010; I2 = 92.2%) and in PDD/DLB (NPDD/DLB/NHC = 265/670; SMD = 1.126 [0.358-1.893], p < 0.001; I2 = 78.2%). Blood neurofilament light chain (NfL) was higher in PD (NPD/NHC = 1848/1130; SMD = 0.747 [0.442-1.052], p < 0.001; I2 = 91.9%) and PDD/DLB (NPDD/DLB/NHC = 183/469; SMD = 1.051 [0.678-1.423], p = 0.004; I2 = 92.7%) than in HC. p-tau 181 (NPD/NHC = 276/164; SMD = 0.698 [0.149-1.247], p = 0.013; I2 = 82.7%) was also higher in PD compared to HC. In exploratory analyses, blood NfL was higher in PD without dementia (NPDND/NHC = 1005/740; SMD = 0.252 [0.042-0.462], p = 0.018; I2 = 71.8%) and higher in PDD (NPDD/NHC = 100/111; SMD = 0.780 [0.347-1.214], p < 0.001; I2 = 46.7%) compared to HC. Qalb (NPDD/NPDND = 63/191; SMD = 0.482 [0.189-0.774], p = 0.010; I2<0.001%) and NfL (NPDD/NPDND = 100/223; SMD = 0.595 [0.346-0.844], p < 0.001; I2 = 3.4%) were higher in PDD than in PD without dementia. CONCLUSIONS: Biofluid markers suggest BBB disruption and neurodegenerative co-pathology involvement in common Lewy body diseases. Greater evidence of BBB breakdown was seen in Lewy body disease with cognitive impairment.

Physical activity estimated by osteogenic potential and energy expenditure has differing associations with bone mass in young adults: the raine study.

Ground impacts during physical activity may be important for peak bone mass. We found differences in how energy expenditure and impact scores estimated from a physical activity questionnaire related to bone health in young adults. Using both estimate types can improve our understanding of the skeletal benefits of physical activity. PURPOSE: It is unclear whether mechanical loading during physical activity, estimated from physical activity questionnaires which assess metabolic equivalents of task (METs), is associated with skeletal health. This longitudinal study investigated how physical activity loading scores, assessed at ages 17 and 20 years, (a) compares with physical activity measured in METs, and (b) is associated with bone mass at age 20 years. METHODS: A total of 826 participants from the Raine Study Gen2 were assessed for physical activity energy expenditure via the International Physical Activity Questionnaire (IPAQ) at age 17 and 20 years. Loading scores (the product of peak force and application rate) per week were subsequently estimated from the IPAQ. Whole-body and appendicular bone mineral density (BMD) at age 20 years were assessed by dual-energy X-ray absorptiometry. RESULTS: Bland-Altman minimal detectable difference for physical activity Z- scores at age 17 and 20 years were 1.59 standard deviations (SDs) and 1.33 SDs, respectively, greater than the a priori minimal clinically important change of 0.5 SDs. Loading score, but not IPAQ score, had significant positive associations with whole-body and leg BMD after adjustment for covariates (ß = 0.008 and 0.012 g/cm2, respectively, for age 17 and 20 years loading scores). IPAQ score at age 20 years, but not loading score, had a significant positive association with arm BMD (ß = 0.007 g/cm2). CONCLUSION: This study revealed disagreement in associations of self-reported METs and loading score estimates with bone health in young adults. Coupling traditional energy expenditure questionnaire outcomes with bone-loading estimates may improve understanding of the location-specific skeletal benefits of physical activity in young adults.

Effect of childhood developmental coordination disorder on adulthood physical activity; Arvo Ylppö longitudinal study.

Individuals at risk of Developmental Coordination Disorder (DCD) have low levels of physical activity in childhood due to impaired motor competence; however, physical activity levels in adulthood have not been established. This study sought to determine the impact of DCD risk on physical activity levels in adults using accelerometry measurement. Participants (n = 656) from the Arvo Ylppö Longitudinal Study cohort had their motor competence assessed at the age of five years, and their physical activity quantified via device assessment at the age of 25 years. Between group differences were assessed to differentiate physical activity measures for individuals based on DCD risk status, with general linear modeling performed to control for the effects of sex, body mass index (BMI), and maternal education. Participants at risk of DCD were found to have a lower total number of steps (d = 0.3, p = 0.022) than those not at risk. Statistical modeling indicated that DCD risk status increased time spent in sedentary light activity (ß = 0.1, 95% CI 0.02 to 0.3, p = 0.026) and decreased time spent in vigorous physical activity via interaction with BMI (ß = 0.04, 95% CI 0.001 to 0.1, p = 0.025). Sensitivity analysis found that visuomotor impairment did not significantly impact physical activity but did increase the role of DCD risk status in some models. This 20-year-longitudinal study indicated that DCD risk status continues to negatively impact on levels of physical activity into early adulthood.

The association of mobilising regimen on immune reconstitution and survival in myeloma patients treated with bortezomib, cyclophosphamide and dexamethasone induction followed by a melphalan autograft.

G-CSF only mobilisation has been shown to enhance immune reconstitution early post-transplant, but its impact on survival remains uncertain. We undertook a retrospective review of 12 transplant centres to examine overall survival (OS) and time to next treatment (TTNT) following melphalan autograft according to mobilisation method (G-CSF only vs. G-CSF and cyclophosphamide [CY]) in myeloma patients uniformly treated with bortezomib, cyclophosphamide and dexamethasone induction. Six centres had a policy to use G-CSF alone and six to use G-CSF + CY. Patients failing G-CSF only mobilisation were excluded. 601 patients were included: 328: G-CSF + CY, 273: G-CSF only. Mobilisation arms were comparable in terms of age, Revised International Staging System (R-ISS) groups and post-transplant maintenance therapy. G-CSF + CY mobilisation generated higher median CD34 + yields (8.6 vs. 5.5 × 106/kg, p < 0.001). G-CSF only mobilisation was associated with a significantly higher lymphocyte count at day 15 post-infusion (p < 0.001). G-CSF only mobilisation was associated with significantly improved OS (aHR = 0.60, 95%CI 0.39-0.92, p = 0.018) and TTNT (aHR = 0.77, 95%CI 0.60-0.97, p = 0.027), when adjusting for R-ISS, disease-response pre-transplant, age and post-transplant maintenance therapy. This survival benefit may reflect selection bias in excluding patients with unsuccessful G-CSF only mobilisation or may be due to enhanced autograft immune cell content and improved early immune reconstitution.

Association between developmental coordination disorder or low motor competence, and risk of impaired bone health across the lifespan: protocol for a systematic review and meta-analysis.

OBJECTIVE: This systematic review will assess the association between developmental coordination disorder or low motor competence and impairments in bone health across the lifespan. INTRODUCTION: Individuals with developmental coordination disorder tend to have a pattern of physical activity associated with bone health impairments. Preliminary studies have found impairments in bone health measures, including fractures, throughout the lifespan with potential public health ramifications. As studies in this area are of small samples across wide age ranges, no comprehensive picture of bone health in this group has been formed, hindering action. A systematic review is needed to determine the potential risk of bone impairment in this population. INCLUSION CRITERIA: Studies that assess the relationship between developmental coordination disorder/low motor competence and bone health, regardless of measures used, will be included in the review. There will be no exclusions based on region, study design, or participant demographic characteristics. METHODS: Published studies and gray literature will be searched, with no limits on publication date or language. Assessment of studies for inclusion, as well as data extraction, will be performed by two reviewers, with data cross checked for accuracy. Studies will be appraised using the appropriate JBI tool for the study design. Data to be extracted include unadjusted results and effect sizes for bone health measures. A narrative synthesis will be performed and if there is a sufficient number of studies, a meta-analysis using the same outcome measures will be performed on odds ratios of abnormal bone phenotype and fracture in this population. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020167301.

Impact of a multimodal exercise program on tibial bone health in adolescents with Development Coordination Disorder: an examination of feasibility and potential efficacy.

OBJECTIVES: Developmental coordination disorder (DCD) compromises bone health purportedly due to lower levels of physical activity. The potential of an exercise intervention to improve bone health parameters in adolescents with DCD has not previously been studied. This study thus aimed to determine the impact of a multimodal exercise intervention on bone health in this population at-risk of secondary osteoporosis. METHODS: Twenty-eight adolescents (17 male, 11 female) aged between 12-17 years (Mage=14.1) with DCD participated in a twice weekly, 13-week generalised multimodal exercise intervention. Peripheral quantitative computed tomography scans of the tibia (4% and 66%) were performed over a six month period. Generalised estimating equations were used to examine the impact of fitness measures on bone parameters over time. RESULTS: An overall improvement trend was observed for bone health, with significant increases at the 66% tibial site for bone mass (4.12% increase, dcohen=0.23, p=0.010) and cortical area (5.42% increase, η2 =12.09, p=0.014). Lower body fitness measures were significantly associated with improvements in bone health parameters, tempered by the degree of motor impairment. CONCLUSION: A multimodal exercise intervention may be effective in improving bone health of adolescents with DCD. Given the impact of motor impairments, gains may be greater over an extended period of study.

Biological basis of bone strength: anatomy, physiology and measurement.

Understanding how bones are innately designed, robustly developed and delicately maintained through intricate anatomical features and physiological processes across the lifespan is vital to inform our assessment of normal bone health, and essential to aid our interpretation of adverse clinical outcomes affecting bone through primary or secondary causes. Accordingly this review serves to introduce new researchers and clinicians engaging with bone and mineral metabolism, and provide a contemporary update for established researchers or clinicians. Specifically, we describe the mechanical and non-mechanical functions of the skeleton; its multidimensional and hierarchical anatomy (macroscopic, microscopic, organic, inorganic, woven and lamellar features); its cellular and hormonal physiology (deterministic and homeostatic processes that govern and regulate bone); and processes of mechanotransduction, modelling, remodelling and degradation that underpin bone adaptation or maladaptation. In addition, we also explore commonly used methods for measuring bone metabolic activity or material features (imaging or biochemical markers) together with their limitations.

Discovery of a Novel Mycobacterial F-ATP Synthase Inhibitor and its Potency in Combination with Diarylquinolines.

The F1 FO -ATP synthase is required for growth and viability of Mycobacterium tuberculosis and is a validated clinical target. A mycobacterium-specific loop of the enzyme's rotary γ subunit plays a role in the coupling of ATP synthesis within the enzyme complex. We report the discovery of a novel antimycobacterial, termed GaMF1, that targets this γ subunit loop. Biochemical and NMR studies show that GaMF1 inhibits ATP synthase activity by binding to the loop. GaMF1 is bactericidal and is active against multidrug- as well as bedaquiline-resistant strains. Chemistry efforts on the scaffold revealed a dynamic structure activity relationship and delivered analogues with nanomolar potencies. Combining GaMF1 with bedaquiline or novel diarylquinoline analogues showed potentiation without inducing genotoxicity or phenotypic changes in a human embryonic stem cell reporter assay. These results suggest that GaMF1 presents an attractive lead for the discovery of a novel class of anti-tuberculosis F-ATP synthase inhibitors.

Nurses' perception and experiences towards medical device-related pressure injuries: A qualitative study.

AIMS AND OBJECTIVES: This study aims to explore nurses' perceptions and experiences regarding pressure injuries caused by medical devices and to understand the perceived challenges and barriers nurses face in preventing medical device-related pressure injuries. BACKGROUND: Nurses have a responsibility to prevent pressure injuries and play a major role in their prevention. As there has been a lack of research on medical device-related pressure injuries, not much is known about nurses' perceptions and experiences. This therefore hinders the establishment of effective and efficient interventions in nurses' education and in the practical environment. DESIGN: A descriptive qualitative design was adopted, and the COREQ checklist was employed to report on the current study. METHODS: The study was conducted at an acute care hospital in Singapore. Purposive sampling was used, and a total of 21 enrolled and registered nurses who had recent experiences with medical device-related pressure injuries were recruited between August and December 2018. Face-to-face interviews were conducted using a semi-structured interview guide. A thematic analysis was performed to analyse the qualitative data. RESULTS: Five themes emerged regarding pressure injuries: (1) preventable yet unavoidable, (2) everyone's responsibility, (3) harmonising theory with practice reality, (4) pre-existing conditions may limit injury prevention and management; and (5) nurses expressed a need for experiential training. CONCLUSIONS: The study's findings could be used to develop improvements in nursing practice and policy at acute care hospitals, as well as to improve awareness of medical device-related pressure injuries among healthcare professionals. Moreover, the findings can also inform future research studies to develop effective evidence-based practices and improve patient outcomes. RELEVANCE TO THE CLINICAL PRACTICE: This study reveals the unique challenges and dilemmas that nurses face and will help to inform healthcare institutions and management in developing programmes and improving protocols to reduce the incidence rate of pressure injuries caused by medical device.

The Effect of Radium-223 Therapy in Agent Orange-Related Prostate Carcinoma.

BACKGROUND: Radium-223 (Ra-223) radioisotope has been reported to increase median survival in bone metastatic prostate carcinoma. The addition of Ra-223 to abiraterone was associated with an increased risk of bone fractures. There has been no comprehensive data for using Ra-223 in veterans who were exposed to Agent Orange (AO+). METHODS: We present a retrospective study of veterans with bone metastatic castration-resistant prostate cancer (CRPC) who received standard doses of Ra-223 and other sequential therapies at US Department of Veterans Affairs Pittsburgh Healthcare System in Pennsylvania from January 2014 to January 2019. Veterans were divided into 2 groups: those who were exposed to Agent Orange (AO+) and those who had no exposure (AO-). Time to study was calculated from the initiation of Ra-223. Time to skeletal-related events (SRE), progression of prostate specific antigen (PSA), bone metastasis, and alkaline phosphatase (ALP) were calculated in months using unpaired t test with 2-tailed P values. Median survival was calculated by Kaplan Meier R log-rank test. RESULTS: There were 34 veterans with bone metastatic CRPC: 17 veterans (50%) were AO+ and 17 veterans (50%) were AO-. The mean age of diagnosis of AO+ veterans was 62 years and 69 years (P = .005) for AO- veterans (the mean Gleason score 8.2 and 8.0, respectively [P = .71]). The median number of Ra-223 cycles was 6 (60%). Ten veterans received Ra-223 as first line (29%) and 24 veterans received Ra-223 later (71%). There were 12 SREs with median survival of 15 months. There was no difference in mean time to SRE between AO+ (8 veterans, 10.6 months) and AO- (4 veterans, 10.3 months) (P = .93). The mean time to PSA progression for AO+ was 5.4 months and AO- was 6.8 months (P = .28). Mean time to bone progression for AO+ was 7.6 months and AO- was 10.1 months (P = .16). Mean time to ALP progression for AO+ and AO- was 6.3 months and 8.7 months, respectively (P = .05). Twenty veterans (58%) had died. Median survival for Ra-223 first was 32 months and for Ra-223 later was 15 months (P = .14; hazard ratio [HR] 0.48; 95% CI, 0.17-1.3). Median survival for AO+ and AO- veterans was 12 months and 18 months, respectively (P = .15; HR, 2.0; 95% CI, 0.77-5.0). CONCLUSIONS: There was no statistical difference between AO+ and AO- veterans in terms of time to SRE, PSA, bone and ALP progression, even though there was a trend of shorter duration in AO+ veterans. There was no median survival difference between Ra-223 first vs Ra-223 later as well as between AO+ and AO- but there is a trend of worse survival in AO+ veterans.

Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness.

Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drugs that modulate the activity of a conserved parasite target. However, no such molecular targets or broad spectrum drugs have been identified to date. Here we describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. Our data provide genetic and chemical validation of the parasite proteasome as a promising therapeutic target for treatment of kinetoplastid infections, and underscore the possibility of developing a single class of drugs for these neglected diseases.

Polycystic ovary syndrome in type 2 diabetes: does it predict a more severe phenotype?

OBJECTIVE: To examine the prevalence of a history of polycystic ovary syndrome (PCOS) in women with type 2 diabetes (DM2) and to compare metabolic and reproductive outcomes between women with and without PCOS. DESIGN: Cross-sectional study. SETTING: Tertiary hospital. PATIENT(S): Female inpatients age 18-75 years with DM2. INTERVENTION(S): A face-to-face questionnaire was administered. MAIN OUTCOME MEASURE(S): Age at diagnosis of diabetes, history of gestational diabetes, family history of diabetes, and reproductive history, fertility history, number of miscarriages, and morbidity in pregnancy. RESULT(S): One hundred seventy-one inpatients with DM2 participated. The prevalence of a history of PCOS was 37%. Women with PCOS had an earlier mean age of diagnosis of DM2 (44.2 vs. 48.8 years), higher recalled peak body mass index (BMI; 43.1 kg/m2 vs. 36.8 kg/m2), higher rate of gestational diabetes (28% vs. 18%), and higher rate of hypertension in pregnancy (40% vs. 22%). Women with PCOS were less likely to have a family history of DM2 than those without PCOS (45% vs. 67%). CONCLUSION(S): A history of PCOS in women with DM2 is associated with earlier onset of DM2, higher BMI, and a more severe phenotype. Since PCOS subjects were less likely to have a family history of DM2, lack of a family history of DM2 in women with PCOS is not reassuring for DM2 risk. We recommend identifying PCOS in early life and intervening to reduce the risk of diabetes and its comorbidities and suboptimal reproductive outcomes.

Spiroindolones, a potent compound class for the treatment of malaria.

Recent reports of increased tolerance to artemisinin derivatives--the most recently adopted class of antimalarials--have prompted a need for new treatments. The spirotetrahydro-beta-carbolines, or spiroindolones, are potent drugs that kill the blood stages of Plasmodium falciparum and Plasmodium vivax clinical isolates at low nanomolar concentration. Spiroindolones rapidly inhibit protein synthesis in P. falciparum, an effect that is ablated in parasites bearing nonsynonymous mutations in the gene encoding the P-type cation-transporter ATPase4 (PfATP4). The optimized spiroindolone NITD609 shows pharmacokinetic properties compatible with once-daily oral dosing and has single-dose efficacy in a rodent malaria model.

Proximal contact areas of the maxillary anterior dentition.

The goal of this study was to quantify the apicoincisal extent of the proximal contact area (PCA) between the eight maxillary anterior teeth. A total of 140 PCA sites and 160 crown lengths were measured in 20 healthy patients. The percentage ratio of PCA to clinical crown length was computed and defined as the proximal contact area proportion (PCAP). Mean PCA dimensions between central incisors (CI/CI), central and lateral incisors (CI/LI), lateral incisors and canines (LI/CA), and canines and first premolars (CA/PM) were 4.2, 2.9, 2.0, and 1.5 mm, respectively. Mesial mean PCAPs were 41%, 32%, 20%, and 18%, respectively. The paired sample t test demonstrated significant differences between all PCAs (P < .0001), except for CA/PM sites (P = .24). Contact areas, not contact points, were observed between neighboring maxillary anterior teeth. Natural PCAPs emerged as well defined in the maxillary anterior dentition bilaterally. Therefore, PCAPs should be taken into consideration for clinical anterior restorations since they determine the papillary and incisal embrasures.