Trends in Mortality after Intensive Care of Patients with Aneurysmal Subarachnoid Hemorrhage in Finland in 2003-2019: A Finnish Intensive Care Consortium study.
Previous studies suggest that case mortality of aneurysmal subarachnoid hemorrhage (aSAH) has decreased during the last decades, but most studies have been unable to assess case severities among individual patients. We aimed to assess changes in severity-adjusted aSAH mortality in patients admitted to intensive care units (ICUs). We conducted a retrospective, register-based study by using the prospectively collected Finnish Intensive Care Consortium database. Four out of five ICUs providing neurosurgical and neurointensive care in Finland participated in the Finnish Intensive Care Consortium. We extracted data on adult patients admitted to Finnish ICUs with aSAH between 2003 and 2019. The primary outcome was 12-month mortality during three periods: 2003-2008, 2009-2014, and 2015-2019. Using a multivariable logistic regression model-with variables including age, sex, World Federation of Neurological Surgeons grade, preadmission dependency, significant comorbidities, and modified Simplified Acute Physiology Score II-we analyzed whether admission period was independently associated with mortality. A total of 1,847 patients were included in the study. For the periods 2003-2008 and 2015-2019, the mean number of patients with aSAH admitted per year increased from 81 to 123. At the same time, the patients' median age increased from 55 to 58 years (p = 0.001), and the proportion of patients with World Federation of Neurological Surgeons grades I-III increased from 42 to 58% (p < 0.001). The unadjusted 12-month mortality declined from 30% in 2003-2008 to 23% in 2015-2019 (p = 0.001), but there was no statistically significant change in severity-adjusted mortality. Between 2003 and 2019, patients with aSAH admitted to ICUs became older and the proportion of less severe cases increased. Unadjusted mortality decreased but age and case severity adjusted-mortality remained unchanged.


A fluorimetric enzyme assay for the diagnosis of Morquio disease type A (MPS IV A).
4-Methylumbelliferyl-beta-D-galactopyranoside-6-sulphate was synthesized and used for the determination of galactose-6-sulphate sulphatase activity. Fibroblasts and leucocytes from 12 different Morquio A patients, showed 0.0-2.7% of mean normal galactose-6-sulphate sulphatase activity. Heterozygotes showed intermediate activities. The enzymatic liberation of the fluorochrome from 4-methylumbelliferyl-beta-D-galactopyranoside-6-sulphate requires the sequential action of galactose-6-sulphate sulphatase and beta-galactosidase. Normal beta-galactosidase activity caused nearly complete hydrolysis of non-fluorescing 4-methylumbelliferyl-galactoside, formed during incubation. In cell extracts with a beta-galactosidase deficiency however, a second incubation in the presence of excess beta-galactosidase is needed to avoid underestimation of galactose-6-sulphate sulphatase activity.


Phosphate-a poison for humans?
Maintenance of phosphate balance is essential for life, and mammals have developed a sophisticated system to regulate phosphate homeostasis over the course of evolution. However, due to the dependence of phosphate elimination on the kidney, humans with decreased kidney function are likely to be in a positive phosphate balance. Phosphate excess has been well recognized as a critical factor in the pathogenesis of mineral and bone disorders associated with chronic kidney disease, but recent investigations have also uncovered toxic effects of phosphate on the cardiovascular system and the aging process. Compelling evidence also suggests that increased fibroblastic growth factor 23 and parathyroid hormone levels in response to a positive phosphate balance contribute to adverse clinical outcomes. These insights support the current practice of managing serum phosphate in patients with advanced chronic kidney disease, although definitive evidence of these effects is lacking. Given the potential toxicity of excess phosphate, the general population may also be viewed as a target for phosphate management. However, the widespread implementation of dietary phosphate intervention in the general population may not be warranted due to the limited impact of increased phosphate intake on mineral metabolism and clinical outcomes. Nonetheless, the increasing incidence of kidney disease or injury in our aging society emphasizes the potential importance of this issue. Further work is needed to more completely characterize phosphate toxicity and to establish the optimal therapeutic strategy for managing phosphate in patients with chronic kidney disease and in the general population.


Correction to: Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome: a consensus statement from the FD/MAS international consortium.
The original version of this article [1] unfortunately included an error to an author's name. Paul Arundel was inadvertently presented as Paul Arunde.


First-Line Treatments for Poor-Prognosis Metastatic Renal Cell Carcinoma: Experts' Prescribing Practices and Systematic Literature Review.
No head-to-head clinical trials are available to help physicians in the decision-making process of first-line therapy in poor-prognosis metastatic renal cell carcinoma (RCC). The objectives of our study were to identify experts' prescribing practices and to review available clinical data in first-line therapies for poor-prognosis metastatic RCC (mRCC). Thirteen RCC experts were asked to fill in a self-administered questionnaire evaluating prescribing practices. A systematic review was performed in July 2015 in MEDLINE for clinical trials evaluating first-line strategy in poor-prognosis mRCC. Ten out of 13 experts completed the questionnaire (76.9%). Sunitinib was the most frequently prescribed first-line therapy (8/10; 80%). The main reason for prescribing sunitinib most frequently was the evidence of effectiveness for the majority (5/8 experts). A total of 21 articles were found suitable. Only one phase III randomized controlled trial in which all patients had a poor prognosis was retrieved. Temsirolimus increases progression-free survival and overall survival compared to IFN-alpha. Increased PFS with sunitinib in poor-prognosis patients was shown in a subgroup analysis of the pivotal trial. An expanded-access trial confirmed this result. Experts tend to prefer sunitinib as first-line therapy even in poor-prognosis mRCC. In light of the systematic review, no targeted therapy appears to be more effective than another. The upcoming challenge is to discover more effective new drugs since the overall survival of poor-prognosis mRCC still remains extremely limited.


Cardiac morphologic observations after operative closure of acquired ventricular septal defect during acute myocardial infarction: analysis of 16 necropsy patients.
Certain cardiac morphologic findings are described in 16 necropsy patients having operative closure of an acquired ventricular septal defect (VSD) during acute myocardial infarction (AMI). Of the 16 patients, 6 were women (mean age 69 +/- 7 years) and 10 were men (mean age 60 +/- 11 years). The AMI associated with the VSD was the first coronary event in 13 patients (81%). At least 6 patients had a history of systemic hypertension. Conduction disturbances were diagnosed by electrocardiogram in 5 patients (31%). The median interval from the onset of the AMI to death was 11 days, and from the onset of the AMI to operative closure of the VSD, 4 days. Eight patients died in the operating room or within 2 hours of operation. Coronary artery bypass grafting was performed simultaneously with the VSD closure in 7 patients. Death was attributed to unsuccessful VSD closure in 5 patients, to inadequate left ventricular cavity after resection of necrotic myocardium in 5 patients and to inadequate viable left ventricular myocardium in 4 patients. Heart weights were increased in 14 patients (88%). The AMI associated with the VSD was anterior in 9 patients and posterior (inferior) in 7. Healed myocardial infarcts were present in 3 patients. All 16 patients had severe (greater than 75% in cross-sectional area) narrowing of 1 or more of the 4 major epicardial coronary arteries.


Autoimmune pancreatitis and non-necrotizing acute pancreatitis: computed tomography pattern.
To retrospectively differentiate diffuse autoimmune pancreatitis from non-necrotizing acute pancreatitis at clinical onset with multi detector row computed tomography. 36 Patients suffering from diffuse autoimmune pancreatitis (14) or non-necrotizing acute pancreatitis (22) were enrolled. Qualitative analysis included stranding, retroperitoneal fluid film, capsule-like rim enhancement and pleural effusion. In quantitative analysis pancreatic density was measured in all phases. The vascularization behaviour was assessed using the relative enhancement rate across all phases. Pancreatic density resulted lower in non-necrotizing acute pancreatitis compared to diffuse autoimmune pancreatitis patients in pre-contrast phase and higher in pancreatic phase. Relative enhancement rate evaluation confirmed different vascularization behaviours of the two diseases. Only non-necrotizing acute pancreatitis Patients presented peripancreatic stranding and fluid in the retromesenteric interfascial plane. Multi detector row computed tomography is a useful technique for differentiating diffuse autoimmune pancreatitis from non-necrotizing acute pancreatitis at clinical onset. Peripancreatic stranding and retroperitoneal fluid film, characteristic of non-necrotizing acute pancreatitis, and late-phase peripheral rim enhancement, characteristic of diffuse autoimmune pancreatitis, provide qualitative clues to the differentiation. A quantitative study of contrast enhancement patterns, considering the relative enhancement rate, can assist in the differential diagnoses of two diseases.


Relationship of the platelet glycoprotein PlA and fibrinogen T/G+1689 polymorphisms with peripheral arterial disease and ischaemic heart disease.
Genetic variation in plasma fibrinogen and the platelet receptor GP IIIa locus has been independently associated with increased risks of ischaemic heart disease, but there have been few reports on the relationship with peripheral arterial disease. This study determined the risk of peripheral arterial disease and ischaemic heart disease associated with polymorphisms of fibrinogen T/G(+1689) and platelet glycoprotein Pl(A) genes and the effects of cigarette smoking and fibrinogen. In the 5-year follow-up phase of the Edinburgh Artery Study, 939 subjects (60-79 years) had DNA extracted from a venous blood sample. One hundred sixteen subjects were identified as having angina, 87 a myocardial infarction, 104 had intermittent claudication and 663 subjects comprised a healthy group. Distribution of the fibrinogen genotype was similar across the disease and healthy groups. Logistic regression analyses found no significant association between fibrinogen genotype and ischaemic heart disease and peripheral arterial disease. A lower percentage of claudicants had the Pl(A2) allele (8.3% vs. 15.2%, p=0.025). After adjustment for age and sex, the risk of IC associated with the Pl(A2) was half that of the homozygous Pl(A1) genotype (OR 0.49, 95% CI 0.25, 0.88; p<==0.05). Adjustment for lifetime smoking and fibrinogen levels increased the odds slightly to nonsignificance. The Pl(A2) genotype was associated with a decreased risk of developing IC. There was no significant relationship between fibrinogen T/G(+1689) genotype and ischaemic and peripheral heart disease in this older population.


Food neophobia among Nigerian consumers: a study on attitudes towards novel turmeric-fortified drinks.
Knowledge on food neophobia among African consumers is scarce. Yet a good understanding in this area is essential to support the acceptance of new foods, for instance, when fortifying familiar foods to improve the health and nutritional status of the populace. In this paper, food neophobia among Nigerian consumers was assessed by their attitudes towards unfamiliar beverages, namely turmeric-fortified drinks. Turmeric was chosen as the Nigerian government is stimulating its production for income generation, but the spice is not commonly used in Nigerian foods and drinks. Familiar street-vended drinks, i.e. soymilk and the hibiscus-based drink zobo, were fortified with turmeric. Respondents (483) were allowed to try both the familiar and unfamiliar (turmeric-fortified) drinks. Subjects also filled in a 20-item questionnaire concerning attitudes toward food and eating. Food neophobia was measured by the Food Attitude Survey (FAS) instrument ratings. Using the FAS, people who reported liking the fortified drinks ('likers') were compared with those who disliked the drinks ('dislikers') and those who were unwilling to try the drinks ('will not tryers'). Males were found to be more food neophobic than females. Middle-class income earners, the age group of 26-35 years and respondents with the highest education levels also showed a more food neophobic attitude towards turmeric-fortified drinks. Practical insights are given regarding the introduction of novel foods to Nigerian consumers by paying attention to attitudes from respondents with different demographic characteristics. The use of influencers seems to be a promising approach to address food neophobia in Nigeria. © 2020 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Hydrogen evolution by chloroplast-hydrogenase systems: improvements and additional observations.
An in vitro system containing isolated chloroplasts, ferredoxin and bacterial hydrogenase on illumination evolves H2 and O2 from water. Maximum rate of hydrogen production so far achieved is two litres H2 per g. chlorophyll per h. The rate of H2 evolution per mg chlorophyll is dependent on concentrations of chlorophyll and ferredoxin in the reaction mixture. The rates as well as duration of H2 production are enhanced by the presence of oxygen scavengers and bovine serum albumin in the system. Hydrogenases and ferredoxins vary in their degree of cross reactivity in the chloroplast system; with some hydrogenases the H2 evolution rates were increased by the presence of additional biological electron carriers. Attempts to couple algal hydrogenases to the chloroplasts system have not succeeded so far.


Internal hemorrhage caused by a twisted malignant ovarian dysgerminoma: ultrasonographic findings of a rare case and review of the literature.
Ovarian cancer presents as an acute abdomen very rarely. The purpose of the study is the description of a right ovarian malignant dysgerminoma presenting as an abdominal emergency. A 16-year-old white female presented with acute abdominal pain in the right iliac fossa. On physical examination the abdomen was acute and a mass in the right lower abdomen was palpated. The patient was sexually active and bimanual gynecological examination revealed the presence of a large lobulated solid tumor in the position of the right adnexa. Ultrasound examination showed the presence of a large, multilobulated, heterogeneous, predominantly solid pelvic mass. Color flow imaging showed intratumoral flow signals. The uterus and the left ovary had normal size and echo-texture. Fluid was found in the cul-de-sac and in Morisson's space. An immediate exploratory laparotomy exposed the presence of a twisted right ovarian mass and intraperitoneal hemorrhage. A superficial tumoral vessel actively bleeding was seen. Peritoneal fluid was obtained for cytology. The intra-abdominal hemorrhage ceased when the ovarian pedicle was clamped. The patient underwent right salpingo-oophorectomy and biopsy of the omentum. Pathologic analysis revealed a malignant dysgerminoma of the right ovary, expanding to the mesosalpinx. Cytology was positive for malignancy. Postoperative CT scan of the upper and lower abdomen was negative. The patient was assigned to FIGO Stage IIC and referred for platinum-based chemotherapy. Ovarian malignant dysgerminoma may present as an acute abdomen because of torsion, passive blood congestion, rupture of superficial tumoral vessels and subsequent intra-abdominal hemorrhage. Ovarian dysgerminoma should be part of the differential diagnosis in a young woman with acute surgical abdomen and a solid heterogeneous pelvic mass detected by ultrasonographic scan.


Preoperative imaging and surgical margins in maxillectomy patients.
High rates of positive surgical margins are reported after a maxillectomy. A large part of tumors that are preoperatively considered "operable" can thus not be resected with tumor-free margins. This was a retrospective study on medical files of 69 patients that underwent maxillectomy as primary treatment for a squamous cell carcinoma. More than one third (39%) of all resections performed is incomplete, with dorsal or dorsocranial-positive surgical margins in two thirds. Correlation of tumor extension on preoperative imaging to surgical margins status revealed that dorsal and cranial tumor extension were significant prognostic factors for tumor positive surgical margins (p = .006 and p = .031, respectively). Positive margins were associated with a 2-fold increased risk of death (hazard ratio, 2.4; 95% confidence interval, 1.2-4.9). Cranial or dorsal tumor extension on preoperative imaging was a significant risk factor for positive surgical margins after maxillectomy with significant negative influence on overall survival.


Brain MRI imaging markers associated with death in children with central nervous system involvement of hemophagocytic lymphohistiocytosis.
To investigate the association of brain MRI and clinical variables with death in children with central nervous system involvement of hemophagocytic lymphohistiocytosis (CNS-HLH). Clinical and brain MRI data of children with CNS-HLH from January 2012 to March 2022 were reviewed retrospectively. Patients were divided into the deceased group and the surviving group. The intergroup differences of seven brain MRI variables, twelve clinical variables, and underlying diseases were studied. One hundred and fourteen patients were included in this study, consisting of 59 who died and 55 who survived. The included clinical variables did not show statistically independent correlation with patients' deaths. For MRI variables, a multivariate analysis demonstrated restricted diffusion of lesion (OR = 9.64, 95% CI: 3.39-27.43, p < 0.001) and count of affected brain regions (CABR) (OR = 1.24, 95% CI: 1.03-1.49, p = 0.02) were independent risk factors for death. ROC curve showed CABR (AUC = 0.79, 95% CI: 0.70-0.87, p < 0.001) is highly predictive for mortality with an optimal cutoff value of 4.5 (sensitivity 76%, specificity 73%). For HLH subtypes, familial HLH (F-HLH, OR = 9.90, 95% CI: 2.01-48.87, p = 0.005) and immune-compromise-related HLH (IC-HLH, OR = 4.95, 95% CI: 1.40-17.46, p = 0.01) presented statistically stronger association with death than infection-related HLH. F-HLH and IC-HLH preferred to have large lesions, restricted diffusion, and more brain regions involved than other subtypes. Brain MRI features exhibit independent prediction for mortality in children with CNS-HLH, and HLH subtypes pose effects on patient outcomes and brain MRI findings. The number of affected brain regions and diffusion restriction of lesion exhibit significant correlation with mortality in children diagnosed with CNS-hemophagocytic lymphohistiocytosis, and may serve as candidate MRI markers for the prediction of the disorder's severity. • The brain MRI markers, restricted diffusion of lesion and count of affected brain regions, significantly correlated with death. • Familial and immune-compromise-related hemophagocytic lymphohistiocytosis presented statistically stronger association with death than infection-related subtype. • Brain MRI is potential in death-predicting for children with central nervous system involvement of hemophagocytic lymphohistiocytosis.


Large-scale international volleyball competition in "bubble" under the COVID-19 pandemic.
To verify whether a large-scale international volleyball competition could be conducted safely using the bubble method, both for our participating team and as a whole. All 32 men's and women's teams were gathered in one place and a large-scale international volleyball competition was held for over a month without spectators using the bubble method. More than 1,000 people participated in the event, and 572 volleyball players played a total of 248 matches during the competition. There were 54 participants from Japan, including 27 male and female staff and players each. There was one team doctor for both men and women. A total of 2,250 PCR tests and 7,920 antigen tests were performed over 38 days. We investigated the incidence of infection in our team and in all participating teams. There were 9 fever cases from our men's team, but all of them tested negative for COVID-19. Overall, a total of 10,170 tests were performed and only one was positive. In order to ensure the health and well-being of all participants, the indoor competition was concluded safely without the occurrence of COIVD-19 clusters in the bubble system with strict adherence to various strict protocols of COVID-19.


Reproducibility of muscle fibre conduction velocity during linearly increasing force contractions.
Muscle fibre conduction velocity (MFCV) is a basic physiological parameter biophysically related to the diameter of muscle fibres and properties of the sarcolemma. The aim of this study was to assess the intersession reproducibility of the relation between voluntary force and estimates of average muscle fibre conduction velocity (MFCV) from multichannel high-density surface electromyographic recordings (HDsEMG). Ten healthy men performed six linearly increasing isometric ankle dorsiflexions on two separate experimental sessions, 4 weeks apart. Each session involved the recordings of voluntary force during maximal isometric (MViF) and submaximal ramp contractions at 35-50-70% of MViF. Concurrently, the HDsEMG activity was detected from the tibialis anterior muscle and MFCV estimates were derived in 250-ms epochs. Absolute and relative reproducibility of MFCV initial value (intercept) and rate of change (regression slope) as a function of force were assessed by within-subject coefficient of correlation (CVw) and with intraclass correlation coefficient (ICC). MFCV was positively correlated with voluntary force (R2 = 0.75 ± 0.12) in all individuals and test conditions (P < 0.001). Average CVw for MFCV intercept and slope were of 2.6 ± 2.0% and 11.9 ± 3.2% and ICC values of 0.96 and 0.94, respectively. Overall, MFCV regression coefficients showed a high degree of intersession reproducibility in both absolute and relative terms. These results may have important practical implications in the tracking of training-induced neuromuscular changes and/or in the monitoring of the progress of neuromuscular disorders when a full sEMG signal decomposition is problematic or not possible.


Fenollaria timonensis sp. nov., A New Bacterium Isolated from Healthy Human Fresh Stool.
The strain Marseille-P2133 is the type strain of a new bacterial species of the order Clostridiales that was isolated from a stool sample from a healthy volunteer. It is a strictly anaerobic Gram-negative coccobacillus. MALDI-TOF MS did not provide any identification. Strain Marseille-P2133T exhibits 97.4% similarity levels with the Fenollaria massiliensis strain 9401234T (NR_133038), a phylogenetically related species with standing in nomenclature. On the basis of these data, we propose the creation of Fenollaria timonensis sp. nov.


Analysis of the inhibition of food spoilage yeasts by vanillin.
The antimicrobial potential of vanillin, the major component of vanilla flavour, was examined against the growth of three yeasts associated with food spoilage, Saccharomyces cerevisiae, Zygosaccharomyces bailii and Zygosaccharomyces rouxii. Minimum inhibitory concentration (MIC) values of 21, 20 and 13 mM vanillin were determined for the three yeast strains, respectively. The observed inhibition was found to be biostatic. During fermentation, the bioconversion of sub-MIC levels of vanillin in the culture medium was demonstrated. The major bioconversion product was identified as vanillyl alcohol, however low levels of vanillic acid were also detected. Neither the vanillyl alcohol nor the vanillic acid was found to be antagonistic to yeast cell growth. The results indicate the importance of the aldehyde moiety in the vanillin structure regarding its antimicrobial activity and that the bioconversion of vanillin could be advantageous for the yeasts, but only at levels below MIC. These bioconversion activities, presumably catalysed by non-specific dehydrogenases, were shown to be expressed constitutively. It was observed that increased vanillin concentrations inhibited its own bioconversion suggesting that the activity required intact cells with metabolic capacity.


Removal of duodenal foreign body with endoscopic snare.
The extraction of a thermometer wedged in the duodenum, which utilized fibrendoscopic techniques, is described. A brief review of methods which are available to the endoscopist to retrieve ingested foreign bodies is presented.


Toward imaging of alpha-synuclein with PET.
Development of radiopharmaceuticals for in vivo positron emission tomography imaging of alpha-synuclein aggregates has the potential to revolutionize Lewy body disease diagnosis and treatment. Reporting in this issue of Cell, Xiang et al. developed a high-affinity positron emission tomography tracer for alpha-synuclein.


SARS-CoV-2 infection negatively affects ovarian function in ART patients.
Several organs, such as the heart, breasts, intestine, testes, and ovaries, have been reported to be target tissues of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To date, no studies have demonstrated SARS-CoV-2 infection in the female reproductive system. In the present study, we investigated the effects of SARS-CoV-2 infection on ovarian function by comparing follicular fluid (FF) from control and recovered coronavirus disease 2019 (COVID-19) patients and by evaluating the influence of these FF on human endothelial and non-luteinized granulosa cell cultures. Our results showed that most FFs (91.3%) from screened post COVID-19 patients were positive for IgG antibodies against SARS-CoV-2. Additionally, patients with higher levels of IgG against SARS-CoV-2 had lower numbers of retrieved oocytes. While VEGF and IL-1β were significantly lower in post COVID-19 FF, IL-10 did not differ from that in control FF. Moreover, in COV434 cells stimulated with FF from post COVID-19 patients, steroidogenic acute regulatory protein (StAR), estrogen-receptor β (Erβ), and vascular endothelial growth factor (VEGF) expression were significantly decreased, whereas estrogen-receptor α (ERα) and 3β-hydroxysteroid dehydrogenase (3β-HSD) did not change. In endothelial cells stimulated with post COVID-19 FF, we observed a decrease in cell migration without changes in protein expression of certain angiogenic factors. Both cell types showed a significantly higher γH2AX expression when exposed to post COVID-19 FF. In conclusion, our results describe for the first time that the SARS-CoV-2 infection adversely affects the follicular microenvironment, thus dysregulating ovarian function.


[The multicenter non-interventional, prospective observational program on the study of practical use of teraligen in patients diagnosed with autonomic disorder (START2): a local Russian experience with the use of the Russian version of The Four-Dimensional Symptom Questionnaire (4DSQ). An intermediate analysis].
To develop a new instrument able to identify pathological states and assess their changes during medication treatment. We aimed to study the typical practice of using alimemazine (teraligen) in patients with the diagnosis of autonomic nervous system disorder and to test the Russian version of @The Four-Dimensional Symptom Questionnaire@ (4DSQ) for measuring distress, depression, anxiety and somatization. We examined 3053 patients (mean age 42.09 ± 11.71 years) who received teraligen in doses gradually increasing from 5 to 15 mg per day. The observational program was carried out in over 600 outpatient clinics of the Russian Federation. The 4DSQ was administered before treatment and 4 weeks after treatment. The Clinical Global Impression (CGI) scale was used before, during (after 2 weeks) and after (4 weeks) treatment with teraligen. There was a significant improvement of patient's state assessed both by physicians (CGI scale) and by patients (96 and 98%, respectively). The 4DSQ was sensitive to the parameters of response to treatment with teraligen: parameters obtained at baseline and 4 weeks after the beginning of treatment differed significantly demonstrating a significant decrease in distress, anxiety and somatization.


The oncocytic subtype is genetically distinct from other pancreatic intraductal papillary mucinous neoplasm subtypes.
In 2010, the World Health Organization reclassified the entity originally described as intraductal oncocytic papillary neoplasm as the 'oncocytic subtype' of intraductal papillary mucinous neoplasm. Although several key molecular alterations of other intraductal papillary mucinous neoplasm subtypes have been discovered, including common mutations in KRAS, GNAS, and RNF3, those of oncocytic subtype have not been well characterized. We analyzed 11 pancreatic 'oncocytic subtype' of intraductal papillary mucinous neoplasms. Nine pancreatic 'oncocytic subtype' of intraductal papillary mucinous neoplasms uniformly exhibited typical entity-defining morphology of arborizing papillae lined by layers of cells with oncocytic cytoplasm, prominent, nucleoli, and intraepithelial lumina. The remaining two were atypical. One lacked the arborizing papilla and had flat oncocytic epithelium only; the other one had focal oncocytic epithelium in a background of predominantly intestinal subtype intraductal papillary mucinous neoplasm. Different components of this case were analyzed separately. Formalin-fixed, paraffin-embedded specimens of all cases were microdissected and subjected to high-depth-targeted next-generation sequencing for a panel of 300 key cancer-associated genes in a platform that enabled the identification of sequence mutations, copy number alterations, and select structural rearrangements involving all targeted genes. Fresh frozen specimens of two cases were also subjected to whole-genome sequencing. For the nine typical pancreatic 'oncocytic subtype' of intraductal papillary mucinous neoplasms, the number of mutations per case, identified by next-generation sequencing, ranged from 1 to 10 (median=4). None of these cases had KRAS or GNAS mutations and only one had both RNF43 and PIK3R1 mutations. ARHGAP26, ASXL1, EPHA8, and ERBB4 genes were somatically altered in more than one of these typical 'oncocytic subtype' of intraductal papillary mucinous neoplasms but not in the other two atypical ones. In the neoplasm with flat oncocytic epithelium, the only mutated gene was KRAS. All components of the intestinal subtype intraductal papillary mucinous neoplasms with focal oncocytic epithelium manifested TP53, GNAS, and RNF43 mutations. In conclusion, this study elucidates that 'oncocytic subtype' of intraductal papillary mucinous neoplasm is not only morphologically distinct but also genetically distinct from other intraductal papillary mucinous neoplasm subtypes. Considering that now its biologic behavior is also being found to be different than other intraductal papillary mucinous neoplasm subtypes, 'oncocytic subtype' of intraductal papillary mucinous neoplasm warrants being recognized separately.


Lack of interlimb transfer following visuomotor adaptation in a person with congenital mirror movements despite the awareness of the visuomotor perturbation.
There is a controversy regarding whether visuomotor adaptation heavily involves both implicit and explicit learning processes or not. Likewise, another controversy exists regarding whether interlimb transfer of visuomotor adaptation is related to explicit processes or not. To address the latter issue, we examined interlimb transfer of visuomotor adaptation in an individual with congenital mirror movements, 'DB'. DB has been tested previously using an experimental paradigm in which neurologically intact individuals demonstrated substantial transfer. DB, however, showed no transfer due to impaired interhemispheric communications. In that study, DB was unaware of the visuomotor perturbation. Here, we informed him of the perturbation prior to the experiment to determine whether providing the information would increase interlimb transfer. DB first adapted to a visuomotor rotation with the left arm, then with the right arm during reaching movements. Data from the present study were compared against those from our previous study. Results indicate no transfer across the arms despite the fact that he was aware of the perturbation. Considering overall findings in the literature, we suggest that interlimb transfer does not depend on one's awareness, although its extent can increase when individuals rely on cognitive strategies to deal with perturbations (c.f., Werner et al., 2019).


Quantifying the risk and dosimetric variables of symptomatic brainstem injury after proton beam radiation in pediatric brain tumors.
Brainstem toxicity after radiation therapy (RT) is a devastating complication and a particular concern with proton radiation (PBT). We investigated the incidence and clinical correlates of brainstem injury in pediatric brain tumors treated with PBT. All patients <21 years with brain tumors treated with PBT at our institution from 2007-2019, with a brainstem Dmean >30 Gy and/or Dmax >50.4 Gy were included. Symptomatic brainstem injury (SBI) was defined as any new or progressive cranial neuropathy, ataxia, and/or motor weakness with corresponding radiographic abnormality within brainstem. A total of 595 patients were reviewed and 468 (medulloblastoma = 200, gliomas = 114, ependymoma = 87, ATRT = 43) met our inclusion criteria. Median age at RT was 6.3 years and median prescribed RT dose was 54Gy [RBE]. Fifteen patients (3.2%) developed SBI, at a median of 4 months after RT. Grades 2, 3, 4, and 5 brainstem injuries were seen in 7, 5, 1, and 2 patients respectively. Asymptomatic radiographic changes were seen in 51 patients (10.9%). SBI was significantly higher in patients with age ≤3 years, female gender, ATRT histology, patients receiving high-dose chemotherapy with stem cell rescue, and those not receiving craniospinal irradiation. Patients with SBI had a significantly higher V50-52. In 2014, our institution started using strict brainstem dose constraints (Dmax ≤57 Gy, Dmean ≤52.4 Gy, and V54≤10%). There was a trend towards decrease in SBI from 4.4% (2007-2013) to 1.5% (2014-2019) (P = .089) without affecting survival. Our results suggest a low risk of SBI after PBT for pediatric brain tumors, comparable to photon therapy. A lower risk was seen after adopting strict brainstem dose constraints.


The slow inward calcium current is responsible for a part of the contraction of patch-clamped rat myoballs.
The slow inward calcium current and the contractile response were simultaneously recorded in voltage clamped (whole cell patch clamp recording) rat myoballs in primary culture. The shape of the contraction(T)/potential(V) relationship and the application of the inorganic calcium channel blocker cadmium (1.5 mM), which suppresses a part of the contractile activity, demonstrate the existence of two components of contraction. One of them is related to the slow calcium current.


Biocompatible In Situ Polymerization of Multipurpose Polyacrylamide-Based Hydrogels on Skin via Silver Ion Catalyzation.
Free radical polymerization is a mature method and can be used for preparing multifunctional hydrogels by simply changing the commercial monomers, but the harsh and time-consuming initiation conditions restrict its injectable ability, which further limits its application in the biomedical field. Though some catalysts can be used to accelerate the polymerization, their application is restrained by the biotoxicity. Hence, finding a biocompatible catalyzer for in situ free radical polymerization of hydrogels has a great prospect in biomedical application but is still challenging. In this study, we discovered that silver ions could catalyze free radical polymerization under ambient by transforming hydrone into hydroxyl radicals in the presence of ammonium persulfate, and the in situ-formed hydrogels prepared by this way showed great histocompatibility, hemocompatibility, cytocompatibility, and immunocompatibility. Benefitting from its convenience and biocompatibility, the in situ polymerization of polyacrylamide-based hydrogels for tissue adhesion, wound dressing, and conductive materials on the skin could be realized by simply blending diverse ingredients. Furthermore, this discovery may be a step toward the in situ-polymerized hydrogels for biomedical applications.


TRPS1 regulates the opposite effect of progesterone via RANKL in endometrial carcinoma and breast carcinoma.
Medroxyprogesterone (MPA) has therapeutic effect on endometrial carcinoma (EC), while it could promote the carcinogenesis of breast cancer (BC) by activating receptor activator of NF-kB ligand (RANKL). However, the selective mechanism of MPA in endometrium and breast tissue remains obscure. Multiomics analysis of chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) were performed in cell lines derived from endometrial cancer and mammary tumor to screen the differential co-regulatory factors of progesterone receptor (PR). Dual-luciferase assays and ChIP-PCR assays were used to validate the transcriptional regulation. Co-immunoprecipitation (Co-IP) and immunofluorescence assays were carried out to explore molecular interactions between PR, the cofactor transcriptional repressor GATA binding 1 (TRPS1), and histone deacetylase 2 (HDAC2). Subsequently, human endometrial cancer/breast cancer xenograft models were established to investigate the regulation effect of cofactor TRPS1 in vivo. In the current study, we found that MPA downregulated RANKL expression in a time- and dose-dependent manner in EC, while had the opposite effect on BC. Then PR could recruit cofactor TRPS1 to the promoter of RANKL, leading to histone deacetylation of RANKL to repress its transcription in EC, whereas MPA disassociated the PR/TRPS1/HDAC2 complex to enhance RANKL histone acetylation in BC. Therefore, TRPS1, the coregulator recruited by PR played a critical role in the selective mechanism of progesterone in EC and BC and could become a potential candidate for targeted therapy to improve the anticancer effect of MPA on EC and avoid its carcinogenic effect on BC.


A switch therapy protocol with intravenous azithromycin and ciprofloxacin combination for severe, relapsing chronic bacterial prostatitis: a prospective non-comparative pilot study.
Chronic bacterial prostatitis (CBP) is characterized by intense clinical symptoms, frequent relapse episodes and poor quality of life. Aggressive antibacterial therapy is warranted to eradicate the causative pathogens and to achieve a permanent cure. We administered a "switch-therapy" protocol to 30 patients showing severe CBP symptoms and two or more relapse episodes in the previous 12 months. Patients received intravenous azithromycin (500 mg/day) and ciprofloxacin (800 mg/day) for 3 days, followed by oral ciprofloxacin (1 g/day) for 25 days.Twenty-seven (90%) patients showed pathogen eradication at test-of-cure (TOC) visit. Five cases of infection relapse were detected at follow-up. At the TOC visit, 25 patients (83%) showed mild/absent symptoms, measured with the NIH-chronic prostatitis symptom index.These results indicate the efficacy of a "switch-therapy" protocol, based on combined azithromycin and ciprofloxacin. Comparative studies on larger CBP patient populations are warranted to confirm these encouraging results.


Evidence for inefficient contraction and abnormal mitochondrial activity in sarcopenia using magnetic resonance spectroscopy.
Mitochondrial dysfunction has been implicated in sarcopenia. 31 P magnetic resonance spectroscopy (MRS) enables non-invasive measurement of adenosine triphosphate (ATP) synthesis rates to probe mitochondrial function. Here, we assessed muscle energetics in older sarcopenic and non-sarcopenic men and compared with muscle biopsy-derived markers of mitochondrial function. Twenty Chinese men with sarcopenia (SARC, age = 73.1 ± 4.1 years) and 19 healthy aged and sex-matched controls (CON, age = 70.3 ± 4.2 years) underwent assessment of strength, physical performance, and magnetic resonance imaging. Concentrations of phosphocreatine (PCr), ATP and inorganic phosphate (Pi) as well as muscle pH were measured at rest and during an interleaved rest-exercise protocol to probe muscle mitochondrial function. Results were compared to biopsy-derived mitochondrial complex activity and expression to understand underlying metabolic perturbations. Despite matched muscle contractile power (strength/cross-sectional area), the ATP contractile cost was higher in SARC compared with CON (low-intensity exercise: 1.06 ± 0.59 vs. 0.57 ± 0.22, moderate: 0.93 ± 0.43 vs. 0.58 ± 0.68, high: 0.70 ± 0.57 vs. 0.43 ± 0.51 mmol L-1 min-1 bar-1 cm-2 , P = 0.003, <0.0001 and <0.0001, respectively). Post-exercise mitochondrial oxidative synthesis rates (a marker of mitochondrial function) tended to be longer in SARC but did not reach significance (17.3 ± 6.4 vs. 14.6 ± 6.5 mmol L-1 min-1 , P = 0.2). However, relative increases in end-exercise ADP in SARC (31.8 ± 9.9 vs. 24.0 ± 7.3 mmol L-1 , P = 0.008) may have been a compensatory mechanism. Mitochondrial complex activity was found to be associated with exercise-induced drops in PCr [citrate synthetase activity (CS), Spearman correlation rho = -0.42, P = 0.03] and end-exercise ADP (complex III, rho = -0.52, P = 0.01; CS rho = -0.45, P = 0.02; SDH rho = -0.45, P = 0.03), with CS also being strongly associated with the PCr recovery rate following low intensity exercise (rho = -0.47, P = 0.02), and the cost of contraction at high intensity (rho = -0.54, P = 0.02). Interestingly, at high intensity, the fractional contribution of oxidative phosphorylation to exercise was correlated with activity in complex II (rho = 0.5, P = 0.03), CS (rho = 0.47, P = 0.02) and SDH (rho = 0.46, P = 0.03), linking increased mitochondrial complex activity with increased ability to generate energy through oxidative pathways. This study used 31 P MRS to assess ATP utilization and resynthesis in sarcopenic muscle and demonstrated abnormal increases in the energy cost during exercise and perturbed mitochondrial energetics in recovery. Associations between mitochondrial complex activity and the fractional contribution to energy requirement during exercise indicate increased ability to generate energy oxidatively in those with better mitochondrial complex activity.


Genipin Inhibits the Development of Osteosarcoma through PI3K/AKT Signaling Pathway.
Osteosarcoma is a highly invasive and early metastatic tumor. At present, the toxic and side effects of chemotherapy affect the quality of life of cancer patients to varying degrees. Genipin is an extract of the natural medicine gardenia with various pharmacological activities. The purpose of this study was to investigate the effect of Genipin on osteosarcoma and its potential mechanism of action. Crystal violet staining, MTT assay and colony formation assay were used to detect the effect of genipin on the proliferation of osteosarcoma. The effects of vitexin on migration and invasion of osteosarcoma were detected by scratch healing assay and transwell assay. Hoechst staining and flow cytometry were used to detect the effect of genipin on apoptosis of osteosarcoma cells. The expression of related proteins was detected by Western blot. An orthotopic tumorigenic animal model was used to verify the effect of genipin on osteosarcoma in vivo. The results of crystal violet staining, MTT method and colony formation method proved that genipin significantly inhibited the proliferation of osteosarcoma cells. The results of the scratch healing assay and transwell assay showed that gen significantly inhibited the migration and invasion of osteosarcoma cells. The results of Hoechst staining and flow cytometry showed that genipin significantly promoted the apoptosis of osteosarcoma cells. The results of animal experiments show that genipin has the same anti-tumor effect in vivo. Genipin may inhibit the growth of osteosarcoma through PI3K/AKT signaling. Genipin can inhibit the growth of human osteosarcoma cells, and its mechanism may be related to the regulation of PI3K/AKT signaling pathway.


Habitual fish consumption and healthy lifestyle behaviours may be associated with higher total serum bilirubin level and anti-inflammatory activity: a cross-sectional study.
Habitual fish consumption and a healthy lifestyle are associated with lower atherosclerotic CVD (ASCVD) risk. Mildly elevated bilirubin, an end product of Hb metabolism, may be associated with anti-inflammatory effects, suppressing ASCVD risk. No data exist on the relationship between fish consumption, total serum bilirubin (TSB) and inflammation in clinical settings. We conducted a cross-sectional study between April 2019 and March 2020 in a cohort of 8292 participants (average age, 46·7 (sd 12·9) years and 58·9 % men) with no history of ASCVD and TSB concentrations < 2·0 mg/dl. Multiple stepwise regression analysis showed Hb concentrations were a solid positive determinant of TSB concentrations (β = 0·302, P< 0·0001). Fish consumption (β = 0·025, P= 0·019) and aerobic exercise (β = 0·021, P= 0·043) were statistically weak but significantly positive determinants of TSB concentrations. Cigarette smoking negatively affected TSB concentrations (β = −0·104, P< 0·0001). Moreover, with increasing fish consumption, the proportion of participants with a habit of cigarette smoking decreased, and that of participants who engaged in aerobic exercises increased (P< 0·0001 for both). Furthermore, as TSB concentrations increased, the leukocyte counts and C-reactive protein concentrations decreased (P< 0·0001 for both). In conclusion, despite the lesser relevance given to TSB concentrations than Hb concentrations, higher fish consumption and healthier lifestyle behaviours related to fish consumption habits may be additively or synergistically associated with higher TSB concentrations and anti-inflammatory activity, leading to attenuated ASCVD risk. Further investigations are needed to clarify the causal relationships between these factors.


Improving communication among nurses and patients.
Patients use nurse call systems to signal nurses for medical help. Traditional push button-flashing lamp call systems are not integrated with other hospital automation systems. Therefore, nurse response time becomes a matter of personal discretion. The improvement obtained by integrating a pager system into the nurse call systems does not increase care efficiency, because unnecessary visits are still not eliminated. To obtain an immediate response and a purposeful visit by a nurse; regardless of the location of nurse in hospital, traditional systems have to be improved by intelligent telephone system integration. The results of the developed Nurse Call System Software (NCSS), the Wireless Phone System Software (WPSS), the Location System Software (LSS) and the communication protocol are provided, together with detailed XML message structures. The benefits of the proposed system are also discussed and the direction of future work is presented.


An Intervention to Increase Knowledge and Utilization of the Low Risk Ankle Rule Among Pediatric Emergency Department Providers.
The Low Risk Ankle Rule (LRAR) can assist pediatric emergency department providers in reducing radiographs without missing significant fractures. Most providers are unaware of this tool. This study sought to educate providers about the LRAR then determine their self-reported use immediately and 2 months after education. A web-based survey was e-mailed to providers at one large pediatric emergency department. The survey assessed knowledge and use of the rule. Clinical scenarios, in which radiographs were not indicated, helped determine radiograph ordering practices. After a brief LRAR tutorial, respondents were requeried about radiograph ordering practices along with likelihood of future LRAR use. At 2 months, radiograph ordering was again assessed using the same scenarios; interim LRAR use was also determined. Response rates on the initial and follow-up surveys were 61.4% and 96.2%, respectively. A minority (20%) had heard of the LRAR. Providers initially reported ordering radiographs on 84% of ankle injuries and 82.5% ordered radiographs in the scenario. Immediately after education, only 32% ordered a radiograph in the scenario; 85% reported that they would use the tool consistently. At 2 months, there was no significant change in radiograph ordering practices (79.5% vs 84%). In the interim, 30% reported using the rule at least once. Most pediatric emergency department providers were unfamiliar with the LRAR. After a brief tutorial, most providers reported that planning to use the tool and self-reported radiograph ordering was significantly reduced; however, at 2 months, clinical practice was unaffected. Further work to implement the tool into practice is necessary.


Streptococcal products and leukocyte activities.
Various streptococcal species are directly responsible for udder infections which should normally be countered by polymorphonuclear neutrophils (PMNs). In order to detect a putative inhibition of streptococcal products on the activities of bovine PMNs, we used a combination of four tests which permits an adequate evaluation of PMNs functions, e.g. PMN adherence on endothelial cells, chemotactic assay, phagocytosis of bacteria labelled with fluorescein isothiocyanate (FITC) and measurement of anion superoxide production. The conclusion is that neither of the two pathogenic streptococcal species isolated from mastitis appeared to produce in vitro factors affecting PMN activities.


Highly stable silver nanoparticles containing guar gum modified dual network hydrogel for catalytic and biomedical applications.
Although many preparation methods have been reported till date, it is still a great challenge to prepare silver nanoparticles (AgNPs) that simultaneously possess high stability and enhanced applicability. We report a rapid and efficient synthesis of AgNPs containing polyvinyl alcohol (PVA)-guar gum (GG) smart hydrogel composite, which exhibited pH-dependent swelling and enhanced mechanical strength. The AgNPs were synthesized in situ in the PVA-GG hydrogel from various concentrations of the AgNO3 precursor solution in the presence of NaBH4. Stable AgNPs (90 days) of 10-20 nm uniformly dispersed in PVA-GG hydrogel was obtained. Simultaneously, at the optimum concentration of AgNO3 (0.01 M), the tensile strength and elongation at break were enhanced by 74 % and 11 %, and swelling capacity was increased by 18 % as compared to PVA-GG hydrogel (control). The PVA-GG-AgNPs hydrogel composite exhibited excellent catalytic activity and antibacterial property, which makes them a suitable candidate for industrial applications.


Periodontal impact of surgically induced dental lesions in mandibular osteodistraction: an animal study.
The objective of the study was to evaluate the impact of dental lesions on the periodontium, in a canine model of mandibular osteodistraction. In six adult male Beagle dogs, an osteotomy was made between the right second lateral incisor and canine, and a distraction device placed. The roots adjacent to the osteotomy were deliberately damaged by the reciprocating saw and chisel, with preservation of the attached gingiva. The osteodistraction protocol used was: latency of 7 days, rate of distraction 1mm per day, and rhythm once a day for 5 days. Vital staining was carried out with tetracycline, Xylenol Orange and Calcein Green. The dogs were sacrificed after 12 weeks of consolidation and the specimens were evaluated with light microscopy (native, polarized light, fluorescence, and after toluidin blue staining). The periodontal ligament (PDL) regeneration was observed in the 2500 slices examined. Cementum and dentine lesions were repaired by cellular cementum. Loose dentine and cementum-dentine fragments were embedded in regenerated PDL and their surface repaired by cementum. By means of light microscopic examination and within the limited observation time, no degenerative pulpal changes were found, when the pulp canal was not entered. Extensive pulp exposure and destruction resulted in ingrowth of the PDL and bone-like tissue. In that case, cellular cementum also lined the dentine surface of the pulp canal. Although there was an extensive reparative response to the para-pulpal lesions, none of the changes observed showed evidence of a loss of functional integrity of the periodontium at the distraction site. The fate of the tooth with exposed pulp canal remains uncertain.


Effect of varying environments on photosynthetic parameters of C3, C3-C4 and C4 species of Panicum.
CO2 exchange characteristics and the activity of the carboxylating enzymes phosphoenolpyruvate carboxylase (PEP-C, E.C. 220.127.116.11) and ribulose 1,5-bisphosphate carboxylase (RuBP-C, E.C. 126.96.36.199) during one year in the greenhouse and at two levels of light and temperature in growth chambers were determined in the C3-C4 intermediate species P. milioides Nees ex. Trin. These results were compared with those of P. bisulcatum Thumb. (C3) and P. maximum Jacq. (C4). Under all tested conditions, and even when the influence of leaf surface temperature on photosynthetic rates and CO2 compensation points were measured, the biochemical and physiological behaviour of the C3-C4 intermediate was more similar to that of the C3 plant than the C4 species. The C4 plant P. maximum, however, responded positively, mainly in terms of PEP-C activity and photosynthetic rate, to the regime of high light and temperature. The results presented indicate that in the C3-C4 Panicum grown in high light and temperature no direct relationships between a low CO2 compesation point and superior growth are evident. It has still to be clarified why in nature a photosynthetic-photorespiratory pathway leading to an intermediate CO2 compensation value has evolved in P. milioides.


Effect on in vitro starch digestibility of Mexican blue maize anthocyanins.
The purpose of this study was to evaluate the effect of blue maize extracts obtained by acid-methanol treatment on the nutritional in vitro starch fractions such as: rapidly digestive starch (RDS), slowly digestive starch (SDS) and resistant starch (RS) of native and gelatinized commercial maize starch. Chromatographic analysis (HPLC-DAD/ESI-MS) of blue maize extracts showed the presence of seven anthocyanins, where cyanidin-3-(6″-malonylglucoside) was the main. Blue maize extracts modified nutritional in vitro starch fractions (decrease of RDS) while RS content increased (1.17 and 2.02 times for native and gelatinized commercial maize starch, respectively) when anthocyanins extracts were added to starch up to 75% (starch weight). This preliminary observation provides the basis for further suitability evaluation of blue maize extract as natural starch-modifier by the possible anthocyanins-starch interaction. Anthocyanin extracts can be a suitable to produce functional foods with higher RS content with potential human health benefits.


Current Resources for Evidence-Based Practice, July 2020.
An extensive review of new resources to support the provision of evidence-based care for women and infants. The current column includes a discussion of whether it is ethical not to offer doula care to all women, and commentaries on reviews focused on folic acid and autism spectrum disorder, and timing of influenza vaccination during pregnancy.


Utilization and impact of cardiovascular magnetic resonance on patient management in heart failure: insights from the SCMR Registry.
Cardiovascular magnetic resonance (CMR) is an important diagnostic test used in the evaluation of patients with heart failure (HF). However, the demographics and clinical characteristics of those undergoing CMR for evaluation of HF are unknown. Further, the impact of CMR on subsequent HF patient care is unclear. The goal of this study was to describe the characteristics of patients undergoing CMR for HF and to determine the extent to which CMR leads to changes in downstream patient management by comparing pre-CMR indications and post-CMR diagnoses. We utilized the Society for Cardiovascular Magnetic Resonance (SCMR) Registry as our data source and abstracted data for patients undergoing CMR scanning for HF indications from 2013 to 2019. Descriptive statistics (percentages, proportions) were performed on key CMR and clinical variables of the patient population. The Fisher's exact test was used when comparing categorical variables. The Wilcoxon rank sum test was used to compare continuous variables. 3,837 patients were included in our study. 94% of the CMRs were performed in the United States with China, South Korea and India also contributing cases. Median age of HF patients was 59.3 years (IQR, 47.1, 68.3 years) with 67% of the scans occurring on women. Almost 2/3 of the patients were scanned on 3T CMR scanners. Overall, 49% of patients who underwent CMR scanning for HF had a change between the pre-test indication and post CMR diagnosis. 53% of patients undergoing scanning on 3T had a change between the pre-test indication and post CMR diagnosis when compared to 44% of patients who were scanned on 1.5T (p < 0.01). Our results suggest a potential impact of CMR scanning on downstream diagnosis of patients referred for CMR for HF, with a larger potential impact on those scanned on 3T CMR scanners.


The first detection and characterization of goose parvovirus (GPV) in Turkey.
Derzsy's disease, which is seen in goslings (Anser anser domestica) and Muscovy ducks (Cairina moschata), progresses to high mortality and causes significant yield losses. The disease agent is goose parvovirus (GPV), which is common in countries with waterfowl production. It has not previously been reported in Turkey. Using qPCR and sequencing of the VP3 protein-encoding gene, GPV is identified as the causative agent of high mortality among geese between 2018 and 2019. The VP3 sequences were also compared with the similar GenBank sequences phylogenetically. All the sequences were found to be most similar (98.90%) with Polish and Taiwan GPV strains. Phylogenetic analysis of the VP3 gene in strains in Turkey and comparison with strains from other countries demonstrated that the Turkish strains are native to the geography and circulated locally. This study detected the presence of the GPV gene for the first time in Turkey and demonstrated the importance of comparing the vaccine strain and wild type.


Inhibition of gastric acid secretion by a glycoprotein isolated from human urine (human urinary gastric inhibitor).
The gastric antisecretory activity of an inhibitor newly isolated from human urine (Human Urinary Gastric Inhibitor or HUGI) has been studied. HUGI was given intravenously and its activity determined in the following test systems: gastric secretion in the rat with pyloric ligation; gastric secretion in the dog with a Heidenhain pouch stimulated with pentagastrin, histamine and a protein meal; acid secretion by the isolated gastric mucosa of the rat; gastrointestinal motility; bile flow and gall-bladder tone and arterial and venous blood pressure and heart rate. HUGI was found to have marked activity only in the pyloric-ligated rats and in the dogs with Heidenhain pouches stimulated by a protein meal. Particularly in the dog, HUGI (0.1 to 6.4 micrograms/kg, i.v) markedly inhibited gastric secretion, dose-dependently and without changing the plasma gastrin concentration. Negative results were obtained in the other tests, but these results serve to demonstrate that HUGI is an inhibitor well-differentiated from other glycoproteins or peptides with gastric antisecretory activity, such as urogastrone and GIP. The results obtained to date are not sufficient to allow the mechanism of action of HUGI to be defined.


Evaluating maternal hyperglycemic exposure and fetal placental arterial dysfunction in a dual cotyledon, dual perfusion model.
Gestational diabetes affects almost 1 in 10 pregnancies and is associated with adverse outcomes including fetal demise. Pregnancy complications related to diabetes are attributed to placental vascular dysfunction. With diabetes, maternal hyperglycemia is thought to promote placental vasoconstriction. However, it remains poorly understood if and how hyperglycemia leads to placental vascular dysfunction or if humoral factors related to maternal diabetes are responsible. Utilizing a human placenta dual cotyledon, dual perfusion assay we examined the arterial pressure response to the thromboxane mimetic U44619, in cotyledons exposed to normal vs. a hyperglycemic infusion into the intervillous space. Tissues were then analyzed for the activity of key signaling molecules related to vascular tone; eNOS, Akt, PKA and VEGFR2. Results indicate a significant increase in fetal vascular resistance with maternal exposure to hyperglycemia. This response corresponded with a reduction in the phosphorylation of eNOS at Ser1177 and Akt at Thr308. In contrast, VEGFR2 at Tyr1175 and PKA at Thr197 were not different with hyperglycemia. Reductions of eNOS and Akt phosphorylation at key residues implicated in nitric oxide production suggest that hyperglycemia alters the vasodilatory signaling of placental vessels. In contrast, acute hyperglycemic exposure may not alter vasoconstriction via VEGF and PKA signaling. Altogether our results link hyperglycemic exposure in human placentas to nitric oxide signaling; a mechanisms that may account for the elevations in vascular resistance commonly observed in diabetic pregnancies.


Novel potent organoselenium compounds as cytotoxic agents in prostate cancer cells.
A series of 17 symmetrical substituted imidothiocarbamate and imidoselenocarbamate derivatives has been synthesized by reacting appropriately substituted acyl chlorides with alkyl imidothiocarbamates and alkyl imidoselenocarbamates. The antitumoral activities of the compounds were evaluated in vitro by examining their cytotoxic effects against human prostate cancer cells (PC-3). Five compounds showed interesting activity levels and 3p (IC(50)=1.85 microM) was 7.3 times more active than the standard etoposide used in the treatment of prostate cancer and emerges as the most interesting compound.


Hardware complications and reoperations following precontoured plate fixation of the olecranon: a population-based study.
Several fixation techniques have been described to treat acute olecranon fractures. Plate fixation is often used because of its superior mechanical properties. The reported rates of reoperation after olecranon plate fixation have been quite heterogeneous. The purpose of this study was to establish an updated reoperation rate based on modern precontoured plate constructs. This retrospective cohort study used population-level administrative data to identify all surgically treated adult patients with olecranon fractures at 4 hospitals in Edmonton, AB, Canada, between 2010 and 2015. Radiographic review was conducted to identify patients who underwent precontoured olecranon plate fixation. Fracture characteristics including Mayo fracture classification and other concomitant upper-extremity injuries were identified. Chart reviews were performed to determine patient characteristics and patients who required reoperation. The primary reason for and type of reoperation were determined. Six hundred patients were surgically treated for olecranon fractures. Precontoured plate fixation was used in 321 patients. The average age of included patients was 56 years (standard deviation [SD], 19.4 years), and there were 173 female patients (53.9%). Reoperation was required in 90 patients (28%). For 50 patients, implant-related irritation was the primary reason for reoperation, representing 55.6% of the patients who underwent reoperation (50 of 90) and 15.6% of the total cohort (50 of 321). Other reasons for reoperation included hardware failure in 17 patients (5.3%), infection in 9 (2.8%), and contracture in 9 (2.8%). Patients who required reoperation were significantly younger (52.9 years [SD, 18.1 years] vs. 57.7 years [SD, 19.4 years]; P = .048) and had significantly higher rates of type III olecranon fractures (17.8% [16 of 90] vs. 8.2% [19 of 231]; P = .04) and Monteggia fractures (13.3% [12 of 90] vs. 4.8% [11 of 231]; P = .008). A multivariate logistic regression model also demonstrated increased odds ratios (ORs) for overall reoperation in patients with Monteggia fractures (OR, 2.99 [95% confidence interval, 1.25-7.17]; P = .014) and for reoperation due to implant-related irritation in younger patients (OR, 0.98 [95% confidence interval, 0.96-0.996]; P = .018). No discerning factors were identified for the 50 patients who underwent hardware removal for implant-related irritation compared with the whole reoperation group (n = 90). This study found that patients with olecranon fractures treated with precontoured plates experienced a hardware removal rate of 15.6% for implant-related irritation. Patients who sustained more complex fractures, such as Monteggia injuries, demonstrated higher rates of reoperation. Increasing age may be associated with lower rates of reoperation. In patients who required reoperation, there were no identifiable radiographic or clinical characteristics that were associated with implant-related irritation as their primary reason for reoperation.


Methods of repair and risk for reoperation in Swedish hernia surgery from 1992 to 1996.
Difficulties in obtaining and analysing outcome measures in hernia surgery may be an obstacle to necessary progress in non-specialized hospitals. Against this background a voluntary register was initiated in 1992 with the aim of describing and evaluating hernia surgery in participating units. Prospective registration of all hernia operations carried out in participating hospitals was undertaken using identification codes specific for each individual. Repair technique, complications, day surgery, type of anaesthesia, and reoperation for recurrence were recorded. Actuarial analysis was used to determine the cumulative incidence of reoperation. Relative risk for reoperation was estimated by the Cox proportional hazards model. The number of participating hospitals and registered operations increased from eight and 1689 respectively in 1992 to 21 and 4056 in 1996. The use of mesh increased from 7 per cent of all operations in 1992 to 51 per cent in 1996. The proportion of operations done for recurrent hernia remained constant at 16-17 per cent throughout the 5-year study period. For all 12542 herniorrhaphies registered, the cumulative incidence of reoperation at 2 years was 3 (95 per cent confidence interval 3-4) per cent. Postoperative complications, recurrent hernia, direct hernia and absorbable suture were associated with increased risk of reoperation for recurrence. An increased incidence of reoperation, although not statistically significant, was noted for conventional open repairs (Bassini, McVay, Marcy and others) versus the Shouldice technique. In this prospective audit an increasing use of mesh was observed for open and laparoscopic surgery, especially for bilateral and recurrent hernia operations. Reoperation rates decreased significantly between 1992 and 1995.


Changes in serum oestrone sulphate and progesterone levels of red deer hinds during pregnancy.
Serum oestrone sulphate (E1S) and progesterone (P) levels were recorded from six red deer hinds throughout the first two-thirds of gestation. E1S was generally undetectable until 30 days post conception when levels rose, peaking between 60 and 80 days, and fell to lower values between 80 and 170 days post conception. P levels rose after conception and remained elevated for the remainder of the study. This study indicates that in general the presence of measurable E1S levels in serum of hinds is associated with pregnancy.


Cytochrome 572 is a conspicuous membrane protein with iron oxidation activity purified directly from a natural acidophilic microbial community.
Recently, there has been intense interest in the role of electron transfer by microbial communities in biogeochemical systems. We examined the process of iron oxidation by microbial biofilms in one of the most extreme environments on earth, where the inhabited water is pH 0.5-1.2 and laden with toxic metals. To approach the mechanism of Fe(II) oxidation as a means of cellular energy acquisition, we isolated proteins from natural samples and found a conspicuous and novel cytochrome, Cyt(572), which is unlike any known cytochrome. Both the character of its covalently bound prosthetic heme group and protein sequence are unusual. Extraction of proteins directly from environmental biofilm samples followed by membrane fractionation, detergent solubilization and gel filtration chromatography resulted in the purification of an abundant yellow-red protein. The purified protein has a cytochrome c-type heme binding motif, CxxCH, but a unique spectral signature at 572 nm, and thus is called Cyt(572). It readily oxidizes Fe(2+) in the physiologically relevant acidic regime, from pH 0.95-3.4. Other physical characteristics are indicative of a membrane-bound multimeric protein. Circular dichroism spectroscopy indicates that the protein is largely beta-stranded, and 2D Blue-Native polyacrylamide gel electrophoresis and chemical crosslinking independently point to a multi-subunit structure for Cyt(572). By analyzing environmental genomic information from biofilms in several distinctly different mine locations, we found multiple genetic variants of Cyt(572). MS proteomics of extracts from these biofilms substantiated the prevalence of these variants in the ecosystem. Due to its abundance, cellular location and Fe(2+) oxidation activity at very low pH, we propose that Cyt(572) provides a critical function for fitness within the ecological niche of these acidophilic microbial communities.


An update on the Barriers to Adherence and a Definition of Self-Report Non-adherence Given Advancements in Antiretroviral Therapy (ART).
Relying on the most frequently reported barriers to adherence and convenient definitions of non-adherence may lead to less valid results. We used a dominance analysis (a regression-based approach) to identify the most important barriers to adherence based on effect size using data collected through an online survey. The survey included the Adherence Barrier Questionnaire, self-reported non-adherence defined as a 4-day treatment interruption, and HIV clinical outcomes. The sample (N = 1217) was largely male, gay identified, and White. Nearly 1 in 3 participants reported "simply forgot" as a barrier; however, in a dominance analysis, it yielded a small effect size it its association with a 4-day treatment interruption. Further, dominance analyses stratified by race/ethnicity and age suggested that not all barriers impact all groups equally. The most frequently reported barriers to adherence were not the most important, and interventions should focus on barriers more strongly linked to clinical outcomes.


Korean red ginseng attenuates hypercholesterolemia-enhanced platelet aggregation through suppression of diacylglycerol liberation in high-cholesterol-diet-fed rabbits.
Intake of Korean red ginseng (KRG, ginseng Radix rubra), rich in glycosylated saponins (ginsenosides), has been known to inhibit platelet aggregation in the normocholesterolemic condition. However, it is unclear whether KRG can attenuate hypercholesterolemia-enhanced platelet aggregation. This study examined whether the daily consumption of a KRG-water extract (WE) could prevent the hypercholesterolemia-enhanced platelet aggregation and progression of hypercholesterolemic atherosclerosis. KRG-WE administration (200 mg/kg/day) for 8 weeks potently inhibited the platelet aggregation induced by low doses of agonists (0.5 microg/mL collagen and 0.025 unit/mL thrombin), whereas it weakly reduced the blood-cholesterol levels and formation of atheromatous lesions. In further investigation, KRG-WE significantly suppressed collagen-induced 1,2-diacylglycerol liberation, but had no significant effect on arachidonic acid liberation. Taken together, it can be suggested that the antiplatelet effect of KRG-WE may, at least partly, be due to the inhibition of 1,2-diacylglycerol generation rather than regulation of blood lipid levels. In conclusion, daily consumption of KRG-WE could be a useful alternative measure for the prevention of thrombus and atheroma formation in hypercholesterolemia.


Binocular visual acuity of neonates: the acuity card procedure.
The acuity card procedure is a variant of the forced-choice preferential looking technique. In this study, four observers each tested 10 infants (all healthy fullterm neonates) with acuity cards containing either a one-aperture or a two-aperture stimulus configuration. For both card types the mean test time was eight minutes. No effect on acuity results was found between the two different configurations. The mean acuity values were within one octave of those reported in most previous behavioral studies of the acuity of neonates. The authors consider that the acuity card procedure provides a rapid, accurate technique for assessment of healthy newborn infants in a hospital setting.


Flow-induced permeation of non-occlusive blood clots: an MRI study and modelling.
The success of clot thrombolysis very much depends on efficient clot permeation with blood plasma carrying the thrombolytic agent. In this paper clot permeation was studied by dynamic magnetic resonance imaging (MRI) on artificial non-occlusive blood clots inserted in an artificial circulation system filled with blood plasma to which an MRI contrast agent was added. The MRI results revealed that clot permeation is much faster and more efficient at the entrance of the flow channel across the clot. Clot permeation with fluid was simulated numerically as well. The simulation was based on numerical solution of Navier-Stokes equations for the flow in the channel and within the clot. The clot was considered as a porous material with known permeability and porosity. Based on the calculated velocity profiles, concentration profiles of fluid in the clot were modelled. These agreed well with the MRI results. The presented model of clot permeation with fluid may also serve as a useful extension to numerical modelling of dissolution of non-occlusive blood clots during thrombolytic therapy.


Environmental pollution influence to soil-plant-air system in organic vineyard: bioavailability, environmental, and health risk assessment.
This study was performed in organic vineyard to assess integrated pollution in soil-plant-air system by potentially toxic elements (PTE). Concentrations of 26 PTE were determined in soil, grapevine, and air biomonitors (moss bags) using ICP-OES and ICP-MS. Environmental implication assessment of soil did not show pollution by PTE, except for B in samples collected in the middle of grapevine season (July). Despite low total Cd concentrations in soil, it has the highest influence on increase of environmental risk. Based on biological accumulation concentration (BAC), grapevine is not hyperaccumulator of PTE from soil. Advanced classification algorithm, Kohonen self-organizing map (SOM), was applied to compare environmental implications in organic with conventional vineyards. PTE concentrations were significantly lower in organic than conventional grapevine. PTE concentrations were higher in the outer (leaf and petiole) than in the inner grapevine parts (skin, pulp, and seed). Some airborne elements have an influence on outer grapevine parts, especially on leaves (ratio factor-RF > 1). Moss bag technique testified about lower enrichment of airborne elements compared with the conventional vineyard and urban microenvironments. Environmental and health risk assessments confirmed that organic production is harmless for field workers and grape consumers.


Title: IL-10-producing T cells and their dual functions.
Interleukin (IL)-10 is considered a prototypical anti-inflammatory cytokine, which significantly contributes to the maintenance and reestablishment of immune homeostasis. However, this classical view fails to fully describe the pleiotropic roles of IL-10. Indeed, IL-10 can also promote immune responses, e.g. by supporting B-cell and CD8+ T-cell activation. The reasons for these seemingly opposing functions are unclear to a large extent. Recent and previous studies suggest that the cellular source and the microenvironment impact the function of IL-10. However, studies addressing the mechanisms which determine whether IL-10 promotes inflammation or controls it have just begun. This review first summarizes the recent findings on the heterogeneity of IL-10 producing T cells and their impact on the target cells. Finally, we will propose two possible explanations for the dual functions of IL-10.


The Social Consequences of Frequent Versus Infrequent Apologizing.
The effectiveness of interpersonal apologies is well established, but most existing research has examined the benefits of isolated apologies. How do apologies function when considered in the context of a transgressor's apology baseline-the frequency with which they tend to apologize for their behavior? We examined whether people consider others' apology baselines when evaluating both their character and specific apologies from them. In Study 1, participants judged a character with a high (vs. low) apology baseline as higher in communion and lower in agency. In Study 2, participants judged romantic partners with high (vs. low) apology baselines as higher in communion, but only lower in agency when they perceived these frequent apologies as low-quality. In both studies, having a high apology baseline was also indirectly associated with more favorable reactions to a specific apology via higher communion judgments, revealing the role of apology baselines in shaping conflict resolution processes.


Genomics reaches the clinic: from basic discoveries to clinical impact.
Today, more than ever, basic science research provides significant opportunities to advance our understanding about the genetic basis of human disease. Close interactions among laboratory, computational, and clinical research communities will be crucial to ensure that genomic discoveries advance medical science and, ultimately, improve human health.


Starting a DBS service for children: It's not the latitude but the attitude - Establishment of the paediatric DBS centre in Northern Finland.
Paediatric movement disorder patients can benefit from deep brain stimulation (DBS) treatment and it should be offered in a timely manner. In this paper we describe our experience establishing a DBS service for paediatric patients. We set out to establish a paediatric DBS (pDBS) procedure in Oulu University Hospital in northern Finland, where up to this point DBS treatment for movement disorders had been available for adult patients. Collaboration with experienced centres aided in the process. A multidisciplinary team was assembled and a systematic protocol for patient evaluation and treatment was created, with attention to special features of the regional health care system. All of our first paediatric patients had very severe movement disorders, which is typical for a new DBS centre. The patients benefitted from pDBS treatment despite variable aetiologies of movement disorders, which included cerebral palsy and rare genetic disorders with variants in PDE10A, TPK1 and ARX. We also present our high-quality paediatric MR-imaging protocol with tractography. Establishment of a pDBS centre requires expertise in classification of paediatric movement disorders, longstanding experience in adult DBS and a committed multidisciplinary team. Besides high-quality imaging and a skilled neurosurgery team, careful patient selection, realistic treatment goals and experience in rehabilitation are imperative in pDBS treatment.


MR diagnosis of superficial femoral artery aneurysm, primarily misdiagnosed as soft tissue tumor. A case report.
We report a 84-year-old man with an aneurysm of the superficial femory artery (SFA). Primarily, after B-mode sonography soft tissue neoplasm was suspected and sectional MR imaging was performed for further diagnostics. Because of blood flow related ghost artifacts, sectional MR led to the diagnosis of an partially thrombosed aneurysm without angiography. Initially, the differential diagnosis of an SFA aneurysm, which is extremely rare, has not been considered. Soft tissue neoplasms may have a similar appearance to partially thrombosed aneurysms. This case demonstrate the importance to notice also artifacts in sectional MRI which can give important informations for correct diagnosis.


Composting and green technologies for remediation of phthalate (PAE)-contaminated soil: Current status and future perspectives.
Phthalate esters (PAEs) are hazardous organic compounds that are widely added to plastics to enhance their flexibility, temperature, and acidic tolerance. The increase in global consumption and the corresponding environmental pollution of PAEs has caused broad public concerns. As most PAEs accumulate in soil due to their high hydrophobicity, composting is a robust remediation technology for PAE-contaminated soil (efficiency 25%-100%), where microbial activity plays an important role. This review summarized the roles of the microbial community, biodegradation pathways, and specific enzymes involved in the PAE degradation. Also, other green technologies, including biochar adsorption, bioaugmentation, and phytoremediation, for PAE degradation were also presented, compared, and discussed. Composting combined with these technologies significantly enhanced removal efficiency; yet, the properties and roles of each bacterial strain in the degradation, upscaling, and economic feasibility should be clarified in future research.


Primary surgery versus primary radiation-based treatment for locally advanced oropharyngeal cancer.
Randomized data comparing surgery to radiation for locally advanced oropharyngeal cancer (OPC) are lacking. This study evaluated practice patterns and overall survival outcomes from the National Cancer Database. A total of 22,676 patients with stage III to IV, locally advanced OPC were treated between 2004 to 2013 with primary chemoradiation (CRT) or surgery with adjuvant radiotherapy with or without chemotherapy (aRT ± CT). Survival rates were estimated using the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were computed using Cox regression modeling. Median follow-up was 40.7 months; 8,555 and 14,121 patients received surgery with aRT ± CT and CRT, respectively. Corresponding 3-year survival was 85.4% and 72.6% (P < 0.0001). On multivariate analysis, adjusting for age, gender, race insurance status, median income, percentage with no high-school degree, Charlson-Deyo score, clinical tumor and node stage, tumor grade, facility type, treatment at > 1 facility, and human papillomavirus (HPV) status, surgery with aRT ± CT had a reduced hazard of death, HR, 0.79 (95% confidence interval 0.69-0.91), P = 0.001. Primary surgery with aRT ± CT for locally advanced OPC has an improved survival compared to primary radiation-based treatment even when stratified by HPV status. 2c. Laryngoscope, 128:1353-1364, 2018.


Evaluation of the effect of Elaeagnus angustifolia alone and combined with Boswellia thurifera compared with ibuprofen in patients with knee osteoarthritis: a randomized double-blind controlled clinical trial.
Osteoarthritis (OA) is one of the most common articular disorders. Many patients do not respond to acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), the mainstay of pharmacotherapy for knee OA. The plants Elaeagnus angustifolia and Boswellia thurifera have anti-inflammatory and analgesic properties. This study aimed to evaluate the effect of E. angustifolia alone and in combination with B. thurifera compared with ibuprofen in patients with knee osteoarthritis. In a randomized double-blind controlled clinical trial, 75 patients with knee OA were randomly and equally assigned to one of three groups Elaeagnus (n = 23), Elaeagnus/Boswellia (n = 26), and ibuprofen (n = 26) to receive the capsules of Elaeagnus, Elaeagnus/Boswellia, and ibuprofen, respectively, three times daily with meals for 4 weeks. Pain severity based on VAS (visual analog scale, 0 to 10 scale) and the scores of LPFI (Lequesne Pain and Function Index) and PGA (patient global assessment) were determined pre- and post-intervention for all patients. All interventions had significant lowering effects on VAS, LPFI, and PGA scores (P < 0.001 for all parameters) with no significant difference between groups in terms of effects on all evaluated parameters. Consumption of E. angustifolia fruit extract either alone or in combination with Boswellia oleo-gum resin extract could decrease pain and improve function in patients with knee osteoarthritis comparable to ibuprofen.


Stability of in vitro fertilization-embryo transfer success rates from the 1989, 1990, and 1991 Clinic-Specific Outcome Assessments.
To determine if the differences in IVF-ET success rates among clinics are due to chance alone. Retrospective analysis of data reported by individual clinics. One hundred seventy-five clinics in 1989, 192 clinics in 1990, and 208 clinics in 1991 that reported IVF-ET success rates to the Society for Assisted Reproductive Technology and the American Society for Reproductive Medicine (formerly The American Fertility Society). Women < 40 years of age with no male factor. In vitro fertilization-ET. Delivery rate per retrieval and delivery rate per transfer. The hypothesis that the differences among IVF-ET success rates for clinics is due to chance alone can be rejected. Seven clinics were found to have pregnancy rates significantly higher than average and six clinics were found to have pregnancy rates significantly lower than average. Significant correlations were found between different years in the success rates for individual clinics but not for success as a function of the number of patients treated. Success rates for a few clinics are significantly different from the average success rate, but success rates must be used with caution in selecting a clinic.


Delivering a hydrophobic anticancer drug for photodynamic therapy by amorphous formulation.
An amorphous formulation of hypocrellin A for photodynamic therapy is reported which can provide stable aqueous dispersion of such hydrophobic photosensitizers. In vitro studies have demonstrated the active uptake of amorphous formulation of hypocrellin A into the mitochondria of tumor cells. Compared with Tween-80 micelle embedded hypocrellin A, low dark-toxicity but similar light-toxicity of the amorphous one to drug impregnated tumor cells was observed. Thus, the potential of using amorphous formulation of hypocrellin A as drug delivery system for photodynamic therapy has been demonstrated.


Probability of 5% or Greater Weight Loss or BMI Reduction to Healthy Weight Among Adults With Overweight or Obesity.
Information on the probability of weight loss among US adults with overweight or obesity is limited. To assess the probability of 5% or greater weight loss, 10% or greater weight loss, body mass index (BMI) reduction to a lower BMI category, and BMI reduction to the healthy weight category among US adults with initial overweight or obesity overall and by sex and race. This cohort study obtained data from the IQVIA ambulatory electronic medical records database. The sample consists of US ambulatory patients 17 years or older with at least 3 years of BMI information from January 1, 2009, to February 28, 2022. Minimum age was set at 17 years to allow for the change in BMI or weight starting at 18 years. Maximum age was censored at 70 years. Initial BMI (calculated as weight in kilograms divided by height in meters squared) category was the independent variable of interest, and the categories were as follows: lower than 18.5 (underweight), 18.5 to 24.9 (healthy weight), 25.0 to 29.9 (overweight), 30.0 to 34.9 (class 1 obesity), 35.0 to 39.9 (class 2 obesity), and 40.0 to 44.9 and 45.0 or higher (class 3 or severe obesity). The 2 main outcomes were 5% or greater weight loss (ie, a ≥5% reduction in initial weight) and BMI reduction to the healthy weight category (ie, BMI of 18.5-24.9). The 18 461 623 individuals in the sample had a median (IQR) age of 54 (40-66) years and included 10 464 598 females (56.7%) as well as 7.7% Black and 72.3% White patients. Overall, 72.5% of patients had overweight or obesity at the initial visit. Among adults with overweight and obesity, the annual probability of 5% or greater weight loss was low (1 in 10) but increased with higher initial BMI (from 1 in 12 individuals with initial overweight to 1 in 6 individuals with initial BMI of 45 or higher). Annual probability of BMI reduction to the healthy weight category ranged from 1 in 19 individuals with initial overweight to 1 in 1667 individuals with initial BMI of 45 or higher. Both outcomes were generally more likely among females than males and were highest among White females. Over the 3 to 14 years of follow-up, 33.4% of persons with overweight and 41.8% of persons with obesity lost 5% or greater of their initial weight. At the same time, 23.2% of persons with overweight and 2.0% of persons with obesity reduced BMI to the healthy weight category. Results of this cohort study indicate that the annual probability of 5% or greater weight loss was low (1 in 10) despite the known benefits of clinically meaningful weight loss, but 5% or greater weight loss was more likely than BMI reduction to the healthy weight category, especially for patients with the highest initial BMIs. Clinicians and public health efforts can focus on messaging and referrals to interventions that are aimed at clinically meaningful weight loss (ie, ≥5%) for adults at any level of excess weight.


Trial-by-trial fluctuations in amygdala activity track motivational enhancement of desirable sensory evidence during perceptual decision-making.
People are biased toward seeing outcomes that they are motivated to see. For example, wanting their favored team to prevail biases sports fans to perceive an ambiguous foul in a manner that is favorable to the team they support. Here, we test the hypothesis that such motivational biases in perceptual decision-making are associated with amygdala activity. We used monetary incentives to experimentally manipulate participants to want to see one percept over another while they performed a categorization task involving ambiguous images. Participants were more likely to categorize an image as the category we motivated them to see, suggesting that wanting to see a particular percept biased their perceptual decisions. Heightened amygdala activity was associated with motivation consistent categorizations and tracked trial-by-trial enhancement of neural activity in sensory cortices encoding the desirable category. Analyses using a drift diffusion model further suggest that trial-by-trial amygdala activity was specifically associated with biases in the accumulation of sensory evidence. In contrast, frontoparietal regions commonly associated with biases in perceptual decision-making were not associated with motivational bias. Altogether, our results suggest that wanting to see an outcome biases perceptual decisions via distinct mechanisms and may depend on dynamic fluctuations in amygdala activity.


The healthy migrant theory: variations in pregnancy outcomes among US-born migrants.
Various studies have observed that infants born to foreign-born women have better birth outcomes (lower rates of preterm, low birth weight, and infant mortality) than those delivered to US-born women. While much attention has been given to the "healthy migrant effect" as an explanation for these positive outcomes, this theory has not been examined in an internally migrant population. The purpose of this study is to examine the relationship between maternal mobility history and birth outcomes among infants born to US resident mothers of Mexican origin. The study used 1995-1999 National Center for Health Statistics (NCHS) live birth/infant death cohort files of singleton infants delivered in the US to white women of Mexican origin (n = 2,446,253). Maternal mobility history (MMH), which refers to the relationship between the maternal place of birth and the state of residence at delivery, was categorized into the four following groups: (a) foreign-born-place of birth outside the US and delivery in the US; (b) outside-region-place of birth in one US region and delivery in another US region; (c) within-region-place of birth in one US region and delivery in a different state in the same US region; and (d) within-state-place of birth and delivery in the same US state. Consistently, there is evidence to support the healthy migrant effect in an internally migrant population. Unique to this study are the findings that infants born to mothers with outside-region MMH had a lower risk of low birth weight (LBW) and small-for-gestational age (SGA) compared to those who did not move. Overall, this study provides evidence that the healthy migrant effect and its relationship to birth outcomes can be applied to an internally migrant population.


Grafting and electrical stimulation of the auditory nerve in cats.
The effect of implanting wire electrodes into the cochlea is limited by the deficit of nerve fibers in most diseases of the cochlea. Therefore, in a series of experiments it was tried, for the first time, to direct new outspreading nerve fibres into the afferent acoustic nerve by grafting a motor nerve to it. A second series of experiments should demonstrate the possibility of direct electrical stimulation of the eighs nerve by implanting wire electrodes via the transoccipital approach. The electrically evoked potentials, recorded at the auditory cortex, were compaired to potentials evoked by auditory stimulation. The answers to acoustic or electric stimulation showed no significant difference.


Treatment of Typical Enneking Stage 3 Thoracic Aggressive Vertebral Hemangiomas with Pain and Neurologic Deficits: Results After at Least 36 Months of Follow-Up.
To evaluate the efficiency of a comprehensive treatment strategy for patients with Enneking stage 3 thoracic aggressive vertebral hemangioma (AVH). A retrospective analysis of radiographic and clinical outcomes was performed for 17 patients who received treatment for Enneking stage 3 thoracic AVH accompanied by pain and neurologic deficits between January 2010 and February 2015. A visual analog scale (VAS) was used to clinically evaluate the level of pain. Neurologic examinations were performed to assess the patients' sensory symptoms, motor deficits, and Frankel grade. The average operative time was 181.8 ± 37.1 minutes, and the average intraoperative blood loss was 1226.5 ± 151.2 mL (range, 900-1450 mL). All patients underwent preoperative embolization to minimize intraoperative blood loss. All patients experienced immediate pain relief and resolution of their neurologic symptoms. All 17 patients achieved Frankel grade D at the final follow-up; moreover, they reported that their pain was relieved (mean VAS score, 2.82 ± 0.81; P < 0.05) and their neurologic deficits had resolved. No surgery-related complications were noted. No patients exhibited signs of recurrence. We recommend a comprehensive treatment strategy for patients with Enneking stage 3 thoracic AVH that includes preoperative embolization, vertebroplasty, posterior decompression, and internal fixation. We recommend that absorbable gelatin sponge particles be used for intraoperative embolization prior to the injection of bone cement, which may significantly reduce intraoperative bleeding, operative time, and occurrence of surgery-related complications.


Elder homicide in the north of Portugal.
The increasing average life expectancy leads to population aging, and growing numbers in the elder population, a population that suffers from great vulnerability. Therefore, a rise in elder homicide is expected. This phenomenon has not been thoroughly described in Portugal. This study aims to analyse and characterize elder homicide, in order to achieve a better understanding of this form of violence. We conducted a retrospective study, reviewing autopsy reports along with data regarding circumstances of death of suspected homicides occurring between 1992 and 2007 (n = 78), whose victims were 65 years old or above, autopsied in the medical-legal services of the north of Portugal. During this period, an overall of 615 suspected homicides occurred, 13% being perpetrated against elders. The age range of the victims was 65-96 years, with an average of 74 years; 58% of them were males and 45% were married. In 61% of the documented cases, the perpetrator was known to the victim, and a family member in 36%. A considerable number of deaths occurred at the victim's residence and in a rural scenario, the motive being robbery in 51% of the documented cases. The supposed perpetrator ran away from the scene in 64% of the cases. The most frequent mechanisms of death were blunt force trauma (31%), followed by stabbing (22%) and gunshot wounds (21%). Fatal wounds were observed mainly in the head (55%) and thorax (35%). In the north of Portugal, elder homicide seems to be uncommon. This study suggests an association between elder homicide and robbery, in which elders, due to their vulnerability, are a preferential target. Contrary to other reports worldwide, there were no cases of death in nursing homes, possibly due to underreport or misidentification. In a large number of the cases, it wasn't possible to collect all the necessary data, due to lack of information regarding circumstances of the events.