Epigenetic and genetic variations at the TNNT1 gene locus are associated with HDL-C levels and coronary artery disease.
To assess whether epigenetic and genetic variations at the TNNT1 gene locus are associated with high-density lipoprotein cholesterol (HDL-C) and coronary artery disease (CAD). Patients, materials & methods: TNNT1 DNA methylation and c.-20G>A polymorphism were genotyped in subjects with and without familial hypercholesterolemia (FH). Lower TNNT1 DNA methylation levels were independently associated with lower HDL-C levels and with the TNNT1 c.-20G>A polymorphism. In FH men, carriers of the TNNT1 c.-20G>A polymorphism had lower HDL-C levels and an increased risk of CAD compared with noncarriers. In non-FH men, a higher TNNT1 DNA methylation level was associated with CAD. These results suggest that TNNT1 genetic and epigenetic variations are associated with HDL-C levels and CAD.


Correlation of serum fructosamine and recurrent pregnancy loss: Case-control study.
Pre-gestational diabetes is associated with an elevated risk of pregnancy loss, but it is unclear whether subclinical glucose intolerance is associated with pregnancy loss, especially recurrent pregnancy loss (RPL). The aim of this study was therefore to compare maternal serum fructosamine (a marker of glycemic control) in patients with and without RPL. A case-control study was carried out of 117 women with unexplained RPL, defined as two or more pregnancy losses with no more than one live birth, and 117 age-matched controls with at least one full-term uncomplicated pregnancy and no more than one pregnancy loss. No RPL patients or controls had a clinical diagnosis of pre-gestational or gestational diabetes. Maternal serum was analyzed for fructosamine on quantitative spectrophotometry. Mean body mass index (BMI) of RPL patients was 26.0 ± 6.4 kg/m(2) compared with 26.6 ± 5.8 kg/m(2) (P = 0.40). Fructosamine was higher in women with RPL (224.1 ± 28.79 μmol/mL) compared with controls (188.9 ± 19.3 μmol/mL, P < 0.001). This difference persisted when RPL patients and controls were stratified by BMI. The proportion of women with elevated fructosamine considered diagnostic of diabetes (>285 μmol/L) was similar in RPL patients and controls. The RPL patients and controls had a similar proportion of women with elevated fructosamine considered diagnostic of diabetes. Serum fructosamine was increased in women with RPL compared with controls. Thus, subclinical glucose intolerance may be associated with an increased risk of RPL. These data support further investigation into the mechanisms of RPL associated with glucose intolerance, but do not support testing for subclinical glucose intolerance in women with RPL.


Silent red blood cell autoantibodies: Are they naturally occurring or an effect of tolerance loss for a subsequent autoimmune process?
Unexpected anti-red blood cell (RBC) alloantibodies are routinely investigated in immunohematology and blood banking since their existence in pregnant women may induce haemolytic disease of the foetus and newborn, and their presence in donors may induce haemolytic transfusion reactions or hyperacute rejection in solid organ transplantation. Unexpected anti-RBC alloantibodies may target antigens of the most blood types excluding the expected antibodies targeting the ABO antigens. Their incidence in humans was originally linked to alloimmunization events such as blood transfusions, transplants, or pregnancies. But later, many findings revealed their existence in pathogenic processes such as malignancies, infections, and autoimmune diseases; and usually (but not always) associated to autoimmune haemolytic anaemia (AIHA). Nevertheless, unexpected anti-RBC autoantibodies are also occasionally found in healthy individuals in the absence of AIHA and with no history of alloimmunization or the associated pathologic processes. Hence, they are generally known as non-clinically significant, are excluded for typification and called "silent red blood cell autoantibodies (SRBCAA)". This review highlights evidence related to genetic predisposition, molecular mimicry, immune dysregulation, and immune tolerance loss surrounding the existence of anti-RBC antibodies, describing the presence of SRBCAA as possible early witnesses of the development of autoimmune diseases.


A finite element study on the interactive effect between the damage of the cup-bone interface and the bone strain of hip implants under various fixation conditions.
Interfacial damage has a high impact on the loosening of the acetabular cup. However, monitoring this damage induced by the variations in loading conditions, such as the angle, amplitude, and frequency in vivo, is challenging. In this study, we evaluated the risk of loosening of the acetabular cup due to interfacial damages induced by the deviation in loading conditions and amplitudes. A three-dimensional model of the acetabular cup component was developed, and the interfacial crack growth between the cup and the bone was modeled using a fracture mechanics approach, which simulated the extent of interfacial damage and associated cup displacement. The interfacial delamination mechanism changed with the increasing inclination angle, wherein a fixation angle of 60° exhibited the largest area of contact loss. The compressive strain of embedding the simulated bone at the remaining bonding area accumulated as the lost contact area widened. Such interfacial damages, namely, the growth of the lost contact area and accumulated compressive strain in the simulated bone, promoted both embedding and rotational displacement of the acetabular cup. In the worst case of a fixation angle of 60°, the total displacement of the acetabular cup exceeded the limit of the modified safe zone, suggesting a quantitative risk of dislocation of the acetabular cup induced by the accumulated interfacial damage. Furthermore, nonlinear regression analyses between the degree of displacement of the acetabular cup and the extent of the two types of interfacial damage demonstrated that the interactive effect of the fixation angle with the loading amplitude showed a significant effect on increasing cup displacement. These findings suggest that proper control of the fixation angle during operation is useful in preventing the loosening of the hip joint.


An infiltrative right ventricular myxoma.
Computed tomographic findings in a 71-year-old patient with an infiltrative right ventricular myxoma are described. The findings included multiple lesions in the right ventricle and stenosis of the trunk of the pulmonary artery.


One-dimensional analytical solution for hydraulic head and numerical solution for solute transport through a horizontal fracture for submarine groundwater discharge.
Submarine groundwater discharge (SGD) has been recognized as a major pathway of groundwater flow to coastal oceanic environments. It could affect water quality and marine ecosystems due to pollutants and trace elements transported through groundwater. Relations between different characteristics of aquifers and SGD have been investigated extensively before, but the role of fractures in SGD still remains unknown. In order to better understand the mechanism of groundwater flow and solute transport through fractures in SGD, one-dimensional analytical solutions of groundwater hydraulic head and velocity through a synthetic horizontal fracture with periodic boundary conditions were derived using a Laplace transform technique. Then, numerical solutions of solute transport associated with the given groundwater velocity were developed using a finite-difference method. The results indicated that SGD associated with groundwater flow and solute transport was mainly controlled by sea level periodic fluctuations, which altered the hydraulic head and the hydraulic head gradient in the fracture. As a result, the velocity of groundwater flow associated with SGD also fluctuated periodically. We found that the pollutant concentration associated with SGD oscillated around a constant value, and could not reach a steady state. This was particularly true at locations close to the seashore. This finding of the role of fracture in SGD will assist pollution remediation and marine conservation in coastal regions.


STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia.
T cell acute lymphoblastic leukemia (T-ALL) is commonly associated with activating mutations in the NOTCH1 pathway. Recent reports have shown a link between NOTCH1 signaling and intracellular Ca2+ homeostasis in T-ALL. Here, we investigate the role of store-operated Ca2+ entry (SOCE) mediated by the Ca2+ channel ORAI1 and its activators STIM1 and STIM2 in T-ALL. Deletion of STIM1 and STIM2 in leukemic cells abolishes SOCE and significantly prolongs the survival of mice in a NOTCH1-dependent model of T-ALL. The survival advantage is unrelated to the leukemic cell burden but is associated with the SOCE-dependent ability of malignant T lymphoblasts to cause inflammation in leukemia-infiltrated organs. Mice with STIM1/STIM2-deficient T-ALL show a markedly reduced necroinflammatory response in leukemia-infiltrated organs and downregulation of signaling pathways previously linked to cancer-induced inflammation. Our study shows that leukemic T lymphoblasts cause inflammation of leukemia-infiltrated organs that is dependent on SOCE.


How healthcare workers reacted to the different COVID-19 waves: An Italian survey.
The COVID-19 pandemic had a huge impact on radiology departments all over the world, affecting both management and healthcare workers (HCWs). Therefore, it became challenging to guarantee high standards of diagnosis while keeping up with the workload. The study was approved by the institutional review board. Its aim was to assess the impact of the COVID-19 pandemic over the radiology departments and HCWs through a survey. The questionnaire was available online from January to March 2022. Twelve areas of interest (sessions) were highlighted in the survey. The number of total responders was 1376 and 73.7% of participants worked in public healthcare facilities. Comparisons between participants working in public versus private healthcare facilities were carried out using chi-square tests and Fisher tests. Within public healthcare workers, 82% affirmed having operating instruction protocols regarding confirmed or suspected COVID-19 patient CT management (p< 0.001). Private healthcare facilities had fewer CT scanners available in general (p< 0.001); in fact, only 18% of them affirmed having two or more CT scanners, and did not have CT scanners dedicated to confirmed or suspected COVID-19 patients (p< 0.001). Finally, public facilities strongly reduced (by 88%) the number of examinations booked during the first wave, compared to private healthcare facilities (p< 0.001). This survey showed that public facilities appeared to be better prepared from an organizational point of view than private facilities. Rescheduling the examinations booked during the first COVID-19 wave was challenging and not always possible.


Transcriptome profiling in adult attention-deficit hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with an estimated heritability of around 70%. Although the largest genome-wide association study (GWAS) meta-analysis on ADHD identified independent loci conferring risk to the disorder, the molecular mechanisms underlying the genetic basis of the disorder remain to be elucidated. To explore ADHD biology, we ran a two-step transcriptome profiling in peripheral blood mononuclear cells (PBMCs) of 143 ADHD subjects and 169 healthy controls. Through this exploratory study we found eight differentially expressed genes in ADHD. These results highlight promising candidate genes and gene pathways for ADHD and support the use of peripheral tissues to assess gene expression signatures for ADHD.


Potential prognostic value of a eight ferroptosis-related lncRNAs model and the correlative immune activity in oral squamous cell carcinoma.
To investigate the prognostic value of ferroptosis-related long noncoding RNAs (lncRNAs) in oral squamous cell carcinoma (OSCC) and to construct a prognostic risk and immune activity model. We obtained clinical and RNA-seq information on OSCC patient data in The Cancer Genome Atlas (TCGA) Genome Data Sharing (GDC) portal. Through a combination of a differential analysis, Pearson correlation analysis and Cox regression analysis, ferroptosis-related lncRNAs were identified, and a prognostic model was established based on these ferroptosis-related lncRNAs. The accuracy of the model was evaluated via analyses based on survival curves, receiver operating characteristic (ROC) curves, and clinical decision curve analysis (DCA). Univariate Cox and multivariate Cox regression analyses were performed to evaluate independent prognostic factors. Then, the infiltration and functional enrichment of immune cells in high- and low-risk groups were compared. Finally, certain small-molecule drugs that potentially target OSCC were predicted via use of the L1000FWD database. The prognostic model included 8 ferroptosis-related lncRNAs (FIRRE, LINC01305, AC099850.3, AL512274.1, AC090246.1, MIAT, AC079921.2 and LINC00524). The area under the ROC curve (AUC) was 0.726. The DCA revealed that the risk score based on the prognostic model was a better prognostic indicator than other clinical indicators. The multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for OSCC. There were differences in immune cell infiltration, immune functions, m6A-related gene expression levels, and signal pathway enrichment between the high- and low-risk groups. Subsequently, several small-molecule drugs were predicted for use against differentially expressed ferroptosis-related genes in OSCC. We constructed a new prognostic model of OSCC based on ferroptosis-related lncRNAs. The model is valuable for prognostic prediction and immune evaluation, laying a foundation for the study of ferroptosis-related lncRNAs in OSCC.


Non-visualization versus normal appearance of cavernous arteries on selective internal pudendal pharmaco-angiograms: comparison with duplex scanning, cavernosal artery systolic occlusion pressure and penile brachial index.
To determine whether selective internal pudendal pharmaco-angiography (SIPA) is the most reliable diagnostic procedure for evaluating the function of the cavernosal arteries. Both sides of the selective internal pudendal pharmaco-angiogram taken in 35 patients (70 cases), whose history was suggestive of post-traumatic arteriogenic impotence, were evaluated separately and compared to the corresponding side using the penile brachial index (PBI), duplex scanning and cavernosal artery systolic occlusion pressure (CASOP). There was no significant difference in the peak flow velocity and diameter changes of the cavernosal arteries on duplex scanning, in pressure differences between the brachial artery systolic pressure and the CASOP, and in the PBI between the group with a normal appearance on SIPA and the other where the cavernosal arteries were not visualized. There was no significant difference in the results of these functional evaluations between the normal group and cases where the cavernosal arteries were not visualized accompanied by a completely obstructed internal pudendal artery or common penile artery visible on SIPA. This study is unable to confirm the value of SIPA in evaluating the function of the cavernosal arteries as it provides only anatomical information.


Dynamic study of methionine uptake in glioma using positron emission tomography.
In order to evaluate the methionine uptake of a glioma with positron emission tomography (PET), the kinetics of carbon-11 methionine was investigated in 11 patients by measuring the free 11C-methionine in plasma as an input function following intravenous administration. When the mean clearance curve of free 11C-methionine in plasma instead of individual 11C-methionine clearance curves was used, mean differences in uptake rate and distribution volume were 4.0% and 4.6% respectively. By applying the mean clearance curve of free 11C-methionine in 18 glioma patients, significant differences in 11C-methionine uptake rate and distribution volume were found according to pathological grading. For the accurate evaluation of the metabolism of 11C-methionine, it is therefore preferable that the actual level of free 11C-methionine in the plasma be measured, especially for the follow-up of individual cases. The study also demonstrated that the mean clearance curve of 11C-methionine in plasma might be employed as an input curve for calculating the uptake rate and distribution volume with small errors.


Binding of C3 molecules to membranes via the SH-residue generated by the cleavage of a thioester bond can initiate complement activation.
Dithiopyridine (DTP)-dipalmitoylphosphatidylethanolamine (DTP-DPPE) was incorporated into liposome membranes to prepare DTP-liposomes. The DTP-liposomes could be lysed by reaction with the alternative complement pathway of any kind of serum tested. Activation of the alternative complement pathway has been shown to be mediated by the binding of C3 molecules to DTP on the liposomes via the SH-residue generated by the cleavage of thioester bond in the alpha-chain of the molecules.


Functional connectomic profile correlates with effective anterior thalamic stimulation for refractory epilepsy.
Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is an effective treatment for refractory epilepsy; however, seizure outcome varies among individuals. Identifying a reliable noninvasive biomarker to predict good responders would be helpful. To test whether the functional connectivity between the ANT-DBS sites and the seizure foci correlates with effective seizure control in refractory epilepsy. We performed a proof-of-concept pilot study of patients with focal refractory epilepsy receiving ANT-DBS. Using normative human connectome data derived from 1000 healthy participants, we investigated whether intrinsic functional connectivity between the seizure foci and the DBS site was associated with seizure outcome. We repeated this analysis controlling for the extent of seizure foci, distance between the seizure foci and DBS site, and using functional connectivity of the ANT instead of the DBS site to test the contribution of variance in DBS sites. Eighteen patients with two or more seizure foci were included. Greater functional connectivity between the seizure foci and the DBS site correlated with more favorable outcome. The degree of functional connectivity accounted for significant variance in clinical outcomes (DBS site: |r| = 0.773, p < 0.001 vs ANT-atlas: |r| = 0.715, p = 0.001), which remained significant when controlling for the extent of the seizure foci (|r| = 0.773, p < 0.001) and the distance between the seizure foci and DBS site (|r| = 0.777, p < 0.001). Significant correlations were independent of variance in the DBS sites (|r| = 0.148, p = 0.57). These findings suggest that functional connectomic profile is a potential reliable non-invasive biomarker to predict ANT-DBS outcomes. Accordingly, the identification of ANT responders could decrease the surgical risk for patients who may not benefit and optimize the cost-effective allocation of health care resources.


Determination of glucose using a coupled-enzymatic reaction with new fluoride selective optical sensing polymeric film coated in microtiter plate wells.
The determination of glucose in beverages is demonstrated using newly developed fluoride selective optical sensing polymeric film that contains aluminum (III) octaethylporphyrin (Al[OEP]) ionophore and the chromoionophore ETH7075 cast at the bottom of wells of a 96-well polypropylene microtiter plate. The method uses a dual enzymatic reaction involving glucose oxidase enzyme (GOD) and horseradish peroxidase (HRP), along with an organofluoro-substrate (4-fluorophenol) as the source of fluoride ions. The concentration of fluoride ions after enzymatic reaction is directly proportional to the glucose level in the sample. The method has a detection limit of 0.8 mmol L(-1), a linear range of 0.9- 40 mmol L(-1) and a sensitivity of 0.125 absorbance unit/decade of glucose concentration. Glucose levels in several beverage samples determined using the proposed method correlate well with a reference spectrophotometric enzyme method based on detection of hydrogen peroxide using bromopyrogallol red dye (BPR). The new method can also be used to determine H(2)O(2) concentrations in the 0.1 - 50 mmol L(-1) range using a single enzymatic reaction involving H(2)O(2) oxidation of 4-fluorophenol catalyzed by HRP. The methodology could potentially be used to detect a wide range of substrates for which selective oxidase enzymes exist (to generate H(2)O(2)), with the high throughput of simple microtiter plate detection scheme.


LINC-PINT Suppresses the Aggressiveness of Thyroid Cancer by Downregulating miR-767-5p to Induce TET2 Expression.
Long noncoding RNA (lncRNA) long intergenic nonprotein-coding RNA, p53-induced transcript (LINC-PINT) has shown anti-invasive activity in lung and colon cancer cells. However, the role of LINC-PINT in thyroid cancer is unclear. In the present work, we explored the expression of LINC-PINT in 60 paired thyroid cancer and adjacent normal tissues. The clinical significance and biological function of LINC-PINT in thyroid cancer were determined. LINC-PINT expression was downregulated in thyroid cancer relative to adjacent normal tissues (p = 0.0002). Low expression of LINC-PINT was significantly associated with advanced tumor node metastasis (TNM) stage (p = 0.0306) and lymph node metastasis (p = 0.0359). Ectopic expression of LINC-PINT suppressed the proliferation, invasion, and tumorigenesis of thyroid cancer cells. Mechanistically, LINC-PINT associated with and downregulated microRNA (miR)-767-5p. Moreover, LINC-PINT overexpression relieved miR-767-5p-mediated repression of ten-eleven translocation 2 (TET2). miR-767-5p promoted aggressiveness of thyroid cancer, which was reversed by overexpression of TET2. Coexpression of miR-767-5p or depletion of TET2 rescued the inhibitory effect of LINC-PINT on thyroid cancer cell proliferation and invasion. In addition, there was a negative correlation between miR-767-5p and LINC-PINT in thyroid cancer (r = -0.34772, p = 0.01789). Taken together, LINC-PINT functions as a tumor suppressor in thyroid cancer via the miR-767-5p/TET2 axis, representing a potential therapeutic target for thyroid cancer.


Treatment of posttraumatic bone defects of the forearm with vascularized fibular grafts. Follow up after fourteen years.
Among several techniques proposed for the reconstruction of posttraumatic bone defects of the forearm, that of free vascularised fibular graft (FVFG) is one of the most widely used. We study the long-term outcomes of 14 patients who underwent FVFG between 1994 and 2009, with a minimum follow up of 8 years and a maximum of 23 years (mean: 13.9 years). Demographic, clinical and radiological variables were collected retrospectively. The DASH scale was used for clinical assessment. Fourteen patients were operated on by the same surgeon, applying FVFG for the reconstruction of posttraumatic bone defects of the forearm (three septic non-union of the ulna or radius, five radius fractures, two ulna fractures and four fractures of both bones). The maximum length of the defect was 11 cm and the minimum length was 6 cm. In four cases, reconstruction of the two bones was achieved using the double barrel technique, and in another four cases, an osteoseptocutaneous flap was used. Fixation was performed with 3.5 mm reconstruction plates in thirteen cases and with 3.5 mm screws in one case. Consolidation was obtained in 12 cases (85.7%) after an average time of 4.2 months (range: 2-6.5 months). In one case, consolidation of the proximal ulnar fracture site was not achieved, and in another, following the failure of reconstruction attempts, an arthrodesis was performed. At the end of the follow-up period, the patients had an average DASH score of 17.1 points (range 1.8-68.1). FVFG is a valid option for the reconstruction of posttraumatic bone defects of the forearm. Its use via the double barrel method or as an osteocutaneous composite graft enables the simultaneous reconstruction of both forearm bones and associated soft tissue injuries. Long-term follow-up of patients who have undergone this technique confirms its satisfactory functional and radiological results.


Developmental trajectories of pregnant and postpartum depression in an epidemiologic survey.
To estimate the prevalence and determinants for the peripartum depression. Data were extracted from the 2 waves of the National Epidemiologic Study of Alcohol and Related Conditions (NESARC), a representative sample of the US population corresponding to 34,653 participants. All women pregnant during the year before the second assessment were included. Peripartum depression was evaluated according a semi-structured interview at Wave 2. Risk factors covering life from childhood through adulthood, and including sexual abuse, family history of depression and psychiatric disorder lifetime were evaluated at wave 1. Stressful life event and obstetric factors were evaluated for the period of 12 months preceding the second interview. In the sample of 1085 participants pregnant at wave 2, the prevalence of peripartum depression was 10.8%. Women with a peripartum depression reported higher rates of sexual abuse in childhood (OR=3.07), family history of depression (OR=3.27). A history of mental disorder was associated with a higher rate of peripartum depression (OR=3.43) Four disorders were specifically associated with higher rate of peripartum depression including depression (OR=4.91), substance use disorder (OR=2.37), bipolar disorder (OR=2.39) and history of suicide attempt (OR=3.79). Peripartum depression was associated with stressful life event in the last year (OR=3.03), and complications during pregnancy (OR=2.10). Not distinguish between depressed women during pregnancy from postpartum depressed women. Depression affects more than one in 10 women during peripartum. The factors associated with peripartum depression are traumatic, personal or family history of mental disorder, in a timeframe covering life from childhood through adulthood.


The influence of educational level in peri-menopause syndrome and quality of life among Chinese women.
Objective: To investigate the influence of education level in the peri-menopausal symptoms and quality of life (QoL) among Chinese women.Methods: We carried out a cross-sectional study of 1632 peri-menopausal women (age 40-60 y) who visited Hangzhou Women's Hospital from November 2018 to November 2019. The menopausal symptoms were evaluated by modified Kupperman index (KI). World Health Organization Quality of Life (WHOQOL-BREF) questionnaire was used to evaluate the QoL.Result: In total, 1501 women were included in the analysis. The mean age of natural menopause was 49.63 years in China. The five most frequent symptoms in menopausal women were Hot flash (75.53%), sexual problems (72.62%), insomnia (67.29%), fatigue (65.56%), and irritability (61.89%). Natural menopausal age, parity, BMI, bone mineral density, depression, skin formication, total score of KI, and the score of WHOQOL-BREF questionnaire were different in different educational background women (p < .05).Conclusions: The results of the study suggest that education level is associated with the age of natural menopause and menopausal symptoms. A high educational level is correlated with a better score of WHOQOL-BREF in peri-menopause women.


Inherited disorders of carbohydrate metabolism in children studied by 13C-labelled precursors, NMR and GC-MS.
Glucose carbon recycling, glucose production and glucose turnover in glycogen storage disease type I and type II patients and control subjects were determined by a novel approach--mass isotopomer analysis of plasma 13C glucose. Changes in the isotopomer distribution of plasma 13C glucose were found only in glycogen storage disease type III patients and control subjects. Glucose carbon recycling parameters were also derived from 13C NMR spectra of plasma glucose C-1 splitting pattern. Our results eliminate a mechanism for glucose production in glycogen storage disease type I children involving gluconeogenesis. However, glucose release by amylo-1,6-glucosidase activity is in agreement with our results. A quantitative determination of the metabolic pathways of fructose conversion to glucose in normal children, and in children with disorders of fructose metabolism was derived from 13C NMR measurement of plasma 13C glucose isotopomer populations following [U-13C]fructose administration. A direct pathway from fructose, bypassing fructose-1-phosphate aldolase, to fructose-1,6-diphosphate in controls and hereditary fructose intolerant children (47% and 27%, respectively) was identified. In children with fructose-1,6-diphosphatase deficiency, only the gluconeogenic substrates were 13C labelled but no synthesis of glucose from [U-13C]fructose occurred. The significantly lower (by 68%) conversion of fructose to glucose in hereditary fructose intolerance, as compared to control subjects, and non-conversion in fructose-1,6-diphosphatase deficient subjects after [U-13C]fructose (approximately 20 mg/kg) administration can serve as the basis of a safe diagnostic test for patients suspected of inborn errors of fructose metabolism and other defects involving gluconeogenesis.


Ruptured abdominal aortic aneurysm in a young male patient, a rare case report.
Abdominal aortic aneurysm (AAA) is commonly a disease of the elderly population with an atherosclerotic aorta. We present a rare case scenario of a large ruptured AAA in a young patient. A 32-year-old man presented to the Emergency Department with abdominal pain. On examination he had hypotension with a severely tender abdomen. Imaging revealed a ruptured 10 cm abdominal aortic aneurysm (AAA). He underwent an emergency open aneurysm repair and was discharged well on post-operative day 12. Apart from smoking, he had no known significant risk factors contributing to an AAA of such size. Clinical features and family history suggested a possible underlying connective tissue disorder. A painful abdomen and hypotension in a young patient should prompt investigations to rule out a rare but life-threatening diagnosis of a ruptured AAA. A possible underlying connective tissue disorder should be investigated for in any young patient presenting with an AAA.


DNA-strand molecular beacon optical processor.
Due to the characteristics of the newly developed DNA computing, many researchers are interested in this specialty. One advantage of DNA " Deoxyribonucleic acid" is that it has ability to resolve a Boolean circuit with various types of gates at the same time in a single level. Most of the prior models suffered from the limitations that each level of the circuit requests the gates to be of some kind. The model proposed in this work increases parallelism and reduces human intervention to a tremendous extent. When level-wise simulation is executed, the simulation for each model shows the decrease in the number of nitrogen bases used, which leads to the processing of the largest number of data with the ability to increase the length of a word, in addition to the adoption of the parallel principle of implementation. The model is designed on a mechanism which includes adder and multiplier.


Pseudo-obstruction of the colon during pelvic radiotherapy.
Pseudo-obstruction of the colon, or Ogilvie's syndrome, is characterized by an adynamic, dilated, unobstructed colon, the exact cause of which remains obscure. Although several precipitating factors have been described in the literature, we have observed three patients whose pseudo-obstruction of the colon occurred during interstitial and intracavitary pelvic irradiation. Such a cause has not been noted previously. Pseudo-obstruction of the colon can have serious consequences if it is not recognized early and treated vigorously.


Study of hepatotoxicity of naltrexone in the treatment of alcoholism.
Since a black box warning was issued by the Food and Drug Administration regarding the use of the opiate antagonist naltrexone (NTX), many clinicians have been concerned about current labeling of the potential hepatotoxicity risk of NTX in the treatment of opiate dependence and alcoholism. Despite many reports that demonstrated that the use of NTX did not cause elevation of liver enzymes, controversy concerning whether NTX is hepatotoxic continues. The current study monitored 74 alcoholic patients who received 25mg of NTX daily in the first week and then 50mg of NTX daily for the rest of the 12-week period. After the 12-week treatment, levels of the hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) did not show any elevation, except in one subject, and the results strongly support that NTX did not induce abnormalities in liver function tests or elevate the liver enzymes. Instead, a statistical significance of decreasing levels of ALT and AST in the liver was shown throughout the study. These findings provide further support that NTX is not hepatotoxic at the recommended daily dose and may be beneficial for patients with elevated liver enzymes.


Cardiovascular event risk estimated by myocardial perfusion SPECT combined with clinical data.
Myocardial scintigraphy plays important roles in the diagnosis of coronary artery disease, prognostic risk stratification, and determination of the treatment policy. Recently, several large-scale clinical trials reported that coronary intervention was not necessarily advantageous for preventing future cardiac events in patients with stable angina. This review summarizes how we can estimate cardiac event risks based on Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS), and describes that the combination of scintigraphy and other clinical features leads to more accurate stratification of prognosis and the determination of subsequent treatment policy.


Tight coupling between coral reef morphology and mapped resilience in the Red Sea.
Lack of knowledge on the conservation value of different reef types can stymie decision making, and result in less optimal management solutions. Addressing the information gap of coral reef resilience, we produce a map-based Remote Sensed Resilience Index (RSRI) from data describing the spatial distribution of stressors, and properties of reef habitats on the Farasan Banks, Saudi Arabia. We contrast the distribution of this index among fourteen reef types, categorized on a scale of maturity that includes juvenile (poorly aggraded), mature (partially aggraded), and senile (fully aggraded) reefs. Sites with high reef resilience can be found in most detached reef types; however they are most common in mature reefs. We aim to stimulate debate on the coupling that exists between geomorphology and conservation biology, and consider how such information can be used to inform management decisions.


Enhanced oil displacement by nanofluid's structural disjoining pressure in model fractured porous media.
Nanofluids for improved oil recovery has been demonstrated through laboratory corefloods. Despite numerous experimental studies, little is known about the efficacy of nanofluids in fractured systems. Here, we present studies of nanofluid injection in fractured porous media (both water-wet and oil-wet) formed by sintering borosilicate glass-beads around a dissolvable substrate. The fracture inside the porous medium is characterized and visualized using a high resolution X-ray microtomography. Based on a simple displacement theory, the nanofluid injection is conducted at a rate where structural disjoining pressure driven oil recovery is operational. An additional 23.8% oil was displaced using nanofluid after brine injection with an overall recovery efficiency of 90.4% provided the matrix was in its native wettability state. But only 6% additional oil was displaced by nanofluid following brine injection when the bead-pack was rendered oil-wet. Nanofluids appear to be a good candidate for enhanced oil recovery (EOR) in fractured water-wet to weakly water-wet media but not necessarily for strongly oil-wet systems. Our laboratory studies enable us to understand limitations of nanofluids for improving oil recovery in fractured media.


Catalyst development for tar reduction in biomass gasification: Recent progress and the way forward.
Biomass valorization via catalytic gasification is a potential technology for commercizalization to industrial scale. However, the generated tar during biomass valorization posing numerous problems to the overall reaction process. Thus, catalytic tar removal via reforming, cracking and allied processes was among the priority areas to researchers in the recent decades. This paper reports new updates on the areas of catalyst development for tar reduction. The catalyst survey include metallic and metal-promoted materials, nano-structured systems, mesoporous supports like zeolites and oxides, group IA and IIA compounds and natural catalysts based on dolomite, palygorskite, olivine, ilmenite, goethite and their modified derivatives. The influence of catalyst properties and parameters such as reaction conditions, catalyst preparation procedures and feedstock nature on the overall activity/selectivity/stability properties were simultaneously discussed. This paper not only cover to model compounds, but also explore to real biomass-derived tar for consistency. The area that require further investigation was identified in the last part of this review.


Gendered division of labor in a Celtic community? A comparison of sex differences in entheseal changes and long bone shape and robusticity in the pre-Roman population of Verona (Italy, third-first century BC).
The presence of a gendered subdivision of labor has been bioarchaeologically investigated in various prehistoric and historical contexts. Little is known, however, about the type of differences in daily activities characterizing men and women among the Celtic communities of Italy. The focus of the present study is the analysis of differences in patterns of entheseal changes (ECs) and long bone shape and robusticity between sexes among the Cenomani Gauls of Seminario Vescovile (SV-Verona, Italy, third-first century BC). The sample includes 56 adult individuals (22 females and 34 males). Presence of ECs on nine bilateral postcranial attachment sites, and values of humeral and femoral shape and robusticity indices based on external measurements were compared between sexes by means of generalized linear models and Mann-Whitney tests. Results show a lack of difference between sexes in long bone shape and robusticity, and a higher incidence of upper and, especially, lower limb ECs in males. These results suggest the presence of sex-specific activities at SV mostly related to farming and differently influencing the considered variables. Also, this study suggests the relevance of a series of nonbiomechanical factors (developmental, hormonal, genetic, and methodological) when attempting biocultural reconstructions from osteoarchaeological samples.


Percutaneous cryoablation and vertebroplasty: a case report.
A 70-year-old man with a painful vertebral metastasis was treated with combined percutaneous cryoablation and vertebroplasty therapy (CVT) in one session. The patient was suffering from diffuse visceral metastasized cholangiocarcinoma. After several weeks of back pain, magnetic resonance imaging documented a single L2 bone metastasis. In consultation with the oncologists, palliative combined CVT was administered with the aim of obtaining pain relief and bone stabilization. In our experience this combined treatment is safe and effective for immediate pain relief in painful bone metastases when other standard palliative treatments have failed.


Neuronal binding by antibodies can be influenced by low pH stress during the isolation procedure.
Low pH stress and its influence on antibody binding is a common consideration among chemists, but is only recently emerging as a consideration in Immunological studies. Antibody characterizations in Multiple Sclerosis (MS), an autoimmune disease of the Central Nervous System (CNS) has revealed that antibodies in the cerebrospinal fluid (CSF) of patients with Multiple Sclerosis bind to myelin-related and non-myelin antigen targets. Many laboratories have used molecular biology techniques to generate recombinant human antibodies (rhAbs) expressed by individual B cells from healthy donors and patients with systemic autoimmune disease to identify antigen targets. This approach has been adapted within the Neuroimmunology research community to investigate antigen targets of individual B cells in the CSF of MS patients. Our laboratory determines which antibodies to clone based on their immunogenetics and this method enriches for cloning of rhAbs that bind to neurons. However, newer technologies to assist in purification of these rhAbs from culture supernatants use an acidic elution buffer which may enhance low pH stress on the antibody structure. Our laboratory routinely uses a basic elution buffer to purify rhAbs from culture supernatants to avoid low pH stress to the antibody structure. Our goal was to investigate whether acidic elution of our rhAbs using Next Generation Chromatography would impact the rhAbs' ability to bind neurons. The limited data presented here for two neuron-binding rhAbs tested indicated that acidic elution buffers used during rhAb purification impacted the ability of rhAbs with low CDR3 charge to maintain binding to neuronal targets. Reproducibility in a larger panel of rhAbs and factors underlying these observations remain untested.


Effects of +Gz Loads on Structural Organization of Central Autonomic Nuclei.
Structural alterations in the central autonomic nuclei (dorsal vagal complex and intermediolateral nucleus) of the centrifuged random-bred male rats subjected to +Gz loads were examined. Acute exposure to gravitational loads predominantly produced the reactive changes in these nuclei, while persistently repeated regular loads resulted in cumulation of the destructive alterations. The structural perturbations in the central autonomic nuclei can disturb the autonomic regulation of physiological functions. The character of such disturbances is partially determined by the peculiarities in structural organization of these nuclei.


Cannabinoid type 2 receptor manipulates skeletal muscle regeneration partly by regulating macrophage M1/M2 polarization in IR injury in mice.
The beneficial effects of cannabinoid type 2 receptor (CB2R) activation have been verified in various tissue repair processes. Our recent study revealed CB2R activation promotes myogenesis partly through Nrf2 signaling in a mouse skeletal muscle ischemia-reperfusion (IR) injury model. Other relevant mechanisms need to be further elucidated. Macrophages orchestrate tissue regeneration mainly by changing their phenotype and function. The aim of this study was to investigate the role of CB2R in IR-induced skeletal muscle regeneration, focusing on its impact on macrophage polarization and the consequences on myogenesis. The effects of CB2R on skeletal muscle regeneration, and the macrophage infiltration and M1/M2 polarization were tested with the IR injury model in wild type (WT) and CB2R knockout (CB2R-KO) mice. The effect of CB2R on peritoneal macrophage polarization, and its impact on the myoblasts differentiation was evaluated by co-culture experiments in vitro. The present study revealed the myofiber regeneration was hindered in the CB2R-KO mice. The infiltration of M1 macrophages and relevant markers' protein expression were enhanced in the CB2R-KO mice, while that of M2 macrophages was decreased compared with the WT mice. The in vitro studies further demonstrated that the absence of CB2R promoted M1 polarization while inhibited M2 polarization. The promoted M1 polarization and retarded M2 polarization in CB2R-KO macrophages hindered myoblasts differentiation. Overall, these results suggested CB2R plays a beneficial effect on skeletal muscle regeneration partly by regulating macrophage M1/M2 polarization after IR injury in mice.


A neural correlate of oculomotor sequences in supplementary eye field.
Complex learned motor sequences can be composed of a combination of a small number of elementary actions. To investigate how the brain represents such sequences, we devised an oculomotor sequence task in which the monkey had to choose the target solely by the sequential context, not by the current stimulus combination. We found that many neurons in the supplementary eye field (SEF) became active with a specific target direction (D neuron) or a specific target/distractor combination (C neuron). Furthermore, such activity was often selective for one among several sequences that included the combination (S neuron). These results suggest that the SEF contributes to the generation of saccades in many learned sequences.


Cost of dialysis in Tanzania: evidence from the provider's perspective.
Although End Stage Renal Disease (ESRD) is a disease of increasing epidemiological relevance very little is known about the cost of providing the respective dialysis services in Tanzania. This paper estimates the costs of dialysis for ESRD patients at Muhimbili National Hospital (MNH) in Tanzania in the year 2014. Cost calculations are based on the provider perspective and include only the direct cost of dialysis treatment. Cost of drugs and consumables were obtained from the price list issued by the Medical Stores Department (MSD) in Tanzania. Additional data were collected through face-to-face interview with experts at the dialysis unit. MNH performs on average 442 hemodialysis per month (34 patients, with three sessions per week) with a personnel placement of 20 nurses, four nephrologists, eight registrars, one nutritionist, two biomedical engineers, four health attendants and nine dialysis machines. The respective average unit cost per hemodialysis is 176 US$. Consequently, an average patient requiring three dialyses per week (i.e. 156 dialyses per year) will cause annual costs of 27,440 US$. The cost of dialysis is enormous for a least developed country like Tanzania where resources and technology are rather limited. Thus, from the economic point of view, it seems rational to allocate health care budgets towards diseases that are curable, have a higher cost-effectiveness and cater for the majority of the population. However, before a final decision on allocation of budgets towards dialysis is made all effort must be invested to improve technical efficiency by cutting the enormous unit cost.


Impact of body weight on long-term survival after lung transplantation.
The purpose of this study was to determine the impact of a pretransplantation determination of body mass index (BMI) on survival after lung transplantation. Univariate and multivariate survival analyses of a single institution database consisting of 85 patients who had undergone lung transplantations between March 1994 and October 1998. University of Florida Health Science Center. Kaplan-Meier survival curves showed that patients who were obese (ie, BMI, > or = 30) at a pretransplantation assessment had a marked decrease in posttransplantation survival time (log rank, p < 0.05; Wilcoxon, p < 0.05). The final Cox regression model revealed that the most powerful predictors of mortality after lung transplantation were higher pretransplantation BMI and the development of obliterative bronchiolitis. Our results suggest that the posttransplantation risk for mortality is possibly three times greater for obese patients than for nonobese patients. Additional study is needed to identify the mechanisms for such higher risk in obese patients. Our data also suggest that transplantation centers should not routinely reject underweight patients (ie, BMI, < 18.5) or overweight patients (ie, BMI, 25 to 29.9) for lung transplantation listing solely on the basis of weight, as their outcomes may not be significantly different than patients with normal BMIs.


Intracellular histidine content of various tissues (brain, striated muscle and liver) in experimental chronic renal failure.
Intracellular histidine levels were determined in brain, striated muscle and liver of rats with chronic renal insufficiency (5/6-nephrectomy) and compared both with normal rats and food-restricted (pair-fed) animals. There was no difference in plasma histidine concentration of the three groups whereas in the brain of the uremic rats histidine was significantly increased. Since there existed no alteration of the cerebral histidine in the corresponding pair-fed group, the finding of a raised histidine level in the renal insufficient rats seems to be due to a specific uremic disorder caused by a cerebral disturbance in histidine metabolism.


Finding downbeats with a relaxation oscillator.
A relaxation oscillator model of neural spiking dynamics is applied to the task of finding downbeats in rhythmical patterns. The importance of downbeat discovery or 'beat induction' is discussed, and the relaxation oscillator model is compared to other oscillator models. In a set of computer simulations the model is tested on 35 rhythmical patterns. The model performs well, making good predictions in 34 of 35 cases. In an analysis we identify some shortcomings of the model and relate model behavior to dynamical properties of relaxation oscillators.


Linked fate and mental health among African Americans.
Linked fate, the feeling that what happens to one's group may indelibly shape one's own life, is variously conceptualized as an aspect of ethnoracial identity, expression of political solidarity, and/or sense of ethnoracial consciousness. In this study, I contend that, within the context of stigmatization, linked fate may also be compellingly conceptualized as an expression of collective threat and vulnerability with potential relevance for the mental health of African Americans, in particular. Nevertheless, existing research on race and mental health has remained silent on this issue, as linked fate has received little scholarly attention from researchers interested in mental health. Building on prior research on ethnoracial identity, stigmatization, and mental health among African Americans, I introduce linked fate as a neglected, yet important phenomenon among stigmatized minorities, which is deeply associated with ethnoracial identification and should also be considered when examining the consequences of ethnoracial identification on the mental health of African Americans. Using nationally-representative data and logistic regression, I find that linked fate not only fails to be health-protective but is significantly associated with poorer mental health among African Americans in the form of increased suffering from major depression, bipolar I, and anxiety disorders.


Neuroprotective effect of cyclic GMP against radical-induced toxicity in cultured spinal motor neurons.
We have previously reported that nitric oxide-related cyclic guanosine-3',5'-monophosphate (GMP) protected spinal nonmotor neurons, but not motor neurons against chronic glutamate-induced toxicity, which is associated with selective motor neuronal death after glutamate stress. In this report, we investigated the effect of cyclic GMP against reactive oxygen species (ROS)-induced toxicity in cultured neurons from embryonic rat spinal cords. Pretreatment with a cGMP analogue, 8-bromoguanosine monophosphate (8br-cGMP), for 12-24 hours protected both spinal motor neurons and nonmotor neurons against injury induced by either hydrogen peroxide (H(2)O(2)), or a glutathione depletor, L-buthionine-[S,R]-sulfoximine (BSO). This protective effect was reversed by coadministration with the cGMP-dependent protein kinase (PKG) inhibitor Arg-Lys-Arg-Ala-Arg-Lys-Glu. Interestingly, when cultures were exposed to BSO for 24 hours to allow irreversible inhibition of glutathione synthesis, 8br-cGMP protected only nonmotor neurons. Our results indicate that cGMP attenuates oxidative injury to cultured spinal neurons, in a mechanism associated with glutathione synthesis.


New friendships and old feuds: relationships between innate lymphoid cells and microbial communities.
Mammalian barrier surfaces, including the skin, lung and intestine, are constantly exposed to environmental stimuli, including beneficial and pathogenic microbes, dietary substances and non-organic materials. At these anatomical sites it is essential to maintain barrier integrity to promote tissue homeostasis and prevent local and systemic inflammation. As such, changes in the composition and localization of commensal bacteria are closely associated with inflammatory, metabolic and infectious disease in mammals. Cells of the innate and adaptive immune systems have a crucial role in the tight regulation of host-commensal relationships. A recently described family of immune cells, termed innate lymphoid cells (ILCs), contributes to inflammation, modulates adaptive immunity and regulates wound healing and tissue regeneration. ILCs are present at barrier surfaces, and thus are in close proximity to environmental antigens, including commensal bacteria. The composition and localization of microbial communities have a profound impact on immunity at barrier surfaces as well as at distant sites. This review will summarize the phenotypic characteristics of ILC family members and discuss recent findings about the interactions between ILCs and the microbiota in the contexts of homeostasis, immunity, inflammation and tissue organization and repair.


Clustering distributions with the marginalized nested Dirichlet process.
We introduce a marginal version of the nested Dirichlet process to cluster distributions or histograms. We apply the model to cluster genes by patterns of gene-gene interaction. The proposed approach is based on the nested partition that is implied in the original construction of the nested Dirichlet process. It allows simulation exact inference, as opposed to a truncated Dirichlet process approximation. More importantly, the construction highlights the nature of the nested Dirichlet process as a nested partition of experimental units. We apply the proposed model to inference on clustering genes related to DNA mismatch repair (DMR) by the distribution of gene-gene interactions with other genes. Gene-gene interactions are recorded as coefficients in an auto-logistic model for the co-expression of two genes, adjusting for copy number variation, methylation and protein activation. These coefficients are extracted from an online database, called Zodiac, computed based on The Cancer Genome Atlas (TCGA) data. We compare results with a variation of k-means clustering that is set up to cluster distributions, truncated NDP and a hierarchical clustering method. The proposed inference shows favorable performance, under simulated conditions and also in the real data sets.


Synthesis of 1-(2-chloro-2-phenylethyl)-6-methylthio-1H-pyrazolo[3,4-d]pyrimidines 4-amino substituted and their biological evaluation.
A new series of 4-amino-6-methylthio-1H-pyrazolo[3,4-d]pyrimidines (2a-m) bearing the 2-chloro-2-phenylethyl chain at the N1 position, has been synthesized. The affinity of these compounds for A1 adenosine receptor (A1AR) was measured. The compounds showed poor affinity. A more interesting result was obtained by 2a, 2d, 2g, which demonstrated inhibitory activity on cell proliferation of the A-431 cell line stimulated by epithelial growth factor (EGF) and on EGF receptor tyrosine kinase (EGFR-TK) phosphorylation.


A brief history of M. C. Schaub's legacies: a life dedicated to heart and muscle research : In memoriam Marcus C. Schaub (1936-2018).


Temporal calcium profiling of specific circadian neurons in freely moving flies.
There are no general methods for reliably assessing the firing properties or even calcium profiles of specific neurons in freely moving flies. To this end, we adapted a GFP-based calcium reporter to luciferase that was expressed in small subsets of circadian neurons. This Tric-LUC reporter allowed a direct comparison of luciferase activity with locomotor activity, which was assayed in the same flies with video recording. The LUC profile from activity-promoting E cells paralleled evening locomotor activity, and the LUC profile from sleep-promoting glutamatergic DN1s (gDN1s) paralleled daytime sleep. Similar profiles were generated by novel reporters recently identified based on transcription factor activation. As E cell and gDN1 activity is necessary and sufficient for normal evening locomotor activity and daytime sleep profiles, respectively, we suggest that their luciferase profiles reflect their neuronal calcium and in some cases firing profiles in wake-behaving flies.


Preeclampsia: a defect in decidualization is associated with deficiency of Annexin A2.
Decidualization defects in the endometrium have been demonstrated at the time of delivery in women with severe preeclampsia and to linger for years, which suggests a maternal contribution to the pathogenesis of this condition. Global transcriptional profiling reveals alterations in gene expression, which includes down-regulation of Annexin A2 in severe preeclampsia patients with decidualization resistance. We investigated the functional role of Annexin A2 deficiency during endometrial decidualization and its potential contribution to shallow trophoblast invasion during implantation and subsequent placentation using in vitro and in vivo modeling. Annexin A2 gene and protein levels were assessed during in vitro decidualization of human endometrial stromal cells isolated from biopsy specimens that were collected from women with previous severe preeclampsia (n=5) or normal obstetric outcomes (n=5). Next, Annexin A2 was inhibited with small interference RNA in control human endometrial stromal cells that were isolated from endometrial biopsy specimens (n=15) as an in vitro model to analyze decidualization defects at the morphologic level and the secretion of prolactin and insulin-like growth binding protein-1. Annexin A2-inhibited cells were used to evaluate motility and promotion of embryo invasion. Decidualization and placentation defects of Annexin A2 deficiency were confirmed with the use of an Annexin A2-null mouse model. Annexin A2 gene and protein levels were down-regulated during in vitro decidualization of human endometrial stromal cells from women with previous severe preeclampsia compared with control individuals. To assess its role in the endometrial stroma, we inhibited Annexin A2 expression and detected decidualization failure as evidenced by impaired morphologic transformation, which was associated with altered actin polymerization and low prolactin and insulin-like growth binding protein-1 secretions. Functionally, in vitro models demonstrated that Annexin A2 inhibition failed to support embryo invasion. This finding was corroborated by reduced trophoblast spreading through human endometrial stromal cells, lack of motility of these cells, and reduced trophoblast invasion in the presence of conditioned media from Annexin A2-inhibited cells. Extending our discovery to an animal model, we detected that Annexin A2-null mice have a functional deficiency in decidualization and placentation that impairs fetal growth as a feature that is associated with severe preeclampsia. Together, in vitro and in vivo results suggest that endometrial defects in Annexin A2 expression impair decidualization of endometrial stromal cells as well as the uterine microenvironment that promotes embryo implantation and placentation. Our findings highlight the maternal contribution to the pathogenesis of severe preeclampsia and suggest that evaluation of Annexin A2 may provide a novel strategy to assess a woman's risk of experiencing this disease and perhaps discover therapeutic interventions to improve decidualization.


HIV reservoirs and strategies for eradication.
Combination antiretroviral therapy (cART) has led to a reduction in morbidity and mortality in HIV-infected patients but therapy is lifelong and there is no cure for HIV. The major barriers to cure include HIV latency, which has been identified in different T-cell subsets, as well as persistence of HIV in anatomical reservoirs. We review recent developments in our understanding of the major reservoirs of HIV in patients on cART as well as how latency is established and maintained in T cells. Finally, we review the scientific rationale of and clinical experience with pharmacotherapeutic strategies aimed at eliminating latently infected cells.


Probiotics can alleviate cardiopulmonary bypass-induced intestinal mucosa damage in rats.
Cardiopulmonary bypass (CPB) is commonly applied to support circulation during heart surgery but frequently causes adverse effects. The purpose of this study was to examine the potential of probiotics to improve small intestinal mucosa barrier function after CPB. Twenty-four adult male SD rats were randomly divided into sham-operated (S), CPB-operated (CPB), and probiotic-fed (Y) groups. Diamine oxidase (DAO) activity and concentrations of D-lactic acid, endotoxin, TNFα, and IL-6 were measured in portal vein blood. IgA concentrations were determined in plasma and the small intestine. Vena cava blood and tissue samples were used to monitor bacterial growth. Intestinal epithelial ultrastructure was analyzed by transmission electron microscopy (TEM). Occludin and ZO-1 expression levels in the intestinal epithelium were detected by western blotting and immunohistochemistry, respectively. D-lactic acid, endotoxin, TNFα and IL-6 levels, DAO activity, and bacterial translocation rate were increased (P < 0.05) in CPB and Y compared to the S group. The above indices were relatively lower (P < 0.05) in Y than in CPB. Plasma and small intestinal IgA levels were significantly lower (P < 0.05) in CPB, while in Y they were significantly increased (P < 0.05) but lower than in S (P < 0.05). These results were confirmed by TEM. Consistently, occludin and ZO-1 expression levels were significantly higher in Y than in CPB (P < 0.05) but still lower compared to S (P < 0.05). Pre-administration of probiotics can improve, to some extent, intestinal barrier function after CPB in rats, and this effect is likely related to inhibition of the CPB-induced inflammatory response, improvement in local intestinal immune function, and increased expression of intestinal epithelial tight junction proteins.


The aging of the endocrine pancreas of the rat. II. Cytoplasmic parameters of the B-cell, including insulin synthesis and secretion.
Comparative ultrastructural stereology of 6 and 24-month-old rat B-cell cytoplasm revealed an increase with age in secondary lysosomes and a decrease in the volume density of RER and Golgi apparatus. The reduction of RER observed in freshly isolated islets could affect (pro)insulin biosynthesis in vitro: if the initial mobilization of precursor molecules for protein synthesis was the same, a delay was noted in their transit to the Golgi apparatus in B-cells of old islets. No further differences were seen in the autoradiographic distribution of radioactive amino-acids. More, the stock of insulin granules was similar in all age groups in both in vivo and in vitro conditions. Neither were any differences observed in the insulin secretion into culture media as well as during a subsequent incubation in supraphysiological glucose concentrations.


Inhibition of apoptosis by recombinant 30K protein originating from silkworm hemolymph.
In a previous study, we reported that silkworm hemolymph inhibits apoptosis and that the anti-apoptotic component in silkworm hemolymph is a 30K protein. In this study, the 30K protein encoded by 30Kc6 was expressed in Escherichia coli. The recombinant 30K protein was expressed as an inclusion body, and the inclusion body was separated and refolded by affinity column chromatography using a 6xHis tag. We demonstrated that apoptosis is inhibited by supplementing the culture medium with this purified recombinant 30K protein. The recombinant 30K protein inhibited the virus- or chemical-induced apoptosis in human cells as well as insect cells. Apoptosis-inhibitory activity of recombinant 30K protein was comparable to that of whole silkworm hemolymph. The recombinant 30K protein can be effectively used to minimize cell death and consequently increase the productivity by extending the production time of host cells in commercial animal cell culture.


Honoring Veterans' Preferences: The Association Between Comfort Care Goals and Care Received at the End of Life.
As part of its Life-Sustaining Treatment (LST) Decisions Initiative, the Veterans Health Administration (VA) in January 2017 began requiring electronic documentation of goals of care and preferences for Veterans with serious illness and at high risk for life-threatening events. To evaluate whether goals of "to be comfortable" were associated with greater palliative care (PC) use and lesser acute care use. We identified Veterans with VA inpatient or nursing home stays overlapping July 2018-January 2019, with LST templates documented by January 31, 2019, and who died by April 30, 2019 (N = 18,163). From template documentation, we identified a "to be comfortable" goal. Using VA and Medicare data, we determined PC use (consultations and hospice) and hospital, intensive care unit, and emergency department use 7 and 30 days before death. Multivariate logistic regression examined the associations of interest. Sixty-four percent of the 18,163 Veterans had comfort-care goals; 80% with comfort care goals received hospice and 57% PC consultations (versus 57% and 46%, respectively, for decedents without comfort-care goals). In adjusted analyses, comfort care documented on the LST template prior to death was associated with significantly lower odds of hospital, intensive care unit, and emergency department use near the end of life. In the last 30 days of life, Veterans with a comfort care goal had 44% lower odds (adjusted odds ratio 0.57; 95% CI: 0.51, 0.63) of being hospitalized. Findings support the VA's commitment to honoring of Veterans' preferences post introduction of its Life Sustaining Treatment Decisions Initiative.


Endoscopic endonasal optic nerve sheath decompression (EONSD) for idiopathic intracranial hypertension: Technical details and meta-analysis.
The neurosurgical management of idiopathic intracranial hypertension (IIH) remains controversial. Although shunting and newer endovascular stenting techniques are part of the neurosurgical armamentarium to treat medically refractory IIH symptoms, optic nerve sheath fenestration has traditionally been performed by ophthalmologists. We present a detailed cadaveric dissection that simulates the endoscopic endonasal optic nerve sheath decompression (EONSD) technique along with the literature review. EONSD was performed in four freshly injected cadaveric specimens. Additionally, a systematic review from different electronic databases has been done. Bilateral EONSD was performed in all specimens without significant technical difficulties. Based on our experience, there is no need to expose the periorbita or orbital apex. The primary anatomic landmarks were the optic canal, the lateral opticocarotid recess, the tuberculum, the limbus, and the clinoid segment of the internal carotid artery. Based on the systematic review, 68 patients (77.9% female) underwent EONSD, with a mean age of 33.4 ± 6.9 years in adult patients. Follow-up ranged from 3 to 58 months across different studies. The pooled meta-analysis showed headache, papilledema, and visual disturbance improvement in 78% [95%CI 0.65-0.90], 72% [95%CI 0.61-0.83], and 88% [95%CI 0.80-0.96] of cases who underwent EONSD, respectively. The subgroup analysis showed there was no statistically significant difference between unilateral and bilateral EONSD in terms of different measured outcomes. EONSD is a feasible surgical procedure that may obviate the need for shunting in patients with IIH. Although clinical studies showed that EONSD is a safe and effective technique, further studies are required to establish the preferences of either unilateral or bilateral approaches.


Magnetic nanoparticles as versatile carriers for enzymes immobilization: A review.
Enzymes are highly efficient biocatalysts and widely employed in biotechnological sectors. However, lack of (re)-purification and efficient recovery of enzymes are among the most critical and challenging aspects, which render them enormously expensive for industrial exploitability. Aiming to tackle these challenges, magnetic nanoparticles (MNPs) have gained a special place as versatile carriers and supporting matrices for immobilization purposes, owing to the exceptional properties of MNPs, such as large surface area, large surface-to-volume ratio, and mobility and high mass transference. More importantly, they can also be easily separated and recovered by applying an external magnetic field. Apart from their biocompatible micro-environment, the utilization of such MNPs represents a noteworthy green chemistry approach, since it lengthens the biocatalyst lifetime through multiple recovery cycles. According to the literature evidence, various modification and/or functionalization approaches have been developed to produce MNPs for the effective immobilization of a broad variety of industrially important enzymes and biomolecules with improved characteristics. Enzymes immobilized on MNPs displayed a wide-working pH and temperature range, as well as, improved thermal and storage stabilities than that of their pristine counterparts. Co-immobilization of multi-enzymes could also be accomplished through nanoparticle-based approaches. This review presents an updated outlook on the development and characterization of MNPs, in particular, iron-based MNPs-derived nano-constructs as support materials for enzyme immobilization.


The bladder mucosal graft for urethral reconstruction.
Single stage repairs of a variety of congenital and acquired urethral anomalies were performed in 16 male patients with free grafts of bladder mucosa. Of the patients 10 previously had undergone unsuccessful attempts at urethral reconstruction, including 9 boys with hypospadias. Grafts ranged between 2 and 8.5 cm. long. A fistula occurred postoperatively in 1 patient and it responded to prolonged suprapubic drainage. Meatal stenosis necessitated a further operation in 1 patient. The bladder mucosal graft technique should be considered for urethral reconstruction when prior attempts at repair have failed or when the disorder is primary, and local penile or preputial skin is deficient.


Double-balloon catheter for induction of labor in 362 women with and without prior cesarean section.
Balloon catheter is the preferred method for induction of labor in women with prior cesarean section. We sought to evaluate the rate of vaginal delivery, induction-delivery time and outcome predictors after induction with double-balloon catheter. We conducted a retrospective cohort study including women with prior cesarean section undergoing induction of labor with a double-balloon catheter during the period January 2007-June 2014 at a large, tertiary Danish university hospital. For comparison, we included women with no prior cesarean section undergoing induction with double-balloon catheter after failed medical induction. Inclusion criteria were singleton pregnancy, an unfavorable cervix, intact membranes, cephalic presentation and either previous cesarean section or failed medical induction of labor. Exclusion criteria included contraindications for vaginal delivery, severe fetal malformation and stillbirth. Study subjects were identified in a local computerized system and data extracted from the medical records. Women with prior cesarean section (n = 304) induced with double-balloon catheter had a vaginal delivery rate of 50.3% (95% CI 44.7-55.9) compared to 51.7% (95% CI 39.2-64.1) in women with no prior cesarean section but preceding failed medical induction of labor (n = 58) (p = 0.85). BMI≥30 was associated with increased frequency of cesarean section. Median time from induction to vaginal delivery was 27.1(20.4-31.1) hours and 28.4(25.5-36.1) hours, respectively (p = 0.05). The rate of complete uterine rupture was 1.0%. Similar success rates of approximately 50% for vaginal delivery were observed after induction of labor with a double-balloon catheter in women with and without prior caesarean section. A BMI ≥ 30 was associated with an increased frequency of caesarean section.


Role strain among male RNs in the critical care setting: Perceptions of an unfriendly workplace.
Traditionally, nursing has been a female-dominated profession. Men employed as registered nurses have been in the minority and little is known about the experiences of this demographic. The purpose of this descriptive, quantitative study was to understand the relationship between the variables of demographics and causes of role strain among male nurses in critical care settings. The Sherrod Role Strain Scale assesses role strain within the context of role conflict, role overload, role ambiguity and role incongruity. Data analysis of the results included descriptive and inferential statistics. Inferential statistics involved the use of repeated measures ANOVA testing for significant difference in the causes of role strain between male nurses employed in critical care settings and a post hoc comparison of specific demographic data using multivariate analyses of variance (MANOVAs). Data from 37 male nurses in critical care settings from the northeast of the United States were used to calculate descriptive statistics standard deviation, mean of the data analysis and results of the repeated ANOVA and the post hoc secondary MANOVA analysis. The descriptive data showed that all participants worked full-time. There was an even split from those participants who worked day shift (46%) vs. night shift (43%), most the participants indicated they had 15 years or more experience as an registered nurse (54%). Significant findings of this study include two causes of role strain in male nurses employed in critical care settings which are: role ambiguity and role overload based on ethnicity. Consistent with previous research findings, the results of this study suggest that male registered nurses employed in critical care settings do experience role strain. The two main causes of role strain in male nurses are role ambiguity and role overload.


Colorectal cancer screening in Vietnamese Americans.
Rates of colorectal cancer screening in Vietnamese Americans are lower than those in non-Hispanic Whites. In this article, we describe rates of colorectal screening, identify determinants, and recommend educational strategies to improve screening. A cross-sectional sample of 867 Vietnamese aged 50 to 74 years drawn from a sampling frame of individuals in the Alameda and Santa Clara Counties, California, and Harris County, Texas, area telephone directories with Vietnamese surnames were interviewed in 2004. Colorectal screening recognition, receipt, currency, and intention rates were low. Although the screening rates are low, Vietnamese are receptive to screening if providers recommend it.


Inhibition of wheat leaves nitrate reductase activity by cibacron blue.
Cibacron Blue F3GA (CB) inhibited the activities of wheat leaves NADH:nitrate reductase and NADH:cytochrome-c reductase in a time-independent and concentration dependent manner. The methyl viologen:nitrate reductase activity of the enzyme was unaffected by various CB concentrations used in the experiment. Inhibition of NADH:nitrate reductase was of mixed type (partial competitive and pure noncompetitive) with respect to NADH and noncompetitive with respect to nitrate. The estimated inhibition constant (Ki) values were 1 microM for NADH and 8.4 microM for nitrate. The secondary plots of inhibition with respect to NADH, indicated a dissociation constant (KI) of 8.8 microM for the enzyme-NADH-CB complex. This KI being greater than the Ki suggested that the noncompetitive inhibition is predominant over the competitive inhibition at the NADH binding site.


Comprehending the intermolecular interaction of JAK inhibitor fedratinib with bovine serum albumin (BSA)/human alpha-1-acid glycoprotein (HAG): Multispectral methodologies and molecular simulation.
The primary coverage of this paper is to investigate the molecular interaction of JAK2 inhibitor, fedratinib (FED) with BSA/HAG proteins through multispectral approaches and molecular docking as well as MD calculation. Arrival at a conclusion, the endogenous fluorescence of BSA/HAG protein was quenched separately in the form of static and mixed quenching. The FED-BSA and FED-HAG complexes with the stoichiometric ratio of 1:1 were formed in the interaction process. And, The Kb values of these complexes were of 104-105 M-1 and 105-106 M-1, respectively, representing that the FED-HAG complex exhibited a comparatively high affinity compared to the FED-BSA complex. It is confimed that FED inserted into the interface area between subdomain IIA and IIB of BSA (marked as site II') and the bucket-shaped hydrophobic cavity of HAG, respectively, resulting in the slight alteration in the secondary structure of BSA/HAG and the micro-environment round Tyr and Trp residues. The expetimental results also confirmed that van der Waals forces (VDW), hydrogen bonds and hydrophobic interaction played a dominant role in the formation of two stable complexes. The above experimental results were supplemented and verified through molecular docking and MD simulation. Meanwhile, the effects of common ions on affinity were explored. This study could shine a light on evaluating the pharmacological properties of the JAK inhibitor FED, understanding the distribution and operation of the drug in the body, and leading to the development of the creation of novel medication devise.


Generation and application of DNA aptamers against HspX for accurate diagnosis of tuberculous meningitis.
Tuberculous meningitis (TBM) is the most severe manifestation of tuberculosis and its diagnosis remains a challenge even today due to the lack of an adequate test. HspX antigen of Mycobacterium tuberculosis was previously established as a reliable diagnostic biomarker for TBM in an ELISA test format using anti-HspX polyclonal antibodies. Towards overcoming the limitations of batch-to-batch variation and challenges of scalability in antibody generation, we utilized Systematic Evolution of Ligands by EXponential enrichment (SELEX) to develop high affinity DNA aptamers against HspX as an alternative diagnostic reagent. Post-SELEX optimization of the best-performing aptamer candidate, H63, established its derivative H63 SL-2 M6 to be superior to its parent. Aptamer H63 SL-2 M6 displayed a specific and high affinity interaction with HspX (Kd ∼9.0 × 10-8 M). In an Aptamer Linked Immobilized Sorbent Assay (ALISA), H63 SL-2 M6 significantly differentiated between cerebrospinal fluid specimens from TBM and non-TBM subjects (n = 87, ***p < 0.0001) with ∼100% sensitivity and ∼91% specificity. Notably, ALISA exhibited comparable performance with previously reported antibody-based ELISA and qPCR. Altogether, our findings establish the utility of HspX aptamer for the reliable diagnosis of TBM and pave the way for developing an aptamer-based point-of-care test for TBM.


The use of a supported base and strong cation exchange (SCX) chromatography to prepare a variety of structurally-diverse molecular libraries prepared by solution-phase methods.
The preparation of molecular libraries of aminomethylbiaryls, allylic amines, and ethanolamines using solution-phase methodology is described. In particular, the use of a solid-supported base reagent (PTBD resin) and strong cation exchange(SCX) resin to effect 'catch and release' purification across these diverse libraries is highlighted.


Characterizing the spatial distributions of spotted lanternfly (Hemiptera: Fulgoridae) in Pennsylvania vineyards.
Spotted lanternfly (SLF) is an invasive insect in the Northeastern U.S. projected to spread nationally and globally. While SLF is a significant pest of vineyards, little is known about the pest in grape agroecosystems including its spatial ecology. SLF spatial patterns were analyzed using a combination of approaches including generalized linear mixed effect models, Moran's I statistic for spatial clustering, and Empirical Bayesian Kriging. Analysis revealed that SLF displayed significantly clumped distributions in monitored vineyards. Approximately 54% and 44% of the respective adult and egg mass populations were observed within the first 15 m of the vineyard edge. Importantly, the spatial concentration of adults at the edge was consistent temporally, both between years and weeks. Moreover, high populations of SLF on vines were significantly correlated with reduced fruit production in the following year. Mark-release-recapture of SLF revealed that higher proportions of SLF were recaptured on vines with high pre-existing SLF populations, indicating that SLF may exhibit aggregation behavior along vineyard perimeters. Monitoring and management efforts for SLF should be prioritized around vineyard edges as it may significantly reduce infestations and subsequent damage.


Quantum noise radar: superresolution with quantum antennas by accessing spatiotemporal correlations.
We suggest overcoming the "Rayleigh catastrophe" and reaching superresolution for imaging with both spatially and temporally correlated field of a superradiant quantum antenna. Considering far-field radiation of two interacting spontaneously emitting two-level systems, we show that for the measurement of the temporally delayed second-order correlation function of the scattered field, the Fisher information does not tend to zero with diminishing the distance between a pair of scatterers even for non-sharp time-averaged detection. For position estimation of more scatterers, the measurement of the time-delayed function is able to provide a considerable accuracy gain over the zero-delayed function. We also show that the superresolution with the considered quantum antenna can be achieved for both near-field imaging and for estimating the antenna parameters.


[Assessment and follow-up of patients with suspected COVID-19 in the first pandemic wave in an urban area of Andalusia (Spain)].
To know the characteristics of the initial care and telephone follow-up of patients with suspected COVID-19 in the first wave of the pandemic. Observational, retrospective (audit of medical records). Urban Primary Care Center of Andalusia (Spain). Probable cases of SARS-CoV-2 (from 20/03/15 to 20/06/15). Initial medical assessment (place and modality) and telephone follow-up (number of calls and duration). Sociodemographic variables (including family structure). Clinical course (symptoms, vulnerability, tests, hospital admission and outcome). Three hundred one patients (51.5±17.8 years; 23% vulnerable people; 17% non-nuclear family structure). First assessment in Primary Care by phone (59.8%) and face-to-face (25.2%). At the hospital emergency department (11%), patients were more frequently from non-nuclear families (P<.05 χ2) and more tests were carried out (P<.05 χ2) despite having similar symptoms. Vulnerable elderly patients needed home health care (P<.01 ANOVA). 8.2±4.4 follow-up phone calls were made per patient, for 17.1±10.3 days. It increases after ≥2 face-to-face consultations (OR 4.8), the presence of alarm symptoms (OR 2.3) and age ≥45 years (OR 2.0). Few confirmatory tests were performed (19.3% antigenic, 13% serology). The 15.3% hospital admissions (all assessed previously in Primary Care), with 6.3% severe cases and 2.3% death. Population chose to be attended in Primary Care during the pandemic first wave, above all by phone. Telephone follow-up was well accepted and useful to select patients with serious complications. Initial medical assessment in the hospital emergency department was related to a lack of social support but not with greater clinical severity.


Effect of Different Implant-Abutment Mismatches on Stress Distribution: A 3-Dimensional Finite Element Study.
Platform-switching reduces peri-implant marginal bone loss (MBL). The aim of this study was to compare the effect of platform-switching on stress within crestal bone using different implant-abutment mismatches (0.65 and 1 mm) under 2 different vertical loads (30 N vs 200 N) for implants placed in posterior jaw sites. Three-dimensional modeling software was used for an implant with a diameter of 4.5 mm and length of 13 mm. Molars were modeled using computerized tomography images of bone density in human maxilla (D3 bone) and mandible (D2 bone). Collected data were analyzed using CATIA software. In posterior mandible, stress of 30 N force with platform mismatches of 0.65 or 1 mm were 2.920 and 2.440 MPa respectively. Using 200 N force, values increased to 19.44 and 16.30 MPa. In posterior maxilla and 30 N force, stresses with mismatches of 0.65 and 1 mm were 3.77 and 3.18 MPa, respectively, increasing to 25.14 and 20.17 MPa with 200 N force. The effect can be predicted to be greatest as the mismatch increases with implants placed into lower quality bone (posterior maxilla with D3 quality).


Temperature dependent cellular, and epigenetic regulatory mechanisms underlying the antiviral immunity in sevenband grouper to nervous necrosis virus infection.
Changes in the thermal optima of fish impacts changes in the physiology and immune response associated with infections. The present study showed that at suboptimal temperatures (17 °C), the host tries to evade viral infection by downregulating the inflammatory response through enhanced neuronal protection. There was significantly less abundance of IgM + B cells in the 17 °C group compared to that in the 25 °C group. An increased macrophage population (Iba1+) during the survival phase in fish challenged at 25 °C demonstrated inflammation. Optimal temperature challenge activated virus-induced senescence in brain cells, demonstrated with a heterochromatin-associated H3K9me3 histone mark. There was an abundant expression of anti-inflammatory cytokines in the brain of fish at the suboptimal challenge. Besides the cytokines, the expression of BDNF was significantly higher in the suboptimally challenged group, suggesting that its neuronal protection activity following NNV infection is mediated through TGFβ. The suboptimal challenge resulted in H3k9ac displaying transcriptional competency, activation of trained immunity H3K4me3, and enrichment of H3 histone-lysine-4 monomethylation (H3K4me1), resulting in a robust re-stimulatory immune response. The observations from the H4 modifications showed that besides H4K12ac and H4K20m3, all the assayed modifications were significantly higher in suboptimal convalescent fishes. The suboptimally challenged fish acquired more methylation along cytosine residues than the optimally infected fish. Together, these observations suggest that optimal temperature results in an immune priming effect, whereas the protection enabled in suboptimal convalescent fishes is operated through epigenetically controlled trained immune functions.


Altered sensorimotor fMRI directed connectivity in Parkinson's disease patients.
Dopamine depletion in the axons of Parkinson's disease (PD) patients precedes depletion in cell bodies thus proposing that macroscopic connectivity can be used to understand disease mechanism. A novel multivariate functional connectivity analysis, based on high order coherence among four fMRI BOLD signals was applied on resting-state fMRI data of controls and PD patients (OFF and ON medication states) and unidirectional multiple-region pathways in the sensorimotor system were identified. Pathways were classified as "preserved" (unaffected by the disease), "damaged" (not observed in patients) and "corrected" (observed in controls and in PD-ON state). The majority of all pathways were feedforward, most of them with the pattern "S1→M1→SMA." Of these pathways, 67% were "damaged," 28% "preserved," and 5% "corrected." Prefrontal cortex (PFC) afferent and efferent pathways that corresponded to goal directed and habitual activities corresponded to recurrent circuits. Eighty-one percent of habitual afferent had internal cue (i.e., M1→S1→), of them 79% were "damaged" and the rest "preserved." All goal-directed afferent had external cue (i.e., S1→M1→) with third "damaged," third "preserved," and third "corrected." Corrected pathways were initiated in the dorsolateral PFC. Reduced connectivity of the SMA and PFC resulted from reduced sensorimotor afferent to these regions. Reduced sensorimotor internal cues to the PFC resulted with reduced habitual processes. Levodopa effects were for pathways that started in region reach with dopamine receptors. This methodology can enrich understudying of PD mechanisms in other (e.g., the default mode network) systems.


Your phrases matter: Third waves in research approaches and new contexts for formulaic language.
This study reports on new contexts in which formulaic language has been used in the years since 2013 when the last synthesis was carried out. The background presents an old but still useful definition and lists themes under which research was arranged in 2013 and which continue to be used. This study has a particular emphasis on the relevance of formulaic language to people living with dementia. Section 3, identifying new directions, reviews new 'third waves' of research priorities in several fields in which formulaic sequences play a major role, including sociolinguistic variation, corpus-based and corpus-driven analyses, pragmatics, human-computer interaction, and psycholinguistics, all of which are relevant to speech-language therapists. Section 4, outreach and expansions, illustrates new contributions from cognitively impaired person-to-person exchanges in online environments, recent examinations of infant- and pet-directed speech incorporating formulaic language, and online graphic explorations such as emojis. Section 5 focuses on growth of research in theoretical and clinical applications by Van Lancker Sidtis, as illustrated by references to her recent work. The paper's main contribution is to summarize the work on formulaic language over the last 10 years, to indicate its continued importance and relevance in ordinary conversation, and especially in allowing people living with dementia to continue to interact with others. The paper concludes by suggesting that more focus be placed on the analysis of formulaic language with an emphasis on its relevance for speech-language therapists and other clinicians. What is already known on the subject Research has been growing since the late 1970s and early 1980s on non-propositional language (as opposed at that time to the Chomskyan paradigm) and especially on lexical bundles, idioms, second language acquisition and multiword expressions. Studies beginning with Hughlings Jackson (1874) have been annotated through early 2012 (Wray, 2013). What this study adds This study examines 'third waves' in pragmatics, sociolinguistics and areas of neurology and speech perception contributing to what Van Lancker Sidtis (2021) calls the third wave of acceptance of the range and depth of formulaic sequences in ordinary or familiar language. What are the clinical implications of this work? Conversations with pet robots or web-based composition with emojis are but two of the developing areas built on formulaic sequences currently being used for communication interventions with persons living with dementia or other major neurocognitive disorder. Overviews of major contributions in theory and social contexts by Wray (2020, 2021) and theoretical and cognitive applications by Van Lancker Sidtis (2021) detail new areas for the study of formulaic sequences and their contributions to a range of neurocognitive disorders.


The uL10 protein, a component of the ribosomal P-stalk, is released from the ribosome in nucleolar stress.
The ribosomal uL10 protein, formerly known as P0, is an essential element of the ribosomal GTPase-associated center responsible for the interplay with translational factors during various stages of protein synthesis. In eukaryotic cells, uL10 binds two P1/P2 protein heterodimers to form a pentameric P-stalk, described as uL10-(P1-P2)2, which represents the functional form of these proteins on translating ribosomes. Unlike most ribosomal proteins, which are incorporated into pre-ribosomal particles during early steps of ribosome biogenesis in the nucleus, P-stalk proteins are attached to the 60S subunit in the cytoplasm. Although the primary role of the P-stalk is related to the process of translation, other extraribosomal functions of its constituents have been proposed, especially for the uL10 protein; however, the list of its activities beyond the ribosome is still an open question. Here, by the combination of biochemical and advanced fluorescence microscopy techniques, we demonstrate that upon nucleolar stress induction the uL10 protein accumulates in the cytoplasm of mammalian cells as a free, ribosome-unbound protein. Importantly, using a novel approach, FRAP-AC (FRAP after photoConversion), we have shown that the ribosome-free pool of uL10 represents a population of proteins released from pre-existing ribosomes. Taken together, our data indicate that the presence of uL10 on the ribosomes is affected in stressed cells, thus it might be considered as a regulatory element responding to environmental fluctuations.


Epidemiologic and genomic investigations of an unusual increase in Salmonella enterica serovar Paratyphi A infection among travelers returning from Myanmar in 2015.
An unusual increase in Salmonella enterica serovar Paratyphi A infection rate in Japanese travelers returning from Myanmar was observed in 2015. We analyzed epidemiologic data of returned travelers with enteric fever from 2005-2019. We also analyzed 193 Salmonella Paratyphi A isolates, including 121 isolates with published genomes. Annual notification trends showed a rapid increase in Salmonella Paratyphi A infection in travelers returning from Myanmar in 2015: 2-4 cases/100,000 travelers in 2012-2014 and 13 cases/100,000 travelers in 2015 (P <0.001). The genomic analyses revealed that 11 Myanmar-related isolates in 2015 formed a tight cluster in clade 3 with a single nucleotide variant (SNV) distance of 0-11 (primarily 0-7), yielding a wider SNV range than outbreak-associated isolates from Cambodia in 2013 (0-6 SNVs) or China in 2010 (0-5 SNVs). Although all Cambodia-related isolates in 2013 harbored the wild-type gyrA sequence, all Myanmar-related isolates in 2015 had a single, identical mutation (Ser83Phe) in the gyrA gene. The epidemiologic and molecular investigations suggested an increase in the infection rate with genetically closely related Salmonella Paratyphi A in travelers returning from Myanmar in 2015. Careful monitoring of the infection in Myanmar as an endemic country is warranted, considering the resumption of cross-border travel during the COVID-19 pandemic.


Predicting hypogonadism in men based upon age, presence of erectile dysfunction, and depression.
Hypogonadism, a disorder associated with aging, can cause significant morbidity. As clinical manifestations of hypogonadism can be subtle, the challenge and the burden of diagnosis remain the responsibility of the clinician. Four different analytic methods were used to predict hypogonadism in men based upon age, the presence of erectile dysfunction (ED) and depression. 218 men were classified by age, serum testosterone level, the presence of ED and depression. Depression was determined by the Center for Epidemiologic Studies Depression Scale (CES-D). ED was assessed by the Sexual Health Inventory for Men (SHIM). Hypogonadism was defined as a serum testosterone level <300 ng/dl. An artificial neural network (ANN) was programmed and trained to predict hypogonadism based upon age, SHIM, and CES-D scores. Subject data was randomly partitioned into a training set of 148 (67.9%) and a test set of 70 (32.1%). The ANN processed the test set only after the training was complete. The discrete predicted binary output was set to (0) if testosterone level was <300 ng/dl or (1) if >300 ng/dl. The data was also analyzed by standard logistic regression (LR), linear and quadratic discriminant function analysis (LDFA and QDFA, respectively). Reverse regression (RR) analysis evaluated the statistical significance of each risk factor. The ANN can accurately predict hypogonadism in men based upon age, the presence of ED, and depression (receiver-operating characteristic=0.725). A four hidden node network was found to have the highest accuracy. RR revealed the depression index score to be most significant variable (P=0.0019), followed by SHIM score (P=0.00602), and then by age (P=0.015). Hypogonadism can be predicated by an ANN using the input factors of age, ED, and depression. This model can help clinicians assess the need for endocrinologic evaluation in men.


Degrees of severe stenoses in sigma-shaped versus C-shaped right coronary arteries.
The right coronary artery (RCA) appears either C-shaped or sigma-shaped during standard angiography. The purpose of the present investigation was to assess whether C-shaped RCAs are associated with more atherosclerotic disease than sigma-shaped RCAs. The study sample comprised 120 consecutive patients who underwent coronary catheterization and multivariate analysis was conducted using several systemic risk factors for atherosclerosis. The proportion of sigma-shaped RCAs found in a group whose angiograms showed little or no obstruction (70%) was significantly higher than that found in the group with significant obstruction (33%, p <0.001). In conclusion, a C-shaped RCA is associated with atherosclerosis.