The approach to 4d/4f-polyphosphides.
The first 4d/4f polyphosphides were obtained by reaction of the divalent metallocenes [Cp*2Ln(thf)2] (Ln = Sm, Yb) with [{CpMo(CO)2}2(μ,η2:2-P2)] or [Cp*Mo(CO)2(η3-P3)]. Treatment of [Cp*2Ln(thf)2] (Ln = Sm, Yb) with [{CpMo(CO)2}2(μ,η2:2-P2)] gave the 16-membered bicyclic compounds [(Cp2*Ln)2P2(CpMo(CO)2)4] (Ln = Sm, Yb) as the major products. From the reaction involving samarocene, the cyclic P4 complex [(Cp*2Sm)2P4(CpMo(CO)2)2] and the cyclic P5 complex [(Cp*2Sm)3P5(CpMo(CO)2)3] were also obtained as minor products. In each reaction, the P2 unit is reduced and a rearrangement occurred. In dedicated cases, a P-P bond formation takes place, which results in a new aggregation of the central phosphorus scaffold. In the reactions of [Cp*2Ln(thf)2] (Ln = Sm, Yb) with [Cp*Mo(CO)2P3] a new P-P bond is formed by reductive dimerization and the 4d/4f hexaphosphides [(Cp*2Ln)2P6(Cp*Mo(CO)2)2] (Ln = Sm, Yb) were obtained.


Quantifying deforestation and forest degradation with thermal response.
Deforestation and forest degradation cause the deterioration of resources and ecosystem services. However, there are still no operational indicators to measure forest status, especially for forest degradation. In the present study, we analysed the thermal response number (TRN, calculated by daily total net radiation divided by daily temperature range) of 163 sites including mature forest, disturbed forest, planted forest, shrubland, grassland, savanna vegetation and cropland. TRN generally increased with latitude, however the regression of TRN against latitude differed among vegetation types. Mature forests are superior as thermal buffers, and had significantly higher TRN than disturbed and planted forests. There was a clear boundary between TRN of forest and non-forest vegetation (i.e. grassland and savanna) with the exception of shrubland, whose TRN overlapped with that of forest vegetation. We propose to use the TRN of local mature forest as the optimal TRN (TRNopt). A forest with lower than 75% of TRNopt was identified as subjected to significant disturbance, and forests with 66% of TRNopt was the threshold for deforestation within the absolute latitude from 30° to 55°. Our results emphasized the irreplaceable thermal buffer capacity of mature forest. TRN can be used for early warning of deforestation and degradation risk. It is therefore a valuable tool in the effort to protect forests and prevent deforestation.


[Lyme disease vaccine: hopes and concerns].
The vaccine against Lyme disease for last decade became an important issue for many researchers. Recently two groups of scientists published data of their trials carried out on humans. The vaccine which was given to volunteers consisted of recombinant outer surface protein (Osp)A. These people were observed for two years when approximately 79% of them developed resistance to Borrelia burgdorferi infection. These data were evaluated by FDA experts who recommended vaccine for approval. Main concerns of experts are: short duration of observation of vaccinated people, no possibility to vaccinate children, problematic vaccination people with undiagnosed Lyme disease. However the moment when effective and safe vaccine against Lyme disease will be available seems to approach.


Investigating automated regression models for estimating left ventricular ejection fraction levels in heart failure patients using circadian ECG features.
Heart Failure (HF) significantly impacts approximately 26 million people worldwide, causing disruptions in the normal functioning of their hearts. The estimation of left ventricular ejection fraction (LVEF) plays a crucial role in the diagnosis, risk stratification, treatment selection, and monitoring of heart failure. However, achieving a definitive assessment is challenging, necessitating the use of echocardiography. Electrocardiogram (ECG) is a relatively simple, quick to obtain, provides continuous monitoring of patient's cardiac rhythm, and cost-effective procedure compared to echocardiography. In this study, we compare several regression models (support vector machine (SVM), extreme gradient boosting (XGBOOST), gaussian process regression (GPR) and decision tree) for the estimation of LVEF for three groups of HF patients at hourly intervals using 24-hour ECG recordings. Data from 303 HF patients with preserved, mid-range, or reduced LVEF were obtained from a multicentre cohort (American and Greek). ECG extracted features were used to train the different regression models in one-hour intervals. To enhance the best possible LVEF level estimations, hyperparameters tuning in nested loop approach was implemented (the outer loop divides the data into training and testing sets, while the inner loop further divides the training set into smaller sets for cross-validation). LVEF levels were best estimated using rational quadratic GPR and fine decision tree regression models with an average root mean square error (RMSE) of 3.83% and 3.42%, and correlation coefficients of 0.92 (p<0.01) and 0.91 (p<0.01), respectively. Furthermore, according to the experimental findings, the time periods of midnight-1 am, 8-9 am, and 10-11 pm demonstrated to be the lowest RMSE values between the actual and predicted LVEF levels. The findings could potentially lead to the development of an automated screening system for patients with coronary artery disease (CAD) by using the best measurement timings during their circadian cycles.


Susceptibility of experimental autoimmune hepatitis in transgenic mice overexpressing the c-H-ras gene.
Results from a recent study of ours have demonstrated the significant role of the wild-type ras gene in the development of hepatocellular carcinoma in rasH2 mice having prototype human c-H-ras genes. Chronic cell death and regeneration have been considered to work as co-carcinogens with wild-type ras gene overexpression in this model. To elucidate a role of gene overexpression in the occurrence of chronic inflammation, we tried to induce inflammation in the liver of rasH2 mice by immunizing them with the supernatant of a freshly prepared syngenic liver homogenate. Immunization resulted in a dense inflammatory infiltrate in the portal tract and focal necrosis with spots of fatty or foamy degeneration in the transgenic mouse liver; however, these observations were less frequently observed in non-transgenic mouse liver. Monocytes, granulocytes and plasma cell infiltration were observed in the livers of transgenic mice. An immunohistochemical study showed that CD3-positive lymphocytes also infiltrated the liver. The inflammatory infiltrate was still present in the transgenic liver 24 weeks after the last injection, but little infiltrate was observed at the same time in non-transgenic mice. No hepatic tumours could be produced over the 6 months duration of the study and the results are only preliminary. However, these results do suggest that overexpression of wild-type ras is partially responsible for the occurrence of autoimmune chronic hepatitis.


Metritis and clinical mastitis events in lactating dairy cows were associated with altered patterns of rumination, physical activity, and lying behavior monitored by an ear-attached sensor.
Understanding changes in parameters recorded by automated health monitoring systems based on ear-attached sensors on the days immediately before and after diagnosis of metritis and clinical mastitis can help develop dairy cow health monitoring strategies. The objective of this observational cohort study was to characterize rumination time, physical activity, and lying time monitored by an ear-attached sensor before, during, and after clinical diagnosis (CD) of metritis and clinical mastitis. Lactating Holsteins monitored daily for 21 DIM for detection of health disorders were retrospectively included in the no-clinical health disorder group (NCHD; n = 616) if no disorders were diagnosed. Cows were included in the metritis (MET; n = 69) or clinical mastitis (MAST; n = 36) group if diagnosed only with non-severe metritis (watery, reddish, and fetid uterine discharge with or without pyrexia) or clinical mastitis (visibly abnormal milk secretion with or without signs of udder inflammation with no pyrexia and no systemic signs of disease), respectively. Cows diagnosed with severe metritis (signs of metritis plus systemic signs of disease) or clinical mastitis (signs of mastitis plus pyrexia and systemic signs of disease), or cows diagnosed with non-severe metritis or clinical mastitis plus another disorder within -7 to +7 d of CD of metritis or clinical mastitis diagnosis were included in the metritis plus (MET+; n = 25) or the clinical mastitis plus (MAST+; n = 15) group, respectively. Cows were fitted with an ear-attached accelerometer to measure rumination time, physical activity, and lying time. Mean daily values, mean value absolute change, and relative change for the mean daily value from 3 or 5 d before CD to the nadir for cows with metritis and clinical mastitis, respectively were analyzed with linear mixed models with or without repeated measures. Rumination time and physical activity were lesser, and lying time was greater for the MET and MET+ groups than for the NCHD group for most days from -4 to +7 d of CD of metritis. Generally, daily rumination time, physical activity, and lying time differences were larger and more prolonged between the MET+ and NCHD than between the MET and NCHD groups. Similarly, cows in the MAST and MAST+ groups had lesser rumination time and physical activity than cows in the NCHD group for several days before diagnosis. Lying time was greater for the MAST+ than the NCHD group on day -1 and 0 relative to CD. Absolute values and relative changes from 3 d before CD to the day of the nadir for rumination time and physical activity, or peak for lying time were different for cows in the MET and MET+ groups than for the NCHD group. Similar results were observed for the MAST and MAST+ groups compared with the NCHD group. For cows with metritis, either an increase in rumination time and physical activity or a decrease in lying time was observed from the day of CD to resolution of clinical signs but no changes were observed for the NCHD. Cows with clinical mastitis and the NCHD group had different rumination time, physical activity, and lying time on the day of CD and resolution of clinical signs, but cows with clinical mastitis had no significant changes from the day of CD to resolution of clinical signs. We conclude that cows affected by metritis and clinical mastitis presented substantial alterations of the pattern of rumination time, physical activity, and lying time captured by an ear-attached sensor. Thus, automated health monitoring systems based on ear-attached sensors might be used as an aid for identifying cows with metritis and clinical mastitis. Moreover, behavioral parameter changes after CD might be good indicators of resolution of clinical signs of metritis but not mastitis.


Practical Guide to Undergraduate Medical Curriculum Alignment and Mapping.
Curriculum development and reviews are of paramount importance for academic programs curriculum management. Medical curricula need proper construction and frequent updates to suits learning outcomes considering their integrative nature and rapid scientific advancement. Curriculum alignment and mapping are fundamental for proper integration and planning of medical curriculum. This process is beneficial in detecting gaps and redundancies, and ensuring proper instruction, integration, and transparency. However, there is a paucity in the literature of a practical guidance to such process. Hence, this manuscript provides a practical guidance that was adopted in our institutes. A detailed description of twelve step-by-step guidance to curriculum alignment and mapping was provided. The process needed for each step and the flow chart of work was detailed. This guide was developed and implemented successfully. Among many benefits encountered, many gaps in the contents, learning outcomes and assessment methods were detected and rectified. Additionally, better curriculum integration has been achieved. The current mapping will make any future curriculum reviews easier. This guide could be utilized by newly developed and existing programs for curriculum alignment and mapping. It fills a gap in academic literature through stepwise workflow which has been tested and implemented.


PHYSICAL AND IMMUNOLOGICAL DIFFERENCES AMONG STREPTOKINASES.
Two strains of Group A streptococci have been shown to produce streptokinases with different physical and immunologic characteristics. These streptokinases have been designated SK-A and SK-B. Examination of additional strains of Group A streptococci has indicated that SK-A is the more commonly encountered streptokinase. Studies comparing the two Group A streptokinases with streptokinase of Group C origin have indicated that the latter streptokinase is intermediate between SK-A and SK-B in regard to its electrophoretic mobility. Immunological data suggest that the Group C streptokinase differs from SK-B but is closely related to SK-A.


Return-to-work interventions for low back pain: a descriptive review of contents and concepts of working mechanisms.
Low back pain is a major medical and social problem associated with disability, work absenteeism and high costs. Given the impact of the problem, there is a need for effective treatment interventions in occupational healthcare that aim at the prevention of chronic disability and the realisation of return to work. These so-called return-to-work (RTW) interventions are becoming increasingly popular. As well as questions concerning the effectiveness of RTW interventions, there are also important questions on the actual content and underlying concepts of these multifactorial intervention strategies. The purpose of this review is to examine the literature on the content and underlying concepts of RTW interventions for low back pain. A systematic literature search identified 14 randomised controlled trials (RCTs) evaluating the effects of 19 RTW interventions. The content and concepts of these RTW interventions are described, compared and discussed in this review. Further, the contents of the RTW interventions are classified by the use of predefined components (physical exercises, education, behavioural treatments and ergonomic measures). The identified RTW interventions varied with respect to the disciplines involved, the target population and the number and duration of sessions. The classification showed that physical exercises were a component of most of the selected interventions, followed by education, behavioural treatments and ergonomic measures. The most prevalent combination of components was the combination of physical exercises, behavioural treatment and education. However, the types of physical exercises, behavioural treatment and education varied widely among the RTW interventions. The described concepts for the physical exercises were an increase of muscle strength, coordination, range of motion of the spine and cardiovascular fitness, and a decrease of muscle tension. Education as a part of RTW interventions is believed to increase the understanding of patients regarding their disorder and treatment. Behavioural treatments were mainly based on the gate control theory of pain (psychophysiological processes are involved in pain perception) and/or the operant conditioning hypothesis (pain behaviour is determined by its consequences). No concepts were described for ergonomic measures. Finally, the plausibility of the described concepts is discussed. Future RCTs on this topic should evaluate the underlying concepts of the RTW intervention in addition to its effectiveness.


Idiopathic and radiation-induced ocular telangiectasia: the involvement of the ATM gene.
To investigate whether individuals, with no family history of ataxia telangiectasia (AT), in whom idiopathic or radiation-induced ocular telangiectasia developed are carriers of ATM gene mutations. The ATM cDNA from lymphoblastoid cell lines established from 16 patients with idiopathic retinal or choroidal telangiectasia and 14 patients with radiation-induced telangiectasia after radiotherapy for age-related macular degeneration (AMD) was screened using the restriction endonuclease fingerprinting technique. The frequency of each detected variant was determined in the French population by either a mass spectrometry-based technique or variant-specific endonuclease digestion. Twenty-one ATM missense alterations, at 10 different sites, 8 of which would result in an amino acid substitution at a conserved position in the ATM protein were found. Four were novel changes, three of which were not detected in the 128 French control subjects screened. Eleven of 16 of the individuals with either idiopathic polypoidal choroidal vasculopathy or juxtafoveolar retinal telangiectasis and 6 of 14 individuals that had choroidal telangiectasis after radiotherapy for AMD carried ATM sequence variants. These latter six individuals had a significantly shorter delay time before the presentation of this vasculopathy compared with those individuals who had a wild-type ATM (11.8 +/- 3.4 months vs. 17.5 +/- 4.5 months, P = 0.024). They had also received a lower average dose of X-rays, although this difference did not reach statistical significance (18.7 +/- 3.9 Gy vs. 23.7 +/- 5.6 Gy, P = 0.09). ATM missense variants could confer an AT-like phenotype and influence the formation of retinal and choroidal vascular abnormalities.


HPV Infection Profiles among People Living with HIV and HPV Vaccine Acceptance among Individuals with Different HIV Infection Statuses in China: A Systematic Meta-Analysis.
To understand the HPV infection profiles among Chinese HIV/AIDS patients and the HPV vaccine acceptance among unvaccinated Chinese people with different HIV infection statuses after the HPV vaccine launch in China, this study searched Web of Science, PubMed, Cochrane Library, Embase, Scopus, CNKI, WANFANG, SinoMed, and VIP databases up to 23 June 2023, according to the registered protocol (CRD42023449913). A total of 58 studies were included. The results showed that the HPV infection rate among Chinese HIV/AIDS patients was 52.54% (95% CI: 42.11-62.86%) and higher in males than in females (74.55% vs. 41.04%); meanwhile, the rate was higher in the anus than in the cervix (69.22% vs. 41.71%). Although there was no statistical difference, the high-risk HPV infection rate (38.98%) was higher than low-risk HPV (23.86%), and single infections were more common (28.84%) than multiple infections (19.23%). HPV vaccine acceptance among the unvaccinated Chinese population was 59.19% (95% CI: 52.50-65.89%), and was slightly higher among HIV-infected rather than non-HIV-infected individuals (67.72% vs. 59.58%). There was a difference in acceptance among respondents from different regions. Although the difference in acceptance rate between males and females was not statistically significant (61.10% vs. 61.18%), MSM had a higher acceptance rate than non-MSM (84.28% vs. 59.05%). HPV infection is prevalent among HIV patients, demonstrating the need to increase the frequency of HPV screening for PLWH. The HPV vaccine acceptance rate is higher than that of non-HIV-infected individuals. Male acceptance is almost the same as female's, with MSM acceptance higher than non-MSM, suggesting that using MSM, especially MSM in PLWH, as an entry point may be a practical avenue to explore to further expand the scope of HPV vaccination.


Systemic Toxoplasmosis in a Horse.
An adult American Quarter Horse gelding with a history of weight loss presented with an acute onset of colic, fever, soft faeces and elevated liver enzymes. At necropsy, there were gastric mucosal masses and evidence of caecal necrosis. Histologically, the masses were lymph nodes with granulomatous inflammation and areas of liquefactive necrosis. Within and surrounding necrotic areas were free and intrahistiocytic clusters of protozoal tachyzoites. Similar but milder inflammation was evident in the spleen, lungs and liver. Necrotizing typhlitis was also evident. Immunolabelling for Toxoplasma gondii was positive and the ultrastructural morphology of the protozoa was compatible with T. gondii. Although studies have shown seropositivity to T. gondii in horses throughout the world, this is the first report of clinical toxoplasmosis in this species.


Real-world experience with elective discontinuation of PD-1 inhibitors at 1 year in patients with metastatic melanoma.
Randomized trials evaluating programmed cell death protein 1 (PD-1) inhibitors in metastatic melanoma either permitted treatment for 2 years (pembrolizumab) or more (nivolumab). The optimal duration of therapy is currently unknown due to limited data, and shorter therapies may be effective. Data of patients with metastatic cutaneous melanoma treated with single-agent PD-1 inhibitors at Huntsman Cancer Institute from January 1, 2015, to December 31, 2018, was reviewed to identify a continuous series of patients who made the joint decision with their provider to electively discontinue therapy at 1 year (>6 months and <18 months) in the setting of ongoing treatment response or disease stability. Patients were excluded if they received PD-1 inhibitors with other systemic therapy, had prior exposure to PD-1 therapy, or discontinued treatment due to disease progression or immune-related adverse event. Best objective response (BOR) per RECIST V.1.1 at treatment discontinuation, progression-free survival (PFS), and retreatment characteristics was analyzed. Of 480 patients who received PD-1 inhibitors, 52 met the inclusion criteria. The median treatment duration from first to the last dose was 11.1 months (95% CI 10.5 to 11.4). BOR was complete response in 13 (25%), partial response in 28 (53.8%), and stable disease in 11 (21.2%) patients. After a median follow-up of 20.5 months (range 3-49.2) from treatment discontinuation, 39 (75%) patients remained without disease progression, while 13 (25%) had progression (median PFS 3.9 months; range 0.7-30.9). On multivariable analysis, younger age, history of brain metastasis, and higher lactate dehydrogenase at the time of anti-PD-1 discontinuation were associated with recurrence. Patients with recurrent melanoma were managed with localized treatment, anti-PD-1 therapies, and BRAF-MEK inhibitors. All patients except one were alive at data cutoff. In this large real-world, observational cohort study, the majority of patients with metastatic melanoma after 1 year of anti-PD-1 therapy remained without progression on long-term follow-up. The risk of disease progression even in patients with residual disease on imaging was low. After prospective validation, elective PD-1 discontinuation at 1 year may reduce financial and immunotherapy-related toxicity without sacrificing outcomes.


Amoxicillin middle ear fluid penetration and pharmacokinetics in children with acute otitis media.
Acute otitis media (AOM) is a common childhood infectious disease. The efficacy of antibiotic dosing regimens is usually assessed by antibiotic plasma pharmacokinetics or middle ear fluid (MEF) concentration at one or two time points. Viral coinfection in AOM reduced antibacterial efficacy of antibiotics. To determine amoxicillin MEF penetration and pharmacokinetics in bacterial and combined bacterial and viral AOM. Thirty-four children with AOM were enrolled, and MEF was collected by tympanocentesis for bacterial culture and viral studies. Nasal wash and venous blood were also obtained for viral culture and serologic studies, respectively. Subjects were treated with amoxicillin 40 mg/kg/day orally, divided in equal doses every 8 h. During the second visit (48 to 72 h later) the subjects, with the regular morning amoxicillin dose withheld, were given an oral amoxicillin dose of 25 mg/kg. Thereafter two blood samples and one MEF sample by tympanocentesis were collected from each child at selected times between 0.5 and 4.0 h after dosing for bacterial and viral studies and amoxicillin concentration determination by high performance liquid chromatography. Eleven (37%) children had only bacterial infection, 6 (20%) had viral infection only, 6 (20%) had both bacterial and viral infections and in 7 (23%) neither bacterial nor viral pathogens were recovered. MEF bacterial culture was positive in 23 of 40 ears (57.5%) before treatment with amoxicillin (40 mg/kg/day) and was still positive in 4 of 38 ears (10.5%) after 2 to 3 days of treatment. Amoxicillin plasma concentration reached its peak at 1.0 to 1.5 h after a 25-mg/kg oral dose. The estimated MEF concentration peak occurred 3.0 h after the dose with MEF concentrations ranging from undetectable to 20.6 microg/ml and a mean of approximately 9.5 microg/ml. Geometric mean amoxicillin concentrations were lowest in virus-infected children (2.7 microg/ml), nearly the same in culture-negative samples from children without viral infection (2.9 microg/ml), higher in children with combined bacterial and viral infection (4.1 microg/ml) and highest in children with bacterial-only infection (5.7 microg/ml). MEF amoxicillin penetration tended to be lower in children with viral infection. The current amoxicillin dosing recommendation of 40 mg/kg/day in three divided dose is inadequate to effectively eradicate resistant Streptococcus pneumoniae, particularly during viral coinfection. A dosing regimen of 75 to 90 mg/kg/day is recommended for AOM.


Sputum completion and conversion rates after intensive phase of tuberculosis treatment: an assessment of the Rwandan control program.
In Rwanda tuberculosis (TB) is one of the major health problems. To contribute to an improved performance of the Rwandan National TB Control Program, we conducted a study with the following objectives: (1) to assess the completion rate of sputum smear examinations at the end of the intensive phase of TB treatment; (2) to assess the sputum conversion rate (SCR); (3) to assess associations between smear completion rate or SCR with key health facility characteristics. TB registers in 89 health facilities in five provinces were reviewed. Data of new and retreatment smear-positive pulmonary TB (PTB+) cases registered between January and June 2006 were included in the study. Data on key characteristics of the selected health facilities were also collected. Among 1509 new PTB + cases, 32 (2.1%) had died by 2 months, and 178 (11.8%) had been transferred-out. Among the remaining 1299 patients, a smear examination at month 2 was done in 1039 (smear completion rate 80.0%). Among these 1039, 852 (82.0%) had become smear-negative. The smear completion rate and SCR varied considerably between health facilities. A high number of new PTB cases at a health facility was the only significant predictor of a low completion rate, while the only independent factor associated with low sputum conversion rates was rural (vs. urban) location of the health facility. In Rwanda, too few patients get a smear examination after 2 months of TB treatment; the SCR among those with smear results was adequate at 82%. A high number of new TB patients at a health facility was a significant predictor of a low completion rate. The national TB control program should design strategies to improve completion rates.


In vitro dissolution and in vivo gamma scintigraphic evaluation of press-coated salbutamol sulfate tablets.
The aim of this study was to investigate the in vitro and in vivo performance of salbutamol sulfate press-coated tablets for delayed release. The in vitro release behavior of press-coated tablets with the outer layer of PEG 6000/ Eudragit S100 blends (2:1) in pH 1.2 (0.1 mol L-1 HCl) and then pH 6.8 buffer solution was examined. Morphological change of the press-coated tablet during in vitro release was recorded with a digital camera. Release of salbutamol sulfate from press-coated tablets was less than 5 % before 3 h and was completed after 8 h in pH 6.8 phosphate buffer solution. In vivo gamma scintigraphy study carried out on healthy men indicated that the designed system released the drug in lower parts of the GI tract after a lag time of 5 hours. The results showed the capability of the system of achieving delayed release of the drug in both in vitro and in vivo gamma scintigraphy studies.


Incessant ovulation and ovarian cancer - a hypothesis re-visited.
Ovarian cancer continues to be a silent killer. Most women have advanced disease at the time of diagnosis. Intensive efforts to develop effective screening strategies have not so far met with success. There is a need to re-visit the potential of prevention strategies. In 1971, the author submitted a hypothesis for a possible relationship between incessant ovulation and development of epithelial ovarian cancer. Subsequent research from different disciplines opened new frontiers to be explored for prevention in the general population and in high-risk groups, and for opportunistic interventions. The protective effect of oral contraceptive pills has been well documented. Widespread use of the pill in the past several decades is credited with a fall in the incidence of ovarian cancer in the general population, countering the effect of low parity. Removing the barriers against contraceptive access and satisfying the still unmet contraceptive need could expand the protective coverage. Enhanced understanding of the biological mechanisms involved in process of ovulation offers the promise of non-hormonal pharmacologic suppression of follicle rupture for women who have risk factors and do not need contraception. The evidence for a possible origin of epithelial cancer in the fimbria of the Fallopian tube presents an opportunity for preventive intervention, during hysterectomy, where salpingectomy alone may provide protection while one or both ovaries are conserved. Finally, the incessant ovulator egg-laying hen has demonstrated its potential as an experimental model for chemoprevention of epithelial ovarian cancer.


Continuous 24-hour esophageal pH monitoring in 285 asymptomatic infants 0-15 months old.
A continuous 24-h esophageal pH monitoring was performed in 283 asymptomatic infants between 5 days and 15 months old. Several parameters (reflux index, duration of the longest reflux episode, number of reflux episodes in 24 h, number of reflux episodes greater than 5 min in 24 h) were studied in different groups of infants according to their age: 5-15 days old, 24-37 days old, 3.5-4.5 months old, 5.5-6.5 months old, 7.5-8.5 months old, 14-16 months old. For all parameters we obtained statistically significant different results in infants younger and older than 4 months. The 24-h esophageal pH monitoring is an investigation technique in physiological circumstances in order to establish normal ranges for gastroesophageal reflux in asymptomatic infants.


Cangrelor for the treatment of patients with Arterial Thrombosis.
All oral P2Y12 receptor blockers are associated with some degree of delayed onset and offset of pharmacodynamic (PD) effects in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Although intravenous glycoprotein IIb/IIIa inhibitors are associated with rapid onset of action, they are also associated with delayed offset and other limitations such as elevated bleeding risk and thrombocytopenia. Areas covered: In this review, the authors focus on cangrelor, an intravenous, reversible P2Y12 receptor blocker with fast onset and offset of effects. The authors also describe the pharmacologic effects of cangrelor and its pharmacologic interaction with other P2Y12 receptor inhibitors. Finally, the authors discuss the large-scale clinical trials that compared the efficacy and safety of cangrelor with clopidogrel. Expert opinion: In ACS patients undergoing PCI, cangrelor is most desirable to effectively prevent periprocedural ischemic events and to avoid excessive bleeding. Indeed, any high-risk patient with ST-segment elevation myocardial infraction or patient who is unable to take oral medications is a potential candidate for intravenous cangrelor therapy. Furthermore, stable patients with coronary artery disease, who are considered for ad hoc PCI following coronary angiography, may be considered for treatment with cangrelor to reduce post-PCI thrombotic events.


Combining parent and child training for young children with ADHD.
The efficacy of the Incredible Years parent and child training programs is established in children diagnosed with oppositional defiant disorder but not among young children whose primary diagnosis is attention-deficit/hyperactivity disorder (ADHD). We conducted a randomized control trial evaluating the combined parent and child program interventions among 99 children diagnosed with ADHD (ages 4-6). Mother reported significant treatment effects for appropriate and harsh discipline, use of physical punishment, and monitoring, whereas fathers reported no significant parenting changes. Independent observations revealed treatment effects for mothers' praise and coaching, mothers' critical statements, and child total deviant behaviors. Both mothers and fathers reported treatment effects for children's externalizing, hyperactivity, inattentive and oppositional behaviors, and emotion regulation and social competence. There were also significant treatment effects for children's emotion vocabulary and problem-solving ability. At school teachers reported treatment effects for externalizing behaviors and peer observations indicated improvements in treated children's social competence.


Predicting Pathology of Missense Mutations through Protein-Specific Evolutionary Pattern.
Missense mutations, which are single base pair genetic alternation resulting in a different amino acid, are among the most common occurring variants in exon regions of the human genome and may lead to diseases. Thus to assess the effects of missense mutations, it is essential to investigate the evolutionary history of the protein under selection pressures. In this study, we employ a continuous-time Markov model to investigate the evolutionary patterns in protein sequences and a Bayesian Markov chain Monte Carlo method to estimate the substitution rates for protein of interest, from which we obtain scoring matrices. Specifically, we examined the evolutionary patterns of protein sequences containing missense mutations using a species tree to define the phylogeny of the protein of interest. We thoroughly studied the evolutionary pattern of human muscle glycogen phosphorylase containing 127 known missense mutations, and identified characteristic evolutionary patterns in 63 proteins with 2,238 missense mutations, including both deleterious and neutral effects. Our results show that the estimated protein-specific evolutionary pattern-based scoring matrices (PSM) lead to higher sensitivity in detecting the pathological effects of missense mutations, compared to the general evolutionary pattern-based scoring matrix of Blosum62 (BL62) matrix. By incorporating PSM, the performance of a recently released structure-based model SPRI for evaluating missense mutations is further improved.


Age- and Gender-Specific Risk of Thyroid Cancer in Patients With Familial Adenomatous Polyposis.
The cribriform-morula variant of papillary thyroid carcinoma (CMV-PTC) is a rare variant of PTC and is associated with familial adenomatous polyposis (FAP). However, the incidence and the nature of CMV-PTC among FAP patients have not been well characterized. The aim of this study was to determine the incidence and characteristics of thyroid cancer screened by neck ultrasonography for FAP patients. Design, Patients, and Intervention: A total of 129 FAP patients were included in this study. Neck ultrasonography was performed using a 12.0-MHz transducer probe. Germline APC gene mutation was examined for by the protein truncation test or DNA sequencing methods. A total of 129 FAP patients were included in this study. Neck ultrasonography was performed using a 12.0-MHz transducer probe. Germline APC gene mutation was examined for by the protein truncation test or DNA sequencing methods. Twenty-one patients (16.3%) had solid nodules, and 24 patients (18.6%) had benign cystic nodules. In total, PTC was found in 11 patients (16% of the women and 0% of the men), 8 of which were CMV-PTC and the rest were classical PTC. In 17 female patients with thyroid nodules, CMV-PTC occurred in 8 of 9 patients who were 35 years age or younger but in none of the 8 patients who were older than 35 (P = .0004 by Fisher's exact test). The APC germline mutations in 8 patients with CMV-PTC were present at the 5' side of the profuse type of FAP region (codons 1249-1330). The prevalence of CMV-PTC in FAP patients was higher than previously reported and this type of tumor was found preferentially in younger (under age 35) female patients with FAP in this cohort.


A Road Map for Translational Research on Artificial Intelligence in Medical Imaging: From the 2018 National Institutes of Health/RSNA/ACR/The Academy Workshop.
Advances in machine learning in medical imaging are occurring at a rapid pace in research laboratories both at academic institutions and in industry. Important artificial intelligence (AI) tools for diagnostic imaging include algorithms for disease detection and classification, image optimization, radiation reduction, and workflow enhancement. Although advances in foundational research are occurring rapidly, translation to routine clinical practice has been slower. In August 2018, the National Institutes of Health assembled multiple relevant stakeholders at a public meeting to discuss the current state of knowledge, infrastructure gaps, and challenges to wider implementation. The conclusions of that meeting are summarized in two publications that identify and prioritize initiatives to accelerate foundational and translational research in AI for medical imaging. This publication summarizes key priorities for translational research developed at the workshop including: (1) creating structured AI use cases, defining and highlighting clinical challenges potentially solvable by AI; (2) establishing methods to encourage data sharing for training and testing AI algorithms to promote generalizability to widespread clinical practice and mitigate unintended bias; (3) establishing tools for validation and performance monitoring of AI algorithms to facilitate regulatory approval; and (4) developing standards and common data elements for seamless integration of AI tools into existing clinical workflows. An important goal of the resulting road map is to grow an ecosystem, facilitated by professional societies, industry, and government agencies, that will allow robust collaborations between practicing clinicians and AI researchers to advance foundational and translational research relevant to medical imaging.


Quantitative structure-pharmacokinetic relationship (QSPkP) analysis of the volume of distribution values of anti-infective agents from J group of the ATC classification in humans.
In this study, a quantitative structure-pharmacokinetic relationship (QSPkR) model for the volume of distribution (Vd) values of 126 anti-infective drugs in humans was developed employing multiple linear regression (MLR), artificial neural network (ANN) and support vector regression (SVM) using theoretical molecular structural descriptors. A correlation-based feature selection (CFS) was employed to select the relevant descriptors for modeling. The model results show that the main factors governing Vd of anti-infective drugs are 3D molecular representations of atomic van der Waals volumes and Sanderson electronegativities, number of aliphatic and aromatic amino groups, number of beta-lactam rings and topological 2D shape of the molecule. Model predictivity was evaluated by external validation, using a variety of statistical tests and the SVM model demonstrated better performance compared to other models. The developed models can be used to predict the Vd values of anti-infective drugs.


Skeletogenic phenotype of human Marfan embryonic stem cells faithfully phenocopied by patient-specific induced-pluripotent stem cells.
Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in the gene coding for FIBRILLIN-1 (FBN1), an extracellular matrix protein. MFS is inherited as an autosomal dominant trait and displays major manifestations in the ocular, skeletal, and cardiovascular systems. Here we report molecular and phenotypic profiles of skeletogenesis in tissues differentiated from human embryonic stem cells and induced pluripotent stem cells that carry a heritable mutation in FBN1. We demonstrate that, as a biological consequence of the activation of TGF-β signaling, osteogenic differentiation of embryonic stem cells with a FBN1 mutation is inhibited; osteogenesis is rescued by inhibition of TGF-β signaling. In contrast, chondrogenesis is not perturbated and occurs in a TGF-β cell-autonomous fashion. Importantly, skeletal phenotypes observed in human embryonic stem cells carrying the monogenic FBN1 mutation (MFS cells) are faithfully phenocopied by cells differentiated from induced pluripotent-stem cells derived independently from MFS patient fibroblasts. Results indicate a unique phenotype uncovered by examination of mutant pluripotent stem cells and further demonstrate the faithful alignment of phenotypes in differentiated cells obtained from both human embryonic stem cells and induced pluripotent-stem cells, providing complementary and powerful tools to gain further insights into human molecular pathogenesis, especially of MFS.


Etoposide plus G-CSF priming compared with G-CSF alone in patients with lymphoma improves mobilization without an increased risk of secondary myelodysplasia and leukemia.
The use of etoposide (VP-16) for stem cell mobilization has been reported as a significant risk factor for the development of therapy-related myelodysplasia/therapy-related AML (tMDS/tAML) after transplantation. We compared the safety and effectiveness of VP-16+G-CSF (VP+G) to G-CSF alone for PBPC mobilization in patients with non-Hodgkin's lymphoma and Hodgkin's lymphoma who underwent autologous transplantation at the Cleveland Clinic and Ohio State University. In the VP+G group, median total CD34+ cells collected were 9.34 × 10(6) per kg (range 0.97-180.89), with 42% of all patients having adequate (2 × 10(6) cells per kg) CD 34+ collection after 2 days of apheresis compared with a median in the G-CSF group of 3.83 × 10(6) per kg (range, 0.72-50.38), with only 16% patients having adequate collection after 2 days (P<0.001). tMDS/tAML occurred in 15 patients (2.3%) in the VP+G and in 12 patients (3.8%) receiving G-CSF alone. (P=0.62). Increased number of days of apheresis was associated with the risk of tMDS/tAML (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.08-1.30, P<0.001). Priming regimen was not a significant variable for relapse-free survival or OS. The addition of etoposide significantly improves the effectiveness of mobilization at the cost of an increased incidence of neutropenic fever though with no mortalities. There is no evidence of increased incidence of tMDS/tAML in patients receiving VP+G compared with those mobilized with G-CSF alone.


Urinary metabolites as biomarkers of polyphenol intake in humans: a systematic review.
To identify associations between polyphenol intake and health and disease outcomes in cohort studies, it is important to identify biomarkers of intake for the various compounds commonly consumed as part of the diet. The objective of this systematic review was to assess the usefulness of polyphenol metabolites excreted in urine as biomarkers of polyphenol intake in humans. The method included a structured search strategy for polyphenol intervention studies on Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases; formal inclusion and exclusion criteria; data extraction into an Access database; validity assessment; and meta-analysis. One hundred sixty-two controlled intervention studies with polyphenols were included, and mean recovery yield and correlations with the dose ingested were determined for 40 polyphenols. Polyphenols such as daidzein, genistein, glycitein, enterolactone, and hydroxytyrosol showed both a high recovery yield (12-37%) and a high correlation with the dose (Pearson's correlation coefficients: 0.67-0.87), which showed good sensitivity and robustness as biomarkers of intake throughout the different studies. Weaker recovery for anthocyanins (0.06-0.2%) and weaker correlations with dose [Pearson's correlation coefficients: 0.21-0.52 for hesperidin, naringenin, (-)-epicatechin, (-)-epigallocatechin, quercetin, and 3 microbial metabolites of isoflavones (dihydrodaidzein, equol, and O-desmethylangolensin)] suggest that they are currently less suitable as biomarkers of intake. These data confirm the value of certain urinary polyphenols as biomarkers of intake. A validation in populations is now needed to evaluate their specificity, sensitivity, and responsiveness to dose under free-living conditions.


Some kinetic and metabolic characteristics of calcium-induced potassium transport in human red cells.
When fresh human erythrocytes or their ghosts are incubated with Ca + IAA (iodoacetic acid) + adenosine, K permeability increases; K permeability also increases when energy-depleted cells or their ghosts are incubated with Ca alone. Na transport decreases or remains unaltered in both situations. The Ca-induced increase in K permeability in the depleted cell system is qualitatively similar to that seen in the fresh cell system and furnishes a means for studying the metabolic dependence of calcium's action. Studies with the depleted system suggest that the normal refractiveness of the cell to calcium is provided by a metabolically dependent substrate. Removal of this substrate allows Ca to enter the cell and exert its effect. By using (47)Ca, a maximum value was obtained (3-7 x 10(-6) moles/liter of red blood cells) for the quantity of calcium that is taken up by the cell and responsible for the change in K permeability. Measurements of the unidirectional fluxes of K, obtained during the time Ca increases K permeability, appear to satisfy the flux ratio equation for passive diffusion through a membrane.


Assessing the potential information content of multicomponent visual signals: a machine learning approach.
Careful investigation of the form of animal signals can offer novel insights into their function. Here, we deconstruct the face patterns of a tribe of primates, the guenons (Cercopithecini), and examine the information that is potentially available in the perceptual dimensions of their multicomponent displays. Using standardized colour-calibrated images of guenon faces, we measure variation in appearance both within and between species. Overall face pattern was quantified using the computer vision 'eigenface' technique, and eyebrow and nose-spot focal traits were described using computational image segmentation and shape analysis. Discriminant function analyses established whether these perceptual dimensions could be used to reliably classify species identity, individual identity, age and sex, and, if so, identify the dimensions that carry this information. Across the 12 species studied, we found that both overall face pattern and focal trait differences could be used to categorize species and individuals reliably, whereas correct classification of age category and sex was not possible. This pattern makes sense, as guenons often form mixed-species groups in which familiar conspecifics develop complex differentiated social relationships but where the presence of heterospecifics creates hybridization risk. Our approach should be broadly applicable to the investigation of visual signal function across the animal kingdom.


Has psychopharmacology got a future?
Fifty years ago pharmacological discoveries transformed psychiatry but progress since then has been relatively slow and there is unease about the role of industry. Despite this, the possibilities of pharmacological treatment have improved in recent years but exploiting developments for the benefit of patients requires psychotherapeutic skill as well as a high level of scientific knowledge.


Brain mechanisms associated with internally directed attention and self-generated thought.
Internal cognition like imagination and prospection require sustained internally directed attention and involve self-generated thought. This fMRI study aimed to disentangle the brain mechanisms associated with attention-specific and task-specific processes during internally directed cognition. The direction of attention was manipulated by either keeping a relevant stimulus visible throughout the task, or by masking it, so that the task had to be performed "in the mind's eye". The level of self-directed thought was additionally varied between a convergent and a divergent thinking task. Internally directed attention was associated with increased activation in the right anterior inferior parietal lobe (aIPL), bilateral lingual gyrus and the cuneus, as well as with extended deactivations of superior parietal and occipital regions representing parts of the dorsal attention network. The right aIPL further showed increased connectivity with occipital regions suggesting an active top-down mechanism for shielding ongoing internal processes from potentially distracting sensory stimulation in terms of perceptual decoupling. Activation of the default network was not related to internally directed attention per se, but rather to a higher level of self-generated thought. The findings hence shed further light on the roles of inferior and superior parietal cortex for internally directed cognition.


Effect of ethnicity on liver transplant for hepatocellular carcinoma.
The incidence of hepatocellular carcinoma associated with nonalcoholic fatty liver disease is increasing. We sought to compare tumor characteristics and outcomes after a liver transplant according to the cause of liver disease and ethnicity. We retrospectively evaluated patients with hepatocellular carcinoma (292, 23%) out of all the liver transplant recipients (N=1266) at the University of Miami between 2000 and 2010. Liver disease was caused by hepatitis C virus in 221 patients (76%), nonalcoholic fatty liver disease in 19 patients (6.5%), hepatitis B virus in 20 patients (7%), alcohol in 44 patients (15%), and other in 18 patients (6%). The median age was 57 years (range, 17 to 77 y), 218 were men (75%), 270 were white (92%), and 92 were Hispanic (31.5%). Patients with hepatocellular carcinoma and nonalcoholic fatty liver disease were more likely to be older (64 vs 57; P = .0006), Hispanic (58% vs 30%; P = .018); nonsmokers (89% vs 65%; P = .041), diabetic (84% vs 26% P < .0001), hypertensive (63% vs 27%; P = .003), and using statins (32% vs 4%; P = .0004) compared with hepatocellular carcinoma without nonalcoholic fatty liver disease. Diabetes, hypertension, and nonalcoholic fatty liver disease are significantly more common in Hispanics than in non-Hispanic persons with hepatocellular carcinoma. In persons without hepatocellular carcinoma, the proportion of Hispanics was similar between those with (n=84) and those without (n=1182) nonalcoholic fatty liver disease. Hispanic ethnicity was not associated with worse tumor behavior or overall survival. Patients transplanted for hepatocellular carcinoma and nonalcoholic fatty liver disease were older, and were more frequently Hispanic than were persons with hepatocellular carcinoma and without [corrected] nonalcoholic fatty liver disease. Hispanic ethnicity may be a risk factor for hepatocellular carcinoma.


Increasing Prevalence of Chronic Hepatitis C Virus Infection in a Southern Academic Obstetrical Clinic.
The opioid epidemic has resulted in rising rates of hepatitis C virus (HCV) infection in women of childbearing age. With this changing epidemiology in mind, the Infectious Diseases Society of America/American Association for the Study of Liver Diseases guidelines were updated in 2018 to recommend screening all pregnant women for HCV infection, irrespective of risk factors. Because HCV infection can affect maternal-fetal health and result in vertical transmission, presentation for pregnancy-related medical care represents an opportunity to diagnose and manage HCV infection, as well as prepare for treatment postpartum. We performed a retrospective chart review spanning 2007-2016 to examine the epidemiology of HCV infection and opioid use disorder in a southern academic obstetrical clinic and to explore the impact of new screening guidelines if implemented. Composite data from the electronic health record and individual chart review were used to determine rates of HCV infection and opioid use disorder in obstetrics, explore patient demographics, and examine perinatal outcomes. Rates of both opioid use disorder and chronic HCV infection increased significantly during the 10-year period of analysis. Patients diagnosed as having chronic HCV infection were primarily white (95%) and there was no observed impact of HCV on perinatal outcomes. HCV testing in pregnancy, even when patients had documented opioid use disorder, was infrequent (0.7% of all pregnancies). Documented follow-up for HCV postpartum for both mothers and infants was incomplete, with only one-third of identified HCV-exposed infants referred and only 9% receiving HCV testing at our institution. HCV prevalence increased between 2007 and 2016, but screening and treatment of HCV in this southern obstetrical cohort was infrequent. The implementation of universal screening in pregnancy will likely identify additional cases, and an improved cascade of care will be necessary to address the HCV epidemic.


STAR3D: a stack-based RNA 3D structural alignment tool.
The various roles of versatile non-coding RNAs typically require the attainment of complex high-order structures. Therefore, comparing the 3D structures of RNA molecules can yield in-depth understanding of their functional conservation and evolutionary history. Recently, many powerful tools have been developed to align RNA 3D structures. Although some methods rely on both backbone conformations and base pairing interactions, none of them consider the entire hierarchical formation of the RNA secondary structure. One of the major issues is that directly applying the algorithms of matching 2D structures to the 3D coordinates is particularly time-consuming. In this article, we propose a novel RNA 3D structural alignment tool, STAR3D, to take into full account the 2D relations between stacks without the complicated comparison of secondary structures. First, the 3D conserved stacks in the inputs are identified and then combined into a tree-like consensus. Afterward, the loop regions are compared one-to-one in accordance with their relative positions in the consensus tree. The experimental results show that the prediction of STAR3D is more accurate for both non-homologous and homologous RNAs than other state-of-the-art tools with shorter running time.


Identification of Temporal Characteristic Networks of Peripheral Blood Changes in Alzheimer's Disease Based on Weighted Gene Co-expression Network Analysis.
Alzheimer's disease (AD) is a progressive neurodegenerative disease. The study of blood-based biomarkers has lasted for a long time in AD, because it supports the concept that peripheral changes are involved in AD pathology. But it is still unclear how peripheral blood is involved in the temporal characteristic molecular mechanisms of AD from aging to mild cognitive impairment (MCI) and which cells are responsible for the molecular mechanisms. The main purpose of our study is to gain a systematic and comprehensive understanding of temporal characteristic networks of peripheral blood in AD using whole blood samples with 329 case-control samples, including 104 normal elderly control subjects (CTL), 80 MCI who are susceptible to AD, and 145 AD, by the weighted gene co-expression network analysis (WGCNA). The module-trait relationships were constructed and module preservation was validated with independent datasets GSE63061, GSE97760, GSE18309, GSE29378, GSE28146, and GSE29652. Our results indicate that the down-regulated protein modification and ubiquitin degradation systems, and the up-regulated insulin resistance both play a major role in MCI, while the up-regulated inflammatory cascade dominates in AD, which is mainly mediated by monocytes, macrophages. Although there is mixed activation of M1 and M2 macrophages in all stages of AD, the immune neutral state or M2 polarization may predominate in MCI, and M1 polarization may predominate in AD. Moreover, we found that TRPV2, NDUFV1, ATF4, HSPA8, STAT3 and LUC7L3 may mediate the pathological changes in MCI, while SIRPA, LAMP-2, NDUFB5, HSPA8, STAT3 and FPR2 may mediate the conversion from MCI-AD or the pathological changes in AD, which provide a basis for the treatment based on the peripheral blood system. In addition, we also found that the combined diagnosis based on a panel of genes from the red, blue, and brown modules have a moderate diagnostic effect on distinguishing MCI and AD from CTL, suggesting that those panels of genes may be used for detection of MCI and prediction of this conversion from MCI to AD. Our research emphasizes that pathological changes, based on temporal characteristics of peripheral blood, provide a theoretical basis for targeted peripheral treatment based on appropriate times and identified several diagnostic markers.


Protective behavioral strategies underutilization mediates effect of a brief motivational intervention among socially anxious undergraduate drinkers.
Social anxiety (SA) is implicated in problematic undergraduate drinking. Brief motivational interventions (BMIs) reduce problematic undergraduate drinking. However, not all students benefit. Identification of vulnerable subgroups is an important next step. The current study examined the role of SA and protective behavioral strategies (PBS) on BMI outcomes. We reanalyzed a subset of data (53.3%; N = 120; 62.5% male) from a randomized trial in which heavy drinking undergraduates were randomized to a BMI or control. SA, past-month typical drinks, peak drinks, weekly quantity, alcohol problems, and PBS were assessed at baseline and 6 weeks. Main effects and interaction among the intervention condition (BMI vs. control) and SA group (low vs. high) were tested on alcohol outcomes and PBS. High SA undergraduates reported greater baseline drinking, more alcohol problems, and lower PBS. Post-BMI, high SA drinkers continued to report greater peak drinks, typical drinks, alcohol problems, and lower PBS use, controlling for baseline use. Among the BMI condition, parallel multiple mediation analyses revealed the PBS subscale Manner of Drinking uniquely mediated the relationship between SA and heavier post-BMI drinking. The PBS Manner of Drinking and Serious Harm Reduction subscales jointly mediated the relationship between SA and greater post-BMI alcohol problems. BMIs may need to be refined to improve outcomes for socially anxious drinkers. Increasing PBS utilization post-BMI may help improve BMI efficacy in this vulnerable group. Clinical implications are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Use of a Qualification Phantom for PET Brain Imaging in a Multicenter Consortium: A Collaboration Between the Pediatric Brain Tumor Consortium and the SNMMI Clinical Trials Network.
The purpose of this study was to assess image quality and quantitative brain PET across a multicenter consortium. Methods: All academic centers and children's hospitals in the Pediatric Brain Tumor Consortium (PBTC) scanned a phantom developed by the Society of Nuclear Medicine and Molecular Imaging Clinical Trials Network (SNMMI CTN) for the validation of brain PET studies associated with clinical trials. The phantom comprises 2 separate, fillable sections: a resolution/uniformity section and a clinical simulation section. The resolution/uniformity section is a cylinder 12.7 cm long and 20 cm in diameter; spatial resolution is evaluated subjectively with 2 sets of rods (hot and cold) of varying diameter (4.0, 5.0, 6.25, 7.81, 9.67, and 12.2 mm) and spacing (twice the rod diameter). The clinical simulation section simulates a transverse section of midbrain with ventricles and gray and white matter compartments. If properly filled, hot rods have a 4:1 target-to-background ratio, and gray-to-white matter sections have a 4:1 ratio. Uniformity and image quality were evaluated using the SUV in a small volume of interest as well as subjectively by 2 independent observers using a 4-point scale. Results: Eleven PBTC sites scanned the phantom on 13 PET scanners. The phantom's complexity led to suboptimal filling, particularly of the hot rod section, in 5 sites. The SUV in the uniformity section was within 10% of unity on only 5 of 13 scanners, although 12 of 13 were subjectively judged to have very good to excellent uniformity. Four of 6 hot rods were discernable by all 13 scanners, whereas 3 of 6 cold rods were discernable by only 5 scanners. Four of 13 scanners had a gray-to-white matter ratio between 3.0 and 5.0 (4.0 is truth); however, 11 of 13 scanners were subjectively judged to have very good or excellent image quality. Conclusion: Eleven sites were able to image a powerful phantom developed by the SNMMI CTN that evaluated image uniformity, spatial resolution, and image quality of brain PET. There was considerable variation in PET data across the PBTC sites, possibly resulting from variations in scanning across the sites due to challenges in filling the phantom.


Interobserver agreement of perceived intelligibility of magnitude of r in children.
This study was designed to test whether independent listeners could correctly classify 162 stimuli (words) that started with a multiple trill, magnitude of r, followed by a vowel magnitude of a. The sounds were from 27 Spanish children between the ages of 3.0 and 6.6 years, pronouncing Spanish words current in their vocabulary. Twelve listeners were presented with the recordings of the children's magnitude of r production and were instructed to rate the intelligibility of the pronounced sound as high, medium, or low. Inter-rater agreement ranged from 85 to 96%. Analyses of variance for each of the three production categories showed that there were significant differences, so it seems possible to classify the words starting with a trilled magnitude of r based on auditory-perceptual features into three broad categories according to intelligibility.


Comparison of the transmission characteristics of low and high pathogenicity avian influenza A virus (H5N2).
Low pathogenicity avian influenza A strains (LPAI) of the H5 and H7 type are noted for their ability to transform into highly pathogenic counterparts (HPAI). Here we compare the transmission characteristics in poultry of LPAI H5N2 (A/Chicken/Pennsylvania/83) and corresponding HPAI virus by means of transmission experiments. In the experiments, five inoculated animals are placed in a cage with five contact animals, and the infection chain is monitored by taking blood samples, and samples from the trachea and cloaca. The data are analysed by final size methods and a generalized linear model. The results show that HPAI virus is more infectious and induces a longer infectious period than LPAI. In fact, fully susceptible animals are invariably infected when confronted with HPAI virus and die within six days after infection. Animals previously infected with LPAI virus, on the other hand, survive an infection with HPAI virus or escape infection all together. This implies that a previous infection with LPAI virus effectively reduces susceptibility of the host to infection and decreases transmission of HPAI virus. We discuss the implications of these conclusions for the control and evolution of avian influenza viruses.


A note on monotonicity of item response functions for ordered polytomous item response theory models.
A monotone relationship between a true score (τ) and a latent trait level (θ) has been a key assumption for many psychometric applications. The monotonicity property in dichotomous response models is evident as a result of a transformation via a test characteristic curve. Monotonicity in polytomous models, in contrast, is not immediately obvious because item response functions are determined by a set of response category curves, which are conceivably non-monotonic in θ. The purpose of the present note is to demonstrate strict monotonicity in ordered polytomous item response models. Five models that are widely used in operational assessments are considered for proof: the generalized partial credit model (Muraki, 1992, Applied Psychological Measurement, 16, 159), the nominal model (Bock, 1972, Psychometrika, 37, 29), the partial credit model (Masters, 1982, Psychometrika, 47, 147), the rating scale model (Andrich, 1978, Psychometrika, 43, 561), and the graded response model (Samejima, 1972, A general model for free-response data (Psychometric Monograph no. 18). Psychometric Society, Richmond). The study asserts that the item response functions in these models strictly increase in θ and thus there exists strict monotonicity between τ and θ under certain specified conditions. This conclusion validates the practice of customarily using τ in place of θ in applied settings and provides theoretical grounds for one-to-one transformations between the two scales.


Correlation between annual change in health status and computer tomography derived lung density in subjects with alpha1-antitrypsin deficiency.
There is increasing recognition that questionnaires of health status and lung density measurements are more sensitive tools for assessing progression of emphysema than forced expiratory volume in 1 second (FEV(1)) and transfer coefficient (KCO). A study was undertaken to investigate prospectively the correlation between annual change in health status and computer tomography (CT) derived lung density in subjects with alpha(1)-antitrypsin deficiency. Twenty two patients of mean (SD) age 40.7 (9.2) years with ZZ type alpha(1)-antitrypsin deficiency were investigated at baseline and 30 months later by FEV(1) and KCO, St George Respiratory Questionnaire (SGRQ), and by a spiral CT scan of the chest. CT data of chest images were analysed using software designed for automated lung contour detection and lung density measurements. The density data were corrected for changes in inspiration levels. Changes in lung density, expressed as 15th percentile point or relative area below -950 HU, correlated well with changes in health status (SGRQ total score): R = -0.56, p = 0.007 or R = 0.6, p = 0.003. Neither changes in health status nor changes in lung density correlated significantly with changes in FEV(1) or changes in KCO. The SGRQ total score (which is a global measure in COPD) and lung density (a specific measure of emphysema) are sensitive to deterioration in patients with alpha(1)-antitrypsin deficiency. This finding may facilitate future studies with new drugs specific for emphysema, a frequently occurring component of COPD.


Vascularized fronto-orbital advancement.
Fronto-orbital advancement is the procedure of choice for correction of fronto-orbital recession resulting from coronal synostosis in children. However, long-term follow-up evaluations often reveal "undercorrection" of the deformity with development of recurrent recession of lateral supraorbital regions. One factor that may contribute to this process is devascularization of the fronto-orbital bar during its reshaping and advancement. If subsequent revascularization is suboptimal, excessive resorption or inadequate growth of the bar may lead to supraorbital recession. On the basis of studies of temporal bone grafts, which have shown that vascularized grafts are superior to free bone grafts in terms of bone graft survival, we postulated that maintaining vascularization of the fronto-orbital bar would favor better healing and growth that would translate to more favorable aesthetic results. Herein, we review the vascular anatomy of the fronto-orbital region and report the application in six patients of a technique for fronto-orbital advancement that preserves a significant portion of this blood supply. Technical caveats involved in the successful application of this approach are discussed. The attachment of the periosteum to the lateral two thirds of the supraorbital bar allows additional stability. This prevented the use of plates and screws in these patients.


Purification and characterization of alkaline serine proteinase from photosynthetic bacterium, Rubrivivax gelatinosus KDDS1.
In order to reduce the protein content of wastewater, photosynthetic bacteria producing proteinases were screened from wastewater of various sources and stocked in culture. An isolated strain, KDDS1, was identified as Rubrivivax gelatinosus, a purple nonsulfur bacterium that secretes proteinase under micro-aerobic conditions under light at 35 degrees C. Molecular weight of the purified enzyme was estimated to be 32.5 kDa. The enzyme showed the highest activity at 45 degrees C and pH 9.6, and the activity was completely inhibited by phenylmethyl sulfonyl fluoride (PMSF), but not by EDTA. The amino-terminal 24 amino acid sequence of the enzyme showed about 50% identity to those of serine proteinases from Pseudoalteromonas piscicida strain O-7 and Burkholderia pseudomallei. Thus, the enzyme from Rvi. gelatinosus KDDS1 was thought to be a serine-type proteinase. This was the first serine proteinase characterized from photosynthetic bacteria.


Why is breast-cancer mortality declining?
Population statistics indicate that age-adjusted breast-cancer mortality rates began to decline during the early 1990s in many developed countries. For several decades before 1990, breast-cancer mortality rates in these countries had been either stable or increasing. Many investigators attribute the decline in mortality to mammography screening. However, randomised prospective trials indicate that there is a delay of 10 years before the effect of such screening can be seen in mortality statistics. In many developed countries, screening programmes were launched in the late 1980s and early 1990s, so the sudden decline in breast-cancer mortality in the early 1990s was much too soon to be attributable to mammography screening. In this review, we argue that although some of the decline in breast-cancer mortality is due to a reduction in breast-cancer risk, most of it can probably be attributed to adjuvant systemic therapy and the earlier detection of palpable tumours. We also explain why advances in the treatment of breast cancer might be outpacing the value of mammography screening. Since age-adjusted mortality rates are the most basic measure of progress in the treatment of breast cancer, we suggest that careful scrutiny of recent trends in breast-cancer mortality may provide important insights into the effectiveness of novel strategies for diagnosis and treatment.


Unveiling Distinct Proteomic Signatures in Complicated Crohn's Disease That Could Predict the Disease Course.
Crohn's disease (CD) is characterized by a chronic, progressive inflammation of the gastrointestinal tract often leading to complications, such as strictures and fistulae. Currently, there are no validated tools anticipating short- and long-term outcomes at an early stage. This investigation aims to elucidate variations in protein abundance across distinct CD phenotypes with the objective of uncovering potential biomarkers implicated in disease advancement. Serum samples collected from 30 CD patients and 15 healthy age-matched controls (HC) were subjected to depletion of highly abundant proteins and to a label-free mass spectrometry analysis. Twenty-four proteins were shown to be significantly different when comparing CD with HC. Of these, WD repeat-containing protein 31 (WDR31), and proteins involved in the acute inflammatory response, leucine-rich alpha-2-glycoprotein (LRG1) and serum amyloid A1 (SAA1), were more abundant in the aggressive subgroup. Against standard biomarkers, a positive correlation between SAA1 and WDR31 and C-reactive protein (CRP) was found. In this study, a unique serum biomarker panel for aggressive CD was identified, which could aid in predicting the disease course.


Effects of cardiac rehabilitation on inflammatory biomarkers in unstable ischemic heart disease patients following percutaneous coronary intervention: a randomized controlled study.
Several blood inflammatory markers, such as high-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), are linked to increased risk for cardiovascular diseases. This study aimed to evaluate these inflammatory markers after cardiac rehabilitation (CR) in patients with unstable ischemic heart disease (UIHD) who underwent successful percutaneous coronary intervention (PCI). A cohort of 115 patients with successful PCI due to UIHD enrolled in the study from January 2018 to March 2021. We used a permuted block stratified randomization technique (2 : 1 ratio). Seventy-seven patients were randomized to the CR group and 38 patients to the control group. The CR group underwent a 12-week pre-specified CR regimen. Blood samples were taken at baseline and follow-up at 12 weeks for both groups. Among the 115 patients, 33 patients were female. The mean age was (53 ± 5.55 years) in the control and (53 ± 6.09 years) in the CR group. The two groups were comparable regarding their baseline characteristics and the values of the inflammatory markers. By contrast, at 12 weeks, the inflammatory marker values were significantly lower in the CR group compared to the control group; hs-CRP: 0.11 [0.08-0.14] vs. 0.21 [0.19-0.21], P -value <0.001; NLR: 2.17 [1.42-2.43] vs. 2.26 [2.07-2.6], P -value: 0.016; PLR: 91.2821 [63.3333-103.2000] vs. 92.600 [84.6154-110.0000], P -value: 0.027. CR after PCI in UIHD patients may attenuate some inflammatory markers, which might benefit cardiovascular health. Further studies are required to evaluate these findings with longer follow-up and the powered to measure major cardiovascular event rates.


Thermal Energy during Irreversible Electroporation and the Influence of Different Ablation Parameters.
Irreversible electroporation (IRE) uses high-voltage electric fields to achieve cell death. Although the mechanism of IRE is mainly designated as nonthermal, development of secondary Joule heating is inevitable. The study purpose was to gain understanding of temperature development and distribution during IRE. IRE was performed in a transparent polyacrylamide gel resembling soft tissue. Mechanical effects, changes in temperature gradient, and absolute temperature changes were measured with three different optical techniques (high-speed, color Schlieren, and infrared imaging) to investigate the effect on temperature of variations in voltage, pulse length, active tip length (ATL), interelectrode distance, electrode configuration (parallel, convergent, and divergent), and sequential pulsing (pulse delivery interrupted by breaks). The total delivered energy was calculated. A temperature gradient, starting at the tips of both electrodes and expanding toward each other, developed immediately with pulse delivery. Temperatures increased with increasing voltage (by 2.5°C-40.4°C), pulse length (by 5.3°C-9.8°C), ATL (by 5.9°C-17.6°C), and interelectrode distance (by 7.6°C-21.5°C), in accordance with higher energy delivery. Nonparallel electrode placement resulted in heterogeneous temperature distribution with the peak temperature focused in the area with the shortest interelectrode distance. Sequential pulse delivery significantly reduced the temperature increase compared with continuous pulsing (4.3°C vs 11.7°C). Voltage, pulse length, interelectrode distance, ATL, and electrode configuration each have a strong effect on temperature development and distribution during IRE. Sequential pulsing reduces the extent and volume of thermal distribution and may prove beneficial with respect to procedural safety.


Kaposi's sarcoma and HTLV-III: a study in Nigerian adult males.
Sera from 37 adult Nigerian men with Kaposi's sarcoma (KS), 30 contemporaneous controls bearing primary cell carcinoma of the liver (PCL), and 150 healthy non-tumour-bearing negative controls were tested for antibody to human T-cell lymphotropic virus type III/lymphadenopathy associated virus (HTLV-III/LAV) by enzyme-linked immunosorbent assays (ELISA). Certain immunocellular functions were also measured: the chemotactic locomotion of peripheral blood monocytes towards casein, delayed-type cutaneous hypersensitivity reaction to tuberculoprotein and opportunistic infection with the fungus Candida albicans. Sera from all these groups were also tested for markers of previous infections with the viruses cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B (HBV) and hepatitis A (HAV). All serum samples tested were reproducibly and consistently negative for anti-HTLV-III/LAV. Peripheral blood monocytes from both KS and PCL patients showed profound depression of chemotaxis; similarly all tumour patients gave markedly depressed cutaneous reactivity to tuberculoprotein and uniformly exhibited seropositivity to CMV, EBV, HBV and HAV. A great majority showed evidence of infection with Candida albicans. It is concluded that tropical African KS is not associated with HTLV-III/LAV infection.


Effect of chondral defect size, shape, and location on MRI diagnostic performance in the porcine knee.
The purpose of this study was to determine the sensitivity and positive predictive value of magnetic resonance imaging (MRI) in the identification of full-thickness articular cartilage defects in the porcine knee. Seventy-two full-thickness chondral defects (small or large; circular, oval, or triangular) were created in 12 porcine knees. The authors used 3.0-T MRI with 3-dimensional gradient echo water-selective/fluid (WATSf) sequences acquired in axial, coronal, and sagittal planes. Sensitivity and positive predictive value parameters were calculated for 2 readers. Magnetic resonance imaging was highly sensitive for detection of full-thickness defects in the knee (85%). The highest sensitivity was observed at the medial femoral condyle (93%), while the lowest was observed at the medial patella (71%). The sensitivities for detecting different shapes were unique to each shape, with oval lesions identified with greatest sensitivity (93%). Small lesions (86%) were detected at a similar sensitivity as large lesions (83%). The positive predictive values for accurate true-positive reads were low for all lesion shapes (18%-57%) and moderate for small (69%) and large (59%) sizes, with significant differences observed between the 2 readers. Magnetic resonance imaging has a high sensitivity in the detection of full-thickness articular cartilage defects in the porcine knee. Variability in defect shape and intra-articular location affects MRI sensitivity, while size does not. Magnetic resonance imaging was not effective in describing lesion shape or size. Further, there was subjectivity in reading defect shape and size between 2 radiologists.


Sensitivity and specificity of presumptive tests for blood, saliva and semen.
Despite their wide use, the limits of presumptive tests can be poorly understood. The aim of this study was to investigate the specificity and sensitivity of conventional, as well as innovative, presumptive tests for blood, semen and saliva. We investigated Kastle-Meyer (KM) and leucomalachite green (LMG) tests for blood with regard to their sensitivity and specificity in the presence of oxidizing (hypochlorite) and anti-oxidizing (ascorbic acid) agents. The suitability and specificity of the red starch paper (RSP) test for saliva was assessed. Finally, the inhibitory effect of detergent on the acid phosphatase (AP) test for semen was investigated along with possible cross reactions to tea stains. Our results confirm previous findings of higher sensitivity and specificity of the KM test compared to LMG test for blood. Contrary to previous studies, no statistically significant difference was observed in the sensitivity of the tests between dry and wet stains. The novel RSP test was found to successfully detect saliva. We demonstrated that acid phosphatase (AP) testing for semen is possible on used RSP. A common multipurpose detergent had an inhibitory effect on AP tests. False positive results were obtained from tea stains. Testing different sorts of tea (black, green and herbal teas) revealed that only Camellia varieties produce positive result with the AP test, due to AP being present in the plants. From our results we conclude that specific knowledge of each test, including substances that may affect the test outcome, is imperative to ensure correct interpretation of presumptive test results.


Anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory conditions induced by PTY-2 against STZ-induced stress in islets.
The earlier assessment of Pueraria tuberosa (PT) has shown anti-diabetic effects through enhancing incretin action and DPP-IV (Dipeptidyl peptidase-IV) inhibition. The aim of this work was to further explore the protective role of aqueous extract of Pueraria tuberosa tuber (PTY-2) against streptozotocin (STZ) induced islet stress in rats. Diabetes was induced by STZ (65 mg/kg body weight) in charles foster male rats. After 60 days of STZ administration, animals with blood glucose levels > 200 g/dL were considered as diabetic. All the rats were later divided into three groups: Group-1 (STZ untreated normal rats), Group-2 (Diabetic control), and Group-3 (PTY-2 [50 mg/100 g bw treatment for next 10 days to diabetic rats). The rats were then sacrificed after the 10th day of treatment accordingly. STZ treatment led to an increase in expression of Matrix metalloproteinases-9 (MMP-9), Tumour necrosis factor-α (Tnf-α), Hypoxia inducible factor-α (HIF-1α), Vascular endothelial growth factor (VEGF), Interleukin-6 (IL-6), Protein kinase C-ε (PKC-ε), Nuclear factor kappa-light-chain-enhancer of activated B-cells (NFkB), and Caspase-3. Reverse Transcriptase-PCR (RT-PCR), Immunohistochemistry and Western-Blot analysis showed an increase in the expressions of Superoxide Dismutase (SOD) and Nephrin, and a decrease in the expressions of NFkB, PKC-ε, TNF-α, MMP-9, HIF-1α, VEGF, Caspase-3 and IL-6 after 10 days of PTY-2 treatment. The results showed that PTY-2 favorably changed all the expressions via anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory pathways, making itself as a protective agent against STZ induced islet stress. Further evaluation of PTY-2 might be helpful in establishing its role in the management of diabetes mellitus.


Low-dose doxorubicin with carotenoids selectively alters redox status and upregulates oxidative stress-mediated apoptosis in breast cancer cells.
The combination of carotenoids and doxorubicin (DOX) selectively alters oxidative stress-mediated apoptosis in breast cancer cells. Primarily, cytotoxic efficiency of carotenoids (β-carotene, BC; lutein, LUT; astaxanthin, AST; or fucoxanthin, FUCO) either with or without a minimal cytotoxic dose of DOX was evaluated in MCF-7 (0.12 μM) and MDA-MB-231 cells (0.28 μM). The higher cell growth inhibition of BC and/or LUT with DOX was selected for testing in further cell-based assays. Low-dose DOX significantly enhanced cytotoxicity in carotenoid (<5 μM)-treated cells compared to high-dose DOX (>1 μM) or carotenoid (20 μM) treatment alone. Depleted glutathione, increased lipid peroxides and increased ROS levels in cells confirmed the cytotoxic effect. Furthermore, mitochondrial dysfunction, cell growth arrest at G0/G1 phase and caspase cascades as well as up- and down-regulated expression levels of related proteins (p21, p27, Bax, p53, Bcl-2, and cyclin D1) revealed the synergistic effect of carotenoid and DOX treatment on ROS-mediated apoptosis. These observations demonstrated increased apoptosis in BC + DOX/LUT + DOX-treated cells due to the pronounced pro-oxidant action. Interestingly, normal breast epithelial cells (MCF 10A) exposed to similar treatments resulted in non-significant cytotoxicity. These newly observed mechanistic differences of anticancer drugs on the mitigation of toxicity with carotenoids may provide insight into the targeting of cancer therapy.


Neuroprotective effect of Clerodendrum serratum Linn. leaves extract against acute restraint stress-induced depressive-like behavioral symptoms in adult mice.
The objective of this study was to study the effect of ethanol extract of Clerodendrum serratum (EECS) Linn. on acute restraint stress (ARS)-induced depressive-like behavior and biochemical alterations in mice. Ethyl acetate and n-butanol fractions of EECS were analytically characterized for the flavonoid components, apigenin (API) and luteolin (LUT) by reverse-phase high-performance liquid chromatography. Behavioral tests, namely, forced-swim test and tail-suspension test were performed for assessing antidepressant-like effect and anxiolytic activity in mice. Oxidative stress parameters and biochemical alterations in mice brain tissue were also performed. Expression of data was done as mean ± standard error of mean. The normally distributed data were subjected to two-way ANOVA followed by Dunnett's test. P < 0.05 was considered statistically significant. The study showed that flavonoids, API and LUT were present in ethyl acetate and n-butanol fractions of EECS, which significantly reversed ARS-induced depressive-like behavior without affecting locomotion. EECS also attenuated oxidative damage caused by ARS. The level of norepinephrine and 5-hydroxytryptamine was also significantly restored by pretreatment with EECS for 7 days. EECS significantly alleviated ARS-induced depressive-like behavior without affecting locomotion.


UV sensitivity of several genetic markers of Haemophilus influenzae DNA.
Studies on inactivation by UV of several genetic markers of the streptomycin and novobiocin resistance regions of H. influenzae DNA have shown that two kinds of markers may be found with respect to frequency of integration, UV sensitivity and reactivability. One class of markers has high integration frequency and low UV sensitivity, which can be partly explained by the reactivability of the irradiated markers. The second class of markers has low integration frequency and high UV sensitivity. Markers of each class have been found in the novobiocin region.-In one recipient strain with decreased transformability the difference in integration frequency between the two classes is enhanced.


The collection of MicroED data for macromolecular crystallography.
The formation of large, well-ordered crystals for crystallographic experiments remains a crucial bottleneck to the structural understanding of many important biological systems. To help alleviate this problem in crystallography, we have developed the MicroED method for the collection of electron diffraction data from 3D microcrystals and nanocrystals of radiation-sensitive biological material. In this approach, liquid solutions containing protein microcrystals are deposited on carbon-coated electron microscopy grids and are vitrified by plunging them into liquid ethane. MicroED data are collected for each selected crystal using cryo-electron microscopy, in which the crystal is diffracted using very few electrons as the stage is continuously rotated. This protocol gives advice on how to identify microcrystals by light microscopy or by negative-stain electron microscopy in samples obtained from standard protein crystallization experiments. The protocol also includes information about custom-designed equipment for controlling crystal rotation and software for recording experimental parameters in diffraction image metadata. Identifying microcrystals, preparing samples and setting up the microscope for diffraction data collection take approximately half an hour for each step. Screening microcrystals for quality diffraction takes roughly an hour, and the collection of a single data set is ∼10 min in duration. Complete data sets and resulting high-resolution structures can be obtained from a single crystal or by merging data from multiple crystals.


Effects of adjuvant tamoxifen on the endometrium in postmenopausal women with breast cancer: a prospective long-term study using transvaginal ultrasound.
To study the value of transvaginal ultrasound (TVS) in endometrial screening of postmenopausal breast cancer patients treated with tamoxifen. In 247 tamoxifen-treated (20 to 30 mg/d for >/= 2 years) women and 98 controls, the endometrium was prospectively followed-up by means of TVS every 6 months for up to 5 years. Patients with homogeneous endometrium of more than 10-mm thickness were then scanned repeatedly every 3 months. The mean endometrial thickness was 3.5 +/- 1.1 mm before treatment and increased to a maximum of 9. 2 +/- 5.1 mm after 3 years of tamoxifen application (P: <.0001), which was significantly (P: <.0001) thicker compared with controls. Fifty-two asymptomatic patients with thickened or morphologically suspect endometrium underwent hysteroscopy and dilatation and curettage (D&C), resulting in four uterine perforations. Histopathologically, atrophy was found in 38 patients (73.1%), polyps in nine, hyperplasia in four, and endometrial cancer in one case. In 20 screened patients who reported vaginal bleeding, five atrophies (25%), five polyps, four hyperplasias, and two endometrial cancers were found. Before hysteroscopy and D&C were performed, 36 (69.2%) of 52 asymptomatic and four (20%) of 20 symptomatic patients were scanned by repeated TVS over 2 to 30 months. Invasive diagnostic procedures were significantly (P: <.05) more frequent in younger and obese patients. In the controls, one asymptomatic polyp and one symptomatic hyperplasia were found. In tamoxifen-treated patients, TVS offered a high false-positive rate, even with a cutoff value of 10 mm for endometrial thickness and repeated TVS scans. Increased iatrogenic morbidity and only one asymptomatic endometrial carcinoma do not warrant endometrial screening by TVS in tamoxifen-treated patients.


Antiepileptic Drugs in the Neurosurgical Intensive Care.
The etiology of seizures in the Neurosurgical/Neurological Intensive Care Unit (NICU) can be categorized as emanating from either primary brain pathology, at either macro- or microscopic level, or from physiological derangements of critical care illness such as toxic or metabolic abnormalities. Particular etiologies at risk for seizures include ischemic or hemorrhagic stroke and traumatic brain injury. The use of prophylactic antiepileptic drug administration remains controversial in many situations, with most of the larger studies having used older antiepileptic drugs prophylactically. If seizures do occur, patients are typically treated with parenteral antiepileptic drugs. The duration of treatment is unknown in most situations, but it should be individualized depending on acute and monophasic injury versus chronic process. Late seizures, which occur after the first 2 weeks from the insult, have a more ominous risk for subsequent epilepsy and should be treated for extended periods of time or indefinitely. Electrolyte and glucose abnormalities and medications at high or low levels, when corrected, usually lead to seizure control. This review discusses the risk for seizures with commonly encountered types of brain injuries in the NICU and ends by examining the treatment algorithms for simple seizures and status epilepticus and the role newer antiepileptics may potentially play.


The macrophage stimulating protein/Ron pathway as a potential therapeutic target to impede multiple mechanisms involved in breast cancer progression.
Macrophage Stimulating Protein (MSP) is the only known ligand for the receptor tyrosine kinase Ron. The MSP/Ron pathway is involved in several important biological processes, including macrophage activity, wound healing, and epithelial cell behavior. A role for MSP/Ron in breast cancer has recently been elucidated, wherein this pathway regulates tumor growth, angiogenesis, and metastasis. Here, we review the recent literature surrounding MSP/Ron function in tumor cells, inflammatory cells, and osteoclasts - cell types that often coexist in breast tumor microenvironments. We discuss the potential implications of MSP/Ron activity occurring concurrently in these cell types on tumor progression and metastasis. Lastly, we outline the potential for targeting MSP/Ron as a novel therapy for breast cancer, and for other cancer types.


Troubleshooting for Ureteroscopy Complicated by Unexpected Guidewire Looping and Entrapment.
This report presents a bizarre and unusual case of looping and entrapment of a hydrophilic guidewire in the ureter of a 65-year-old woman with a stone in the lower ureter at the time of ureteroscopy and laser lithotripsy. We describe endourology maneuvers to remove the retained guidewire. Looping and entrapment of guidewire is a rare complication that urologists may face when they do not follow the basic principles of guidewire insertion. In that case, successful resolution is based both on surgeon's inspiration to apply the appropriate endourology maneuvers and availability of a variety of endourology tools in the theater. Both may lead urologists to avoid more invasive and morbid approaches for their patients.


Evidence for the confinement of magnetic monopoles in quantum spin ice.
Magnetic monopoles are hypothesised elementary particles connected by Dirac strings that behave like infinitely thin solenoids (Dirac 1931 Proc. R. Soc. A 133 60). Despite decades of searching, free magnetic monopoles and their Dirac strings have eluded experimental detection, although there is substantial evidence for deconfined magnetic monopole quasiparticles in spin ice materials (Castelnovo et al 2008 Nature 326 411). Here we report the detection of a hierarchy of unequally-spaced magnetic excitations via high resolution inelastic neutron spectroscopic measurements on the quantum spin ice candidate [Formula: see text] [Formula: see text] [Formula: see text]. These excitations are well-described by a simple model of monopole pairs bound by a linear potential (Coldea et al Science 327 177) with an effective tension of 0.642(8) K [Formula: see text] at 1.65 K. The success of the linear potential model suggests that these low energy magnetic excitations are direct spectroscopic evidence for the confinement of magnetic monopole quasiparticles in the quantum spin ice candidate [Formula: see text] [Formula: see text] [Formula: see text].


Evaluation of an In Silico PBPK Post-Bariatric Surgery Model through Simulating Oral Drug Bioavailability of Atorvastatin and Cyclosporine.
An increasing prevalence of morbid obesity has led to dramatic increases in the number of bariatric surgeries performed. Altered gastrointestinal physiology following surgery can be associated with modified oral drug bioavailability (Foral). In the absence of clinical data, an indication of changes to Foral via systems pharmacology models would be of value in adjusting dose levels after surgery. A previously developed virtual "post-bariatric surgery" population was evaluated through mimicking clinical investigations on cyclosporine and atorvastatin after bariatric surgery. Cyclosporine simulations displayed a reduced fraction absorbed through gut wall (fa) and Foral after surgery, consistent with reported observations. Simulated atorvastatin Foral postsurgery was broadly reflective of observed data with indications of counteracting interplay between reduced fa and an increased fraction escaping gut wall metabolism (FG). Inability to fully recover observed atorvastatin exposure after biliopancreatic diversion with duodenal switch highlights the current gap regarding the knowledge of associated biological changes.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e47; doi:10.1038/psp.2013.23; advance online publication 12 June 2013.


Transform coded image reconstruction exploiting interblock correlation.
Transmission of still images and video over lossy packet networks presents a reconstruction problem at the decoder. Specifically, in the case of block-based transform coded images, loss of one or more packets due to network congestion or transmission errors can result in errant or entirely lost blocks in the decoded image. This article proposes a computationally efficient technique for reconstruction of lost transform coefficients at the decoder that takes advantage of the correlation between transformed blocks of the image. Lost coefficients are linearly interpolated from the same coefficients in adjacent blocks subject to a squared edge error criterion, and the resulting reconstructed coefficients minimize blocking artifacts in the image while providing visually pleasing reconstructions. The required computational expense at the decoder per reconstructed block is less than 1.2 times a non-recursive DCT, and as such this technique is useful for low power, low complexity applications that require good visual performance.


A comparative study of the tapetum, retina and skull of the ferret, dog and cat.
Results of this investigation indicate that the ferret (Mustela putorius) closely resembles the dog (Canis familiaris) and should be a useful research animal alternative. The tapetum lucidum is a common structure present in the eyes of dogs, cats (Felis catus) and other nocturnal animals. Our study showed that this structure was present in ferret eyes. The color or reflection of the ferret and dog tapetum was remarkably reduced by the general fixation with glutaraldehyde. However, this color fading phenomenon was not observed in the cat tapetum. These observations led to this comparative study on several morphological, histochemical and biochemical parameters on mature ferrets, dogs and cats including: (1) the number of center tapetum cell layers, (2) thickness of center tapetum, (3) presence of a microtubule-like structure in each tapetal rod, (4) presence of electron-dense cores in tapetal rods after prolonged fixation in glutaraldehyde, (5) retention of reflection or color of tapetum after prolonged glutaraldehyde fixation, (6) zygomatic bones of eye orbits, (7) zinc content in tapetum, (8) cysteine in the tapetum, (9) cysteine sulfinic acid decarboxylase in liver, (10) thickness of retina from center tapetum, (11) anterior view of skull configuration, and (12) lateral view of skull configuration (jaw and teeth). Among these 12 parameters, ferret and dog were similar in the first nine points; ferret and cat were similar to each other only in the last two points. There was no difference in retinal thickness among these three animals.