Hearing loss in Australian First Nations children at 6-monthly assessments from age 12 to 36 months: Secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules.

BACKGROUND: In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations. METHODS AND FINDINGS: In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size. CONCLUSIONS: In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01735084 and NCT01174849.

Reducing economic burden through split-shared care model for people living with uncontrolled type 2 diabetes and polypharmacy: a multi-center randomized controlled trial.

BACKGROUND: Interprofessional collaborative care such as a split-shared care model involving family physicians and community pharmacists can reduce the economic burden of diabetes management. This study aimed to evaluate the economic outcome of a split-shared care model between family physicians and community pharmacists within a pharmacy chain in managing people with uncontrolled type 2 diabetes and polypharmacy. METHOD: This was a multi-center, parallel arm, open label, randomized controlled trial comparing the direct and indirect economic outcomes of people who received collaborative care involving community pharmacists (intervention) versus those who received usual care without community pharmacist involvement (control). People with uncontrolled type 2 diabetes, defined as HbA1c > 7.0% and taking ≥ 5 chronic medications were included while people with missing baseline economic data (such as consultation costs, medication costs) were excluded. Direct medical costs were extracted from the institution's financial database while indirect costs were calculated from self-reported gross income and productivity loss, using Work Productivity Activity Impairment Global Health questionnaire. Separate generalized linear models with log link function and gamma distribution were used to analyze changes in direct and indirect medical costs. RESULTS: A total of 175 patients (intervention = 70, control = 105) completed the trial and were included for analysis. The mean age of the participants was 66.9 (9.2) years, with majority being male and Chinese. The direct medical costs were significantly lower in the intervention than the control group over 6 months (intervention: -US$70.51, control: -US$47.66, p < 0.001). Medication cost was the main driver in both groups. There were no significant changes in productivity loss and indirect costs in both groups. CONCLUSION: Implementation of split-shared visits with frontline community partners may reduce economic burden for patient with uncontrolled type 2 diabetes and polypharmacy. TRIAL REGISTRATION: Clinicaltrials.gov Reference Number: NCT03531944 (Date of registration: June 6, 2018).

Evaluating the internalisation of the intrinsic role of health advocacy of student pharmacists in a new integrated Bachelor of Pharmacy curriculum: a mixed-methods study.

To keep up with the contemporary health landscape, there is an imperative need for healthcare professionals to practise health advocacy through health promotion on the individual, population, and systems levels. In the Academic Year of 2020/2021, the National University of Singapore (NUS) Department of Pharmacy implemented a new spiral curriculum integrating basic, clinical, and systems sciences with one of its aims to deepen students' health advocacy internalisation and prepare them as future health advocates. A mixed-methods approach was adopted. Questionnaires were disseminated across three time-points to elicit students' levels of internalisation of health advocacy, which were then categorised into levels, and a Mann-Whitney U test was conducted. In comparison with prematriculation, no significant difference was found after students underwent the first year of the curriculum, while a significant difference was found after students underwent two years of the curriculum. Semi-structured interviews were also conducted after each Academic Year to gain deeper insights into the questionnaire results. Thematic analysis of the interviews revealed that curricular integration in the first year was perceived to be lacking. However, with learnt knowledge constantly reinforced and more experiential learning opportunities incorporated throughout the second year, students found the integrated curriculum beneficial in instilling confidence to practise health advocacy. This study offers insights into the prospects of a spiral integrated curriculum in imparting health advocacy, and may even suggest its potential to be applied to other educational settings. Future follow-up studies can also be conducted on the same study population to evaluate long-term impacts and areas for improvement of the curriculum.

Are 2 Radiographic Views As Good as 3 Views to Diagnose Ankle Fractures in Children and Adolescents?

OBJECTIVES: Ankle radiographs are among the most commonly obtained trauma images in the pediatric population, with the standard 3 views (AP/mortise [M]/lateral [L]) routinely ordered in the emergency department. The purpose of this study was to compare the diagnostic accuracy, sensitivity, and specificity of sets of 2 views (AP/L or M/L) with the standard 3 views. METHODS: One hundred twenty sets of ankle radiographs of skeletally immature patients obtained in the emergency department of a level 1 pediatric trauma center were used. These included sets with and without fractures. Sets of 3 and 2 views were reviewed by pairs of pediatric-trained orthopedic surgeons, radiologists, and emergency physicians. Each completed 3 randomized viewing sessions where all possible combinations for each set of radiographs were reviewed. Diagnoses for the 3 sets of views were compared for accuracy, sensitivity, and specificity. RESULTS: Overall accuracy, sensitivity, and specificity for all reviewers were as follows: AP/M/L 74%, 94%, and 90%, AP/L 71%, 90%, and 94%, as well as M/L 69%, 90%, and 91%. P values for accuracy, sensitivity, and specificity of AP/L and M/L compared with 3 views were 0.34, 0.04, and 0.52, as well as 0.04, 0.004, and 1.00, respectively. CONCLUSIONS: In skeletally immature patients, statistically significant differences in accuracy were obtained when comparing the standard 3 AP/M/L views with more limited M/L views, suggesting that this set of 2 views is not as accurate. Differences in sensitivity of limited views were also statistically significant. Conversely, differences in accuracy between the standard 3 views and AP/Lateral views were not statistically significant. While more limited AP/L views may be comparable in accuracy and specificity and lead to dramatically decreased radiation and costs, this can be at the expense of less diagnostic sensitivity and increased risk of misdiagnosing or missing certain fractures. LEVEL OF EVIDENCE: Level III.

Two-Experiment Examination of Habitual and Manipulated Foot Placement Angles on the Kinetics, Kinematics, and Muscle Forces of the Barbell Back Squat in Male Lifters.

This two-experiment study aimed to examine the effects of different habitual foot placement angles and also the effects of manipulating the foot placement angle on the kinetics, three-dimensional kinematics and muscle forces of the squat. In experiment 1, seventy lifters completed squats at 70% of their one repetition maximum using a self-preferred placement angle. They were separated based on their habitual foot angle into three groups HIGH, MEDIUM and LOW. In experiment 2, twenty lifters performed squats using the same relative mass in four different foot placement angle conditions (0°, 21°, 42° and control). Three-dimensional kinematics were measured using an eight-camera motion analysis system, ground reaction forces (GRF) using a force platform, and muscle forces using musculoskeletal modelling techniques. In experiment 1, the impulse of the medial GRF, in the descent and ascent phases, was significantly greater in the HIGH group compared to LOW, and in experiment 2 statistically greater in the 42° compared to the 21°, 0° and control conditions. Experiment 2 showed that the control condition statistically increased quadriceps muscle forces in relation to 0°, whereas the 0° condition significantly enhanced gluteus maximus, gastrocnemius and soleus forces compared to control. In experiment 1, patellofemoral joint stress was significantly greater in the HIGH group compared to LOW, and in experiment 2, patellar and patellofemoral loading were statistically greater in the control compared to the 42°, 21°, 0° and control conditions. Owing to the greater medial GRF's, increased foot placement angles may improve physical preparedness for sprint performance and rapid changes of direction. Reducing the foot angle may attenuate the biomechanical mechanisms linked to the aetiology of knee pathologies and to promote gluteus maximus, gastrocnemius and soleus muscular development. As such, though there does not appear to be an optimal foot placement angle, the observations from this study can be utilised by both strength and conditioning and sports therapy practitioners seeking to maximise training and rehabilitative adaptations.

A prospective observational study to identify the effectiveness of intravenous magnesium replacement in an intensive care setting.

Background and Aims: To estimate the incidence of hypomagnesemia and identify the effectiveness of a calculated dose of intravenous magnesium sulfate (MgSO4) in correction of hypomagnesemia and its relationship with renal function in critically ill patients. Material and Methods: All patients admitted in the adult intensive care unit were enrolled in the study and magnesium levels were monitored. Patients with serum magnesium levels <1.7 mg/dL received calculated doses of Intravenous MgSO4. The average rise in serum magnesium levels per gram of MgSO4 administered was calculated and relationship with estimated glomerular filtration rate (eGFR) was identified. Results: In total, 27.27% of patients admitted in our intensive care unit had an incidence of hypomagnesemia. The average rise of serum magnesium levels in patients with hypomagnesemia was 0.13 (±0.05) mg/dl. The average rise of serum magnesium levels was 0.10 (±0.04) mg/dL in patients with eGFR ≥ 90 mL/min/1.73 m2 and 0.15 (± 0.05) mg/dL in patients with eGFR < 90 mL/min/1.73 m2. This difference between the two groups (P-value = 0.002) and the trend of increasing average rise in serum magnesium levels with declining eGFR values (P-value = 0.013) were both statistically significant. Conclusion: Incidence of hypomagnesemia in the critically ill population is around 27.27%. Intravenous administration of 1 g of MgSO4 results in a rise of serum magnesium levels by 0.1 mg/dL in patients with normal eGFR and around 0.15 mg/dL in patients with eGFR values between 30 and 89 mL/min/1.73 m2.

Facility-level characteristics associated with family planning and child immunization services integration in urban areas of Nigeria: a longitudinal analysis.

BACKGROUND: Unmet need for postpartum contraception is high. Integration of family planning with routine child immunization services may help to satisfy unmet need. However, evidence about the determinants and effects of integration has been inconsistent, and more evidence is required to ascertain whether and how to invest in integration. In this study, facility-level family planning and immunization integration index scores are used to: (1) determine whether integration changes over time and (2) identify whether facility-level characteristics, including exposure to the Nigerian Urban Reproductive Health Initiative (NURHI), are associated with integration across facilities in six urban areas of Nigeria. METHODS: This study utilizes health facility data collected at baseline (n = 400) and endline (n = 385) for the NURHI impact evaluation. Difference-in-differences models estimate the associations between facility-level characteristics, including exposure to NURHI, and Provider and Facility Integration Index scores. The two outcome measures, Provider and Facility Integration Index scores, reflect attributes that support integrated service delivery. These indexes, which range from 0 (low) to 10 (high), were constructed using principal component analysis. Scores were calculated for each facility. Independent variables are (1) time period, (2) whether the facility received the NURHI intervention, and (3) additional facility-level characteristics. RESULTS: Within intervention facilities, mean Provider Integration Index scores were 6.46 at baseline and 6.79 at endline; mean Facility Integration Index scores were 7.16 (baseline) and 7.36 (endline). Within non-intervention facilities, mean Provider Integration Index scores were 5.01 at baseline and 6.25 at endline; mean Facility Integration Index scores were 5.83 (baseline) and 6.12 (endline). Provider Integration Index scores increased significantly (p = 0.00) among non-intervention facilities. Facility Integration Index scores did not increase significantly in either group. Results identify facility-level characteristics associated with higher levels of integration, including smaller family planning client load, family planning training among providers, and public facility ownership. Exposure to NURHI was not associated with integration index scores. CONCLUSION: Programs aiming to increase integration of family planning and immunization services should monitor and provide targeted support for the implementation of a well-defined integration strategy that considers the influence of facility characteristics and concurrent initiatives.

Otitis media outcomes of a combined 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine and 13-valent pneumococcal conjugate vaccine schedule at 1-2-4-6 months: PREVIX_COMBO, a 3-arm randomised controlled trial.

BACKGROUND: Aboriginal children living in Australian remote communities are at high risk of early and persistent otitis media, hearing loss, and social disadvantage. Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are the primary pathogens. We compared otitis media outcomes in infants randomised to either a combination of Synflorix™ (PHiD-CV10, with protein D of NTHi) and Prevenar13™ (PCV13, with 3, 6A, and 19A), with recommended schedules for each vaccine alone. We previously reported superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months. METHODS: In an open-label superiority trial, we randomised (1:1:1) Aboriginal infants at 28 to 38 days of age, to either Prevenar13™ (P) at 2-4-6 months (_PPP), Synflorix™ (S) at 2-4-6 months (_SSS), or Synflorix™ at 1-2-4 months plus Prevenar13™ at 6 months (SSSP). Ears were assessed using tympanometry at 1 and 2 months, combined with otoscopy at 4, 6, and 7 months. A worst ear diagnosis was made for each child visit according to a severity hierarchy of normal, otitis media with effusion (OME), acute otitis media without perforation (AOMwoP), AOM with perforation (AOMwiP), and chronic suppurative otitis media (CSOM). RESULTS: Between September 2011 and September 2017, 425 infants were allocated to _PPP(143), _SSS(141) or SSSP(141). Ear assessments were successful in 96% scheduled visits. At 7 months prevalence of any OM was 91, 86, and 90% in the _PPP, _SSS, and SSSP groups, respectively. There were no significant differences in prevalence of any form of otitis media between vaccine groups at any age. Combined group prevalence of any OM was 43, 57, 82, 87, and 89% at 1, 2, 4, 6, and 7 months of age, respectively. Of 388 infants with ear assessments at 4, 6 and 7 months, 277 (71.4%) had OM that met criteria for specialist referral; rAOM, pOME, or CSOM. CONCLUSIONS: Despite superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months, there were no significant differences in prevalence of otitis media nor healthy ears throughout the first months of life. TRIAL REGISTRATION: ACTRN12610000544077 registered 06/07/2010 and ClinicalTrials.gov NCT01174849 registered 04/08/2010.

Development of integration indexes to determine the extent of family planning and child immunization services integration in health facilities in urban areas of Nigeria.

BACKGROUND: Integrating family planning into child immunization services may address unmet need for contraception by offering family planning information and services to postpartum women during routine child immunization visits. However, policies and programs promoting integration are often based on insubstantial or conflicting evidence about its effects on service delivery and health outcomes. While integration models vary, many studies measure integration as binary (a facility is integrated or not) rather than a multidimensional and varying continuum. It is thus challenging to ascertain the determinants and effects of integrated service delivery. This study creates Facility and Provider Integration Indexes, which measure capacity to support integrated family planning and child immunization services and applies them to analyze the extent of integration across 400 health facilities. METHODS: This study utilizes cross-sectional health facility (N = 400; 58% hospitals, 42% primary healthcare centers) and healthcare provider (N = 1479) survey data that were collected in six urban areas of Nigeria for the impact evaluation of the Nigerian Urban Reproductive Health Initiative. Principal Component Analysis was used to develop Provider and Facility Integration Indexes that estimate the extent of integration in these health facilities. The Provider Integration Index measures provider skills and practices that support integrated service delivery while the Facility Integration Index measures facility norms that support integrated service delivery. Index scores range from zero (low) to ten (high). RESULTS: Mean Provider Integration Index score is 5.42 (SD 3.10), and mean Facility Integration Index score is 6.22 (SD 2.72). Twenty-three percent of facilities were classified as having low Provider Integration scores, 32% as medium, and 45% as high. Fourteen percent of facilities were classified as having low Facility Integration scores, 38% as medium, and 48% as high. CONCLUSION: Many facilities in our sample have achieved high levels of integration, while many others have not. Results suggest that using more nuanced measures of integration may (a) more accurately reflect true variation in integration within and across health facilities, (b) enable more precise measurement of the determinants or effects of integration, and (c) provide more tailored, actionable information about how best to improve integration. Overall, results reinforce the importance of utilizing more nuanced measures of facility-level integration.

Ethnically diverse urban transmission networks of Neisseria gonorrhoeae without evidence of HIV serosorting.

OBJECTIVE: We aimed to characterise gonorrhoea transmission patterns in a diverse urban population by linking genomic, epidemiological and antimicrobial susceptibility data. METHODS: Neisseria gonorrhoeae isolates from patients attending sexual health clinics at Barts Health NHS Trust, London, UK, during an 11-month period underwent whole-genome sequencing and antimicrobial susceptibility testing. We combined laboratory and patient data to investigate the transmission network structure. RESULTS: One hundred and fifty-eight isolates from 158 patients were available with associated descriptive data. One hundred and twenty-nine (82%) patients identified as male and 25 (16%) as female; four (3%) records lacked gender information. Self-described ethnicities were: 51 (32%) English/Welsh/Scottish; 33 (21%) white, other; 23 (15%) black British/black African/black, other; 12 (8%) Caribbean; 9 (6%) South Asian; 6 (4%) mixed ethnicity; and 10 (6%) other; data were missing for 14 (9%). Self-reported sexual orientations were 82 (52%) men who have sex with men (MSM); 49 (31%) heterosexual; 2 (1%) bisexual; data were missing for 25 individuals. Twenty-two (14%) patients were HIV positive. Whole-genome sequence data were generated for 151 isolates, which linked 75 (50%) patients to at least one other case. Using sequencing data, we found no evidence of transmission networks related to specific ethnic groups (p=0.64) or of HIV serosorting (p=0.35). Of 82 MSM/bisexual patients with sequencing data, 45 (55%) belonged to clusters of ≥2 cases, compared with 16/44 (36%) heterosexuals with sequencing data (p=0.06). CONCLUSION: We demonstrate links between 50% of patients in transmission networks using a relatively small sample in a large cosmopolitan city. We found no evidence of HIV serosorting. Our results do not support assortative selectivity as an explanation for differences in gonorrhoea incidence between ethnic groups.

Impaired decision making following escalation of cocaine self-administration predicts vulnerability to relapse in rats.

Impairments in cost-benefit decision making represent a cardinal feature of drug addiction. However, whether these alterations predate drug exposure, thereby contributing to facilitating loss of control over drug intake, or alternatively arise as a result of drug use and subsequently confer vulnerability to relapse has yet to be determined. Male Sprague-Dawley rats were trained to self-administer (SA) cocaine during 19 daily long-access (12-h) sessions; conditions reliably shown to promote escalation. One week after cocaine SA, rats underwent an extinction/relapse test immediately followed by conditioned stimuli-, stress-, and drug-primed reinstatement challenges. The influence of escalated cocaine intake on decision making was measured over time by four test sessions of a rodent analogue of the Iowa Gambling Task (rGT), once prior to cocaine exposure and then 1 day, 1 week, and 1 month after the last SA session. Substantial individual variability was observed in the influence of escalated cocaine SA on decision-making performance. A subset of rats displayed pronounced deficits, while others showed unaffected or even improved performance on the rat Gambling Task (rGT) 24 hours after the last SA session. When challenged with a relapse test after 1 week of forced abstinence, animals that showed impaired decision making following SA displayed an increased propensity to respond for cocaine under extinction. These data suggest that decision-making deficits in individuals with drug addiction are not antecedent to-but arise as a consequence of-drug exposure. Moreover, these data indicate that susceptibility to the deleterious effects of drugs on decision making confers vulnerability toward relapse.

Genomes of ubiquitous marine and hypersaline Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira spp. encode a diversity of mechanisms to sustain chemolithoautotrophy in heterogeneous environments.

Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda and salt lakes and marine sediments. Their genome sequences confirm their membership in a deeply branching clade of the Gammaproteobacteria. Several adaptations to heterogeneous habitats are apparent. Their genomes include large numbers of genes for sensing and responding to their environment (EAL- and GGDEF-domain proteins and methyl-accepting chemotaxis proteins) despite their small sizes (2.1-3.1 Mbp). An array of sulfur-oxidizing complexes are encoded, likely to facilitate these organisms' use of multiple forms of reduced sulfur as electron donors. Hydrogenase genes are present in some taxa, including group 1d and 2b hydrogenases in Hydrogenovibrio marinus and H. thermophilus MA2-6, acquired via horizontal gene transfer. In addition to high-affinity cbb3 cytochrome c oxidase, some also encode cytochrome bd-type quinol oxidase or ba3 -type cytochrome c oxidase, which could facilitate growth under different oxygen tensions, or maintain redox balance. Carboxysome operons are present in most, with genes downstream encoding transporters from four evolutionarily distinct families, which may act with the carboxysomes to form CO2 concentrating mechanisms. These adaptations to habitat variability likely contribute to the cosmopolitan distribution of these organisms.

Whole genome sequencing of Neisseria gonorrhoeae reveals transmission clusters involving patients of mixed HIV serostatus.

OBJECTIVES: Prevention and control of gonorrhoea depends on understanding the nature of sexual networks and risk factors for infection. We aimed to use high-resolution typing (whole genome sequencing (WGS)) of Neisseria gonorrhoeae isolates plus patient questionnaire data to gain insights into transmission patterns in a high prevalence setting. METHODS: During a 9-month period (July 2014-March 2015), patients diagnosed with gonorrhoea attending sexual health service in Brighton, UK, were invited to provide anonymised detailed information by questionnaire about risk factors for infection. Questionnaire data plus WGS data from cultured isolates were analysed to yield information about sexual networks and risk factors for infection. RESULTS: 104/149 individuals who consented to participate in the study were culture positive. 97/104 (93%) were male. 80 self-reported to be men who have sex with men (MSM). 35/104 (34%) of patients were HIV positive. 51/104 (49%) individuals reported using geosocial networking applications to facilitate contact. Sex under the influence of drugs was reported by 16/34 (46%) of HIV-positive MSM, 17/41 (41%) of HIV-negative MSM and 5/15 (31%) of heterosexuals. WGS data were available for 100 isolates from 83 patients. 55 isolates (66%) belonged to genetically related subtypes involving one or more patients, who could be plausibly linked through recent direct or indirect transmission. Four transmission clusters containing 3-12 individuals were composed of MSM of mixed HIV serostatus. CONCLUSIONS: We show that data obtained from WGS of N. gonorrhoeae and enhanced epidemiological data obtained from patient questionnaires are mutually supportive and reveal insights into sexual networks. Our findings suggest that serosorting may have declined as a practice and indicate the importance of designing public health interventions that target infection risks associated with recreational drug use and contact made using geosocial networking applications.

The absence of maternal pineal melatonin rhythm during pregnancy and lactation impairs offspring physical growth, neurodevelopment, and behavior.

Maternal melatonin provides photoperiodic information to the fetus and thus influences the regulation and timing of the offspring's internal rhythms and preparation for extra-uterine development. There is clinical evidence that melatonin deprivation of both mother and fetus during pregnancy, and of the neonate during lactation, results in negative long-term health outcomes. As a consequence, we hypothesized that the absence of maternal pineal melatonin might determine abnormal brain programming in the offspring, which would lead to long-lasting implications for behavior and brain function. To test our hypothesis, we investigated in rats the effects of maternal melatonin deprivation during gestation and lactation (MMD) to the offspring and the effects of its therapeutic replacement. The parameters evaluated were: (1) somatic, physical growth and neurobehavioral development of pups of both sexes; (2) hippocampal-dependent spatial learning and memory of the male offspring; (3) adult hippocampal neurogenesis of the male offspring. Our findings show that MMD significantly delayed male offspring's onset of fur development, pinna detachment, eyes opening, eruption of superior incisor teeth, testis descent and the time of maturation of palmar grasp, righting reflex, free-fall righting and walking. Conversely, female offspring neurodevelopment was not affected. Later on, male offspring show that MMD was able to disrupt both spatial reference and working memory in the Morris Water Maze paradigm and these deficits correlate with changes in the number of proliferative cells in the hippocampus. Importantly, all the observed impairments were reversed by maternal melatonin replacement therapy. In summary, we demonstrate that MMD delays the appearance of physical features, neurodevelopment and cognition in the male offspring, and points to putative public health implications for night shift working mothers.

A case of blackwater fever with persistent Plasmodium falciparum parasitaemia detected by PCR after artemether-lumefantrine treatment.

BACKGROUND: Blackwater fever is a complication of malaria infection consisting of a syndrome of febrile intra-vascular haemolysis with severe anaemia and intermittent passage of dark-red to black colour urine. Despite numerous reports and studies of this condition, its pathogenesis remains incompletely understood. CASE PRESENTATION: This report describes a case of classic blackwater fever in a returning traveller, without prior history of malaria infection nor usage of anti-malarial prophylaxis, treated with two courses of oral artemether-lumefantrine combination therapy. Unusual persistence of submicroscopic Plasmodium falciparum parasitaemia was detected by PCR for 18 days after initiation of treatment. CONCLUSION: To the authors' knowledge this is the first reported occurrence of a case of blackwater fever associated with prolonged submicroscopic parasitaemia. This unusual case challenges the current knowledge of the pathogenesis of this condition and opens questions that may have important diagnostic and treatment implications.

The ALCCaS Trial: A Randomized Controlled Trial Comparing Quality of Life Following Laparoscopic Versus Open Colectomy for Colon Cancer.

BACKGROUND: This study reports the quality-of-life assessment of the ALCCaS trial. The ALCCaS trial compared laparoscopic and open resection for colon cancer. It reported equivalence of survival at 5 years. Quality of life was measured as a secondary outcome. OBJECTIVE: This study aimed to report on the quality of life data of the ALCCaS Trial. DESIGN: This study reports a randomized controlled trial comparing laparoscopic with open colonic resection. SETTINGS: The study was conducted in Australasia. PATIENTS: Patients with a single adenocarcinoma of the right, left, or sigmoid colon, presenting for elective treatment, were eligible for randomization. INTERVENTIONS: Open and laparoscopic colonic resections were performed. MAIN OUTCOME MEASURES: Patient symptoms and quality of life were measured using the Symptoms Distress Scale, the Quality of Life Index, and the Global Quality of Life Score preoperatively, and at 2 days, 2 weeks, and 2 months postoperatively. RESULTS: Of the 592 patients enrolled in ALCCaS, 425 completed at least 1 quality-of-life measure at 4 time points (71.8% of cohort). Those who received the laparoscopic intervention had better quality of life postoperatively in terms of the Symptoms Distress Scale (p < 0.01), Quality of Life Index (p < 0.01), and Global Quality of Life (p < 0.01). In intention-to-treat analyses, those assigned to laparoscopic surgery had a better quality of life postoperatively in terms of the Symptoms Distress Scale (p < 0.01) and Quality of Life Index (p < 0.01), whereas Global Quality of Life was not significant (p = 0.056). The subscales better for laparoscopic resection at all 3 postoperative time points were appetite, insomnia, pain, fatigue, bowel, daily living, and health (p < 0.05). LIMITATIONS: The primary limitation was the different response rates for the 3 quality-of-life measures. CONCLUSIONS: There was a short-term gain in quality of life maintained at 2 months postsurgery for those who received laparoscopic relative to open colonic resection. See Video Abstract at http://links.lww.com/DCR/A691.

The effects of contemporary selection and dispersal limitation on the community assembly of acidophilic microalgae.

Extremophilic microalgae are primary producers in acidic habitats, such as volcanic sites and acid mine drainages, and play a central role in biogeochemical cycles. Yet, basic knowledge about their species composition and community assembly is lacking. Here, we begin to fill this knowledge gap by performing the first large-scale survey of microalgal diversity in acidic geothermal sites across the West Pacific Island Chain. We collected 72 environmental samples in 12 geothermal sites, measured temperature and pH, and performed rbcL amplicon-based 454 pyrosequencing. Using these data, we estimated the diversity of microalgal species, and then examined the relative contribution of contemporary selection (i.e., local environmental variables) and dispersal limitation on the assembly of these communities. A species delimitation analysis uncovered seven major microalgae (four red, two green, and one diatom) and higher species diversity than previously appreciated. A distance-based redundancy analysis with variation partitioning revealed that dispersal limitation has a greater influence on the community assembly of microalgae than contemporary selection. Consistent with this finding, community similarity among the sampled sites decayed more quickly over geographical distance than differences in environmental factors. Our work paves the way for future studies to understand the ecology and biogeography of microalgae in extreme habitats.

Serological Detection of Antibodies against Anaplasma spp. in Cattle Reared in the Gyeongsangbuk-do, Korea.

Anaplasmosis is a tick-borne, non-contagious, zoonotic disease caused by Anaplasma spp., which include Anaplasma marginale, A. centrale, A. phagocytophilum, A. platys, A. ovis, and A. bovis. Recently, in Korea, the prevalence of Anaplasma spp. has been investigated in some animals, such as dogs, horses, goats, cats, and Korean water deer. In cattle, A. marginale is the most virulent species and regarded as the typical type of species. However, data on the seroprevalence of Anaplasma spp. in cattle in Korea during the last decade is limited. This study was designed to investigate the seroprevalence of bovine anaplasmosis in Korea. From 2010 to 2013, blood samples were collected from 568 cattle. Forty animals (7.0%) tested seropositive for Anaplasma spp. by cELISA. Despite that current bovine anaplasmosis seropositivity rate in the Gyeongsangbuk-do is lower than those in tropical countries, anaplasmosis needs to be regarded as a concerning disease. The identification of the specific Anaplasma species infecting cattle in this province requires additional molecular studies. Moreover, further monitoring and control programs for bovine anaplasmosis is required, and the information from this study will be beneficial to develop these programs.

Reduced Ets Domain-containing Protein Elk1 Promotes Pulmonary Fibrosis via Increased Integrin αvß6 Expression.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with high mortality. Active TGFß1 is considered central to the pathogenesis of IPF. A major mechanism of TGFß1 activation in the lung involves the epithelially restricted αvß6 integrin. Expression of the αvß6 integrin is dramatically increased in IPF. How αvß6 integrin expression is regulated in the pulmonary epithelium is unknown. Here we identify a region in the ß6 subunit gene (ITGB6) promoter acting to markedly repress basal gene transcription, which responds to both the Ets domain-containing protein Elk1 (Elk1) and the glucocorticoid receptor (GR). Both Elk1 and GR can regulate αvß6 integrin expression in vitro We demonstrate Elk1 binding to the ITGB6 promoter basally and that manipulation of Elk1 or Elk1 binding alters ITGB6 promoter activity, gene transcription, and αvß6 integrin expression. Crucially, we find that loss of Elk1 causes enhanced Itgb6 expression and exaggerated lung fibrosis in an in vivo model of fibrosis, whereas the GR agonist dexamethasone inhibits Itgb6 expression. Moreover, Elk1 dysregulation is present in epithelium from patients with IPF. These data reveal a novel role for Elk1 regulating ITGB6 expression and highlight how dysregulation of Elk1 can contribute to human disease.