Transcranial alternating current stimulation for treating depression: a randomized controlled trial.
Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.


Patient-Reported Outcome Measures following Coblation Nucleoplasty for Cervical Discogenic Dizziness.
There is little research in the literature comparing the efficacy of coblation nucleoplasty with conservative treatment in the treatment of cervical discogenic dizziness and reporting the achieved rate of minimal clinically important differences (MCID) and patient acceptable symptom state (PASS) after surgery. This retrospective study aims to explore the patient-reported outcome measures (PROM) following coblation nucleoplasty for cervical discogenic dizziness and to compare the therapeutic effect of coblation nucleoplasty with prolonged conservative treatment. Sixty-one patients with cervical discogenic dizziness and a positive intradiscal diagnostic test eligible for single-level cervical coblation nucleoplasty were included in the study. Among these 61 patients, 40 patients underwent cervical coblation nucleoplasty, while the remaining 21 patients refused surgery and received continued conservative treatment. The primary PROMs were the intensity and frequency of dizziness and secondary PROMs were related to the neck disability index (NDI) and visual analog scale (VAS) for neck pain (VAS-neck) during a 12-month follow-up period. Moreover, the achieved rate of MCID and PASS in both groups was assessed 12 months after surgery. Dizziness intensity, dizziness frequency, VAS-neck score, and NDI score were significantly improved from the baseline at all follow-up time points in both treatment groups, except for showing no significant improvement in dizziness frequency in the conservative treatment group at 6 and 12 months after surgery. However, at each follow-up time point, the above indexes were lower in the surgery group than in the conservative treatment group. In addition, the achieved rates for PASS and MCID in all indexes in the surgery group were significantly higher than those in the conservative treatment group at 12 months after surgery. Cervical coblation nucleoplasty significantly improved the intensity and frequency of dizziness, neck pain, and NDI in patients with cervical discogenic dizziness, and the results were superior to those from prolonged conservative treatment. Meanwhile, cervical coblation nucleoplasty is a good choice for patients with chronic neck pain and refractory cervical discogenic dizziness who have not demonstrated the indications for open surgery and have not responded well to conservative treatment.


Thromboembolism in patients with the 'lupus'-type circulating anticoagulant.
Thirty-five patients with the lupus anticoagulant (LA) were followed up between 1975 and 1982. The most prevalent clinical manifestation occurring in these patients was thrombosis. Nineteen patients (54.3%) had a single or recurrent thrombotic episode. Fifteen patients (42.8%) had venous thrombosis, and arterial thrombosis manifested by stroke or transient ischemic attacks occurred in six patients. Bleeding occurred in only five patients, four of whom had severe thrombocytopenia, while no excessive bleeding was noted during 18 operative procedures. Various therapeutic regimens, including corticosteriods, nonsteroidal anti-inflammatory drugs, cytotoxic or immunosuppressive agents, had no effect on the presence of the LA in these patients. Anticoagulants were successful in the treatment and prevention of thrombotic episodes.


MPLs-Pred: Predicting Membrane Protein-Ligand Binding Sites Using Hybrid Sequence-Based Features and Ligand-Specific Models.
Membrane proteins (MPs) are involved in many essential biomolecule mechanisms as a pivotal factor in enabling the small molecule and signal transport between the two sides of the biological membrane; this is the reason that a large portion of modern medicinal drugs target MPs. Therefore, accurately identifying the membrane protein-ligand binding sites (MPLs) will significantly improve drug discovery. In this paper, we propose a sequence-based MPLs predictor called MPLs-Pred, where evolutionary profiles, topology structure, physicochemical properties, and primary sequence segment descriptors are combined as features applied to a random forest classifier, and an under-sampling scheme is used to enhance the classification capability with imbalanced samples. Additional ligand-specific models were taken into consideration in refining the prediction. The corresponding experimental results based on our method achieved an appreciable performance, with 0.63 MCC (Matthews correlation coefficient) as the overall prediction precision, and those values were 0.604, 0.7, and 0.692, respectively, for the three main types of ligands: drugs, metal ions, and biomacromolecules. MPLs-Pred is freely accessible at http://icdtools.nenu.edu.cn/.


Role for Thrombin Receptor Antagonism With Vorapaxar in Secondary Prevention of Atherothrombotic Events: From Bench to Bedside.
In spite of treatment with the current standard of care antiplatelet regimens including dual antiplatelet therapy, recurrence rates of ischemic events remain elevated for high-risk patients with atherosclerotic disease. This may be in part attributed to the fact that other key platelet activation pathways remain uninhibited and can thus continue to trigger platelet activation and lead to thrombotic complications. Thrombin is a powerful inducer of platelet activation and mediates its effects directly on platelets through protease activator receptors (PARs), particularly the PAR-1 subtype, making PAR-1 inhibition an attractive approach for reducing atherothrombotic events. These observations have led to the development of several PAR-1 antagonists. Vorapaxar is a direct inhibitor of PAR-1 and the only agent of this class approved for the prevention of recurrent ischemic events in patients with prior myocardial infarction or peripheral artery disease. In the present manuscript, we present a review of the pathophysiologic role of thrombin on thrombotic complications, the impact of vorapaxar on outcomes, including the most recent updates deriving from clinical trials, as well as future perspectives in the field.


Handedness and cognitive ability: Using meta-analysis to make sense of the data.
The literature on the relationship between handedness and cognitive ability is riddled with studies using different conceptualizations of handedness (e.g., hand preference vs hand skill, direction vs degree, consistency vs inconsistency) and different conceptualizations of cognitive ability (intelligence vs distinct abilities), as well as different measurements thereof. Recently the literature was summarized by means of meta-analytic techniques. The findings show quite robustly that when handedness is assessed as hand preference and individuals are classified according to direction (i.e., as left-handers vs right-handers), no differences in cognitive ability emerge between handedness groups. However, other evidence points to the importance of assessing degree rather than direction of handedness and of employing hand skill rather than hand preference measures. A meta-analysis of such studies has not been possible to date, due to their scarcity. It is here suggested that degree of handedness and hand skill measures are employed in future studies exploring the possible relationship between handedness and cognitive ability so as to elaborate whether or not such a relationship exists and if so, what its characteristics are.


NIPAAm-MMA nanoparticle-encapsulated visnagin ameliorates myocardial ischemia/reperfusion injury through the promotion of autophagy and the inhibition of apoptosis.
The main method for the treatment of acute myocardial infarction (AMI) is percutaneous coronary intervention; however percutaneous coronary intervention will induce ischemia/reperfusion (IR) injury, resulting in the loss of cardiac function and cardiomyocyte death. An effective drug to target this condition is necessary. N-isopropylacrylamide and methacrylic acid were used to synthesize drug delivery nanoparticles (NP) containing the natural compound visnagin for IR injury treatment. It was demonstrated that NP containing fluorescein isothiocyanate localized to the site of myocardial IR, and that NP-visnagin treatment induced cardioprotection, reducing the size of the MI and ameliorating cardiac dysfunction through the induction of autophagy and the inhibition of apoptosis. In the future, visnagin may be suitable as a drug for IR injury treatment, and NP may be an effective drug delivery system.


Rapid antibiotic susceptibility testing of Mycobacterium tuberculosis: its utility in resource poor settings.
To compare the rapid colorimetric nitrate reductase based antibiotic susceptibility (CONRAS) test performed on Mycobacterium tuberculosis isolates with the conventional method i.e, the proportion method. One hundred clinical isolates of M. tuberculosis were tested for susceptibility to isoniazid (INH) and rifampicin (RIF) by the conventional proportion method and CONRAS in Middlebrook 7H9 liquid medium enriched with growth supplements (MB7H9S). The performance of the CONRAS test was evaluated using proportion method as the gold standard. The sensitivity (ability to detect true drug resistance) and specificity (ability to detect true drug susceptibility) of the CONRAS test to INH was 93.75 and 98.52% and for RIF it was 96.10 and 100% respectively. The mean time for reporting was 6.3 days and the test showed excellent reproducibility. The kappa (k) value for INH was 0.92 and for RIF was 0.99, indicating excellent agreement between the two methods. CONRAS test is a rapid and reliable method of drug susceptibility for M. tuberculosis.


Management of traumatically intruded permanent incisors.
Intrusive luxation of permanent teeth has great psychologic impact on both parents and children and presents clinical challenge for the dentist, all the more due to severe complications it is difficult to manage this group of dental injuries. This paper describes the management of traumatically intruded permanent maxillary-central incisor in an 11-year-old girl. After 12-month follow-up, it was seen that teeth were fully re-erupted and are in functional alignment with other teeth.


Necrotising soft tissue infection in a UK metropolitan population.
Necrotising soft tissue infection (NSTI) is a rare but life threatening diagnosis. Geographic, economic and social variances influence presentation and prognosis. As the current literature does not reflect a UK metropolitan population, we conducted a retrospective chart review to establish pertinent features relevant to our practice. Patients with histologically confirmed diagnoses of NSTI presenting to two London teaching hospitals between January 2007 and July 2013 were included in the study. Features of presentation, surgical and medical management, microbiological findings and outcome were evaluated. Twenty-four patients with histologically confirmed NSTI were included. Two age clusters were identified, with means of 46 years (standard deviation [SD]: 10 years) and 80 years (SD: 6 years). Pain, erythema and sepsis were common findings. Hypertension, hypercholesterolaemia and type II diabetes mellitus were common co-morbidities. A third of younger patients had human immunodeficiency virus or hepatitis C, with a quarter dependent on drugs and/or alcohol. The mean Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score was 5.8 (SD: 3.3). The lower extremities, groin and perineum were common sites of infection. Fourteen patients required inotropic support and seventeen required transfusions. The median number of surgical procedures was 5 (range: 1-17). Group A Streptococcus was the most frequently identified pathogen. Five patients died. Being elderly, female sex and failure to use clindamycin as a first-line antibiotic were associated with significantly higher mortality. In contrast to other recent series, group A streptococcal monomicrobial NSTI remains the most common presentation in our population. Survival is anticipated in young patients, regardless of premorbid status. Elderly patients have a poor prognosis. The negative predictive value of the LRINEC score is questioned. Use of clindamycin as a first-line antibiotic is supported.


The effects of small class sizes on students' academic achievement, socioemotional development and well-being in special education: A systematic review.
Class size reductions in general education are some of the most researched educational interventions in social science, yet researchers have not reached any final conclusions regarding their effects. While research on the relationship between general education class size and student achievement is plentiful, research on class size in special education is scarce, even though class size issues must be considered particularly important to students with special educational needs. These students compose a highly diverse group in terms of diagnoses, functional levels, and support needs, but they share a common need for special educational accommodations, which often entails additional instructional support in smaller units than what is normally provided in general education. At this point, there is however a lack of clarity as to the effects of special education class sizes on student academic achievement and socioemotional development. Inevitably, such lack of clarity is an obstacle for special educators and policymakers trying to make informed decisions. This highlights the policy relevance of the current systematic review, in which we sought to examine the effects of small class sizes in special education on the academic achievement, socioemotional development, and well-being of children with special educational needs. The objective of this systematic review was to uncover and synthesise data from studies to assess the impact of small class sizes on the academic achievement, socioemotional development, and well-being of students with special educational needs. We also aimed to investigate the extent to which the effects differed among subgroups of students. Finally, we planned to perform a qualitative exploration of the experiences of children, teachers, and parents with class size issues in special education. Relevant studies were identified through electronic searches in bibliographic databases, searches in grey literature resources, searches using Internet search engines, hand-searches of specific targeted journals, and citation-tracking. The following bibliographic databases were searched in April 2021: ERIC (EBSCO-host), Academic Search Premier (EBSCO-host), EconLit (EBSCO-host), APA PsycINFO (EBSCO-host), SocINDEX (EBSCO-host), International Bibliography of the Social Sciences (ProQuest), Sociological Abstracts (ProQuest), and Web of Science (Clarivate, Science Citation Index Expanded & Social Sciences Citation Index). EBSCO OPEN Dissertations was also searched in April 2021, while the remaining searches for grey literature, hand-searches in key journals, and citation-tracking took place between January and May 2022. The intervention in this review was a small special education class size. Eligible quantitative study designs were studies that used a well-defined control or comparison group, that is, studies where there was a comparison between students in smaller classes and students in larger classes. Children with special educational needs in grades K-12 (or the equivalent in European countries) in special education were eligible. In addition to exploring the effects of small class sizes in special education from a quantitative perspective, we aimed to gain insight into the lived experiences of children, teachers, and parents with class size issues in special education contexts, as they are presented in the qualitative research literature. The review therefore also included all types of empirical qualitative studies that collected primary data and provided descriptions of main methodological issues such as selection of informants, data collection procedures, and type of data analysis. Eligible qualitative study designs included but were not limited to studies using ethnographic observation or field work formats, or qualitative interview techniques applied to individual or focus group conversations. The literature search yielded a total of 26,141 records which were screened for eligibility based on title and abstract. From these, 262 potentially relevant records were retrieved and screened in full text, resulting in seven studies being included: three quantitative and five qualitative studies (one study contained both eligible quantitative and qualitative data). Two of the quantitative studies could not be used in the data synthesis as they were judged to have a critical risk of bias and, in accordance with the protocol, were excluded from the meta-analysis on the basis that they would be more likely to mislead than inform. The third quantitative study did not provide enough information enabling us to calculate an effect size and standard error. Meta-analysis was therefore not possible. Following quality appraisal of the qualitative studies, three qualitative studies were judged to be of sufficient methodological quality. It was not possible to perform a qualitative thematic synthesis since in two of these studies, findings particular to special education class size were scarce. Therefore, only descriptive data extraction could be performed. Despite the comprehensive searches, the present review only included seven studies published between 1926 and 2020. Two studies were purely quantitative (Forness, 1985; Metzner, 1926) and from the U.S. Four studies used qualitative methodology (Gottlieb, 1997; Huang, 2020; Keith, 1993; Prunty, 2012) and were from the US (2), China (1), and Ireland (1). One study, MAGI Educational Services (1995), contained both eligible quantitative and qualitative data and was from the U.S. The major finding of the present review was that there were virtually no contemporary quantitative studies exploring the effects of small class sizes in special education, thus making it impossible to perform a meta-analysis. More research is therefore thoroughly needed. Findings from the summary of included qualitative studies reflected that to the special education students and staff members participating in these studies, smaller class sizes were the preferred option because they allowed for more individualised instruction time and increased teacher attention to students' diverse needs. It should be noted that these studies were few in number and took place in very diverse contexts and across a large time span. There is a need for more qualitative research into the views and experiences of teachers, parents, and school administrators with special education class sizes in different local contexts and across various provision models. But most importantly, future research should strive to represent the voices of children and young people with special needs since they are the experts when it comes to matters concerning their own lives.


[Verification of tuberculosis prognosis in Poland to the year 2000].
In 1978 year a tuberculosis prognosis in Poland up to 2000 year was prepared in the Institute of Tuberculosis and Lung Diseases in Warsaw, according to epidemiological and epidemiologic-metric model (efficacy of "diagnosis-therapy program" from 60 to 90% and efficacy of BCG vaccination to 60%). The aim of study was to compare epidemiological data for registered tuberculosis cases in 1980-1990 (incidence morbidity and mortality) with the same parameters presented in prognosis for 1980-1991). Efficacy of analyzed programme was similar to predicted values: for incidence of tuberculosis-64%, for morbidity-65% and for mortality-66%.


Pharmacokinetic and pharmacodynamic properties of atenolol in acute myocardial infarction.
A commonly used combined intravenous (i.v.) and oral dose regimen of atenolol was evaluated in 21 patients with acute myocardial infarction (MI). Atenolol 5-10 mg was administered i.v. and was followed by 50 mg twice daily during the first 24 h. Starting on the second day, 100 mg was administered as a single dose. Dose adjustments were made as necessary. The i.v. dose resulted in a rapid plasma peak concentration, but absorption of the first oral dose appeared to be delayed. The half-life (t1/2) was significantly prolonged on day 2 as compared with day 6, but the tmax, Cmax, and area under the curve (AUC) were all comparable to what has been reported in patients without MI. The change in heart rate (HR) or blood pressure (BP) was not related to the initial plasma level of atenolol. The interindividual variation was large, but most patients obtained plasma levels of atenolol which in studies of other diseases have been shown to be effective.


Transparency and self-disclosure in family therapy: dangers and possibilities.
Therapy is a paid intimate relationship that thrusts clients and therapists into navigating personal and professional boundaries. When, where, why, and how is it appropriate and ethical for family therapists to be transparent, and when is it damaging? Theorists take varied stances from Haley's position of tight boundaries around therapist disclosure--whether in treatment or training--to the narrative viewpoint that therapists should be transparent about models of therapy, personal values, and life experiences that inform their practice and beliefs. However, these positions are not research based, and theorists who support disclosure offer few guidelines other than general statements. This article examines the history of ideas about disclosure in six major family therapy models, and the dangers and possibilities of transparency. It looks at the research on self-disclosure in individual therapy and whether and how it could apply to family therapy. Guidelines are proposed that take into account the multiple social identities of therapists and clients, and issues of safety and transparency.


[Effect of the completion time of initial 30 mL/kg fluid resuscitation on the prognosis of patients with septic shock].
To investigate the effect of the completion time of initial 30 mL/kg fluid resuscitation on the prognosis of patients with septic shock. An observational study was conducted. The inpatients with septic shock admitted to intensive care unit (ICU) of Northern Jiangsu People's Hospital, Affiliated Hospital of Yangzhou University and Jiangdu People's Hospital from October 1st, 2018 to September 30th, 2020 were enrolled. The general data including gender, age, body mass index (BMI), patient source, site of infection, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score and arterial blood lactic acid (Lac) at ICU admission, fluid resuscitation dose, completion time of initial 30 mL/kg fluid resuscitation, mechanical ventilation, incidence of acute kidney injury (AKI), continuous renal replacement therapy (CRRT), length of ICU stay and 28-day mortality. The relationship between the completion time of initial 30 mL/kg fluid resuscitation and ΔSOFA score (the difference between SOFA score 3 hours of fluid resuscitation and initial SOFA score) was analyzed. In addition, according to the completion time (T) of initial 30 mL/kg fluid resuscitation, the patients were divided into T ≤ 1 hour group, 1 hour < T ≤ 2 hours group, 2 hours < T ≤ 3 hours group and T > 3 hours group, and the observation parameters among the groups were compared. (1) A total of 131 patients were enrolled, including 94 males and 37 females with an average age of (68.3±15.0) years old. The median APACHE II score was 27 (21, 34), the median of initial SOFA score was 12 (10, 14), the median of initial Lac was 5.0 (3.4, 7.1) mmol/L, and the most common source of infection was lung, with a total of 87 patients (66.41%). The completion time of initial 30 mL/kg fluid resuscitation and ΔSOFA score fitted the Logistic curve (Y = -1.062 6X2+4.407 9X+0.961 8), which suggested that the early or late completion time of initial fluid resuscitation had adverse effects on the prognosis of patients with septic shock. (2) There was no significant difference in infection site, initial APACHE II score, initial Lac, and initial SOFA score among different completion time of initial 30 mL/kg fluid resuscitation groups. The respiratory support rate, the incidence of AKI and the ratio of CRRT in the T ≤ 1 hour group were significantly higher than those in the 1 hour < T ≤ 2 hours group, 2 hours < T ≤ 3 hours group and T > 3 hours group (respiratory support rate: 78.57% vs. 75.51%, 42.86%, 75.00%; incidence of AKI: 57.14% vs. 20.41%, 21.43%, 50.00%; ratio of CRRT: 35.71% vs. 0%, 7.14%, 16.67%), the differences among the groups were statistically significant (all P < 0.05). The 28-day mortality was the highest in the T ≤ 1 hour group (64.29%), and the lowest in the 1 hour < T ≤ 2 hours group (22.45%), 35.71% in the 2 hours < T ≤ 3 hours group, 33.33% in the T > 3 hours, and the difference among the groups was statistically significant (P < 0.01). Completion of initial 30 mL/kg fluid resuscitation in 1-2 hours after septic shock may reduce the 28-day mortality and improve organ dysfunction, and initial fluid resuscitation prematurely or too late may increase 28-day mortality. But further research and verification are needed.


Hypothalamic regulation of adiposity: the role of 11beta-hydroxysteroid dehydrogenase type 1.
Following extensive suprasellar operations for excision of hypothalamic tumors, some patients develop morbid obesity despite receiving replacement doses of glucocorticoids. Urine analysis of cortisol and cortisone metabolites show that 11-OH/11-oxo ratios are significantly higher in patients with hypothalamic obesity, indicating enhanced 11beta-HSD1 activity. This correlates with the visceral-to-subcutaneous fat ratio. The consequence of increased 11beta-HSD1 activity and a shift of the steroid inter-conversion towards cortisol may contribute to the effects of the latter in adipose tissue. The message from the hypothalamus to adipocyte 11beta-HSD-1 involves hormones, the sympathetic nervous system and cytokines. CRH and ACTH downregulate 11beta-HSD-1 activity and induce lipolysis. Tumor necrosis factor-alpha and interleukin-1beta upregulate 11beta-HSD-1 expression and activity, while enhancing lipolysis. The sympathetic nervous system exerts its effects through beta-adrenergic upregulation and alpha-adrenergic downregulation of 11beta-HSD-1 activity. Inhibition of 11beta-HSD-1 suppresses preadipocyte differentiation into mature adipocytes, and may provide a therapeutic tool.


A post-colonial analysis of healthcare discourses addressing aboriginal women.
Annette Browne and Vicki Smye use post-colonial theoretical perspectives to inform a critical analysis of healthcare discourses related to cervical cancer among Canadian aboriginal women. They also examine how decontextualised discourses addressing aboriginal women's risks for cervical cancer can perpetuate negative stereotypical images of aboriginal women while downplaying or ignoring the historical, social and economic context of women's health risks.


Adsorption geometry and self-assembling of chiral modifier (R)-(+)-1-(1-naphthylethylamine) on Pt(111).
A mechanistic study on interaction of a chiral modifier - (R)-(+)-1-(1-naphthylethylamine) (R-NEA) - with a single crystalline Pt(111) surface is reported. The details of the adsorption geometry of individual R-NEA molecules and their intermolecular interactions are addressed by combination of infrared reflection absorption spectroscopy (IRAS) and scanning tunneling microscopy (STM). The spectroscopic observations suggest that the molecules are tilted with respect to the underlying metal substrate with the long axis of the naphthyl ring being parallel and the short axis tilted with respect to the surface. In the medium coverage range, formation of directed 3-5 membered chains was observed by STM for the first time, which points to intermolecular bonding between individual molecules and might account for an unusual tilted adsorption geometry deduced from the IR spectra. Based on the STM images revealing the atomic structure of the Pt grid close to the R-NEA chains, we propose the adsorption configuration of NEA fitting both the IRAS and STM data. The obtained results suggest that this strong intermolecular interaction energetically stabilizes the tilted adsorption geometry of the naphthyl ring, which otherwise would be expected to lie flat on the metal to maximize the dispersive interactions. At the coverage close to saturation, R-NEA builds a self-assembled overlayer with hexagonal symmetry, exhibiting intermolecular distances larger than in the directed chains.


Obstetric Outcomes in Military Servicewomen: Emerging Knowledge, Considerations, and Gaps.
The number of women in the U.S. military is dramatically increasing. Similarly, the roles of active-duty women are greatly expanding, thus exposing them to new occupational risks. Determining the impact of pregnancy outcomes for women while in the military is difficult due to changing exposures over time, difficulty in utilizing appropriate comparison groups, and the lack of prospective investigations. Despite these limitations, it was concerning that the available data suggest that servicewomen delivering within 6 months of their first deployment have an increased preterm birth risk (adjusted odds ratio [aOR]: 2.1), and those with three prior deployments have an even greater risk (aOR: 3.8). Servicewomen also have an increased risk of hypertensive disorders with a rate of 13% compared with 5% in the general obstetric population. Furthermore, depression is higher for women who deploy after childbirth and are exposed to combat when compared with those who have not deployed since the birth of their child (aOR: 2.01). Due to the importance of this issue, prospective research designs are necessary to better understand and address the unique health care needs of this population.


Carcinoid tumors of the duodenum. A clinicopathologic study of 99 cases.
Ninety-nine carcinoid tumors of the duodenum were studied. Seventy-seven patients were followed up for a mean period of 65 months, 20 tumors were autopsy findings, and two patients were unavailable for follow-up. Sixteen tumors (21%) produced metastases, all discovered initially; 3 patients (4%) died from metastatic disease (mean survival, 37 months postoperatively). Features associated with metastatic risk were involvement of muscularis propria, size greater than 2 cm, and the presence of mitotic figures. For 51 tumors, there was no correlation between immunohistochemical somatostatin and history of diarrhea, cholelithiasis, or diabetes mellitus (somatostatin syndrome). Five tumors were associated with Zollinger-Ellison syndrome and had immunohistochemical gastrin, but in the others there was no correlation between ulcer disease and gastrin positivity. Duodenal carcinoids are indolent, especially when small and localized to the submucosa. Immunohistochemical identification of somatostatin and gastrin has little clinical relevance.


TiD-Introducing and Benchmarking an Event-Delivery System for Brain-Computer Interfaces.
In this paper, we present and analyze an event distribution system for brain-computer interfaces. Events are commonly used to mark and describe incidents during an experiment and are therefore critical for later data analysis or immediate real-time processing. The presented approach, called Tools for brain-computer interaction interface D (TiD), delivers messages in XML format via a buslike system using transmission control protocol connections or shared memory. A dedicated server dispatches TiD messages to distributed or local clients. The TiD message is designed to be flexible and contains time stamps for event synchronization, whereas events describe incidents, which occur during an experiment. TiD was tested extensively toward stability and latency. The effect of an occurring event jitter was analyzed and benchmarked on a reference implementation under different conditions as gigabit and 100-Mb Ethernet or Wi-Fi with a different number of event receivers. A 3-dB signal attenuation, which occurs when averaging jitter influenced trials aligned by events, is starting to become visible at around 1-2 kHz in the case of a gigabit connection. Mean event distribution times across operating systems are ranging from 0.3 to 0.5ms for a gigabit network connection for 106 events. Results for other environmental conditions are available in this paper. References already using TiD for event distribution are provided showing the applicability of TiD for event delivery with distributed or local clients.


Statins and autoimmune diseases.
Besides the well-known lipid-lowering effect, statins display nonlipid-lowering pharmacological activities. In vitro and in vivo studies suggest that statins have direct anti-inflammatory, anti-thrombotic and plaque-stabilizing effects via a number of mechanisms. A direct immunomodulatory effect has been also demonstrated in in vitro and in vivo experimental models. In addition to traditional risk factors, systemic inflammation, immune-mediated responses and thrombophilia have been suggested to play a major role in sustaining the premature atherosclerosis in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. This review focuses on the anti-inflammatory and immunomodulating mechanisms of statins as demonstrated in in vitro and in vivo experimental models, providing new insights for the use of statins in treating systemic autoimmune diseases both for their anti-atherosclerotic activity and for their pleiotropic effects on inflammation, haemostasis and the immune responses.


Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2.
Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. A possibility of a resurgence of COVID-19 in places where lockdowns have already worked is also developing. Thus, for controlling COVID-19, vaccines may be a better option than drugs. An mRNA-based anti-COVID-19 candidate vaccine has entered a phase 1 clinical trial. However, its efficacy and potency have to be evaluated and validated. Since vaccines have high failure rates, as an alternative, we are presenting a new, designed multi-peptide subunit-based epitope vaccine against COVID-19. The recombinant vaccine construct comprises an adjuvant, cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes joined by linkers. The computational data suggest that the vaccine is non-toxic, non-allergenic, thermostable, with the capability to elicit a humoral and cell-mediated immune response. The stabilization of the vaccine construct is validated with molecular dynamics simulation studies. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host-receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as a public health priority.


Fatal paraphenylenediamine poisoning due to black henna.
Paraphenylenediamine (PPD) is an oxidative chemical allergen that can cause hypersensitivity reactions. PPD intoxication could cause severe systemic adverse effects like acute renal failure, rhabdomyolysis and multiple organ failure. In this text we present a 9 year-old female patient who developed multiple organ failure and cardiac arrhythmia as a result of extensive application of PPD added to henna to the skin. Plasma exchange (PE) and continuous venovenous hemodiafiltration (CVVHDF) were started. The patient died on day 4 after developing ventricular fibrillation that was resistant to antiarrhythmic treatment and defibrillation. In summary, the most commonly seen clinical signs in PPD intoxication are cervical, upper respiratory and muscle edema, intravascular hemolysis, rhabdomyolysis, severe cardiac arrhythmias and acute renal failure. These symptoms would be suggestive of PPD poisoning.


Arthrodesis of the arthritic wrist.
Although arthroplasty has developed tremendously in the last few years, there are still indications for arthrodesis of the wrist, particularly in nonrheumatoid patients where fairly heavy loads are imposed on the joint. Fusion is also a salvage procedure for failures of other procedures. The authors recommend fusion in a neutral position for unilateral or bilateral cases. Neutral is defined as 0 degree on the lateral with about 10 degrees ulnar deviation. This gives an arc of motion from pronation and supination, which substitutes for palmar flexion and dorsiflexion. The important factors in securing arthrodesis are: internal fixation with intramedullary pins, bony contact, bone graft if necessary, compression, and obtaining or maintaining rotation of the forearm. In selected cases arthrodesis of the wrist produces a very good result.


Eutrophication modeling in Shihmen Reservoir, Taiwan.
Based on the measured data, including total phosphorus, chlorophyll a, and Secchi disk depth, the Shihmen Reservoir in the state of mesotrophic to eutrophic. A two-dimensional, laterally averaged, finite-difference hydrodynamic, and water quality model was applied to simulate water quality conditions in the reservoir to determine appropriate strategies for the management of water quality. Data collected in the field for a two-year period were utilized to calibrate and verify the model. The model calibration and verification were achieved with water surface elevation, temperature, and water quality constituents such as nutrients, dissolved oxygen, and chlorophyll a. Then the model was used to simulate chlorophyll a concentrations under several scenarios corresponding to various waste load reduction ratios. A 90% reduction of nutrient loadings will upgrade the existing eutrophic/mesotrophic conditions to oligotrophic condition in both 2001 and 2002, exception January in 2001. The modeling effort had yielded valuable information that can be used by decision maker for the evaluation of different management strategies of reduction of nutrients coming from the catchment area.


Frequency, pattern and management of acute abdomen in dengue fever in Karachi, Pakistan.
This study aimed to determine the frequency, pattern and management of acute abdomen in patients with dengue fever. This descriptive case series is a prospective analysis of acute abdomen in dengue fever that was performed at three secondary care hospitals in Karachi, Pakistan from June 1, 2005 to December 31, 2008. The inclusion criterion was all patients with confirmed diagnosis of dengue fever. Patients with incomplete laboratory, ultrasound or histopathology data were excluded. Among 357 patients with dengue fever, 43 (12.04%) had acute abdomen. There were 15 men and 28 women, with a median age of 29 years. These included 26 cases of acute cholecystitis, 7 cases of acute appendicitis, 7 cases of nonspecific peritonitis, and 3 cases of acute pancreatitis. Dengue hemorrhagic fever/shock syndrome was found in acute pancreatitis, and two of these patients died. Emergency surgery was required in eight patients (5 appendectomy and 3 open cholecystectomy). Substantial transfusion of blood and its components was required in eight patients who underwent emergency surgery. Early diagnosis and prompt conservative management of dengue acute abdomen is necessary to avoid mortality and emergency surgery-related morbidity. However, if needed, surgery can be performed with acceptable morbidity.


The distribution and use of feedback bulletins among national immunization program management teams in East and Southern Africa.
Immunization program monitoring includes numerous activities, some of which include monitoring of vaccination coverage, surveillance performance and epidemiological patterns. The provision of timely, high quality and actionable feedback is an essential component of strengthening health systems. Within the African region of the WHO, various bulletins are produced and disseminated regularly to provide feedback on the performance of immunization programs and vaccine preventable disease control initiatives. The 2019 annual national immunization program managers' meeting for countries in the eastern and southern African subregion was held in Asmara from 18 - 20 March 2019. A survey questionnaire was administered to the participants representing the national programs and in-country partners across the 20 countries. On average, the 75 respondents receive 1.8 e-mailed feedback bulletins monthly. Twenty-three (31%) respondents receive 3 or more written feedback bulletins per month, and 72% receive the bulletins regularly. On a scale of 1 - 5 (from lowest to highest), 87% participants rated the relevance of the bulletins they receive at 4 - 5. Only 19% of the respondents responded that the results are discussed within the national immunization program, and 14% stated that action points are generated based on the feedback received. Fifty-nine (79%) respondents want to receive more frequent feedback on routine immunization performance. Among the EPI program managers and the EPI program data managers, the access to these feedback bulletins was quite limited. Even though the primary objective of the bulletins is to initiate discussions and action based on the provided feedback, such discussions do not happen regularly at country level. The programmatic use and advocacy value of the bulletins is not optimal. We recommend integrating program feedback, regularly updating the distribution lists, the additional use of instant messaging platforms for distribution, as well as online posting of the bulletins for wider availability.


Associations between maternal folate status and choline intake during pregnancy and neurodevelopment at 3-4 years of age in the Alberta Pregnancy Outcomes and Nutrition (APrON) study.
Folate and choline are methyl donor nutrients that may play a role in fetal brain development. Animal studies have reported that prenatal folate and choline supplementation are associated with better cognitive outcomes in offspring and that these nutrients may interact and affect brain development. Human studies that have investigated associations between maternal prenatal folate or choline levels and neurodevelopmental outcomes have reported contradictory findings and no human studies have examined the potential interactive effect of folate and choline on children's neurodevelopment. During the second trimester of pregnancy, maternal red blood cell folate was measured from blood samples and choline intake was estimated using a 24-h dietary recall in 309 women in the APrON cohort. At 3-5 years of age, their children's neurodevelopment was assessed using the Wechsler Preschool and Primary Scales of Intelligence - Fourth EditionCND, NEPSY-II language and memory subtests, four behavioral executive function tasks, and the Movement Assessment Battery for Children - Second Edition. Adjusted regressions revealed no associations between maternal folate and choline levels during pregnancy and most of the child outcomes. On the Dimensional Change Card Sort, an executive function task, there was an interaction effect; at high levels of choline intake (i.e., 1 SD above the mean; 223.03 mg/day), higher maternal folate status was associated with decreased odds of receiving a passing score (β = -0.44; 95%CI -0.81, -0.06). In conclusion, maternal folate status and choline intake during the second trimester of pregnancy were not associated with children's intelligence, language, memory, or motor outcomes at 3-4 years of age; however, their interaction may have an influence children's executive functions.


Cytomegalovirus pneumonia with pulmonary mucormycosis.
Solid organ transplantation is becoming increasingly common in the treatment of end-stage organ failure. However, despite improvements in patient and allograft survival, immunosuppression-induced compromised cell-mediated immunity predisposes transplant recipients to opportunistic infections. We describe a case of mixed opportunistic lung infection in the form of cytomegalovirus pneumonia and mucormycosis in a renal transplant recipient. Prompt recognition and treatment of infection is imperative for successful transplantation.


Insulin drug delivery systems: rectal gels.
In continuation of a previous study on insulin gels administered deep rectally by means of an applicator, 16 further rectal formulations were evaluated, using the nondiabetic White New Zealand rabbit as animal model. The highest pharmacologic availability, P.A., defined as the ratio of the areas under the % glucose reduction-time curves rectally versus I.V., corrected for dose size and body weight, in the previous experiments was about 29%. In the present study the highest mean P.A. was 42% and 31%, both obtained with Gelucire bases (50/22 and 44/14), pH 8 buffer solution and sodium deoxycholate, using Cab-O-Sil as stiffening agent. Simple gels prepared from gelatine and polyethylene glycol, or Veegum, resulted in mean P.A. of about 23 and 24%, respectively. Addition of Gelucire or sodium deoxycholate did not result in a further increase of P.A. of the latter two gels.


Differential glucose metabolism in mice and humans affected by McArdle disease.
McArdle disease (muscle glycogenosis type V) is a disease caused by myophosphorylase deficiency leading to "blocked" glycogen breakdown. A significant but varying glycogen accumulation in especially distal hind limb muscles of mice affected by McArdle disease has recently been demonstrated. In this study, we investigated how myophosphorylase deficiency affects glucose metabolism in hind limb muscle of 20-wk-old McArdle mice and vastus lateralis muscles from patients with McArdle disease. Western blot analysis and activity assay demonstrated that glycogen synthase was inhibited in glycolytic muscle from McArdle mice. The level and activation of proteins involved in contraction-induced glucose transport (AMPK, GLUT4) and glycogen synthase inhibition were increased in quadriceps muscle of McArdle mice. In addition, pCaMKII in quadriceps was reduced, suggesting lower insulin-induced glucose uptake, which could lead to lower glycogen accumulation. In comparison, tibialis anterior, extensor digitorum longus, and soleus had massive glycogen accumulation, but few, if any, changes or adaptations in glucose metabolism compared with wild-type mice. The findings suggest plasticity in glycogen metabolism in the McArdle mouse that is related to myosin heavy chain type IIB content in muscles. In patients, the level of GLUT4 was vastly increased, as were hexokinase II and phosphofructokinase, and glycogen synthase was more inhibited, suggesting that patients adapt by increasing capture of glucose for direct metabolism, thereby significantly reducing glycogen buildup compared with the mouse model. Hence, the McArdle mouse may be a useful tool for further comparative studies of disease mechanism caused by myophosphorylase deficiency and basic studies of metabolic adaptation in muscle.


F-cells in the adult: normal values and levels in individuals with hereditary and acquired elevations of Hb F.
Specific antibodies to human fetal hemoglobin were prepared and, after conjugation with a fluorescent dye, were used to determine the distribution of Hb F-containing cells in blood smears from normal adults and individuals with hereditary and acquired conditions associated with abnormal levels of Hb F. The mean proportion of F-cells in normal persons was 2.7% +/- 1.4%, with a range of 0.5%-7.0%. Proportions of F-cells were increased in persons with several acquired and inherited disorders that are associated with an increased percentage of Hb F in hemolysates. A strong linear correlation between the amount of Hb F and proportion of F-cells was observed. This technique may prove useful in studies of a variety of disorders associated with Hb F elevations and also in investigations of the mechanisms controlling the transition from fetal to adult hemoglobin during the course of human development.


Mannose-binding lectin and mannose-binding lectin-associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults.
Community-acquired pneumonia (CAP) is the leading cause of death from infection in developed countries. Mannose-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) deficiencies are common primary immunodeficiencies the clinical penetrance of which remains controversial. MBL is a serum lectin that mediates phagocytosis and activates the lectin pathway of complement involving MASP-2. We sought to evaluate the significance of MBL deficiency (O/O genotypes) and insufficiency (O/O plus XA/O genotypes), as well as MASP-2 deficiency (D105G mutation), in the susceptibility to and severity and outcome of CAP in adults. MBL and MASP-2 serum levels, as well as lectin pathway activity with regard to MBL2 and MASP2 genotypes, were measured in healthy control subjects. For susceptibility, 848 patients with CAP, 1447 healthy control subjects, and a control group of 519 patients without relevant infectious diseases were studied in a case-control study. Severity and outcome were evaluated in a prospective study of the 848 patients. We found similar frequencies of MBL2 and MASP2 alleles and genotypes among patients and control subjects. However, in a multivariate analysis MBL insufficiency was associated with the development of the most severe forms of sepsis (P = .007), acute respiratory failure (P = .009), multiorgan dysfunction syndrome (P = .036), intensive care unit admission (P = .020), and death (P = .003). Our large study suggests that MBL plays a redundant role in human defenses against primary infection, at least in adults with CAP, and provides, for the first time, evidence that MBL insufficiency predisposes to higher severity and fatal outcome in patients with CAP, irrespective of the causal microorganisms.


Clinical aspects of rifampicin-associated pseudomembranous colitis.
Pseudomembranous colitis (PMC) is known to develop after antibiotic administration, but antituberculosis agents are rarely associated with this disorder. We report 6 cases of PMC after rifampicin administration; the clinical manifestations, laboratory findings, imaging findings, and clinical course are described. The median age of patients was 68 years (range, 54 to 82 y). All patients were diagnosed with active pulmonary tuberculosis by sputum smear and culture, and 2 suffered from type 2 diabetes mellitus. The average interval between initiation of antituberculosis therapy and the onset of diarrhea was 19.8 days. The anatomic distribution of PMC included the rectum and sigmoid colon in 5 cases and up to the hepatic flexure in 1 case. All patients were cured with medical treatment, which include discontinuation of rifampicin and oral metronidazole and vancomycin. PMC recurred in 1 patient after retreatment with rifampicin. Our findings suggest that patients who are treated with antituberculosis agents, who develop acute diarrhea during or after therapy, should be evaluated for PMC.


A new isoquinoline alkaloid with anti-microbial properties from Berberis jaeschkeana Schneid. var. jaeschkeana.
One new isoquinoline alkaloid named berberidione (1) along with four new source alkaloids berberine (2), palmatine (3), jatrorrhizine (4) and chondrofoline (5) and three new source non-alkaloids syringic acid (6), β-sitosterol (7) and stigmasterol (8) was isolated and characterised from different fractions of Berberis jaeschkeana Schneid var. jaeschkeana. All the structures were determined from 1D and 2D spectroscopic data. Crude extract, sub-fractions and isolated compounds showed excellent anti-microbial properties. The toxicity level for the alkaloids was found to be very low on THP-1 cells.


Photoacoustic tomography as a method to estimate the optical fluence distribution in turbid media.
Currently, there are no non-invasive experimental methods available for measuring optical fluence distributions in tissue. We present photoacoustic tomography (PAT) as a method to approximate the relative optical fluence distribution in a homogeneous optically scattering medium. Three-dimensional photoacoustic images were captured with a near-full view PAT scanner in phantoms with known optical absorption and scatter properties. Resultant 3D PAT images were compared to the expected optical fluence distributions from Monte Carlo simulations and diffusion theory using volumetric and shape analysis. Volumetric analysis of PAT images compared well with the optical fluence distributions from simulation. Dice similarity coefficients ranged from 51 to 82%. The reduced scattering coefficient estimated from PAT images compared well to estimates from simulations for values below 0.5 mm-1. Near full-view PAT has been found to be useful for estimating the optical fluence distribution in an optically scattering medium. Further development is needed to extend the measurement range.


Targeting cellular senescence in cancer and aging: roles of p53 and its isoforms.
Cellular senescence and the associated secretory phenotype (SASP) promote disease in the aged population. Targeting senescent cells by means of removal, modulation of SASP or through cellular reprogramming represents a novel therapeutic avenue for treating cancer- and age-related diseases such as neurodegeneration, pulmonary fibrosis and renal disease. Cellular senescence is partly regulated by the TP53 gene, a critical tumor suppressor gene which encodes 12 or more p53 protein isoforms. This review marks a significant milestone of 40 years of Carcinogenesis publication history and p53 research and 15 years of p53 isoform research. The p53 isoforms are produced through initiation at alternative transcriptional and translational start sites and alternative mRNA splicing. These truncated p53 isoform proteins are endogenously expressed in normal human cells and maintain important functional roles, including modulation of full-length p53-mediated cellular senescence, apoptosis and DNA repair. In this review, we discuss the mechanisms and functions of cellular senescence and SASP in health and disease, the regulation of cellular senescence by p53 isoforms, and the therapeutic potential of targeting cellular senescence to treat cancer- and age-associated diseases.


Development of scholars interested in community-based health promotion research.
Culturally consistent community-based health promotion interventions have been identified as integral components of strategies to decrease health disparities. The limited number of culturally competent scholars impedes the development of appropriate interventions. This article examines issues relevant to the development of scholars interested in community-based health promotion research. It is the outcome of a series of discussions by the authors held over a 3-month period. Specific topics include classroom and communal educational opportunities to enhance cultural competence and creation of supportive environments for aspiring community-based scholars. Particular attention is given to the importance of ongoing opportunities for interaction between students and lay community scholars.


Efficient manipulation of microparticles in bubble streaming flows.
Oscillating microbubbles of radius 20-100 μm driven by ultrasound initiate a steady streaming flow around the bubbles. In such flows, microparticles of even smaller sizes (radius 1-5 μm) exhibit size-dependent behaviors: particles of different sizes follow different characteristic trajectories despite density-matching. Adjusting the relative strengths of the streaming flow and a superimposed Poiseuille flow allows for a simple tuning of particle behavior, separating the trajectories of particles with a size resolution on the order of 1 μm. Selective trapping, accumulation, and release of particles can be achieved. We show here how to design bubble microfluidic devices that use these concepts to filter, enrich, and preconcentrate particles of selected sizes, either by concentrating them in discrete clusters (localized both stream- and spanwise) or by forcing them into narrow, continuous trajectory bundles of strong spanwise localization.


IL-1 beta regulates the expression of the Gi2 alpha gene via lipid mediators in guinea pig tracheal muscle.
When isolated guinea pig muscle preparations were incubated with human recombinant IL-1 beta, mRNA level of Gi2 alpha but not of Gs alpha increased in a time and dose dependent manner. The increase was partially blocked by inhibitors of lipoxygenase (NDGA) and cyclooxygenase (indomethacin) and PAF antagonist (SC47014A), while U46619 (thromboxane A2 mimetic), LTD4, 15-HETE and PAF partially mimicked it. The IL-1 beta induced Gi2 alpha expression was almost completely inhibited by anti-phospholipase A2 antiserum, whereas preimmune serum had no apparent effects. From these observations, we suggest that IL-1 beta first induces the synthesis and release of Type II inflammatory phospholipase A2, which in turn stimulates the expression of Gi2 alpha gene via production of various lipid mediators.


Prevention of the teardrop areola following the inferior pedicle technique of breast reduction.
Elevation of the inferior portion of the areola with placement of dermal traction sutures will reduce the risk of an inverted teardrop areola deformity following inferior pedicle reduction mammaplasty. The long-term results in creation of a circular areola have been uniformly successful.


S-100 protein detection in "follicular macrophages" of mouse lymphoid organs by ABC immunoperoxidase method.
The distribution of S-100 protein was investigated in normal or reactive lymphoid organs from adult mice, rats and humans by the avidin-biotin complex ABC) immunoperoxidase method. In mouse lymph nodes and spleen the protein appeared to be confined to the "tingible-body macrophages" and occasionally in sinus histiocytes in the lymph nodes. No immunoreaction product was detected in the other cell types present inside or outside the follicles. In the thymus the immunostained cells were located in the medullary area and corresponded morphologically to mononuclear PAS-positive cells with histiocytic appearance. By contrast, in rat and human organs S-100 protein was detected in interdigitating reticulum cells and dendritic reticulum cells. The present findings indicate that S-100 protein is located differently in mouse lymphoid organs and in other mammalian species.


Role of cholangioscopy as a rescue technique in the retrieval of proximally migrated biliary stents.
A 15-years-old boy with a medical history of an orthotopic liver transplant in 2021 due to methylmalonic aciduria, on a multi-stenting strategy for biliary anastomotic strictures, underwent a reassessment endoscopic retrograde cholangiopancreatography and the two previously placed biliary stents had migrated proximally, above the anastomosis. A digital single-operator cholangioscopy was performed (SpyGlass, Boston Scientific, Marlborough, Massachusetts) with direct visualization of the migrated stents, however, the accessories through the cholangiocope, such as the SpyBite forceps or the SpySnare (Boston Scientific), were not available in our department at that time. Nevertheless, the cholangioscopy allowed a successful guidewire advancement into the lumen of the stents and its subsequent removal to the duodenum using a Soehendra Stent Retriever (Cook Japan, Tokyo, Japan). Endoscopic removal of proximally migrated stents can be challenging and cholangioscopy has emerged as an additional tool in these cases. This case report represents a successful retrieval of two biliary stents guided by cholangioscopy, avoiding further invasive procedures or even surgery with significant morbidity and mortality.


Safety and Efficacy of Ondansetron and Simvastatin as Potential Adjunctive Treatment for Patients With Schizophrenia: A Systematic Review of Randomized Controlled Trials.
In a generation where advancements in research and understanding have led to remarkable achievements in medicine, it is still unfathomable that, after more than a century, the cause of schizophrenia is still a mystery. While antipsychotics, without a doubt, have brought on an exemplary revolution in the way psychiatric disorders are now treated, there are still imperative deficits that need to be addressed to ultimately enable individuals with schizophrenia to function normally in society. However, without a definite cause of schizophrenia, even though speculation has been made on its inflammatory and neurodegenerative nature, it has provided an unnecessary hindrance to finding further potential treatment modalities for these patients. Nevertheless, some trials are investigating potential adjunctive treatment regimens to antipsychotics, which can help achieve complete remission. Exploring these drugs will have significant implications for managing schizophrenia in future clinical practices. This systematic review was conducted between January 2012 to July 2022 according to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines to evaluate the safety and efficacy of ondansetron and simvastatin as adjunctive treatment to antipsychotics in adult patients with schizophrenia. This review included nine randomized controlled trials. Overall, both simvastatin and ondansetron, when used as adjunctive treatment in schizophrenia, appear to be safe. Ondansetron showed promising results, with all studies on this drug showing positive overall results on schizophrenia symptoms. On the other hand, simvastatin demonstrated mixed results, which can be attributed to the limited participants in the studies and the shorter duration of the trials. However, more extensive trials with uniform assessment tools are needed to demonstrate concrete evidence of the effectiveness of these drugs, whether alone or in combination with each other or perhaps another drug such as aspirin in schizophrenia.


Human fetal adiponectin and retinol-binding protein (RBP)-4 levels in relation to birth weight and maternal obesity.
Recent studies suggest that the perinatal period is a sensitive part in human development with respect to the pathogenesis of metabolic diseases in adulthood. Neonates, who are either small or large for gestational age (SGA or LGA) have a greater risk of developing obesity and insulin resistance in later life. The term "perinatal priming" is used to describe this phenomenon. Therefore, in the present study we first aimed to investigate if birth weight influences fetal adiponectin and RBP-4 metabolism. Umbilical cord blood was obtained form 40 neonates born on term+/-4 weeks and the adipokine concentrations in the serum were measured. In this analysis adiponectin but not RBP-4 levels showed a positive significant correlation to birth weight. Since maternal preconceptional obesity is associated with an increased birth weight and the risk for LGA neonates, we further aimed to investigate, if the maternal nutritional state influences fetal adiponectin and RBP-4. Therefore umbilical cord blood levels of the adipokines were correlated to maternal preconceptional BMI. In this analysis, neither adiponectin nor RBP-4 levels showed a significant correlation. Taken together, in the present study for the first time we directly compare fetal adiponectin and RBP-4 levels in respect to birth weight and maternal preconceptional BMI. Our data suggest that (1) adiponectin is more likely to have a role in perinatal priming of obesity and insulin resistance than RBP-4 and (2) that birth weight has a greater impact on fetal adipokine serum levels than maternal preconceptional obesity.


Evaluation of body composition in neonates and infants.
A better understanding of the nutritional needs of both healthy and sick infants is important. Not only does too much or too little nutrition during early life have long-term effects on health, but periods of rapid growth during the first year of life also have long-term consequences. Knowledge of the changes in body composition in early life can help to better define nutritional needs at these ages. Several methods are available for measuring body composition of neonates and infants. Most focus on an assessment of either body fatness or bone mineralization; only a few can monitor the quality of the non-fat lean tissues. This paper provides an evaluation of the different approaches currently available to monitor infant body composition, identifying both their strengths and limitations.


The emergence of spatial rotation deficits in dementia and normal aging.
The mental rotation required in the Road Map Test of Direction Sense (the "Road Map Test"; J. Money, 1976; J. Money, D. Alexander, & H. T. Walker, 1965) has been thought to be impaired as a function of age, but not dementia. However, spatial rotation in dementia has not been investigated in reference to spatial coordinate systems. Patients with dementia (Alzheimer's and ischemic vascular dementias) and elderly control participants were administered the Road Map Test. The authors analyzed whether the geocentric or egocentric coordinate system determined rotation of Road Map Test turns and predicted impairment in dementia patients. They found equivalent impairment in both types of dementia, greater angulation effect in the geocentric system in patients relative to normal controls, and no egocentric effect. Results also suggest early emergence of spatial rotation deficit in dementia. Spatial rotation is most often associated with working memory, which predicts the correlations found.


Development and validation of a low-cost laparoscopic simulation box.
The acquisition of laparoscopic technique skills in an operating room is conditioned by the expertise of the tutor and the number of training interventions by the trainee. For students and surgeons to use a laparoscopic simulator to train their skills, it must be validated beforehand. A laparoscopic simulator box was designed, along with 6 interchangeable training games. The simulator was validated by a group of 19 experts, physicians with an experience from at least 100 laparoscopic surgeries, and 20 students of 4th to 6th grades of medical school (non-experts). To evaluate its construct validity, time-to-completion and the number of successfully completed games were assessed. We used 11 and 9-item questionnaires to gather information on content and face validity respectively. In both questionnaires, answers were collected through Likert-type scales, scored from 1 to 5. The group of experts required less time and successfully completed more games than the group of non-experts (p < 0.01). The group of non-experts gave a score ≥ 4 points on each of the questions regarding the content validity of the tool, however, the experts rated with a significant lower mean score the need for the simulator to learn the surgical technique (3.68 points; p < 0.01). Regarding the face validity, all items were graded with a score ≥ 4 points except for the question relating to the spatial realism (3.82 points). The laparoscopy simulation box and the games were valid means for training surgeons and medical students to develop the skills required for the laparoscopic technique.


Cross-country comparison: does social democratic party power increase an employee's perceived employability?
Individuals strive to be highly employable, yet, we lack a uniform definition of 'employability'. Within the labour market, employability can be seen as a product of individual human capital resources. However, this study argues that employability is also affected by the structure of the labour market and therefore also considers a country's economic situation and political power to quantify employees' perceived employability. Using data from the International Social Survey Programme, the Manifesto Project Dataset, and the International Labour Organization, this study uses a multilevel regression model with data from 30 countries. This paper disentangles the impact of individual careers and country policies (micro-macro linkage) on the perceived employability of their employees. At the individual level, initial education is the main predictor of employees' current perceived employability, but vocational training is not. At the country level, the share of social democratic party power in each country, as a driver of active labour market policies, has a net effect on employee's perceived employability, irrespective of their individual human capital investments. The generalisability of the findings is relevant to current debates about whether workers should become managers of their own careers or whether policymakers should take responsibility.


Effects of morphine, clonidine, and intensity change on electric-shock discrimination.
The effects of morphine, clonidine, and changes in stimulus intensity were examined in squirrel monkeys responding on one of two levers following brief presentations of one of two electric-shock intensities (0.1 and 0.5 mA). Responses were designated as correct or incorrect depending on which shock intensity had been presented and which lever was pressed. Morphine (0.42 to 1.80 mg/kg) and clonidine (0.075 to 0.18 mg/kg) decreased percentage correct responding. Morphine and clonidine also increased response latency and the number of shock presentations that were not followed by responses. Changes in shock intensity also decreased percentage correct responding but had no effect on response latency or on the number of shock presentations not followed by responses.


Effects of Lignocaine Administered Intravenously or Intratracheally on Airway and Hemodynamic Responses during Emergence and Extubation in Patients Undergoing Elective Craniotomies in Supine Position.
Sympathoadrenergic responses during emergence and extubation can lead to an increase in heart rate (HR) and blood pressure whereas increased airway responses may lead to coughing and laryngospasm. The aim of our study was to compare the effects of lignocaine administered intravenously (IV) or intratracheally on airway and hemodynamic responses during emergence and extubation in patients undergoing elective craniotomies. Sixty patients with physical status American Society of Anaesthesiologists Classes I and II aged 18-70 years, scheduled to undergo elective craniotomies were included. The patients were randomly divided into three groups of twenty patients; Group 1 receiving IV lignocaine and intratracheal placebo (IV group), Group 2 receiving intratracheal lignocaine and IV placebo (I/T group), and Group 3 receiving IV and intratracheal placebo (placebo group). The tolerance to the endotracheal tube was monitored, and number of episodes of cough was recorded during emergence and at the time of extubation. Hemodynamic parameters such as HR and blood pressure (systolic, diastolic, mean arterial pressure) were also recorded. There was a decrease of HR in both IV and intratracheal groups in comparison with placebo group (P < 0.005). Rise in blood pressure (systolic blood pressure, diastolic blood pressure and mean arterial pressure) was comparable in both Groups 1 and 2 but was lower in comparison with placebo group (P < 0.005). Cough suppression was comparable in all the three groups. Grade III cough (15%) was documented only in placebo group. Both IV and intratracheal lignocaine are effective in attenuation of hemodynamic response if given within 20 min from skull pin removal to extubation. There was comparable cough suppression through intratracheal route and IV routes than the placebo group.


Recent range expansion of an intermediate host for animal schistosome parasites in the Indo-Australian Archipelago: phylogeography of the freshwater gastropod Indoplanorbis exustus in South and Southeast Asia.
The planorbid snail Indoplanorbis exustus is the sole intermediate host for the Schistosoma indicum species group, trematode parasites responsible for cattle schistosomiasis and human cercarial dermatitis. This freshwater snail is widely distributed in Southern Asia, ranging from Iran to China eastwards including India and from the southeastern Himalayas to Southeast Asia southwards. The veterinary and medical importance of this snail explains the interest in understanding its geographical distribution patterns and evolutionary history. In this study, we used a large and comprehensive sampling throughout Indo-Malaya, including specimens from South India and Indonesia, areas that have been formerly less studied. The phylogenetic inference revealed five highly divergent clades (genetic distances among clades: 4.4-13.9%) that are morphologically indistinguishable, supporting the assumption that this presumed nominal species may represent a cryptic species complex. The species group may have originated in the humid subtropical plains of Nepal or in southern adjacent regions in the Early Miocene. The major cladogenetic events leading to the fives clades occurred successively from the Early Miocene to the Early Pleistocene, coinciding with major periods of monsoonal intensification associated with major regional paleogeographic events in the Miocene and repeated climate changes due to the Plio-Pleistocene climatic oscillations. Our coverage of the Indo-Australian Archipelago (IAA) highlights the presence of a single clade there. Contrary to expectations, an AMOVA did not reveal any population genetic structure among islands or along a widely recognised zoogeographical regional barrier, suggesting a recent colonisation independent of natural biogeographical constraints. Neutrality tests and mismatch distributions suggested a sudden demographic and spatial population expansion that could have occurred naturally in the Pleistocene or may possibly result of a modern colonisation triggered by anthropogenic activities. Even though Indoplanorbis is the main focus of this study, our findings may also have important implications for fully understanding its role in hosting digenetic trematodes. The existence of a cryptic species complex, the historical phylogeographical patterns and the recent range expansion in the IAA provide meaningful insights to the understanding and monitoring of the parasites potential spread. It brings a substantial contribution to veterinary and public health issues.


Safety evaluation of gentian violet for breeder chickens.
Four treatment levels (1.0, 2.5, 5.0 and 10.0 x the recommended use level) of a gentian violet premix (Dye-Gen) were compared with non-medicated controls for breeder chickens during a 168-day study. There were no treatment effects up to and including 10 x the recommended use level on: average daily feed consumption, feed/dozen eggs, hatchability of fertile eggs, or mortality. Fertility was higher for the birds receiving 2.5 x the recommended use level than for the non-medicated controls. Egg production was higher (P less than .05) for the non-medicated controls and 10x groups than for the birds receiving the gentian violet premix at 2.5 x the recommended use level. Semen of breeder males was observed for % abnormal sperm, % dead sperm, % motility, vigor, and semen volume. There was no treatment effect on any of the semen characteristics evaluated. It can be concluded from these data that the gentian violet premix is safe for breeder chickens under the conditions of this study.


[Flubendazole in human Echinococcus granulosus hydatidosis. Preoperative care: parasit-pharmacologic study].
The effect of flubendazole in human hydatic disease due to E. granulosus has been studied in 22 patients with one or several hydatic cysts of different sites. Flubendazole has been given orally before surgery for a 10 days mean period, at 4 g daily in adults and 1 g daily in children. Flubendazole has been titrated by radioimmuno-assay in sera, urines and bile taken 12 to 24 hours after the last ingestion and in the hydatic cyst (membranes and liquid). The scolex vitality was determined by direct optic microscopy and by intra-peritoneal mouse inoculation. Seven non-treated patients, without hydatic disease, were considered as controls. The flubendazole concentrations in sera (3.01 +/- 3.73 ng/ml) and in urines (7.6 +/- 7.5 ng ml) are low. They are also low in membranes (3.21 +/- ng/mg) and in hydatic liquid, but significantly more elevated in the hepatic localisation than in the pulmonary localisation. The bile concentrations are high (167.9 +/- 133.2 ng/ml). There is no correlation between these concentrations and the amounts of flubendazole administered. The scolex vitality was correlated neither with the amounts of flubendazole administered, nor with the concentrations of flubendazole in the hydatic cyst. Further studies are necessary before judging of the efficacy of flubendazole in the human hydatic disease.


Small-molecule xenomycins inhibit all stages of the Plasmodium life cycle.
Widespread resistance to most antimalaria drugs in use has prompted the search for novel candidate compounds with activity against Plasmodium asexual blood stages to be developed for treatment. In addition, the current malaria eradication programs require the development of drugs that are effective against all stages of the parasite life cycle. We have analyzed the antimalarial properties of xenomycins, a novel subclass of small molecule compounds initially isolated for anticancer activity and similarity to quinacrine in biological effects on mammalian cells. In vitro studies show potent activity of Xenomycins against Plasmodium falciparum. Oral administration of xenomycins in mouse models result in effective clearance of liver and blood asexual and sexual stages, as well as effective inhibition of transmission to mosquitoes. These characteristics position xenomycins as antimalarial candidates with potential activity in prevention, treatment and elimination of this disease.


Nonfluoroscopic Imaging as Guidance for Radiofrequency Ablation of Atrioventricular Nodal Reentrant Tachycardia after Mustard Repair.
Most tachycardias in the pulmonary venous atrium are inaccessible by direct means and require either a retrograde approach or a transseptal approach for ablation. We present a case in which successful radiofrequency ablation of common atrioventricular nodal reentrant tachycardia was accomplished via a retrograde transaortic approach guided by nonfluoroscopic mapping with use of the NavX™ mapping system. The patient was a 49-year-old woman who at the age of 4 years had undergone Mustard repair for complete dextrotransposition of the great arteries. Three-dimensional reconstructions of the ascending aorta, right ventricle, systemic venous atrium, left ventricle, and superior vena cava-inferior vena cava baffle complex were created, and the left-sided His bundle was marked. After a failed attempt at ablation from the systemic venous side, we eliminated the atrioventricular nodal reentrant tachycardia by ablation from the pulmonary venous side. This case is, to our knowledge, the first report of successful radiofrequency ablation of common atrioventricular nodal reentrant tachycardia after Mustard repair for this congenital cardiac malformation in which ablation was guided by 3-dimensional nonfluoroscopic imaging. This imaging technique enabled accurate anatomic location of the ablation catheters in relation to the His bundle marked from the systemic venous side.


Quantitative analysis of the thermal requirements for stepwise physical dormancy-break in seeds of the winter annual Geranium carolinianum (Geraniaceae).
Physical dormancy (PY)-break in some annual plant species is a two-step process controlled by two different temperature and/or moisture regimes. The thermal time model has been used to quantify PY-break in several species of Fabaceae, but not to describe stepwise PY-break. The primary aims of this study were to quantify the thermal requirement for sensitivity induction by developing a thermal time model and to propose a mechanism for stepwise PY-breaking in the winter annual Geranium carolinianum. Seeds of G. carolinianum were stored under dry conditions at different constant and alternating temperatures to induce sensitivity (step I). Sensitivity induction was analysed based on the thermal time approach using the Gompertz function. The effect of temperature on step II was studied by incubating sensitive seeds at low temperatures. Scanning electron microscopy, penetrometer techniques, and different humidity levels and temperatures were used to explain the mechanism of stepwise PY-break. The base temperature (Tb) for sensitivity induction was 17·2 °C and constant for all seed fractions of the population. Thermal time for sensitivity induction during step I in the PY-breaking process agreed with the three-parameter Gompertz model. Step II (PY-break) did not agree with the thermal time concept. Q10 values for the rate of sensitivity induction and PY-break were between 2·0 and 3·5 and between 0·02 and 0·1, respectively. The force required to separate the water gap palisade layer from the sub-palisade layer was significantly reduced after sensitivity induction. Step I and step II in PY-breaking of G. carolinianum are controlled by chemical and physical processes, respectively. This study indicates the feasibility of applying the developed thermal time model to predict or manipulate sensitivity induction in seeds with two-step PY-breaking processes. The model is the first and most detailed one yet developed for sensitivity induction in PY-break.


Connectivity Profile of Middle Inferior Parietal Cortex Confirms the Hypothesis About Modulating Cortical Areas.
According to the correlated transmitter-receptor based structure of the inferior parietal cortex (IPC), this brain area is divided into three clusters, namely, the caudal, the middle and the rostral. Nevertheless, in associating different cognitive functions to the IPC, previous studies considered this part of the cortex as a whole and thus inconsistent results have been reported. Using multiband echo planar imaging (EPI), we investigated the connectivity profile of the middle IPC while forty-five participants performed a task requiring cognitive control. The middle IPC demonstrated functional associations which do not have similarities to a contributing part in the frontoparietal network, in processing cognitive control. At the same time, this cortical area showed negative functional connectivity with both the precuneus cortex, which is resting- state related, and brain areas related to general cognitive functions. That is, the functions of the middle IPC are not accommodated by the traditional categorization of different brain areas i.e. resting state-related or task-related networks and this advanced our hypothesis about modulating cortical areas. Such brain areas are characterized by their negative functional connectivity with parts of the cortex involved in task performance, proportional to the difficulty of the task; yet, their functional associations are inconsistent with the resting state-related cortical areas.


Inferring Interaction Networks From Multi-Omics Data.
A major goal in systems biology is a comprehensive description of the entirety of all complex interactions between different types of biomolecules-also referred to as the interactome-and how these interactions give rise to higher, cellular and organism level functions or diseases. Numerous efforts have been undertaken to define such interactomes experimentally, for example yeast-two-hybrid based protein-protein interaction networks or ChIP-seq based protein-DNA interactions for individual proteins. To complement these direct measurements, genome-scale quantitative multi-omics data (transcriptomics, proteomics, metabolomics, etc.) enable researchers to predict novel functional interactions between molecular species. Moreover, these data allow to distinguish relevant functional from non-functional interactions in specific biological contexts. However, integration of multi-omics data is not straight forward due to their heterogeneity. Numerous methods for the inference of interaction networks from homogeneous functional data exist, but with the advent of large-scale paired multi-omics data a new class of methods for inferring comprehensive networks across different molecular species began to emerge. Here we review state-of-the-art techniques for inferring the topology of interaction networks from functional multi-omics data, encompassing graphical models with multiple node types and quantitative-trait-loci (QTL) based approaches. In addition, we will discuss Bayesian aspects of network inference, which allow for leveraging already established biological information such as known protein-protein or protein-DNA interactions, to guide the inference process.


Accessibility of and client satisfaction with dental services in Melbourne.
Public dental clinics play an important role in delivering dental services to Australian adults on low incomes. Our objective was to compare the accessibility of and client satisfaction with the two main types of public dental service providers in Victoria and with private practice services. Clients attending the Royal Dental Hospital of Melbourne, Northcote Community Health Centre and private practices in Melbourne were surveyed. The hospital's clients faced the greatest ecological and organisational obstacles, while private clients faced the greatest financial and desirability obstacles. Community centre clients faced fewer ecological and organisational obstacles than hospital clients, with the exception of long waiting times. Private practice clients were more satisfied overall, and had better continuity of care. Private practice clients were more satisfied with access, availability and convenience than community centre clients, who in turn were more satisfied than hospital clients. There was no distinction between private practice and hospital clients on satisfaction with 'pain and treatment', but community centre clients were less satisfied. There was no significant difference between client group evaluations of interaction with the dentist. Regardless of the effects of the Commonwealth Dental Health Program, distinctions between various service types and public clinic types are likely to remain, because of their different settings. The contrast between a central hospital and a community health centre, in terms of the ecological and organisational obstacles to care, points to the advantages of putting dental services close to the communities they serve.


Electrochemical and Structural Characterization of Lanthanum-Doped Hydroxyapatite: A Promising Material for Sensing Applications.
In the quest to find powerful modifiers of screen-printed electrodes for sensing applications, a set of rare earth-doped Ca10-xREx(PO4)6(OH)2 (RE = La, Nd, Sm, Eu, Dy, and Tm and x = 0.01, 0.02, 0.10, and 0.20) hydroxyapatite (HAp) samples were subjected to an in-depth electrochemical characterization using electrochemical impedance spectroscopy and cyclic and square wave voltammetry. Among all of these, the inorganic phosphates doped with lanthanum proved to be the most reliable, revealing robust analytical performances in terms of sensitivity, repeatability, reproducibility, and reusability, hence paving the way for their exploitation in sensing applications. Structural data on La-doped HAp samples were also provided by using different techniques, including optical microscopy, X-ray diffraction, Rietveld refinement from X-ray data, Fourier transform infrared, and Raman vibrational spectroscopies, to complement the electrochemical characterization.


Microbial profile of pelvic inflammatory disease.
A total of 100 cases were studied. Fallopian tubes removed at operation constituted a very good material to study the infections of upper genital tract. Along with fallopian tubes, HVS from same patients were cultured both for aerobic and anaerobic organisms. Bacteriological analysis of 100 cases of fallopian tubes and same number of HVS showed bacterial growth in 30 cases (30%) whereas in HVS samples growth was obtained in 50 cases (50%). In 66.67% of cases same bacteria were isolated both from HVS and fallopian tubes which strongly favours the theory of ascending infection. Out of all antibiotics ciprofloxacin showed the widest spectrum of activity (94.20%). All anaerobes were sensitive to metronidazole.


Wound breakdown after total ankle arthroplasty.
Wound breakdown of the operative incision is commonly encountered as a complication following ankle replacement surgery. Healing problems can progress to full thickness necrosis of the skin and deeper tissues jeopardizing the ultimate retention of the implants leading to compromised patient outcomes. The medical records of 57 consecutive primary total ankle arthroplasties (TAA) were retrospectively reviewed after observing a higher than expected rate of wound-healing problems consistently involving the central third of the operative incision. The rate of wound breakdown was 28% in this series. Analysis of various possible risk factors showed a statistically significant increase in rate of wound breakdown associated with smoking greater than 12 pack years, peripheral vascular disease, and cardiovascular disease. Preoperative identification of patient risk factors associated with breakdown of the operative incision after TAA should improve outcome of the procedure. Screening of those patients with risk factors for wound breakdown is recommended prior to total ankle arthroplasty.


Unexpected causes of gynecological pelvic pain.
During our day-to-day practice, we, as clinicians, occasionally come across patients whose symptomatology is atypical. In major teaching hospitals, it is usually easy to consult with other specialists to optimize patient management and standard of care. Our study patients were treated by the authors between January 1998 and January 2003. In this article, the authors report on 6 different cases of unexpected causes of pelvic pain, all of which were managed in a general gynecological unit at a major tertiary referral institution.


Robust self-calibration three-dimensional shape measurement in fringe-projection photogrammetry.
Commonly, fringe-projection photogrammetry involves two independent stages: system calibration and measurement. The measurement accuracy largely depends on the calibration procedure. However, the results of system calibration may be unstable in different occasions. In this Letter, we propose a robust self-calibration 3D shape measurement in fringe-projection photogrammetry by combining control and measurement points. The control points with known 3D coordinates are provided on the checkerboard, and the measurement points are identified by absolute phase information in the deformed fringes. The introduction of control points in the nonlinear collinearity equations can be regarded as invariant in the optimization procedure, which enhances the measurement robustness. Compared to the binocular model in fringe-projection technique, moreover, multiple-view ray intersection is utilized to reflect the advantage of photogrammetry in the fringe-projection 3D measurement.


A review of the efficacy and safety of docetaxel as monotherapy in metastatic breast cancer.
To date, although statistically significant, the overall impact of adjuvant chemotherapy on the survival of women with nonmetastatic breast cancer has been disappointing. Hence, new agents that have shown good activity against metastatic disease should be assessed quickly in the adjuvant setting. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) is one of the most promising drugs that has emerged in recent years, with phase II studies in previously untreated metastatic breast cancer indicating a high overall response rate of approximately 60%. A recent large, randomized comparison demonstrated docetaxel to be superior to doxorubicin with regard to response rate, and it is the only agent to have shown this superiority. Docetaxel was also tolerated better. A second randomized trial in patients who had already failed an anthracycline-containing regimen showed that docetaxel-treated patients survived significantly longer than those treated with the combination of mitomycin C and vinblastine. The apparent superiority of docetaxel over doxorubicin and the lack of complete cross-resistance between these drugs, which has been demonstrated in trials involving anthracycline-resistant patients, suggest a possible future role for docetaxel, either alone or in combination with the anthracycline, in earlier stages of metastatic breast cancer and indeed in the adjuvant treatment of early stage disease. The combination of docetaxel with doxorubicin appears particularly promising in this regard and, unlike the doxorubicin/paclitaxel doublet, has not been reported to produce clinically significant cardiomyopathy. The high activity of docetaxel provides a compelling rationale for its study as a component of adjuvant therapies. Investigators in Brussels and Dublin have recently demonstrated the feasibility of two candidate adjuvant programs. Large phase II adjuvant trials involving docetaxel are now being assessed.


Revision of the Australian leaf beetle genus Cheiloxena Baly, 1860 (Coleoptera: Chrysomelidae: Spilopyrinae).
The endemic Australian leaf beetle genus Cheiloxena Baly, 1860 is revised, with eight valid species, three new: C. aitori sp. nov.; C. blackburni Reid, 1992; C. conani sp. nov.; C. frenchae Blackburn, 1893; C. insignis Blackburn, 1896; C. monga sp. nov.; C. tuberosa Reid, 1992; C. westwoodii Baly, 1860. A key is provided for their identification and all species are described. Cheiloxena species occur from southern Victoria to central Queensland. Hosts are Araliaceae (Astrotricha), Proteaceae (Lomatia) and possibly Myrtaceae (Eucalyptus).


Associative learning and sensory neuroplasticity: how does it happen and what is it good for?
Historically, the body's sensory systems have been presumed to provide the brain with raw information about the external environment, which the brain must interpret to select a behavioral response. Consequently, studies of the neurobiology of learning and memory have focused on circuitry that interfaces between sensory inputs and behavioral outputs, such as the amygdala and cerebellum. However, evidence is accumulating that some forms of learning can in fact drive stimulus-specific changes very early in sensory systems, including not only primary sensory cortices but also precortical structures and even the peripheral sensory organs themselves. This review synthesizes evidence across sensory modalities to report emerging themes, including the systems' flexibility to emphasize different aspects of a sensory stimulus depending on its predictive features and ability of different forms of learning to produce similar plasticity in sensory structures. Potential functions of this learning-induced neuroplasticity are discussed in relation to the challenges faced by sensory systems in changing environments, and evidence for absolute changes in sensory ability is considered. We also emphasize that this plasticity may serve important nonsensory functions, including balancing metabolic load, regulating attentional focus, and facilitating downstream neuroplasticity.


Indication-specific pricing of pharmaceuticals in the US healthcare system.
To explore the potential of indication-specific pricing (ISP) of pharmaceuticals and to discuss prospects for implementation in the US healthcare system. The Institute for Clinical and Economic Review convened a policy forum with 44 healthcare leaders from 22 payer and life sciences companies. Models of ISP were discussed. Payers and drug manufacturers saw the potential benefits of an ISP system that balances affordability for payers, sustainability for manufacturers and access for patients. The US healthcare system presents many challenges to implementation, including potential conflicts with existing pricing policies (Medicaid Best Price, average sales price and 340B) and insufficient data systems and analytic capabilities. Possible solutions and policy recommendations for payers and manufacturers are provided.