Teenage motherhood and infant mortality in Bangladesh: maternal age-dependent effect of parity one.
Nuptiality norms in rural Bangladesh favour birth during the teenage years. An appreciable proportion of teenage births are, in fact, second births. This study examines the relationship between teenage fertility and high infant mortality. It is hypothesized that if physiological immaturity is responsible, then the younger the mother, the higher would be the mortality risk, and the effect of mother's 'teenage' on mortality in infancy, particularly in the neonatal period, would be higher for the second than the first births. Vital events recorded by the longitudinal demographic surveillance system in Matlab, Bangladesh, in 1990-92 were used. Logistic regression was used to estimate the effects on early and late neonatal (0-3 days and 4-28 days respectively) and post-neonatal mortality of the following variables: mother's age at birth, parity, education and religion, sex of the child, household economic status and exposure to a health intervention programme. The younger the mother, the higher were the odds of her child dying as a neonate, and the odds were higher for second children than first children of teenage mothers. First-born children were at higher odds of dying in infancy than second births if mothers were in their twenties. Unfavourable mother's socioeconomic conditions were weakly, but significantly, associated with higher odds of dying during late neonatal and post-neonatal periods. The results suggest that physical immaturity may be of major importance in determining the relationship between teenage fertility and high neonatal mortality.


Modeling of biomass and stored carbon in a seasonal semidecidual forest in Brazil.
This study estimated biomass and carbon from components, future carbon values and to obtain economic productive value of carbon fixation of a Seasonal Semideciduous Forest. Biomass and carbon were estimated using adjusted equations and selected using regression statistics. The prognosis of the diametric distribution was performed using the movement ratio method. In the economic evaluation, it was estimated productive value of the stand, referring to the current and future carbon fixation capacity. The coefficients of determination (adjusted R²) of the equations ranged from 0.11 to 0.90 and the standard error of the estimate (Syx) ranged from 41.53% to 141.89% for the biomass of the components, and from 0.03 to 0.87 for adjusted R² and from 46.20% to 143.64% for the error, for stored carbon in the components. The total biomass of the tree component estimated was 56.25 t ha-1 and 25.88 t ha-1 of total carbon. Using the future distributions by the method of the ratio of movements, total stored carbon (aerial + roots) estimated was 14.44 t. ha-1 over the 20-year period. The productive value for the fragment reached R$ 299.95 per ha. year-1.


The potential yield of non-exercise physical activity energy expenditure in public health.
Previous work has shown prospective associations between total daily physical activity energy expenditure and various health outcomes including metabolic risk. Limited evidence is available on the health benefits of standing and light-intensity activity. Therefore, these behaviours are not supported in contemporary physical activity guidelines. Moreover, people may be more willing to replace sedentary activities with standing or light activities that can be incorporated into their daily lives, rather than activities of moderate intensity, as there are fewer potential barriers. With the rapid advancement of objective physical activity monitoring there is now potential to explore total daily physical activity energy expenditure in more depth. This article highlights the need for further research into all areas of total daily physical activity energy expenditure, in particular standing and light-intensity activities. Future physical activity guidelines may benefit from the inclusion of recommendations on physical activity energy expenditure rather than solely focusing on activities of a moderate or vigorous intensity.


Impact of SARS-CoV-2 Pandemic and Strategies for Resumption of Activities During the Second Wave of the Pandemic: A Report From Eight Paediatric Hospitals From the ECHO Network.
The Severe Acute Respiratory Syndrome CoronaVirus type 2 (SARS-CoV-2) pandemic impacted the organization of paediatric hospitals. This study aimed to evaluate the preparedness for the pandemic among a European network of children's hospitals and to explore the strategies to restart health care services. A cross-sectional, web-based survey was distributed in May 2020 to the 13 children's tertiary care hospitals belonging to the European Children's Hospitals Organisation. Responses were obtained from eight hospitals (62%). Significant reductions were observed in accesses to the emergency departments (41.7%), outpatient visits (35.7%), intensive and non-intensive care unit inpatient admissions (16.4 and 13%, respectively) between February 1 and April 30, 2020 as compared with the same period of 2019. Overall, 93 children with SARS CoV-2 infection were admitted to inpatient wards. All the hospitals created SARS-CoV-2 preparedness plans for the diagnosis and management of infected patients. Routine activities were re-scheduled. Four hospitals shared their own staff with adult units, two designated bed spaces for adults and only one admitted adults to inpatient wards. The three main components for the resumption of clinical activities were testing, source control, and reorganization of spaces and flows. Telemedicine and telehealth services were used before the SARS-CoV-2 pandemic by three hospitals and by all the hospitals during it. Conclusion: The present study provides a perspective on preparedness to SARS-CoV-2 pandemic among eight large European children's hospitals, on the impact of the pandemic on the hospital activities and on the strategies adopted to restart clinical activities.


[Colonic involvement in systemic mastocytosis (author's transl)].
The most common gastrointestinal lesions encountered in systemic mastocytosis are the gastric, duodenal and small bowell lesions. The authors present a case of diffuse colonic involvement diagnosed on a double contrast examination. The radiological signs correlated with the endoscopical and histological findings are due to a submucosal edema and a polymorphic cellular infiltrate. The involvement of the colon is probably more frequent then previously thought. It could explain the diarrhea encountered in some patients affected by this disease.


Identifying dementia in Down syndrome with the Severe Impairment Battery, Brief Praxis Test and Dementia Scale for People with Learning Disabilities.
Individuals with Down syndrome (DS) are at high risk for dementia, specifically Alzheimer's disease. However, many measures regularly used for the detection of dementia in the general population are not suitable for individuals with DS due in part to floor effects. Some measures, including the Severe Impairment Battery (SIB), Brief Praxis Test (BPT) and Dementia Scale for People with Learning Disabilities (DLD), have been used in clinical trials and other research with this population. Validity research is limited, particularly regarding the use of such tools for detection of prodromal dementia in the DS population. The current project presents baseline cross-sectional SIB, BPT and DLD performance in order to characterise their predictive utility in discriminating normal cognition, possible dementia and probable dementia in adult DS. Baseline SIB, BPT and DLD performances from 100 individuals (no dementia = 68, possible dementia = 16 & probable dementia = 16) were examined from a longitudinal cohort of aging individuals with DS. Receiver operating characteristic curves investigated the accuracy of these measures in relation to consensus dementia diagnoses, diagnoses which demonstrated high percent agreement with the examining neurologist's independent diagnostic impression. The SIB and BPT exhibited fair discrimination ability for differentiating no/possible versus probable dementia [area under the curve (AUC) = 0.61 and 0.66, respectively]. The DLD exhibited good discrimination ability for differentiating no versus possible/probable dementia (AUC = 0.75) and further demonstrated better performance of the DLD Cognitive subscale compared with the DLD Social subscale (AUC = 0.77 and 0.67, respectively). Results suggest that the SIB, BPT and DLD are able to reasonably discriminate consensus dementia diagnoses in individuals with DS, supporting their continued use in the clinical assessment of dementia in DS. The general performance of these measures suggests that further work in the area of test development is needed to improve on the AUCs for dementia status discrimination in this unique population. At present, however, the current findings suggest that the DLD may be the best option for reliable identification of prodromal dementia in this population, reinforcing the importance of including informant behaviour ratings in assessment of cognition for adults with DS.


Scheduling primary care appointments online: Differences in availability based on health insurance.
Digital platforms that allow patients to go online or use smartphone applications to view and schedule physician appointments have not been well evaluated. We conducted systematic searches for primary care physician appointments in 20 cities using ZocDoc, an online appointment scheduling platform. Availability was determined for three insurance types (self-pay, Medicare, and Medicaid) in states with and without Medicaid expansion. We collected data on physician characteristics, number of appointments available, and distance to clinics. The sample comprised 4150 physician observations across 17 states. Overall, the mean distance to clinic was 8.9 miles (SD: 8.4 miles), mean total number of appointments available within 3 days for the 10 closest physicians was 20.1 (SD: 27.1), and the mean number of physicians available within 5 miles was 5.4 (SD: 6.6). There were no differences in physician characteristics by insurance type. Access to appointments did not differ between Medicare and self-pay. However, compared to self-pay, appointments for Medicaid were further away (Mean difference in miles: 5.4, P < 0.001), and there were fewer physicians available within 5 miles (Mean difference in # of physicians: -4.9, P < 0.001). States that did not adopt Medicaid expansion had fewer appointments within proximity, but this differed similarly across insurance types. There were a substantial number of available appointments at close distances. However, Medicaid patients had less access to appointments within proximity than self-pay or Medicare patients.


Preparation of targeted isoniazid microspheres.
Isoniazid (INH) albumin microspheres were prepared by two different stabilization processes: chemical denaturation using glutaraldehyde and heat denaturation. The extent of stabilization was characterized by the solubility of the microspheres. In vitro drug release rates were correlated to the stability of the microspheres and the results showed that the more denatured the albumin by heat stabilization, the slower the drug release rate. A factorial concept has been utilized to synthesize microspheres suitable for passive targeting to the lungs by varying protein concentration, stabilization temperature, time and aqueous volume. These factors significantly affected the sphere size, payload and a release profile of the drug. As the severity of the denaturation conditions increased, the payload decreased and the rate of drug release was slowed. The microspheres carrying isoniazid were followed in experimental animals to validate the targeting process.


High tidal volume decreases adult respiratory distress syndrome, atelectasis, and ventilator days compared with low tidal volume in pediatric burned patients with inhalation injury.
Inhalation injury, which is among the causes of acute lung injury and acute respiratory distress syndrome (ARDS), continues to represent a significant source of mortality in burned patients. Inhalation injury often requires mechanical ventilation, but the ideal tidal volume strategy is not clearly defined in burned pediatric patients. The aim of this study was to determine the effects of low and high tidal volume on the number of ventilator days, ventilation pressures, and incidence of atelectasis, pneumonia, and ARDS in pediatric burned patients with inhalation injury within 1 year post burn injury. From 1986 to 2014, inhalation injury was diagnosed by bronchoscopy in pediatric burned patients (n = 932). Patients were divided into 3 groups: unventilated (n = 241), high tidal volume (HTV, 15 ± 3 mL/kg, n = 190), and low tidal volume (LTV, 9 ± 3 mL/kg, n = 501). High tidal volume was associated with significantly decreased ventilator days (p < 0.005) and maximum positive end expiratory pressure (p < 0.0001) and significantly increased maximum peak inspiratory pressure (p < 0.02) and plateau pressure (p < 0.02) compared with those in patients with LTV. The incidence of atelectasis (p < 0.0001) and ARDS (p < 0.02) was significantly decreased with HTV compared with LTV. However, the incidence of pneumothorax was significantly increased in the HTV group compared with the LTV group (p < 0.03). High tidal volume significantly decreases ventilator days and the incidence of both atelectasis and ARDS compared with low tidal volume in pediatric burned patients with inhalation injury. Therefore, the use of HTV may interrupt sequences leading to lung injury in our patient population.


Extraction of primary (baby) teeth for unerupted palatally displaced permanent canine teeth in children.
The permanent canine tooth in the maxillary (upper) jaw sometimes does not erupt into the mouth correctly. In about 1% to 3% of the population these teeth will be diverted into the roof of the mouth (palatally). It has been suggested that if the primary canine is removed at the right time this palatal eruption might be avoided. This is an update of a Cochrane review first published in 2009. To evaluate the effect of extracting the primary maxillary canine on the eruption of the palatally ectopic maxillary permanent canine. We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 20 April 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE via OVID (1946 to 20 April 2012) and EMBASE via OVID (1980 to 20 April 2012). There were no restrictions regarding language or date of publication. Trials were selected if they met the following criteria: a randomised or quasi-randomised controlled trial, involving the extraction of the deciduous maxillary canine and assessing eruption/non-eruption of the palatally displaced maxillary permanent canine. Data extraction was undertaken independently by two review authors. The primary outcome was the reported prevalence of eruption or non-eruption of the ectopic permanent canine into the mouth following observation or intervention. Results were to be expressed as risk ratios for dichotomous outcomes with 95% confidence intervals and mean differences for continuous outcomes. Heterogeneity was to be investigated, including both clinical and methodological factors. Authors of trials were contacted to request unpublished data. Reports of two randomised controlled trials previously excluded from an earlier version of the review due to "deficiencies in reporting, insufficient data" have now been included. These two trials included approximately 128 children, with more than 150 palatally displaced canine teeth, and both were conducted by the same research group. Data presented in the trial reports are either incomplete or inconsistent. Both trials are at high risk of bias. It must be emphasised that both trials have serious deficiencies in the way they were designed, conducted, and reported, and attempts to contact the authors to obtain detailed information and clarify inconsistencies have been unsuccessful. Allocation to treatment appears to be at the level of the individual, but outcomes of successful treatment relate to included teeth and data are not reported for each treatment group. Adverse effects are not reported. Neither trial provides any evidence to guide clinical decision making. There is currently no evidence of the effects of extraction of primary canine teeth in 10-13 year old children with one or two palatally displaced permanent canine teeth.


Similarities and dissimilarities between teachers' and students' relationship views in upper elementary school: The role of personal teacher and student attributes.
The present study aimed to advance insight into similarities and dissimilarities between teachers' and students' views of closeness and conflict in their dyadic relationship, and personal teacher and student attributes that contribute to these views. In total, 464 students (50.2% girls) and 62 teachers (67.5% females) from grades 4 to 6 participated in this study. Teachers filled out questionnaires about their background characteristics, self-efficacy (TSES), and student-teacher relationship perceptions (STRS) and students answered questions about their demographics and the student-teacher relationship quality (SPARTS). Peer-nominations were used to measure students' internalizing and externalizing behavior. Tests for measurement invariance suggested that the conflict and closeness constructs both approximated similarity across students and teachers. Multilevel structural equation models furthermore indicated that students' relationship perceptions, and conflict in particular, were predicted by their own gender, socioeconomic status, and internalizing and externalizing behavior. Additionally, teaching experience negatively predicted students' perceived conflicts. Teachers' relationship perceptions were both predicted by their own characteristics (teaching experience) and student features (gender, socioeconomic status, and externalizing behavior). These predictors explained between 39% and 61% of the variance in student- and teacher-perceived closeness and conflict. Last, teachers' general self-efficacy was positively associated with mean levels of closeness, and negatively associated with mean levels of conflict across student-teacher dyads.


[Aspects of animal welfare with regard to the production of farmed fish in aquaculture systems].
The most important aspects on animal welfare with reference to fish are presented in this paper. World-wide a fast growing trend with regard to the production of aquatic organisms in aquaculture systems is observed. For the future an increase of the number of basic questions with relevance to animal welfare in this area is to be expected. The main precondition for the creation of appropriate welfare conditions with regard to the farmed fish species is the optimisation of the environmental quality. Careful handling in the course of necessary farming activities minimises the appearance of distrees and damages in live fish.


Determination of physical properties of bitumens by use of near-infrared spectroscopy with neural networks. Joint modelling of linear and non-linear parameters.
The fact that bitumens behave as non-Newtonian fluids results in non-linear relationships between their near-infrared (NIR) spectra and the physico-chemical properties that define their consistency (viz. penetration and viscosity). Determining such properties using linear calibration techniques [e.g. partial least-squares regression (PLSR)] entails the previous transformation of the original variables by use of non-linear functions and employing the transformed variables to construct the models. Other properties of bitumens such as density and composition exhibit linear relationships with their NIR spectra. Artificial neural networks (ANNs) enable modelling of systems with a non-linear property-spectrum relationship; also, they allow one to determine several properties of a sample with a single model, so they are effective alternatives to linear calibration methods. In this work, the ability of ANNs simultaneously to determine both linear and non-linear parameters for bitumens without the need previously to transform the original variables was assessed. Based on the results, ANNs allow the simultaneous determination of several linear and non-linear physical properties typical of bitumens.


Multimodal porous carbon derived from ionic liquids: correlation between pore sizes and ionic clusters.
In this proof of concept study on the synthesis of ionic liquid (IL)-derived multimodal porous carbon using ionic clusters of different sizes as porogens, the carbonization behaviors of binary IL mixtures of 1-ethyl-3-methylimidazolium dicyanamide (EMIM-dca) and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIM-Tf2N) were systematically investigated to demonstrate the formation of multimodal porous carbons with hierarchical structures originating from the ionic cluster porogens. The multimodal porous structures of the resulting IL-derived porous carbons were characterized based on the quenched solid density functional theory, and the role of the ionic clusters as porogens is discussed. From the viewpoint of green and sustainable chemistry, the IL-based synthesis using ionic clusters as porogens is a simple, effective, and sustainable technique for synthesizing multimodal porous carbons with hierarchical structures. To the best of our knowledge, this is the first study demonstrating that a multimodal porous structure of IL-derived porous carbons could be systematically manipulated with the aid of ionic clusters of different sizes as porogens.


Complementary planar terahertz metamaterials.
Planar electric split ring resonator (eSRR) metamaterials and their corresponding inverse structures are designed and characterized computationally and experimentally utilizing finite element modeling and THz time domain spectroscopy. A complementary response is observed in transmission. Specifically, for the eSRRs a decrease in transmission is observed at resonance whereas the inverse structures display an increase in transmission. The frequency dependent effective complex dielectric functions are extracted from the experimental data and, in combination with simulations to determine the surface current density and local electric field, provide considerable insight into the electromagnetic response of our planar metamaterials. These structures may find applications in the construction of various THz filters, transparent THz windows, or THz grid structures ideal for constructing THz switching/modulation devices.


[Evaluation of second-line antituberculosis drug susceptibilities of multidrug-resistant Mycobacterium tuberculosis complex isolates by E-test method].
Multidrug-resistant (MDR) tuberculosis (TB) constitutes a restricting factor for the effective treatment of TB worldwide. Early diagnosis and appropriate treatment of patients are the most effective strategy in the control of MDR-TB. Therefore, knowledge of drug resistance patterns of the MDR-TB clinical isolates are necessary in planning of an appropriate treatment regimen for the patient. The aims of this study were to detect the susceptibilities of MDR-TB isolates to second-line anti-TB drugs by E-test method, and to compare their results with Löwenstein-Jensen (LJ) proportion method. A total of 122 MDR (resistant to isoniazid and rifampicin) Mycobacterium tuberculosis complex (MTC) strains isolated from samples of patients with pulmonary TB were included in the study. The isolates were identified by conventional methods and first-line anti-TB drug susceptibility testing was performed by the proportion method using LJ medium. The susceptibilities of the isolates to second-line anti-TB drugs [kanamycin (KN), ofloxacin (OFL), ethionamid (ETN), linezolid (LIN)] were tested by proportion method on LJ medium and E-test method on Middlebrook 7H11 medium. For this purpose, E-test strips (bioMerieux, Fransa) of KN (0.016-256 mg/ml), OFL (0.02-32 mg/ml), ETN (0.016-256 mg/ml), and LIN (0.016-256 mg/ml) were used. The susceptibility tests were evaluated in 5., 7., and 10. days after application of the E-test strips, and proportion method on LJ medium was evaluated 28 days later. Second line-anti-TB drug susceptibility results were obtained in 5 to 10 days by E-test. Of the MDR MTC strains 98% (119/122) were susceptible to KN, OFL and LIN, while 2% (3/122) of the strains were resistant to KN and ETN. The correlation between E-test and LJ proportion method was estimated as 96% for KN and ETN, 98% for OFL, and 100% for LIN. When compared with LJ proportion method, the specificity of E-test in the detection of susceptibility to KN, OFL, ETN and LIN were 60%, 38%, 60%, and 100%, respectively, while the sensitivity was 100% for all drugs. Our results indicated that E-test method exhibited high sensitivity and specificity (100%) for LIN, so it may be used alone in susceptibility testing for this drug, however since the specificity is low (38%) for OFL it should be used together with the proportion method. In conclusion, E-test method might contribute for initiation of an early and effective anti-TB drug treatment and control of infection by rapid diagnosis in MDR-TB cases.


Fatal maternal beta-hemolytic group B streptococcal meningitis: a case report.
Meningitis secondary to beta-hemolytic group B streptococcus is rare and represents less than 1% of cases of adult meningitis. We report the first known case of maternal mortality attributed to beta-hemolytic group B streptococcal meningitis. A 23-year-old African-American woman with a benign prenatal course delivered a viable male infant at term. Labor was complicated by thick meconium for which a saline amnioinfusion was utilized. On postpartum Day 1, the patient complained of right hip pain and a headache. Within 12 hr the patient was comatose with fixed and dilated pupils. Life support measures were discontinued secondary to absence of electrocortical activity. Postmortem examination revealed endomyometritis and fulminant meningitis with gram-positive cocci. Placental histologic sections demonstrated acute chorioamnionitis and bateriological cultures noted beta-hemolytic group B streptococcus. The virulence of beta-hemolytic group B streptococcus in the neonate is well recognized. This case demonstrates that beta-hemolytic group B streptococcus is also a potentially fatal maternal pathogen.


Method for the determination of photomultiplier collection efficiency, F.
Photomultiplier collection efficiency, F, is a fundamental, but difficult, parameter to measure with certainty. A method for its determination, based on the gain of the first dynode, has been devised and applied to two different types of photomultiplier. The measurements are substantially free from the sources of error, which have compromised previously reported results by other authors. F may be determined by the proposed method with an accuracy of better than +/-3% for any photomultiplier tube with sufficient gain to uncover its single electron response.


Life and dinner under the shared umbrella: patterns in felid and primate communities.
Sympatry between primates and felids is potentially relevant to both their behavioural ecology and their conservation. This paper briefly introduces felids and primates, for the purposes of assessing their interrelationships and the patterns in their spatial congruence using IUCN spatial data. First, we review evidence and opportunity for predator-prey interactions between the felids and primates. Second, we analyse the overlap between species of the two taxa to reveal the potential of particular felid species or guilds (unique combinations of 2 or more felids) to act as umbrellas for the conservation of co-occurring primates. Felid guilds vary in terms of their geographical ranges and numbers of members. Some felid species overlap the ranges of many primate species, and the most speciose felid guilds, while geographically limited in distribution, have the potential to act as protective umbrellas to large numbers of primate species. This prompts the hypothesis that threatened primates and felids are facing similar threats and might thus benefit from similar interventions, which is evaluated in a sister paper by Macdonald et al. in this special issue.


Pityriasis rotunda. A cutaneous marker of hepatocellular carcinoma in South African blacks.
Although paraneoplastic phenomena occur frequently in patients with hepatocellular carcinoma, cutaneous changes have rarely been reported. During the past two years, ten South African blacks with hepatocellular carcinoma and pityriasis rotunda have been seen in a single hospital. The rash affected the trunk, especially the lower back and buttocks. The lesions ranged in size from 1.5 to 25 cm and were always multiple. They had a characteristic circular or arcuate configuration with scaling and varying degrees of hyperpigmentation. Pityriasis rotunda may prove to be a useful cutaneous marker of hepatocellular carcinoma in South African blacks.


Evaluation and management of facial fractures.
Facial fractures may portend intracranial and skullbase injury and may lead to rapid compromise of the airway. Primary care physicians may provide emergency care for patients who have sustained facial trauma. After immediate resuscitation and stabilization, management of facial fractures requires knowledge of the anatomy, rapid treatment methods and identification of potential associated injuries for each type of facial fracture. Differentiation between the life-threatening aspects of these injuries and the less urgent, but more apparent, facial injuries will lessen the risk of complications such as bleeding, meningitis and asphyxia. Knowledge of the anatomy of the facial skeleton and of the potential injuries associated with each of the various types of facial fractures will facilitate effective management decisions. Consultation should be sought when functional features are involved or when the injury threatens to produce future cosmetic anomalies.


Cognitive performance enhancement: misuse or self-treatment?
This cross-sectional survey study examines the link between ADHD medication misuse and a positive screen for adult ADHD symptoms. Surveys from 184 college student volunteers in Northern Virginia are collected and analyzed. A total of 71% of ADHD stimulant misusers screen positive for ADHD symptoms. Misusers are 7 times more likely to be symptomatic for ADHD than those who do not misuse. Also, 87% of misusers indicate that they do so for academic reasons, and 76% believe that the misuse of the ADHD stimulants improve their grades. ADHD stimulant misuse in college students is found to be strongly linked to having symptoms of adult ADHD. The desire for cognitive performance enhancement in college students may be a form of self-treatment for undiagnosed ADHD. College students need more accessibility to medical diagnosis and treatment of adult ADHD to reduce the incidence of misuse in the future.


Detection of Neisseria gonorrhoeae antigen by a solid-phase enzyme immunoassay.
The Gonozyme test (Abbott Laboratories) is a new enzyme immunoassay for detecting Neisseria gonorrhoeae antigens in specimens from the urethra in men and the endocervix in women. To evaluate the usefulness of the assay 249 patients were investigated. The results obtained with the immunoassay were compared with those of culture and microscopy of Gram-stained smears. The sensitivity and specificity of the test were high in men with urethritis and acceptable in different groups of women. As the sensitivity of the Gonozyme test was much higher than that of microscopy for endocervical specimens it might be useful as a rapid screening test for the detection of gonorrhoea in women.


An easy method for quantification of anaerobic and microaerobic gene expression with fluorescent reporter proteins.
Fluorescent proteins, such as green fluorescent proteins, are invaluable tools for detecting and quantifying gene expression in high-throughput reporter gene assays. However, they introduce significant inaccuracies in studies involving microaerobiosis or anaerobiosis, as oxygen is required for the maturation of these proteins' chromophores. In this study, the authors highlight the errors incurred by using fluorescent proteins under limited oxygenation by comparing standard fluorescence-based reporter gene assays to quantitative real-time PCR data in the study of a complex oxygen-regulated gene network. Furthermore, a solution to perform quantification of anaerobic and microaerobic gene expression with fluorescent reporter proteins using a microplate reader with an oxygen control system and applying pulses of full oxygenation before fluorescence measurements is provided.


Serum beta-endorphin in primary fibromyalgia syndrome: a controlled study.
Serum beta-endorphin was assayed without knowledge of study subject category in 44 consecutive patients with primary fibromyalgia syndrome, 3 patients with rheumatoid arthritis (RA), and 30 normal controls, all females. Mean serum beta-endorphin levels were 81 +/- 28 pg/ml in patients with fibromyalgia, whereas those in normal controls and patients with RA were 73 +/- 17 pg/mg and 73 +/- 18 pg/ml, respectively. These differences were not statistically significant. Serum beta-endorphin levels did not correlate with relevant clinical variables in either fibromyalgia or RA groups.


Three-Dimensional Assessment of Descemet Membrane Reflectivity by Optical Coherence Tomography in Fuchs Endothelial Corneal Dystrophy.
This study aimed to evaluate Descemet membrane reflectivity using anterior segment optical coherence tomography (AS-OCT) in eyes with Fuchs endothelial corneal dystrophy (FECD). We retrospectively assessed 144 eyes of 88 consecutive participants (41 FECD, 15 pseudophakic bullous keratopathies [BKs], and 32 healthy controls, 63.5 ± 16.5 years). FECD was graded 0 to 3 based on the guttae areas using specular microscopy. The sum of AS-OCT reflectivity of the 3-dimensional volume from 10 μm thickness from the endothelial surface of the cornea and residual stromal area was calculated as Dsum(endo) and Dsum(stroma) in the central area of 3- and 6-mm diameters, respectively. The DES ratio was defined as the ratio of Dsum(endo) to Dsum(stroma). The percentage of the guttae area in the specular images was calculated using MATLAB. Dsum(endo) and DES ratio were compared among FECD, BK, and healthy controls. Dsum(endo) in FECD grade 3 was significantly higher than that in healthy control eyes, FECD patients with mild and moderate guttae, and BK (all P ≤ 0.040). The DES ratio in FECD patients with mild to severe guttae (grade 1-3) was significantly higher than that in healthy control eyes and BK (all P ≤ 0.035). The percentage of the guttae area was significantly correlated with Dsum(endo) (R = 0.488, P < 0.001 for 3 mm, R = 0.512, P < 0.001 for 6 mm) and DES ratio (R = 0.450, P < 0.001 for 3 mm, R = 0.588, P < 0.001 for 6 mm). Descemet membrane reflectivity in AS-OCT can be objective biomarkers for assessing guttae and FECD severity from early to end-stage FECD.


Diverticular disease.
Diverticular disease comprises a spectrum of illness beginning with the irritable bowel syndrome and progressing to the life-threatening complications of diverticulitis and hemorrhage. Step-wise progression of this disease may be seen but is not invariably present; many patients with diverticulosis do not have preceding symptoms of the irritable bowel syndrome. The typical complaints of irregularity of bowel habits and abdominal pain will usually respond to the relatively new treatment modality of a high fiber diet with added wheat bran. Barium enema x-ray examination remains the primary diagnostic modality in the investigation of diverticular disease, and colonoscopy should be used only in the presence of certain specific circumstances. Surgery, aimed at the treatment of complications of this disease, has progressed to the point where one-stage extirpation of the diseased bowel is recommended.


Oxidation of hemoproteins by Streptococcus pneumoniae collapses the cell cytoskeleton and disrupts mitochondrial respiration leading to the cytotoxicity of human lung cells.
Streptococcus pneumoniae (Spn) colonizes the lungs, killing millions every year. During its metabolism, Spn produces abundant amounts of hydrogen peroxide. When produced in the lung parenchyma, Spn-hydrogen peroxide (H2O2) causes the death of lung cells, and details of the mechanism are studied here. We found that Spn-H2O2 targets intracellular proteins, resulting in the contraction of the cell cytoskeleton and disruption of mitochondrial function, ultimately contributing to cell death. Intracellular proteins targeted by Spn-H2O2 included cytochrome c and, surprisingly, a protein of the cell cytoskeleton, beta-tubulin. To study the details of oxidative reactions, we used, as a surrogate model, the oxidation of another hemoprotein, hemoglobin. Using the surrogate model, we specifically identified a highly reactive radical whose creation was catalyzed by Spn-H2O2. In sum, we demonstrated that the oxidation of intracellular targets by Spn-H2O2 plays an important role in the cytotoxicity caused by Spn, thus providing new targets for interventions.


Prevalence and severity of periodontitis in patients with established rheumatoid arthritis and osteoarthritis.
Periodontitis is associated with many chronic health conditions including diabetes, cardiovascular disease, and rheumatoid arthritis (RA). RA and periodontitis have similarities in inflammatory mechanism, morphology, and histopathology. Osteoarthritis (OA) is a chronic, multifactorial degenerative disease characterized by the deterioration of cartilage in joints. The aim of this study was to evaluate the prevalence and severity of periodontal disease in patients with established RA and OA. A total of 200 patients reporting to the Department of Orthopaedics, KIMSDU, Karad were included in the study. Patients were divided into two groups: Group 1 that included 100 patients with established RA diagnosed according to American College of Rheumatology (ACR) classification 1987 criteria and Group 2 that comprised 100 patients diagnosed with OA. Demographic profile, medical and dental history, oral hygiene practices, and smoking status of study participants were recorded. Periodontal status of the patients were evaluated using the simplified oral hygiene index (OHI-S), Loe and Silness gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL). On the basis of the CAL score periodontitis severity was defined as slight, moderate, and severe. Rheumatoid Factor (RF) and C-reactive protein (CRP) were considered as a serological marker in RA. Serological tests were performed to measure RF and CRP. Periodontal parameters and serological tests were correlated. This study reported 45% severe periodontitis prevalence in RA compared to OA group, which was 33%. Severity of periodontitis is significantly greater in RF positive RA group with mean CAL 5.38 mm compared to RF negative RA group with mean CAL 2.81 mm (P = 0.001). There was moderate positive correlation found between RF titer and severity of periodontitis (r = 0.311). The severity of periodontitis was significantly higher among the patients with established RA as compared to patients with OA. RF positive patients had higher periodontal disease compared to RF negative patients. There was an increase in the mean clinical attachment loss with increase in RF titer.


Efficacy and safety of rifampin containing regimen for staphylococcal prosthetic joint infections treated with debridement and retention.
The aim of this study was to evaluate the efficacy and safety of rifampin for Staphylococcus aureus (SA) or coagulase negative staphylococci (CNS) prosthetic joint infection (PJI) treated with debridement and retention (D/R). We calculated the treatment failure cumulative incidence (TF) of a cohort of 101 patients with SA or CNS PJI treated with D/R and antimicrobial therapy. The effect of the use of a rifampin-based regimen was evaluated. Cox proportional hazards regression evaluated the association between treatment and time-to-TF controlling for the propensity to treat with rifampin and temporal confounders. Seven percent (1/14) of the prospective rifampin-treated patients, 32% (10/31) of the historical rifampin-treated patients and 38% (21/56) of the historical non-rifampin treated patients developed TF. After controlling for the propensity to treat with rifampin and American Society of Anesthesia scores, patients in the prospective cohort had a lower risk of TF compared to patients in the historical cohort not treated with rifampin (HR 0.11; 95%CI 0.01-0.84). None (0/14) of the patients in the prospective study developed hepatotoxicity. The outcome of staphylococcal PJI treated with D/R and rifampin-based regimens was better when compared with a historical cohort treated without rifampin.


A framework for using signal, noise, and variation to determine whether the brain controls movement synergies or single muscles.
We have used an analysis of signal and variation in motor behavior to elucidate the organization of the cerebellar and brain stem circuits that control smooth pursuit eye movements. We recorded from the abducens nucleus and identified floccular target neurons (FTNs) and other, non-FTN vestibular neurons. First, we assessed neuron-behavior correlations, defined as the trial-by-trial correlation between the variation in neural firing and eye movement, in brain stem neurons. In agreement with prior data from the cerebellum, neuron-behavior correlations during pursuit initiation were large in all neurons. Second, we asked whether movement variation arises upstream from, in parallel to, or downstream from a given site of recording. We developed a model that highlighted two measures: the ratio of the SDs of neural firing rate and eye movement ("SDratio") and the neuron-behavior correlation. The relationship between these measures defines possible sources of variation. During pursuit initiation, SDratio was approximately equal to neuron-behavior correlation, meaning that the source of signal and variation is upstream from the brain stem. During steady-state pursuit, neuron-behavior correlation became somewhat smaller than SDratio for FTNs, meaning that some variation may arise downstream in the brain stem. The data contradicted the model's predictions for sources of variation in pathways that run parallel to the site of recording. Because signal and noise are tightly linked in motor control, we take the source of variation as a proxy for the source of signal, leading us to conclude that the brain controls movement synergies rather than single muscles for eye movements.


Post-dural puncture headache: pathogenesis, prevention and treatment.
Spinal anaesthesia developed in the late 1800s with the work of Wynter, Quincke and Corning. However, it was the German surgeon, Karl August Bier in 1898, who probably gave the first spinal anaesthetic. Bier also gained first-hand experience of the disabling headache related to dural puncture. He correctly surmised that the headache was related to excessive loss of cerebrospinal fluid (CSF). In the last 50 yr, the development of fine-gauge spinal needles and needle tip modification, has enabled a significant reduction in the incidence of post-dural puncture headache. Though it is clear that reducing the size of the dural perforation reduces the loss of CSF, there are many areas regarding the pathogenesis, treatment and prevention of post-dural puncture headache that remain contentious. How does the microscopic pattern of collagen alignment in the spinal dura affect the dimensions of the dural perforation? How do needle design, size and orientation influence leakage of CSF through the dural perforation? Can pharmacological methods reduce the symptoms of post-dural puncture headache? By which mechanism does the epidural blood patch cure headache? Is there a role for the prophylactic epidural blood patch? Do epidural saline, dextran, opioids and tissue glues reduce the rate of CSF loss? This review considers these contentious aspects of post-dural puncture headache.


Effect of green garlic/cucumber crop rotation for 3 years on the dynamics of soil properties and cucumber yield in Chinese anthrosol.
Long-term drastic anthropic inputs in conventional monoculture systems cause negative plant-soil feedback that will largely affect sustainable cucumber cultivation. The inclusion of multicropping in intensive cropping systems could reduce the detrimental effects of continuous cropping obstacles. The present study investigated the dynamics of soil microbial communities, soil enzyme activities and cucumber yield under plastic tunnel cultivation for three successive growing seasons (2013, 2014 and 2015). In the amended crop rotation system, soil pH decreased with increasing number of cropped garlic bulbs. The soil electrical conductivity significantly changed during the entire growth period and increased with increasing number of incorporated garlic bulbs. The level of soil organic matter content increased in the last year (2015). Soil catalase activity was generally induced by the treatments of 10, 15, 20 and 25 garlic bulbs, and soil invertase activity was also enhanced by all the treatments in the last year. Similarly, fungal species richness dramatically increased under these crop rotation systems. In this study, we found the highest cucumber yield under the cropping treatment of 20 garlic bulbs. The results indicate that the green garlic/cucumber cropping system is a sustainable and efficient cropping system for cucumber production and can improve the soil environment to a certain extent. © 2019 Society of Chemical Industry.


Assessment of Plasmodium falciparum drug resistance molecular markers from the Blue Nile State, Southeast Sudan.
Plasmodium falciparum malaria is a public health problem worldwide. Malaria treatment policy has faced periodic changes due to emergence of drug resistant parasites. In Sudan chloroquine has been replaced by artesunate and sulfadoxine/pyrimethamine (AS/SP) in 2005 and to artemether-lumefantrine (AL) in 2017, due to the development of drug resistance. Different molecular markers have been used to monitor the status of drug resistant P. falciparum. This study aimed to determine the frequency of malaria drug resistance molecular markers in Southeast Sudan. The samples of this study were day zero dried blood spot samples collected from efficacy studies in the Blue Nile State from November 2015 to January 2016. A total of 130 samples were amplified and sequenced using illumina Miseq platform. The molecular markers included were Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfk13, exonuclease and artemisinin resistant (ART-R) genetic background (Pfmdr2, ferroredoxine, Pfcrt and Pfarps10). Resistance markers for chloroquine were detected in 25.8% of the samples as mutant haplotype Pfcrt 72-76 CVIET and 21.7% Pfmdr1 86Y. Pfdhfr mutations were detected in codons 51, 59 and 108. The ICNI double-mutant haplotype was the most prevalent (69%). Pfdhps mutations were detected in codons 436, 437, 540, 581 and 613. The SGEGA triple-mutant haplotype was the most prevalent (43%). In Pfdhfr/Pfdhps combined mutation, quintuple mutation ICNI/SGEGA is the most frequent one (29%). Six of the seven treatment failure samples had quintuple mutation and the seventh was quadruple. This was significantly higher from the adequately responsive group (P < 0.01). Pfk13 novel mutations were found in 7 (8.8%) samples, which were not linked to artemisinin resistance. Mutations in ART-R genetic background genes ranged from zero to 7%. Exonuclease mutation was not detected. In this study, moderate resistance to chloroquine and high resistance to SP was observed. Novel mutations of Pfk13 gene not linked to treatment failure were described. There was no resistance to piperaquine the partner drug of dihydroartemisinin/piperaquine (DHA-PPQ).


Energy and temperature dependent dissociation of the Na(+)(benzene)1,2 clusters: importance of anharmonicity.
Chemical dynamics simulations were performed to study the unimolecular dissociation of randomly excited Na(+)(Bz) and Na(+)(Bz)2 clusters; Bz = benzene. The simulations were performed at constant energy, and temperatures in the range of 1200-2200 K relevant to combustion, using an analytic potential energy surface (PES) derived in part from MP2/6-311+G* calculations. The clusters decompose with exponential probabilities, consistent with RRKM unimolecular rate theory. Analyses show that intramolecular vibrational energy redistribution is sufficiently rapid within the clusters that their unimolecular dynamics is intrinsically RRKM. Arrhenius parameters, determined from the simulations of the clusters, are unusual in that Ea is ∼10 kcal/mol lower the Na(+)(Bz) → Na(+) + Bz dissociation energy and the A-factor is approximately two orders-of-magnitude too small. Analyses indicate that temperature dependent anharmonicity is important for the Na(+)(Bz) cluster's unimolecular rate constants k(T). This is consistent with the temperature dependent anharmonicity found for the Na(+)(Bz) cluster from a Monte Carlo calculation based on the analytic PES used for the simulations. Apparently temperature dependent anharmonicity is quite important for unimolecular dissociation of the Na(+)(Bz)1,2 clusters.


Subclinical atherosclerosis and cardiovascular markers in patients with lichen planus: A case-control study.
Lichen planus is an idiopathic and chronic inflammatory disease that affects the skin and the mucous membranes, and has been associated with an increased risk for cardiovascular diseases. Hyperhomocysteinemia has been regarded as a risk factor for atherosclerosis and cardiovascular diseases. Increased plasma fibrinogen levels are also associated with increased risk of myocardial infarction. The main aim of this study is the evaluation of common carotid artery mean intima media wall thickness, serum fibrinogen and homocysteine levels in patients with lichen planus. Forty-three patients with lichen planus and 43 age, gender and body mass index (BMI) matched healthy controls (from general population without the disease) were included in this study. Compared to the healthy controls, patients had statistically significant greater mean intima media wall thickness of the common carotid artery. Moreover, a positive correlation was observed between lichen planus and increased serum homocysteine and c-reactive protein levels. The main limitation of this study is the small sample size due to the time limitation and financial constraints. Early diagnosis of atherosclerosis in patients with lichen planus might afford better prophylaxis, including weight control and/or lipid profile monitoring. Measurement of the mean intima media wall thickness of the common carotid artery by duplex high-resolution B-mode ultrasound scanning could be beneficial as a valuable method for early diagnosis of atherosclerosis in lichen planus.


Assessment of shape variation of the levator ani with optimal scan planning and statistical shape modeling.
To capture 3D shape variation of the levator ani during straining with open access MR imaging. Optimal scan-planning based on statistical shape modeling is developed for recovering the entire 3D structure of the levator ani from a limited number of 2D imaging planes. Statistical shape modeling ensures optimum material correspondence, and Subspace Reprojection is used to identify the optimum orientation of the imaging plans. The accuracy of the method in using limited 2D imaging planes to instantiate the dynamic structure of the levator ani is assessed with data acquired from 10 asymptomatic subjects. Leave-one-out analysis was performed whereby a model based on a training set consisting of all but one surface was used to instantiate the dynamic surface structure from the corresponding optimal planes. The mean surface distance error for the proposed Subspace Reprojection method is 3.989 +/- 0.790 mm, which is significantly smaller than other approaches. Surfaces of the levator ani may be instantiated using a limited number of imaging planes as well as a statistical shape model based on a training set of subjects. The proposed technique offers a new way forward for studying dynamic shape changes of 3D structures where complete volumetric imaging is prohibited by the inherent temporal resolution of the scanning technique.


Poor adherence to medication as assessed by the Morisky Medication Adherence Scale-8 and low satisfaction with treatment in 237 psoriasis patients.
Previously we assessed the medication adherence for oral and topical remedies by a translated Japanese version of the Morisky Medication Adherence Scale-8 (MMAS-8) together with socioeconomic backgrounds in 3096 Japanese dermatological patients, and found the medication adherence, especially to topical drugs, was poor in these patients. In order to elucidate the disease-specific sociomedical factors, we further sub-analyzed the medication adherence in 237 psoriasis patients and compared it with that in other dermatological diseases such as atopic dermatitis, urticaria or tinea. This study was conducted among patients registered in monitoring system and 3096 eligible patients were enrolled. Our web-based questionnaire included the following items such as age, sex, annual income, main health-care institution, experience of effectiveness by oral or topical medication, overall satisfaction with treatment, and MMAS-8 for oral or topical medication. Mean adherence score by MMAS-8 was 5.2 for oral and 4.3 for topical medication. More patients with psoriasis used a university hospital and fewer used a private clinic compared with those with the other skin disease patients. Experience of drug effectiveness by oral medication and overall satisfaction with treatment was lower in psoriasis patients than in other patients. In oral medication, significantly better adherence was observed in those of higher age and with higher annual income. The adherence to medication, especially to topical drugs, was poor in 237 psoriasis patients. We speculated that some severe psoriasis patients were not sufficiently treated systemically and were resistant to topical therapy, leading to poor adherence.


The state of research on ego identity: A review and appraisal : Part I.
Considerable research on ego identity has appeared over the past 15 years, indicating the need for an overall review. Part I commences by considering the complexity of Erikson's concept and suggesting several different theoretical contexts in which it has been used. The validity of investigators' attempts to operationalize the concept "ego identity" is assumed to depend in part upon their interpretations of its meaning. The subsequent review of empirical literature is organized according to different procedures which have been used to measure ego identity. A first section summarizes and evaluates research utilizing Q-sort and self-report questionnaire measures, while a second considers the large number of investigations that have employed James Marcia's Identity Status Interview. The latter group of studies are ordered according to the type of dependent variable (e.g., cognitive, behavioral, personality, developmental) examined in relation to ego identity status (i.e., achievement, moratorium, foreclosure, diffusion). Part II of the review, to appear in the next issue of this journal, will recapitulate the identity status literature, present an overall evaluation of the identity status paradigm, and suggest a number of issues for future research.


Diagnosis and management of cracked tooth by quantitative light-induced fluorescence technology.
The aim of this case report was to describe the process of diagnosis and treatment of a cracked tooth using quantitative light-induced fluorescence (QLF). A 43-year-old male presented at our dental clinic with a complaint of cold pain in #17 tooth. A routine oral examination with radiography was performed for evaluation of the oral condition and treatment planning. Additionally, QLF image capture was performed using Qraycam and Qraypen (AIOBIO, Seoul, Republic of Korea), to collect white-light and fluorescence images. The #17 tooth was observed to have a crack line, showing red fluorescence, from the distal to mesial aspect on the occlusal surface. Even though there was no visible root fracture in the radiographic image, bone loss was observed. Therefore, we performed periodontal treatment. One month later, a root canal treatment was performed because the patient still complained of pain in the #17 tooth. During this treatment, one fluorescent image and one white light image set was captured with the Qraypen. A crack line showing red fluorescence was observed, while the line was not visible to the naked eye. After treatment, the patient has had no complaint related to this tooth for 3 years until today. Clinically, use of QLF confirmed the presence of a crack before and during a root canal treatment. Therefore, it is postulated that the QLF technology could objectively facilitate the diagnosis and treatment of a cracked tooth.


Parent cognitive, behavioural, and affective factors and their relation to child pain and functioning in pediatric chronic pain: a systematic review and meta-analysis.
Previous studies have demonstrated that parental cognitive, behavioral, and emotional factors are related to child functioning in children and adolescents with chronic pain. This is particularly important to understand how to potentially enhance the efficacy of psychological interventions for children by incorporating interventions targeting parents. We conducted a systematic review and meta-analysis to identify the specific parent factors that have been examined in the literature and to quantify the associations observed between parent factors and child pain and disability. A search of the electronic databases EMBASE, PsychINFO, Medline, and PubMed was conducted, using search terms related to chronic pain, pediatric population, and parents. Fifty-four studies met criteria and were included in the review. Parent pain catastrophizing and protective behavior were the most commonly assessed parental constructs in the literature. Meta-analyses were conducted for associations between parent pain catastrophizing, parent protective behaviors, parent anxiety and depression, and parent stress associated with parenting a child with chronic pain with child pain, disability, school functioning, and emotional functioning. Correlation coefficients were pooled using the random-effects model. A medium relationship was observed between higher protective behavior and poorer school functioning (r = -0.39), and small relationships were found between higher parent pain catastrophizing and increased child disability (r = 0.29); higher protective behaviors and increased child disability (r = 0.25); and increased parent depression and anxiety with increased child disability (r = 0.23 and r = 0.24, respectively). Future research is needed to investigate broader parent variables and overcome methodological weaknesses in this field.


Potential use of procalcitonin as a diagnostic criterion in febrile neutropenia: experience from a multicentre study.
In order to assess the diagnostic value of procalcitonin, 158 patients with febrile neutropenia from centres across Europe were studied. Patients with fever were diagnosed on the basis of either: (1) clinical, radiological and microbiological criteria; or (2) the procalcitonin value. In the latter case, concentrations of 0.5-1.0 ng/mL were considered diagnostic of localised infection, concentrations of 1.0-5.0 ng/mL of bacteraemia, and concentrations of > 5.0 ng/mL of severe sepsis. Procalcitonin and C-reactive protein were estimated daily in serum by immunochemiluminescence and nephelometry, respectively. Overall, the sensitivity (specificity) of procalcitonin for bacteraemia was 44.2% (64.3%) at concentrations of 1.0-5.0 ng/mL, and 83.3% (100%) for severe sepsis at concentrations of > 5.0 ng/mL. It was concluded that procalcitonin is a marker strongly suggestive of severe sepsis at concentrations of > 5.0 ng/mL. Estimated concentrations of < 0.5 ng/mL indicate that infection is unlikely, but it was observed that bacteraemia associated with coagulase-negative staphylococci may fail to elevate serum procalcitonin levels.


Penicillin Allergy Testing Is Cost-Saving: An Economic Evaluation Study.
Having a penicillin allergy label is associated with the use of less appropriate and more expensive antibiotics and increased healthcare utilization. Penicillin allergy testing results in delabeling most allergy claimants and may be cost-saving. This study aimed to project whether penicillin allergy testing in patients reporting a penicillin allergy is cost-saving. In this economic evaluation study, we built decision models to project the economic impact of 2 strategies for a patient with a penicillin allergy label: (1) perform diagnostic testing (drug challenges, with or without skin tests); and (2) do not perform diagnostic testing. The health service perspective was adopted, considering costs with penicillin allergy tests, and with hospital bed-days/outpatient visits, antibiotic use, and diagnostic testing. Twenty-four base case decision models were built, accounting for differences in the diagnostic workup, setting (inpatient vs outpatient) and geographic region. Uncertainty was explored via probabilistic sensitivity analyses. Penicillin allergy testing was cost-saving in all decision models built. For models assessing the performance of both skin tests and drug challenges, allergy testing resulted in average savings (in United States [US] dollars) of $657 for inpatients (US: $1444; Europe: $489) and $2746 for outpatients (US: $256; Europe: $6045). 75% of simulations obtained through probabilistic sensitivity analysis identified testing as the less costly option. Penicillin allergy testing was projected to be cost-saving across different scenarios. These results are devised to inform guidelines, supporting the adoption of policies promoting widespread testing of patients with a penicillin allergy label.


Improving the accuracy of beef cattle methane inventories in Latin America and Caribbean countries.
On-farm methane (CH4) emissions need to be estimated accurately so that the mitigation effect of recommended practices can be accounted for. In the present study prediction equations for enteric CH4 have been developed in lieu of expensive animal measurement approaches. Our objectives were to: (1) compile a dataset from individual beef cattle data for the Latin America and Caribbean (LAC) region; (2) determine main predictors of CH4 emission variables; (3) develop and cross-validate prediction models according to dietary forage content (DFC); and (4) compare the predictive ability of these newly-developed models with extant equations reported in literature, including those currently used for CH4 inventories in LAC countries. After outlier's screening, 1100 beef cattle observations from 55 studies were kept in the final dataset (∼ 50 % of the original dataset). Mixed-effects models were fitted with a random effect of study. The whole dataset was split according to DFC into a subset for all-forage (DFC = 100 %), high-forage (94 % ≥ DFC ≥ 54 %), and low-forage (50 % ≥ DFC) diets. Feed intake and average daily gain (ADG) were the main predictors of CH4 emission (g d-1), whereas this was feeding level [dry matter intake (DMI) as % of body weight] for CH4 yield (g kg-1 DMI). The newly-developed models were more accurate than IPCC Tier 2 equations for all subsets. Simple and multiple regression models including ADG were accurate and a feasible option to predict CH4 emission when data on feed intake are not available. Methane yield was not well predicted by any extant equation in contrast to the newly-developed models. The present study delivered new models that may be alternatives for the IPCC Tier 2 equations to improve CH4 prediction for beef cattle in inventories of LAC countries based either on more or less readily available data.


Adverse effects and tolerability of medications for the treatment of tobacco use and dependence.
Tobacco use is the leading cause of preventable death and disability in the world. Although gradually declining in most developed countries, the prevalence of tobacco use has increased among developing countries. Treatment for tobacco use and dependence is effective, although long-term abstinence rates remain disappointingly low. In response, new treatments continue to be developed. In addition, many of the pharmacotherapies that have been available for years have found new applications with the use of medication combinations, higher doses and a longer duration of therapy for approved medications. There are now seven medications (nicotine patch, nicotine gum, nicotine lozenge, nicotine inhaler, nicotine nasal spray, bupropion sustained release and varenicline) approved for tobacco dependence treatment in most countries, and many national and professional society practice guidelines recommend their use. Although each of the medications used for tobacco dependence treatment has been rigorously tested for efficacy and safety, broader experience in clinical trials and in observational population-based studies suggests that adverse events associated with these medications are relatively common. Since 2008, two of the medications (varenicline and bupropion) have come under increasing scrutiny because of reports of unexplained serious adverse events (SAEs), including behaviour change, depression, self-injurious thoughts and suicidal behaviour. To date, this association has not been shown to be caused by these medications, but concerns about medication safety continue. Prescribers require a working knowledge of the common adverse effects for all of these medications as well as a more detailed knowledge of the SAE potential. Nicotine replacement therapy (NRT) has been rigorously tested in clinical trials for over 30 years. A number of adverse effects are commonly associated with NRT use, although SAEs are rare. The adverse effects associated with NRT are due to the pharmacological action of nicotine as well as the mode and site of the NRT application. Bupropion has been tested in over 40 controlled clinical trials and has been associated with higher rates of treatment discontinuation due to adverse events than NRTs. A number of SAEs are associated with bupropion and new warnings were recently added to bupropion prescribing information because of observed neuropsychiatric symptoms including suicidal thoughts and behaviours. Varenicline is the most recently approved medication for tobacco dependence treatment and, although proven safe in clinical testing, new safety concerns have arisen based on post-marketing reports. Warnings have been added to the prescribing information for varenicline because of neuropsychiatric symptoms also including suicidal thoughts and behaviours. Informed decision making regarding the use of pharmacotherapy for the treatment of tobacco dependence requires knowledge about the risks of drug treatment that is weighed against the risks of continued tobacco use and the benefits of treatment. Over half of all long-term smokers will die of a tobacco-related disease and the risk of a serious or life-threatening adverse event with tobacco cessation pharmacotherapy is vanishingly small. Pharmacotherapy for tobacco dependence is also among the most cost-effective preventive health interventions. Given these factors, the benefit : risk ratio is strongly in favour of pharmacotherapy for tobacco dependence treatment in virtually all smokers who are motivated to quit.


Comparative study of peritoneal adhesions after intraperitoneal implantation in rats of meshes of polypropylene versus polypropylene/polyglecaprone versus polyester/porcine collagen.
To Compare the extent and intensity of adhesions formed between the intra-abdominal organs and the intraperitoneal implants of polypropylene mesh versus polypropylene/polyglecaprone versus polyester/porcine collagen used for correction of abdominal wall defect in rats. After the defect in the abdominal wall, thirty Wistar rats were placed in three groups (ten animals each) for intraperitoneal mesh implant: polypropylene group, polypropylene/polyglecaprone group, and polyester/porcine collagen group. The macroscopic evaluation of the extent and intensity of adhesions was performed 21 days after the implant. The polypropylene group had a higher statistically significant impairment due to visceral adhesions (p value = 0.002) and a higher degree of intense adherence in relation to polypropylene/polyglecaprone and polyester/porcine collagen groups (p value<0.001). The polyester/porcine collagen group showed more intense adhesions than the polypropylene/polyglecaprone group (p value=0.035). The intraperitoneal implantation of polypropylene meshes to correct defects of the abdominal wall caused the appearance of extensive and firm adhesions to intra-abdominal structures. The use of polypropylene/polyglecaprone or polyester/porcine collagen tissue-separating meshes reduces the number and degree of adhesions formed.


Granulocyte and plasma cytokine activity in acute cadmium intoxication in rats.
Changes in the number and ex vivo function of peripheral blood neutrophils were investigated following intraperitoneal administration of cadmium-chloride in rats. Besides a dose-dependent increase in the number of peripheral blood neutrophils, changes were found in the functional state of isolated polymorphonuclear leukocytes (PMNs). Increased spontaneous adhesion and activation, and TNF activity in a conditioned medium were observed in cultures of granulocytes in comparison to granulocytes from control (saline-treated) animals. Increased levels of plasma activity of inflammatory cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6) were noted following cadmium administration. Cytological signs of pulmonary inflammation were revealed histologically and the majority of neutrophils recovered from the lungs by enzyme digestion exhibited a capacity of nitroblue tetrazolium (NBT) reduction. Our data demonstrate that acute cadmium intoxication leads to a systemic inflammatory response characterized by numerical and functional changes in the granulocyte compartment and to increased levels of inflammation-related cytokine activity in the circulation. Correlations between the increased number of peripheral blood neutrophils and IL-6 plasma activity (r=0.776, p<0.00001) and the number of neutrophils recovered from the lung tissue (r=0.893, p<0.00001) suggested that systemic cadmium-induced inflammation might be involved in the pulmonary toxicity of cadmium.


Protective activity of Borrelia duttonii-specific immunoglobulin subclasses in mice.
To analyse the immune response of mice to Borrelia duttonii infection, BALB/c mice were inoculated intraperitoneally with B. duttonii strain 406K, and the titres of B. duttonii-specific immunoglobulins - IgM, IgG1, IgG2a, IgG2b and IgG3 - were determined by ELISA. IgM antibodies appeared first, followed by IgG2a and IgG3, and then IgG1 and IgG2b. The protective activity of individual classes and subclasses of B. duttonii-specific immunoglobulins was then determined by passive immunisation of BALB/c mice with immunoglobulin preparations purified by affinity chromatography. The mice were then challenged by intraperitoneal inoculation of B. duttonii. The study demonstrated that B. duttonii-specific IgM and IgG3 protected against the development of spirochaetaemia and death after borrelial infection, whereas B. duttonii-specific IgG1, IgG2a and IgG2b had low protective activities.


The feasibility of a multidimensional intervention in lymphoma survivors with chronic fatigue.
Chronic fatigue (CF) affects 25-30% of lymphoma survivors, but interventions designed to reduce fatigue are lacking. The main aim of this study was to test the feasibility of a multidimensional intervention study in lymphoma survivors with CF. Secondary aims were to describe individual changes in fatigue, quality of life (QoL) and physical performance from pre (T0) to post (T1) intervention. This feasibility study was as a one-armed intervention study performed in 2021. Hodgkin or aggressive non-Hodgkin lymphoma survivors received mailed study information and Chalder Fatigue Questionnaire and were asked to respond if they suffered from fatigue. The 12-week intervention included patient education, physical exercise, a cognitive behavioural therapy (CBT)-based group program and nutritional counselling. Feasibility data included patient recruitment, completion of assessments, adherence to the intervention and patient-reported experience measures. Participants responded to questionnaires and underwent physical tests at T0 and T1. Seven lymphoma survivors with CF were included. Of all assessments, 91% and 83% were completed at T0 and T1, respectively. Adherence to the interventional components varied from 69% to 91%. At T1, all participants rated exercise as useful, of whom five rated the CBT-based program and five rated individual nutritional counselling as useful. Five participants reported improved fatigue, QoL and physical performance. Lymphoma survivors with CF participating in a multidimensional intervention designed to reduce the level of fatigue showed high assessment completion rate and intervention adherence rate. Most of the participants evaluated the program as useful and improved their level of fatigue, QoL and physical performance after the intervention. ClinicalTrials.gov, identifier: NCT04931407. Registered 16. April 2021-Retrospectively registered. https://www. gov/ct2/show/NCT04931407.


First-Phase Ejection Fraction, a Measure of Preclinical Heart Failure, Is Strongly Associated With Increased Mortality in Patients With COVID-19.
Presence of heart failure is associated with a poor prognosis in patients with coronavirus disease 2019 (COVID-19). The aim of the present study was to examine whether first-phase ejection fraction (EF1), the ejection fraction measured in early systole up to the time of peak aortic velocity, a sensitive measure of preclinical heart failure, is associated with survival in patients hospitalized with COVID-19. A retrospective outcome study was performed in patients hospitalized with COVID-19 who underwent echocardiography (n=380) at the West Branch of the Union Hospital, Wuhan, China and in patients admitted to King's Health Partners in South London, United Kingdom. Association of EF1 with survival was performed using Cox proportional hazards regression. EF1 was compared in patients with COVID-19 and in historical controls with similar comorbidities (n=266) who had undergone echocardiography before the COVID-19 pandemic. In patients with COVID-19, EF1 was a strong predictor of survival in each patient group (Wuhan and London). In the combined group, EF1 was a stronger predictor of survival than other clinical, laboratory, and echocardiographic characteristics including age, comorbidities, and biochemical markers. A cutoff value of 25% for EF1 gave a hazard ratio of 5.23 ([95% CI, 2.85-9.60]; P<0.001) unadjusted and 4.83 ([95% CI, 2.35-9.95], P<0.001) when adjusted for demographics, comorbidities, hs-cTnI (high-sensitive cardiac troponin), and CRP (C-reactive protein). EF1 was similar in patients with and without COVID-19 (23.2±7.3 versus 22.0±7.6%, P=0.092, adjusted for prevalence of risk factors and comorbidities). Impaired EF1 is strongly associated with mortality in COVID-19 and probably reflects preexisting, preclinical heart failure.


Fusion of Leishmania amazonensis parasitophorous vacuoles with phagosomes containing zymosan particles: cinemicrographic and ultrastructural observations.
Studies on fixed preparations have shown that vacuoles containing zymosan (Z) particles internalized by infected macrophages can selectively fuse with the large parasitophorous vacuoles (PVs) that shelter Leishmania amazonensis. To examine the kinetics of vacuolar fusion in individual cells, particles were followed by time-lapse cinemicrography from their uptake to their entry in a PV. Newly formed Z-containing vacuoles moved centripetally and, if they contacted a PV, the two vacuoles remained closely apposed for variable, often extended, periods of time before they eventually fused. Transmission electron microscopy confirmed that the cytoplasm separating the partner vacuoles could be reduced to a very thin layer. Initiation of fusion was indicated by reduced refractility of the boundary between Z vacuoles and target PVs. Within a few minutes the PV enlarged and encompassed the Z particles, which remained immobile throughout. The interval between phagocytosis and fusion, 50 +/- 7.4 min (N = 17; range, 4 to 108 min), suggests that most but not all Z vacuoles underwent significant maturation by the time of fusion. Some particles were transferred singly, others entered PVs in groups of 2 or more, and additional clustered transfers to the same vacuole were also observed. These observations provide a baseline for studies of the biochemical mechanisms and the pharmacological control of the fusion of Leishmania PVs, and for the comparison of the fusion behavior of the PVs with that of other phagocytically derived vacuoles.


Application description and policy model in collaborative environment for sharing of information on epidemiological and clinical research data sets.
Sharing of epidemiological and clinical data sets among researchers is poor at best, in detriment of science and community at large. The purpose of this paper is therefore to (1) describe a novel Web application designed to share information on study data sets focusing on epidemiological clinical research in a collaborative environment and (2) create a policy model placing this collaborative environment into the current scientific social context. The Database of Databases application was developed based on feedback from epidemiologists and clinical researchers requiring a Web-based platform that would allow for sharing of information about epidemiological and clinical study data sets in a collaborative environment. This platform should ensure that researchers can modify the information. A Model-based predictions of number of publications and funding resulting from combinations of different policy implementation strategies (for metadata and data sharing) were generated using System Dynamics modeling. The application allows researchers to easily upload information about clinical study data sets, which is searchable and modifiable by other users in a wiki environment. All modifications are filtered by the database principal investigator in order to maintain quality control. The application has been extensively tested and currently contains 130 clinical study data sets from the United States, Australia, China and Singapore. Model results indicated that any policy implementation would be better than the current strategy, that metadata sharing is better than data-sharing, and that combined policies achieve the best results in terms of publications. Based on our empirical observations and resulting model, the social network environment surrounding the application can assist epidemiologists and clinical researchers contribute and search for metadata in a collaborative environment, thus potentially facilitating collaboration efforts among research communities distributed around the globe.


Banksia born to burn.
• Historical evidence of recurrent fire in many of the world's biomes suggests that fire may have had profound evolutionary influences on their extant floras. However, the role of fire as a selective force in the origin and evolution of plant traits remains controversial. • Using Bayesian Monte-Carlo-Markov-Chain procedures and calibration points from the fossil record, we generated a dated phylogeny for the iconic Australian genus Banksia, and reconstructed the evolutionary/chronological position of five putatively fire-related traits. • The fire-dependent trait, on-plant seed storage (serotiny), and associated fire-enhancing trait, dead floret retention, co-originated with the first appearance of Banksia 60.8 million yr ago (Palaeocene). Whether nonsprouting or resprouting is ancestral was indeterminable, but the first banksias were nonclonal. Derived traits, such as dead leaf retention (fire-enhancing) and clonality (underground budbanks; fire-avoiding), first appeared 26-16 million yr ago (Miocene) with the onset of seasonal drought and thus more frequent fire, and culminated in dead florets/bracts completely covering the persistent fruits in some species. • Thus, fire may have been a selective force in the very origin of Banksia 40 million yr before the onset of climate seasonality in the Miocene, and continued to have an impact on the direction of evolution, favouring traits consistent with adaptation to an increasingly (sometimes less) fire-prone environment.


Telemedicine in extreme conditions: disasters, war, remote sites.
Telemedicine has developed around certain assumptions about connectivity and format. From the pioneer work of Kenneth Bird in the 1970's medical events separated by distance were connected for videoconference interaction [1]. The connection implied well developed telecommunications tools at both ends of the interaction. Telemedicine in its most common manifestations relies upon electronic and professional familiarity plus training with proper technical support. This is true even with Internet telemedicine at the low end of bandwidth. A workable Internet service provider and intact telecommunication services are required at both ends. The assumption of intact, robust telecommunications fails when there is any significant disruption of services, power, or trained people to initiate a telemedicine request. The very nature of disasters whether made by nature, made by fellow humans or in war declarations implies a rupture of the social fabric, a failure of infrastructure. This loss of infrastructure and connection happens at a cruel time when the need for services in health matters is generally very much exacerbated. Extreme remote sites have never had infrastructure and therefore fit into this chapter. Is telemedicine incompatible with support and relief in disasters of remote places? Certainly not. However, telemedicine must adapt to the situation in ways not generally associated with standard telemedicine. New solutions can meet the expectation of being wherever services are need whenever the need arises. This chapter looks at the experiences, successes and failures of telemedicine in natural disaster, war, and extreme remote sites. The presentation is concluded with recommendations to make telemedicine integral to any disaster response and a natural tool for any human endeavor that requires sending people to remote and hostile environments.


Off to the organelles - killing cancer cells with targeted gold nanoparticles.
Gold nanoparticles (AuNPs) are excellent tools for cancer cell imaging and basic research. However, they have yet to reach their full potential in the clinic. At present, we are only beginning to understand the molecular mechanisms that underlie the biological effects of AuNPs, including the structural and functional changes of cancer cells. This knowledge is critical for two aspects of nanomedicine. First, it will define the AuNP-induced events at the subcellular and molecular level, thereby possibly identifying new targets for cancer treatment. Second, it could provide new strategies to improve AuNP-dependent cancer diagnosis and treatment. Our review summarizes the impact of AuNPs on selected subcellular organelles that are relevant to cancer therapy. We focus on the nucleus, its subcompartments, and mitochondria, because they are intimately linked to cancer cell survival, growth, proliferation and death. While non-targeted AuNPs can damage tumor cells, concentrating AuNPs in particular subcellular locations will likely improve tumor cell killing. Thus, it will increase cancer cell damage by photothermal ablation, mechanical injury or localized drug delivery. This concept is promising, but AuNPs have to overcome multiple hurdles to perform these tasks. AuNP size, morphology and surface modification are critical parameters for their delivery to organelles. Recent strategies explored all of these variables, and surface functionalization has become crucial to concentrate AuNPs in subcellular compartments. Here, we highlight the use of AuNPs to damage cancer cells and their organelles. We discuss current limitations of AuNP-based cancer research and conclude with future directions for AuNP-dependent cancer treatment.


Optimum feeding and growth in preterm neonates.
Approximately 10% of all babies worldwide are born preterm, and preterm birth is the leading cause of perinatal mortality in developed countries. Although preterm birth is associated with adverse short- and long-term health outcomes, it is not yet clear whether this relationship is causal. Rather, there is evidence that reduced foetal growth, preterm birth and the long-term health effects of both of these may all arise from a suboptimal intrauterine environment. Further, most infants born preterm also experience suboptimal postnatal growth, with potential adverse effects on long-term health and development. A number of interventions are used widely in the neonatal period to optimise postnatal growth and development. These commonly include supplementation with macronutrients and/or micronutrients, all of which have potential short-term risks and benefits for the preterm infant, whereas the long-term health consequences are largely unknown. Importantly, more rapid postnatal growth trajectory (and the interventions required to achieve this) may result in improved neurological outcomes at the expense of increased cardiovascular risk in later life.


Morphologic, cytometric and functional characterisation of abalone (Haliotis tuberculata) haemocytes.
This work presents the first detailed microscopic and functional analysis of the haemocytes of an abalone; the European Haliotis tuberculata. It is shown that in contrast to the situation in bivalves, only very few basophilic "granulocytes" could be found and exclusively with a histological stain. Neither flow cytometry, phase contrast observation nor transmission electron microscopy were able to detect any granular cells. The large majority of cells was constituted of "hyalinocytes", which could be sorted by flow cytometry, for the first time, into small (blast-like) and large cells. This permits a detailed analysis of haemocytes and especially of the lowly represented blast-like cells. The differences in haemolymph cell composition between bivalves and gastropods is reviewed in depth and discussed in view of the new data we present. Most of the abalone haemocytes analysed harbour many vacuoles, large glycogen deposits, lipid inclusions and acidic compartments. However, although the number of these "inclusions" was rather variable in between individual hyalinocytes, these experiments did not allow to discern subpopulations using these criteria, and the population appears more as a "differentiation continuum". Haemocytes adhere very rapidly and are immunologically active as they quickly phagocytose latex beads and zymozan particles. This study is the first step towards understanding the H. tuberculata immune system by adapting new tools to gastropods and in providing a first detailed morpho-functional study of their haemocytes.


New insights on mitochondrial heteroplasmy observed in ovarian diseases.
The reportedly high mutation rate of mitochondrial DNA (mtDNA) may be attributed to the absence of histone protection and complete repair mechanisms. Mitochondrial heteroplasmy refers to the coexistence of wild-type and mutant mtDNA. Most healthy individuals carry a low point mutation load (<1%) in their mtDNA, typically without any discernible phenotypic effects. However, as it exceeds a certain threshold, it may cause the onset of various diseases. Since the ovary is a highly energy-intensive organ, it relies heavily on mitochondrial function. Mitochondrial heteroplasmy can potentially contribute to a variety of significant ovarian disorders. of Review: In this review, we have elucidated the close relationship between mtDNA heteroplasmy and ovarian diseases, and summarized novel avenues and strategies for the potential treatment of these ovarian diseases. Key Scientific Concepts of Review: Mitochondrial heteroplasmy can potentially contribute to a variety of significant ovarian disorders, including polycystic ovary syndrome, premature ovarian insufficiency, and endometriosis. Current strategies related to mitochondrial heteroplasmy are untargeted and have low bioavailability. Nanoparticle delivery systems loaded with mitochondrial modulators, mitochondrial replacement/transplantation therapy, and mitochondria-targeted gene editing therapy may offer promising paths towards potentially more effective treatments for these diseases, despite ongoing challenges.


Evaluation of errors in preparation and administration of intravenous medications in critically ill patients.
Intravenous medications have greater complexity and require multiple steps in their preparation and administration, which is considered a high risk for patients. To determine the incidence of intravenous medications preparation and administration errors in critically ill patients. This was an observational, cross-sectional, prospective study design. The study was performed in Wad Medani Emergency Hospital, Sudan . All nurses working at the study setting were observed over nine days. During the study period, a total number of 236 drugs were observed and evaluated. The total error rate was 940 (33.4%), of which 136 (57.6%) errors with no harm, 93 (39.4%) errors with harm and 7 (3%) of errors associated with mortality. 17 different drug categories were involved, in which antibiotic was the highest error rate 104 (44.1%) and 39 different drugs were involved, in which metronidazole was the most drug involved 34 (14.4%). The total error rate was associated with nurse experience, OR (95% CI); 3.235 (1.834-5.706), and nurse education level, OR (95% CI); 0.125 (0.052-0.299). The study reported high frequency of IV medications preparation and administration errors. Nurse education level, and experiences were influenced the total errors.


Cellular heterogeneity in red and melanized focal muscle changes in farmed Atlantic salmon (Salmo salar) visualized by spatial transcriptomics.
Spatial transcriptomics is a technique that provides insight into gene expression profiles in tissue sections while retaining structural information. We have employed this method to study the pathological conditions related to red and melanized focal changes in farmed Atlantic salmon (Salmo salar). Our findings support a model where similar molecular mechanisms are involved in both red and melanized filet discolorations and genes associated with several relevant pathways show distinct expression patterns in both sample types. Interestingly, there appears to be significant cellular heterogeneity in the foci investigated when looking at gene expression patterns. Some of the genes that show differential spatial expression are involved in cellular processes such as hypoxia and immune responses, providing new insight into the nature of muscle melanization in Atlantic salmon.


Mitochondrial abnormalities in neurodegenerative models and possible interventions: Focus on Alzheimer's disease, Parkinson's disease, Huntington's disease.
Mitochondrial abnormalities in the brain are considered early pathological changes in neurogenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). The mitochondrial dysfunction in the brain can be induced by toxic proteins, including amyloid-beta (Aβ), phosphorylated tau, alpha-synuclein (α-syn) and mutant huntingtin (mtHTT). These proteins cause mitochondrial genome damage, increased oxidative stress, decreased mitochondrial membrane permeability, and diminished ATP production. Consequently, synaptic dysfunction, synaptic loss, neuronal apoptosis, and ultimately cognitive impairment are exhibited. Therefore, the restoration of mitochondrial abnormalities in the brain is an alternative intervention to delay the progression of neurodegenerative diseases in addition to reducing the level of toxic proteins, especially Aβ, and restored synaptic dysfunction by interventions. Here we comprehensively review mitochondrial alterations in the brain of neurodegenerative models, specifically AD, PD and HD, from both in vitro and in vivo studies. Additionally, the correlation between mitochondrial changes, cognitive function, and disease progression from in vivo studies is described. This review also summarizes interventions that possibly attenuate mitochondrial abnormalities in AD, PD and HD models from both in vitro and in vivo studies. This may lead to the introduction of novel therapies that target on brain mitochondria to delay the progression of AD, PD and HD.


Role of the subunit interactions in the conformational transitions in adult human hemoglobin: an explicit solvent molecular dynamics study.
Hemoglobin exhibits allosteric structural changes upon ligand binding due to the dynamic interactions between the ligand binding sites, the amino acids residues and some other solutes present under physiological conditions. In the present study, the dynamical and quaternary structural changes occurring in two unligated (deoxy-) T structures and two fully ligated (oxy-) R, R2 structures of adult human hemoglobin were investigated with molecular dynamics. It is shown that, in the submicrosecond time scale, there is no marked difference in the global dynamics of the amino acid residues in both the oxy- and the deoxy-forms of the individual structures. In addition, the R, R2 are relatively stable and do not present quaternary conformational changes within the time scale of our simulations, while the T structure is dynamically more flexible and exhibited the T → R quaternary conformational transition, which is propagated by the relative rotation of the residues at the α(1)β(2) and α(2)β(1) interface.


Protocol to assess the impact of tobacco-induced volatile organic compounds on cardiovascular risk in a cross- sectional cohort: Cardiovascular Injury due to Tobacco Use study.
Tobacco use leads to increased mortality, the majority of which is attributed to cardiovascular disease. Despite this knowledge, the early cardiovascular impact of tobacco product use is not well understood. Tobacco use increases exposure to harmful and potentially harmful constituents including volatile organic compounds (VOCs) such as acrolein and crotonaldehyde, which may contribute to cardiovascular risk. The link between exposure patterns, risk profiles and demographic distribution of tobacco product users, particularly users of new and emerging products, are not well known. Therefore, we designed the Cardiovascular Injury due to Tobacco Use (CITU) study to assess population characteristics, demographic features, exposure patterns and cardiovascular risk in relation to tobacco. We present the design and methodology of the CITU study, a cross-sectional observational tobacco study conducted in Boston, Massachusetts and Louisville, Kentucky starting in 2014. Healthy participants 21-45 years of age who use tobacco products, including electronic nicotine devices, or who never used tobacco are being recruited. The study aims to recruit an evenly split cohort of African-Americans and Caucasians, that is, sex balanced for evaluation of self-reported tobacco exposure, VOC exposure and tobacco-induced injury profiling. Detailed information about participant's demographics, health status and lifestyle is also collected. The study protocol was approved institutional review boards at both participating universities. All study protocols will protect participant confidentiality. Results from the study will be disseminated via peer-reviewed journals and presented at scientific conferences.


Applications of Catalytic Hairpin Assembly Reaction in Biosensing.
Nucleic acids are considered as perfect programmable materials for cascade signal amplification and not merely as genetic information carriers. Among them, catalytic hairpin assembly (CHA), an enzyme-free, high-efficiency, and isothermal amplification method, is a typical example. A typical CHA reaction is initiated by single-stranded analytes, and substrate hairpins are successively opened, resulting in thermodynamically stable duplexes. CHA circuits, which were first proposed in 2008, present dozens of systems today. Through in-depth research on mechanisms, the CHA circuits have been continuously enriched with diverse reaction systems and improved analytical performance. After a short time, the CHA reaction can realize exponential amplification under isothermal conditions. Under certain conditions, the CHA reaction can even achieve 600 000-fold signal amplification. Owing to its promising versatility, CHA is able to be applied for analysis of various markers in vitro and in living cells. Also, CHA is integrated with nanomaterials and other molecular biotechnologies to produce diverse readouts. Herein, the varied CHA mechanisms, hairpin designs, and reaction conditions are introduced in detail. Additionally, biosensors based on CHA are presented. Finally, challenges and the outlook of CHA development are considered.


Zio® XT Patches in Pediatrics During the COVID-19 Pandemic: Comparisons Between In-Person and Mail-Home Application.
The Zio® (Zio) XT Patch is a 14-day continuous ambulatory ECG monitor. During the Covid-19 pandemic, Zios were mailed directly to patients for self-application. The purpose of this study was to compare the percent artifact, a marker for quality, of in-clinic (IC) to mail-home (MH) applications in a pediatric population. A single-center, IRB-approved study of patients 0- < 21 years of age with Zios was studied for wear and artifact time filtered out based on iRhythm's proprietary algorithm. In total, 284 Zios were randomly selected and analyzed for total wear time and artifact. Of these, 149 were IC prior to 12/31/2019 and 135 MH patches prescribed after 1/1/2020. No significant difference was found for percent artifact between the IC (7.8%) and MH (8.3%) group. Average IC wear-time was 127 h compared to MH at 99 h (p = 0.02). In conclusion, application of Zio patches outside of the pediatric cardiology clinic offers equivalent artifact, a marker of quality, as those applied in clinic and should be consideration as a viable alternative.