Fluroxypyr-1-methylheptyl ester causes apoptosis of bovine mammary gland epithelial cells by regulating PI3K and MAPK signaling pathways and endoplasmic reticulum stress.
Fluroxypyr-1-methylheptyl ester (FPMH) is an auxin herbicide that is widely applied to crops and pastures to block growth of post-emergence weeds. Several studies have reported the toxicity of FPMH in aquatic vertebrates. However, the adverse impacts of FPMH on mammals, including domestic animals, have not been reported. The purpose of our current study is to assess the impact of FPMH on the bovine mammary system and milk production. To evaluate the toxicity of FPMH on the mammary glands of lactating cows, the bovine mammary gland epithelial cell line, MAC-T, was exposed to various concentrations (0, 5, 7.5, 10, 15, and 20 μM) of FPMH for 24 h, and then various assessments were performed. The results showed that FPMH dose-dependently reduced MAC-T cell viability following exposure to FPMH and induced mitochondrial depolarization and apoptosis. FPMH also modulated signaling through the PI3K and MAPK pathways. In addition, the expression levels of proteins related to endoplasmic reticulum (ER) stress were upregulated, indicating induction of ER stress, and calcium homeostasis was disrupted following FPMH treatment. In conclusion, our investigation suggests that FPMH may be toxic to the bovine mammary system and may decrease dairy production.


Uses of mHealth in Injury Prevention and Control: a Critical Review.
The purpose of this review was to summarize the current state of the literature on the use of "mHealth" (the use of mobile devices for health promotion) for injury prevention and control. mHealth is being used to measure, predict, and prevent the full spectrum of injuries. However, most literature remains preliminary or in a pilot stage. Use of best-of-class design principles (e.g., user-centered design, theory-based development) is uncommon, and wide-scale dissemination of effective monitoring or intervention tools is rare. mHealth for injury prevention holds promise, but further work is needed across the full spectrum of development and translation.


Cutaneous abscess caused by Corynebacterium lactis in a companion dog.
Many new, emerging and re-emerging diseases of humans are caused by pathogens which originate from animals or products of animal origin. Corynebacterium lactis, a recently described species of the genus Corynebacterium, was first isolated from milk of asymptomatic cows. In the present study a cutaneous abscess caused by C. lactis in a dog was recognized by cytologic and histologic examination in addition to 16S rRNA gene analysis of the microorganism. Therefore, C. lactis should be included among other bacterial species recognized as emerging pathogens for companion animals.


RNA interference targeting ANGPTL3 for triglyceride and cholesterol lowering: phase 1 basket trial cohorts.
Elevated triglycerides and non-high-density lipoprotein cholesterol (HDL-C) are risk factors for atherosclerotic cardiovascular disease (ASCVD). ARO-ANG3 is an RNA interference therapy that targets angiopoietin-like protein 3 (ANGPTL3), a regulator of lipoprotein metabolism. This first-in-human, phase 1, randomized, placebo-controlled, open-label trial investigated single and repeat ARO-ANG3 doses in four cohorts of fifty-two healthy participants and one cohort of nine participants with hepatic steatosis, part of a basket trial. Safety (primary objective) and pharmacokinetics (in healthy participants) and pharmacodynamics (secondary objectives) of ARO-ANG3 were evaluated. ARO-ANG3 was generally well tolerated, with similar frequencies of treatment-emergent adverse events in active and placebo groups. Systemic absorption of ARO-ANG3 in healthy participants was rapid and sustained, with a mean Tmax of 6.0-10.5 h and clearance from plasma within 24-48 h after dosing with a mean t½ of 3.9-6.6 h. In healthy participants, ARO-ANG3 treatment reduced ANGPTL3 (mean -45% to -78%) 85 days after dose. Reductions in triglyceride (median -34% to -54%) and non-HDL-C (mean -18% to -29%) (exploratory endpoints) concentrations occurred with the three highest doses. These early-phase data support ANGPTL3 as a potential therapeutic target for ASCVD treatment. ClinicalTrials.gov identifier: NCT03747224.


Electrically induced release of [3H]dopamine from slices obtained from different rat brain cortex regions. Evidence for a widespread dopaminergic innervation of the neocortex.
Slices obtained from the deeper layers of the rat dorsal frontal, parietal and occipital brain cortex were incubated in vitro with 6.25 X 10-7 M [3H]dopamine (DA), and subsequently superfused and electrically stimulated, while held on quick transfer electrodes, and changes in the efflux of 3H and of the individual amines measured. The separation of the amines, with quantitative recoveries, was performed by chromatography on cation-exchange resins eluted sequentially with water, 1 N HCL AND 6 M urea i 1 N HCl. When no drugs were used, the prestimulation efflux was entirely formed by deaminated metabolites, while following stimulation there was an increase in the efflux of deaminated metabolites, and considerable amounts of [3H]-noradrenaline (NA) now appeared. No DA was present in the pre- or poststimulation medium. Similar results were obtained in all the regions studied. When the slices were incubated with 10-5 M desmethylimipramine (DMI), 10-4 Mnialamide and 10-4 M tropolone, before and during incubation with [3H]DA, it was observed that, prior to stimulation, the efflux was composed of deaminated metabolites, DA and 3-methoxytyramine (MTA), and following the electrical stimulus there was an increased release of DA, NA and deaminated compounds (in order of decreasing release), while no change in that of MTA was evident. The stimulus-induced release of DA was greatest from frontal slices, intermediate from parietal, and lowest from occipital ones. DMI-resistant uptake of [3H]DA also diminished when passing from frontal to occipital. These findings are interpreted as due to the presence of dopaminergic axon terminals in all the regions studied, but with a density that diminishes in a rostrocaudal direction.


Adjuvant gemcitabine and concurrent continuous radiation (45 Gy) for resected pancreatic head carcinoma: a multicenter Belgian Phase II study.
To evaluate the feasibility and tolerance of a postoperative course of gemcitabine (GEM) combined with continuous radiation after curative resection of pancreatic adenocarcinoma. Thirty patients (median age, 61 years; performance status, 0 to 1) with Stage II and III curatively resected pancreatic head adenocarcinoma were included. Gemcitabine 1000 mg/m2 (3 out of 4 weeks, two cycles) was given within 8 weeks of surgery and followed by GEM 300 mg/m2 weekly combined with continuous radiation (45 Gy in 25 fractions, 1.8 Gy per fraction). For GEM alone, all patients received the two courses with dose reductions in 14 of 30 patients (46%). All but 3 patients completed full chemoradiation; 1 stopped radiation because of subocclusion of a gastroenterostomy, and 2 did not start owing to disease progression. Reduction in GEM during radiation was necessary in 12 of 30 patients (40%). No toxic death was noted; World Health Organization Grade 3/4 hematologic and nonhematologic toxicities were seen in 10 of 30 patients (33%) and 3 of 30 patients (10%), respectively. After a median follow-up of 19 months, no late toxicity was reported. Eleven patients died from progressive disease; median disease-free survival and overall survival were 14.5 and 19 months, respectively. This adjuvant combination is well tolerated and can be safely administered after curative surgery for pancreatic cancer. Further evaluation of this regimen is ongoing.


Cooling history and emplacement of a pyroxenitic lava as proxy for understanding Martian lava flows.
Terrestrial analogues are often investigated to get insights into the geological processes occurring on other planetary bodies. Due to its thickness and petrological similarities, the pyroxenitic layer of the 120m-thick magmatic pile Theo's Flow (Archean Abitibi greenstone belt Ontario, Canada), has always been regarded as the terrestrial analogue for Martian nakhlites. However, its origin and cooling history and, as a consequence those of nakhlites, have always been a matter of vigorous debate. Did this lava flow originate from a single magmatic event similar to those supposed to occur on Mars or do the different units derive from multiple eruptions? We demonstrate, by a combination of geothermometric constraints on augite single crystals and numerical simulations, that Theo's Flow has been formed by multiple magma emplacements that occurred at different times. This discovery supports the idea that the enormous lava flows with similar compositions observed on Mars could be the result of a process where low viscosity lavas are emplaced during multiple eruptions. This has profound implications for understanding the multiscale mechanisms of lava flow emplacement on Earth and other planetary bodies.


Effects of osteoporosis on the biomechanics of various supplemental fixations co-applied with oblique lumbar interbody fusion (OLIF): a finite element analysis.
Oblique lumbar interbody fusion (OLIF) is an important surgical modality for the treatment of degenerative lumbar spine disease. Various supplemental fixations can be co-applied with OLIF, increasing OLIF stability and reducing complications. However, it is unclear whether osteoporosis affects the success of supplemental fixations; therefore, this study analyzed the effects of osteoporosis on various supplemental fixations co-applied with OLIF. We developed and validated an L3-S1 finite element (FE) model; we assigned different material properties to each component and established models of the osteoporotic and normal bone lumbar spine. We explored the outcomes of OLIF combined with each of five supplemental fixations: standalone OLIF; OLIF with lateral plate fixation (OLIF + LPF); OLIF with translaminar facet joint fixation and unilateral pedicle screw fixation (OLIF + TFJF + UPSF); OLIF with unilateral pedicle screw fixation (OLIF + UPSF); and OLIF with bilateral pedicle screw fixation (OLIF + BPSF). Under the various working conditions, we calculated the ranges of motion (ROMs) of the normal bone and osteoporosis models, the maximum Mises stresses of the fixation instruments (MMSFIs), and the average Mises stresses on cancellous bone (AMSCBs). Compared with the normal bone OLIF model, no demonstrable change in any segmental ROM was apparent. The MMSFIs increased in all five osteoporotic OLIF models. In the OLIF + TFJF + UPSF model, the MMSFIs increased sharply in forward flexion and extension. The stress changes of the OLIF + UPSF, OLIF + BPSF, and OLIF + TFJF + UPSF models were similar; all stresses trended upward. The AMSCBs decreased in all five osteoporotic OLIF models during flexion, extension, lateral bending, and axial rotation. The average stress change of cancellous bone was most obvious under extension. The AMSCBs of the five OLIF models decreased by 14%, 23.44%, 21.97%, 40.56%, and 22.44% respectively. For some supplemental fixations, the AMSCBs were all reduced and the MMSFIs were all increased in the osteoporotic model, compared with the OLIF model of normal bone. Therefore, the biomechanical performance of an osteoporotic model may be inferior to the biomechanical performance of a normal model for the same fixation method; in some instances, it may increase the risks of fracture and internal fixation failure.


Biological Relevance of Network Architecture.
Mathematical representations of brain networks in neuroscience through the use of graph theory may be very useful for the understanding of neurological diseases and disorders and such an explanatory power is currently under intense investigation. Graph metrics are expected to vary across subjects and are likely to reflect behavioural and cognitive performances. The challenge is to set up a framework that can explain how behaviour, cognition, memory, and other brain properties can emerge through the combined interactions of neurons, ensembles of neurons, and larger-scale brain regions that make information transfer possible. "Hidden" graph theoretic properties in the construction of brain networks may limit or enhance brain functionality and may be representative of aspects of human psychology. As theorems emerge from simple mathematical properties of graphs, similarly, cognition and behaviour may emerge from the molecular, cellular and brain region substrate interactions. In this review report, we identify some studies in the current literature that have used graph theoretical metrics to extract neurobiological conclusions, we briefly discuss the link with the human connectome project as an effort to integrate human data that may aid the study of emergent patterns and we suggest a way to start categorizing diseases according to their brain network pathologies as these are measured by graph theory.


Aortopulmonary window due to balloon angioplasty after arterial switch operation.
We report 2 cases of aortopulmonary window that developed after balloon angioplasty for pulmonary artery stenosis. Both patients had undergone arterial switch operations for complete transposition of the great arteries before the angioplasty. These aortopulmonary windows were repaired through elective operations. The clinical features, diagnosis, management, and proposed mechanisms of this complication are described.


Effects of dietary whey proteins, their peptides or amino-acids on the ileal mucosa of normally fed and starved rats.
The effects of three liquid diets, differing only in the molecular form of the nitrogen source (whole whey proteins, WP; trypsic whey protein hydrolysate, WPH, and amino-acid mixture, AAM) were studied on the mucosa morphology and brush border hydrolase (BBH) activities (disaccharidases, peptidases) of the ileum of normally fed male Wistar rats (controls) and during refeeding of rats starved for 72h. All three diets produced repair of the fasting induced mucosal atrophy; the AAM diet gave the most rapid response and highest villus height (p < 0.01). This was correlated with an increase in crypt mitoses (p < 0.01). Similar results were obtained in controls with AAM. The sucrase (S) and acid amino peptidase (AAP) specific activities of controls were higher (p < 0.01) on the WPH diet; neutral amino peptidase (NAP) was unaffected. Dipeptidyl peptidase IV (DDP) was lowest on AAM while glucoamylase (G) highest on WP. Fasting increased S and DDP activity, and produced no change in the other BBH. Large variations in BBH occurred during refeeding except for NAP which remained stable. Control values were restored at 96h, except for AAP. The results show that BBH and mucosa morphology of the ileum in the rat can be modified by the molecular form of the nitrogen source and that the nutritional status interferes with this adaptation. These data could have implications for the therapy of small bowel disease.


[Structured reporting in radiology].
The radiology report plays a key role in the radiological procedure and is used both for documentation of internal procedures as well as in a variety of communication processes within and outside the radiology department. Due to the various communication processes the question arises whether and how the report should be structured. The first stage of such a structured report implies a thematic structure only. This corresponds to the current practice in Germany whereby the reports are structured according to the X-ray act. In the second stage a structure of the contents is added, which is usually implemented by selecting predefined text modules. In the third stage the wording of the text modules is selected from controlled vocabularies, such as the RadLex which allows complete encoding of the report. Templates like this are provided by the Radiological Society of North America (RSNA) reporting initiative and are available to the general public. As advantages of structured reports of levels 2 and 3 it is expected that they provide a better structure and greater clarity of the findings to the referring physician. By using predefined blocks of text a higher degree of completeness and a shorter reporting time is expected. These benefits have been tested in several studies but have not yet yielded clear results. Within a radiology department the structured reports are communicated according to the integrating the healthcare enterprise (IHE) controlled reporting workflow as DICOM structured reports and outside radiology departments the reports are exchanged as CDA objects using HL7 standards.


Superoxide dismutase and catalase activities in Ataxia telangiectasia and normal fibroblast cell extracts.
Superoxide dismutase (EC 184.108.40.206) and catalase (EC 22.214.171.124) are important enzymes involved in protection of the cell from harmful effects of oxidative degradation. The respective substrates for these enzymes, superoxide anion and hydrogen peroxide, can be generated within the cell either by normal metabolism or by ionizing radiation. The hypothesis that the inherent radiosensitivity associated with the human autosomal recessive disease Ataxia telangiectasia is due to decreased levels of SOD and/or catalase was tested. The results suggest that fibroblast cells derived from ataxia patients are normal with respect to these two enzymes.


Inadequate plasma concentrations in some high-dose methadone maintenance patients.
The author studied 18 heroin addicts who had been maintained on 80 mg/day of methadone and who abused drugs or alcohol. His findings suggest that in some cases of aberrant methadone metabolism, the dose can be raised to achieve plasma concentrations adequate to eliminate drug and alcohol abuse.


Early urinary biomarkers for renal tubular damage in spontaneously hypertensive rats on a high salt intake.
A high salt intake exacerbates hypertension and accelerates renal tubular damage in hypertensive patients. However, data concerning early biomarkers for renal tubular change induced by a high salt intake are limited. The objective of this study was to clarify the time course of new biomarkers for renal tubular damage during high salt intake in spontaneously hypertensive rats (SHR). Male SHR received a regular or high-salt diet from 9 to 17 weeks of age. At 10 weeks of age, a high salt intake caused renal tubular damage, which was further exacerbated at 17 weeks of age. Although albuminuria was detected in salt-loaded SHR at 14 weeks of age, urinary excretion of vanin-1 and neutrophil gelatinase-associated lipocalin (NGAL) was elevated in these animals from 10-17 weeks of age. However, kidney injury molecule-1 (Kim-1) was elevated at 15 weeks of age in salt-loaded SHR. These results suggest that urinary vanin-1 and NGAL are potentially early biomarkers for renal tubular damage in SHR under a high salt intake.


The human THE-LTR(O) and MstII interspersed repeats are subfamilies of a single widely distributed highly variable repeat family.
Fifteen examples of the transposon-like human element (THE) LTR and thirteen examples of the MstII interspersed repeat are aligned to generate new consensus sequences for these human repetitive elements. The consensus sequences of these elements are very similar, indicating that they compose subfamilies of a single human interspersed repetitive sequence family. Members of this highly polymorphic repeat family have been mapped to at least 11 chromosomes. Seven examples of the THE internal sequence are also aligned to generate a new consensus sequence for this element. Estimates of the abundance of this repetitive sequence family, derived from both hybridization analysis and frequency of occurrence in GenBank, indicate that THE-LTR/MstII sequences are present every 100-3000 kb in human DNA. The widespread occurrence of members of this family makes them useful landmarks, like Alu, L1, and (GT)n repeats, for physical and genetic mapping of human DNA.


The neurobiology of tumours and head injury, and the neuroimmunology of central nervous system malignancy.
The application of modern investigative techniques in molecular biology, cytogenetics and immunocytochemistry has yielded much new information on central nervous system tumours both in vitro and in vivo. Although the clinical potential of these findings is yet to be fully realized, preliminary clinical studies based on this new information are now in progress. The mechanisms and consequences of brain damage in head injury have been studied both clinically and experimentally for many years; new investigative techniques focusing on the cellular and subcellular basis of brain damage have provided information which is interesting not only in terms of basic neurobiology but also in the identification of new areas for possible therapeutic intervention.


Microalbuminuria and C-reactive protein: similar messengers of cardiovascular risk?
C-reactive protein (CRP) and urinary albumin excretion are both determinants of cardiovascular risk. The first is closely related to systemic and vascular low-grade inflammation, the latter is considered to be a marker of endothelial dysfunction. Because of these properties, one might presume them to be closely interrelated. In this article, we review the available evidence concerning the relationships of CRP and urinary albumin excretion, with each other and with other cardiovascular risk markers and factors. Should they be considered as dependent or independent risk markers, and which risk markers might be present in the cardiovascular risk estimation formula of the near future? The reasons that this formula might or should include CRP and urinary albumin excretion, rather than diabetes mellitus and the metabolic syndrome, are discussed.


Comparison of the characteristics of hot tap water scalds and other scalds in Germany.
Mortality associated with hot tap water scalds remains significant, owing to a lack of up-to-date regulations on tap water temperature. We aimed to evaluate the effect of hot tap water scalds on patients admitted to our adult burn intensive care unit (BICU), and compare them to those with other scald types. We enrolled patients treated for scalds at the BICU of Cologne-Merheim Medical Center from 1989 to 2014, and retrospectively analyzed their age, sex-specific differences, characteristics, length of hospital stay, number of operations, and mortality. Patients were categorized into two groups: patients with hot tap water scalds and those with all other types of scalds. A total of 333 patients were enrolled. In 23.4% (n=78) of the cases, the scalds were associated with hot tap water. Such injuries were more commonly observed in older men than women. Hot tap water scalds involved a significantly higher total burned surface area (TBSA) than other scalds, with TBSA values of 24.0% and 15.9% for men, and 21.8% and 10.9% for women, respectively. Hot tap water scald patients had a greater number of surgeries and longer BICU stays (27.8 days vs 9.1 days), and significantly higher mortality values (30.8% (n=24) vs 4.7% (n=12)) than those with the other scald types. Hot water scalds are associated with large TBSAs, long stays in the BICU, and worse outcomes compared to the other scald types.


Drug-induced tolerance to allografts in mice II. Tolerance to tumor allografts of large doses associated with rejection of skin allografts and tumor allografts of small doses.
Antigen-specific tolerance to tumor allografts in mice was obtained by stimulation with allogeneic spleen cell antigens and treatment with cyclophosphamide (CY) 2 days later in various strain combinations between donor mice of spleen cell antigens and recipients. In such tolerant mice, skin allografts were rejected in various combinations of the donor-recipient. Furthermore, some of the tolerant mice showed accelerated rejection of tumor allografts of small doses, even though they allowed progressive growth of the same tumor allografts of large doses. Our results suggest that the rejection of tumor allografts of large doses may depend upon a mechanism that is distinct, qualitatively or quantitatively, from that one responsible for the rejection of tumor allografts of small doses and skin allografts. One of the most important properties of lymphocytes to separate these two different mechanisms may be a capacity of clonal expansion, namely, sensitivity to CY-induced tolerance of the lymphocytes mediating allograft rejection.


Leading a Hospital Incident Command System during a global pandemic.
Responding to a healthcare crisis such as COVID-19 requires a practiced, nimble incident command structure. Our medical center is in one of the areas in the US that was hardest hit by the initial wave. Effective leadership of incident command was critical in our response.


Primary total knee arthroplasty in a patient with a chronic extensor mechanism deficiency.
A 44-year-old female presented with a chief complaint of left knee pain and dysfunction. The patient had a complex surgical history including patellar fracture repair, subsequent patellar ligament repair, and ultimately allograft reconstruction which was complicated by septic arthritis requiring graft resection. On presentation to our clinic, she was noted to have significant degenerative disease in addition to chronic extensor mechanism deficiency. She underwent primary total knee arthroplasty with concomitant tibial tubercle osteotomy and advancement. The patient has had an excellent result postoperatively including return of full range of motion without residual extensor lag.


Cord blood unit bankability can be predicted by prenatal sonographic parameters.
To identify possible sonographic prenatal parameters and postnatal parameters in order to obtain more bankable cord blood units (CBUs) containing a high number of primitive progenitor cells, allowing CBUs to be used as a source of haematopoietic progenitors for clinical transplantation. Prospective study undertaken in the Department of Gynaecology, Obstetrics and Reproductive Science, Second University of Naples, Italy. In total, 219 unrelated CBU donors were enrolled. Ultrasound parameters (biparietal diameter, head circumference, abdominal circumference, femur length, estimation of fetal weight, umbilical artery pulsatility index), collected at hospital admission, together with birth weight and placental weight, were correlated with bankable CBU parameters (CBU volume, total nucleated cell count, CD34+ cell count). Femur length and abdominal circumference correlated positively with bankable CBUs. Receiver operating curve analysis showed that these parameters can identify bankable CBUs. This is the first prospective study to show the relationship between ultrasonographic fetal parameters at term and the possibility of obtaining high-quality CBUs. As such, cord blood banking could be improved worldwide by performing low-cost ultrasonographic scans.


Increased (99m)Tc-sestamibi washout reflects impaired myocardial contractile and relaxation reserve during dobutamine stress due to mitochondrial dysfunction in dilated cardiomyopathy patients.
This study investigated whether the technitium-99m sestamibi (MIBI) washout rate (WR) would predict mitochondrial damage and myocardial dysfunction in patients with dilated cardiomyopathy (DCM). Myocardial mitochondrial damage reduces adenosine triphosphate production, resulting in myocardial dysfunction. Increased myocardial (99m)Tc-MIBI washout is reportedly caused by mitochondrial dysfunction. Twenty DCM patients (New York Heart Association functional class I-III) underwent myocardial (99m)Tc-MIBI scintigraphy and cardiac catheterization. Myocardial MIBI uptake was quantified as an early and delayed heart-to-mediastinum ratio, and WR was calculated. Maximum first derivative of left ventricular (LV) pressure (LV dP/dtmax) (an index of myocardial contractility) and LV pressure half-time (T1/2) (an index of myocardial relaxation) were calculated by the left ventricular pressure curve at baseline and during dobutamine infusion (15 μg/kg/min at maximum). Endomyocardial biopsy specimens were obtained for quantitative mRNA analysis and electron microscopy. The patients were divided into two groups as follows: 1) group A of 10 patients showing a WR ≤ 24.3% (median value) and 2) group B of 10 patients showing a WR >24.3%. WR was significantly correlated with the percentage changes in LV dP/dtmax (%LV dP/dtmax) (r: -0.59; p = 0.01) and T1/2 (r: -0.57; p = 0.03) from baseline to peak dobutamine stress. The %LV dP/dtmax was significantly greater in group B than in group A. The abundance of mRNAs for mitochondrial electron transport-related enzymes was more significantly reduced in group B than in group A. Electron microscopy revealed significant correlations between WR and the severity of mitochondrial damage (r: 0.88; p = 0.048) and glycogen accumulation (r: 0.90; p = 0.044). Increased (99m)Tc-MIBI washout may predict mitochondrial dysfunction and the impairment of myocardial contractile and relaxation reserves during dobutamine stress in DCM patients.


Effect of Multicomponent Exercise on Cognition, Physical Function and Activities of Daily Life in Older Adults With Dementia or Mild Cognitive Impairment: A Systematic Review and Meta-analysis.
To review the evidence for the effectiveness of multicomponent exercise (an exercise program combining aerobic, endurance, balance, and flexibility exercises) on cognition, physical function, and activities of daily living in people with dementia and mild cognitive impairment (MCI). We conducted this study under the guidance of a designated protocol (PROSPERO CRD42022324641). Pertinent randomized controlled trials were selected from PubMed, Embase, Web of Science, and the Cochrane Library by 2 independent authors through May 2022. Two authors independently extracted the data and assessed the quality of the included studies following the Cochrane Risk of Bias tool. Outcome data were extracted in a random effects model and estimated as Hedges' g and 95% confidence interval (CI). To validate specific results, the Egger test combined the Duval and Tweedie "trim and fill" method and sensitivity analysis with study removed were performed. A total of 21 publications were eligible for the quantitative analysis. In dementia, estimates of Hedges' g showed effects on global cognition (g=0.403; 95% CI, 0.168-0.638; P<.05), especially executive function (g=0.344; 95% CI, 0.111-0.577; P<.05), flexibility (g=0.671; 95% CI, 0.353-0.989; P<.001), agility and mobility (g=0.402; 95% CI, 0.089-0.714; P<.05), muscle strength (g=1.132; 95% CI, 0.420-1.845; P<.05), and activities of daily living (g=0.402; 95% CI, 0.188-0.615; P<.05). Also, a positive trend was observed in gait speed. Additionally, multicomponent exercise had positive effects on global cognition (g=0.978; 95% CI, 0.298-1.659; P<.05) and executive function (g=0.448; 95% CI, 0.171-0.726; P<.05) in patients with MCI. Our findings confirm the viability of multicomponent exercise as a management strategy for patients with dementia and MCI.


Circulation of DENV2 and DENV4 in Aedes aegypti (Diptera: Culicidae) mosquitoes from Praia, Santiago Island, Cabo Verde.
Arthropod-borne viruses, such as Dengue (DENV), Chikungunya (CHIKV), and Zika (ZIKV), pose a challenge to public health, due to their worldwide distribution and large-scale outbreaks. Dengue fever is currently one of the most important diseases and it is caused by four serotypes of DENV and is mainly transmitted by the mosquito Aedes aegypti. It is estimated that 50-100 million cases are reported every year worldwide. More recently, CHIKV and ZIKV, which are also transmitted by Ae. aegypti, have caused epidemics in countries in the Caribbean region, the Pacific region, and Americas. Cabo Verde faced its first dengue outbreak in 2009, with more than 21,000 reported cases and four registered deaths. The epidemic was caused by DENV-3 transmitted by Ae. aegypti mosquitoes. In addition, the country faced a Zika outbreak with more than 7,500 notified cases from October 2015 to May 2016. In the present study, we conducted a survey in mosquito samples to detect arboviruses circulating in the local vector population. Collections were performed from November 2014 to January 2015, in the City of Praia, the capital of Cabo Verde, using aspirators and BG-sentinel traps. Samples were examined by multiplex Reverse Transcription-polymerase chain reaction. A total of 161 Ae. aegypti adult females were analyzed (34 pools) and from these samples, eight pools were found positive for DENV-2 and DENV-4. Our results revealed a very high natural infection rate in the vector population and showed two different serotypes co-circulating in the island that differ from the one detected in the 2009 outbreak in Cabo Verde.


Overview of the mechanisms of induction of labor.
Here we provide a brief overview of the natural process of labor and its biochemical, hormonal, and mechanical characteristics that can be exploited in methods employed for induction of labor.


Mental contamination: the effects of imagined physical dirt and immoral behaviour.
There is a growing body of empirical support for Rachman's (1994, 2004, 2006) conceptualization of mental contamination. The aim of this study was to tease apart manipulations of imagined physical descriptions (i.e., clean versus dirty), in the context of both morally sound and reprehensible acts (i.e., consensual versus non-consensual kiss) to expand our understanding of the experimental variables which may evoke mental contamination and address limitations of previous research. Female undergraduate student participants (n = 140) were randomly assigned to listen to one of four audio recordings and imagine receiving either a consensual or non-consensual kiss from a man described as either physically clean or physically dirty. Results indicated that participants who imagined a non-consensual kiss from a physically dirty man reported the greatest feelings of mental contamination; whereas, participants who imagined a consensual kiss from a physically clean man reported the lowest feelings of mental contamination. However, there were few significant differences in mental contamination feelings between those who imagined a consensual kiss from a physically dirty man and those who imagined a non-consensual kiss from a physically clean man. Results are discussed in terms of cognitive-behavioural conceptualizations of and treatments for contamination fears.


Deposition patterns of feruloylarabinoxylan during cell wall formation in moso bamboo.
The feruloylarabinoxylan deposition was initiated at the formation of the secondary cell wall, especially S2 layer in moso bamboo, which may affect crosslinking between cell wall components and plant growth. Hemicelluloses, major components of plant cell walls that are hydrogen bonded to cellulose and covalently bound to lignin, are crucial determinants of cell wall properties. Especially in commelinid monocotyledons, arabinoxylan is often esterified with ferulic acid, which is essential to crosslinking with cell wall components. However, the deposition patterns and localization of ferulic acid during cell wall formation remain unclear. In this study, developing moso bamboo (Phyllostachys pubescens) culms were used to elucidate deposition patterns of hemicelluloses including feruloylarabinoxylan. Ferulic acid content peaked with cessation of elongation growth, and thereafter decreased and remained stable as culm development proceeded. During primary cell wall (PCW) formation, xyloglucan and (1,3;1,4)-β-glucan signals were detected in all tissues. Along with culm development, arabinoxylan and feruloylarabinoxylan signals were sequentially observed in the protoxylem, vascular fibers and metaxylem, and parenchyma. Feruloylarabinoxylan signals were observed slightly later than arabinoxylan signals. Arabinoxylan signals were observed throughout the compound middle lamella and secondary cell wall (SCW), whereas the feruloylarabinoxylan signal was localized to the S2 layer of the SCW. These results indicate that the biosynthesis of hemicelluloses is regulated in accordance with cell wall layers. Feruloylarabinoxylan deposition may be initiated at the formation of SCW, especially S2 layer formation. Ferulic acid-mediated linkages of arabinoxylan-arabinoxylan and arabinoxylan-lignin would arise during SCW formation with the cessation of elongation growth.


Centerless Clustering.
Although lots of clustering models have been proposed recently, k-means and the family of spectral clustering methods are both still drawing a lot of attention due to their simplicity and efficacy. We first reviewed the unified framework of k-means and graph cut models, and then proposed a clustering method called k-sums where a k-nearest neighbor ( k-NN) graph is adopted. The main idea of k-sums is to minimize directly the sum of the distances between points in the same cluster. To deal with the situation where the graph is unavailable, we proposed k-sums-x that takes features as input. The computational and memory overhead of k-sums are both O(nk), indicating that it can scale linearly w.r.t. the number of objects to group. Moreover, the costs of computational and memory are Irrelevant to the product of the number of points and clusters. The computational and memory complexity of k-sums-x are both linear w.r.t. the number of points. To validate the advantage of k-sums and k-sums-x on facial datasets, extensive experiments have been conducted on 10 synthetic datasets and 17 benchmark datasets. While having a low time complexity, the performance of k-sums is comparable with several state-of-the-art clustering methods.


Muscular control of a learned movement: the speed control system hypothesis.
The "speed control system" hypothesis, which represents an attempt to identify an invariant characteristic of learned movements, postulates that movements of variable extent are controlled by regulating the intensity of muscle contractions such that the contraction duration remains constant. The contingency set originally utilized to develop this hypothesis was expanded by examining a movement that was multidirectional and multiarticular, and executed by large muscle groups generating near maximum torques. The investigation focused on the techniques utilized by weightlifters to control lower extremity displacement during the initial phase of the double knee bend execution of the "clean" in Olympic weightlifting. The combination of the quantified muscle activity and the angular velocity, both about the knee joint, revealed a sequence of shortening-lengthening muscle contractions throughout the movement. The first two periods of net muscular activity, one extensor and the other flexor, were utilized to examine the movement for invariant characteristics. As predicted by the speed control system hypothesis, the duration of the first period of net muscle torque activity (extensor) did not vary significantly, for either group of subjects, over the relative loads examined. The duration of the second period of activity (resultant flexor muscle torque), however, was not constant across loads, and further, the direction of the change depended upon the level of expertise. The more capable lifters tended to increase the duration of the resultant flexor involvement while the less skilled athletes utilized the reverse strategy when the load was increased. Conversely, the intensity of the muscle activity for both groups of subjects and both the extensor and flexor periods covaried with load, as predicted by the hypothesis. The speed control system hypothesis, therefore, provided an appropriate explanation for the first component of the movement, the period of extensor dominated (shortening contraction) muscle torque, but was inappropriate for the subsequent interval, a resultant flexor (largely lengthening contraction) muscle torque.


Selective Cell-Surface Expression of Triheteromeric NMDA Receptors.
The NMDA-type ionotropic glutamate receptors play pivotal roles in many brain functions, but are also involved in numerous brain disorders. Seven NMDA receptor subunits exist (GluN1, GluN2A-D, and GluN3A-B) that assemble into a diverse array of tetrameric receptor subtypes with distinct functional properties and physiological roles. Most NMDA receptors are composed of two GluN1 and two GluN2 subunits, which can assemble into four diheteromeric receptor subtypes composed of GluN1 and one type of GluN2 subunit (e.g., GluN1/2A), and presumably also six triheteromeric receptor subtypes composed of GluN1 and two different GluN2 subunits (e.g., GluN1/2A/2B). Despite accumulating evidence that a large proportion of native NMDA receptors are triheteromers, little is known about their function and pharmacology due to the lack of methods to faithfully express triheteromeric NMDA receptors in heterologous expression systems. The problem is that co-expression of GluN1 with two different GluN2 subunits generates two distinct diheteromeric receptor subtypes as well as one triheteromeric receptor subtype, thereby confounding studies on a homogenous population of triheteromeric NMDA receptors. Here, we will describe a method to selectively express recombinant triheteromeric GluN1/2A/2B receptors without interfering co-expression of diheteromeric GluN1/2A and GluN1/2B receptors. This method enables quantitative evaluation of functional and pharmacological properties of triheteromeric GluN1/2A/2B receptors, which are presumably the most abundant NMDA receptors in the adult cortex and hippocampus.


Vector competence of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) for DEN2-43 and New Guinea C virus strains of dengue 2 virus.
The vector competence of Aedes albopictus and Aedes aegypti with regard to DEN2-43 and New Guinea C (NGC) virus strains of Dengue 2 viruses was assessed and compared. The infection and dissemination rate and distribution of DEN2-43 antigens in orally infected Ae. albopictus was investigated using the reverse transcription polymerase chain reaction and an indirect immunofluorescence assay. To better understand the initial infection, dissemination and transmission of these viral strains in vector mosquitoes, Ae. albopoictus and Ae. aegypti were fed an artificial blood meal containing either the DEN2-43 or NGC strain. There was no significant difference in the infection and dissemination rates of DEN2-43 and NGC virus strains in Ae. albopictus, however, Ae. aegypti was more susceptible to infection by NGC than DEN2-43 vrius strain. Ae. albopictus mosquitoes infected with the NGC strain developed a higher percentage of midgut infections than those infected with the DEN2-43 strain (t=2.893, df=7, P=0.024). Approximately 26.7% of midgut samples were positive for the NGC antigen 5 days after infection, and 80% of mosquitoes had infected midgets after 15 days. The NGC antigen first became evident in mosquito salivary glands on Day 5, and 40% of mosquitoes had infected salivary by Day 9. In contrast, the DEN2-43 antigen first became evident in salivary glands on Day 7. The infection rate of NGC and DEN2-43 virus strains in salivary glands were similar. These results indicate that Ae. albopictus and Ae. aegypti are moderately competent vectors for the DEN2-43 virus, which could provide basic data for the epidemiology study of dengue fever in China.


Long-term effects of temperature during early life on growth and fatty acid metabolism in age-0 Lake Sturgeon (Acipenser fulvescens).
Environmental temperature during early life may have prolonged effects on growth and fatty acid metabolism, which could strongly influence overwintering survival in the first year of life for temperate-zone fish. In the present study, we examined how temperature during early life history might influence growth performance and fatty acid metabolism in age-0 Lake Sturgeon (Acipenser fulvescens) when exposed to cold temperatures at later stages. Fish were initially at 16 °C and subsequently held at 16 °C or 20 °C for 60 days beginning at 34 days post fertilization (dpf). Then, all fish were subsequently raised at the same temperature of 16 °C until the onset of cold conditioning at 158 dpf where temperature was gradually decreased to 3.5 °C and remained there for two weeks. Samples were collected before (151 dpf) and after cold conditioning (199 dpf) to measure total length, body mass, whole body metabolic rate, fatty acid profile in phospholipids and triglycerides and mRNA expression of genes associated with fatty acid desaturation, elongation and β-oxidation. Results revealed that before cold conditioning, total length and body mass did not differ between temperature groups, but fish raised at 20 °C showed a lower condition factor. During the cold conditioning, only fish raised at 16 °C grew significantly longer and heavier. There was no difference in metabolic rates between treatments. Significant increases in total monounsaturated fatty acids with decreases in total saturated fatty acids were identified in phospholipids and triglycerides in both temperature groups after the cold conditioning; however, the 20 °C group did not significantly increase levels of gene expression associated with fatty acid desaturation (SCD and FADS1) whereas the 16 °C group did. Our results suggest that thermal experience during early life may influence overwintering survival of age-0 Lake Sturgeon.


Goth Music and Depressive Symptoms among Adolescents: A Longitudinal Study.
Identification with Goth youth culture has been related to elevated levels of depression, self-harm and suicide ideation. However, this identification may be difficult to assess as Goth is stigmatized and adolescents may hesitate to self-identify. Conversely, adolescents readily respond to questions on their music preferences. This study addresses the potential link between liking Goth music and depressive symptoms in a four-year study among 10 to 15-year-olds (N = 940, M age = 12.4 at T1, 49% female). In this study, it was found that Goth music is only liked by a small minority of adolescents (4 to 11%). Both girls and boys who liked Goth music reported increased levels of depressive symptoms as they grew older. The findings of this study suggest that a preference for Goth music emerges as an early, sensitive marker of dormant or developing depressive symptoms in adolescents. The mechanisms through which music preferences can translate into or sustain depressive symptoms are discussed.


Adherence to Mediterranean diet and close dietetic supervision increase total dietary antioxidant intake and plasma antioxidant capacity in subjects with abdominal obesity.
To determine the effect of Mediterranean-type diet and close dietetic supervision on dietary antioxidant intake and plasma total antioxidant capacity (TAC) in patients with abdominal obesity. Ninety subjects with abdominal obesity, 46 in intervention group, 44 in control group, participated in a 2-month, randomized, parallel dietary intervention. All participants were counseled on Greek Mediterranean diet. The intervention group was under close dietetic supervision, followed a specific relevant daily and weekly food plan consuming antioxidant-rich foods and food products. Total dietary antioxidant intake was calculated from the volunteers' food diaries, and plasma TAC using plasma ORAC assay and plasma ferric-reducing antioxidant power (FRAP) assay, both at baseline and at 2 months. Following the 2-month period, total dietary antioxidant intake was increased in the intervention group compared to the control group (P = 0.000). In addition, increased intake of total fat, due to higher consumption of monounsaturated fatty acids, as well as increased intakes of dietary fiber, vitamin C and alcohol was also observed in the intervention group compared to the control group (P < 0.05). Plasma TAC was increased in the intervention group compared to the control group (P = 0.039) using the ORAC assay, while there was a trend toward a TAC increase (P = 0.077) using the FRAP assay. Adherence to a Mediterranean-type diet, with emphasis on an increase in foods rich in antioxidants and close dietetic supervision, can increase total dietary antioxidant intake and plasma TAC in patients with abdominal obesity.


Impaired Pulmonary Diffusion in Heart Failure With Preserved Ejection Fraction.
The purpose of this study was to compare measures of gas exchange at rest and during exercise in patients with heart failure and preserved ejection fraction (HFpEF) with age- and sex-matched control subjects. Patients with HFpEF display elevation in left heart pressures, but it is unclear how this affects pulmonary gas transfer or its determinants at rest and during exercise. Patients with HFpEF (n = 20) and control subjects (n = 26) completed a recumbent cycle ergometry exercise test with simultaneous measurement of ventilation and gas exchange. Diffusion of the lungs for carbon monoxide (DLCO) and its subcomponents, pulmonary capillary blood volume (VC) and alveolar-capillary membrane conductance (DM), were measured at rest, and matched for low-intensity (20 W) and peak exercise. Stroke volume was measured by transthoracic echocardiography to calculate cardiac output. Compared with control subjects, patients with HFpEF displayed impaired diastolic function and reduced exercise capacity. Patients with HFpEF demonstrated a 24% lower DLCO at rest (11.0 ± 2.3 ml/mm Hg/min vs. 14.4 ± 3.3 ml/mm Hg/min; p < 0.01) related to reductions in both DM (18.1 ± 4.9 ml/mm Hg/min vs. 23.1 ± 9.1 ml/mm Hg/min; p = 0.04), and VC (45.9 ± 15.2. ml vs. 58.9 ± 16.2 ml; p = 0.01). DLCO was lower in patients with HFpEF compared with control subjects in all stages of exercise, yet its determinants showed variable responses. With low-level exercise, patients with HFpEF demonstrated greater relative increases in VC, coupled with heightened ventilatory drive and more severe symptoms of dyspnea compared with control subjects. At 20-W exercise, DM was markedly reduced in patients with HFpEF compared with control subjects. From 20 W to peak exercise, there was no further increase in VC in patients with HFpEF, which in tandem with reduced DM, led to a 30% reduction in DLCO at peak exercise (17.3 ± 4.2 ml/mm Hg/min vs. 24.7 ± 7.1 ml/mm Hg/min; p < 0.01). Subjects with HFpEF display altered pulmonary function and gas exchange at rest and especially during exercise, which contributes to exercise intolerance. Novel therapies that improve gas diffusion may be effective to improve exercise tolerance in patients with HFpEF.


Development and validation of nomogram to improve the specificity of multiparametric MRI for clinically significant prostate cancer.
To develop and validate a nomogram to improve the specificity of prostate imaging reporting and data system (PI-RADS) on multiparametric magnetic resonance imaging (MRI) for clinically significant prostate cancer on targeted fusion biopsy. A retrospective review of patients who underwent fusion biopsy for PI-RADS 3-5 lesions using UroNav and Artemis systems between 2016 and 2022 was performed. Patients were divided into those with CS disease on fusion biopsy (Gleason grade group ≥2) versus those without. Multivariable analysis was used to identify variables associated with CS disease. A 100-point nomogram was constructed, and ROC curve was generated. 1485 lesions (1032 patients) were identified, 510 (34%) were PI-RADS 3, 586 (40%) were PI-RADS 4, and 389 (26%) were PI-RADS 5. Of these, 11% of PI-RADS 3, 39% of PI-RADS 4, and 61% of PI-RADS 5 showed CS disease. CS disease was associated with older age (OR 1.04, 95% CI 1.02-1.06, p < 0.01), previous negative biopsy (OR 0.52, 95% CI 0.36-0.74, p < 0.01), presence of multiple PI-RADS 3-5 lesions (OR 0.61, 95% CI 0.45-0.83, p < 0.01), peripheral zone location (OR 1.88, 95% CI 1.30-2.70, p < 0.01), PSA density (OR 1.48 per 0.1 unit, 95% CI 1.33-1.64, p < 0.01), PI-RADS score 4 (OR 3.28, 95% CI 2.21-4.87, p < 0.01), and PI-RADS score 5 (OR 7.65, 95% CI 4.93-11.85, p < 0.01). Area under ROC curve was 82% for nomogram compared to 75% for PI-RADS score alone. We report a nomogram that combines PI-RADS score with other clinical parameters. The nomogram outperforms PI-RADS score for the detection of CS prostate cancer.


Urologic Disorders are Still the Leading Cause of In-hospital Death in Patients With Spina Bifida.
To assess and analyze the contemporary causes of in-hospital deaths of spina bifida patients. It was a cross-sectional observational study of the longitudinal national cohort of all patients hospitalized in French public and private hospitals. We analyzed the data from the French hospital discharge database (Programme de Médicalisation des Systemes d'Information, PMSI) from 2009 to 2014. The number of in-hospital deaths was extracted using the combination of the ICD-10 codes "Q05" or "Q760" and a discharge code = 9. There were 138 in-hospital deaths of spina bifida patients over the 6-year study period. The median age at death was 41 years (IQR: 25-52). The median age at death was significantly lower in patients with vs without hydrocephalus (26.6 vs 45.5 years; P <.0001). The leading cause of in-hospital death was urologic disorders (n = 24; 17.3%). Other main causes of death were pulmonary disorders (n = 23; 16.7%), neurologic disorders (n = 19; 13.8%), and bowel disorders (n = 15; 10.9%). Upper urinary tract damage accounted for most of the urologic causes of death: 8 patients died from urinary tract infections (33.3%), 7 patients died from renal failure (29.2%), 4 died from bladder cancer (16.7%), and 5 from other urologic causes. The only variable significantly associated with a death from urologic causes was the absence of hydrocephalus (OR = 0.26; P = .009). Urologic disorders remain the leading cause of in-hospital death in spina bifida patients in France. The present study highlights that efforts to improve the urologic management of the spina bifida population are still greatly needed.


Room temperature ferroelectricity in fluoroperovskite thin films.
The NaMnF3 fluoride-perovskite has been found, theoretically, to be ferroelectric under epitaxial strain becoming a promising alternative to conventional oxides for multiferroic applications. Nevertheless, this fluoroperovskite has not been experimentally verified to be ferroelectric so far. Here we report signatures of room temperature ferroelectricity observed in perovskite NaMnF3 thin films grown on SrTiO3. Using piezoresponse force microscopy, we studied the evolution of ferroelectric polarization in response to external and built-in electric fields. Density functional theory calculations were also performed to help understand the strong competition between ferroelectric and paraelectric phases as well as the profound influences of strain. These results, together with the magnetic order previously reported in the same material, pave the way to future multiferroic and magnetoelectric investigations in fluoroperovskites.


Partial posterior vertebrectomy for anterior thoracic cord compression.
Compression of the anterior aspect of the thoracic cord is a common neurosurgical emergency. Treatment is generally unrewarding. Decompression by the anterior and antero-lateral approach is difficult and time consuming, and decompressive laminectomy offers poor results. It is suggested that in selected cases the removal of a small part posterior of the vertebral body via a posterolateral approach is an appropriate alternative treatment.


Neoplasms of the immune system in rheumatoid arthritis.
Two studies are reported of patients with rheumatoid arthritis. The first was a retrospective-prospective-prospective study and comprised a cohort of 489 patients with rheumatoid arthritis followed for a mean of 12.2 years. Lymphoproliferative malignancies developed in 10 patients (2.2 percent) after a mean interval of 11.8 years. The second was a study of 30 patients, from various centers in England, with rheumatoid arthritis and lymphoproliferative malignancies. The effects of chronicity of rheumatoid arthritis, drug therapy, and possible predisposing factors in the etiology of the lymphoproliferative malignancies were examined. Cytotoxic drugs could not be implicated in the pathogenesis of the lymphoproliferative malignancies, but phenylbutazone and D-penicillamine may have played a role in some cases. Current evidence supports the hypothesis that chronic synovitis in rheumatoid arthritis is associated with persistent activation of lymphocytes in lymph nodes and eventual malignant transformation in some cases.


Effect of sagittal shape on proximal junctional kyphosis following thoracopelvic corrective fusion for adult spinal deformity: postoperative inflection vertebra cranial to T12 is a significant risk factor.
This was a retrospective analysis of a prospectively collected consecutive case series of patients with adult spinal deformity (ASD). This study aimed to investigate the impact of the geometrical sagittal shape of the corrected spine on the development of proximal junctional kyphosis (PJK). Several studies have documented risk factors for PJK in ASD surgery. Geometrical assessment is vital for evaluating sagittal spinal deformity. It is essential to assess the postoperative geometrical shape of the spine and the location of the correction in the spine to decrease postoperative junctional stress and PJK. Consecutive patients with ASD who underwent corrective fusion with long constructs to the pelvis were included. Patients with neuromuscular disease, congenital and adolescent scoliosis, infection, and spinal tumor were excluded. We investigated the spinopelvic and geometrical parameters of the whole spine. The locations of the thoracic and lumbar apical vertebrae and the inflection vertebrae (IV), where the curvature of the associated adjacent vertebral bodies changes from kyphosis to lordosis, were investigated. The subjects were divided into PJK included patients who underwent revision surgery for junctional failure or with a change in proximal junctional angle ≥ 20°, and non-PJK groups. A total of 139 patients (mean age, 69.6 years; range 18-82 years) were included. There were 47 and 92 patients in the PJK and non-PJK groups, respectively. The IV were located significantly cranial and posterior, the lumbar apex were located significantly posterior in the PJK group at the immediate postoperative time points. The significant risk factors for PJK on binary logistic regression were cranial IV and posterior lumbar apical vertebrae. The incidence of PJK in patients with IV at T12 or cranial tends PJK significantly higher (69%) than at L1 or caudal (26%). Geometrical spinal shape should be taken into account to reduce the rate of postoperative mechanical complications. Level of evidence III.


Genetic variation in constitutive and inducible pyrrolizidine alkaloid levels inCynoglossum officinale L.
The constitutive pyrrolizidine alkaloid (PA) concentration of both shoots and roots differed significantly between 17 selfed families. The broad-sense heritability accounted for 33-43% of the variation in PA levels. Families also differed significantly in the amount and the direction of PA induction in both shoots and roots, 24 h after punching 15 holes in the leaves. We found a significantly negative relationship between the changes in PA content of the shoots and changes in PA content of the roots. The total PA content of the plants did not increase. We thus concluded that changes in PA distribution over the plant resulted from transport of PAs within the plant. The direction of transport differed between families: some transported PAs to the shoots, others to the roots. This makes it questionable whether PAs act as damage-induced defences. The effect of damage on the PA concentration is far less than the differences found between families in the constitutive PA concentration. This again strongly suggests that damage-induced defences inCynoglossum officinale do not play an important role. We argue that the general lack of attention that is given to genotype in induction experiments, has led to false conclusions.


Retinopathy of prematurity in infants of 24-30 weeks' gestational age.
Over the 10-year period from January 1, 1977 to December 31, 1986, 1114 infants with gestational ages of 24 to 30 completed weeks were cared for on a long-term basis in our nursery; 757 (68%) infants survived. As expected, both the mortality rate and the prevalence of stage-3 or stage-4 retinopathy of prematurity among survivors fell with increasing maturity at birth (P less than 0.0001). Adjusting for gestational age, and excluding infants with lethal malformations, the mortality rate decreased significantly (P = 0.018) over time by an estimated 11.5%; also the survival rate of infants with at least stage-3 retinopathy of prematurity increased significantly (P = 0.005) by an estimated 6.8%. In other words, for every 10 additional survivors over the decade, six survivors would have been expected to show at least stage-3 retinopathy of prematurity in either eye. Although the prevalence of advanced stages of retinopathy of prematurity increased in immature survivors, it was not in epidemic proportions; however, it was more likely to be related to the survival of the increasing numbers of at-risk immature infants who, in earlier times, would have died.


Seed fate in a population of Carex pilulifera L. : II. Seed predation and its consequences for dispersal and seed bank.
Seed predation of the myrmecochorous Carex pilulifera (Cyperaceae) was studied in a wood land area in NE Zealand, Denmark. Experiments demonstrated that predation by mice, Sylvaemus flavicollis, and ground beetles, Harpalus fuliginosus, reduced the seed pool of a C. pilulifera population by approx. 21% and 65%, respectively. The use of exclosure experiments in studies of predation is discussed and criticized. Evidence indicated only a small degree of competitive interaction between the two predator species and between predators and seed-dispersing ants. The possible evolutionary consequences of predation for seed set, dispersal, and phenology are discussed. Although the study indicated that the number of seeds surviving in soil decreased exponentially with time, the presence of a persistent seed bank in C. pilulifera was demonstrated.


Are all pulmonary embolism clinical decision rules equal?
Are four common clinical decision rules, in combination with normal D-dimer results, comparable in their ability to clinically exclude the diagnosis of pulmonary embolism? Douma RA, Mos ICM, Erkens PMG, et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study. Ann Intern Med 2011;154:709-18. To directly compare the performance of four different clinical decision rules, the Wells rule, revised Geneva score, simplified Wells rule, and simplified revised Geneva score, in combination with D-dimer results, to exclude pulmonary embolism.


Expression and prognostic significance of CIP2A mRNA in hepatocellular carcinoma and nontumoral liver tissues.
This study was undertaken to determine the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in predicting prognosis of hepatocellular carcinoma (HCC). CIP2A mRNA level of 136 pairs of tumor and nontumoral liver tissues of HCC patients after hepatectomy were investigated by quantitative real-time reverse transcription polymerase chain reaction. Intratumoral CIP2A mRNA was not associated with patients' prognosis. However, nontumoral CIP2A mRNA, which was correlated with lack of tumor encapsulation, poor tumor differentiation, intrahepatic metastasis, and high tumor-node-metastasis stage was an independent risk factor for overall survival and recurrence-free survival. Nontumoral CIP2A mRNA expression might serve as a novel biomarker for HCC patients undergoing resection.


ING5 inhibits lung cancer invasion and epithelial-mesenchymal transition by inhibiting the WNT/β-catenin pathway.
ING5 is the last member of the Inhibitor of Growth (ING) candidate tumor suppressor family that has been implicated in multiple cellular functions, including cell cycle regulation, apoptosis, and chromatin remodeling. Our previous study showed that ING5 overexpression inhibits lung cancer aggressiveness and epithelial-mesenchymal transition (EMT), with unknown mechanisms. Western blotting was used to detect total and phosphorylated levels of β-catenin and EMT-related proteins. Immunofluorescent staining was used to observe E-cadherin expression. Proliferation and colony formation, wound healing, and Transwell migration and invasion assays were performed to study the proliferative and invasive abilities of cancer cells. ING5 overexpression promotes phosphorylation of β-catenin at Ser33/37, leading to a decreased β-catenin protein level. Small hairpin RNA-mediated ING5 knockdown significantly increased the β-catenin level and inhibited phosphorylation of β-catenin S33/37. Treatment with the WNT/β-catenin inhibitor XAV939 inhibited ING5-knockdown promoted proliferation, colony formation, migration, and invasion of lung cancer A549 cells, with increased phosphorylation of β-catenin S33/37 and a decreased β-catenin level. XAV939 also impaired ING5-knockdown-induced EMT, as indicated by upregulated expression of the EMT marker E-cadherin, an epithelial marker; and decreased expression of N-cadherin, a mesenchymal marker, and EMT-related transcription factors, including Snail, Slug, Twist, and Smad3. Furthermore, XAV939 could inhibit the activation of both IL-6/STAT3 and PI3K/Akt signaling pathways. ING5 inhibits lung cancer invasion and EMT by inhibiting the WNT/β-catenin pathway.


Investigation of the expansin gene family in sugar beet (Beta vulgaris) by the genome-wide level and their expression responses under abiotic stresses.
Sugar beet (Beta vulgaris ssp. vulgaris) is primarily used in sugar production worldwide. Expansins are a gene family of cell wall proteins effective in regulating cell wall structure. They also participate in developmental stages, including cell and leaf growth, root development, and fruit ripening. This study comprehensively characterizes the expansin gene family members found in the sugar beet genome. In addition, in silico expression analysis of sugar beet expansin genes under variable abiotic stress conditions and expression profiles of expansin genes under combined drought and heat stresses by the qRT-PCR method were evaluated in the study. A total of 31 sugar beet expansin genes were identified. BvuEXLA-02 and BvuEXLB-02 genes can have abiotic stress tolerance roles besides their roles in normal development. Determining the properties of sugar beet expansin, family members can help enable the cellulose hydrolysis mechanism and raise plant biomass. Elucidating expression profiles of the sugar beet expansin genes under variable stress conditions can support improving plant productivity. The results of the current study may also contribute to the deep understanding of sugar beet expansin genes in the future.


Short-term changes in intracellular ROS localisation after the silver nanoparticles exposure depending on particle size.
Silver nanoparticles (AgNPs) induce the production of reactive oxygen species (ROS) and apoptosis. These effects are enhanced by smaller particles. Using live-cell imaging, we show that AgNPs induced ROS production rapidly in a size-dependent manner after exposure of cells to 70-nm and 1-nm AgNPs (AgNPs-70, AgNPs-1), but not AgNO3. Exposure of cells to 5 μg/mL each of AgNPs-70, AgNPs-1 or AgNO3 for 1 h decreased the cell viability by approximately 40%, 100% and 20%, respectively. ROS were rapidly induced after 5 and 60 min by AgNPs-1 and AgNPs-70, respectively, whereas AgNO3 had no detectable effect. ROS production detected using the reporter dichlorodihydrofluorescein was observed in whole cells and mitochondria 5 and 60 min after exposure to AgNPs-1. The present study is the first, to our knowledge, to report the temporal expression and intracellular localisation of ROS induced by AgNPs.


The superposition principle applied to grasping an object producing moments outside anatomically-defined axes.
The superposition principle suggests that motor commands can be divided into individually controlled components that summate to produce complex motor actions. Previous studies have examined the validity of this principle in human grasping by changing moments acting on an object about a single anatomically-defined axis and asking subjects to hold the object while their forearm was constrained. Superposition was reflected as separate control of the grip force and moments required to prevent object slip and maintain orientation. The objective of this study was to examine the robustness of this principle by: 1) expanding the range of tasks to include those where moments act on an object with respect to moment arms not necessarily in line with the anatomically-defined axes; 2) asking subjects to hold the object in an unconstrained manner. Ten subjects were asked to lift and hold an object vertically under eighteen moment conditions. Force and moment data from all digits were analysed using principal components analysis (PCA). Different PCAs were run for variable sets corresponding to moments about the long axis of the forearm (M(x)), the vertical (M(y)) and grip (M(z)) axes, and for the entire dataset (M(3D)). The PCA showed grip force and moment variables on separate PCs for the M(x), M(y), and M(3D) variable sets. The M(3D) PCA also showed a separation of variables corresponding to moments about each anatomically-defined axis. Thus, the present results show that the superposition principle holds during natural manipulation of an object experiencing external moments outside the anatomically-defined axes.


The effect of ischemia on thallium-201 clearance from the myocardium.
To determine the effect of ischemia on myocardial clearance of thallium-201 (201Tl), we studied 12 dogs with ischemia produced after the injection of Tl. Tl was given I.V. 10 minutes before left anterior descending (LAD) coronary artery ligation. 85Sr-microspheres (MS) were administered 5 minutes later, and control biopsies were obtained from the myocardium. The LAD was tied and repeat biopsies obtained from the ischemic zone (IZ) and normal zone (NZ) 15 minures and 2 hours later. 46Sc-MS were given just before the final giopsy. Tl activity in the IZ was not significantly different from that in the NZ either before LAD occlusion or 15 minutes and 2 hours later. Tl clearance at the end of 2 hours was not significantly different (27 +/- 5% vs 28 +/- 5%, IZ vs NZ respectively) between the two zones. The half-time of Tl clearance from both the IZ and NZ was calculated at 4.5 hours (consistent with previously reported normal values). This occurred despite a decrease in regional myocardial blood flow to 24 +/- 6% of control (P less than 0.01) in the IZ and an increase to 47 +/- 14% of control (P less than 0.01) in the NZ during the study. We conclude that myocardial ischemia does not alter the normal rate of Tl clearance from the myocardium.


Increasing incidence of malignant melanoma of skin can be modeled as a response to suddenly imposed environmental stress.
The aim was to determine whether the increasing age-standardized incidence of malignant melanoma of the skin in some countries can be explained by a suddenly imposed environmental stress to the whole population. Incidence data were retrieved from the cancer registries of the USA and four Nordic countries. A four-parameter incidence model was developed and its parameters were varied to optimally fit age-standardized data from the investigated countries. Two parameters were used for a log-normally distributed exposure time to illness; the other two were the starting year for the imposed exposure and the critical age (age at which the exposure starts having an effect on incidence). Reported age-specific incidence data from the investigated countries were also analyzed to see at what age melanoma of the skin actually starts to occur. Similar parameters for exposure time to illness were calculated for all five countries. The staring year was found to be 1967 for the USA, while for the Nordic countries it ranged between 1953 to 1955. The modeled critical age for all countries varied from 13 to 18 years; the actual average critical age was found to be 14.3 years for the investigated countries analyzed based on reported age-specific data. An environmental stress suddenly imposed in the mid-1950s for the Nordic countries and in the late 1960s for the USA, affecting people from 13 years of age and above, can mathematically explain the age-specific pattern for melanoma of the skin noticed in the investigated countries.


Chandelier retroillumination-assisted cataract surgery during vitrectomy.
PurposeTo present an alternative cataract surgical technique in patients with cataract and intravitreal hemorrhage.MethodsTwelve cases with poor fundus reflex caused by severe vitreus hemorrhage were included in the study. All patients underwent combined phaco surgery and 23-gauge vitrectomy. Chandelier retroillumination was inserted into the infusion trochar during the cataract operations and was used with low power (50-75%) in necessary steps.ResultsWe did not experience phaco complications or complications due to technique during surgery. Retroillumination assistance was especially useful during final stages of cataract surgery, particularly irrigation-aspiration of cortical material.ConclusionRetroillumination in absence of red fundus reflex may be helpful and can be practiced more often in cataract surgery combined with vitrectomy.


Comment on "Simulations of ionization equilibria in weak polyelectrolyte solutions and gels" by J. Landsgesell, L. Nová, O. Rud, F. Uhlík, D. Sean, P. Hebbeker, C. Holm and P. Košovan, Soft Matter, 2019, 15, 1155-1185.
In a recent review Landsgesell et al., Soft Matter 2019, 15, 1155 stated that pH - pKa is a "universal parameter" for titrating systems. We show that this is not the case. This broken symmetry has important implications for constant pH (cpH) simulations. In particular, we show that for concentrated suspensions the error resulting from the use of cpH algorithm described by Landsgesell et al. is very significant, even for suspension containing 1 : 1 electrolyte. We show how to modify the cpH algorithm to account for the grand-canonical nature of the cpH simulations and for the charge neutrality requirement.


Characterizing contrast-enhancing and re-enhancing lesions in multiple sclerosis.
In multiple sclerosis (MS), contrast-enhancing lesions (CELs) in T1-weighted postcontrast MRI are considered markers of blood-brain barrier breakdown. It remains unknown if re-enhancement can be considered a radiologic indicator of different pathology in CELs. We investigated 1) the incidence of re-enhancing lesions (re-CELs) from chronic lesions; 2) differences in size, magnetization transfer ratio (MTR), and likelihood to appear as acute black holes (aBHs) between new lesions (n-CELs) and re-CELs; and 3) associations between re-CELs and features indicating more advanced disease. In this retrospective natural history study, we examined 264 monthly MRI scans performed at month 1 (M1), month 2 (M2), and month 3 (M3) for 88 patients with MS. CELs were defined as n-CELs if not present in the M1 T2W MRI and re-CELs if present in the M1 T2W MRI. A total of 311 (82.7%) n-CELs and 65 (17.3%) re-CELs were identified. Of the 88 patients, 54 presented only n-CELs, 8 presented only re-CELs, and 26 presented both CEL types. Patients with both lesion types presented more CELs than those presenting only one type (p = 0.01). Re-CELs were larger (z = 2.72, p = 0.007) and had lower MTR (z = -2.80, p = 0.005) than n-CELs but the estimated proportion of aBHs from n-CELs was similar (z = -0.09, p = 0.1) from the proportion of aBHs from re-CELs. Nearly 20% of CELs represent the reoccurrence of enhancement in chronic plaques. Re-CELs represent larger areas of inflammation, not necessarily associated with larger areas of edema.


A Golgi study on the cerebrospinal fluid (CSF)-contacting neurons in the paraventricular nucleus of the Pekin duck.
The present investigation based on classical neurohistological techniques (Nissl-staining, Golgi-impregnation) was focussed on the cytoarchitecture of the periventricular layer of the paraventricular nucleus in the Pekin duck. This region is endowed with intraependymal neurons, the perikarya of which are mostly covered by a thin ependymal lamella. Several of the intraependymal neurons were shown to give rise to dendrites extending into the third ventricle. An additional population of nerve cells located in the deeper layers of the periventricular region also gained direct access to the cerebrospinal fluid by means of long dendrites terminating with a bulbous-like swelling in the third ventricle. This cerebrospinal fluid (CSF)-contacting dendrite branched off several times in a rectangular fashion to give rise to collaterals running in the subependymal or periventricular layers. The axons of these CSF-contacting neurons were followed into the magnocellular portion of the paraventricular nucleus. Small bipolar nerve cells with processes parallel to the surface of the third ventricle occupied a subependymal position. The isodendritic magnocellular neurons of the paraventricular nucleus emitted dendritic processes that reached the basal pole of the ependymal cells. The complex arrangement of the periventricular layer of the paraventricular nucleus might provide the structural basis for the mechanisms of cerebral osmoreception defined by means of physiological parameters.


How to Assess Drug Resistance in Cancer Stem Cells.
Banks of genetically characterized cancer stem cells (CSCs) isolated from individual patients and grown as spheroids offer an invaluable approach to identify genetic determinants of drug resistance versus sensitivity, and to study new stem cell-directed therapies. Here, we describe our standardized procedure for in vitro drug screening on colorectal CSCs, taking irinotecan as an example.


Electron paramagnetic resonance studies of ferric cytochrome c' from photosynthetic bacteria.
Electronic ground nature of ferric cytochromes c' isolated from five photosynthetic bacteria. Chromatium vinosum ATCC 17899, Rhodobacter capsulatus ATCC 11166, Rhodopseudomonas palustris ATCC 17001, Rhodospirillum molischianum ATCC 14031, and Rhodospirillum rubrum ATCC 11170 has been investigated by electron paramagnetic resonance (EPR) spectroscopy. EPR spectra indicate that the electronic ground state of five ferric cytochromes c' is a quantum mechanical admixed-spin state of a high spin (S = 5/2) and an intermediate spin (S = 3/2) at pH 7.2 and is high-spin state at pH 11.0. At physiological pH, however, the content of an intermediate spin state differs with the bacterial source of the protein: approximately 50%, Chromatium vinosum; approximately 40%, Rhodobacter capsulatus and Rhodopseudomonas palustris; approximately 10%, Rhodospirillum molischianum and Rhodospirillum rubrum. Computer simulation of the spectra supports this diversity of the contribution of an intermediate spin state. Model studies of the ferric porphyrin complexes suggest that the correlation between content of an intermediate spin state and heme iron displacement from the mean heme plane. Therefore, the variation of the content of an intermediate spin state observed in the present study reflects the subtle difference in the degree of heme iron displacement among the proteins.


Prevalence and Burden of Illness of Rome IV Chronic Idiopathic Constipation, Opioid-Induced Constipation, and Opioid-Exacerbated Constipation in the United States.
Chronic idiopathic constipation (CIC) and opioid-induced constipation (OIC) are disorders that negatively affect quality of life. We sought to assess the prevalence, symptom severity, and medication use among people with Rome IV CIC, OIC, and opioid-exacerbated constipation (OEC) using a nationally representative data set with nearly 89,000 people in the United States. From May 3, 2020, to June 24, 2020, we recruited a representative sample of people in the United States ≥ 18 years to complete an online national health survey. The survey guided participants through the Rome IV CIC and OIC questionnaires, Patient-Reported Outcome Measurement Information System gastrointestinal scales (percentile 0-100; higher = more severe), and medication questions. Individuals with OEC were identified by asking those with OIC whether they experienced constipation before starting an opioid and whether their symptoms worsened afterward. Among the 88,607 participants, 5,334 (6.0%) had Rome IV CIC, and 1,548 (1.7%) and 335 (0.4%) had Rome IV OIC and OEC, respectively. When compared with people with CIC (Patient-Reported Outcome Measurement Information System score, 53.9 ± 26.5; reference), those with OIC (62.7 ± 28.0; adjusted P < 0.001) and OEC (61.1 ± 25.8, adjusted P = 0.048) had more severe constipation symptoms. People with OIC (odds ratio 2.72, 95% confidence interval 2.04-3.62) and OEC (odds ratio 3.52, 95% confidence interval 2.22-5.59) were also more likely to be taking a prescription medication for their constipation vs those with CIC. In this nationwide US survey, we found that Rome IV CIC is common (6.0%) while Rome IV OIC (1.7%) and OEC (0.4%) are less prevalent. Individuals with OIC and OEC have a higher burden of illness with respect to symptom severity and prescription constipation medication use.


Tetracenomycin X sequesters peptidyl-tRNA during translation of QK motifs.
As antimicrobial resistance threatens our ability to treat common bacterial infections, new antibiotics with limited cross-resistance are urgently needed. In this regard, natural products that target the bacterial ribosome have the potential to be developed into potent drugs through structure-guided design, provided their mechanisms of action are well understood. Here we use inverse toeprinting coupled to next-generation sequencing to show that the aromatic polyketide tetracenomycin X primarily inhibits peptide bond formation between an incoming aminoacyl-tRNA and a terminal Gln-Lys (QK) motif in the nascent polypeptide. Using cryogenic electron microscopy, we reveal that translation inhibition at QK motifs occurs via an unusual mechanism involving sequestration of the 3' adenosine of peptidyl-tRNALys in the drug-occupied nascent polypeptide exit tunnel of the ribosome. Our study provides mechanistic insights into the mode of action of tetracenomycin X on the bacterial ribosome and suggests a path forward for the development of novel aromatic polyketide antibiotics.


Celiac Disease Presenting in a Community-Based Gastroenterology Practice: Obesity and Bone Disease Are Common.
The description of the clinical presentation of celiac disease (CeD) has usually come from studies at referral centers. Data about CeD presentation in the community are sparse. We aim to describe the clinical presentation of patients with biopsy-proven CeD at a community-based adult gastroenterology practice and compare it to a referral center. We performed a retrospective study of two cohorts of patients diagnosed with CeD between 2000-2007 (n = 117) and 2013-2016 (n = 91) in a community practice, and a third cohort (n = 188) diagnosed between 2000 and 2007 in a tertiary referral center. The clinical presentation, body mass index, tissue-transglutaminase levels, DEXA scan, vitamin D levels, and vaccine recommendations were assessed. Celiac disease presentation changed over time in the two community cohorts. Recently, fewer patients presented with diarrhea and anemia, but constipation and neurologic symptoms were more common. The most recent cohort had a higher proportion of patients who were overweight or obese than the first cohort. However, the body mass index in both community cohorts was higher than in the tertiary referral center. The frequency of osteopenia and osteoporosis was high in both community cohorts. The tertiary referral center patients were younger, presented with a higher proportion of diarrhea and a lower body mass index. The clinical presentation of CeD differs between the community setting and a tertiary referral center. Patients with CeD presenting to the community setting tended to be older, overweight, and to have a high proportion of mineral bone disease.


Method development for genomic Legionella pneumophila DNA quantification by inductively coupled plasma mass spectrometry.
The development of a method for the quantification of Legionella pneumophila genomic deoxyribonucleic acid is considered. The method is based on the quantification by inductively coupled plasma mass spectrometry (ICP-MS) of the mass fraction of phosphorus, stoichiometrically presented in the DNA molecules. Through the DNA sequencing data, it was possible to convert the ICP-MS analysis results into DNA genome units. L. pneumophila DNA samples were analyzed using ICP-sector field MS and ICP-quadrupole MS with a collision/reaction cell. Spectrophotometric measurements of the absorbance at 260nm and real-time PCR techniques were used to independently confirm the ICP-MS results. The comparison of the methods showed that the ICP-MS method provides better accuracy with respect to currently applied analytical techniques such as UV spectrophotometry, fluorescent dye methods, and real-time PCR. Moreover, with the use of calibration standards whose values are traceable to the International System of Units and the possibility of evaluating the contribution to the overall uncertainty of each step of the measurement procedure, the method enables long-term comparability of the measurement results. These advantages make the ICP-MS method suitable for nucleic acid investigation, from nucleotides to genomic DNA, as well as for the certification of the reference materials containing nucleic acids.


Functional endoscopic surgery of paranasal fungus ball: clinical outcome, patient benefit and health-related quality of life.
Paranasal fungus ball can cause chronic rhinosinusitis. Removal via functional endoscopic sinus surgery is usually performed; however objective data on the overall benefit and patient satisfaction are very scarce. The study focuses on the clinical outcome and the quality of life following endoscopic surgery due to fungus ball sinusitis. Forty patients diagnosed with fungus ball sinusitis who underwent functional endoscopic surgery were included. Epidemiologic data, pre-, intra- and postoperative findings were recorded. Surgical success, the detailed benefit and the health-related quality of life were objectively assessed 1 year after the surgery based on a standardized questionnaire (modified SNOT 20) and the Glasgow Benefit Inventory. Health-related quality of life improved significantly in >90% of patients (p < 0.05). There were no serious complications or recurrences. As the treatment of choice functional endoscopic sinus surgery of paranasal fungus ball sinusitis is associated with exceptionally high patient satisfaction.


Novel system for real-time ex vivo lactate monitoring in human whole blood.
The objective of the study was to evaluate the performance of an amperometric enzyme based lactate sensor and to investigate the possibility of replacing a double lumen catheter based blood withdrawal system with a heparin coated single lumen system. The inner lumen of a double lumen catheter which was placed in a peripheral vein was perfused with heparin solution. The outer lumen was used to collect heparinized blood samples at a defined flow rate. The single lumen system was attached to a heparinized catheter which was also placed in a peripheral vein. The undiluted blood samples were collected at a specified flow rate. A sensor flow chamber incorporating an amperometric thin-film lactate microbiosensor was placed in the sampling line for real-time lactate monitoring. Plasma lactate concentrations were measured during frequently performed hyperlactatemia bicycle ergometer experiments in six healthy volunteers (age 25.8 +/- 2.8 years, BMI 22.7 +/- 1 kg/m2). Additionally, plasma lactate was measured in real-time using the lactate sensors. The first three experiments were performed with a double lumen based catheter system whereas the following three experiments were performed with a heparin coated catheter system. The correlation coefficients of sensor readings and laboratory analyzer results in all six experiments were between 0.93 and 0.99, respectively (P < 0.001). The miniaturized lactate sensors showed a linear range up to 25 mmol/l lactate concentration and 95% response times < 30 s in undiluted serum. During the experiments maximum lactate concentrations of 14 mmol/l were achieved. Improvements of system performance using heparin coated catheter systems could be shown. The overall SD of the sensor readings compared to laboratory results using three double lumen catheter based systems was 0.91 mmol/l whereas the SD using three heparin coated systems was 0.65 mmol/l. In summary, real-time monitoring of lactate in human whole blood is feasible with such a device and can be improved by using heparin coated catheter systems.


Effects of occupational balance and client-centered occupational management in a patient with schizophrenia.
Occupational balance is an essential element for social participation and quality of life. However, it is difficult for patients with schizophrenia to participate in occupation and achieve occupational balance in daily life due to physical and mental symptoms. This study investigated the form of time use and occupational balance in a schizophrenic patient, and examined the effect of client-centered occupation-based case management. The research was conducted at a private center visited using one-on-one weekly client interactions for 10 weeks from September 1, 2020, and time use was analyzed using the Occupational Questionnaire (OQ) and the 2019 Life Time Survey Table of the National Statistical Office. In addition, data on work performance and satisfaction were collected using Canadian Occupational Performance Measure (COPM), and client-centered occupation-based interventions were conducted. As a result of identifying the balance of work of clients, 38.46% of rest and sleep during the day, 30.77% of IADL, 17.94% of Work, 10.26% of BADL, and 2.57% of leisure. Through occupation-based case management for child care and work, which are the main goals of the client, the COPM score increased on average by 2 or more points per item, showing a positive effect. In order to resolve the occupation imbalance of schizophrenic patients, it is necessary to closely understand the type of time use and actively intervene in client-centered occupation-based interventions. Data pertinent to this report will be made available upon reasonable request to the author.


The study of boron-nitride nanotube behavior as an atomic nano-pump for biomedicine applications.
Complex physical and chemical interactions take place in drug delivery using nanotube structures. Various descriptions of the ultrastructural arrangement to various nanotube design features ranging from geometries to surface modifications on the nano levels have been put forward. In this work, molecular dynamics simulations were applied to understand the boron nitride nanotube (BNNT) performance for drug delivery applications. Here, we have carried out the molecular dynamic (MD) simulation using the Tersoff force field to obtaining optimum performance of BNNT and fullerene molecules for the first time. The result of the equilibrated system accomplished excellent stability of BNNT during MD simulation, which proves the appropriateness of chosen force field. Furthermore, to describe the BNNT nano pumping process, we have calculated the fullerene molecule's velocity and translational/rotational kinetic energy. Numerically, by increasing simulated structures' temperature from 275 to 350 K, the nano pumping time varies from 9.31 to 8.55 ps. Moreover, the outcoming results indicate that atomic wave production in BNNT is an essential parameter for the nano pumping process. Therefore, with the help of the simulation result, we succeed in decreasing the nano pumping time to 7.79 ps by adjusting the nano pumping process parameters. Our study revealed the molecular-level dispersion mechanism of BNNT as a drug delivery tool. Concerning the medical applications of fullerenes as drug molecules, including antiviral activity, antioxidant activity, and drug delivery use, the current study can shed light on the understanding of the dispersion of nanotubes to optimize the process for several biomedical applications.


Deep learning model to quantify left atrium volume on routine non-contrast chest CT and predict adverse outcomes.
Low-dose computed tomography (LDCT) are performed routinely for lung cancer screening. However, a large amount of nonpulmonary data from these scans remains unassessed. We aimed to validate a deep learning model to automatically segment and measure left atrial (LA) volumes from routine NCCT and evaluate prediction of cardiovascular outcomes. We retrospectively evaluated 273 patients (median age 69 years, 55.5% male) who underwent LDCT for lung cancer screening. LA volumes were quantified by three expert cardiothoracic radiologists and a prototype AI algorithm. LA volumes were then indexed to the body surface area (BSA). Expert and AI LA volume index (LAVi) were compared and used to predict cardiovascular outcomes within five years. Logistic regression with appropriate univariate statistics were used for modelling outcomes. There was excellent correlation between AI and expert results with an LAV intraclass correlation of 0.950 (0.936-0.960). Bland-Altman plot demonstrated the AI underestimated LAVi by a mean 5.86 mL/m2. AI-LAVi was associated with new-onset atrial fibrillation (AUC 0.86; OR 1.12, 95% CI 1.08-1.18, p < 0.001), HF hospitalization (AUC 0.90; OR 1.07, 95% CI 1.04-1.13, p < 0.001), and MACCE (AUC 0.68; OR 1.04, 95% CI 1.01-1.07, p = 0.01). This novel deep learning algorithm for automated measurement of LA volume on lung cancer screening scans had excellent agreement with manual quantification. AI-LAVi is significantly associated with increased risk of new-onset atrial fibrillation, HF hospitalization, and major adverse cardiac and cerebrovascular events within 5 years.


Pediatric diabetic ketoacidosis: clinical presentations and nursing considerations.
Pediatric diabetic ketoacidosis is a life-threatening medical condition that requires rapid recognition yet gradual organized treatment. This article discusses the pathophysiology and morbidity of diabetic ketoacidosis and cerebral edema, in addition to treatment and nursing considerations. Three case studies are presented to reintroduce the reader to varying severity of ketoacidosis.


Sensory nerve endings in the anterior cruciate ligament (Lig. cruciatum anterius) of sheep.
This study examines the structure of sensory nerve endings in the sheep anterior cruciate ligament (ACL). Three types of nerve endings are found: free nerve endings (FNE), Ruffini corpuscles, and lamellated corpuscles. The FNE (more than 100) are found subsynovially. The afferent nerve fibres are either thin myelinated axons (Adelta) or C fibres with diameters of 1-2 microm. FNE have been reported to function as thermoreceptors and polymodal nociceptors. In addition, FNE are also seen between fascicles of collagen fibres, often close to blood vessels. Part of this group may be efferent autonomic fibres controlling local blood flow. The corpuscles are seen subsynovially and between fascicles of connective tissue close to the attachment points of the ACL. A ligament contains about 20 Ruffini corpuscles, which are mainly located in the subsynovial connective tissue. They consist of cylinders formed from perineural cells surrounding the afferent myelinated axons (diameters 4-5 microm) with enlarged nerve terminals anchored between collagen fibres. These enter in bundles from the surrounding connective tissue at one open pole, pass through the length of the cylinder, and leave at the other pole. Functionally, Ruffini corpuscles have been described as slowly adapting stretch receptors. Lamellated corpuscles (usually between 5 and 15) are found in the subsynovial connective tissue. The afferent myelinated axon has a diameter of 4-6 microm, and the nerve terminal is located in the centre of numerous layers formed by lamellated terminal glial cells and by a perineural capsule. They are known to function as rapidly adapting pressure receptors. The most important function of the ACL is its mechanical function, but additional sensory functions must be considered triggering reflex mechanisms in case of extreme positioning or overload.


Painless versus painful myocardial ischemia: different left ventricular dysfunction detected by echocardiography.
The mechanism responsible for the absence of anginal pain in patients who have episodes of both painless and painful myocardial ischemia, still remains unknown. Does the pain depend on an overstimulation of receptive structures or is this symptom the product of the excitation of a well-defined receptive system? The aim of this work is to test the first hypothesis: whether silent attacks are accompanied by the same degree of mechanical impairment as symptomatic ones. The authors compared the echocardiographic left ventricular functional behavior in the same patient (6 patients) during painful and painless myocardial ischemia. The echocardiographic changes observed during silent ischemic attacks were significantly different from those detected during symptomatic attacks. The latter were characterized by a larger extension of the ischemic myocardium and, as a consequence, by a larger functional impairment. Symptomatic and asymptomatic ischemic attacks were recorded echocardiographically in the same patient during repeated attacks on the same day, and were always clearly differentiated by the degree of wall motion abnormalities. The echocardiographic monitoring during the ischemic attack seemed to confirm that the greater functional impairment preceded the onset of pain leading to the occurrence of this symptom. Nevertheless, it was impossible to identify a threshold value above which the ischemic attack will be symptomatic. Our data seem to indicate a close relationship between painful ischemia and a higher degree of ischemic damage. Thus, in patients with predominantly painful myocardial ischemia, the extension and the severity of ischemia could play an important role in determining this symptom.