Ultrastructural morphology of hypomelanosis in equine cutaneous papilloma.
The morphology of hypomelanosis occurring in experimentally induced equine papillomas was investigated. Histologically, dopa-positive functioning melanocytes were decreased in number from the basal layer in the epidermis. Electron-microscopically, melanogenic organelles in the melanocytes were degenerate and melanosomes were decreased in number and size. In addition, the melanocytes had some abnormal melanosomes including melanosome complexes and giant melanosomes. Some abnormal melanosomes were also present in the keratinocytes. The hypomelanosis seemed to be related to a disturbance in melanin synthesis and melanocytic-keratinocytic interaction in the epidermal melanin unit.


Purification and properties of cytochrome c-553, an electron acceptor for formate dehydrogenase of Desulfovibrio vulgaris, Miyazaki.
Cytochrome c-553 of Desulfovibrio vulgaris, Miyazaki, was purified to homogeneity. The absorption spectrum of the ferro form has four peaks at 553, 525, 417 and 317 nm with a plateau near 280 nm, and that of the ferri form has three peaks at 525, 410 and 360 nm with a plateau near 280 nm and a shoulder at 560 nm. The millimolar absorbance coefficient of the alpha-peak of the ferro form is 23.9. The molecular weight of cytochrome c-553 is 8000, and it contains one heme. Its isoelectric point is rather alkaline, and its standard redox potential is -0.26 V at pH 7.0. Its amino acid composition is unique; it lacks proline, isoleucine and tryptophan. Ferrocytochrome c-553 does not combine with CO, nor does it transfer electrons directly to various redox carriers such as flavin nucleotides, methylene blue, indigodisulfonate, 5-methylphenazinium methyl sulfate, 1-methoxy-5-methylphenazinium methyl sulfate, viologens and cytochrome c3, but is oxidized by ferricyanide or by O2. Cytochrome c-553 can be reduced by formate dehydrogenase of this bacterium in the presence of formate, but not by hydrogenase under H2. The formate dehydrogenase does not reduce cytochrome c3 in the presence of formate. The systematic name for formate dehydrogenase of D. vulgaris is, therefore, established as formate:ferricytochrome c-553 oxidoreductase in EC subclass 1.22.-.


Use, satisfaction, and preference of online health services among older adults with multimorbidity in Hong Kong primary care during COVID-19.
The use of online and mobile internet and social media has been increasing in healthcare service delivery. However, there is limited literature on the acceptance and use of online health services for older adults with multimorbidity who require more medical care and assistance. This study aims to explore the use of social media in older adults with multimorbidity in Hong Kong primary care and to assess the feasibility and usage of online health services in this population, including satisfaction, preference, and problems encountered. This is a cross-sectional study among older adults with multimorbidity conducted between November 2020 and March 2021 in a Hong Kong primary care programme. Online and face-to-face services were offered based on the needs of the participants. Demographic characteristics and health conditions were assessed at baseline. Participants using online services were invited to complete a feedback questionnaire. The study included 752 participants, of which 66.1% use social media every day. Participants who declined to use online services were found to be significantly older, live alone, have lower income, have social security assistance, have greater cognitive decline, and be less depressed (p < 0.05). Non-responders to the online questionnaire had fewer years of education and greater cognitive decline (p < 0.05). The median satisfaction with the online services was 8 (interquartile range: 7, 9), and 14.6% of the participants preferred online more than face-to-face services. Lower education levels, fewer internet connection issues, and more self-efficacy on mobile apps were associated with a higher level of online satisfaction after adjustment (p < 0.05). Fewer internet connection issues and more self-efficacy on mobile apps were associated with participants' preference for online services (p < 0.05). More than half of Hong Kong older adults with multimorbidity in primary care use social media daily. Internet connection issues can be a significant barrier to the usage of online services in this population. Prior use and training can be beneficial to enhance use and satisfaction in older adults.


Short communication: Is there any benefit of initiating aspirin before the 11th week of gestation?
Aspirin initiated between 11 and 14 weeks of gestation reduces the risk of preterm preeclampsia and other placenta-mediated complications in screen-positive women. Most of these adverse outcomes are associated with maternal vascular malperfusion of the placenta, a disease that begins during the early first trimester. Assuming that aspirin has direct beneficial actions on the developing placenta, tempts clinicians to believe in the maxim that "the earlier the better", however neither the safety nor the effectiveness of aspirin started before 11th week of gestation has been demonstrated. Therefore, outside of research protocols, aspirin should not be started before the 11th week of pregnancy for the prevention of preeclampsia.


A new small temperate DNA phage BcP15 isolated from Burkholderia cepacia DR11.
A Burkholderia cepacia DR11 strain was isolated during the survey of microorganisms from coastal water of deltaic Sunderbans. This strain always released temperate phage BcP15 into culture supernatant. UV irradiation of the strain also induced phage induction. The phage titer was 2.3 x 10(8). New temperate phage BcP15 has unusual structure. It has a hexagonal head, 65 nm in diameter and a tail 200 nm long, attached with single thick wavy tail fiber (424-705 nm). Phage DNA is double stranded 11.9 kb long. Southern hybridization result indicated that the phage DNA was in lysogenic state into the B. cepacia DR11 genome. SDS-PAGE of phage protein showed two major bands of molecular weight 20 kDa and 40 kDa.


Are modified Fisher Scale and bleeding pattern helpful predictors of neurological complications in non-aneurysmal subarachnoid hemorrhage?
Non-aneurysmal subarachnoid hemorrhage (NA-SAH) is a clinical-radiological entity with a different prognosis than aneurysmal SAH (A-SAH). The purpose of this study is to assess the predictive value of the modified Fisher Scale (mFS) for neurological complications in patients with this diagnosis. We recruited patients admitted at our hospital services between 2009 and 2017 who were diagnosed with spontaneous SAH, with either perimesencephalic (PM-SAH) or diffuse pattern (D-SAH), an initial negative angio-CT, and at least one digital subtraction angiography of brain vessels discarding underlying brain aneurysms or other vascular malformations. The retrospective observational study included 116 patients. The mean age was 54.4, and the sample included predominantly male subjects (62.9%). Hunt and Hess (HH) scores on admission ranged from 3 to 5 in 18.1% of patients. The prevalence of hydrocephalus requiring ventricular drainage was 18.1%. The prevalence of symptomatic vasospasm was 4.3%. A modified Rankin Scale (mRS) 0-2 at discharge was found in 95.6%. In a multivariate logistic regression for the presence of neurological complications including age, sex, admission HH 3-5 compared with < 3, mFS 4 compared with mFS < 4, D-SAH compared with PM-SAH, and mRS score at discharge of 0-2 compared with > 2, the only significant predictors were mFS 4 compared with mFS < 4 (OR 4.47 (95% CI 1.21, 16.66) p value = 0.03) and D-SAH compared with PM-SAH (OR 7.10 (95% CI 1.24, 40.8) p value = 0.03). In patients with NA-SAH, a mFS score of 4 and/or a D-SAH bleeding pattern in non-contrast cranial CT on admission predicted the development of relevant neurological complications.


Evaluation and comparison of errors on nursing notes created by online and offline speech recognition technology and handwritten: an interventional study.
Despite the rapid expansion of electronic health records, the use of computer mouse and keyboard, challenges the data entry into these systems. Speech recognition software is one of the substitutes for the mouse and keyboard. The objective of this study was to evaluate the use of online and offline speech recognition software on spelling errors in nursing reports and to compare them with errors in handwritten reports. For this study, online and offline speech recognition software were selected and customized based on unrecognized terms by these softwares. Two groups of 35 nurses provided the admission notes of hospitalized patients upon their arrival using three data entry methods (using the handwritten method or two types of speech recognition software). After at least a month, they created the same reports using the other methods. The number of spelling errors in each method was determined. These errors were compared between the paper method and the two electronic methods before and after the correction of errors. The lowest accuracy was related to online software with 96.4% and accuracy. On the average per report, the online method 6.76, and the offline method 4.56 generated more errors than the paper method. After correcting the errors by the participants, the number of errors in the online reports decreased by 94.75% and the number of errors in the offline reports decreased by 97.20%. The highest number of reports with errors was related to reports created by online software. Although two software had relatively high accuracy, they created more errors than the paper method that can be lowered by optimizing and upgrading these softwares. The results showed that error correction by users significantly reduced the documentation errors caused by the software.


Soluble CD4, CD8 in patients with polymyositis/dermatomyositis.
The concentrations of soluble CD4 (sCD4) and soluble CD8 (sCD8) were determined in 64 patients with polymyositis/dermatomyositis (PM/MD). The patients with PM/DM had significantly higher concentrations of sCD8, though the concentrations of sCD4 did not significantly increase. Patients with high concentrations of sCD8 tended to have too high concentrations of soluble interleukin-2 receptor (sIL-2R). The patients with high levels of myogenic enzymes tended to have high concentrations of sCD8. The results of a serial study indicated that the concentrations of sCD8 decreased simultaneously with the decrease of the myogenic enzymes. These results may suggest that the activation of CD8+ cells are related to muscular involvement.


Analysis of morbidity and mortality in patients 70 years of age and over undergoing isolated coronary artery bypass surgery.
With increasing frequency more elderly patients are referred for coronary artery bypass surgery. The operative results of 201 patients 70 years of age and over were compared with the results of 1242 patients under 70 years operated on since 1981. A larger percentage of the elderly patients had triple-vessel disease (66.2% vs 51.0%, p less than 0.001), left main coronary artery obstruction (34.8% vs 16.3%, p less than 0.01), and an ejection fraction of less than or equal to 45% (30.8% vs 21.1%, p less than 0.001). An increase percentage of the patients 70 years of age and over had perioperative myocardial infarction (7.9% vs 4.1%, p less than 0.05), required prolonged ventilatory support (7.9% vs 3.1%, NS), and had major neurologic complications (4.0% vs 1.1%, p less than 0.001). The mortality rate was significantly higher in the elderly patients (5.9% vs 1.9%, p less than 0.01) but did not correlate with degree of coronary artery disease, anginal pattern, or preoperative ventricular function. Only 2 of 12 deaths in the elderly patients were from cardiac causes. This data would suggest that elderly patients have an increased risk for significant cardiac and noncardiac morbidity and mortality following coronary artery bypass surgery and that the higher mortality rate in this age group may be a result of noncardiac organ failure.


Regional cerebral blood flow changes in depression after electroconvulsive therapy.
A large number of studies have documented regional cerebral blood flow (rCBF) abnormalities in depression. A smaller yet significant number of studies have examined changes in rCBF before and after treatment. The findings, however, have been variable with regard to changes before and after electroconvulsive therapy (ECT). A consecutive series of patients (n=10) with drug-resistant major depressive episode according to DSM-IV with 17-item Hamilton Rating Scale for Depression (HRSD) scores greater than or equal to 14 gave their informed consent and were studied with technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (99mTc-ECD SPECT) before and after a course of ECT. The results were analyzed with statistical parametric mapping version 99. No region showed significant positive correlations between rCBF patterns of changes and HRSD changes, but three clusters emerged as showing significant negative correlations. These regions corresponded with left frontopolar gyrus, left amygdala, globus pallidus and nucleus accumbens, and left superior temporal gyrus. It was speculated that ECT affected both the prefrontal cortex, commonly assumed to be involved in depression, and the amygdala, known to play a central role in the processing of emotional stimuli, through the limbic-cortical-striatal-pallidal-thalamic circuit.


Morphologic aspects of bone healing after third-degree open fractures. An experimental study.
The morphologic aspects of undisturbed and disturbed bone healing following third-degree open fractures is demonstrated by means of experimental investigations using animals. As an experimental model we used a canine thigh fractured by a shot. The data was obtained as part of bioballistic investigations of the effect of highvelocity bullets in living tubular bones. The shot fracture was immobilized by external fixation. Progressive radiological controls, as well as microangiographic, microradiographic and histological findings are used to show bone healing. Bone healing following shot fractures follows the basic pattern of secondary bone healing, which is manifested in an X-ray by the formation of periosteal callus. The periosteal callus tissue has its own vascular system and receives blood from the extraosseous vessels of the adjacent soft tissue surrounding it. It not only fulfills the function of the biological stabilizer of the fragments, but also contributes decisively to their revascularization through transcortical anastomosis. The morphologic appearance and the causes for the disruption of bone healing are demonstrated using individual examples. Predominant are insufficient stability and above all circulatory disturbances. In the case of fractures with considerable soft-tissue damage, not only is the intramedullary vascular system destroyed, but the blood supply to the periosteal vessels is also disrupted. The resulting delay to or absence of callus formation leads on the one hand to insufficient biological stabilization, and on the other hand to an impairment of fragment revascularization. The morphologic appearance is dominated by the fragment necroses and related complications, such as pseudarthrosis induced by bone necrosis and infected pseudarthrosis.


Concomitant transabdominal MIDCAB and abdominal aortic aneurysm repair.
We present 2 patients who underwent transabdominal minimally invasive direct coronary artery bypass with the right gastroepiploic artery combined with abdominal aortic aneurysm repair. The surgical procedures, both performed through a median laparotomy, proved safe and of limited invasiveness. The one-stage surgical intervention prevented catastrophic complications, such as acute myocardial infarction or rupture of abdominal aortic aneurysm. We believe that concomitant transabdominal minimally invasive direct coronary artery bypass and abdominal aortic aneurysm repair should be considered as a single combined surgical strategy in selected patients.


The effect of tendon on muscle force in dynamic isometric contractions: a simulation study.
Recently, Baratta and Solomonow J. Biomechanics 24, 109-116 (1991) studied the effect of tendon on muscle-tendon complex behavior in cat tibialis anterior (TA) muscle. This was done by determining the relation between neural stimulation and muscle force in a dynamic isometric experiment, both before and after the removal of the distal tendon. From their results, Baratta and Solomonow concluded that in isometric and concentric contractions at mid-range force levels, tendon behaves as a rigid force conductor. This conclusion is in conflict with literature in which several functions are attributed to the elastic behavior of the series elastic element (SEE), of which tendon is the major part. The present study investigates the expected generalizability of their findings, by simulating the experiments using a straightforward Hill-type muscle model. First, model predictions are shown to be in line with the experimental results on cat TA: in dynamic isometric experiments at mid-range force levels, the effect of SEE removal is indeed negligible. Second, the effect of SEE removal is predicted to vary largely among muscles. Third, the most important determinants of the effect of SEE removal in dynamic isometric contractions are shown to be maximum fiber shortening velocity and the ratio of SEE slack length to fibre optimum length.


Autoradiographic analysis of [35S]TBPS binding in entorhinal cortex-kindled rat brains.
A quantitative autoradiographic analysis of [35S]t-butylbicyclophosphorothionate (TBPS) binding to the gamma-aminobutyric acid (GABA)-mediated chloride ionophore was carried out in 104 brain areas of entorhinal cortex-kindled and control rats. Subjects were sacrificed either 24 h or 28 days after the last kindled seizure. Kindled subjects in the 24 h group showed reductions in mean [35S]TBPS binding in the lateral nucleus of the amygdala (-31%), the infralimbic cortex (-14%), and the paracentral nucleus of the thalamus (-22%). At 28 days, reductions in binding were observed in the infralimbic cortex (-15%) and the paracentral nucleus of the thalamus (-18%). These data suggest that repeated seizures (kindling) modify the GABA-mediated chloride ionophore, and that in some brain areas related to seizure generalization the modifications are very long lasting.


Fertilization makes strong associations between organic carbon composition and microbial properties in paddy soil.
Fertilization changes the soil organic carbon (SOC) composition, affecting the carbon cycle of paddy soil. Understanding the mechanisms of physical fraction and chemical composition of SOC responding to fertilization can help regulate the nutrient release and carbon sequestration. However, it is unclear whether these changes in SOC composition to fertilization are consistent and how these are regulated by biotic and abiotic properties. Therefore, a positioning experiment in a rice field was conducted with a total of nine treatments. Chemical fertilizers (0, 337.5, and 675 kg ha-1; C0, C50, and C100, respectively) and fungal residue (0, 10,000, and 20,000 kg ha-1; F0, F50, and F100, respectively) were applied to evaluated (i) changes in the physical fraction and chemical composition of SOC, (ii) changes in soil properties, microbial biomass and community, and (iii) establish relationships among soil properties, microbial community, microbial biomass, and SOC composition. Our results showed that the application of fungal residue exhibited more significant effects on SOC physical fractions than those with the chemical fertilizers. Furthermore, the chemical composition of SOC was more respond to the application of chemical fertilizers than fungal residue. The partial least squares path model indicated that soil properties mainly affected the mineral-associated organic carbon (MAOC) by microbial biomass. In addition, bacterial diversity played an important role in improving the accumulation of MAOC. The SOC chemical composition was mediated by fungal community composition and bacterial diversity. In conclusion, fungal residue application affected SOC physical fraction by increasing soil properties, microbial biomass, and bacterial diversity. Chemical fertilizers application mainly mediated the chemical composition of SOC by altering fungal community composition and decreasing bacterial diversity.


Mechanisms and clinicophysiological implications of the sniff- and gasp-like aspiration reflex.
Mechanical stimulation of the pharyngeal mucosa in cats and some other mammals evokes the 'aspiration reflex' (AR) characterized by rapid and strong inspiratory efforts not followed by active expirations. It resembles other spasmodic inspiratory acts such as the sniff, the gasp, and the sigh in several aspects, e.g. reflex or semireflex triggering from the upper airways, the sudden onset and termination of such inspirations, the massive recruitment, steep rise and high-peak amplitude of inspiratory unit activity, analogous ventilatory pattern, and contribution to arousal. The similarity of these spasmodic acts is manifested mainly in enhanced speed and volume of inhalation, although of different intensity, which is determined by the varying degree of forced inspiratory activity and a concomitant inhibition of expiratory activity. The extent of the inspiratory dilation of the glottis and the timing and range of late-inspiratory and/or postinspiratory glottal narrowing modulate the depth of aspiration. Thus, the inhalation can be moderate as in sniffing, which provides a transfer of odorants to the olfactory mucosa. In AR the airstream is presumably strong enough to tear off the mechanical particles from the naso- and oropharynx and to convey them into the hypopharynx to allow their subsequent elimination by reflex swallowing or coughing. Prolonged glottal opening allows either the transfer of some additional air to the bronchi by sighing to prevent the development of atelectasis, or redistribution of a larger amount of fresh air into the lungs by gasping to support autoresuscitation. Should aspiration be a common effective component in these spasmodic processes, then the easily elicitable AR could be beneficial as a simple model for studying their properties in health and disease.


LC-MS/MS of permethylated N-glycans derived from model and human blood serum glycoproteins.
LC-MS/MS is one of the most powerful tools for N-glycan structure elucidation; however, it is still challenging to identify some glycan structures with low abundance. In this study, we investigated the chromatographic behavior of permethylated N-glycans. The relationship between retention times versus molecular weight of dextran, dextrin, and model glycans was investigated. Also, the nonpolar surface area of glycans was calculated and compared to their experimental retention times. Both retention time and nonpolar surface area trends are similar when the intermolecular interaction is included in the calculation. Moreover, retention time corresponds to glycan types and branch types. The N-glycans analysis model, which combines high mass accuracy and retention time, was applied to confirm serum N-glycans. In total, there were 78 N-glycan compositions identified. A linear relationship between retention times and molecular weights were observed for each subgroup of glycan structures, for example, R(2) value for complex N-glycans was determined to be > 0.98. Moreover, the retention time could be further applied to distinguish between structural isomers as well as linkage isomers. MS/MS data were used to confirm the structural isomers.


Dietary assessment of adolescents undergoing laparoscopic Roux-en-Y gastric bypass surgery: macro- and micronutrient, fiber, and supplement intake.
Extremely obese adolescents are increasingly undergoing bariatric procedures, which restrict dietary intake. However, as yet, no data are available describing the change in caloric density or composition of the adolescent bariatric patient's diet pre- and postoperatively. Our objective was to assess the 1-year change in the dietary composition of adolescents undergoing bariatric surgery at a tertiary care children's hospital. A total of 27 subjects (67% female, 77% white, age 16.7 ± 1.4 yr, baseline body mass index 60.1 ± 14.1 kg/m(2)) were prospectively enrolled into an observational cohort study 1 month before undergoing laparoscopic Roux-en-Y gastric bypass from August 2005 to March 2008. The 3-day dietary intake was recorded at baseline (n = 24) and 2 weeks (n = 16), 3 months (n = 11), and 1 year (n = 9) postoperatively. The dietary record data were verified by structured interview and compared with the Dietary Reference Intake values for ages 14-18 years. By 1 year after surgery, the mean caloric intake, adjusted for body mass index was 1015 ± 182 kcal/d, a 35% reduction from baseline. The proportion of fat, protein, and carbohydrate intake did not differ from baseline. However, the protein intake was lower than recommended postoperatively. The calcium and fiber intake was also persistently lower than recommended. Calcium and vitamin B(12) supplementation increased the likelihood of meeting the daily minimal recommendations (P ≤ .02). At 1 year after Roux-en-Y gastric bypass, the adolescents' caloric intake remained restricted, with satisfactory macronutrient composition but a lower than desirable intake of calcium, fiber, and protein.


Repeated exercise paired with "imperceptible" dead space loading does not alter VE of subsequent exercise in humans.
We employed an associative learning paradigm to test the hypothesis that exercise hyperpnea in humans arises from learned responses forged by prior experience. Twelve subjects undertook a "conditioning" and a "nonconditioning" session on separate days, with order of performance counterbalanced among subjects. In both sessions, subjects performed repeated bouts of 6 min of treadmill exercise, each separated by 5 min of rest. The only difference between sessions was that all the second-to-penultimate runs of the conditioning session were performed with added dead space in the breathing circuit. Cardiorespiratory responses during the first and last runs (the "control" and "test" runs) were compared for each session. Steady-state exercise end-tidal PCO(2) was significantly lower (P = 0.003) during test than during control runs for both sessions (dropping by 1.8 +/- 2 and 1.4 +/- 3 Torr during conditioning and nonconditioning sessions, respectively). This and all other test-control run differences tended to be greater during the first session performed regardless of session type. Our data provide no support for the hypothesis implicating associative learning processes in the ventilatory response to exercise in humans.


Retromer regulates apical-basal polarity through recycling Crumbs.
Epithelial cells are characterized by an "apical-basal" polarization. The transmembrane protein Crumbs (Crb) is an essential apical determinant which confers apical membrane identity. Previous studies indicated that Crb did not constantly reside on the apical membrane, but was actively recycled. However, the cellular mechanism(s) underlying this process was unclear. Here we showed that in Drosophila, retromer, which was a retrograde complex recycling certain transmembrane proteins from endosomes to trans-Golgi network (TGN), regulated Crb in epithelial cells. In the absence of retromer, Crb was mis-targeted into lysosomes and degraded, causing a disruption of the apical-basal polarity. We further showed that Crb co-localized and interacted with retromer, suggesting that retromer regulated the retrograde recycling of Crb. Our data presented here uncover the role of retromer in regulating apical-basal polarity in epithelial cells and identify retromer as a novel regulator of Crb recycling.


Modelling the viral dynamics of the SARS-CoV-2 Delta and Omicron variants in different cell types.
We use viral kinetic models fitted to viral load data from in vitro studies to explain why the SARS-CoV-2 Omicron variant replicates faster than the Delta variant in nasal cells, but slower than Delta in lung cells, which could explain Omicron's higher transmission potential and lower severity. We find that in both nasal and lung cells, viral infectivity is higher for Omicron but the virus production rate is higher for Delta, with an estimated approximately 200-fold increase in infectivity and 100-fold decrease in virus production when comparing Omicron with Delta in nasal cells. However, the differences are unequal between cell types, and ultimately lead to the basic reproduction number and growth rate being higher for Omicron in nasal cells, and higher for Delta in lung cells. In nasal cells, Omicron alone can enter via a TMPRSS2-independent pathway, but it is primarily increased efficiency of TMPRSS2-dependent entry which accounts for Omicron's increased activity. This work paves the way for using within-host mathematical models to understand the transmission potential and severity of future variants.


Interleukin-7 and immune reconstitution in cancer patients: a new paradigm for dramatically increasing overall survival.
Although great effort is being expended in the development of cancer immunotherapies, it is surprising that global lymphopenia and its various dimensions are not being systematically assessed in cancer patients. The incident pathologies associated with various immunosuppressed conditions such as those found in HIV infection have taught us that measuring various T cell populations including CD4 provides the clinician with a reliable measure for gauging the risk of cancer and opportunistic infections. Importantly, recent data emphasize the key link between lymphocyte T cell counts and overall survival in cancer patients receiving chemotherapy. Treatment of immunocompromised patients with interleukin-7 (IL-7), a critical growth and homeostatic factor for T cells, has been shown to produce a compelling profile of T cell reconstitution. The clinical results of this investigational therapy confirm data obtained from numerous preclinical studies and demonstrate the long-term stability of this immune reconstitution, not only on CD4 but also on CD8 T cells, involving recent thymic emigrants as well as naive, memory, and central memory T cells. Furthermore, IL-7 therapy also contributes to restoration of a broadened diversity of the T cell repertoire as well as to migration of these cells to lymph nodes and tissues. All these properties support the initiation of new clinical studies aimed at reconstituting the immune system of cancer patients before or immediately after chemotherapy in order to demonstrate a potentially profound increase in overall survival.


Gamma-endorphin-like peptides in pituitary tissue: evidence for their existence in vivo.
Beta and gamma endorphin-like peptides were measured by radioimmunoassay in whole pituitary. Boiling of acetic acid extracts prior to tissue disruption increased the concentration of both beta E- and gamma E-like peptides. The gamma E-like immunoreactivity from the neurointermediate lobe of the pituitary co-eluted with synthetic gamma E upon gel permeation chromatography. Immunoreactivity for beta E-like and gamma E-like peptides in the intermediate lobe of the pituitary was also shown by immunoperoxidase staining. The results suggest that gamma E-like peptides are present primarily in the pars intermedia in vivo and do not arise as artifacts of acid extraction of pituitary tissue.


Outcome of surgical treatment of pelvic osteosarcoma.
Surgical treatment of pelvic osteosarcoma is often challenging. The objective of this study was to assess the oncologic and functional outcome and the operation-related complications of patients with pelvic osteosarcoma who were treated in a single center in the past decade. Nineteen patients underwent surgical procedures between June 2000 and June 2009. There were 11 males and 8 females with a mean age of 30 years. According to Enneking and Dunham pelvic classification system, there were: Type I-3, Type I + IV-3, Type I + II-2, Type II + III-4, Type I + II+ III-1, Type III-1, and type I + II+ IV-5. All patients received chemotherapy. Local recurrence rate was 26.3% (5/19). The 5-year overall survival rate was 44.9%. Seventeen patients received reconstruction after tumor resection. The average MSTS 93 score was 18 (10-23) for the 11 patients with hemipelvic endoprosthetic reconstruction and 23 (20-25) for 6 patients with rod-screw reconstruction. Complication was found in 7 of 19 patients (36.8%). The oncological results of pelvic osteosarcoma are poor at best. Even with a higher complication rate, we believe restoration of pelvic ring continuity and hip joint mobility is reasonable option to achieve favorable functional outcomes in selected patients.


Unexpected Symptomatic Pneumonitis Following Breast Tangent Radiation: A Case Report.
Symptomatic radiation pneumonitis (RP) following radiation therapy (RT) to the breast alone is very uncommon. We report a case of an 80-year-old female who presented with fatigue, exertional dyspnea, fever, and cough 11.5 weeks following adjuvant breast RT with tangent fields alone. Imaging was consistent with RP, and she responded to a tapering course of steroids.


Factors associated with caregivers' underestimation of quality of life in patients with Alzheimer's disease.
The aim of this study was to identify the factors associated with differences between how Alzheimer's disease (AD) patients and their caregivers rate the patient's health-related quality of life (QoL). Cross-sectional, multicentre study. Patients were 65 years or more, suffering from mild to moderate AD, native French speakers, with a main caregiver. Interrater agreement of the QoL-AD was assessed using the intraclass coefficient. A generalised linear model was used to identify factors related to the difference in health-related QoL scores between patients and their caregivers. The 122 patients of the study were 82 ± 6 years old and mainly women (69%). Independent factors related to the difference between patients and caregivers were: Mini Mental State Exam score (β = 0.32; 95% CI = 0.05-0.59); instrumental activities of daily living score (β = -0.61; 95% CI = -1.14 to -0.07); total Neuropsychiatric Inventory score (β = 0.10; 95% CI = 0.05-0.59), and Zarit's burden score (β = 0.09; 95% CI = 0.01-0.17). Practitioners must take into account the trend towards underestimation when health-related QoL is rated by caregivers or proxies.


Impact of crop insurance on cocoa farmers' income: an empirical analysis from Ghana.
Risk is associated with every sector of an economy, and the pervasiveness of risk in agriculture is not new to farmers; they have, over the decades, developed ways to minimize and cope with it. The question is whether traditional strategies employed by farmers are adequate to curb unavoidable natural disasters. This study aims to see how crop insurance affects cocoa producers' incomes in Ghana. A well-structured questionnaire was delivered to a sample of 600 cocoa farmers in Ghana's Ashanti region, and data was collected using a multi-stage random sampling technique. Tobit and propensity score matching effect estimators were used to examine crop insurance's impact on cocoa farmers' income. We found that the age of a cocoa farmer has a negative effect on the farmer's income and is statistically significant. Our result also shows that the marital status of cocoa farmers has a significant positive impact on their income. The relationship between savings and farmers' income was positive in our estimation. It indicates that an increase in savings attitude leads to a higher income for the farmers. The result indicates that crop insurance had a significant positive impact on cocoa farmers' income in the Ashanti region. The study recommends that the government of Ghana, with urgency, design agricultural insurance policy that can capture various farmers in the country to enhance their income and reduce poverty. Again, insurers need to promote publicity through public seminars, training, and media advertising to improve farmer awareness and knowledge of the insurance scheme.


Obsessive-compulsive disorder in people that abuse codeine.
The author describes patients with severe obsessive-compulsive disorder observed only when they abused codeine.


AF-2364 [1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide] is a potential male contraceptive: a review of recent data.
Earlier studies have shown that 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (AF-2364) is a potential male contraceptive when administered orally to adult Sprague-Dawley rats. This compound induces reversible germ cell loss from the seminiferous epithelium by disrupting cell adhesion function between Sertoli and germ cells, in particular, elongating/elongate/round spermatids and spermatocytes but not spermatogonia. Thus, this event is accompanied by a transient loss of fertility in treated rats. Once the drug is metabolically cleared, the remaining spermatogonia can begin repopulating the epithelium, and fertility bounces back. In this review, we summarize recent findings regarding the possible use of this drug for male contraception and its mechanism of action in the rat testis. We also provide an update on the efficacy results of using different treatment regimens in adult rats where AF-2364 was administered by gavage vs. intraperitoneal and intramuscular administration. These results have clearly indicated that AF-2364 is indeed a reversible male contraceptive. Furthermore, the tissue distribution in multiple organs and biological fluids using [3H]-AF-2364 is also reviewed. These data have clearly illustrated the low bioavailability of AF-2364 in rats and that this compound is not specifically taken up by any organs including the testis or the epididymis. These summaries are helpful to investigators in the field who seek to understand the molecular mechanism of action of AF-2364 in the rat testis and to explore its possible use for male contraception.


Thymomas and extrathymic cancers.
Patients with thymoma may have a predisposition toward extrathymic neoplasia. To understand the lifetime risk and incidence of extrathymic neoplasia in patients with thymoma, we evaluated extrathymic neoplasms diagnosed either before or after the diagnosis of thymoma. We queried the Surveillance, Epidemiology, and End Results (SEER) cancer database and identified patients with thymoma and extrathymic neoplasms. We collected demographic and treatment data, calculated the incidence of each extrathymic neoplasm (adjusting for age), and compared the incidence of extrathymic neoplasm in patients with thymoma with the age-adjusted incidence in the SEER database general population. Of 2,171 patients with thymoma in the SEER database, 306 (14.1%) had extrathymic primary cancers. Extrathymic neoplasms were diagnosed before the diagnosis of thymoma in 88 patients and after the diagnosis of thymoma in 206 patients. In 12 patients, separate extrathymic neoplasms were diagnosed both before and after thymoma diagnosis. The incidence of extrathymic cancers in patients with thymoma (8,224 per 100,000 persons) was significantly higher than in the SEER general population (459 per 100,000 persons; p<0.001). The standardized incidence ratio for extrathymic cancer was also significantly increased, in particular for lymphomas, leukemias, esophageal cancer, and lung cancer. Increased age at diagnosis (p<0.001), longer survival after diagnosis (p<0.001), and male sex (p=0.041)-but not radiation therapy or surgery-were significant risk factors for the development of extrathymic cancers in patients with thymoma. The incidence of extrathymic neoplasia is significantly higher in patients with thymoma than in the general population and occurs both before and after the diagnosis of thymoma.


Medical referral for chiropractic care: a survey of "unconventional" medical practitioners.
To ascertain the attitude toward chiropractic care of Australian medical practitioners who had previously demonstrated a willingness to contemplate a nonconventional mode of clinical intervention. A descriptive study in which eight hundred and twenty (820) medical practitioners were invited to respond to a mailed questionnaire. Only medical practitioners who had demonstrated an interest in at least one form of nonconventional intervention were surveyed. Seven hundred and ninety-six (796) medical practitioners who subscribe to a professional organization committed to 'alternative' nutritional approaches in health care were mailed a questionnaire. Twenty-four practitioners known to be sympathetic to chiropractic were also included. The response rate was 27%. One quarter of respondents never refer patients to a chiropractor. The major reason given for nonreferral is that physiotherapy is the preferred option. Almost half of the medical practitioners who never refer to chiropractors use manipulation themselves. Half of the medical practitioners who have never referred or have occasionally referred were unsure which of their patients would benefit from chiropractic care. Important referral criteria used by medical practitioners who do undertake chiropractic referral are, in order of importance: prior personal knowledge, the practitioner's professional reputation, qualifications and practice location. These medical practitioners believe that between one and three of every four patients referred received benefit from chiropractic care. Increased contact between chiropractors and the medical practitioners who were surveyed could lead to a better appreciation of chiropractic's potential contribution in health care.


Measurement of naphthoxylactic and naphtoxyacetic acid in human plasma following propranolol administration.
A method for the quantitative determination of naphthoxylactic acid and naphthoxyacetic acid, two acidic metabolites of propranolol, in human plasma is described. Preliminary data from hypertensive patients receiving chronic propranolol therapy and from normal volunteers who took a single 80 mg oral propranolol dose revealed that naphthoxylactic acid plasma levels were 4 to 20 times that of propranolol whereas naphthoxyacetic acid levels were equivalent to or less than the plasma concentrations of propranolol.


miR-199b-5p-DDR1-ERK signalling axis suppresses prostate cancer metastasis via inhibiting epithelial-mesenchymal transition.
The investigation of underlying mechanism and the exploitation of novel therapies for metastatic prostate cancer (PCa) are still urgently needed. miR-199b-5p has been suggested to function as tumour suppressor in various human cancers. However, the clinical significance and role of miR-199b-5p in PCa remain unclear. The current study sought to investigate the expression status of miR-199b-5p in PCa and the involved molecular mechanisms in PCa metastasis by using bioinformatics analyses, loss-and gain-of-functions and rescue experiments in vitro and in vivo. We demonstrated that miR-199b-5p was significantly downregulated in metastatic PCa tissues and cells when compared with the normal prostate tissue, the localised disease, the weakly metastatic and androgen-dependent PCa cell and the normal prostate epithelial cell. We also found that miR-199b-5p drastically suppressed PCa cell proliferation, migration and invasion in vitro and inhibited xenografts tumour growth and metastasis in vivo. Mechanistically, our results showed that miR-199b-5p could inhibit discoidin domain receptor tyrosine kinase 1 (DDR1) expression by directly targeting its 3'-UTR, thereby hindering epithelial-mesenchymal transition (EMT)-associated traits, which were induced by DDR1 activating ERK signalling pathway. Moreover, PCa patients with low miR-199b-5p expression level had a remarkably shorter overall survival than those with high miR-199b-5p level, indicating an association of miR-199b-5p loss with poor prognosis in patients with PCa. Furthermore, DDR1 was upregulated in PCa, and significantly correlated with high Gleason score, advanced pathological stage, tumour metastasis and shorter overall survival. Our study, for the first time, provide evidence of a tumour-suppressive function of miR-199b-5p in the invasion and metastasis of PCa, supporting the translational exploitation of miR-199b-5p-based therapeutic approaches for PCa metastases. Also, the miR-199b-5p-DDR1-ERK signalling axis identified in this study represents a novel mechanism of regulating EMT in PCa metastases.


Evaluation of melanoma vaccines with molecularly defined antigens by ex vivo monitoring of tumor-specific T cells.
Immunotherapy of melanoma is aimed to mobilize cytolytic CD8+ T cells playing a central role in protective immunity. Despite numerous clinical vaccine trials, only few patients exhibited strong antigen-specific T-cell activation, stressing the need to improve vaccine strategies. For a rational development, we propose to focus on molecularly defined vaccine components, and evaluate their immunogenicity with highly reproducible and standardized methods for ex vivo immune monitoring. Careful immunogenicity comparison of vaccine formulations in phase I/II studies allow to select optimized vaccines for subsequent clinical efficacy testing in large scale phase III trials.


Involvement of cytochrome P-450 in conferring chloroquine resistance to the malarial parasite, Plasmodium falciparum.
The higher levels of cytochrome P-450 dependent enzyme activities reported earlier are traced to higher levels of cytochrome P-450 (CYPIIB1/B2 like) messenger RNA in the chloroquine resistant than the sensitive strains. The messenger RNA is also induced by phenobarbitone in the sensitive strain. Pretreatment with phenobarbitone affords partial protection to chloroquine toxicity in the sensitive strain and this is not due to a differential accumulation of the drug.


Brain adenosine production in the rat during 60 seconds of ischemia.
In rats, cerebral perfusion pressure were altered abruptly by aortic transection to determine the production by ischemic brain of adenosine and its metabolites, inosine and hypoxanthine. Brain samples were obtained after 0, 5, 10, 15, 30, and 60 seconds of ischemia. Also measured were ATP, ADP, AMP, phosphocreatine (PCr), lactate, and pyruvate. Blood pressure was monitored continuously, and arterial PO2, PCO2, and pH were measured just prior to induction of ischemia. Adenosine was elevated t 2.30 +/- 0.31 (SE) nmol/g at 5 seconds from a control value of 0.96 +/- 0.07. A significant elevation of adenosine continued to 60 seconds (5.50 +/- 1.24). Furthermore, inosine showed a progressive upward trend during the entire 60 seconds of ischemia, whereas no change in hypoxanthine occurred between the moment of transection (31.81 +/- 2.01 nmol/g) and 60 seconds of ischemia (34.72 +/- 2.93). PCr decreased by 1.24 mumol/g within the first 5 seconds. After the onset of hypotension, significant changes did not occur in AMP and ADP until 30 seconds, and in ATP and pyruvate until 60 seconds after aortic transection; lactate was elevated by 10 seconds. The rapid rise of cerebral adenosine within 5 seconds after the onset of ischemia supports a role for adenosine in the regulation of cerebral blood flow.


Postoperative radiotherapy for patients with carcinoma of the prostate undergoing radical prostatectomy with positive surgical margins, seminal vesicle involvement and/or penetration through the capsule.
Between 1970 and 1983, 442 patients were treated for carcinoma of the prostate at our university medical center. Of the patients 319 underwent radical prostatectomy and 159 (50 per cent) had positive surgical margins and/or seminal vesicle involvement. Of these 159 patients 46 received postoperative irradiation and the actuarial survival was 96, 90 and 90 per cent at 5, 10 and 15 years, respectively. Among the remaining 113 patients who were treated with an operation alone the corresponding figures were 82, 62 and 21 per cent, respectively (p equals 0.02). Considering deaths only of cancer, the surgery only patients had a 15-year actuarial survival of 25 per cent compared to 90 per cent for those who underwent postoperative radiotherapy (p equals 0.07). Actuarial survival free of disease for the surgery plus postoperative irradiation group at 15 years was 40 per cent compared to 28 per cent for the surgery only group (p equals 0.34). Actuarial local control in the irradiated patients was 96 per cent at 15 years versus 32 per cent for the surgery only group (p equals 0.009). Actuarial survival free of distant disease at 15 years was 42 per cent in the irradiated versus 72 per cent in the nonirradiated groups (p equals 0.104). Severe complications attributable to radiation included 3 cases of radiation cystitis, 1 patient with urinary incontinence and leg edema in 9 per cent of the patients undergoing postoperative irradiation compared to 2 per cent of those treated with radical prostatectomy only. Postoperative irradiation appears to be indicated in patients with carcinoma of the prostate who undergo radical prostatectomy and who have positive margins and/or seminal vesicle involvement. Local control is markedly improved (p equals 0.009) and actuarial survival also is benefitted. There was a trend toward decreased deaths of cancer with postoperative irradiation that approached statistical significance. Postoperative irradiation did not improve survival rates free of disease and free of distant disease over those achieved with surgery alone. This finding suggests that while postoperative irradiation may not improve the ultimate cure rate by controlling local disease, early deaths of cancer are reduced resulting in a meaningful increase in survival for these patients.


The Lack of Sexual Health Education in Medical Training Leaves Students and Residents Feeling Unprepared.
Despite physicians frequently caring for patients with sexual health issues, only 50% of United States medical schools require formal education in sexual medicine, and there are currently no guidelines pertaining to this with research which found that medical trainees are ill-equipped to provide sexual healthcare. This study aims to identify areas to improve sexual health training in order to increase physician confidence and competence in evaluating and training patients with sexual health problems. A prospective survey was sent via REDCap to medical students (n = 190, 68.6%), residents (n = 75, 27.1%), and fellows (n = 11, 3.9%) via a known listserv. Participants (N = 276, ∼15% response rate) were asked to provide demographic information, whether they received sexual health training during medical school and rate their confidence in addressing patients' sexual health concerns. Medical students and residents currently do not receive sufficient education on sexual health and medicine, particularly in fields outside of OB-GYN and Urology, leaving them underqualified and less confident than needed for adequate patient care. 65.6% of trainees reported receiving formal sexual health education, while 13.9% received informal education, and 20.6% received no education during medical school. Although trainees desire to understand a patients' sexual health (P < .001), only residents in a relevant field (Urology, OB-GYN) felt confident in their ability to assist patients with a sexual health issue (P = .013). All other trainees lacked confidence in attending to sexual health concerns (P < .001), regardless of training level (P > .1). More efforts should be made to integrate sexual health education into medical school curriculum. The strength of this study includes specific evaluation of medical student and resident confidence level with 15 individual sexual health topics. The limitations include that the demographic was regionally confined to the Midwest of the United States and women were more strongly represented among medical students. Due to the lack of standardized education, medical trainees (except for Urology and OB-GYN residents) feel unprepared to treat patients with sexual health issues, and medical schools should make sexual health education mandatory. Beebe S, Payne N, Posid T, et al. The Lack of Sexual Health Education in Medical Training Leaves Students and Residents Feeling Unprepared. J Sex Med 2021;18:1998-2004.


Evaluation of a venous-return assist device to treat severe post-thrombotic syndrome (VENOPTS). A randomized controlled trial.
Severe post-thrombotic syndrome (PTS) is responsible for considerable disability, reduced quality of life and increased health care costs. Current therapies are limited and often ineffective. We performed a two-centre, randomized, cross-over controlled trial to evaluate Venowave, a novel lower-limb venous-return assist device, for the treatment of severe PTS. Eligible subjects were allocated to receive, in randomized order, Venowave for eight weeks and a control device for eight weeks. The eight-week treatment periods were separated by a four-week period when no device was used (i.e. wash-out period). The primary outcome measure was a 'clinical success' defined as: i) reported benefit from the device; and ii) moderate or greater improvement in symptoms of PTS; and iii) willingness to continue using the device. Secondary outcome measures included quality of life (QOL) as measured by VEINES-QOL questionnaire (higher scores indicate better QOL), and PTS severity as measured by the Villalta PTS scale (higher scores indicate more severe PTS). The study was registered with Clinical Trials. gov (NCT00182208). Thirty-two patients were enrolled. Of these, 26 (80%) were also using graduated compression stockings. Twenty-six participants completed both trial periods. Clinical success occurred in 10 (31%) participants receiving Venowave and four (13%) participants receiving the control device, with two (6%) participants reporting a clinical success with both devices (P = 0.11). Mean VEINES-QOL score at the end of study period was significantly greater (P = 0.004) for Venowave (52.5; SD 5.8) compared to control (50.2; SD 6.2). Mean Villalta scale score at the end of study period was significantly decreased (P = 0.004) for Venowave (12.2; SD 6.3) compared to control (15.0; SD 6.1). In conclusion, Venowave appears to be a very promising new therapy for patients with severe PTS, which may be used alone or in combination with graduated compression stockings.


Genetic analysis of patients with retinitis pigmentosa using a cloned cDNA probe for the human gamma subunit of cyclic GMP phosphodiesterase.
We have cloned cDNAs corresponding to the human gamma subunit of retinal cyclic GMP phosphodiesterase (gamma-cGMP-PDE). The coding region of these cDNAs was identical to that reported previously by Tuteja et al. (Gene 1990, 88, 227-32). We also confirmed their assignment of gamma-cGMP-PDE to human chromosome 17. The fragment was used to search for mutations of the corresponding gamma-cGMP-PDE gene in patients with autosomal dominant, autosomal recessive, or isolate case retinitis pigmentosa, and Usher's syndrome type I. No gene deletions or rearrangements could be detected in any patient by Southern blotting. We discovered restriction fragment length polymorphisms (RFLPs) with the enzymes BstE II and EcoR I defining sets of alleles at the gamma-cGMP-PDE locus in the normal population. We used these RFLPs to analyse the genomic DNA of large sets of unrelated patients with the autosomal dominant, autosomal recessive, or isolate form of retinitis pigmentosa. Within each of these three groups, BstE II and EcoR I RFLP alleles at the gamma-cGMP-PDE locus showed no linkage disequilibrium (departure from Hardy-Weinberg equilibrium). In addition, one autosomal dominant, three autosomal recessive, and two Usher's syndrome type I pedigrees each showed no cosegregation of the gamma-cGMP-PDE locus and the disease locus. Thus, we find no evidence that mutations of the gene for the gamma subunit of cGMP phosphodiesterase are associated with the common forms of retinitis pigmentosa and Usher's syndrome type I.


Joint Injection Techniques and Indications.
Indications for injecting synovial joints may include diagnostic, therapeutic, or combination. Diagnostic injectates aim to reduce or eliminate the contribution of pain to lameness and may be assessed both subjectively or objectively by the clinician. Diagnostic joint injections are not specific for a disease and their limitations must be remembered when interpreting a response-including false-negative results. Patient selection and sterile technique throughout the procedure minimize adverse effects. Risks of intra-articular (IA) injections may include transient soreness, cartilage damage, and, rarely, septic arthritis. Ultrasound guidance with a trained clinician may provide further benefits including the reduction of periprocedural discomfort, reduction in iatrogenic cartilage damage during needle insertion, and improvement in synovial fluid feedback. The removal of some synovial fluid before administering an IA injection should be considered to confirm needle placement, provide diagnostic sampling, and help accommodate injectate volume.


Abietic acid alleviates endoplasmic reticulum stress and lipid accumulation in human primary hepatocytes through the AMPK/ORP150 signaling.
Abietic acid (AA), the main component of pine resin that has been traditionally used as Asian medicine, has been reported to demonstrate anti-inflammatory activities. Despite this, little is known about the effects of AA on hepatic endoplasmic reticulum (ER) stress and lipid metabolism. This study investigated the impacts of AA on ER stress and steatosis in in vitro obesity models. We found that Treatment with AA reduced lipid deposition and lipogenesis-related proteins expression in human primary hepatocytes. Augmented expression of ER stress markers (phospho-eukaryotic initiation factor-2α (eIF2α) and C/EBP homologous protein (CHOP)) in palmitate-treated hepatocytes were reversed by AA treatment. Further, AA treatment increased the expression of phospho-AMPK and oxygen-regulated protein 150 (ORP150) in hepatocytes. siRNA-associated knockdown of AMPK or ORP150 expression reduced the effects of AA on not only hepatic ER stress but also lipogenesis and apoptosis. These results denote that AA attenuates lipid accumulation in hepatocytes in the presence of palmitate through the suppression of ER stress by AMPK/ORP150 signaling. AA could be a potential candidate for treating non-alcoholic fatty liver disease.


The UDCA dosage deficit: a fate shared with CDCA.
Ursodeoxycholic acid (UDCA) is used both as the treatment of choice in many cholestatic syndromes and as complementary therapy in many liver diseases. However, few dose-finding studies exist, and none has evaluated the efficacy and long-term safety of UDCA therapy in primary biliary cirrhosis (PBC). There is an open debate about UDCA's impact on the natural history of PBC, and no universal evidence of benefits on the major endpoint exists. This is perhaps due to a UDCA dosage deficit. Most clinical trials on PBC therapy have used conservative dosages of UDCA similar to those of chenodeoxycholic acid (CDCA) used for dissolution of gallstones. It may be necessary to re-evaluate the dosage of UDCA that provides the most effective treatment.


Genetic polymorphism of CYP2D6∗2 C→T 2850, GSTM1, NQO1 genes and their correlation with biomarkers in manganese miners of Central India.
Manganese (Mn) intoxication is most often regarded as an occupational manifestation and occurs in places such as manganese mines, dry cell battery plants and ceramic industries. In the present study, the influence of genetic polymorphism in cytochrome P450 2D6 (CYP2D6∗2), glutathione S-transferase M1 (GSTM1) and NAD(P)H quinone oxidoreductase 1 (NQO1) genes on blood manganese and plasma prolactin concentrations in manganese miners was investigated. Genotyping of CYP2D6∗2 C→T 2850 and NQO1 C→T 609 was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) whereas the genotyping of GSTM1 was carried out by multiplex PCR using beta globin as an internal control. Manganese miners with CYP2D6∗2 C→T 2850 variant genotype had relatively low Mn concentration [GM: 21.4±8.9 μg L(-1)] than the subjects with wild (GM: 36.3±8.5 μg L(-1)) and heterozygous (GM: 34.4±6.9 μg L(-1)) genotypes. Miners with CYP2D6∗2 variant genotypes showed low prolactin levels (GM: 13.13±1.6 ng mL(-1)) compared to the wild (GM: 16.4.4±1.5 μg L(-1)) and heterozygous (GM: 18.7±1.6 ng mL(-1)) genotypes. Gene-gene interaction studies also revealed that the subjects with CYP2D6∗2 C→T 2850 variant genotypes had low levels of Mn and prolactin. Our new findings suggest that CYP2D6∗2 C→T 2850 variant genotypes can regulate plasma prolactin levels in manganese miners of Central India and could be involved in the fast metabolism of blood manganese, compared to wild and heterozygous genotypes.


Management of Radiographic Lesions of the Breast.
Breast imaging plays an essential role in the diagnosis and management of breast disease. From screening asymptomatic patients to evaluating clinical abnormalities on diagnostic studies, breast imaging provides critical information to the breast surgeon. Available imaging studies include those that have been proved over many years, like mammography, and those that take advantage of increasingly sophisticated technology, like breast MRI. Image-guided biopsy provides a safe means of evaluating indeterminate findings on imaging. Understanding how these tools are best used can help breast surgeons provide the best care for their patients.


Elevated BTG2 improves the radiosensitivity of non-small cell lung cancer (NSCLC) through apoptosis.
To identify radio-responsive genes and explore the biological function of encoded proteins in non-small cell lung cancer (NSCLC). Radio-responsive genes in irradiated H460 cells were screened from microarray data deposited in the Gene Expression Omnibus (GEO) database. A quantitative real time polymerase chain reaction assay was used to detect the expression of candidate radio-responsive genes in irradiated cells. CCK-8 assay, EDU assay, clone formation assay, immunofluorescence and flow cytometry were conducted to evaluate the biological function of B cell translocation gene 2 (BTG2) in NSCLC. Bioinformatic analysis using GES20549 showed that BTG2 was a radio-responsive gene in irradiated H460 cells. The mRNA expression level of BTG2 was lower in H460 cells compared with that in BEAS-2B normal lung epithelial cells. BTG2 expression was elevated upon IR exposure, in a dose-dependent but not a time-dependent manner. CCK-8 and EDU assays revealed that BTG2 overexpression inhibited the growth rate of irradiated cells. Clone formation showed that elevated BTG2 promoted DNA damage of irradiated H460 cells. The number of γ-H2AX foci induced by DNA damage was also markedly increased upon BTG2 overexpression. Flow cytometry showed that BTG2 increased IR-induced cell apoptosis. BTG2 may be a novel radio-responsive factor and a promising therapeutic target for radiotherapy of NSCLC.


Acute Babesiosis in Pregnancy: A Novel Imitator of Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome.
Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a serious complication of pregnancy associated with significant maternal and fetal morbidity and mortality. Several medical conditions have been described as imitators of this syndrome, presenting with similar signs and symptoms. A term, multiparous woman with a history of prior pregnancy complicated by preeclampsia developed symptoms and laboratory abnormalities suggestive of HELLP syndrome. After an uncomplicated repeat caesarean delivery of a healthy newborn, infection with Babesia species was diagnosed incidentally on a peripheral blood smear. She was treated with antibiotics postpartum without sequelae for her or her newborn. The laboratory abnormalities normalized by postoperative day 4. Babesiosis complicating pregnancy may be a novel imitator of HELLP syndrome and should be considered in the differential diagnosis, especially where geographically prevalent infection exists.


[The clinical significance of S100β protein in cerebrospinal fluid and serum from the patients with cerebral hemorrhage].
To observe the change and the clinical significance of S100β protein level in cerebrospinal fluid and serum from the patients with cerebral hemorrhage (CH). ELISA was used to detect the expression of S100β protein in CSF and serum from CH patients control with Inguinal Hernia or great saphenous varix patients. Meanwhile, rabbit CH model at 6 h, 12 h, 24 h, 48 h, 72 h and 96 h . The levels of CSF S100β protein at acute stage of CH patients increased significantly compared with those at recovery stage of CH patients and control group(P<0.01). The levels of S100β protein in CSF from CH patients increased significantly compared with those in serum (P<0.01).The levels of S100β protein in CSF of rabbit experimental group increased significantly compared with those of sham operation group at different time points(P<0.01). The level of S100β protein in CSF from CH patients increases. It may be a biomarker as reflecting degree of pathogenetic and predicting outcome in the CH patients.


Reprint of "Repeated adolescent activity-based anorexia influences central estrogen signaling and adulthood anxiety-like behaviors in rats".
Anorexia nervosa (AN) typically presents in adolescence and is highly comorbid with anxiety and depression, which often persist after elimination of AN symptomology. The activity-based anorexia (ABA) paradigm allows for evaluation of behavioral and neuroendocrine consequences of AN-like behaviors, including voluntary anorexia, hyperactivity, and disruption of the hypothalamic-pituitary-gonadal (HPG) and the hypothalamic pituitary adrenal (HPA) axis. Because ABA in adolescent females results in increased anxiety-like behavior in adulthood and the estrogen signaling system has been shown to play a role in anxiety and food intake, we investigated the role of ovarian hormones in adolescent ABA-treated rats, and long-term effects of mid- and late adolescent ABA exposure on behavior and estrogen signaling. While previous research demonstrated that two bouts of ABA during adolescence resulted in decreased time in the open arm of the elevated plus maze (EPM) and increased activity of the HPA axis in response to a novel stressor, here we show that one bout of ABA in mid-or late-adolescence did not result in the same behavioral outcome. Two exposures to ABA during adolescence were necessary to produce long-term anxiety-like behavior on the EPM. Finally, removal of ovarian hormones by ovariectomy (OVX) prior to puberty did not attenuate long-term behavioral consequences of ABA in adolescence, and estrogen receptor β (ERβ) expression level in the amygdala of ABA rats was significantly lower than control subjects. Taken together, these studies identify enduring effects of ABA in adolescent females that may be mediated by ABA-induced changes to CNS ERβ signaling that increase anxiety-like behaviors.


The SARS-CoV-2 Pandemic and Cancer Trials Ireland: Impact, Resolution and Legacy.
Cancer Trials Ireland (CTI) is the national cooperative group in Ireland. The SARS-CoV-2 pandemic led to significant ongoing disruptive change in healthcare from March 2020 to the present day. Its impact and legacy on a national clinical trials organisation was assessed. A review was conducted of prospectively acquired communications, team logs and time sheets, trial activation, closure and accrual, for the period 2019 to September 2021. An online survey of the impact of the pandemic on clinical investigators and of clinical trials units was performed. A National Cancer Retreat was organised on 21 May 2021 to identify and address pandemic related disruption and develop adaptive strategies. In the weeks after the pandemic was declared, remote working was initiated by all central office staff. Nationally, clinical trial accrual fell by 54% compared to the same period in 2019, radiotherapy trial accrual by 90%, and translational studies by 36%. Staff reassignment of research nurse staff occurred in 60% of units, trial monitoring was reduced in 42%, and trial initiations fell by 67%. Extreme fluctuations in monitoring hours were noted paralleling lockdown measures. Significant impact on all clinical trials units was noted including staff reassignments, reduced access to diagnostic imaging and reduced institutional supports. Remote clinic visits and remote monitoring was widely adopted. The National Cancer Retreat identified flexibility in trial conduct, staff recruitment and retention, the need for harmonisation of processes, and research staff support in the context of remote working as priorities. The pandemic has had a significant ongoing negative impact on cancer clinical trial activity in Ireland. Adaptive strategies including trial flexibility, expanded telehealth and remote monitoring, harmonisation of processes and staff support have been identified as priorities to ameliorate this impact, and develop a more sustainable clinical trial ecosystem.


"Because it is a rare disease…it needs to be brought to attention that there are things out of the norm": a qualitative study of patient and physician experiences of Wilson disease diagnosis and management in the US.
Wilson disease (WD) is a genetic disorder of copper metabolism that leads to copper accumulation in various organs, primarily the liver and brain, resulting in heterogenous hepatic, neurologic, and psychiatric symptoms. Diagnosis can occur at any age, requiring lifelong treatment, which can involve liver transplantation. This qualitative study aims to understand the wider patient and physician experience of the diagnosis and management of WD in the US. Primary data were collected from 1:1 semi structured interviews with US-based patients and physicians and thematically analyzed with NVivo. Twelve WD patients and 7 specialist WD physicians (hepatologists and neurologists) were interviewed. Analysis of the interviews revealed 18 themes, which were organized into 5 overarching categories: (1) Diagnosis journey, (2) Multidisciplinary approach, (3) Medication, (4) The role of insurance, and (5) Education, awareness, and support. Patients who presented with psychiatric or neurological symptoms reported longer diagnostic journeys (range 1 to 16 years) than those presenting with hepatic symptoms or through genetic screening (range 2 weeks to 3 years). All were also affected by geographical proximity to WD specialists and access to comprehensive insurance. Exploratory testing was often burdensome for patients, but receipt of a definitive diagnosis led to relief for some. Physicians emphasized the importance of multidisciplinary teams beyond hepatology, neurology, and psychiatry and recommended a combination of chelation, zinc, and a low-copper diet; however, only half the patients in this sample were on a chelator, and some struggled to access prescription zinc due to insurance issues. Caregivers often advocated for and supported adolescents with their medication and dietary regimen. Patients and physicians recommended more education and awareness for the healthcare community. WD requires the coordination of care and medication among several specialists due to its complex nature, but many patients do not have access to multiple specialties due to geographical or insurance barriers. Because some patients cannot be treated in Centers of Excellence, easy access to reliable and up-to-date information is important to empower physicians, patients, and their caregivers in managing the condition, along with general community outreach programs.


An active site-tail interaction in the structure of hexahistidine-tagged Thermoplasma acidophilum citrate synthase.
Citrate synthase (CS) plays a central metabolic role in aerobes and many other organisms. The CS reaction comprises two half-reactions: a Claisen aldol condensation of acetyl-CoA (AcCoA) and oxaloacetate (OAA) that forms citryl-CoA (CitCoA), and CitCoA hydrolysis. Protein conformational changes that `close' the active site play an important role in the assembly of a catalytically competent condensation active site. CS from the thermoacidophile Thermoplasma acidophilum (TpCS) possesses an endogenous Trp fluorophore that can be used to monitor the condensation reaction. The 2.2 Å resolution crystal structure of TpCS fused to a C-terminal hexahistidine tag (TpCSH6) reported here is an `open' structure that, when compared with several liganded TpCS structures, helps to define a complete path for active-site closure. One active site in each dimer binds a neighboring His tag, the first nonsubstrate ligand known to occupy both the AcCoA and OAA binding sites. Solution data collectively suggest that this fortuitous interaction is stabilized by the crystalline lattice. As a polar but almost neutral ligand, the active site-tail interaction provides a new starting point for the design of bisubstrate-analog inhibitors of CS.


Immunosuppressive effect of cyclosporin A on insect humoral immune response.
Cyclosporin A suppressed humoral immune response of Galleria mellonella larvae. Insects were immunized with LPS Pseudomonas aeruginosa and then injected with cyclosporin A. Immunosuppressive effects were expressed both, in larvae treated with cyclosporin A at the initial phase of immune response and at the effector phase of antibacterial immunity. Cyclosporin A moderately decreased lysozyme activity and significantly decreased antibacterial activity peptides against Escherichia coli. Immunosuppressive effects of cyclosporin A were observed after immunoblotting with antibodies anti-G. mellonella lysozyme. Tricine SDS/PAGE shown that synthesis of antibacterial peptides of larvae treated with cyclosporin A was considerably inhibited. Insects of impaired immune response by cyclosporin A action lost protective immunity to insect bacterial pathogen P. aeruginosa.


Discovering small-molecule senolytics with deep neural networks.
The accumulation of senescent cells is associated with aging, inflammation and cellular dysfunction. Senolytic drugs can alleviate age-related comorbidities by selectively killing senescent cells. Here we screened 2,352 compounds for senolytic activity in a model of etoposide-induced senescence and trained graph neural networks to predict the senolytic activities of >800,000 molecules. Our approach enriched for structurally diverse compounds with senolytic activity; of these, three drug-like compounds selectively target senescent cells across different senescence models, with more favorable medicinal chemistry properties than, and selectivity comparable to, those of a known senolytic, ABT-737. Molecular docking simulations of compound binding to several senolytic protein targets, combined with time-resolved fluorescence energy transfer experiments, indicate that these compounds act in part by inhibiting Bcl-2, a regulator of cellular apoptosis. We tested one compound, BRD-K56819078, in aged mice and found that it significantly decreased senescent cell burden and mRNA expression of senescence-associated genes in the kidneys. Our findings underscore the promise of leveraging deep learning to discover senotherapeutics.


Objective quantification of responses to the clinical pull-test in people with Parkinson's disease.
Postural instability can occur in the later-stages of Parkinson's disease (PD). The clinical pull-test is scored on a 0-4 scale on the Unified Parkinson's disease rating scale (UPDRS), with postural instability scored 2 or higher. This ordinal scale does not adequately track progression in early-PD or predict development of postural instability. To develop a test that quantifiably measured the backward stepping response on the pull-test in early-PD. Participants (35 controls and 79 PD participants) were prospectively enrolled in this study. Participants stepped backwards with each shoulder pull at four strengths on an instrumented gait mat. Four spatiotemporal parameters (reaction-time, step-back-time, step-back-distance, step-back-velocity) were quantified using Protokinetics Movement Analysis Software. Spatiotemporal pull-test parameters were compared to standard PD measures using linear regression and correlation coefficients. Repeated measures analysis was used to determine group differences in pull-test parameters. In a subset of participants repeated testing was performed and Bland-Altman plots were used to determine reproducibility of the pull-test parameters. Step-back-distance and step-back-velocity were inversely related to motor UPDRS and freezing of gait questionnaire scores. PD participants had shorter step-back-distance than controls adjusted for age and sex. Repeat assessments in 16 participants, on average 0.7 years apart, showed good agreement on most of the quantified parameters. The backward stepping response in PD participants was quantifiable, reproducible, and related to disease severity and could be used to quantify progression towards postural instability in early-PD.


Voluntary Blood Donation Among Bahir Dar University Students: Application of Integrated Behavioral Model, Bahir Dar, Northwest Ethiopia, 2020.
The World Health Organization recommends that 1% to 3% of a country's population should donate blood to meet its demand and should focus on young people to achieve 100% voluntary blood donation. The aim of this study was to assess voluntary blood donation among Bahir Dar University students by using an integrated behavioral model. An institution-based cross-sectional study was conducted on Bahir Dar University students from March 1-21, 2020. A multi-stage sampling technique was applied to select 625 study participants. Data were entered in Epi data version 3.1 and then exported to SPSS version 23.0 for analysis. Path analysis was done using Stata 15 to check the causal effect of the integrated behavioral model constructs on voluntary blood donation. Internal consistency and validity of constructs were checked using Cronbach's alpha and exploratory factor analysis, respectively. Multivariable linear and logistics regression were used to predict independent predictors on intention and voluntary blood donation, respectively. The significant independent predictor was declared at 95% confidence interval and P-value < 0.05. One hundred and four (16.8%) university students donated blood voluntarily. Being female (AOR = 1.92 (1.15-3.22)), being third year (AOR = 2.88 (1.55-5.35)), knowledge (AOR = 1.53 (1.32-1.77)), descriptive norm (AOR = 1.10 (1.01-1.12)) and intention (AOR = 1.42 (1.28-1.57)) were positively associated with blood donation. Injunctive norm (B = 0.06) and self-efficacy (B = 0.36) have significant association with intention. Intention, descriptive norm and knowledge have significant effect on blood donation with path coefficient 0.0, 0.09 and 0.48, respectively. The magnitude of voluntary blood donation was low as compared to other similar studies. Descriptive norm, intention, knowledge, sex, year of study were significant predictors associated with voluntary blood donation. Therefore, behavioral change health communication strategies should develop to address these factors among the students. Researchers should conduct prospective analytical study design to examine the causal relationship of constructs of the model to develop better interventional strategy.


Current challenges and future directions in cardiac imaging.
Imaging is one of the most important accomplishments of medicine during the last 1000 years. The contribution of modern imaging to progress in the delivery of health care is unquestioned. However, we need to refine our use of imaging, limiting its use to those occasions when it can contribute directly or indirectly to improving and lengthening the lives of patients. Technology prowess in imaging alone is not sufficient to deliver value to individuals or to society. Continued investment in imaging technology requires critical appraisal of its use in clinical decision making and patient outcomes.


Evaluation of the IMMULITE® 2000 CMV IgM assay.
Diagnosis of cytomegalovirus (CMV) infection is challenging because of the high rate of asymptomatic infection and the low specificity of associated symptoms and signs. As a result, laboratory testing is an essential aid in making an accurate diagnosis. The presence of CMV IgM is indicative of primary CMV infection. In pregnancy, diagnosis of primary infection is important because primary maternal infection increases fetal infection risk substantially. Fetal infection can result in serious sequelae ranging from neurological deficits to death. Diagnosis among the immunocompromised is also critical for the timely initiation of therapy that can reduce morbidity and mortality risk. The IMMULITE® 2000 CMV IgM assay qualitatively detects CMV IgM antibodies in human serum or plasma to aid in the diagnosis of current or recent CMV infection. To determine expected values in apparently healthy subjects, 136 samples were tested. Reproducibility, normal range, and method comparison studies were also performed to evaluate the assay's performance. The assay's reproducibility was evaluated across three sites. Seven hundred and eighteen (n = 718) individual patient serum samples, which included samples from CMV IgM-positive (n = 109, determined by the Abbott IMx CMV or the Diamedix CMV IgM assays), pregnant (n = 210), HIV-positive (n = 30), immunosuppressed (n = 102), and transplant patients (n = 17) and from patients with potentially cross-reacting conditions (n = 136) were evaluated in the method comparison study. The positive, negative, and overall agreement between the IMMULITE 2000 CMV IgM assay and the VIDAS CMV IgM assay (predicate assay) were determined. The assay demonstrated excellent reproducibility with a total CV of less than 10%. The positive, negative, and overall agreement between the IMMULITE 2000 assay and the VIDAS assay were > 95% for the method comparison samples. Among potentially cross-reactive samples, the overall agreement between the two assays was 96%. Similarly, among the immunocompromised and pregnant subjects, the overall agreement was ~96% and ~97%, respectively. The IMMULITE 2000 CMV IgM assay demonstrated excellent reproducibility, minimal cross-reactivity, and performance comparable to that of the VIDAS CMV IgM assay. It can aid in the diagnosis of acute CMV or recent CMV infection by qualitatively detecting the CMV IgM antibodies in human serum or plasma.


Interplay between gene expression noise and regulatory network architecture.
Complex regulatory networks orchestrate most cellular processes in biological systems. Genes in such networks are subject to expression noise, resulting in isogenic cell populations exhibiting cell-to-cell variation in protein levels. Increasing evidence suggests that cells have evolved regulatory strategies to limit, tolerate or amplify expression noise. In this context, fundamental questions arise: how can the architecture of gene regulatory networks generate, make use of or be constrained by expression noise? Here, we discuss the interplay between expression noise and gene regulatory network at different levels of organization, ranging from a single regulatory interaction to entire regulatory networks. We then consider how this interplay impacts a variety of phenomena, such as pathogenicity, disease, adaptation to changing environments, differential cell-fate outcome and incomplete or partial penetrance effects. Finally, we highlight recent technological developments that permit measurements at the single-cell level, and discuss directions for future research.


Role of sexual intercourse in hematuria and proteinuria in males and females.
A probable association has been proposed between sexual intercourse and hematuria and proteinuria in either sex. The present study was to assess the role of sexual intercourse in hematuria and proteinuria in immediate dipstick urine test and morning urine sample analysis and whether sexual intercourse might be a cause of microscopic hematuria and proteinuria. Forty-two healthy married adult volunteers (27 male and 15 female; age range 20-48) were enrolled in a prospective clinical trial. Immediately after sexual intercourse urine samples were analyzed regarding hematuria and proteinuria with a dipstick, and the next morning samples for standard urinalysis. For categorical data analysis Fisher's exact test was utilized. p < 0.05 was considered significant. Proteinuria immediately after intercourse was significantly higher in males (88.9 vs. 13.3%, p < 0.001) but females showed significant higher hematuria (73.3 vs. 22.2%). None of the women developed hematuria and/or proteinuria in morning after urinalysis samples but males indicated significant proteinuria (33.3 vs. 0%, p = 0.02). Proteinuria and hematuria following sexual intercourse are gender-dependent, and temporally related to the timing of the testing and sexual activity. Testing the urine in the morning following intercourse may give false-positive protein results in men, but there is no evidence of false-positive hematuria in women unless the activity immediately precedes the testing.


Synthesis and Biocidal Activity of Some Naphthalene-Based Cationic Surfactants.
In this study, different cationic surfactants were prepared by reacting dodecyl bromide with tertiary amines to produce a series of quaternary ammonium salts that were converted subsequently to stannous and cobalt cationic complexes via complexing them with stannous (II) or cobalt (II) ions. Surface properties such as surface- and interfacial-tension, and the emulsifying power of these surfactants were investigated. The surface parameters including critical micelle concentration, maximum surface excess, minimum surface area, tension lowering efficiency and effectiveness were studied. The free energy of micellization and adsorption were calculated. Antimicrobial activity was determined via the inhibition zone diameter of the prepared compounds, which was measured against six strains of a representative group of microorganisms. The antimicrobial activity of some of the prepared surfactants against sulfate reducing bacteria was determined by the dilution method. FTIR spectra, elemental analysis and a H(1) NMR spectrum were examined to confirm compound structure and purity. The results obtained indicate that these compounds have good surface properties and good biocidal effect on broad spectrum of micro organisms.


Deconstructing emotion regulation in schizophrenia: the nature and consequences of abnormalities at the identification stage.
Existing evidence suggests that emotion regulation is abnormal in schizophrenia and associated with undesirable clinical outcomes. However, this literature is based predominantly on trait self-report and does not indicate which stages of emotion regulation (identification, selection, implementation) are impaired. The current study focused on determining the nature of abnormalities at the identification stage using ecological momentary assessment (EMA). Participants included clinically stable outpatients with schizophrenia (SZ; n = 48) and healthy controls (CN; n = 52) who completed 6 days of EMA. The EMA surveys assessed emotional experience, emotion regulation, and symptoms. Results indicated that SZ identified the need to regulate at a higher rate than CN. Specifically, SZ displayed an inefficient threshold for identifying the need to regulate, such that they regulated too much when negative affect was low and too little when negative affect was high. Emotion regulation effort exertion was also inefficient, such that effort was too high at low levels of negative affect and too low at high levels of negative affect in SZ. These identification stage abnormalities also demonstrated differential associations with positive and negative symptoms. Findings suggest that identification stage abnormalities may create a bottleneck that feeds forward and impacts subsequent stages of emotion regulation in SZ that are critically related to symptoms. Targeting the psychological processes underlying these identification stage abnormalities might offer a novel means of treating positive and negative symptoms in schizophrenia.


The feasibility of quantitative MRI of perivascular spaces at 7T.
Dilated brain perivascular spaces (PVSs) are found to be associated with many conditions, including aging, dementia, and Alzheimer's disease (AD). Conventionally, PVS assessment is mainly based on subjective observations of the number, size and shape of PVSs in MR images collected at clinical field strengths (≤3T). This study tests the feasibility of imaging and quantifying brain PVS with an ultra-high 7T whole-body MRI scanner. 3D high resolution T2-weighted brain images from healthy subjects (n=3) and AD patients (n=5) were acquired on a 7T whole-body MRI scanner. To automatically segment the small hyperintensive fluid-filling PVS structures, we also developed a quantitative program based on algorithms for spatial gradient, component connectivity, edge-detection, k-means clustering, etc., producing quantitative results of white matter PVS volume densities. The 3D maps of automatically segmented PVS show an apparent increase in PVS density in AD patients compared to age-matched healthy controls due to the PVS dilation (8.0±2.1 v/v% in AD vs. 4.9±1.3 v/v% in controls, p<0.05). We demonstrated that 7T provides sufficient SNR and resolution for quantitatively measuring PVSs in deep white matter that is challenging with clinical MRI systems (≤3T). Compared to the conventional visual counting and rating for the PVS assessment, the quantitation method we developed is automatic and objective. Quantitative PVS MRI at 7T may serve as a non-invasive and endogenous imaging biomarker for diseases with PVS dilation.


Dose optimization of fractionated external radiation and high-dose-rate intracavitary brachytherapy for FIGO stage IB uterine cervical carcinoma.
To determine the optimal dose combination scheme of external beam radiotherapy (EBRT) and high-dose-rate (HDR) intracavitary radiation (ICR) for maximizing tumor control while conferring an acceptable late complication rate in the treatment of Stage IB uterine cervical cancer. We retrospectively analyzed 162 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IB squamous cell carcinoma of the uterine cervix who received definitive RT between May 1979 and December 1990. Before HDR-ICR, all patients received EBRT to a total dose of 40-46 Gy (median 45), administered during 4-5 weeks to the whole pelvis. HDR-ICR was given 3 times weeks to a total dose of 24-51 Gy (median 39) at point A, using a dose of 3 Gy/fraction. Central shielding from EBRT was begun after the delivery using 20-45 Gy (median 40) of the external dose. The total dose to point A, calculated by adding the EBRT biologically effective dose (BED) and the ICR BED to point A, was 74.1-118.1 Gy (mean 95.2). The rectal point dose was calculated at the anterior rectal wall at the level of the cervical os. The local control rate, survival rate, and late complication rate were analyzed according to the irradiation dose and BED. The initial complete response rate was 99.4%. The overall 5-year survival rate and 5-year disease-free survival rate was 91.1% and 90.9%, respectively. The local failure rate was 4.9%, and the distant failure rate was 4.3%. Late complications were mild and occurred in 23.5% of patients, with 18.5% presenting with rectal complications and 4.9% with bladder complications. The mean rectal BED (the sum of the external midline BED and the ICR rectal point BED) was lower in the patients without rectal complications than in those with rectal complications (125.6 Gy vs. 142.7 Gy, p = 0.3210). The late rectal complication rate increased when the sum of the external midline BED and the rectal BED by ICR was >or=131 Gy (p = 0.1962). However, 5-year survival rates did not increase with the external midline BED (p = 0.4093). The late rectal complication rate also increased, without a change in the survival rate, when the sum of the external midline BED and the ICR point A BED was >90 Gy. In treating Stage IB carcinoma of the uterine cervix with HDR-ICR, using fractions of 3 Gy, it is crucial to keep the point A BED at <or=90 Gy to minimize late rectal complications without compromising the survival rate. To achieve this goal, appropriate central shielding from EBRT is needed.


Topological structure of a vortex in the Fulde-Ferrell-Larkin-Ovchinnikov state.
We find theoretically that the vortex core in the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state is quite different from the ordinary core for a simple topological reason. The intersection point of a vortex and nodal plane of the FFLO state empties the excess spins. This leads to observable consequences in the spatial structure of the spontaneous magnetization. We analyze this topological structure based on the low lying excitation spectrum by solving a microscopic Bogoliubov-de Gennes equation to clarify its physical origin.


Monoepoxy octadecadienoates and monoepoxy octadecatrienoates 2: mass spectral characterization.
Methyl esters of C18 polyunsaturated fatty acids, including gamma-linolenic acid, alpha-linolenic acid and stearidonic acid, were epoxidised using m-chloroperbenzoic acid. Nine monoepoxides were obtained by normal-phase HPLC, identified using LC-MS and NMR, and characterized by NMR spectroscopy and mass spectrometry. This study is focused on structural characterization using LC-MS and LC/APCI/MS/MS. The elution profiles of these monoepoxides in RP-HPLC are determined as 12,13->9,10->6,7-epoxy, 9,10->15,16->12,13-epoxy and 15,16->12,13->9,10-epoxy derivatives of gamma-linolenic, alpha-linolenic and stearidonic acid methyl esters, respectively. The major diagnostic fragmentations in MS/MS identified are postulated to be induced by cleavages of the epoxide ring and alpha-bond cleavage to the epoxy group from [M+H]+ and/or [M+H-MeOH]+.


The distribution and characteristics of LDL receptor mutations in China: A systematic review.
Familial hypercholesterolemia (FH) is a common and serious dominant genetic disease, and its main pathogenic gene is the low-density lipoprotein receptor (LDLR) gene. This study aimed to perform a systematic review of LDLR mutations in China. Using PubMed, Embase, Wanfang (Chinese), the Chinese National Knowledge Infrastructure (Chinese), and the Chinese Biological and Medical database (Chinese), public data were limited to December 2014. The Medical Subject Headings terms and the following key words were used: "familial hypercholesterolemia", "Chinese", "China", "Hong Kong", and "Taiwan". A total of 74 studies including 295 probands with 131 LDLR mutations were identified. Most of the mutations were located in exon 4 of LDLR and approximately 60% of the mutations were missense mutations. Thirty new mutations that were not recorded in the LDLR databases were found. In silico analysis revealed that most of the mutations were pathogenic. The primary LDLR mutations were C308Y, H562Y, and A606T, and all of the mutations had functional significance. Prevalence data suggest that there are nearly 3.8 million FH patients in China, although reported numbers are much smaller, suggesting that FH is widely misunderstood. This systematic review provides information that is specific to China for inclusion in the international FH database.


Teamwork in skull base surgery: An avenue for improvement in patient care.
During the past several decades, numerous centers have acquired significant expertise in the treatment of skull base pathologies. Favorable outcomes are not only due to meticulous surgical planning and execution, but they are also related to the collaborative efforts of multiple disciplines. We review the impact of teamwork on patient care, elaborate on the key processes for successful teamwork, and discuss its challenges. Pubmed and Medline databases were searched for publications from 1970 to 2012 using the following keywords: "teamwork", "multidisciplinary", "interdisciplinary", "surgery", "skull base", "neurosurgery", "tumor", and "outcome". Current literature testifies to the complexity of establishing and maintaining teamwork. To date, few reports on the impact of teamwork in the management of skull base pathologies have been published. This lack of literature is somewhat surprising given that most patients with skull base pathology receive care from multiple specialists. Common factors for success include a cohesive and well-integrated team structure with well-defined procedural organization. Although a multidisciplinary work force has clear advantages for improving today's quality of care and propelling research efforts for tomorrow's cure, teamwork is not intuitive and requires training, guidance, and executive support. Teamwork is recommended to improve quality over the full cycle of care and consequently patient outcomes. Increased recognition of the value of an integrated team approach for skull base pathologies will hopefully encourage centers, physicians, allied health caregivers, and scientists devoted to treating these patients and advancing the field of knowledge to invest the time, effort, and resources to optimize and organize their collective expertise.