Recruiting Medical Students for a First Responder Project in the Social Age: Direct Contact Still Outperforms Social Media.
Efficient recruitment of first responders (FRs) is crucial for long-term success of any FR project. FRs are laypersons who are trained in cardiopulmonary resuscitation (CPR), medical professionals, and firemen, police officers, and other professions with a duty of help. As social media are widely used for rapid communication, we carried out a prospective observational study to test the hypothesis that recruitment of FRs via social media is more efficient than recruitment via direct face-to-face contact. Following ethics committee agreement, we informed 600 medical students about becoming FRs when they attended a didactic lecture about the FR project or during their mandatory CPR-course. Furthermore, recruitment was opened to medical students through Facebook, which accessed ∼1,000 medical students to see if they expressed interest in becoming FRs. All of the recruited students successfully completed the FR training. We then used an online questionnaire to ask these students how they had been recruited. Out of 63 registered student FRs, 59 responded to the online questionnaire. Overall, 15.3% of these FR students were recruited via social media. The majority (78.0%) were recruited through direct contact. Despite widespread use of social media, over three-quarters of these medical students were recruited to the FR project via direct personal contact. This suggests that the advantage of a larger reachable population using social media does not outweigh the impact of personal contact with experts.


Is frequent religious attendance really conducive to better health? Toward an epidemiology of religion.
Although hundreds of published studies have addressed the effects of religion on morbidity and mortality, many investigators may be unaware of this literature. This paper begins with an analysis of an important subset of these studies--those 27 which operationalize 'religiosity' as religious attendance--and which, taken as a whole, point to a consistent salutary effect for frequent attendance. Upon identifying several pervasive epistemological, methodological, and analytical problems with these studies, however, this paper shows that there is insufficient evidence to conclude that religious attendance is positively and significantly related to health. Nevertheless, the authors present a theoretical basis for expecting such associations. This framework is included in a brief primer on religion for epidemiologists and other sociomedical scientists interested in exploring the health-related effects of religious factors. Finally, a possible scenario for the development of an epidemiology of religion is discussed.


Genetic study of an American family with DYT3 dystonia (lubag).
X-linked dystonia-parkinsonism (XDP, DYT3), endemic in the Philippine island of Panay, is characterized by the clinical onset with dystonia followed by parkinsonism. We found a 35-year-old American male patient, originally from Panay with typical XDP, has a 2-year history of parkinsonism, dystonia, and tremor. Ancestral DYT3 haplotype and disease-specific SVA (short interspersed nuclear element, variable number of tandem repeats, and Alu composite) retrotransposon insertion were identified in the DYT3 proband and two female unaffected family members. No mutation(s) and expression changes in peripheral blood lymphocytes were observed in the TATA-binding protein-associated factor 1 gene (TAF1) or the chemokine CXC motif receptor 3 gene (CXCR3) of the proband or other DYT3 carriers. These findings indicate blood DNA test has a diagnostic utility and implications for genetic counseling in families with DYT3. In contrast, TAF1 and CXCR3 gene expression in peripheral blood lymphocytes is not a suitable surrogate disease marker for DYT3.


Power spectrum and spectrogram of EEG analysis during general anesthesia: Python-based computer programming analysis.
The commonly used principle for measuring the depth of anesthesia involves changes in the frequency components of the electroencephalogram (EEG) under general anesthesia. Therefore, it is essential to construct an effective spectrum and spectrogram to analyze the relationship between the depth of anesthesia and the EEG frequency during general anesthesia. This paper reviews the computer programming techniques for analyzing the spectrum and spectrogram derived from a single-channel EEG recorded during general anesthesia. A periodogram is obtained by repeating a Fourier transform on EEG segments separated by short time intervals, but spectral leakage (i.e., dissociation from the true spectrum) occurs as a consequence of unnatural segmentation and noise. While offsetting the securing of the dynamic range, practical analyses of the adaptation of the window function are explained. Finally, the multitaper method, which can suppress artifacts caused by the edges of the analysis segments, suppress noise, and probabilistically infer values that are close to the real power spectral density, is explained using practical examples of the analysis. All analyses were performed and all graphs plotted using Python under Jupyter Notebook. The analyses demonstrated the effectiveness of Python-based programming under the integrated development environment Jupyter Notebook for constructing an effective spectrum and spectrogram for analyzing the relationship between the depth of anesthesia and EEG frequency analysis in general anesthesia.


Lenalidomide in chronic lymphocytic leukemia: the present and future in the era of tyrosine kinase inhibitors.
Lenalidomide is an immunomodulatory agent (IMiD) clinically active in chronic lymphocytic leukemia (CLL), both in heavily pre-treated patients and upfront. Lenalidomide has a unique mechanism of action in CLL. Its efficacy relies on a multifactorial mode-of-action (MOA), comprising a plethora of immunomodulatory actions, the disruption of mutualistic interactions inside CLL microenvironment and direct effects against leukemic cells. In the last few years, a number of new and highly effective drugs appeared in the scenario of CLL therapeutic options, i.e. tyrosine kinase inhibitors (TKIs), showing a good safety profile and impressive clinical response, also in high-risk patients. In this review, we describe the data from clinical studies about lenalidomide efficacy in CLL and we critically dissect the different mechanisms of action of this drug. We point the attention on open issues, including drug dosage and administration schedule, prediction of clinical response to lenalidomide, and combination therapeutic strategies. This overview would be useful to envision a possible role of lenalidomide in the treatment flow-chart of CLL, exploiting its peculiar MOA and also exploring the possible synergetic effect with new drugs.


Developmental changes of amniotic fluid alpha-fetoprotein subfractions in early gestation.
Using both concanavalin A crossed-line affinity immunoelectrophoresis and lentil lectin crossed-line affinity immunoelectrophoresis, developmental changes of alpha-fetoprotein (AFP) subfractions were studied in 11 samples of human amniotic fluid obtained between 43 and 121 days of gestation. In the amniotic fluid at 43 or 48 days of gestation, only subfractions produced by the yolk sac were evident. The initial appearance of the subfractions produced by the fetal liver was first detected at 51 days of gestation. Percentages of liver-originated subfractions rose rapidly with gestational age and reached a level of 50% at 54 days of gestation. The subfractions produced by the yolk sac disappeared from the amniotic fluid at 121 days of gestation. These findings suggest that, in early gestation, the yolk sac is mainly responsible for the fetal AFP synthesis and that initiation of AFP production by the fetal liver takes place between 48 and 51 days of gestation. In the present study, attention was also given to the origin of four subfractions separated by the lentil lectin crossed-line affinity immunoelectrophoresis.


Effect of adrenalectomy on chlordecone potentiation of carbontetrachloride hepatotoxicity.
The propensity of chlordecone (CD) to potentiate CCl4 hepatotoxicity in rats of either sex has been well documented. The objective of the present study was to investigate the hepatotoxic effects of CD-CCl4 interaction in adrenalectomized rats. Adrenalectomized rats were maintained on 0 or 10 ppm CD and on day 15 they received a single ip injection of 25 microL CCl4/kg. Hepatotoxicity was assessed by hepatofunctional, biochemical and histopathological parameters, 24 hrs after CCl4 challenge. CCl4-induced hepatobiliary dysfunction and elevation of serum enzymes (GPT, GOT, ICD and OCT) were evident. Hepatic dysfunction was most severe in adrenalectomized rats receiving CD-CCl4 combination treatment. Histopathology of liver exhibited extensive fatty infiltration in the entire lobular structure accompanied by some necrosis. These data indicate that the capacity of CD to potentiate CCl4 hepatotoxicity is unaffected in adrenalectomized rats.


Multi-spatial scale effects of multidimensional landscape pattern on stream water nitrogen pollution in a subtropical agricultural watershed.
Multidimensional (coupled land use, soil properties, and topography) landscape effects on stream water nitrogen (N) are complex and scale-dependent. However, studies that identify critical buffer zones that explain large variations in riverine N, and estimate specific thresholds of multidimensional landscape patterns at the class level, result in a sudden changes in riverine N pollution, are still limited. Here, a new multidimensional landscape metric that combined land use, soil properties, and topography effects was applied to various riparian buffer zones and sub-watershed scales, and their relationships to riverine N levels were investigated. We used stream water ammonium-N, nitrate-N, and total-N concentrations datasets, from 2010 to 2017, in the nine subtropical sub-watersheds in China. The results of model selection and model averaging in ordinary least squares regressions, indicated that the riparian buffer zone with widths of 400 m, had more pronounced influence on water NH4-N and TN levels than at other scales. Within the 400 m buffer zone, the key landscape metrics for NH4-N, NO3-N and TN concentrations in stream water were different, and explained up to 43.35%-76.55% (adjusted R2) of the total variation in river N levels. When ENN_MNClass17 below 39-56 m, PDClass8 above 4.63-6.55 n/km2, PLANDClass27 above 23-29%, and CONTIG_MNClass42 below 0.35-0.37% within the 400 m buffer zone, riverine NH4-N and TN would be abruptly increased. This study provided practical ideas for regulation regarding landscape management linked to watershed structure, and identified reference thresholds for multidimensional landscape metrics, which should help reduce riverine N pollution in subtropical China.


5,10-methylenetetrahydrofolate reductase C677T gene polymorphism and peripheral arterial disease: A meta-analysis.
Peripheral arterial disease is one common vascular disease most caused by atherosclerosis. As with stroke and coronary heart disease, peripheral arterial disease is one clinical type of atherosclerotic cardiovascular disease with many unmeasured environmental and genetic components. MTHFR C677T polymorphism is associated with the increased risk of ischemic stroke and coronary heart disease. MTHFR C677T polymorphism is associated with decreasing enzyme activity and increasing homocysteine levels. Meta-analysis of studies had demonstrated an association between elevated plasma homocysteine levels and peripheral arterial disease. Elevated plasma homocysteine level is closely related to MTHFR C677T polymorphism. Recent studies had clarified the relationship of MTHFR C677T polymorphism and peripheral arterial disease. So we performed a meta-analysis to investigate the association between MTHFR C677T polymorphism and peripheral arterial disease. We searched the database PubMed, Embase, and Cochrane Library for all English-language articles related to peripheral arterial disease and MTHFR C677T through 30 June 2020. Analysis results were shown by forest plot. Publication bias was estimated using funnel plot. A total of 15 studies comprising 1929 patients with peripheral arterial disease and 2952 healthy controls were included in the meta-analysis. Significant associations between MTHFR C677T genetic polymorphism and peripheral arterial disease were found (OR = 1.31, 95% CI: 1.09-1.58, P <0.01). But there was no significant association (poor OR = 1.11, 95% CI: 0.98-1.26, P =0.11) between the T allele carrier and peripheral arterial disease. Our meta-analysis suggested that MTHFR C677T genetic polymorphism TT genotype may be associated with increased peripheral arterial disease risk. But further studies with large sample sizes are needed to confirm our findings.


Safety evaluation and fluorine concentration of Pu'er brick tea and Bianxiao brick tea.
Pu'er brick tea and Bianxiao brick tea are both compressed types of tea. Fluorine analysis was carried out on samples of Pu'er brick tea produced at different times in Yunnan Province and on samples of Bianxiao brick tea made in Hunan and Sichuan Province for supply especially to minority ethnic groups in border areas of China. The levels of water-soluble and water-insoluble fluorine were measured in the tea samples using an ion-specific electrode potentiometer. The concentration of water-soluble fluorine was much greater in Bianxiao brick tea than in Pu'er brick tea (mean levels 441 and 77 mg/kg, respectively). According to these figures, the fluorine intake associated with consuming an infusion of 30 g Pu'er brick tea/person/day is safe because it does not exceed the maximum recommended daily allowance (RDA) of up to 4.0 mg for adults. In contrast, the almost six times higher intake of fluorine from Bianxiao brick tea greatly exceeds the 4 mg RDA and is unsafe. The difference in the fluorine levels of the two types of brick tea can be attributed to differences in the materials used to make them: Pu'er brick tea is made from tender leaves whereas Bianxiao brick tea is made from old tough leaves in which fluorine has accumulated. We conclude that consumption of Pu'er brick tea is unlikely to induce fluorosis, which has been associated with consumption of Bianxiao brick tea.


Glucagon-like peptide 1-potentiated insulin secretion and proliferation of pancreatic β-cells.
Glucagon-like peptide-1 (GLP-1) is the primary incretin hormone secreted from the intestine upon uptake of food to stimulate insulin secretion from pancreatic β-cells. GLP-1 exerts its effects by binding to its G-protein coupled receptors and subsequently activating adenylate cyclase, leading to generation of cyclic adenosine monophosphate (cAMP). cAMP stimulates insulin secretion via activation of its effectors PKA and Epac2 in pancreatic β-cells. In addition to its insulinotropic effects, GLP-1 also preserves pancreatic β-cell mass by stimulating β-cell proliferation. Unlike the action of sulphonylureas in lowering blood glucose levels, action of GLP-1 is affected by and interplays with glucose levels. Due to such advantages, GLP-1-based therapeutics have been rapidly developed and used clinically for treatment of type 2 diabetes. However, molecular mechanisms underlying how GLP-1 potentiates diminished glucose-stimulated insulin secretion and β-cell proliferation under diabetic conditions are not well understood. Here, we review the actions of GLP-1 in regulation of insulin secretion and pancreatic β-cell proliferation.


Carcinogenesis from the standpoint of view of molecular geometry and synergism: relevance of oxygen and magnesium.
An attempt at a unified explanation of carcinogenesis, comprising physical, chemical and viral agents which are mutually synergistic involves the idea that continually replicated partially denatured chromosomal DNA carries the cancer genetic information. The evidence is circumstantial to date. While interactions and reactions of various heterogeneous chemical agents and absorption of radiant energy are detrimental to the helicity of the DNA, the interactions of magnesium and oxygen seem to be beneficial and thus may protect against cancer. Mechanisms for the damaging effects of various carcinogenic agents as well as for the protective effects of magnesium and oxygen are proposed. The increasing probability of cancer with age could be due to the cumulative actions of diverse carcinogenic agents. Some experimental results in vitro which are relevant to this hypothesis are discussed.


[Surgical technics indicated for spontaneous pneumothorax. Personal experience in 266 operations].
The surgical techniques best suited for timely management of spontaneous pneumothorax are described. Results in 266 cases are discussed and compared with the recent literature. Reference is also made to a little known technique: photothermostimulation, and the results it offers are illustrated. Encouraging results have been obtained from rapid frottage of the parietal pleura and this is described. Emphasis is placed on the advisability of early operation to forestall possible surgical and anatomofunctional complications, to ensure good recovery of respiratory capacity, and to prevent mechanical sequelae involving the cardiorespiratory system.


A long-term high-fat diet increases oxidative stress, mitochondrial damage and apoptosis in the inner ear of D-galactose-induced aging rats.
In humans, chronic dyslipidemia associated with elevated triglycerides may reduce auditory function. However, there is little evidence available in the literature concerning the effects of a long-term high-fat diet (HFD) on the inner ears of animals. The purpose of this study was to investigate the effect of 12 month-HFD on the inner ear of Sprague-Dawley rats and on the D-galactose (D-gal)-induced aging process in the inner ear. We found that 12 month-HFD markedly elevated the auditory brainstem response (ABR) threshold in the high-frequency region. The HFD significantly increased the generation of reactive oxygen species (ROS) and the expressions of NADPH oxidase (NOX) and the uncoupling proteins (UCP). Furthermore, an elevated accumulation of the mitochondrial DNA (mtDNA) common deletion (CD) and mitochondrial ultrastructural changes in the inner ear suggested that there was mitochondrial damage in response to the excessive fat intake. The expression level of cleaved caspase-3 and the number of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labelling (TUNEL)-positive cells in the inner ear were increased by the HFD. The effects of D-gal on the inner ears were similar with 12 month-HFD. We found that rats receiving both the HFD and D-gal exhibited a greater shift in the ABR threshold, larger increases in the expression levels of NOX, UCP and cleaved caspase-3 and an increased number of TUNEL-positive cells in the inner ear. The present study demonstrated that HFD may induce oxidative stress, mitochondrial damage and apoptosis in the inner ear, and it provided evidence regarding the link between HFD and an increased risk of age-related hearing loss.


A standardized protocol for manually segmenting stroke lesions on high-resolution T1-weighted MR images.
Although automated methods for stroke lesion segmentation exist, many researchers still rely on manual segmentation as the gold standard. Our detailed, standardized protocol for stroke lesion tracing on high-resolution 3D T1-weighted (T1w) magnetic resonance imaging (MRI) has been used to trace over 1,300 stroke MRI. In the current study, we describe the protocol, including a step-by-step method utilized for training multiple individuals to trace lesions ("tracers") in a consistent manner and suggestions for distinguishing between lesioned and non-lesioned areas in stroke brains. Inter-rater and intra-rater reliability were calculated across six tracers trained using our protocol, resulting in an average intraclass correlation of 0.98 and 0.99, respectively, as well as a Dice similarity coefficient of 0.727 and 0.839, respectively. This protocol provides a standardized guideline for researchers performing manual lesion segmentation in stroke T1-weighted MRI, with detailed methods to promote reproducibility in stroke research.


Mesenchymal-like stem cells in canine ovary show high differentiation potential.
Recent studies have reported the existence of stem cells in ovarian tissue that show enhanced proliferative and differentiation potential compared to other adult tissues. Based on this evidence, we hypothesized that ovarian tissue contained mesenchymal-like stem cells (MSC) that could be isolated using a novel rapid plastic adhesion technique. We established MSC lines derived from ovarian and adipose tissue based on their ability to rapidly adhere to plastic culture dishes in the first 3 hours after plating and studied their potentiality in terms of molecular markers and differentiation capacity. Morphological and kinetic properties of in vitro cultured ovarian MSC were similar to adipose-derived MSC, and both reached senescence after similar passage numbers. Ovarian-derived MSC expressed mesenchymal (CD90 and CD44) but not haematopoietic markers (CD34 and CD45), indicating similarity to adipose-derived MSC. Moreover, ovarian-derived MSC expressed NANOG, TERT, SOX2, OCT4 and showed extensive capacity to differentiate not only into adipogenic, osteogenic and chondrogenic tissue but also towards neurogenic and endodermal lineages and even precursors of primordial germ cells. These results show for the first time the derivation of ovarian cells with the molecular properties of MSC as well as wide differentiation potential. Canine ovarian tissue is accessible, expandable, multipotent and has high plasticity, holding promise for applications in regenerative medicine.


Inhibition of blood-brain barrier permeability to DL-propranolol by serum from acute renal failure rats.
The effect of uranyl nitrate-induced acute renal failure on the brain uptake of DL-propranolol was investigated in rats with a series of tissue-sampling single-carotid injection techniques. When the buffer solution was used as an injection solution, the brain uptake index (BUI), the extraction ratio (ET), and the blood-brain barrier (BBB) permeability-surface area product (PSapp) and PSu (corrected PSapp for the unbound fraction) in uremic rats were significantly lower than those in control rats. These parameters for DL-propranolol were decreased significantly in both control and uremic rats receiving injection of the uremic serum. The PSu values in both of the control and uremic rats injected with either control or uremic rat serum were significantly higher than those in rats injected with the buffer solution, suggesting the presence of a protein-mediated transport mechanism; that is, the conventional assumption that the fraction of the drug which is available for the uptake in vivo is equal to the unbound fraction as measured in vitro may not hold. In contrast, the brain extraction of D-[14C]glucose, [3H]inulin and [3H]water, which show no binding to serum protein, was not affected by the coinjection of either control or uremic rat serum. On the other hand, using either the ultrafiltrate from serum (control and uremic) or supernatant fraction from heat-treated serum (control and uremic) as the injection solution, no significant difference in the PSu value for DL-propranolol was observed between control and uremic serum. These results suggest that (1) the decrease in the PSu value for DL-propranolol in uremic rats may be attributed mainly to the presence of an endogenous inhibitory substance(s) for the brain uptake or to the decrease in the exchangeable fraction in vivo in the uremic serum; (2) the decrease in the PSu value for DL-propranolol may also be partly attributed to the change in the BBB permeability and/or surface area; (3) the inhibitor for the brain uptake may be characterized as a temperature-sensitive and nonfiltrable substance(s) at physiological pH; and (4) the ability of protein-mediated transport for DL-propranolol into brain was decreased in uremic rats.


Isolation of Coxiella burnetii from serum of patients with acute Q fever.
Worldwide there are few isolate collections of the intracellular bacterium Coxiella burnetii, due to the difficulties associated with working with the organism and the scarcity of suitable samples from which to attempt isolation. Particularly lacking are isolates from acute Q fever patients. The aim of this study was to evaluate whether the serum samples taken from patients with confirmed acute Q fever during the early stage of their disease represented a potential source of viable C. burnetii. Isolation was attempted from 65 of these samples by inoculation of the serum into Vero cell culture and was successful in 36 cases (55%). This high success rate was likely due to extended incubation of up to twelve weeks of the inoculated cultures, allowing the growth of the organism to levels detectable by PCR. Retrospective analysis of the time the sera was stored prior to inoculation into culture demonstrated that C. burnetii remained viable for 224 days in samples stored refrigerated and 371 days in samples stored frozen at -20 °C. These results demonstrate that standard serum samples taken from acute Q fever patients are a valuable source of new isolates of C. burnetii, with no special handling of the specimens required to maintain the organism's viability.


Volatile-Mediated Induced and Passively Acquired Resistance in Sagebrush (Artemisia tridentata).
Plants produce a diversity of secondary metabolites including volatile organic compounds. Some species show discrete variation in these volatile compounds such that individuals within a population can be grouped into distinct chemotypes. A few studies reported that volatile-mediated induced resistance is more effective between plants belonging to the same chemotype and that chemotypes are heritable. The authors concluded that the ability of plants to differentially respond to cues from related individuals that share the same chemotype is a form of kin recognition. These studies assumed plants were actively responding but did not test the mechanism of resistance. A similar result was possible through the passive adsorption and reemission of repellent or toxic VOCs by plants exposed to damage-induced plant volatiles (DIPVs). Here we conducted exposure experiments with five chemotypes of sagebrush in growth chambers; undamaged receiver plants were exposed to either filtered air or DIPVs from mechanically wounded branches. Receiver plants exposed to DIPVs experienced less herbivore damage, which was correlated with increased expression of genes involved in plant defense as well as increased emission of repellent VOCs. Plants belonging to two of the five chemotypes exhibited stronger resistance when exposed to DIPVs from plants of the same chemotypes compared to when DIPVs were from plants of a different chemotype. Moreover, some plants passively absorbed DIPVs and reemitted them, potentially conferring associational resistance. These findings support previous work demonstrating that sagebrush plants actively responded to alarm cues and that the strength of their response was dependent on the chemotypes of the plants involved. This study provides further support for kin recognition in plants but also identified volatile-mediated associational resistance as a passively acquired additional defense mechanism in sagebrush.


MiR-1 and miR-200 inhibit EMT via Slug-dependent and tumorigenesis via Slug-independent mechanisms.
Epithelial-mesenchymal transition (EMT) is a developmental program of signaling pathways that determine commitment to epithelial and mesenchymal phenotypes. In the prostate, EMT processes have been implicated in benign prostatic hyperplasia and prostate cancer progression. In a model of Pten- and TP53-null prostate adenocarcinoma that progresses via transforming growth factor β-induced EMT, mesenchymal transformation is characterized by plasticity, leading to various mesenchymal lineages and the production of bone. Here we show that SLUG is a major regulator of mesenchymal differentiation. As microRNAs (miRs) are pleiotropic regulators of differentiation and tumorigenesis, we evaluated miR expression associated with tumorigenesis and EMT. Mir-1 and miR-200 were reduced with progression of prostate adenocarcinoma, and we identify Slug as one of the phylogenetically conserved targets of these miRs. We demonstrate that SLUG is a direct repressor of miR-1 and miR-200 transcription. Thus, SLUG and miR-1/miR-200 act in a self-reinforcing regulatory loop, leading to amplification of EMT. Depletion of Slug inhibited EMT during tumorigenesis, whereas forced expression of miR-1 or miR-200 inhibited both EMT and tumorigenesis in human and mouse model systems. Various miR targets were analyzed, and our findings suggest that miR-1 has roles in regulating EMT and mesenchymal differentiation through Slug and functions in tumor-suppressive programs by regulating additional targets.


Validity of a selective policy for ultrasound examination of fetal congenital anomalies.
The validity of the Stage II ultrasound examination for fetal congenital anomalies has been determined. Only pregnancies that fulfilled certain criteria, i.e. obstetric complications (IUGR, polyhydramnios, immature-premature uterus contractions), or women with a history of congenital anomalies qualified. Five hundred and fifteen pregnant women were examined. Follow-up evaluation was available on 481 pregnancies (494 neonates). Of these children 102 (21%) appeared to have one or more structural anomaly following birth. In 88 of them at least one congenital anomaly had been detected antenatally by the Stage II ultrasound examination. The sensitivity of the ultrasound scanning procedure was 86%, the specificity 100%. The validity of the applied selection criteria for the Stage II ultrasound examination was studied in 2059 women who had delivered consecutively in our hospital. One hundred and eighty-one had the Stage II ultrasound examination performed. Thirty-six of these 181 women delivered an infant with a structural anomaly (20.0%). The remaining 1878 did not qualify for the Stage II ultrasound examination. From these pregnancies 24 infants were born with a structural anomaly (1.3%). The sensitivity of the applied selection criteria was 60% and the specificity 93%. The incidence of congenital anomalies was strikingly higher in pregnancies scanned for reasons of obstetric complications than in the pregnancies scanned for a history of congenital anomalies. The necessity of the Stage II ultrasound examination in every pregnancy is questioned on the basis of the results.


Release of prostaglandins E and F from rat uterine strips incubated in depolarizing and hyperpolarizing solutions.
The purpose of this study was investigate the effect of depolarizing (high K+, procaine 5 mM, high K+-Ca2+ free) or hyperpolarizing (K+ free) solutions on the generation and release of prostaglandins (PGs) E and F from the rat uterus. The output of PGs in the bathing solution was measured by bioassay. Results are expressed as ng/g dry weight/min. Under basal conditions in Krebs Ringer Bicarbonate medium, the total output of PGs (E + F) was 12.8 +/- 0.9, 20.5 +/- 2.5 and 39.1 +/- 4.3 ng/dw/min at 0-60, 60-80, 80-100 min intervals respectively, the major proportion being PGF like material in all cases. When the strips were bathed in depolarizing solution the total output increased significantly PGE being the most augmented. However, when K+ free solution was used there was a marked reduction in prostaglandins release as compared with basal conditions or depolarizing media. These results can not be attributed to osmotic effect, muscular work or neurotransmitter release from nerve endings. A close relationship between the variations in membrane potential and prostaglandins release seems to indicate that both parameters might correlate well.


Electrocardiographic abnormalities in patients with pericardial disease--Association of PR segment depression with arrhythmias and clinical signs: Experience of cardiac surgery center.
We aimed to describe clinical, morphological, intraoperative, echocardiographic and electrocardiographic (ECG) associations of PR segment depression (PRsd), as well as its relationship with arrhythmias and outcomes in pericardial diseases (PD). Overall, 79 patients among 197 patients with PD, referred to cardiac surgery center for treatment, were eligible for inclusion in the study. ECGs were analyzed for presence of PRsd, abnormal P-wave, low voltage QRS, QRS alternans, STj deviation and arrhythmias. We analyzed patients' clinical, echocardiographic and intraoperative data, as well as arrhythmias and outcomes (death, rehospitalization, heart failure). Overall 45.5% of patients with PD had signs of PRsd. PRsd was associated with elevated markers of inflammation, purulent content of pericardial fluid, extent of effusion and pericardial calcification, signs of constriction and tamponade. We also observed significant association of PRsd with ECG abnormalities--STj changes, notched P-wave, low voltage QRS and QRS alternans, as well as arrhythmias. Overall, 30.6% of patients with PRsd had unfavorable composite outcome as compared to 7% in patients without PRsd (p=0.006). Logistic regression analysis results demonstrated compression (tamponade or constriction) (OR 14.93, 95% CI 2.71-82.0, p=0.002), inflammation (OR -11.42, 95% CI 2.16-60.35, p=0.004) and notched P-wave (OR -5.27, 95% CI 1.32-20.99, p=0.018) as independent predictors of PRsd. The model allowed predicting presence of PRsd in 80% of cases. PRsd in patients with PD is associated with signs of inflammation, diffuse effusion and calcification, and compression (tamponade and constriction), arrhythmias and unfavorable outcomes. The independent predictors of PR segment depression are signs of compression, inflammation and notched P-wave.


Effect of biological, psychological, and social factors on maternal depressive symptoms in late pregnancy: a cross-sectional study.
Depression commonly occurs during pregnancy and has become a major public health concern. Depression not only affects the individual but also causes adverse consequences for families and children. However, little is known regarding the depression status and its influencing factors in women during late pregnancy in China. This study aimed to assess the prevalence of maternal depressive symptoms in late pregnancy during the coronavirus disease 2019 (COVID-19) pandemic and further explore the effect of biological, psychological, and social factors on depressive symptoms. An institution-based cross-sectional survey was conducted among eligible women in the late pregnancy stage and underwent prenatal examination at Lianyungang Maternal and Child Health Hospital in Jiangsu Province, Eastern China from December 2022 to February 2023. Data regarding depressive symptoms and biological, psychological, and social factors of the pregnant women were collected via a structured questionnaire. Chi-square test, Fisher's exact tests, and binary logistics regression were used to analyze the data. In total, 535 women in the late pregnancy stage were included in this study, 75 (14.0%) of whom exhibited depressive symptoms. A binary logistic regression analysis revealed that pregnant women who were multiparous (OR: 2.420, 95% CI: 1.188-4.932) and had moderate or severe insomnia symptoms (OR: 4.641, 95% CI: 1.787-12.057), anxiety (OR: 8.879, 95% CI: 4.387-17.971), high fear of COVID-19 (OR: 2.555, 95% CI: 1.255-5.199), moderate or severe family dysfunction (OR: 2.256, 95% CI: 1.141-4.461), and poor social support (OR: 2.580, 95% CI: 1.050-6.337) tended to show depressive symptoms. Conversely, pregnant women who received regular prenatal care (OR: 0.481, 95% CI: 0.243-0.951) and had good drinking water quality at home (OR: 0.493, 95% CI: 0.247-0.984) were more likely to avoid developing depressive symptoms. This study found that the prevalence of maternal depressive symptoms during late pregnancy was high and had multiple influencing factors. Thus, screening for depressive symptoms in women in the late pregnancy stage and providing special intervention programs are necessary, especially for those with risk factors.


What do patients know about anesthesiologists? Results of a comparative survey in an U.S., Australian, and German university hospital.
To determine patients' knowledge of the role of the anesthesiologist in the hospital. Prospective survey instrument. Three university hospitals (University of Virginia, Charlottesville, VA, USA; St. George Hospital University of New South Wales, Sydney, Australia; and University Hospital, Ruhr-University Bochum, Bochum, Germany). 900 patients (300 pts per center) undergoing elective surgery. Patients completed a standardized questionnaire before surgery and before speaking to an anesthesiologist. Most patients knew that anesthesiologists were medical doctors (Charlottesville, 58%; Bochum, 83%; Sydney, 71%). The majority (> 75%) underestimated the amount of training required to become anesthesiologist. While patients recognized the role of anesthesiologists in keeping patients asleep and awakening them, many patients did not understand the anesthesiologists' role in treating intraoperative medical problems. Patients had diverse concerns including infection, awakening during surgery, and failure to awaken, although patients were unclear about who was responsible for treating these issues. Outside the operating room (OR), 71% of patients rated Intensive Care Unit treatment as a duty of the anesthesiologist in Bochum, but fewer (P < 0.05) did so from Charlottesville (42%) and Sydney (49%). Understanding of duties outside the OR (resuscitation, teaching medical students, or chronic pain treatment) was very low (< 50%) in all centers. Patients underestimated the training and role of the anesthesiologist in the OR and hospital.


Influence of phenobarbital and diphenylhydantoin on the healing of rickets in the rat.
Male weanling Sprague-Dawley rats were administered phenobarbital or diphenylhydantoin (phenytoin, dilantin, DPH), or a combination of the two drugs, while receiving a high calcium, low phosphorus vitamin D-deficient diet. A Line Test evaluation for calcification of the distal end of the radius was performed to determine the presence of rickets and the healing of the disease. After a period of 16 days, rickets had developed in a uniform manner in all groups regardless of drug treatment. Four I.U. of vitamin D3 were then administered to each animal and they were sacrificed either 3 or 9 days later. Three days after the administration of D3, bone calcification had started in all groups, with the greatest response being observed in the control group. Nine days after D3 administration, bone calcification was clearly impaired in PB and PB-DPH treated animals and slightly impaired in the DPH treated group when compared to controls. Weight gain was also impaired after PB and combined PB-DPH treatments. Based on these observations, it is suggested that anticonvulsant drugs, and in particular PB, inhibit, in a yet undetermined fashion, the normal calcification of the growth cartilage which accompanies a single physiological dose of cholecalciferol in the rat.


Impact of Size and Location of Metastases on Early Tumor Shrinkage and Depth of Response in Patients With Metastatic Colorectal Cancer: Subgroup Findings of the Randomized, Open-Label Phase 3 Trial FIRE-3/AIO KRK-0306.
The Response Evaluation Criteria in Solid Tumors (RECIST) are used to define degrees of response to chemotherapy. For accelerated response evaluation, early tumor shrinkage (ETS) of ≥ 20% has been suggested as a predictor for outcome in metastatic colorectal cancer (mCRC). Together with depth of response (DpR), new alternative metrics have been provided, yielding promising outcome parameters. In this analysis, we aimed to further characterize ETS and DpR. This analysis was based on FIRE-3, a randomized phase 3 trial comparing first-line FOLFIRI plus either cetuximab or bevacizumab in KRAS exon 2 wild-type mCRC. ETS and DpR were determined on the basis of RECIST 1.1 in a blinded radiologic review. ETS was evaluated as a categorized (≥ 20% shrinkage) and continuous parameter. The impact of baseline location and size of metastases on ETS and DpR were evaluated by univariate and multivariate analyses. Of 592 patients, 395 (66.7%) had data available for radiologic review. Median continuous ETS for lung, liver, and suspected lymph node metastases was 20%, 23%, and 30%, respectively. The median DpR was -32%, -44%, and -50%, respectively (all P < .01). In multivariate analysis, lung metastases were significantly associated with inferior DpR (P = .021), whereas hepatic metastases led to higher DpR (P = .024). Large metastases were associated with favorable ETS, whereas small metastases were correlated with higher DpR (P < .001). ETS and DpR depend on the location and size of metastases in mCRC. These associations may establish the basis for further research to optimize the predictive accuracy of both parameters. This may help basing treatment decisions on ETS and DpR.


Ultra-high dose rate dosimetry for pre-clinical experiments with mm-small proton fields.
To characterize an experimental setup for ultra-high dose rate (UHDR) proton irradiations, and to address the challenges of dosimetry in millimetre-small pencil proton beams. At the PSI Gantry 1, high-energy transmission pencil beams can be delivered to biological samples and detectors up to a maximum local dose rate of ∼9000 Gy/s. In the presented setup, a Faraday cup is used to measure the delivered number of protons up to ultra-high dose rates. The response of transmission ion-chambers, as well as of different field detectors, was characterized over a wide range of dose rates using the Faraday cup as reference. The reproducibility of the delivered proton charge was better than 1 % in the proposed experimental setup. EBT3 films, Al2O3:C optically stimulated luminescence detectors and a PTW microDiamond were used to validate the predicted dose. Transmission ionization chambers showed significant volume ion-recombination (>30 % in the tested conditions) which can be parametrized as a function of the maximum proton current density. Over the considered range, EBT3 films, inorganic scintillator-based screens and the PTW microDiamond were demonstrated to be dose rate independent within ±3 %, ±1.8 % and ±1 %, respectively. Faraday cups are versatile dosimetry instruments that can be used for dose estimation, field detector characterization and on-line dose verification for pre-clinical experiments in UHDR proton pencil beams. Among the tested detectors, the commercial PTW microDiamond was found to be a suitable option to measure real time the dosimetric properties of narrow pencil proton beams for dose rates up to 2.2 kGy/s.


Influence of age and of desmotropic drugs on the step phenomenon observed in rat skin.
Comprehensive analysis of the mechanical properties of rat skin revealed the "step phenomenon". This particular observation was made after constant strain rate (analysis of stress strain curves) as well as after constant load (creep experiments). Relative low extensions or low loads were necessary to provoke the steps. In most cases two, sometimes three steps were observed. The step phenomenon was found mainly in skin strips punched out perpendicularly to the body axis. Probably some bonds in the fibrous network are broken giving way to additional elongation whereafter stronger links take over the stress. Since earlier studies demonstrated a pronounced influence of age and of desmotropic drugs on mechanical properties at ultimate load, e.g., tensile strength, ultimate modulus of elasticity, and ultimate strain, also the step phenomenon was studied under these conditions. In stress-strain experiments most of the steps were found at the ages of 2 and 4 months. Total stress loss and total work loss due to the steps were the highest at the age of 4 months. If, however, these values were calculated as percentage of ultimate values, the highest figures were found in young animals. Elongation gain due to the steps also showed a maximum at time of maturation, e.g., 4 months. Similar findings were achieved in creep experiments at medium load (200 g). After treatment with prednisolone acetate more steps and after treatment with D-penicillamine fewer steps were observed. In stress-strain experiments total stress loss and total work loss due to steps were more than twice as high than controls after prednisolone treatment and only one half after D-penicillamine. If calculated as percentage of ultimate stress or percentage of work input, these changes disappeared because of similar changes at ultimate load. However, elongation gain due to steps, which was not significantly influenced by prednisolone acetate but significantly decreased by D-penicillamine, showed the same changes when calculated as percentage of ultimate strain. Under all conditions the step phenomenon mainly influenced the extension parameters. The data presented here confirm earlier observations that mechanical properties at low loads or low and medium extensions show at least to some extent a different pattern under the influence of maturation and age and after treatment with desmotropic drugs compared to the mechanical parameters at ultimate load.


Highly selective and sensitive gold nanoparticle-based colorimetric assay for PO₄³⁻ in aqueous solution.
A rapid, simple and real-time colorimetric assay for detecting phosphate anions (PO₄(3-)) in aqueous solution was developed. The method was based on a novel functionalized gold nanoparticles (MPTP-Zn-AuNPs), which was synthesized by the ligand-exchange reaction of 4'-(4-mercaptophenyl)-2,2':6',2″-terpyridine zinc(II) complex (MPTP-Zn) with citrate-stabilized aqueous AuNPs. The strong coordination between MPTP-Zn-AuNPs and PO₄(3-) anion gave rise to a color change from wine-red to blue-gray that was discernible by the naked eye and an easily measurable alteration in the absorption spectrum of the particles in aqueous solution. And the new technique exhibited the high selectivity for PO₄(3-) over 11 other anions and could be used to determine PO₄(3-) with a detection limit of 11 ppm.


Leptin, reproduction and sex steroids.
Leptin is a hormone secreted mainly by the adipose cells with a primary role in the regulation of body weight by establishing a feedback loop between the energy reserves and the hypothalamic centers that control food intake. Recent data suggest that, in addition, leptin interacts with other endocrine systems to provide critical information about the size of the fat stores, acting as a permissive factor that allows the triggering of energy-demanding situations, as the onset of puberty and the reproduction, only when the size of the fuel reserve is large enough to guarantee its success. In addition, leptin appears to play a role during pregnancy and lactation, as it is produced by the placenta and is present in maternal milk. The fact that leptin levels are always higher in females, even after correcting for body fat content, suggests that the interaction between the adipose tissue and the reproductive system is modulated in a different way in males and females by androgenic and estrogenic hormones. In fact, adipose tissue samples taken from male donors are completely refractory in vitro to the action of both estrogens and androgens. On the contrary, dihydrotestosterone, androstenedione and dehydroepiandrosterone-S are potent inhibitors of leptin secretion, while estradiol induces a strong stimulation in adipose tissue taken from women. Testosterone is devoid of activity in either gender.


External Validity of Randomised Controlled Trials on Carotid Revascularisation: Trial Populations May Not Always Reflect Patients in Clinical Practice.
The external validity of randomised controlled trials (RCTs) and their transferability to clinical practice is under investigated. This study aimed to analyse the exclusion criteria of recent carotid RCTs comparing carotid endarterectomy (CEA) and carotid artery stenting, and to assess the eligibility of consecutive clinical practice cohorts to those RCTs. An analysis of the clinical and anatomical exclusion criteria of RCTs for asymptomatic (SPACE-2, ACST-2, CREST-1, and CREST-2) and symptomatic carotid stenosis (SPACE-1, CREST-1, ICSS, and EVA-3S) was performed. Two hundred consecutive asymptomatic and 200 consecutive symptomatic patients, treated by CEA, or transfemoral or transcarotid artery stenting at a tertiary referral university centre were assessed for their potential eligibility for each corresponding RCT. RCT patient data were pooled and differences from the clinical practice cohort analysed. Statistics were descriptive and comparative using Fisher's exact and t tests. The number of clinical and anatomical exclusion criteria differed widely between RCTs. Potential eligibility rates of the clinical practice cohort for RCTs with regard to asymptomatic carotid stenosis were 80.5% (ACST-2), 79.5% (SPACE-2), 47% (CREST-1), and 20% (CREST-2). For RCTs on symptomatic carotid stenosis the eligibility rates were 89% (ICSS), 86.5% (EVA-3S), 64% (SPACE-1), and 39% (CREST-1). Both clinical practice cohorts were older by about three years and patients were more often male vs. the RCTs. Furthermore, a history of smoking (asymptomatic patients), hypertension (symptomatic patients), and atrial fibrillation was diagnosed more often, whereas hypercholesterolaemia and coronary heart disease (asymptomatic patients) were less prevalent. More clinical practice patients were on antiplatelets, anticoagulants, and lipid lowering drugs. Symptomatic clinical practice patients presented more often with retinal ischaemia and less often with minor hemispheric strokes than patients in the RCTs. The external validity of contemporary carotid RCTs varies considerably. Patients in routine clinical practice differ from RCT populations with respect to age, comorbidities, and medication. These data are of interest for clinicians and guideline authors and may be relevant for the design of future comparative trials.


Light-Guided Percutaneous Neck Rejuvenation With Division of Platysma Bands and Suture Suspension: A Multicenter Retrospective Study.
Traditional invasive suture suspension techniques have proven efficacy and durability. A previously described percutaneous placement of a neck suspension suture with light guidance has transformed this into a minimally invasive technique. This novel technique provides a major advance for minimally invasive neck rejuvenation. The authors sought to describe their experience with light-guided percutaneous neck rejuvenation over the past 4.5 years, including technique, patient selection, safety profile, and expected outcomes. Data were retrospectively reviewed for all patients who underwent the procedure with 5 surgeons across 4 aesthetic plastic surgery practices from January 2018 through May 2022. Inclusion criteria were mild to moderate neck laxity, prominent anterior platysma bands, and desire to improve neck contour. Patients undergoing concurrent skin incision >5 mm (ie, open rhytidectomy or platysmaplasty) were excluded. A total of 391 patients meeting criteria were identified during the study period. No hematomas were documented. Four patients (1%) developed infection at the suture site, 1 resolving on antibiotics and 3 requiring suture removal. Eighteen (4.6%) developed recurrent platysmal bands, and 7 (1.8%) had residual loose skin. Four (1%) experienced transient marginal mandibular neuropraxia. Mean length of follow-up time was 240 days. Light-guided percutaneous suture suspension is a safe and viable option for improving neck contours. Although it does not address extensive skin laxity or excess submental fat, it can be combined with energy-based tissue tightening, submental liposuction, or skin excision. In selected patients, this minimally invasive procedure provides predictable results with a low risk of complications.


Improved Survival of Calreticulin-Mutated Patients Compared With Janus Kinase 2 in Primary Myelofibrosis: A Meta-Analysis.
Next to janus kinase 2 (JAK2) and myeloproliferative leukemia protein, calreticulin (CALR) is a recently discovered mutation present in > 20% of patients diagnosed with primary myelofibrosis (PMF). Six studies published from December 2013 to December 2014 met the inclusion criteria for the present meta-analysis: 2 of an Asian and 4 of a non-Asian population. We assessed the biologic characteristics at diagnosis and investigated overall survival. The analyses were stratified by ethnic origin (Asian vs. non-Asian). A total of 816 patients with the JAK2 mutation and 307 patients with the CALR mutation were included. The patients with the JAK2 mutation were older than those with the CALR mutation, and no statistically significant difference was noted in the gender distribution of the patients with PMF with the JAK2 versus CALR mutation. Patients with JAK2-mutated PMF had a higher white blood cell count, but no statistically significant evidence was found for a difference in the platelet count or hemoglobin level. No difference was found in thrombosis risk or acute leukemic transformation in those 2 populations. Major differences were found between the Asian and non-Asian populations. The difference in characteristics between JAK2 and CALR was larger in the Asian population than in the non-Asian population (P = .007). Also, in the non-Asian population, those with JAK2 mutation had lower platelet counts than the Asians (P = .06). In the non-Asian population, the patients diagnosed with JAK2-positive PMF had worse overall survival than the patients with CALR-positive PMF, with a combined hazard ratio of 2.43 (95% confidence interval, 1.83-3.22). The results of the present meta-analysis have confirmed the role of the CALR mutation in the diagnosis of, and as a prognostic tool for, PMF. Our results suggest that patients with the CALR mutation will have better overall survival than patients with the JAK2 mutation in a non-Asian population.


Brief resolved unexplained event: Severity-associated factors at admission in the pediatric emergency ward.
A brief resolved unexplained event (BRUE) is a recent clinical entity that has now replaced the term "infant discomfort". Despite the availability of recent recommendations, identification of patients requiring further examination remains difficult. We aimed to identify factors associated with severe pathology and/or recurrence by studying the medical files of 767 patients admitted to the pediatric emergency department of a French university hospital for a BRUE. Overall, 255 files were studied; 45 patients had a recurrence and 23 patients had a severe diagnosis. The most frequently found etiology was gastroesophageal reflux in the benign diagnosis group and apnea or central hypoventilation in the severe diagnosis group. Prematurity (p = 0.032) and time since last meal >1 h (p = 0.019) were the main factors associated with severe disease. Most of the routine examination results remained non-contributive to the etiology. As prematurity is a factor associated with severe diagnosis, special attention should be given to this population, without subjecting them to multiple tests, since the main complication was found to be apnea or central hypoventilation. Prospective research is needed to establish the usefulness and prioritization of diagnostic tests for infants who are at "high risk" of experiencing a BRUE.


Presence of an activator of pyruvate dehydrogenase in human circulation: elevation following a glucose load and possible relation to an insulin mediator.
Our earlier observation that the chemical mediator of insulin action stimulates lipid synthesis in primary cultures of rat hepatocytes prompted us to examine its presence in human serum and its regulation by changes in insulin levels. Serum samples were obtained from normal subjects following an oral 100 gm glucose tolerance test (GTT; n = 10). An acid soluble, heat stable and charcoal non-absorbable substance was extracted from different sera and tested for their ability to stimulate liver mitochondrial pyruvate dehydrogenase (PDH). This substance obtained from GTT samples at 1/1000 final dilution caused significantly higher stimulation of PDH when compared to that obtained from fasting samples. These results demonstrate the presence of an activator of PDH (molecular weight approximately 1000-2000) in human circulation. Since the activator of PDH is modulated by physiological perturbation such as oral glucose ingestion, known to cause changes in circulating insulin levels, it may possibly be related to insulin mediator.


Anal mucosal electric sensation in postoperative patients with anorectal malformations.
No previous report has, to our knowledge, been made on anal mucosal electric sensation in postoperative patients with anorectal malformations (ARMs). We studied the anal mucosal electric sensory threshold (AMEST) in comparison with clinical manifestation. The study included 25 patients with ARMs who underwent anorectoplasty (ARMs group) and 10 subjects (control group). Based on the type of ARMs, patients were divided into 3 subgroups: high type, n = 14; intermediate type, n = 6; low type, n = 5. The AMEST was measured at 3 positions, at the anal skin margin and 1 and 2 cm from the anal skin margin. The AMEST was analyzed compared with the type of ARMs and clinical manifestation. The AMEST clearly increased at the 3 sites in patients with ARMs, especially those with high and intermediate types, compared with control subjects. The sensitivity threshold in the lower anal canal in the low-type subgroup was about the same as that in the control group. An analysis of clinical manifestations showed significantly increased thresholds in the upper and middle anal canal in the group of patients with difficulty in discriminating between gas and defecation and with fecal incontinence (P < .01 and P < .05). The AMEST for the high-type and intermediate-type subgroups in the ARMs group was worse than that in the low-type subgroup and control group. The AMEST in the upper and middle anal canal was important for gas and defecation distinction and fecal maintenance.


Optimizing Deep Learning for Cardiac MRI Segmentation: The Impact of Automated Slice Range Classification.
Cardiac magnetic resonance imaging is crucial for diagnosing cardiovascular diseases, but lengthy postprocessing and manual segmentation can lead to observer bias. Deep learning (DL) has been proposed for automated cardiac segmentation; however, its effectiveness is limited by the slice range selection from base to apex. In this study, we integrated an automated slice range classification step to identify basal to apical short-axis slices before DL-based segmentation. We employed publicly available Multi-Disease, Multi-View & Multi-Center Right Ventricular Segmentation in Cardiac MRI data set with short-axis cine data from 160 training, 40 validation, and 160 testing cases. Three classification and seven segmentation DL models were studied. The top-performing segmentation model was assessed with and without the classification model. Model validation to compare automated and manual segmentation was performed using Dice score and Hausdorff distance and clinical indices (correlation score and Bland-Altman plots). The combined classification (CBAM-integrated 2D-CNN) and segmentation model (2D-UNet with dilated convolution block) demonstrated superior performance, achieving Dice scores of 0.952 for left ventricle (LV), 0.933 for right ventricle (RV), and 0.875 for myocardium, compared to the stand-alone segmentation model (0.949 for LV, 0.925 for RV, and 0.867 for myocardium). Combined classification and segmentation model showed high correlation (0.92-0.99) with manual segmentation for biventricular volumes, ejection fraction, and myocardial mass. The mean absolute difference (2.8-8.3 mL) for clinical parameters between automated and manual segmentation was within the interobserver variability range, indicating comparable performance to manual annotation. Integrating an initial automated slice range classification step into the segmentation process improves the performance of DL-based cardiac chamber segmentation.


Overcoming barriers to the use of metformin: patient and provider perspectives.
Metformin is the first-line treatment for type 2 diabetes mellitus. Observational studies show lower rates of use than would be expected from clinical guidelines. We undertook a qualitative study of barriers to metformin use from the patient and provider perspective. Patient focus group, patient individual interviews, provider interviews, and chart review. Purposive sampling of patients and providers in New York State. Seven one-on-one patient interviews, one focus group with 13 patients, 10 provider interviews, and manual review of 1259 charts. Grounded theory. Both providers and patients cited potential health benefits as strong reasons to take metformin and describe it as the first-line drug for diabetes. Patients and providers both cited gastrointestinal side effects as the primary barrier to metformin use. Patients described adapting to these side effects and taking metformin at a time that minimizes them. In contrast, providers emphasized dose titration and the use of extended-release formulation as tools for minimizing side effects but were uncertain about the effectiveness of these strategies. Metformin is positively viewed by patients and providers, but gastrointestinal side effects are a barrier to its use. There is some consensus on basic measures to improve its tolerability, but these measures are not consistently applied and lack evidence establishing their effectiveness. Pragmatic clinical trial research on optimal dose, formulation, and counseling for new metformin users should be considered.


A phylogenetic study of Feline Immunodeficiency Virus (FIV) among domestic cats in Turkey.
Feline Immunodeficiency Virus (FIV) is the most prominent retrovirus in cats. Molecular studies on FIV are of great importance to enable further studies, for example, understanding the pathogenesis and developing improved vaccines. We aimed to elucidate the molecular status of FIV and provide a detailed characterization of FIV in Turkey because at present there is very limited information available in the literature. We also evaluated a potential link between clinical symptoms and FIV subtypes according to results obtained from molecular tests. Whole blood was collected from 200 client-owned domestic cats and molecular diagnosis and characterization was performed. The env, gag and vif gene regions were amplified and sequenced for phylogenetic analysis. We obtained specific amplicons based on bothenvand gag for FIV in 21 cats; only 2 of the 21 positive samples could also be characterized based on the vif gene region. Separate clusters were identified according to previously determined genotyping strategies; however, they were observed in FIV subtype B. The molecular findings of some individual cats were evaluated in conjunction with their clinical symptoms in an attempt to determine potential relationships between the genetic characteristics of FIV and symptoms of disease. As a result, overexpression of the vif gene could be important in leading to serious clinical symptoms. Our results emphasize the necessity of considering FIV in diagnosis and performing the neccesary diagnostics to confirm or rule out FIV infection. The molecular dynamics of FIV should be periodically updated by further analyses to establish a successful prevention strategy.


Intravenous disodium etidronate therapy in spinal cord injury patients with heterotopic ossification.
The goal of the present study was to use intravenous etidronate in the acute phase of heterotopic ossification (HO) in an attempt to achieve a high initial drug concentration at the site of the active ectopic ossification. The study included 27 consecutive patients with an acute onset of HO after spinal cord injury (SCI). The three-phase bone scan was used to confirm clinical diagnosis of HO. Disodium etidronate (Didronel) 300 mg was administered intravenously daily for 3 to 5 days. In 20 patients there was a rapid (1-2 days) decrease of soft tissue swelling (p < 0.01) with no side effects associated with the intravenous administration. In seven patients there was minimal or no improvement of edema after intravenous etidronate. In these patients deep vein thrombosis was found in the affected limbs. The effect of high dose etidronate on HO was determined in the group of 13 patients with positive clinical and scintigraphic finding of an acute HO, but negative radiographic studies. After intravenous administration of etidronate for 3 days (300 mg/day) the drug was continued orally with 20 mg/kg/day for 6 months. A placebo was not used in this study. In eight patients there was no radiographic evidence of HO after therapy while two patients had minimal ossifications. In three patients therapy was interrupted and all developed HO in 1-2 months.


Improved yields of factor VIII from heparinized plasma.
The Factor VIII procoagulant activity in plasma, cryoprecipitate, and their polyethylene glycol (PEG) precipitates is markedly increased if blood is collected into heparin rather than into citrate phosphate dextrose (CPD). There is a 34% increase in the initial level of the Factor VIII activity in the heparinized plasma with 78% of this initial activity (184 U) recovered in the cryoprecipitated. As well, the stability of the Factor VIII activity is improved: after 24 h of incubation at 22 degrees C, 99% of the initial activity is retained in heparinized plasma whereas only 64% remains in CPD plasma. The cryoprecipitate prepared from heparinized plasma is equally stable after 24 h. The PEG concentrate prepared from the cryoprecipitate of heparinized plasma is increased to 128 U compared to only 54 U from CPD plasma. Relative recoveries were 531 U/l for heparinized plasma versus 215 U/l for CPD plasma. This represents a 147% increase in yield.


Comparative analysis of postoperative pain after transvaginal hybrid NOTES versus traditional laparoscopic cholecystectomy in obese patients.
Even though obesity is a known risk factor for needing cholecystectomy, most research excludes patients with higher degrees of obesity. The aim of this retrospective study was to compare postoperative pain and analgesic consumption in obese patients, who underwent either transvaginal hybrid Natural Orifice Transluminal Endoscopic Surgery (NOTES) cholecystectomy (NC) or traditional laparoscopic cholecystectomy (LC). Between 12/2008 and 01/2017, 237 NC were performed, of which 35 (14.8%) showed a body mass index (BMI) of 35 kg/m2 or more (obesity II and III according to the World Health Organization). Of these, procedural time, postoperative pain, analgesic requirements, and other early postoperative parameters were collected and compared with 35 matched LC patients from the same time period. There were no differences in the baseline characteristics between the two groups, but we found significant benefits for the hybrid NOTES technique in terms of less pain (P = 0.006), coherent with significantly less intake of peripheral (paracetamol; P = 0.005), and of centrally acting analgesics (piritramide; P = 0.047) within the first two-day post-surgery. We also found that those in the NC group had shorter hospital stays (P < 0.001). The postoperative complication rates and the procedural time did not differ between the two groups. With regard to postoperative pain and analgesic requirements and without an increase in postoperative complications, obese patients experience short-term benefits from the hybrid NOTES technique compared to traditional laparoscopic cholecystectomy.


No influence of number of donor CFU-GM on granulocyte recovery in bone marrow transplantation for acute leukemia.
The possible interrelation between infused bone marrow CFU-GM and peripheral granulocyte recovery was studied in 16 patients transplanted for acute leukemia. The influence of several clinical events that could modify the graft fate were also analysed. Our results show that: 1) There was no correlation between the number of infused nucleated cells and granulocyte recovery. 2) There was no correlation between the number of infused CFU-GM and granulocyte regeneration. 3) There were significant differences between the day of engraftment in patients with clinically documented HSV infection compared to patients without infection.


Preferred RNA binding sites for a threading intercalator revealed by in vitro evolution.
In pursuit of small molecules capable of controlling the function of RNA targets, we have explored the RNA binding properties of peptide-acridine conjugates (PACs). In vitro evolution (SELEX) was used to isolate RNAs capable of binding the PAC Ser-Val-Acr-Arg, where Acr is an acridine amino acid. The PAC binds RNA aptamers selectively and with a high degree of discrimination over DNA. PAC binding sites contain the base-paired 5'-CpG-3' sequence, a known acridine intercalation site. However, RNA structure flanking this sequence causes binding affinities to vary over 30-fold. The preferred site (K(D) = 20 nM) contains a base-paired 5'-CpG-3' step flanked on the 5' side by a 4 nt internal loop and the 3' side by a bulged U. Several viral 5'- and 3'-UTR RNA sequences that likely form binding sites for this PAC are identified.


Protein identification by 3D OrbiSIMS to facilitate in situ imaging and depth profiling.
Label-free protein characterization at surfaces is commonly achieved using digestion and/or matrix application prior to mass spectrometry. We report the assignment of undigested proteins at surfaces in situ using secondary ion mass spectrometry (SIMS). Ballistic fragmentation of proteins induced by a gas cluster ion beam (GCIB) leads to peptide cleavage producing fragments for subsequent OrbitrapTM analysis. In this work we annotate 16 example proteins (up to 272 kDa) by de novo peptide sequencing and illustrate the advantages of this approach by characterizing a protein monolayer biochip and the depth distribution of proteins in human skin.


[New aspects of field blocks and peripheral nerve blocks (author's transl)].
There have been no new developments concerning field blocks. The need for limiting the dosage of local anesthetic agents is stressed. Two methods for perivascular block are described and the use of CO2 containing local anesthetic solutions is discussed as well as the employment of peripheral nerve stimulators.


Phytochemical analysis of mite-infested tea leaves of Darjeeling Hills, India.
Darjeeling tea of India is one of the most famous beverages globally. However, a large amount of tea crop is damaged every year by the attack of mites. The study aimed to determine the changes in different pigments and biochemical components of tea leaves due to mite infestation. We used UV-visible and Fourier-transform infrared (FTIR) spectroscopy simultaneously to understand the damages in pigment contents of the leaves of tea (Camellia sinensis (L.) Kuntze) due to attack of phytophagus mite, Oligonychus coffeae Nietner. Furthermore, chemical analysis of infested tea leaves was also performed to compare the nutrients of the plants, namely total phenol, protein and soluble sugar. The UV-visible study reveals severe reduction of the pigments such as chlorophyll (Chl), carotenoids and xanthophylls in the tea leaf due to mite infestation. The findings of the FTIR study, also shows variation in different physiochemical components in the leaf Chl. The sugar and protein content of the infested leaves have been reduced compared to uninfested ones. Results in the case of tea leaves plucked during first (March) and third (November) flushes show similar trends. The increase in phenolic and alcoholic components and decrease in Chl contents may affect the quality of Darjeeling tea. The extent of damages done by the pests measured here could aid the pest management in tea gardens.


The effect of early oral nutritional supplements on improving nutritional outcomes and radiation-induced oral mucositis for nasopharyngeal carcinoma patients undergoing concurrent chemoradiotherapy.
To explore the value of early oral nutritional supplements (ONS) in patients with nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy (CCRT). Patients with newly diagnosed II-IVA stage NPC were analyzed and divided into Early and Routine ONS groups according to whether they received early ONS at the beginning of CCRT. Changes in nutritional indicators, incidence of treatment-related toxicity, radiation interruption, and completion of CCRT were compared. In total, 161 patients with NPC were analyzed, including 72 in the Early ONS group and 89 in the Routine ONS group. Multivariate analysis showed that early ONS was an independent protective factor for concurrent chemotherapy ≥2 cycles, and a protective factor against ≥grade 3 radiation-induced oral mucositis (RIOM) and weight loss >5%. In stage III-IVA patients, early ONS was beneficial in decreasing the risk of severe malnutrition. Early ONS can improve nutritional outcomes, reduce RIOM, and enhance treatment adherence.


Cancer therapy and replication stress: forks on the road to perdition.
Deregulated DNA replication occurs in cancer where it contributes to genomic instability. This process is a target of cytotoxic therapies. Chemotherapies exploit high DNA replication in cancer cells by modifying the DNA template or by inhibiting vital enzymatic activities that lead to slowing or stalling replication fork progression. Stalled replication forks can be converted into toxic DNA double-strand breaks resulting in cell death, i.e., replication stress. While likely crucial for many cancer treatments, replication stress is poorly understood due to its complexity. While we still know relatively little about the role of replication stress in cancer therapy, technical advances in recent years have shed new light on the effect that cancer therapeutics have on replication forks and the molecular mechanisms that lead from obstructed fork progression to cell death. This chapter will give an overview of our current understanding of replication stress in the context of cancer therapy.


FGFR2 gene polymorphism rs2981582 is associated with non-functioning pituitary adenomas in Chinese Han population: a case-control study.
The association of the fibroblast growth factor receptor 2 gene (FGFR2) polymorphism rs2981582 with breast cancer has been extensively studied, whereas the role of this polymorphism in non-functioning pituitary adenoma (NFPA) has not been elucidated. We thus investigated a potential association of rs2981582 with NFPA. A total of 79 patients and 142 healthy control participants were enrolled in our study. DNA of the participants was extracted from peripheral blood samples and genotyped by using the MassARRAY method. We found that the AA genotype was associated with a higher risk of developing NFPA (OR = 1.743, 95%CI: 1.151-2.64, P=0.008). After adjusting for risk factors, significant difference was still observed between the two groups (OR = 1.862, 95%CI: 1.172-2.957, P=0.008). Moreover, under the assumptions of the recessive model (OR = 3.051, 95%CI: 1.403-6.635, P=0.005) and the additive model (AG: OR = 0.329, 95%CI: 0.144-0.755, P=0.009; AA: OR = 0.326, 95%CI: 0.141-0.757, P=0.009), rs2981582 was associated with an increased risk of NFPA. Our results proved that FGFR2 rs2981582 AA genotype was associated with a higher risk of NFPA. The recessive model and additive model also showed increased the risk of NFPA.


Measurement of the T Cell Response to Preerythrocytic Vaccination in Mice.
Whole attenuated parasite vaccines designed to elicit immunity against the clinically silent preerythrocytic stage of Plasmodium infection represent the most efficacious experimental platforms currently in clinical trial. Studies in rodents and humans show that T cells mediate vaccine-induced protection. Thus, determining the quantitative and qualitative properties of these T cells remains a major research focus. Most rodent models of preerythrocytic anti-Plasmodium vaccination focus on circumsporozoite-specific CD8 T cell responses in BALB/c mice. However, CD4 T cells and non-circumsporozoite-specific CD8 T cells also significantly contribute to protection. Here we describe alternative approaches that enable detection and functional characterization of total CD8 and CD4 T cell responses induced by preerythrocytic vaccination in mice. These flow cytometry-based approaches rely on monitoring the modulation of expressed integrins and co-receptors on the surface of T cells in vaccinated mice. The approaches enable direct determination of the magnitude, kinetics, distribution, phenotype, and functional features of T cell responses induced by infection or whole-parasite vaccination using any mouse-parasite species combination.


Appraisal of the Quality and Contents of Clinical Practice Guidelines for Hypertension Management in Chinese Medicine: A Systematic Review.
To evaluate the quality and consistency of recommendations in the clinical practice guidelines (CPGs) for hypertension in Chinese medicine (CM). CM CPGs were identified from 5 electronic databases and hand searches through related handbooks published from January 1990 to December 2013. Three reviewers independently appraised the CPGs based on the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, and compared the CPGs' recommendations on CM syndrome pattern classification and treatment. Five CM CPGs for hypertension were included. The quality score of the evidence-based (EB) guideline was higher than those of the consensus-based with no explicit consideration of evidence-based (CB-EB) and the consensus-based (CB) guidelines. Three out of five patterns in the CPGs were recommended by the EB guideline. Tianma Gouteng Formula () in the EB guideline was recommended mostly for hypertension patients with pattern of ascendant hyperactivity of Gan (Liver)-yang and pattern of yin deficiency with yang hyperactivity in the CPGs. Acupuncture and massage were recommended for Grade I and Grade II hypertension with severe symptoms weakening the quality of life in the EB guideline. For Grade I and Grade II hypertension, CM could be used alone, while for Grade III hypertension, they should be used in combination with Western medicines. The quality of EB guideline was higher than those of CB and CB-EB CPGs in CM for hypertension and CM should be prescribed alone or combined with Western medicines based on the grade of hypertension.


Mapping on the calf estrogen receptor of the binding domain for an antibody interfering with receptor activation.
The localization on the calf estrogen receptor of the binding domain for B36 (an IgM antibody which prevents and reverses the effects of receptor activation) has been studied by means of controlled proteolysis of the receptor-estradiol complex using trypsin, chymotrypsin, and papain. We successively determined for intact and proteolyzed receptor-estradiol complex (i) the abilities of estradiol-binding species to aggregate in low salt medium, to bind to nonspecific DNA absorbed onto cellulose, and to interact with B36 antibody in sucrose gradients; (ii) the hydrodynamic properties of estradiol-binding species, by gel permeation chromatography and sucrose gradient centrifugation in high salt media and (iii) the molecular weights of B36-reactive species, by immunoblot analysis. Three tryptic receptor fragments of Mr 36,000, 34,000, and 33,000 and two chymotryptic fragments of Mr 36,000 and 33,000 included both the hormone- and B36-binding domains but did not interact with DNA, whereas at least two receptor fragments resulting from the action of chymotrypsin and papain bound estradiol with high affinity but interacted neither with DNA nor with B36. Taking into account these results and assuming that structure of the calf estrogen receptor is similar to those of sequenced estrogen receptors (which show a highly conserved organization with considerable homologies in the functional domains), we propose that the B36-binding domain is located either between the DNA- and hormone-binding domains (model I) or at the C-terminal end of the estrogen receptor (model II). The regions that include the main proteolytic cleavage sites of the receptor are also specified, and the abilities of the two models of the calf estrogen receptor to account for the effect of B36 on receptor activation are discussed.


Helping postacute traumatically brain injured clients return to work: three case studies.
This paper presents three case studies of individuals who had sustained a severe brain injury and who are clients of a return to work programme emphasizing a supported employment approach. The case studies illustrate the types of interventions which are utilized, including job placement; job site and off-site training, advocacy, and compensatory strategies; and ongoing assessment and maintenance of social and productive gains in order to assist with job retention. The results of the case studies may be generalized to the population of brain injury survivors who require intensive and long-term intervention and support in order to return to employment.


Decreased integrity of exercise-induced plasma cell free nuclear DNA - negative association with the increased oxidants production by circulating phagocytes.
Strenuous exercise increases circulating cell free DNA (cfDNA) and stimulates blood phagocytes to generate reactive oxygen species (ROS) which may induce DNA strand breaks. We tested whether: (A) elevated cfDNA in response to three repeated bouts of exhaustive exercise has decreased integrity; (B) each bout of exercise increases luminol enhanced whole blood chemiluminescence (LBCL) as a measure of ROS production by polymorphonuclear leukocytes. Eleven men performed three treadmill exercise tests to exhaustion separated by 72 hours of resting. Pre- and post-exercise concentrations and integrity of cf nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) and resting (r) and fMLP (n-formyl-methionyl-leucyl-phenylalanine)-stimulated LBCL were determined. Each bout increased concentrations of cf n-DNA by more than 10-times which was accompanied by about 2-times elevated post-exercise rLBCL and fMLP-LBCL. Post-exercise cf n-DNA integrity (integrity index, I229/97) decreased after the first (0.59 ± 0.19 vs. 0.48 ± 0.18) and second (0.53 ± 0.14 vs. 0.44 ± 0.17) bout of exercise. There were negative correlations between I229/97 and rLBCL (ƍ = -0.37), and I229/97 and fMLP-LBCL (ƍ = -0.40) - analysis of pooled pre- and post-exercise data (n = 66). cf mt- DNA integrity (I218/78) did not alter in response to exercise. This suggests an involvement of phagocyte ROS in cf n-DNA strand breaks in response to exhaustive exercise.


Donor-Acceptor Cyclopropanes: Activation Enabled by a Single, Vinylogous Acceptor.
A novel class of highly activated donor-acceptor cyclopropanes bearing only a single, vinylogous acceptor is presented. These strained moieties readily undergo cycloadditions with aldehydes, ketones, thioketones, nitriles, naphth-2-ols and various other substrates to yield the corresponding carbo- and heterocycles. Diastereocontrol can be achieved through the choice of catalyst (Brønsted or Lewis acid). The formation of tetrahydrofurans was shown to be highly enantiospecific when chiral cyclopropanes are employed. A series of mechanistic and kinetic experiments was conducted to elucidate a plausible catalytic cycle and to rationalize the stereochemical outcome.


Expression of the yeast LEU4 gene is subject to four different modes of control.
A translational fusion of yeast LEU4 and Escherichia coli lacZ which contains 679 bp of the LEU4 5'-flanking region and the first two codons of LEU4 was used to study LEU4 expression. Eight recipient strains with different genetic backgrounds, transformed with a plasmid containing the fusion, were grown under a variety of conditions, and beta-galactosidase activity was measured. Evidence was obtained for at least four modes of expression of LEU4: general amino acid control, leucine-specific control, basal level expression, and branched-chain amino acid-mediated repression. Determination of steady-state levels of LEU4 mRNA suggested that LEU4 expression is regulated transcriptionally.


Relationships in hydrogen metabolism between hydrogenase and nitrogenase in phototrophic bacteria.
Purple bacteria Rhodospirillum rubrum and Thiocapsa roseopersicina form two enzymes, hydrogenase and nitrogenase, which participate in hydrogen metabolism. H2 photoproduction in these bacteria is associated mainly or completely with the action of nitrogenase. The soluble and membrane-bound hydrogenases of T. roseopersicina have similar physicochemical properties (mol. weight, subunit composition, N-terminal amino acids, Fe2+ and S2- content, pl. Eo'). In comparison with other hydrogenases the enzyme from R. rubrum and T. roseopersicina evolve H2 with high rate from reduced cytochrome c3, but not from ferredoxins. H2 production and N2 fixation take place in the presence of NAD(P)H. NADP-reductase, ferredoxin and cytochrome c3 participate in this reaction. Possible relationships between hydrogenase-nitrogenase in the metabolism of molecular hydrogen are discussed.


The effect of carnitine supplementation on carnitine balance in patients with persistent post-operative infection.
The effect of L-carnitine (C) supplementation on body C balance, muscle C concentration, the leg exchange of C and some amino-acids was investigated in 8 patients with persistent post-operative infection. Before supplementation, total C concentration was 81 +/- 13 micromol/l plasma (SEM) and 15.4 +/- 1.5 micromol/g dry weight muscle, urinary excretion was 19 +/- 4 micromol/kg x 24 h and the arterial-femoral venous concentration difference over the leg (A-FV) of free C was -2.90 +/- 0.97 micromol/l, p < 0.05. Plasma-free C concentration correlated inversely with the A-FV of free C. The excretion of free C in urine was directly related to the plasma-free C concentration. A total C dose of 110 mg/kg during 4 days resulted in a 30% retention (range 12-48), a doubling of plasma C levels but no measurable alteration in either muscle C content or the arterial concentration and exchange of amino-acids over the leg. Plasma-free C concentration correlated inversely with the clearance of creatinine. In patients with persistent post-operative infection, muscle C concentration was normal and C was released from muscle as a consequence of muscle catabolism. The rate of C release was a major determinant of the plasma C concentration. At normal or low plasma C levels, the renal tubular reabsorption of C was a major determinant of body C balance. At elevated plasma concentrations of C, such as during C supplementation, the tubular capacity for reabsorption is exceeded and body carnitine balance is mainly dependent on the glomerular filtration.


Development of an inflammatory bowel disease (IBD) Patient-Reported Experience Measure (PREM): A patient-led consensus work and 'think aloud' study for a quality improvement programme.
Patient-Reported Experience Measures (PREMs) are key in improving healthcare quality, but no PREM exists for inflammatory bowel disease (IBD). This study aimed to co-produce a PREM with IBD service users for IBD service evaluation and quality improvement programme. A pool of 75 items was drawn from published survey instruments covering interactions with services and aspects of living with IBD. In Stage 1, during two workshops, eight expert service users reduced candidate items through a ranked-choice voting exercise and suggested further items. During Stage 2, 18 previously uninvolved people with IBD assessed the face and content validity of the candidate items in 'Think Aloud' interviews. During two final workshops (Stage 3), the expert service users removed, modified and added items based on the interview findings to produce a final version of the PREM. Stage 1 generated a draft working PREM mapped to the following four domains: Patient-Centred Care; Quality; Accessibility; Communication and Involvement. The PREM included a set of nine items created by the expert group which shifted the emphasis from 'self-management' to 'living with IBD'. Stage 2 interviews showed that comprehension of the PREM was very good, although there were concerns about the wording, IBD-relevance and ambiguity of some items. During the final two workshops in Stage 3, the expert service users removed 7 items, modified 15 items and added seven new ones based on the interview findings, resulting in a 38-item PREM. This study demonstrates how extensive service user involvement can inform PREM development. Patients were involved as active members of the research team and as research participants to co-produce and validate a PREM for IBD services. In Stage 1, eight expert service users ('the expert group') reduced candidate items for the PREM through a voting exercise and suggested new items. During Stage 2, 18 previously uninvolved people with IBD (the 'think aloud' participants) assessed the validity of the candidate items in 'Think Aloud' interviews as research participants. In Stage 3, the expert group removed, changed and added items based on the interview findings to produce a final version of the 38-item PREM. This study shows how service user involvement can meaningfully inform PREM development.


Treatment of osteochondral fracture of the trochlea of the PIP joint.
Osteochondral (OC) fractures of the trochlea of the PIP joint are rare but the treatment of these fractures can be challenging [2, 5, 6, 10]. And the therapeutic guideline is not determined. All of the three cases were male. Two were delayed union with minimal displacement and the other was a fresh displaced fracture. All cases were treated with ORIF using small K-wires. In delayed union cases, bone grafting was added. Although bone union was obtained in all cases, rotation of the fragment due to the absorption of the grafted bone resulted in deformity of the trochlea in one of the delayed union cases. The functional recovery at the 2-year follow-up was satisfactory in all cases. Although OC fracture of the trochlea of PIP joint carry significant fixation implications, successful treatment could be done with ORIF using small K-wire fixation technique.


Hepatitis B virus genotypes, precore mutations, and basal core promoter mutations in HBV-infected Chinese patients with persistently normal alanine aminotransferase and low serum HBV-DNA levels.
Hepatitis B virus (HBV) genotype and precore and basal core promoter (BCP) mutants in the patients with persistently normal alanine aminotransferase (ALT) and low serum HBV-DNA levels are unclear. The aim of this study was to determine HBV genotypes, precore and BCP mutations, and their association with chronic hepatitis and liver fibrosis in HBV-infected patients with persistently normal ALT, and low serum HBV-DNA levels in northeast China. Patients (n = 89) with normal ALT and serum HBV-DNA levels below 20000 IU/mL but detectable with real-time PCR were included in this study. HBV genotypes were determined by real-time PCR. The precore and BCP mutations were detected by sequencing. All the patients had biopsy results. Of the 89 patients, 11 (12.4%) were genotype B and 78 (87.6%) were genotype C. The most common mutations were G1896A (23.6%), G1764A (9.0%), and A1762T (6.7%). The prevalence of precore mutation was significantly higher in genotype B patients than in genotype C patients (54.5% vs. 19.2%, p < 0.01). There was no significant difference in the prevalence of BCP mutations between genotype B and genotype C (18.2% vs. 10.2%). Multivariate analysis showed that old age (> 40 years) and BCP mutations were independent predictors of liver necroinflammation and fibrosis. Thus, BCP mutations may be associated with liver necroinflammation and fibrosis in patients with persistently normal ALT and low serum HBV-DNA levels in northeast China.


Challenging Contrast-Enhanced Mammography-Guided Biopsies: Practical Approach Using Real-Time Multimodality Imaging and a Proposed Procedural Algorithm.
Contrast-enhanced mammography (CEM) is an emerging functional breast imaging technique that entails the acquisition of dual-energy digital mammographic images after IV administration of iodine-based contrast material. CEM-guided biopsy technology was introduced in 2019 and approved by the U.S. FDA in 2020. This technology's availability enables direct sampling of suspicious enhancement seen only on or predominantly on recombined CEM images and addresses a major obstacle to the clinical implementation of CEM technology. The literature describing clinical indications and procedural techniques of CEM-guided biopsy is scarce. This article describes our initial experience in performing challenging CEM-guided biopsies and proposes a step-by-step procedural algorithm designed to proactively address anticipated technical difficulties and thereby increase the likelihood of achieving successful targeting.


Long-term survival after xenograft versus homograft aortic root replacement: Results from a prospective randomized trial.
The study objective was to investigate the long-term survival of patients undergoing xenograft versus homograft full root aortic valve replacement. A total of 166 patients requiring aortic valve surgery were randomized to undergo the Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis (N = 90) or a homograft (N = 76) full root aortic valve replacement between 1997 and 2005 in a single institution. Six patients randomly assigned to the homograft crossed over to the Freestyle bioprosthesis because of the unavailability of suitably sized homografts. All surgeons were required to adhere to the standard surgical technique for homograft root implantation previously described. Follow-up was 98.5% complete. The mean age of the study population was 65 ± 8 years. Coronary artery bypass grafting was associated with root aortic valve replacement in 76 of 166 patients (46%, P = not significant between groups), and overall hospital mortality was 4.8% (8/166, P = not significant between groups). Median follow-up was 13.8 years (range, 0-21.8 years; 2033 patient-years). The Kaplan-Meier survival analysis showed that there was no significant difference in overall survival between the 2 arms at 5, 10, and 15 years. Twenty-year survival was 28.3% ± 5% for the Freestyle group versus 25.1% ± 5.7% for the homograft group (P = .90), which was comparable to the age- and sex-matched UK general population. The freedom from aortic valve reoperation at 20 years was comparable for the Freestyle group versus the homograft group (67.9% ± 8.8% vs 67.2% ± 10.3%, respectively; P = .74). This is the first study to investigate the long-term survival of xenograft versus homograft full root aortic valve replacement from a prospective randomized trial. The observed 20-year overall survival and freedom from aortic valve reoperation serve as a benchmark for future studies on interventions for aortic valve disease in the elderly.


CD4+ cell oligoclonality in Crohn's disease: evidence for an antigen-specific response.
To identify disease-specific T cell changes that occur in Crohn's disease (CD) the T-cell receptor (TCR) BV repertoires of lamina propria lymphocytes (LPL) from both disease-active and disease-inactive colonic tissue of three CD patients were compared by a quantitative polymerase chain reaction (qPCR) and CDR3 length analysis. It was observed that the BV repertoires of LPL isolated from the disease-active and disease-inactive parts of the colon of the same individual were different, and most of the differences occurred in CD4+ LPL with very few differences in the CD8+ populations of LPL. Although the pattern of BV segments that was increased in disease-active relative to disease-inactive tissue was different for all three CD patients, there was an increase in the levels of BV11, 13S2, 15, 16, and 17 segments in the disease-active tissue of all three patients. Standard CDR3 length analysis of BV11, 13S2, 15, 16, and 17 segments revealed that in two of the three CD patients there was a striking degree of TCR oligoclonality in the disease-active tissue that was absent from disease-inactive tissue of the same individual. Additional differences between the disease-active and disease-inactive tissues were observed using a more refined method of CDR3 length analysis, which employs BV- and BJ-specific primers. These observations suggest that at least some of the inflammation in CD is the result of responses by CD4+ T cells to specific antigens.


A higher number of school meals is associated with a less-processed diet.
To compare the participation of food groups - fresh and minimally processed, processed, and ultra-processed - in the diet of students (n=1357) from Belo Horizonte, MG, Brazil, in accordance with the number of school meals consumed daily. Four groups were defined: children that did not consume school meals and children that consumed one, two, or three school meals daily. Food groups participation, in g/1000kcal, was obtained using two 24-hour recalls. Three linear regression models were analyzed, in which the consumption of each of the food groups was the dependent variable, the number of school meals was the independent variable, and sociodemographic data (gender, age, health vulnerability) and overweight condition were the control variables. Children that consumed 2 or 3 school meals daily showed, respectively, 7.3% and 10.5% higher ingestion of fresh and minimally processed food in comparison to children that did not consume school meals. Moreover, ultra-processed food participation was 18.0% lower among students that consumed two school meals and 26.0% lower among children that consumed three meals daily, in comparison to students that did not consume school meals. The study showed a possible dose-response effect in children's daily diets with two or three school meals and highlighted the relevance of the prolonged stay at school for healthy eating promotion in children.