Development and psychometric properties of the Washington Primary Care Interest Inventory.
To describe the development of the Washington Primary Care Interest Inventory (WPCII), which was designed to assess attitudes toward what constitutes appropriate psychosocial concerns for visiting a family physician, and to demonstrate the relationship between these attitudes and specialty selection in matriculating medical students. Five entering classes of medical students (1990 to 1995, without 1992) at the University of Washington were administered the WPCII during orientation. Reliability, factor, and predictive validity analyses were performed to measure the utility of the WPCII. Factor analysis revealed three interpretable factors to underlie the WPCII: stressors, physical complaints, and familial complaints. Scales developed from these factors correlated with students' early career preferences and showed significant differences across students who were selected under different interviewing formats. Differences between the sexes were found for both specific items and scales. The WPCII is a reliable and valid measure of attitudes toward the appropriateness of family physicians' treating psychosocial complaints. These attitudes have implications for the selection of medical students, curriculum development, assessment, and health education research.


Prediction of margin involvement and local recurrence after skin-sparing and simple mastectomy.
Skin-sparing mastectomy (SSM) facilitates immediate breast reconstruction. We investigated locoregional recurrence rates after SSM compared with simple mastectomy and the factors predicting oncological failure. Patients with early breast cancer that underwent mastectomy between 2000 and 2005 at a single institution were studied to ascertain local and systemic recurrence rates between groups. Kaplan-Meier curves and log-rank test were used to evaluate disease-free survival. Patients (n = 577) underwent simple mastectomy (80%) or SSM (20%). Median follow up was 80 months. Patients undergoing SSM were of younger average age, less often had involved lymph nodes (22% vs 44%, p < 0.001), more often had DCIS present (79% vs 53%, p < 0.001) and involved margins (29% vs 15%, p = 0.001). Involved surgical margins were associated with large size (p = 0.001). The 8-year local recurrence (LR) rates were 7.9% for SSM and 5% for simple mastectomy respectively (p = 0.35). Predictors of locoregional recurrence were lymph node involvement (HR 8.0, for >4 nodes, p < 0.001) and involved surgical margins (HR 3.3, p = 0.002). In node negative patients, SSM was a predictor of locoregional recurrence (HR 4.8 [1.1, 19.9], p = 0.033). Delayed reconstruction is more appropriate for node positive early breast cancer after post-mastectomy radiotherapy. Re-excision of involved margins is essential to prevent local recurrence after mastectomy.


Desensitization of renal vasopressin-stimulated adenylate cyclase by a vasopressor and antidiuretic antagonist, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-ethyl)-D-tyrosine, 4-valine]arginine vasopressin.
Desensitization of the renal antidiuretic (V2) receptor has been regarded as agonist-specific. We found that a vasopressor and antidiuretic (V1V2) antagonist d(CH2)5DTyr(Et)VAVP induced desensitization of the receptor and that a vasopressor (V1) antagonist d(CH2)5Tyr(Me)AVP, which is a weak antidiuretic (V2) agonist, counteracted the potent desensitizing action of 1-deamino-8-D-arginine-vasopressin and endogenous arginine vasopressin.


A surgical strategy for intrahepatic cholangiocarcinoma - the hilar first concept.
The present study assesses long-term overall survival (OS) and disease-free survival (DFS) after curative resection for intrahepatic cholangiocarcinoma (ICCA) depending on resection margin (RM) status and lymph node (LN) status. Clinical data of all consecutively resected patients with ICCA at a single high-volume center between 2005 and 2018 were collected. Minimum follow-up was 36 months. Perioperative and long-term oncological outcome was assessed. One hundred ninety-two cases were included in the analysis. Thirty- and 90-day-mortality was 5.2% (n = 10) and 10.9% (n = 21). OS was 26 months with 1-, 2-, and 5-year-OS rates of 72%, 53%, and 26%. One-, 2-, and 5-year-DFS rates were 54%, 42%, and 35% (N0 vs. N1: 29 vs. 9 months, p = 0.116). R1 was not found to be an independent risk factor for reduced survival in the overall cohort (p = 0.098). When differentiating according to the LN status, clear resection margins were significantly associated with increased DFS for N0 cases (50 months vs. 9 months, p = 0.004). For N1 cases, no significant difference in DFS was calculated for R0 compared to R1 cases (9 months vs. 9 months, p = 0.88). For N0 cases, clear resection margins > 10 mm were associated with prolonged OS (p = 0.048). For N1 cases, there was no significant survival benefit when comparing R0 versus R1, while the complication rate remained high for the extended resection types. In view of merging multimodal treatment, the hilar first concept assesses locoregional LN status for optimal surgical therapy.


Social Support Among Women With Potential Essure-Related Complaints: Analysis of Facebook Group Content.
Social support groups are an important resource for people to cope with problems. Previous studies have reported the different types of support in these groups, but little is known about the type of reactions that sharing of personal experiences induce among members. It is important to know how and to what extent members of support groups influence each other regarding the consumption of medical care. We researched this in a web-based Facebook group of women sterilized with Essure. Essure was a device intended for permanent contraception. From 2015 onward, women treated with Essure for tubal occlusion raised safety concerns and numerous complaints. This study aimed to evaluate the use of social support in a Facebook community named "Essure problemen Nederland" (EPN; in English, "Essure problems in the Netherlands"). All posts in the closed Facebook group EPN between March 8 and May 8, 2018, were included. In total, 3491 Facebook posts were analyzed using a modified version of the Social Support Behavior Codes framework created by Cutrona and Suhr in 1992. Posts were abstracted and aggregated into a database. Two investigators evaluated the posts, developed a modified version of the Social Support Behavior Codes framework, and applied the codes to the collected data. We found that 92% of messages contained a form of social support. In 68.8% of posts, social support was provided, and in 31.2% of posts, social support was received. Informational and emotional support was the most frequently used form of provided social support (40.6% and 55.5%, respectively). The same distribution was seen with received social support: informational support in 81.5% and emotional support in 17.4% of cases. Our analysis showed a strong correlation between providing or receiving social support and the main form of social support (P<.001). In a total of only 74 (2.2%) cases, women advised each other to seek medical care. The main purpose of women in the EPN Facebook group was to provide and receive informational or emotional support or both.


Strut failure of the Starr-Edwards cloth-covered metallic ball prosthesis. Report of two asymptomatic cases and review of the overall experience.
Two cases of asymptomatic strut failure of an aortic Starr-Edwards cloth-covered metallic ball prosthesis are reported. Strut failure can be asymptomatic for years. Available information on the overall worldwide experience of six cases is reviewed and suggestions made for early diagnosis and treatment of this rare complication.


Impaired control in addiction involves cognitive distortions and unreliable self-control, not compulsive desires and overwhelmed self-control.
Impaired control in addiction involves a characteristic but obscure kind of partial control. Certain aspects of control over drug use are clearly reduced, reflected in difficulty cutting back and relapse. However, other aspects of control are clearly preserved, as reflected in substantial sensitivity to situational incentives-for example, the ability to defer use when needed. This juxtaposition is puzzling, and a clear mechanistically precise understanding of impaired control has yet to emerge. In this article, a Distortion model of impaired control is put forward. The key insight of the model is that the puzzling pattern of partial control seen in addiction can be understood in terms of unreliable control. The model posits large populations of distorted automatic thoughts (e.g., about drugs, one's self, one's circumstances, and one's abilities to cope), coupled with unreliable control over these distorted thoughts. These distorted thoughts, typically gradually and cumulatively, lead to illusion-like misvaluation of costs and benefits of drug use, in turn eventually leading to decisions to use. The model captures an elusive middle ground in addiction in which substantially preserved control over drug use for briefer intervals coexists with difficulty maintaining sobriety over the long-term. Moreover, the model explains a range of clinical findings in addiction that are not easily accommodated on leading alternative views.


Response of whole blood, erythrocyte and plasma vitamin E content to dietary vitamin E intake in the chick.
Whole blood, red blood cells (RBC), and plasma vitamin E (VE) levels in chicks fed dietary VE (dl-alpha-tocopheryl acetate, dl-alpha Ta) supplementation in steps of 0.0, 5.0, 10.0, 15.0, 20.0 and 30.0 mg/Kg were determined to examine their usefulness as an index of VE status. The increase in VE level was significant and linear in whole blood (r = 0.90), RBC (r = 0.89) and plasma (r = 0.93) in response to dietary VE intake. There was a close correlation between VE in plasma vs whole blood (r = 0.90), plasma vs RBC (r = 0.91) and whole blood vs RBC (r = 0.95). The plasma VE content was 1.2-1.8 times greater than that of whole blood, and 6.6-12.5 times greater than that of RBC. The plasma total lipids content was not affected by the dietary VE intake, whereas the level of VE in the plasma total lipids was significantly increased with increasing supplementation. Alpha tocopherol was the major isomer (ca 92%) of VE in whole blood, RBC and plasma at hatching. The small proportions of beta-tocopherol (ca 2%), gamma-tocopherol (ca 5%) and alpha-tocotrienol (ca 1%) observed at 1 day of age had decreased or totally disappeared by 7 days of age after feeding the VE-free basal diet. The data showed that in the chick, the whole blood and RBC levels of VE were as sensitive and reliable indexes of dietary VE status as was that of the plasma.


Do personalised letters in Vietnamese increase cervical cancer screening among Vietnamese women?
In Australia, Vietnamese women are at greater risk of cervical cancer than other Australian women. To increase their participation in cervical screening, the Vietnamese community was exposed to a media campaign about the advantages of cervical smear screening which was delivered in Vietnamese through Vietnamese newspapers and radio. In addition, 689 Vietnamese (18-67 years) were selected from the electoral roll. They were randomly assigned to either receive a personal letter written in Vietnamese promoting cervical screening, or not. We report on the effect of the letter on smear rates. Being randomised to be sent such a letter was not associated with any increase in screening (relative rate of appropriate screening in the intervention versus the control group was 0.85, 95% CI 0.55-1.3). It is important to carefully evaluate untested health promotion interventions.


Stimulation of human lymphocytes by oxidized red blood cells (RBC) in the presence of polyethylene glycol (PEG).
In the present work, it is shown that oxidized red blood cells (RBC) in the presence of polyethylene glycol (PEG) is a powerful cellular class-II MHC-free mitogen for human lymphocytes. Human lymphocytes were stimulated with oxidized autologous human RBC or sheep RBC in the absence or presence of PEG, M.W. 10,000. The RBC were oxidized with the enzyme combination neuraminidase-galactose oxidase or with sodium periodate. The presence of PEG strongly potentiated the response. Optimal stimulatory conditions were obtained with a 10:1 ratio of oxidized RBC to lymphocytes and a PEG concentration of 25 +/- 5%.


High Prevalence of Indications for Pre-exposure Prophylaxis Among People Who Inject Drugs in Boston, Massachusetts.
In Massachusetts, recent outbreaks of HIV have been fueled by injection and sexual exposures among people who inject drugs. Understanding pre-exposure prophylaxis need, knowledge, and use among people who inject drugs will help inform and evaluate interventions. In 2019, investigators analyzed 2018 National HIV Behavioral Surveillance data from people who inject drugs in Boston, MA, who met eligibility criteria. Proportions of people who inject drugs with U.S. Preventive Services Task Force-based pre-exposure prophylaxis indication were estimated by types of HIV acquisition risk in the past year: injection exposure only, sexual exposure only, and overlapping injection and sexual exposures. Investigators then evaluated pre-exposure prophylaxis awareness, conversations with healthcare providers about pre-exposure prophylaxis, and self-reported pre-exposure prophylaxis use among those with and without pre-exposure prophylaxis indications. The prevalence of pre-exposure prophylaxis indication was 92% overall (389/423), with 290 (69%) participants indicated for injection exposures only, 3 (<1%) indicated for sexual exposures only, and 96 (23%) indicated for both injection and sexual exposures. Among those indicated for pre-exposure prophylaxis (n=389), 152 (39%) reported being aware of pre-exposure prophylaxis, 41 (11%) had discussed pre-exposure prophylaxis with a healthcare provider, and 8 (2%) had used pre-exposure prophylaxis in the past year. There were no statistically significant differences between pre-exposure prophylaxis‒indicated and ‒nonindicated people who inject drugs with respect to pre-exposure prophylaxis awareness, discussion with a healthcare provider, and pre-exposure prophylaxis use. Indication for pre-exposure prophylaxis was high, but awareness was low, conversations about pre-exposure prophylaxis with healthcare providers were uncommon, and pre-exposure prophylaxis use was extremely low. These findings highlight important areas for clinical and community-based interventions to improve pre-exposure prophylaxis uptake among and delivery to people who inject drugs.


Association between occlusal support and cognitive impairment in older Chinese adults: a community-based study.
The loss of occlusal support due to tooth loss is associated with systemic diseases. However, there was little about the association between occlusal support and cognitive impairment. The cross-sectional study aimed to investigate their association. Cognitive function was assessed and diagnosed in 1,225 community-dwelling adults aged 60 years or older in Jing'an District, Shanghai. Participants were diagnosed with mild cognitive impairment (MCI) by Peterson's criteria, or dementia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. We determined the number of functional occlusal supporting areas according to Eichner classifications. We used multivariate logistic regression models to analyze the relationship between occlusal support and cognitive impairment and mediation effect models to analyze the mediation effect of age. Six hundred sixty participants were diagnosed with cognitive impairment, averaging 79.92 years old. After adjusting age, sex, education level, cigarette smoking, alcohol drinking, cardiovascular disease, and diabetes, individuals with poor occlusal support had an OR of 3.674 (95%CI 1.141-11.829) for cognitive impairment compared to those with good occlusal support. Age mediated 66.53% of the association between the number of functional occlusal supporting areas and cognitive impairment. In this study, cognitive impairment was significantly associated with the number of missing teeth, functional occlusal areas, and Eichner classifications with older community residents. Occlusal support should be a significant concern for people with cognitive impairment.


Chronic pure radiculopathy in patient with organizing epidural hematoma around C8 nerve root.
Spontaneously occurring spinal epidural hematomas are uncommon clinical findings, and the chronic form is the rarest and its most frequent location is the lumbar spine. Pure radicular involvement is far less frequent than myelopathy. We report a case of progressive radiculopathy in a 52-year-old man with spontaneously occurring cervical epidural hematoma (SCEH). The patient had left hand weakness and numbness for 4 months. MRI scan showed small space-occupying lesion around left 8th cervical nerve root. After surgery we confirmed chronic organizing epidural hematoma. To the best of our knowledge, this is the second reported case in the worldwide literature of pure radiculopathy in a patient with chronic SCEH.


A primary squamous cell carcinoma of the sigmoid colon in a young patient: A case report and literature review.
Colon cancer is among the most common types of cancer with adenocarcinomas being the most common type. Herein we report a young patient who presented with primary colonic squamous cell carcinoma without risk factors. To the best of our knowledge, this is the youngest patient with such diagnosis worldwide.


AChR-and MuSK-positive myasthenia gravis: Double trouble.
This is a report of an early onset AChR-and MuSK-positive myasthenia gravis. The double seropositivity was detected at the onset of the disease and persisted during 3.5 years follow-up despite the chronic immunotherapy and thymectomy. It is the second reported case of this rare immunological coexistence with sufficient follow-up and available clinical details. At the detection of double positive AChR and MuSK Abs, the treating physician often feels unsecure about the optimal treatment strategy and the long-term prognosis. The detailed clinical record and the long observation of these rare cases, are mandatory for best management in clinical practice.


Effects of surrounding sequence on the suppression of nonsense codons.
Using a lacI-Z fusion system, we have determined the efficiency of suppression of nonsense codons in the I gene of Escherichia coli by assaying beta-galactosidase activity. We examined the efficiency of four amber suppressors acting on 42 different amber (UAG) codons at known positions in the I gene, and the efficiency of a UAG suppressor at 14 different UGA codons. The largest effects were found with the amber suppressor supE (Su2), which displayed efficiencies that varied over a 35-fold range, and with the UGA suppressor, which displayed a 170-fold variation in efficiency. Certain UGA sites were so poorly suppressed (less than 0.2%) by the UGA suppressor that they were not originally detected as nonsense mutations. Suppression efficiency can be correlated with the sequence on the 3' side of the codon being suppressed, and in many cases with the first base on the 3' side. In general, codons followed by A or G are well suppressed, and codons followed by U or C are poorly suppressed. There are exceptions, however, since codons followed by CUG or CUC are well suppressed. Models explaining the effect of the surrounding sequence on suppression efficiency are considered in the Discussion and in the accompanying paper.


Disturbance observer based fault estimation and dynamic output feedback fault tolerant control for fuzzy systems with local nonlinear models.
This paper addresses the problems of fault estimation (FE) and fault tolerant control (FTC) for fuzzy systems with local nonlinear models, external disturbances, sensor and actuator faults, simultaneously. Disturbance observer (DO) and FE observer are designed, simultaneously. Compared with the existing results, the proposed observer is with a wider application range. Using the estimation information, a novel fuzzy dynamic output feedback fault tolerant controller (DOFFTC) is designed. The controller can be used for the fuzzy systems with unmeasurable local nonlinear models, mismatched input disturbances, and measurement output affecting by sensor faults and disturbances. At last, the simulation shows the effectiveness of the proposed methods.


Carbohydrate composition of the human cataractous lenses.
Specific chemical assays, including carbohydrate, hexosamines and hexuronic acid, were determined on the lens insoluble albumoid. It was noticed that the carbohydrate composition varies with age. The significance of carbohydrate in the lens is discussed.


On the diagnosis of polycythaemia vera as assessed in the health and medical care in the Västra Götaland region, Sweden.
The aim was to assess how the diagnosis of polycythaemia vera (PV) was established and to study to which extent the classic Polycythemia Vera Study Group (PVSG) criteria and the revised criteria for the diagnosis of PV as proposed by Pearson and Messinezy in 1996 (PM criteria) were fulfilled when the diagnosis of PV was made. A questionnaire was sent to physicians in charge of haematological patients at the departments of medicine in 12 hospitals in the Health and Medical Care in the Västra Götaland Region (VGR), Sweden, with a population of 1.5 million inhabitants; they were asked to provide reports as regards all patients with an unequivocal diagnosis of PV during a 5-year period from January 1994 to December 1998. Full reports were obtained from six hospitals, which serve about 1.1 million inhabitants. The results from a total of 129 PV patients, 62 from two university hospitals (UHs) and 67 from four county hospitals (CHs), were the subject of the present analysis. Results. It was shown that measurement of the red cell mass (RCM) had been carried out in 61 of 62 (98%) patients in UHs compared with 24 of 67 (36%) patients at CHs (P < 0.01). By using ultrasound imaging and/or scintigraphy the spleen size had been determined in 55 of 62 (89%) patients at UHs and in 24 of 67 (36%) patients at CHs (P < 0.01). At the UHs, arterial oxygen saturation had been measured in 32 of 62 (52%) patients; the corresponding figure for the CH patients was 22 of 67 (33%). Plasma or serum erythropoietin (EPO) concentrations had been measured in 44 of 62 (71%) of PV patients at UHs and in 31 of 67 (46%) of patients at CHs; in all these cases the EPO concentrations were subnormal or not measurable. At the UHs only 37% of the PV patients fulfilled the PVSG criteria for the diagnosis of PV whereas the corresponding figure for CHs was 4% (P < 0.01). The adherence to PM criteria was, however, 71% at UHs compared with 16% at CHs (P < 0.01).


The use of shadow-casting technique for measurement of the width of elongated particles.
A method is described for the estimation of the true width of fibrillar or rod-like structures from electron micrographs of metal-shadowed preparations. The method is based on variations in the image width as a function of the angle (beta) between the long axis of the fibril and the direction of the shadow in the plane of the preparation. The image width when beta = 0 degrees practically represents the real width of the elongated particle but is often indistinguishable from the background. The fibril image width is conveniently measured at beta values between 15 degrees and 90 degrees . The true width is obtained by plotting the image width versus sin beta and extrapolating to beta = 0 degrees . Latex spheres are sprayed with the fibrils or rods to indicate the direction of shadow. Tobacco mosaic virus (TMV) was used as a model structure because of its known constant diameter of 150 A (5). The width (in the case of TMV equal to the diameter) found by the present method was 150 A +/- 8 A.


Microsatellite Status Detection in Gastrointestinal Cancers: PCR/NGS Is Mandatory in Negative/Patchy MMR Immunohistochemistry.
Microsatellite instability (MSI) is a predictive biomarker for immune checkpoint inhibitors. The main goal was to investigate the discordance between IHC and PCR/NGS for MSI testing in gastrointestinal cancers. Two series were analyzed through IHC for mismatch-repair-system proteins (MMRP) and PCR, with one series of 444 colorectal cancers (CRC) and the other of 176 gastric cancers (GC). All cases with discordant results between IHC and PCR were analyzed by NGS. IHC staining was evaluated as follows: proficient MMR (pMMR), with all MMR positive; deficient MMR (dMMR), with the loss of one heterodimer; and cases with the loss/patchy expression of one MMR (lo-paMMR). Cases with instability in at least two markers by PCR were MSI-high (MSI-H) and with instability in one marker, MSI-low (MSI-L). Cases without instability were evaluated as microsatellite-stable (MSS). In the CRC cohort, 15 out of 444 cases were dMMR and 46 lo-paMMR. Among the 15 dMMR, 13 were MSI-H and 2 MSS. Among the 46 lo-paMMR, 13 were MSI-H and 33 were MSS. In the GC cohort, 13 out of 176 cases were dMMR and 6 cases lo-paMMR. Among the 13 dMMR, 12 were MSI-H and only 1 was MSS. All six lo-paMMR cases were MSS. All NGS results were in agreement with PCR. In clinical practice, MMR-IHC could be used as a screening test and additional molecular analysis is mandatory exclusively in cases carrying loss/patchy MMR-IHC.


Histochemical alterations of re-innervated rat extensor digitorum longus muscle after end-to-end or graft repair: a comparative histomorphological study.
Changes in the histochemical profile of 43 rat extensor digitorum longus muscles undergoing de-innervation and re-innervation were recorded. Assessment of fibre type composition and muscle fibre cross-sectional area was performed at 15, 30, 90 and 180 days post operative (p.o.) after either primary end-to-end repair or autologous graft repair of the common peroneal nerve (n = 5 per time point and type of repair). The size and histochemical profile of single muscle fibres were analysed by computer-assisted quantification on the basis of their myofibrillar ATPase (pH 4.3) and succinate dehydrogenase (SDH) activities in serial, whole-muscle cross-sections. Accordingly, four muscle-fibre types could be functionally identified: (1) slow oxidative (SO, type I); (2) fast-oxidative glycolytic (FOG, type IIA); (3) fast glycolytic (FG, type IIB); and (4) succinate dehydrogenase intermediate (SDH-INT). At 15 days following end-to-end repair, the SDH-INT muscle fibre type was observed. By contrast, 15 days following graft repair, no changes in fibre type composition were observed (vs. control). At 30 days p.o. in the group that received end-to-end repair, type SDH-INT reached its maximum and was significantly higher than in the group that underwent graft repair. At 90 days p.o., the amount of SDH-INT fibres declined after end-to-end repair, but it was still significantly higher than in the group treated with a nerve graft. The increase of the SDH-INT fibre type was mirrored by a proportional disappearance of FG and FOG fibres. These changes were time-dependent, not reversible at 180 days p.o and largely blunted after nerve graft. Muscle-fibre size decreased at 15 and 30 days after both types of nerve repair. This decrease was transient and reversible within 90 days p.o. These findings reflect the fact that the reorganization of the histochemical profile in re-innervated muscles is both time dependent and long lasting. The degree of this reorganization is significantly higher after end-to-end repair than after graft repair.


Two bronze medals for Switzerland at the 43rd International Chemistry Olympiad in Ankara, Turkey.
At the 2011 International Chemistry Olympiad in Ankara, with 71 participating countries, Switzerland achieved two bronze medals thanks to two outstanding students.


Case report: ultrasound and MRI findings in a scrotal epidermoid cyst.
Intrascrotal masses in the adult are worrisome due to their possible malignancy. Most intratesticular masses are malignant whereas most extratesticular masses are benign. The differential diagnosis of intrascrotal cysts usually includes simple testicular cysts, intratesticular epidermoid and dermoid cysts, tunica albuginea cysts, epididymal cysts and spermatoceles [1-7]. This case report describes a large epidermoid cyst of the scrotum presenting as an enlarging scrotal tumour.


Liver abscess of Actinomyces israelii in a hemodialysis patient: case report and review of the literature.
We had encountered a 74-year-old woman on hemodialysis therapy suffering from liver abscess of Actinomyces israelii. Percutaneous drainage of the abscess before starting antimicrobial therapy followed by correct microbiological identification and susceptibility test led us to determine long treatment with ampicillin and to a successful outcome. Periodontitis was thought to be a possible entry of actinomyces. Hepatic actinomycosis should be recognized as one of the important infectious diseases among patients of end-stage renal disease.


Degradability of chlorophenols using ferrate(VI) in contaminated groundwater.
The production and use of chlorophenolic compounds in industry has led to the introduction of many xenobiotics, among them chlorophenols (CPs), into the environment. Five CPs are listed in the priority pollutant list of the U.S. EPA, with pentachlorophenol (PCP) even being proposed for listing under the Stockholm Convention as a persistent organic pollutant (POP). A green procedure for degrading such pollutants is greatly needed. The use of ferrate could be such a process. This paper studies the degradation of CPs (with an emphasis on PCP) in the presence of ferrate both in a spiked demineralized water system as well as in real contaminated groundwater. Results proved that ferrate was able to completely remove PCP from both water systems. Investigation of the effect of ferrate purity showed that even less pure and thus much cheaper ferrate was applicable. However, with decreasing ferrate purity, the degradability of CPs may be lower.


Analysis of regulator of G-protein signaling-2 (RGS-2) expression and function in osteoblastic cells.
Regulator of G-protein signaling-2 (RGS-2) belongs to a novel family of GTPase-activating proteins that rapidly turn-off G-protein coupled receptor signaling. RGS proteins contain a characteristic RGS domain by which they interact with the alpha-subunit of G-proteins and drive them into their inactive GDP-bound forms. Previously, we have reported that RGS-2 mRNA is rapidly and transiently increased by PTH in rat bone and in osteoblast cultures in vitro. In this study, we further explored the molecular basis for the regulation of RGS-2 by cloning and functionally characterizing the RGS-2 gene promoter. We cloned 2.3- and 2.8-kb fragments of the 5'-flanking regions of the rat and mouse RGS-2 genes, respectively, and generated a stable clone of UMR106 osteoblastic cells containing the rat RGS-2 promoter driving the beta-gal reporter gene (p2.3RGS-2-beta-gal). Treatment of the stable clone with PTH resulted in a maximal 2.2- to 3.6-fold increase in promoter activity at 8 h, reminiscent of the early response observed with endogenous RGS-2 mRNA regulation. Further, PTH (1-38), (1-31), PTHrP (1-34), and forskolin, which elevate cAMP levels, stimulated the promoter, while PTH (3-34) and (7-34), which do not readily stimulate cAMP accumulation, and PMA that directly activates protein kinase C, had no effect on promoter activity. Taken together, these results implicate the involvement of the Galpha(s)-adenylate cyclase-protein kinase A pathway in stimulating RGS-2 expression. Maintenance of a hyperphosphorylated state via the inhibition of type 2A protein phosphatases by okadaic acid, resulted in a strong dose-dependent increase in transcriptional activity of the RGS-2 promoter as well as that of the endogenous RGS-2 gene. Furthermore, overexpression of the osteoblast-specific transcription factor Runx2 also led to a stimulation of RGS-2 promoter activity. Functional analysis using RGS-2 overexpression suggests the potential negative regulatory effects of RGS-2 on PTH- and forskolin-induced cAMP production in osteoblastic cells. In summary, our data suggest that PTH treatment results in a direct transcriptional stimulation of RGS-2 that in turn may play a role in modulating the duration/intensity of PTH receptor signaling.


Breast metastasis as the first clinical manifestation of ileal neuroendocrine tumor. A challenging diagnosis with relevant clinical implications.
Ileal neuroendocrine tumors are slow-growing grade 1 or, more rarely, grade 2 neuroendocrine tumors which, however, are frequently metastatic to regional lymph nodes and the liver. A few cases of ileal neuroendocrine tumors that are metastatic to the breast have also been reported in the medical literature. The knowledge of this uncommon clinical presentation is of great importance because it needs to be differentiated from primary breast carcinomas with neuroendocrine features, which represent completely different entities with a different therapeutic approach. The diagnosis of a breast metastasis from an ileal neuroendocrine tumor and its distinction from a well-differentiated primary neuroendocrine tumor of the breast is a challenging task for clinicians and pathologists. This workup is particularly difficult when the breast lesion is the first sign of malignancy. In the present paper, we describe the clinicopathological features of an ileal neuroendocrine tumor first presenting with a breast metastasis in a 50-year-old woman and we discuss the key diagnostic features for the differential diagnosis with primary well-differentiated neuroendocrine tumor of the breast. Moreover, we have reviewed the medical literature to give the reader a comprehensive overview on this topic.


There is no relation between mild malalignment and meniscal extrusion in trauma emergency patients.
To evaluate whether an alteration of the lower limb axis is associated with meniscal extrusion. Ninety-four patients who had complained of knee pain with good knee function and had a knee magnetic resonance image (MRI) and a full-length X-ray taken of the lower limb were included in the study. Meniscal extrusion was measured in the coronal MRI. Subluxation of the meniscus was considered minor or physiological if ≤ 3 mm, and major if >3 mm. The extrusion as a percentage of meniscus size was also calculated. Knee alignment (varus, negative value; valgus, positive value) was correlated with the presence of minor and major extrusion. There were varus knees in 61 cases (58.7%), with a mean measured deviation of -2.63°. Valgus knees were observed in 27 knees (26%) and had a mean deviation of 2.22°. The medial meniscus showed major extrusion in 18 cases (17.3%). It corresponded to 44.7% of the meniscus size. The lateral menisci showed no subluxation in most cases. There was no correlation between alignment and meniscal extrusion in this series, either for the medial meniscus (p = 0.760) or for the lateral meniscus (p = 0.381). In patients complaining of knee pain with good knee function, there is no relationship between mild malalignment and the degree of meniscus extrusion.


Prognostic significance of increased thallium-201 lung uptake during dipyridamole myocardial scintigraphy: comparison with exercise scintigraphy.
To compare the incidence of cardiac events among patients with increased lung uptake of thallium after dipyridamole stress, matched subjects without such uptake and matched subjects with increased lung uptake during exercise stress. Retrospective case control study based on quantitative and semiquantitative visual consensus analysis of thallium scintigraphy. Nuclear cardiology laboratory of a university teaching hospital. Thirty-six patients with increased lung activity after dipyridamole stress and two groups of matched control subjects identified from 3150 consecutive thallium single photon emission computed tomography studies. Telephone follow-up and chart reviews to determine the incidence of cardiac events. Cardiac events were significantly less frequent in the study group with increased lung uptake after dipyridamole stress (two of 36,5%) than in the control group with increased thallium lung uptake at exercise scintigraphy (nine of 36,25%; P = 0.046). Increased lung uptake of thallium has less ominous short term prognostic significance when observed in association with dipyridamole stress rather than with exercise.


Development of tolerance to the inhibitory effects of ethanol in the isolated rat vas deferens. Effect of selective agonists and antagonists.
Our previous experiments demonstrated that chronic ethanol treatment of rats produces tolerance to the in vitro inhibitory effects of ethanol on norepinephrine-, KCl-, and electrically evoked contractions of the vas deferens. In the present study, ethanol dependence also resulted in subsensitivity of the vas to the effects induced by alpha 2-adrenoceptor agonist clonidine, the alpha-receptor antagonists phentolamine and phenoxybenzamine, as well as to adenosine and naloxone. These results indicate that the biochemical mechanisms of ethanol express themselves at both the pre- and postjunctional level involved in the modulation of neurotransmission in the rat vas deferens.


An indirect enzyme-linked immunosorbent assay for the detection of diacetoxyscirpenol in wheat and corn.
An indirect enzyme-linked immunosorbent assay (ELISA) was developed for quantitation of diacetoxyscirpenol (DAS) in wheat flour and corn meal. Diacetoxyscirpenol was first converted to its "b"-carboxymethoxyl oxime and then conjugated to bovine serum albumin (BSA) via a water-soluble carbodiimide method. This conjugate was then coated to a microtiter plate and incubated with rabbit anti-DAS antibody and sample extract. The amount of anti-DAS antibody bound to the plate was then determined by reaction of goat anti-rabbit IgG-peroxidase complex, and subsequent reaction with substrate. Samples spiked with DAS were extracted with acetone and subjected to a simple cleanup procedure by passing them through a reversed-phase Sep-Pak C-18 cartridge. The minimum detection level for DAS was 5 picograms per assay. Average recoveries from samples of wheat flour spiked with DAS in the 1 - 100 ppb range were 97.5 ± 17.8% for one gram samples, and 97.2 ± 19.9 % for fifty gram samples. Average recoveries from corn meal samples spiked in the same range were 98.8 ± 22.6 % for one gram samples, and 99.7 ± 17.3 % for fifty gram samples.


Establishing a Standardized Surveillance System for Health Care-Associated Infections in Vietnam.
Standardized surveillance for health care-associated infections (HAI) is critical to understand HAI burden and inform prevention strategies at a national level. Due to differing and generally limited resources in Vietnam's health care facilities, implementation of HAI surveillance has been variable and data quality has not been systematically assessed. In 2016, the Vietnam Administration for Medical Services (VAMS) under the Ministry of Health, with the support of partners, began to establish a context-appropriate, standardized HAI surveillance system for bloodstream infections (BSI) and urinary tract infections (UTI) among 6 pilot hospitals in Vietnam. We identified 5 key elements of our HAI surveillance implementation process that have been conducive to ensuring data quality and program sustainability and scalability. These include: (1) engaging stakeholders, (2) designating roles and responsibilities, (3) developing context-sensitive, standardized surveillance protocols, (4) creating a surveillance implementation strategy, and (5) linking HAI surveillance and prevention activities. With the active participation of infection prevention and control staff from the 6 pilot hospitals, standardized HAI surveillance for BSIs and UTIs was expanded to 12 additional hospitals in 2019. Together, VAMS and partners are helping Vietnam fulfill its commitment to safe health care for all patients.


Characteristics of phospholipids in microvillar membranes of octopus photoreceptor cells.
Characteristics of lipids in the microvillar membranes of octopus photoreceptor cells were studied in order to obtain some information on the membrane environment with rhodopsin in the invertebrate. (1) The membranes contain lipid and protein in almost equal proportion. The majority of lipids are phospholipids. Neutral lipids make up 16% of the total lipids, the major constituent of which is cholesterol. (2) Phosphatidylethanolamine and phosphatidylcholine are the major phospholipids. Phosphatidylserine, ceramide 2-aminoethylphosphonate and sphingomyelin occur as minor components. An unidentified alkaline and acid stable phospholipid was found. (3) The predominant fatty acids of phosphatidylethanolamine and phosphatidylcholine are highly unsaturated such as 22 : 6, 20 : 5 and 20 : 4. The 22 : 6 and 20 : 5 are exclusively linked at the 2-position, but the 20 : 4 is linked significantly at the 1-position of the phospholipids. (4) Major molecular species are 16 : 0/22 : 6 (48.4%) and 16 : 0/20 : 4 (19.6%) in phosphatidylcholine, and 20 : 4/22 : 6 (50.7%) and 16 : 0/22 : 6 (25.6%) in phosphatidylethanolamine.


Autophagy-nutrient sensing pathways in diabetic complications.
The incidence of diabetes has been increasing in recent decades which is affecting the population of both, developed and developing countries. Diabetes is associated with micro and macrovascular complications which predominantly result from hyperglycemia and disrupted metabolic pathways. Persistent hyperglycemia leads to increased reactive oxygen species (ROS) generation, formation of misfolded and abnormal proteins, and disruption of normal cellular functioning. The inability to maintain metabolic homeostasis under excessive energy and nutrient input, which induces insulin resistance, is a crucial feature during the transition from obesity to diabetes. According to various study reports, redox alterations, intracellular stress and chronic inflammation responses have all been linked to dysregulated energy metabolism and insulin resistance. Autophagy has been considered a cleansing mechanism to prevent these anomalies and restore cellular homeostasis. However, disrupted autophagy has been linked to the pathogenesis of metabolic disorders such as obesity and diabetes. Recent studies have reported that the regulation of autophagy has a beneficial role against these conditions. When there is plenty of food, nutrient-sensing pathways activate anabolism and storage, but the shortage of food activates homeostatic mechanisms like autophagy, which mobilises internal stockpiles. These nutrient-sensing pathways are well conserved in eukaryotes and are involved in the regulation of autophagy which includes SIRT1, mTOR and AMPK. The current review focuses on the role of SIRT1, mTOR and AMPK in regulating autophagy and suggests autophagy along with these nutrient-sensing pathways as potential therapeutic targets in reducing the progression of various diabetic complications.


Tropomyosin requires an intact N-terminal coiled coil to interact with tropomodulin.
Tropomodulins (Tmods) are tropomyosin (TM) binding proteins that bind to the pointed end of actin filaments and modulate thin filament dynamics. They bind to the N termini of both "long" TMs (with the N terminus encoded by exon 1a of the alpha-TM gene) and "short" nonmuscle TMs (with the N terminus encoded by exon 1b). In this present study, circular dichroism was used to study the interaction of two designed chimeric proteins, AcTM1aZip and AcTM1bZip, containing the N terminus of a long or a short TM, respectively, with protein fragments containing residues 1 to 130 of erythrocyte or skeletal muscle Tmod. The binding of either TMZip causes similar conformational changes in both Tmod fragments promoting increases in both alpha-helix and beta-structure, although they differ in binding affinity. The circular dichroism changes in the Tmod upon binding and modeling of the Tmod sequences suggest that the interface between TM and Tmod includes a three- or four-stranded coiled coil. An intact coiled coil at the N terminus of the TMs is essential for Tmod binding, as modifications that disrupt the N-terminal helix, such as removal of the N-terminal acetyl group from AcTM1aZip or striated muscle alpha-TM, or introduction of a mutation that causes nemaline myopathy, Met-8-Arg, into AcTM1aZip destroyed Tmod binding.


Triiodothyronine stimulates glucose transport in bone cells.
Thyroid hormones increase energy expenditure and bone turnover in vivo. To study whether 3,3',5-triiodo-l-thyronine (T₃) stimulates the uptake of glucose in osteoblastic cells, PyMS (a cell line derived from rat bone) cells were kept in serum-free culture medium and treated with T₃. We measured [1-¹⁴C]-2-deoxy-D: -glucose (2DG) uptake and looked for expression of the high-affinity glucose transporters GLUT1 and GLUT3 by northern and western analysis. T₃ did not influence the cell number but slightly (1.3-fold) increased the protein content of the cell cultures. 2DG uptake was low in serum-deprived cell cultures and was increased by T₃ (up to 2.5-fold at 1 nmol l⁻¹ after 4 days) in a dose- and time-dependent manner. Triiodothyronine at 1 nmol l⁻¹ increased GLUT1 and GLUT3 abundance in membranes. Therefore, increased glucose uptake induced by T₃ in osteoblasts may be mediated by the known high-affinity glucose transporters GLUT1 and GLUT3.


Validation of an informant-based cognitive screening tool for Parkinson disease.
The objective of this study was to establish the psychometric properties of the AD8 Dementia Screening Interview in patients with Parkinson disease (PD) with or without cognitive impairment using the Montreal Cognitive Assessment Tool (MoCA) for comparison. The AD8 was translated into Malay for Malay-speaking participants. A correlation analysis and a receiver operator characteristic curve were generated to establish the psychometric properties of the AD8 in relation to the MoCA. One hundred fifty patients and their caretakers completed the AD8 and MoCA. Using a cutoff score of 1/8, the AD8 had 81% sensitivity and 59% specificity for the detection of cognitive impairment in PD. With a cutoff score of 2/8, the AD8 had 83% specificity and 64% sensitivity. The area under the receiver operator characteristic curve was 80%, indicating good-to-excellent discriminative ability. These findings suggest that the AD8 can reliably differentiate between cognitively impaired and cognitively normal patients with PD and is a useful caregiver screening tool for PD.


The structure of stiripentol: 4,4 dimethyl- 1-(3,4-methylenedioxyphenyl)-1-penten-3-ol-a novel antiepileptic drug.
C14H18O3, Mr = 234.29, monoclinic, P2(1)/a, a = 14.550 (8), b = 6.133 (4), c = 15.703 (7) A, beta = 116.1 (4) degree, V = 1254.4 (5) A3, Z = 4, Dm = 1.24 (4), Dx = 1.239 g cm-3, lambda (Cu K alpha) = 1.54184 A, mu = 6.15 cm-1, F(000) = 504, room temperature, R = 0.065 for 2426 observed reflections. The five-membered ring A has an envelope conformation, the apical atom C(7)* being out of the plane. The conformation of the side chain attached to C(1)* is almost fully extended. The molecules are packed in a head-to-tail fashion as hydrogen-bonded dimers: O(3)...O(4)* [1-x, y, 1-z] = 3.124 (8), HO(3)...O(4)* = 2.19 (9) A, O(3)-HO(8)...O(4)* V 160.2 (6) degree.


Identification of a panel of five serum miRNAs as a biomarker for Parkinson's disease.
Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease. The aim of this work was to determine whether the differences of serum miRNAs profiling could distinguish PD patients from healthy individuals. We collected serum samples from 106 sporadic PD patients and 91 age/gender-matched healthy controls. Serum miRNAs were analysed by Solexa sequencing followed by a qRT-PCR examination. The qRT-PCR assay, which was divided into two phases, was used to validate the expression of miRNAs screened by Solexa sequencing. Receiver operating characteristic (ROC) curve analysis and clustering analysis were performed to determine the diagnostic usefulness of the selected miRNAs for PD. In this study, we generated a profile of 5 serum miRNAs: miR-195 was up-regulated, and miR-185, miR-15b, miR-221 and miR-181a were down-regulated. This group of five miRNAs can precisely distinguish PD patients from health individuals and may be used as a potential serum-based biomarker for the diagnosis of PD.


Catching hold of COVID-19-related encephalitis by tracking ANGPTL4 signature in blood: An Editorial Highlight for "Endothelial cell biomarkers in critically ill COVID-19-patients with encephalitis": An Editorial Highlight for "Endothelial cell biomarkers in critically ill COVID-19-patients with encephalitis" on page 492.
Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in humans is characterized by a plethora of symptoms varying in intensity, such as non-specific febrile illness, dry cough, dyspnea, hypoxemia to severe lung damage, and even death. In addition to pulmonary complications associated with coronavirus disease-19 (COVID-19), perturbations in the physiology of multiple other organ systems have been reported, resulting in multiorgan failure (MoF) that is frequently observed in severe COVID-19 cases. Central nervous system (CNS) infection by SARS-CoV-2 is characterized by neurological impairments in patients with COVID-19, with the development of encephalopathy at the severe end of the spectrum. While mechanistic investigations of SARS-CoV-2-related encephalitis may reveal promising therapeutic candidates for reducing COVID-19-associated disease morbidity, the discovery of biomarkers capable of diagnosing and predicting prognosis in patients with encephalitis upon SARS-CoV-2 infection will afford significant value for the rapid detection of encephalitis and predicting disease outcomes. This will ultimately enable appropriate modifications of therapeutic regimens aimed at reducing disease morbidity and mortality. In this editorial, we highlight a study by Le Guennec and colleagues, entitled "Endothelial cell biomarkers in critically ill COVID-19-patients with encephalitis", reporting the association of increased serum angiopoietin-like 4 (ANGPTL4) abundance with COVID-19-related encephalitis. The study highlights ANGPTL4 as a potential molecular marker for this disease. These novel findings may catalyze developments in the field of COVID-19-associated encephalitis by facilitating accurate and rapid diagnosis of encephalitis and timely treatment initiation, thus improving patient outcomes by ameliorating disease burden.


The American Brachytherapy Society consensus statement for accelerated partial breast irradiation.
To develop clinical guidelines for the quality practice of accelerated partial breast irradiation (APBI) as part of breast-conserving therapy for women with early-stage breast cancer. Members of the American Brachytherapy Society with expertise in breast cancer and breast brachytherapy in particular devised updated guidelines for appropriate patient evaluation and selection based on an extensive literature search and clinical experience. Increasing numbers of randomized and single and multi-institution series have been published documenting the efficacy of various APBI modalities. With more than 10-year followup, multiple series have documented excellent clinical outcomes with interstitial APBI. Patient selection for APBI should be based on a review of clinical and pathologic factors by the clinician with particular attention paid to age (≥50 years old), tumor size (≤3cm), histology (all invasive subtypes and ductal carcinoma in situ), surgical margins (negative), lymphovascular space invasion (not present), and nodal status (negative). Consistent dosimetric guidelines should be used to improve target coverage and limit potential for toxicity following treatment. These guidelines have been created to provide clinicians with appropriate patient selection criteria to allow clinicians to use APBI in a manner that will optimize clinical outcomes and patient satisfaction. These guidelines will continue to be evaluated and revised as future publications further stratify optimal patient selection.


Spectroscopic details on the molecular structure of pyrimidine‑2‑thiones heterocyclic compounds: computational and antiviral activity against the main protease enzyme of SARS-CoV-2.
Computational tools in investigating of spectral heterocyclic compounds ranges based on pyrimidine‑2‑thiones, take some importance in identifying their molecular and electronic behavior. Some charcoal heterocyclic compounds were previously synthesized in our laboratory and their experimental results were compared with the computational evaluation. Computational spectroscopic analytical items (IR, NMR and UV-Vis) were calculated using the more popular DFT methods and the predicted results were compared with the reported experimental ones. Quantum and chemical parameters were calculated and molecular electrostatic surface potential (MEP) was studied which predicted the highly electronic sites around the compounds. Some molecular properties (ionization energy, electron affinity, energy gap, hardness, electronegativity, electrophilicity index, static dipole moment and average linear polarizability) of these Schiff bases which were computed at B3LYP/6-31G(d,p) level in aqueous phase. Benchmark analysis was performed for three ab initio functionals such B3LYP, BPV86 and B3PW91 methods to explain the data resulted from NMR spectra. The docking study of some selected previously synthesized compounds was performed using the viral Mpro enzyme protein in compared to a k36 reference ligand inhibitor. The study indicated the ability of the synthesized compounds to form H-bond and hydrophobic (VDW, π-alkyl and π-sulfur) interactions with Mpro enzyme receptor with high inhibition effect of compound L2.


Factors affecting participation in the colorectal cancer screening program: a cross-sectional population study.
Fecal immunochemical test (FIT) once a year or colonoscopy once in 10 years is the option approved for colorectal cancer (CRC) screening for asymptomatic individuals aged ≥ 50 years in the Czech Republic. We analyzed participation in the screening program to determine possible improvements. In this observational cross-sectional study, data were collected from 4044 randomly chosen individuals from the Czech population (1866 men, 2178 women) aged ≥ 50 years by questionnaires. Individuals who underwent colonoscopy within the last 10 years or/and FIT within the last 2 years were classified as participants in the screening. 1050 individuals underwent FIT, 464 colonoscopy, and 558 underwent both. Adjusted for age, gender, and education, a higher chance of participation in the screening was observed in groups of non-smokers (OR = 1.25; CI 1.05-1.48), ex-smokers (OR = 1.51; CI 1.26-1.83), consuming smoked meat products less than once a week (OR = 1.26; CI 1.09-1.45), practicing physical activity at least once a week (OR = 1.25; CI 1.03-1.51), hospitalized in the past 12 months (OR = 1.73; CI 1.47-2.05), or consulting a general practitioner (GP) in the past 12 months (OR = 2.26; CI 1.87-2.74). The chance of participation of individuals having a risk factor for CRC (obesity, smoking, diabetes, low physical activity, alcohol drinking) was not higher compared to those without the risk factors. Individuals with a tendency to a healthy lifestyle or being in recent contact with the healthcare system by various means, mainly visiting a GP, had a higher participation in the screening for CRC. Among groups with an increased risk for CRC, higher participation was not shown.


Effects of external crushing forces on a novel below-the-knee vascular implant.
The Tack Endovascular System® is a novel vascular implant designed to focally treat dissections with low radial force and minimal metal burden. As there are currently no approved below-the-knee (BTK) implants in the USA, a unique, 3-stage model was developed to characterize crush deformation and fracture potential of the Tack Endovascular System in BTK arteries. First, 35 Tack® implants were deployed bilaterally in the posterior tibial, anterior tibial, and peroneal arteries of 3 cadavers, and clinically relevant external forces were applied to simulate BTK crushing deformation including focal load, leg crossing, and leg bending. Intravascular ultrasound images of the implanted vessels were used to assess the magnitude of artery deformation. Outputs of the cadaver testing were input into a finite element analysis (FEA) model to determine the appropriate conditions for subsequent bench testing. Tack implants were then subjected to increasing crush forces at 30Hz for up to 650,000 cycles at 25% flat plate deformation within the worst-case FEA test condition. Crush deformation across all arteries ranged from 0% to 23.1%. The posterior tibial artery and large male cadaver exhibited the most vulnerability to external crush forces, while the small female model exhibited the most resistance. No fractures were observed during cadaver or bench testing. This study characterized deformation forces in tibial arteries during various loading conditions. Tack implants withstood the loading conditions without fracture within the limits of this ex-vivo human vascular model and in-vitro bench testing.


Isoelectric focusing sample injection for capillary zone electrophoresis in a fused silica capillary.
An improvement has been made to couple isoelectric focusing (IEF) sample injection and capillary zone electrophoresis in an untreated fused silica capillary. Electroosmotic flow is efficiently prevented by simply using a rubber block at the outlet end of the capillary during IEF sample injection. The experimental conditions that affect the concentration effect are discussed. A concentration enhancement factor of over 100-fold can be easily obtained for two model proteins: lysozyme and ribonuclease A.


Chemometric data analysis application to Sparus aurata samples from two offshore farming plants along the Apulian (Italy) coastline.
The levels of polychlorodibenzo-p-dioxins (PCDDs), polychlorodibenzofurans (PCDFs), dioxin-like polychlorobiphenyls (DL-PCBs), non-dioxin-like polychlorobiphenyls (NDL-PCBs), and polybromodiphenyl ethers (PBDEs) in fish collected from two marine offshore farming plants were determined. Each sample was constituted by specimens of the same size collected at the same time in four different seasons along the farming year. The feeds given were of industrial origin and the plants were positioned in two different sites respectively exposed to different environmental characteristics. A chemometric approach was applied to interpret the subtle differences observed in fish body burdens across the three chemical groups taken into consideration. The approach consisted in a stepwise multivariate process including a hierarchical cluster analysis (CA) and a linear discriminant analysis (DA). The two main clusters determined by CA were subjected to the canonical DA, backward and forward selection procedures to select the best discriminative functions. A clear temporal and spatial discrimination was found among the samples. Across the three chemical groups, the monthly separation seemed to depend on the growth process and the main exposure was due to the feed. In addition, the two plants differed significantly from the environmental point of view and the most important discriminating group of chemicals were the NDL-PCBs. The approach resulted really effective in discriminating the subtle differences and in individuating suggestions to improve the quality of culturing conditions.


Diabetes induced by checkpoint inhibition in nonobese diabetic mice can be prevented or reversed by a JAK1/JAK2 inhibitor.
Immune checkpoint inhibitors have achieved clinical success in cancer treatment, but this treatment causes immune-related adverse events, including type 1 diabetes (T1D). Our aim was to test whether a JAK1/JAK2 inhibitor, effective at treating spontaneous autoimmune diabetes in nonobese diabetic (NOD) mice, can prevent diabetes secondary to PD-L1 blockade. Anti-PD-L1 antibody was injected into NOD mice to induce diabetes, and JAK1/JAK2 inhibitor LN3103801 was administered by oral gavage to prevent diabetes. Flow cytometry was used to study T cells and beta cells. Mesothelioma cells were inoculated into BALB/c mice to induce a transplantable tumour model. Anti-PD-L1-induced diabetes was associated with increased immune cell infiltration in the islets and upregulated MHC class I on islet cells. Anti-PD-L1 administration significantly increased islet T cell proliferation and islet-specific CD8+ T cell numbers in peripheral lymphoid organs. JAK1/JAK2 inhibitor treatment blocked IFNγ-mediated MHC class I upregulation on beta cells and T cell proliferation mediated by cytokines that use the common γ chain receptor. As a result, anti-PD-L1-induced diabetes was prevented by JAK1/JAK2 inhibitor administered before or after checkpoint inhibitor therapy. Diabetes was also reversed when the JAK1/JAK2 inhibitor was administered after the onset of anti-PD-L1-induced hyperglycaemia. Furthermore, JAK1/JAK2 inhibitor intervention after checkpoint inhibitors did not reverse or abrogate the antitumour effects in a transplantable tumour model. A JAK1/JAK2 inhibitor can prevent and reverse anti-PD-L1-induced diabetes by blocking IFNγ and γc cytokine activities. Our study provides preclinical validation of JAK1/JAK2 inhibitor use in checkpoint inhibitor-induced diabetes.


[Fleas of small mammals in northern Amur Province and their distribution by biotopes (Aphaniptera)].
In June-September of 1975 on the southern slope of the Stanovoy ridge, in the region of construction of the Baikal-Amur main line 2014 small mammals of 14 species were examined, on which 1499 fleas of 13 species were collected. Most species of fleas are widely distributed throughout the territory. Ceratophyllus penicilliger, C. advenarius, Catallagia dacencoi, C. ioffi are mass species, Ceratophyllus calcarifer, C. indages, Leptopsylla ostsibirica, Doratopsylla birulai, Rhadinopsylla pseudodahurica are common species. Ceratophyllus taiganus, Amphipsylla marikovskii, Neopsylla acanthina and Tarsopsylla octodecimdentata are rather rare.


Diseases of the ear.
Otitis media with effusion is a major disorder in children and the most common cause for both major surgery (adenoidectomy with or without tonsillectomy) and minor surgery (middle ear ventilating tubes) in both the United States and Britain. It is frequently associated with respiratory allergy. Medical evaluation, diagnosis, and therapy are discussed. Environmental control measures and pharmacotherapy are reviewed, with a critical review of published appropriately designed studies for its treatment and prevention.


Radiomics analysis from magnetic resonance imaging in predicting the grade of nonfunctioning pancreatic neuroendocrine tumors: a multicenter study.
To explore the potential of radiomics features to predict the histologic grade of nonfunctioning pancreatic neuroendocrine tumor (NF-PNET) patients using non-contrast sequence based on MRI. Two hundred twenty-eight patients with NF-PNETs undergoing MRI at 5 centers were retrospectively analyzed. Data from center 1 (n = 115) constituted the training cohort, and data from centers 2-5 (n = 113) constituted the testing cohort. Radiomics features were extracted from T2-weighted images and the apparent diffusion coefficient. The least absolute shrinkage and selection operator was applied to select the most important features and to develop radiomics signatures. The area under receiver operating characteristic curve (AUC) was performed to assess models. Tumor boundary, enhancement homogeneity, and vascular invasion were used to construct the radiological model to stratify NF-PNET patients into grade 1 and 2/3 groups, which yielded AUC of 0.884 and 0.684 in the training and testing groups. A radiomics model including 4 features was constructed, with an AUC of 0.941 and 0.871 in the training and testing cohorts. The fusion model combining the radiomics signature and radiological characteristics showed good performance in the training set (AUC = 0.956) and in the testing set (AUC = 0.864), respectively. The developed model that integrates radiomics features with radiological characteristics could be used as a non-invasive, dependable, and accurate tool for the preoperative prediction of grade in NF-PNETs. Our study revealed that the fusion model based on a non-contrast MR sequence can be used to predict the histologic grade before operation. The radiomics model may be a new and effective biological marker in NF-PNETs. The diagnostic performance of the radiomics model and fusion model was better than that of the model based on clinical information and radiological features in predicting grade 1 and 2/3 of nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs). Good performance of the model in the four external testing cohorts indicated that the radiomics model and fusion model for predicting the grades of NF-PNETs were robust and reliable, indicating the two models could be used in the clinical setting and facilitate the surgeons' decision on risk stratification. The radiomics features were selected from non-contrast T2-weighted images (T2WI) and diffusion-weighted imaging (DWI) sequence, which means that the administration of contrast agent was not needed in grading the NF-PNETs.


Winter sports-related urologic trauma.
There is no characteristic pattern of ski-related urologic injuries except those associated with major blunt abdominal trauma. Isolated urologic injuries and injuries of the lower urinary tract are relatively uncommon.


Some clinical aspects of late onset parkinsonism.
Thirty-six parkinsonian patients were selected by age of onset of over 70 and a minimum of five years duration of illness. The mean age of onset was 73.5 years and 30 patients were still alive after a mean of 7.2 years. We found that late onset Parkinson's disease has a relatively benign course with more "axial symptoms" especially dysarthria, freezing and postural instability. Dyskinesias and fluctuations are rare and dementia occurs in few patients in spite of their old age.


Preoperative Three-Dimensional Angiography May Reduce Ischemic Complications During Clipping of Ruptured Intracranial Aneurysms.
Microsurgical clipping of aneurysms demands precise spatial understanding of aneurysm morphology and vascular geometry. We analyzed the impact of preoperative three-dimensional (3D) angiographic imaging on clinical and angiographic outcome after clipping of ruptured intracranial aneurysms. This is a retrospective analysis of consecutive patients who underwent microsurgical clipping during the acute phase of subarachnoid hemorrhage between 2010 and 2017. Surgical planning was made based on two-dimensional (2D) or 3D angiographic images. We retrospectively compared complication rates, morbidity, and angiographic outcome between these 2 groups. A total of 157 patients (mean age: 54.8 ± 13.1 years) were included in the study. Preoperative 3D angiographic imaging was available for 117 cases. The rate of procedure-related ischemia was significantly lower in the 3D group (16.2%) than in the 2D group (35.0%; P = 0.013). In the multivariate analysis, 2D imaging alone remained as independent factor for subsequent brain ischemia (odds ratio: 2.8, 95% confidence interval 1.2-6.6; P = 0.018). Favorable outcome (modified Rankin scale ≤2) was more often attained in the 3D group (70.0%) than in the 2D group (41.9%; P = 0.002). The rate of complete aneurysm occlusion was not significantly different between the 2 groups (P = 0.967). In our study, accurate operation planning using 3D angiography was associated with a lower ischemic complication rate after clipping of ruptured intracranial aneurysms, which may potentially influence clinical outcome.


Evolution of crystal and electronic structures of magnesium dicarbide at high pressure.
Carbon-based compounds exhibit unexpected structures and electronic behavior at high pressure arising from various bonding features of carbon (e.g., sp, sp(2) and sp(3) C-C bonds). Here we report evolution of crystal structures of MgC2 in a wide pressure range of 0-200 GPa as predicted through ab-initio calculations in combination with an unbiased swarm structure search. Three pressure-induced structural transformations are unraveled, following the phase sequence of ambient-pressure P42/mnm (α-phase) → Cmcm (β-phase) → C2m (γ-phase) → EuGe2-type P-3m1 (δ-phase), where significant C-C bonding modifications from C-C dimer to quasi 1-dimensionzigzag chain, to polymerized ribbon and then to winkled quasi 2- dimension graphite sheet are evident. The predicted β- and γ-phases with sp(2) C-C hybridization are metals, while the δ- phase characterized by a sp(3)C-C hybridization is a narrow-gap semiconductor with a band gap of 0.667 eV. Strong electron-phonon couplings in the compressed β- and γ- phases arepredicted with β-phase showing a high superconducting critical temperature of 11.2 K. The current results indicate that pressure is effective in tuning the crystal and electronic structures of MgC2, which is expected to have impact on physical properties for potential applications.


Increasing access to oral health care for people living with HIV/AIDS in the U.S.: baseline evaluation results of the Innovations in Oral Health Care Initiative.
We provide an overview of the Health Resources and Services Administration HIV/AIDS Bureau's Special Projects of National Significance Innovations in Oral Health Care Initiative, describe the models developed by the 15 demonstration sites and associated evaluation center, and present initial descriptive data about the characteristics of the multisite evaluation study sample. Baseline data were collected from May 2007-August 2009 for 2,469 adults living with HIV/AIDS who had been without dental care, except for emergency care, for 12 months or longer. Variables included sociodemographic characteristics, HIV status, medical care, history of dental care and oral health symptoms, oral health practices, and physical and mental health quality of life. Descriptive statistics of baseline variables were calculated. The study sample included 2,469 adults who had been HIV-positive for a decade; most were engaged in HIV care. The majority (52.4%) of patients had not seen a dentist in more than two years; 48.2% reported an unmet oral health-care need since testing positive for HIV, and 63.2% rated the health of their teeth and gums as "fair" or "poor." This study is the largest to examine oral health care among people living with HIV/AIDS in more than a decade. The need for access to oral health care among members of this HIV-positive patient sample is greater than in the general population, following previous trends. Findings from our study reinforce the necessity for continued federal and statewide advocacy and support for oral health programs targeting people living with HIV/AIDS; findings can be extended to other vulnerable populations.


Teaching evidence-based public health to public health practitioners.
The purpose of the Evidence Based Public Health (EBPH) course is to train public health practitioners to utilize a comprehensive approach for program development and evaluation from a scientific perspective, including principles of scientific reasoning and systematic uses of data and information systems. The increasing technical sophistication of public health problems and approaches emphasizes the importance for an evidence-based approach to developing policy and interventions. The training methods used highlight the linkages between data systems and program/policy initiatives. Participants learn to access and interpret existing data systems and methods of using data to impact specific policies or decision-makers. From 1992 through mid-2004 the EBPH course was offered a total of 20 times, in Missouri, nationally and internationally. In March 2002, the workshop was taped and pressed into a 16-CD set that public health workers can use as a self-teaching program in their own homes and offices. The group exercises from the classroom workshop have been adapted into individual self-guided applications, and background readings are included in the set. Compiled results of course evaluations indicate average ratings for course satisfaction ranging from 8.50 to 10.00 on a scale from 1 to 10. Satisfaction with course instructors ranged between 8.00 and 10.00 on the same scale. Ninety-four to ninety-six per cent of participants reported that they would use the course in their day-to-day work. Qualitative comments from participants at the time of and after the course show that the material is applied in a variety of ways. The EBPH course is making a valuable contribution in strengthening the application of scientific methods to public health practice. To expand the offerings of this training, a train-the-trainer component for the EBPH course is being developed, to be made available in 2005.


[Breech Presentation: CNGOF Guidelines for Clinical Practice - External Cephalic Version and other Interventions to turn Breech Babies to Cephalic Presentation].
To provide guidelines regarding efficiency and safety of external cephalic version (ECV) attempt and alternatives methods to turn breech babies to cephalic presentation. MedLine and Cochrane Library databases search in French and English and review of the main foreign guidelines between 1980 and 2019. ECV is associated with a decreasing rate of breech presentation at birth (LE2), and potentially with a lower rate of cesarean section (LE3) without an increase of severe maternal (LE3) and perinatal morbidity (LE3). It is therefore recommended to inform women with a breech presentation at term that ECV should be attempt (Professional consensus). ECV attempt should be performed with immediate access to an operating room for emergency cesarean (Professional consensus). The ECV attempt before 37 weeks, compared to ECV attempt after 37 weeks, increases the rate of cephalic presentation at birth (LE2) but with a small increase risk of moderate prematurity (LE2). ECV attempt should be performed from 36SA (Professional consensus). The main factors associated with successful ECV attempt are multiparity (LE3) and no maternal obesity (LE3). Parenteral tocolysis (β mimetic or atosiban), for ECV attempt at term is associated with a higher success rate (LE2), higher rate of achieved cephalic presentation in labor (LE2) and a lower cesarean section rate (LE2). It is recommended to use parenteral tocolysis for ECV attempt at term in order to increase its success rate (grade B). The ECV attempt is associated with an increase in transient FHR abnormalities (LE3), it is therefore recommended that cardiotocography should be performed prior and during 30minutes after the procedure (Professional consensus). There is no argument for recommending the practice of delayed cardiotocography after ECV attempt (Professional consensus). The risk of significant positivity (>30mL) of the Kleihauer test after ECV attempt is low (<0.1%) (LE3), it is not recommended to systematically perform a Kleihauer test after ECV attempt (professional consensus). In case of RH-1 negative women, it is recommended to ensure systematic RH-1 prophylaxis (Professional consensus). In case of breech presentation at term, acupuncture, moxibustion and postural methods are not effective in reducing breech presentation at birth (LE2), and are therefore not recommended (Grade B). According to the clear benefits and the low risks of ECV attempt, all women with a breech presentation at term should be informed that ECV should be attempted to decrease breech presentation at birth and cesarean section.


Zinc uptake into synaptosomes.
Zinc uptake was studied in synaptosomes, isolated by the Ficoll flotation technique, using the radiotracer 65Zn. True uptake of zinc could be discriminated from binding to the outside of the synaptosomes by the absence of accumulation at 0 degree C and the dependency of the rate of uptake on the medium osmolarity. The zinc uptake, studied in the presence of various zinc-complexing agents, showed saturation kinetics when analyzed in terms of [Zn]free, yielding Km = 0.25 microM. The zinc uptake was independent of both ATP and the Na+ gradient. No efflux of zinc could be demonstrated from preloaded synaptosomes due to the formation of insoluble zinc complexes inside the synaptosomes. The results are discussed in terms of the modulation of diverse neurochemical processes by zinc.


Quantitative separation of nucleotides on mercurated dextran.
Dextran gels of varying porosites (Sephadex G series) were chemically modified so as to contain covalently bound monofunctional mercury. Mercurated Sephadex of the porosity G-25 was then used to fractionate mixtures of mono- and dinucleotides into the constituent components. Separation is based on the affinity of the nitrogen binding sites of the purine and pyrimidine derivatives for organomercurial Hg+. Thus, a mixture composed of the four mononucleotides Cyd-5'-P, Ado-3'-P, Guo-2'(3')-P, dThd-5'-P and of the four dinucleotides Cyd-P-Cyd, Ado-P-Ado, Guo-P-Urd, and Urd-P-Urd could be separated into eight well-resolved fractions by using a combination Tris-bicarbonate/carbonate buffer system of increasing pH as an eluent. Complete separation was also achieved when a mixture of Ado 3:5'-P, Ado 5'-P, Ado-5'-PP, and Ado-5'-PPP was fractionated on mercurated Sephadex G-25. Again, Tris-bicarbonate/carbonate buffer served as an eluent. Lastly, fractionation can also be performed at a constant pH by offering other suitable ligands, for instance Cl-, that will compete with nucleotides for monofunctional Hg+. The fractionation behavior of mercurated Sephadex G-25 can be fully understood on the basis of the complexing properties of monofunctional Hg+. This has been shown by calculating the net retention volume ratios of several nucleotides with the help of the known interaction parameters of corresponding nucleosides with CH3 HgOH and by comparing the predicted ratios with the experimentally measured ones. Finally, the acid-base properties of mercurated Sephadex G-25 as well as its affinity for chloride and iodide ions have been determined. The data agree quite well with those known for CH3 HgOH.


Successful and unsuccessful recruitment and retainment strategies in a UK multicentre drug trial for a rare chronic pain condition which performed above target.
Recruitment into trials in rare chronic pain conditions can be challenging, so such trials consequently are underpowered or fail. Drawing from our experience in conducting, to date, the largest academic trial in a rare chronic pain condition, complex regional pain syndrome, we have identified recruitment and retention strategies for successful trial conduct. We present 13 strategies grouped across the categories of 'setting the recruitment rate', 'networking', 'patient information', 'trial management' and 'patient retention'. Moreover, six recruitment risks are also discussed. A conservative recruitment estimate, based on audits of newly referred patients to the trial centres without taking into account availability of 'old' patients or recruitment from outside centres, and assuming a 55% patient refusal rate yielded accurate numbers. Appreciation of these identified recruitment challenges and opportunities may contribute to supporting prospective investigators when they design clinical trials for chronic pain patient population groups where it has been historically difficult to conduct high-quality and robust clinical trials.


Assessing the effects of COVID-19 restrictions on alcohol consumption in Melbourne, Australia using high-resolution wastewater sampling.
The impact of the COVID-19 pandemic and related restrictions on alcohol consumption in Australia remains unclear. High-resolution daily samples from a wastewater treatment plant (WWTP) which served one of the largest cities in Australia, Melbourne, were analysed for temporal trends in alcohol consumption under extended periods of COVID-19 restrictions in 2020. Melbourne experienced two major lockdowns in 2020, which divided the year of 2020 into five periods (pre-lockdown, first lockdown, between lockdown, second lockdown and post second-lockdown). In this study, daily sampling identified shifts in alcohol consumption during different periods of restrictions. Alcohol consumption in the first lockdown period, when bars closed and social and sports events ceased, was lower than pre-lockdown period. However, alcohol consumption was higher in the second lockdown period than the previous lockdown period. There were spikes in alcohol consumption at the start and end of each lockdown (except for post lockdown). For most of 2020, the usual weekday-weekend variations in alcohol consumption were less evident but there was a significant difference in alcohol consumption between weekdays and weekends after the second lockdown. This suggests that drinking patterns eventually returned to normal after the end of the second lockdown. This study demonstrates the usefulness of high-resolution wastewater sampling in evaluating the effects on alcohol consumption of social interventions in specific temporal locations.


Utility of oral dissolution therapy in the management of referred patients with secondarily treated uric acid stones.
Uric acid stones are best managed by chemolysis. Some patients with acutely symptomatic stones opt for endourologic therapies. The radiolucent nature of these stones makes secondary interventions difficult to plan. Computed tomography becomes the modality of choice to identify stone locations and size in these patients. We analyzed patients with uric acid stones referred to our stone center after primary treatment had failed to establish the efficacy of oral alkalinization therapy. Eleven patients presented after one or more failed attempts to intervene for uric acid stones. Charts were reviewed for age, sex, time with stone before referral, medical therapies undertaken, number of antecedent urologic interventions, number of radiographic studies performed, subsequent procedures performed, and outcomes with a minimal follow-up of 6 months. Eight patients were men and four presented with bilateral stone disease (overall, 15 involved upper tracts). Sixty-seven percent of patients had right-sided solitary calculi. All patients at presentation filled out urinary pH diaries. Of the 11 patients, 4 stated they had been prescribed oral alkaline therapy but were found to be noncompliant, 4 were never prescribed this therapy, and 3 took the medication sporadically. All patients were counseled on self-dosing to maintain their urinary pH between 6.0 and 6.5 and to continue the diaries. Computed tomography scans were done in 9 patients, and intravenous urography and ultrasonography in the other 2 patients confirmed the stone burden. Only 3 patients (27%) required subsequent interventions (ureteroscopic laser lithotripsy). Secondarily referred patients with uric acid stones are best treated with medical therapy. These findings suggest that the initial medical regimens had failed because of noncompliance or lack of effective follow-up by the primary urologist. Seventy-three percent of these patients had dissolution of the stones, requiring no further endourologic intervention.


Three Lessons from Accelerating Scientific Insight Discovery via Visual Querying.
Exploratory data analysis is a crucial part of data-driven scientific discovery. Yet, the process of discovering insights from visualization can be a manual and painstaking process. This article discusses some of the lessons we learned from working with scientists in designing visual data exploration system, along with design considerations for future tools.


Mulberry polyphenol extracts attenuated senescence through inhibition of Ras/ERK via promoting Ras degradation in VSMC.
Ageing is one of the major risk factors of human diseases, including cancer, diabetes, and cardiovascular disease. Mulberry exhibits a wide range of functions, such as anti-oxidant, anti-inflammation, and anti-diabetes. In this study, we investigated the role of mulberry polyphenol extract (MPE) in K-Ras-induced senescence of smooth muscle cells. Forced expression of K-Ras enhanced senescence of smooth muscle A7r5 cells as shown by the elevation of β-galactosidase activity. Treatment with MPE significantly repressed the Ras, phosphorylated ERK, and β-galactosidase level. MPE triggered the association of cyclins with their corresponding cyclin-dependent protein kinases and hyperphosphorylated retinoblastoma (RB). MPE also down-regulated the levels of K-Ras-induced CDK inhibitors. MPE enhanced the phosphorylated AMP-dependent protein kinase (AMPK) and inducible nitric oxide synthase (iNOS) level in the presence of K-Ras. Pretreatment with either L-NAME or AMPK inhibitor reversed the effects of MPE. In addition, L-NAME and AMPK inhibitor repressed the MPE-induced total and phosphorylated 3-hydroxy-3-methylglutaryl coenzyme A (HMG-Co A) level. MPE repressed K-Ras-induced G0/G1 arrest, whereas L-NAME and AMPK inhibitor blocked the effects of MPE. Our results indicated that MPE recovered the K-Ras-induced senescence of vascular smooth muscle cells through iNOS and AMPK-dependent pathway. Our findings suggested that MPE may prevent ageing-induced atherosclerosis.


Interlimb and within limb force coordination in static bimanual manipulation task.
The aim of the study was to compare the coordination of hand grip (G) and load force (a force that tends to cause slippage of a grasped object; L) in static bimanual manipulation tasks with the same data obtained from the similar dynamic tasks. Based on the previous findings obtained from dynamic tasks, it was hypothesized that an increase in the rate of L change would be predominantly associated with a decrease in the coordination of the within limb forces (coordination of G and L of each hand as assessed through the correlation coefficients), while a decrease in coordination of interlimb forces (between two G and two L) will be less pronounced. Regarding the pattern of modulation of G, the same increase in L frequency was also expected to be associated with a decrease in G gain and an increase in G offset (as assessed by slope and intercept of the regression lines obtained from G to L diagrams, respectively), as well as with an increase in average G/L ratio. Subjects exerted oscillatory isometric L profiles by simultaneous pulling out two handles of an externally fixed device under an exceptionally wide range of L frequencies (0.67-3.33 Hz). The results demonstrated relatively high correlation coefficients between both the interlimb and within limb forces that were only moderately affected under sub-maximal L frequencies. Furthermore, the hypothesized changes in G gain and offset appeared only under the highest L frequency, while the G/L ratio remained unaffected. We conclude that, when compared with the dynamic tasks based on the unconstrained movements of hand-held objects that produce similar pattern of L change, the static manipulation tasks demonstrate a consistent and highly coordinated pattern of bilateral G and L under a wide range of frequencies. However, the neural mechanisms that play a role in the revealed differences need further elucidation.


A heart failure themed escape room approach to enhance pharmacy student learning.
The purpose of this study was to design, pilot, and evaluate the efficacy of an educational escape room to enhance second professional year doctor of pharmacy students' knowledge of heart failure medicinal chemistry, pharmacology, and therapeutics in an integrated Modular Organ Systems Therapeutics (MOST) course and to assess students' perceptions of the game. Heart failure pharmacology, medicinal chemistry, and pharmacotherapeutics were taught in MOST prior to the escape room activity. Students were randomized into groups of approximately eight. At the completion of the activity, students were asked to fill out a perceptions survey. A follow up survey of their perceptions was again administered four weeks after the activity. One-hundred-ninety-three students participated in the escape room activity. Overall, performance indicated that the escape room satisfactorily reinforced students' learning of the course material. Students expressed satisfaction toward the escape room activity on both surveys, with response rates of 92.22% and 56.99% for the initial and follow up surveys, respectively. Findings revealed no statistically significant differences between the first and the second group of responses, confirming that positive attitudes toward the activity did not alter over time. Students' satisfaction levels were inversely related to their grade point average (r = -0.20, p = 0.05). Positive student perceptions reported immediately after the completion of the escape room activity and measured in the follow-up survey demonstrated that the escape room is a satisfying learning activity that can engage all students.


Electronic photoreceptors enable prosthetic visual acuity matching the natural resolution in rats.
Localized stimulation of the inner retinal neurons for high-acuity prosthetic vision requires small pixels and minimal crosstalk from the neighboring electrodes. Local return electrodes within each pixel limit the crosstalk, but they over-constrain the electric field, thus precluding the efficient stimulation with subretinal pixels smaller than 55 μm. Here we demonstrate a high-resolution prosthetic vision based on a novel design of a photovoltaic array, where field confinement is achieved dynamically, leveraging the adjustable conductivity of the diodes under forward bias to turn the designated pixels into transient returns. We validated the computational modeling of the field confinement in such an optically-controlled circuit by in-vitro and in-vivo measurements. Most importantly, using this strategy, we demonstrated that the grating acuity with 40 μm pixels matches the pixel pitch, while with 20 μm pixels, it reaches the 28 μm limit of the natural visual resolution in rats. This method enables customized field shaping based on individual retinal thickness and distance from the implant, paving the way to higher acuity of prosthetic vision in atrophic macular degeneration.


Influence of patient axial malpositioning on the trueness and precision of pelvic parameters obtained from 3D reconstructions based on biplanar radiographs.
Radiographs are often performed to assess pelvic and hip parameters, but results depend upon correct pelvis positioning. Three-dimensional (3D) reconstruction from biplanar-radiographs should provide parameters that are less sensitive to pelvic orientation, but this remained to be evaluated. Computerized-tomographic scans of six patients were used both as a reference and for generating simulated frontal and lateral radiographs. These simulated radiographs were generated while introducing axial rotations of the pelvis ranging from 0° to 20°. Simulated biplanar-radiographs were utilized by four operators, three times each, to perform pelvic 3D-reconstructions. These reconstructions were used to assess the trueness, precision and global uncertainty of radiological pelvic and hip parameters for each position. In the neutral position, global uncertainty ranged between ± 2° for pelvic tilt and ± 9° for acetabular posterior sector angle and was mainly related to precision errors (ranging from 1.5° to 7°). With increasing axial rotation, global uncertainty increased and ranged between ± 5° for pelvic tilt and ± 11° for pelvic incidence, sacral slope and acetabular anterior sector angle, mainly due to precision errors. Radiological parameters obtained from 3D-reconstructions, based on biplanar-radiographs, are less sensitive to axial rotation compared to plain radiographs. However, the axial rotation should nonetheless not exceed 10°. • Pelvic radiological parameters could be affected by patient malpositioning. • Biplanar radiograph-based 3D reconstructions were performed at increments of axial rotation. • Trueness, precision and global uncertainty were evaluated for pelvic and hip radiological parameters. • Hip parameters were less affected by rotation compared to pelvic parameters. • Maintaining the pelvis close to the neutral position is recommended to ensure the highest possible accuracy.


Wettability reversal on oil-wet calcite surfaces: Experimental and computational investigations of the effect of the hydrophobic chain length of cationic surfactants.
Oil recovery from carbonate reservoirs is often low, in a large part due to the oil-wet state of the constituent rocks. Cationic surfactants are among the most effective compounds capable of reversing the carbonate wettability to more water-wet, which significantly enhances oil recovery. Screening for the most effective cationic surfactants can be facilitated by studying the effects of specific molecular properties, such as the hydrophobic chain length, on the wettability reversal efficiency using molecular dynamics (MD) simulations. Wettability reversal by quaternary ammonium cationic surfactants with varying hydrophobic chain length was studied by the combination of MD simulation and experimental contact angle measurements on oil-wet calcite chips. Both experiments and simulations also featured model oils consisting of different size hydrocarbons in order to explore the potential size-specific interactions between the surfactants and oil molecules. We found strong correlation between the wettability reversal and the surfactant length, with the longer surfactants universally rendering calcite surfaces more water-wet. By contrast, the wettability reversal is independent of the model oil used, implying that the effect is not due to specific hydrocarbon size. Instead, the superior wettability reversal performance of the more hydrophobic surfactants is due to their greater affinity to the oil/brine interfaces.


Measuring psychological, cognitive, and social domains of physical literacy in school-aged children with neurodevelopmental disabilities: a systematic review and decision tree.
To identify and assess the clinimetric properties of psychological, cognitive, and social competence assessment tools relevant to physical activity for school-aged children (5-17 years) with neurodevelopmental disabilities. Seven electronic databases were searched. Study findings and methodologies were evaluated using the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist. Psychometric strength of assessment tools was determined using Grading of Recommendations Assessment, Development and Evaluation principles (GRADE) (Trial registration: CRD42020180616). Study criteria were met by eight subscales from the BRIEF2, DMQ17, QI-Disability, SAID, and SDQ. Most subscales examined psychological competence (n = 5), with fewer addressing social competence (n = 2), or cognitive competence (n = 1). Validity was moderate to high strength for most subscales. Reliability was of moderate and unclear strength for two subscales. A five-level decision tree was devised to summarise: (1) physical literacy domains/elements, (2) populations, (3) assessment focus, (4) required resources, and (5) psychometric evidence. Subscales are available to assess psychological, cognitive, or social competence. For school-aged children with neurodevelopmental disabilities, these have moderate to high strength psychometric support. A decision tree will assist practitioners in subscale selection. Future studies are needed to establish gold standard assessment of physical literacy for this population.IMPLICATIONS FOR REHABILITATIONPsychological Activity Competence can be measured for children with neurodevelopmental disabilities, subscales from The Behaviour Rating Inventory of Executive Function, Second Edition (BRIEF2; The Dimensions of Mastery Questionnaire 17.0 (DMQ17); and The Quality of Life Inventory-Disability (QI-Disability).Cognitive Activity Competence can be measured using a subscale from The Scale of Attention in Intellectual Disability (SAID).Social Activity Competence can be measured using subscales from the BRIEF2, and The Strengths and Difficulties Questionnaire (SDQ).Clinicians can use the Physical Literacy decision tree to guide selection of these tools.


Constituents from the fruiting bodies of Ganoderma applanatum and their aldose reductase inhibitory activity.
Eight compounds were isolated from the fruiting bodies of Ganoderma applanatum, and were identified as 2-methoxyfatty acids (1), 5-dihydroergosterol (2), ergosterol peroxide (3) 3beta,7beta, 20,23xi-tetrahydroxy-11,15-dioxolanosta-8-en-26-oic acid (4), 7beta,20,23xi-trihydroxy-3,11,15-trioxolanosta-8-en-26-oic acid (5), cerevisterol (6), 7beta,23xi-dihydroxy-3,11,15-trioxolanosta-8,20E (22)-dien-26-oic acid (7), and 7beta-hydroxy-3,11,15,23-tetraoxolanosta-8,20E(22)-dien-26-oic acid methyl ester (8) by spectral analysis. All compounds were isolated for the first time from this fruiting bodies, and their effect on rat lens aldose reductase (RLAR) activity was tested. Among these eight compounds, ergosterol peroxide (3) was found to exhibit potent RLAR inhibition, its IC50 value being 15.4 microg/mL.