Magnetic resonance T1-mapping quantitatively assesses the severity of thyroid destruction in patients with autoimmune thyroiditis.
Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease. Longitudinal relaxation time mapping (T1-mapping) analyzed by magnetic resonance imaging is a new method for evaluating inflammation or fibrosis. This study aimed to investigate the relationship between thyroid T1-mapping value and degree of intrathyroidal inflammation and destruction in euthyroid AIT patients. This case-control study recruited 28 drug-naïve AIT patients and 18 healthy controls. Thyroid specimens were collected for assessing the mRNA expression of inflammatory factors and histopathologic examination. T1-mapping values were measured using a modified look-locker inversion-recovery sequence in all participants. The positive rate of pathological diagnosed AIT was only 83.3% in the AIT group diagnosed by positive TPOAb and/or TgAb and typical ultrasonic manifestations, while 7.1% of the control group was diagnosed as AIT by pathological manifestations. Receiver operating characteristic curve analysis revealed a very high diagnostic value of thyroid T1-mapping values for pathological diagnosed AIT (area under the curve was 0.950, 95%CI: 0.843 - 0.993, P < 0.001). In the patients with pathological diagnosed AIT, thyroid T1-mapping values were significantly associated with the mRNA expression of INF-γ (r = 0.343, P < 0.05), TNF-α (r = 0.352, P < 0.01), and IL-1β (r = 0.673, P < 0.01) in thyroid tissues. Moreover, histopathologic examination showed that thyroid T1-mapping values can properly reflect the degree of thyroid destruction in AIT patients. Thyroid T1-mapping values had a very high diagnostic value for AIT. In euthyroid AIT patients, thyroid T1-mapping values better reflect degree of intrathyroidal inflammation and destruction.


Beta 3: a new member of nicotinic acetylcholine receptor gene family is expressed in brain.
Screening of a rat brain cDNA library with a radiolabeled probe made from an alpha 3 cDNA (Boulter, J., Evans, K., Goldman, D., Martin, G., Treco, D., Heinemanns, S., and Patrick, J. (1986) Nature 319, 368-374) resulted in the isolation of a clone whose sequence encodes a protein, beta 3, which is homologous (40-55% amino acid sequence identity) to previously described neuronal nicotinic acetylcholine receptor subunits. The encoded protein has structural features found in other nicotinic acetylcholine receptor (nAChR) subunits. Two cysteine residues that correspond to cysteins 128 and 142 of the Torpedo nAChR alpha subunit are present in beta 3. Absent from beta 3 are 2 adjacent cysteine residues that correspond to cysteines 192 and 193 of the Torpedo subunit. In situ hybridization histochemistry, performed using probes derived from beta 3 cDNAs, demonstrated that the beta 3 gene is expressed in the brain. Thus, beta 3 is the fifth member of the nAChR gene family that is expressed in the brain. The pattern of beta 3 gene expression partially overlaps with that of the neuronal nAChR subunit genes alpha 3, alpha 4, or beta 2. These results lead us to propose that the beta 3 gene encodes a neuronal nAChR subunit.


Exercise training during rehabilitation of patients with COPD: a current perspective.
Patients with chronic obstructive pulmonary disease (COPD) suffer frequently from physiologic and psychological impairments, such as dyspnea, peripheral muscle weakness, exercise intolerance, decreased health-related quality of life (HRQOL) and emotional distress. Rehabilitation programmes have shown to result in significant changes in perceived dyspnea and fatigue, utilisation of healthcare resources, exercise performance and HRQOL. Exercise training, which consists of whole-body exercise training and local resistance training, is the cornerstone of these programmes. Regrettably, the positive effects of respiratory rehabilitation deteriorate over time, especially after short programmes. Hence, attention should be given to the aftercare of these patients to prevent them to revert again to a sedentary lifestyle. On empirical basis three possibilities seem to be clinically feasible: (1) continuous outpatient exercise training; (2) exercise training in a home-based or community-based setting; or (3) exercise training sessions in a group of asthma and COPD patients.


Lymphadenectomy in gallbladder adenocarcinoma: Are we doing enough?
Current AJCC guidelines recommend evaluating ≥6 lymph nodes during gallbladder cancer resection but real world data suggest this is rarely achieved. We evaluated the extent of lymphadenectomy and survival among patients with gallbladder adenocarcinoma. Patients with resected pT1b-T3 gallbladder adenocarcinoma were identified from the NCDB (2004-2017). Propensity scores were created for the odds of sufficient lymphadenectomy (≥6 nodes), patients were matched 1:1 and survival was analyzed using the Kaplan-Meier method. Overall, 4760 patients were identified: 16.7% underwent sufficient lymphadenectomy, which was predictive of nodal disease (OR 1.77, 95%CI 1.51-2.08) and demonstrated a survival benefit in N0 (median OS 140.8 versus 44.4 months; p < 0.0001) and N1-2 disease (median OS 27.7 versus 17.7 months; p < 0.0001) after matching. The majority of patients with gallbladder adenocarcinoma do not undergo the recommended nodal dissection, resulting in a survival disadvantage, likely due to understaging, decisions regarding adjuvant therapy and local tumor recurrence.


Synthesis of human progesterone receptors in T47D cells. Nascent A- and B-receptors are active without a phosphorylation-dependent post-translational maturation step.
Human progesterone receptors (PR) are structurally complex. At basal states there are two forms: A-receptors of approximately 94 kDa and B-receptors which are triplets of approximately 114, 117, and 120 kDa. All the proteins bind hormone and are phosphorylated. By using PR-rich T47Dco human breast cancer cells, pulse-labeling with [35S]methionine, and receptor immunopurification with anti-PR monoclonal antibodies, we show that PR are synthesized as single B-proteins of 114 kDa and single A-proteins of 94 kDa. The mature B-triplets form 6-10 h later by post-translational phosphorylation at sites restricted to the B-proteins. This slow maturation is not required for PR activation to hormone binding states, however, since A- and B-receptors that are less than 15 min old respond to progestins by undergoing transformation and nuclear binding accompanied by a rapid secondary phosphorylation common to both proteins. These studies explain the complex structure of the mature human B-receptors and the transformed A- and B-receptors, and address issues dealing with A- and B-proreceptor synthesis and receptor activation rates.


Photomodulation of glutamate dehydrogenase properties by red light.
To gain some insight into the mechanism by which red light-biosystem interaction occurs, an investigation was made of certain features of purified glutamate dehydrogenase from beef liver (E.C. 126.96.36.199.) irradiated with either an He-Ne laser (632.8 nm) or a red light-emitting diode (650 +/- 20 nm). In both cases the energy dose was 0.24 J cm-2. Significant changes in the glutamate dehydrogenase extinction coefficient measured at 275 nm, the capability of the enzyme to bind the reduced form of nicotinamide adenine dinucleotide (NADH), certain kinetic parameters, the pH and temperature dependence and the sensitivity to guanosine 5 triphosphate (GTP) and adenosine diphosphate (ADP) were found, probably due to the interaction of light with a protein domain containing a metal ion or ions. He-Ne laser and diode irradiation were found to differ with regard to their interaction with glutamate dehydrogenase. Interestingly, different effects were also found when an He-Ne laser and a non-coherent Xe-Hg lamp were used to irradiate glutamate dehydrogenase under the same experimental conditions. This confirms that non-coherent light at various power levels affects the isolated glutamate dehydrogenase.


The association between nonsteroidal anti-inflammatory drugs and potassium concentrations: A pharmacoepidemiological study in Saudi Arabia.
Several nonsteroidal anti-inflammatory drugs (NSAIDs) have been linked to cardiac death. The mechanism that is responsible for this adverse effect appears to be ischemic insult; however, another possible mechanism involves hyperkalemia. The objective of the present study was to determine the feasibility of conducting pharmacoepidemiological studies in Saudi Arabia using refill prescription data to investigate the association between NSAIDs and increased serum potassium concentrations. This retrospective cohort study included patients from an academic medical center in Riyadh, Saudi Arabia. The patients who were recently prescribed NSAIDs were compared to a control group of paracetamol users, with respect to the drugs' effects on serum potassium concentrations. The covariates that affected the potassium concentration or the use of NSAIDs were controlled for in the analysis. The studied outcome was the first serum potassium concentration of more than 5 mEq/L. A total of 184 patients were prescribed NSAIDs (n = 101) or paracetamol (n = 83) and met the inclusion criteria. Compared to the control group, the patients who received NSAIDs were more likely to be women, were less likely to use angiotensin-converting enzyme inhibitors, and were more likely to have lower baseline serum creatinine concentrations. The other baseline characteristics were similar between the patients in the NSAID group and the patients who received paracetamol. Compared to the patients who were prescribed paracetamol, those who were prescribed NSAIDs did not have an increased risk of hyperkalemia (odds ratio, 1.1, 95% confidence interval, 0.17-6.7, P = 0.95). In the present, small feasibility study, no increase in the risk of hyperkalemia was associated with NSAIDs compared to paracetamol. The present study was exploratory and included only a small number of patients; therefore, this study may not be sufficiently powered to detect small differences between the groups. Future studies with larger sample sizes are needed to investigate the association between NSAIDs and hyperkalemia.


The use of medical cognition in medical curriculum reform in Taiwan.
Medical cognition studies have generated a great deal of knowledge that can be used to improve the quality of medical education. This review summarizes medical cognition research, the trends in medical education, and how the results of cognitive research can be applied to medical curriculum reform in Taiwan. The current trend in medical education is to develop a student-centered, outcome-oriented curriculum that integrates basic and clinical science, introduces students to patients at an early stage, reduces redundancy, and promotes active learning. To help students to develop and maintain their expertise in medicine, extensive supervised training with evaluation and feedback should be provided. The curriculum should also be designed to provide a learning context in which students are helped to develop a knowledge structure and diagnostic strategies similar to those used by experts. Finally, the curriculum should be flexible and responsive to the needs of students to train them to be excellent physicians in the future.


Renal impairment following biliary tract surgery.
Postoperative mortality has been directly attributed to renal failure in approximately 5 per cent of patients after surgery for obstructive jaundice. An analysis of 334 patients undergoing biliary tract surgery was undertaken to identify the perioperative factors associated with the development of renal impairment, and to estimate the contribution of renal failure to mortality. Thirty-eight patients (11 per cent) developed postoperative renal impairment (a two-fold increase in serum creatinine postoperatively or a rise of greater than 100 mumol/l). Ninety-three factors were examined in these and 196 control patients. Stepwise logistic regression analysis identified only three factors which were significantly associated with renal impairment: postoperative sepsis (P less than 0.0005), pre-operative serum bilirubin (P less than 0.0005), and pre-operative urea (P less than 0.05). Renal impairment developed at a median 4 days after surgery and was associated with a median of two additional major postoperative complications, particularly sepsis and haemorrhage, for which 17 patients underwent reoperation. Twenty-eight (74 per cent) of the patients with renal impairment died in hospital, but in only one case was the cause of death directly related to renal failure. Twenty patients received specific therapy for renal failure, but only one of these survived. Pre-operative obstructive jaundice and postoperative infection are the major factors associated with renal impairment after biliary tract surgery. Renal impairment appears to be related to postoperative complications rather than directly to the surgical procedure itself. The development of postoperative renal impairment predicts a low chance of survival but appears to be an indicator, rather than a direct cause of a poor prognosis.


The unfolded map using 201T1 myocardial SPECT.
The unfolded map is a new method to show the 201T1 distribution of left ventricle using SPECT. In 52 cases these maps were obtained at the stress study and 4 h later. The maximal count profiles of the perimeters for each short axis image were unfolded and were arranged from the apex to base of the left ventricle into a two dimensional map. All patients had chest pain and were suspected of coronary artery disease. The unfolded map had significant correlations between coronary arteriogram and exercise ECG findings. In conclusion, this method reflects the ischemic area of left ventricular myocardium, closer to the real left ventricular myocardium than Bull's eye display and is useful in the diagnosis of coronary heart disease.


Expression and subcellular localization of thymosin beta15 following kainic acid treatment in rat brain.
Thymosin beta15 (Tbeta15) is a pleiotropic factor which exerts multiple roles in the development of nervous system and brain diseases. In this study, we found that the expressions of Tbeta15 mRNA and protein were substantially increased in several brain regions including hippocampal formation and cerebral cortex, following kainic acid (KA)-evoked seizures in rat. Interestingly, a subset of cortex neurons exhibited nuclear Tbeta15 immunoreactivity upon KA treatment. Furthermore, translocation of Tbeta15 from cytosol to nuclei was observed in cultured neurons or HeLa cells during staurosporine (STS)-induced apoptosis, which was also verified by time-lapse imaging of YFP-tagged Tbeta15. It appeared that localization of Tbeta15 is restricted to the cytosol in normal condition by its G-actin-interacting domain, because site-directed mutagenesis of this region resulted in the nuclear localization of Tbeta15 in the absence of STS treatment. To explore the role of nuclear Tbeta15, we enforced Tbeta15 to localize in the nuclei by fusion of Tbeta15 with nuclear localization signal (NLS-Tbeta15). However, overexpression of NLS-Tbeta15 did not alter the viability of cells in response to STS treatment. Collectively, these results suggest that nuclear localization of Tbeta15 is a controlled process during KA or STS stimulation, although its functional significance is yet to be clarified.


Ketogenic diet: rapid onset of selenium deficiency-induced cardiac decompensation.
Selenium-deficiency cardiomyopathy is a known secondary complication from long-term treatment with a ketogenic diet for medical refractory epilepsy. Our patient, a 5-year-old boy on a ketogenic diet for intractable seizures, had a normal selenium level before starting the diet, but he shortly thereafter developed acute reversible cardiomyopathy and ventricular tachycardia, which was unmasked during a hospitalization for an elective operative procedure. His cardiomyopathy was suspected to be secondary to a selenium-deficient state and was confirmed by way of a markedly low serum selenium level and supported by rapid improvement with the initiation of selenium supplementation and cessation of the ketogenic diet. For patients being initiated on a ketogenic diet, current screening guidelines call for baseline and follow-up selenium levels every 3 months during the first year along with RDA selenium supplementation, which is 30 mcg/day. Most of the new ketogenic diet formulas meet this requirement. Our patient underwent elective surgery before his planned 3-month selenium level check and had potentially preventable complications. Secondary to this experience, we suggest that all patients initiated on a ketogenic diet should have a preoperative electrocardiogram (EKG), an echocardiogram, and selenium level determined before any elective surgery. These steps would prevent unnecessary perioperative morbidity and mortality.


EUS-guided cholecystostomy versus endoscopic transpapillary cholecystostomy for acute cholecystitis in high-risk surgical patients.
Endoscopic gallbladder drainage (GBD) has been performed as an alternative to percutaneous drainage for acute cholecystitis. To date, there has been no comparative study between EUS-guided cholecystostomy (EUSC) and endoscopic transpapillary cholecystostomy (ETC). The aim of this study was to compare the outcomes of EUSC and ETC. A retrospective review of an endoscopic GBD database prospectively collected at the Asan Medical Center (between July 2010 and December 2014) was performed to identify consecutive patients with acute cholecystitis who underwent attempted endoscopic GBD. Procedural and long-term outcomes were evaluated using inverse probability of treatment weighting (IPTW). A total of 172 patients (76 in the EUSC group and 96 in the ETC group) were included in this study. Seven patients who failed to undergo ETC crossed over to the EUSC group. After adjustment with the IPTW method, technical success (99.3% vs 86.6%, P < .01) and clinical success (99.3% vs 86%, P < .01) rates were significantly higher in the EUSC group than in the ETC group. The procedure-related adverse event rate was significantly higher in the ETC group (7.1% vs 19.3%, P = .02). The cholecystitis or cholangitis recurrence rate (12.4% vs 3.2%) was also higher in the ETC group than in the EUSC group, as identified using Cox analysis (hazard ratio, 3.01; 95% confidence interval, .73-12.9; P = .04). In patients with acute cholecystitis who are unfit for surgery, EUSC may be a more suitable treatment method than ETC.


Theoretical study on the radical anions and reductive dechlorination of selected polychlorinated dibenzo-p-dioxins.
For the effective use of remediation technologies for PCDDs contamination, it is essential to study the reactivity and dechlorination pathways of these compounds. In this study, density functional theory (DFT) calculations (B3LYP/6-31+G(d), B3LYP/6-311+G(d,p)) were performed to investigate the neutrals and different anionic states of selected PCDD congeners. The calculated adiabatic electron affinities and frontier orbital energies of the PCDD congeners (in gas-phase and in solution) are significantly correlated with the reported dechlorination rate constants, showing that this kind of reductive cleavage reaction is kinetically controlled by the electron transfer step. The predicted major dechlorination pathways of 1,2,3,4-TeCDD and its daughter products based on the energies of the anionic states were found to be satisfactorily consistent with the reported experimental results. Simulation of the 1,2,3,4-TeCDD dechlorination process showed that not only the dechlorination regioselectivity but also the reactivity of the PCDDs played an important role in the distribution of dechlorinated products. An exponential correlation was found between the sum of the concentration of the PCDD congeners and the reaction time in the simulation, indicating that the time required for the conversion of the PCDD congeners to the fully dechlorinated product (dibenzo-p-dioxin) might not be significantly dependent on the initial concentration of 1,2,3,4-TeCDD.


High-performance bamboo composites based on the chemical bonding of active bamboo interface and chitosan.
Nowadays, green, clean, and efficient sustainable development has become the world's mainstream industrial development. However, the bamboo/wood industry is still in the status quo with high fossil resource dependence and significant greenhouse gas emissions. Herein, a low-carbon and green strategy to produce bamboo composites is developed. The bamboo interface was modified directionally to a bamboo carboxy/aldehyde interface by using a TEMPO/NaIO4 system, and then chemically cross-linked with chitosan to produce active bonding bamboo composite (ABBM). It was confirmed that the chemical bond cross-linking (CN, N-C-N, electrostatic interactions, hydrogen bonding) in the gluing region was helpful to obtain the excellent dry bonding strength (11.74 MPa), water resistance (5.44 MPa), and anti-aging properties (decreased by 20 %). This green production of ABBM solves the problem of poor water resistance and aging resistance of all-biomass-based chitosan adhesives. It can replace bamboo composites produced using fossil-based adhesives to meet the requirements of the construction, furniture, and packaging industries, changing the previous situation of composite materials requiring high temperature pressing and highly dependent on fossil-based adhesives. This provides a greener and cleaner production method for the bamboo industry, as well as more options for the global bamboo industry to achieve green and clean production goals.


A statement of principles for health care journalists.
Many journalism organizations have published codes of ethics in recent years. The Association of Newspaper Editors, for example, lists 47 different codes on its website. But an organization of health care journalists felt that none of those codes addressed the unique challenges of covering complex health care topics. The Association of Health Care Journalists (AHCJ) is an independent, non-profit organization dedicated to advancing public understanding of health care issues. Its mission is to improve the quality, accuracy and visibility of health care reporting, writing and editing. AHCJ has written a statement of principles for its 750 members. In it, AHCJ states some of the unique challenges faced by journalists covering health care, and offers suggestions on how to face those challenges. Bioethicists are invited to comment on the statement, and to help generate continued discussion of the issues addressed therein.


Intrathoracic kidney: a case report with a review of the world literature.
We report a case of a right intrathoracic kidney and review the literature. The possible etiologies of intrathoracic kidneys are discussed.


Solvent-Free and Skin-Like Supramolecular Ion-Conductive Elastomers with Versatile Processability for Multifunctional Ionic Tattoos and On-Skin Bioelectronics.
The development of stable and biocompatible soft ionic conductors, alternatives to hydrogels and ionogels, will open up new avenues for the construction of stretchable electronics. Here, a brand-new design, encapsulating a naturally occurring ionizable compound by a biocompatible polymer via high-density hydrogen bonds, resulting in a solvent-free supramolecular ion-conductive elastomer (SF-supra-ICE) that eliminates the dehydration problem of hydrogels and possesses excellent biocompatibility, is reported. The SF-supra-ICE with high ionic conductivity (>3.3 × 10-2 S m-1 ) exhibits skin-like softness and strain-stiffening behaviors, excellent elasticity, breathability, and self-adhesiveness. Importantly, the SF-supra-ICE can be obtained by a simple water evaporation step to solidify the aqueous precursor into a solvent-free nature. Therefore, the aqueous precursor can act as inks to be painted and printed into customized ionic tattoos (I-tattoos) for the construction of multifunctional on-skin bioelectronics. The painted I-tattoos exhibit ultraconformal and seamless contact with human skin, enabling long-term and high-fidelity recording of various electrophysiological signals with extraordinary immunity to motion artifacts. Human-machine interactions are achieved by exploiting the painted I-tattoos to transmit the electrophysiological signals of human beings. Stretchable I-tattoo electrode arrays, manufactured by the printing method, are demonstrated for multichannel digital diagnosis of the health condition of human back muscles and spine.


Preparation, characterization and bioactivities of selenized polysaccharides from Lonicera caerulea L. fruits.
Native polysaccharide was obtained from Lonicera caerulea L. fruits (PLP). Two selenized polysaccharides (PSLP-1 and PSLP-2) were synthesized by the microwave-assisted HNO3-Na2SeO3 method, where the selenium (Se) contents were 228 ± 24 and 353 ± 36 μg/g, respectively. The molecular weights of PLP, PSLP-1, and PSLP-2 were 5.9 × 104, 5.6 × 104, and 5.1 × 104 kDa, respectively. PSLP-1 and PSLP-2 contained the same type of monosaccharides as PLP but with different molar ratios. The main chain structure of the native polysaccharide was not changed after selenization. PLP, PSLP-1, and PSLP-2 contained the same six types of glycosidic bonds. Bioactivity assays revealed that the two selenized polysaccharides possessed better antioxidant activities than PLP, but their bile acid-binding abilities and inhibitory activities on acetylcholinesterase (AChE) had weakened. In summary, PLP, PSLP-1, and PSLP-2 may be promising Se supplements in functional foods and inhibitors for the treatment of AChE.


Healthcare professionals' experiences of providing individualized nutritional care for Older People in hospital and home care: a qualitative study.
Recent studies indicate inadequate nutritional care practices in healthcare institutions and identify several barriers to perform individualized nutritional care to older persons. Organisation of care can become rigid and standardised, thus failing to be respectful of and responsive to each person's needs and preferences. There is limited research exploring health professionals' views on how structure of care allows them to individualize nutritional care to older persons. In this study we aim to explore how healthcare professionals' experience providing individualised nutritional care within the organisational frames of acute geriatric hospital care and home care. Semi-structured interviews with 23 healthcare professionals from hospital acute geriatric care and home care. Interviews were analyzed using thematic analysis. Two main themes and six sub-themes emerged from the material. Theme 1: 'Meeting patients with complex nutritional problems' with the sub-themes: 'It is much more complex than just not eating' and 'seeing nutrition as a part of the whole'. Theme 2: 'The structure of the nutritional care', with the sub-themes: 'Nutritional routines: Much ado, but for what?', 'lack of time to individualize nutritional care', 'lack of interdisciplinary collaboration in nutritional care' and 'meeting challenging situations with limited resources in home care'. The healthcare professionals described having a high focus on and priority of nutritional care when caring for older persons. They did however find it challenging to practice individualized nutritional care due to the complexity of the patients' nutritional problems and constraints in the way nutritional care was organised. By describing the challenges the healthcare professionals face when trying to individualize the nutritional care, this study may provide important knowledge to health professionals and policy makers on how to decrease the gap between older patients' preferences for care and nutritional care practice.


Boo, a novel negative regulator of cell death, interacts with Apaf-1.
In this report, we describe the cloning and characterization of Boo, a novel anti-apoptotic member of the Bcl-2 family. The expression of Boo was highly restricted to the ovary and epididymis implicating it in the control of ovarian atresia and sperm maturation. Boo contains the conserved BH1 and BH2 domains, but lacks the BH3 motif. Like Bcl-2, Boo possesses a hydrophobic C-terminus and localizes to intracellular membranes. Boo also has an N-terminal region with strong homology to the BH4 domain found to be important for the function of some anti-apoptotic Bcl-2 homologues. Chromosomal localization analysis assigned Boo to murine chromosome 9 at band d9. Boo inhibits apoptosis, homodimerizes or heterodimerizes with some death-promoting and -suppressing Bcl-2 family members. More importantly, Boo interacts with Apaf-1 and forms a multimeric protein complex with Apaf-1 and caspase-9. Bak and Bik, two pro-apoptotic homologues disrupt the association of Boo and Apaf-1. Furthermore, Boo binds to three distinct regions of Apaf-1. These results demonstrate the evolutionarily conserved nature of the mechanisms of apoptosis. Like Ced-9, the mammalian homologues Boo and Bcl-xL interact with the human counterpart of Ced-4, Apaf-1, and thereby regulate apoptosis.


Astrocytes in glaucomatous optic neuropathy.
Glaucoma, the second most prevalent cause of blindness worldwide, is a degenerative disease characterized by loss of vision due to loss of retinal ganglion cells. There is no cure for glaucoma, but early intervention with drugs and/or surgery may slow or halt loss of vision. Increased intraocular pressure (IOP), age, and genetic background are the leading risk factors for glaucoma. Our laboratory and other investigators have provided evidence that astrocytes are the cells responsible for many pathological changes in the glaucomatous optic nerve head (ONH). Over several years, in vivo and in vitro techniques characterized the changes in quiescent astrocytes that lead to the reactive phenotype in glaucoma. Reactive astrocytes alter the homeostasis and integrity of the neural and connective tissues in the ONH of human and experimental glaucoma in monkeys. During the transition of quiescent astrocytes to the reactive phenotype altered astrocyte homeostatic functions such as cell-cell communication, migration, growth factor pathway activation, and responses to oxidative stress may impact pathological changes in POAG. Our data also suggests that the creation of a non-supportive environment for the survival of RGC axons through remodeling of the ONH by reactive astrocytes leads to progression of glaucomatous optic neuropathy.


Medial malleolar window approach for varus-type tibial pilon fractures: a retrospective study.
Choosing a suitable surgical approach is crucial and challenging for type C pilon fractures. This article aims to explore the clinical efficacy of the medial malleolar window approach for varus-type tibial pilon fractures. A retrospective analysis was conducted on 38 patients with type C varus-type pilon fractures treated between May 2018 and June 2021. In total, 16 cases underwent surgical treatment through the medial malleolar window approach and 22 cases were treated with the traditional anteromedial approach combined with a posterior approach. The operation time, hospitalization time, fracture healing time, the American Orthopedic Foot and Ankle score, Visual Analogue Scale, and complications were recorded to comprehensively evaluate the clinical efficacy of the technique. Fracture reduction quality was evaluated using the criteria proposed by Burwell and Charnley. All patients were followed up. No patients presented delayed union or nonunion. Compared with the conventional approach, the medial malleolar window approach had the advantage of better clinical effect recovery and better fracture reduction (P < 0.05). Meanwhile, the medial malleolar window approach had a shorter operation time, although the statistics suggest no significant difference with the control group. No implant exposure or infection occurred. There was good wound healing at two weeks after surgery in all but two cases. Local wound edge necrosis developed in one case in the medial malleolar window approach group, and the wound could not be closed at one stage in another case in the conventional group because of excessive tension, requiring secondary closure. The medial malleolar window approach provides excellent exposure to type C pilon fractures, allowing for satisfactory fracture reduction and functional rehabilitation. The medial window approach is recommended for varus-type pilon fractures, which can effectively avoid a posterior incision and reduce the operation time.


Chemically surface-modified carbon nanoparticle carrier for phenolic pollutants: Extraction and electrochemical determination of benzophenone-3 and triclosan.
Chemically surface-modified (tosyl-functionalized) carbon nanoparticles (Emperor 2000 from Cabot Corp.) are employed for the extraction and electrochemical determination of phenolic impurities such as benzophenone-3 (2-hydroxy-4-methoxybenzophenone) or triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol). The hydrophilic carbon nanoparticles are readily suspended and separated by centrifugation prior to deposition onto suitable electrode surfaces and voltammetric analysis. Voltammetric peaks provide concentration information over a 10-100microM range and an estimated limit of detection of ca. 10microM (or 2.3ppm) for benzophenone-3 and ca. 20microM (or 5.8ppm) for triclosan. Alternatively, analyte-free carbon nanoparticles immobilized at a graphite or glassy carbon electrode surface and directly immersed in analyte solution bind benzophenone-3 and triclosan (both with an estimated Langmuirian binding constants of K approximately 6000mol(-1)dm(3) at pH 9.5) and they also give characteristic voltammetric responses (anodic for triclosan and cathodic for benzophenone-3) with a linear range of ca. 1-120microM. The estimated limit of detection is improved to ca.5microM (or 1.2ppm) for benzophenone-3 and ca. 10microM (or 2.3ppm) for triclosan. Surface functionalization is discussed as the key to further improvements in extraction and detection efficiency.


Effectiveness of collaborative care for depression in Italy. A randomized controlled trial.
This was a multicenter cluster-randomized controlled trial. A total of 227 patients ≥18 years old with a new onset of depressive symptoms who screened positive on the first two items of the Patient Health Questionnaire-9 (PHQ-9) were recruited by primary care physicians (PCPs) of eight health districts of three Italian regions from September 2009 to June 2011. PCPs of the intervention group received a specific collaborative care program including 2 days of intensive training, implementation of a stepped care protocol, depression management toolkit and scheduled meetings with a dedicated consultant psychiatrist. The objective was to determine whether a collaborative care program for depression management in primary care leads to higher remission rate than usual PCP care. Outcome was clinical remission as expressed on PHQ-9 <5 at 3 months. An independent researcher used computer-generated randomization to assign involved primary care groups to the two alternative arms. PCPs and research personnel were not blinded. The 223 PCPs enrolled recruited 227 patients (128 in collaborative care arm, 99 in the usual care arm). At 3 months (n=210), the proportion of patients who achieved remission was higher, though the difference was not statistically significant, in the collaborative care group. The effect size was of 0.11. When considering only patients with minor/major depression, collaborative care appeared to be more effective than usual care (P=.015). The present intervention for managing depression in primary care, designed to be applicable to the Italian context, appears to be effective and feasible.


A novel inflammation-based prognostic score in esophageal squamous cell carcinoma: the C-reactive protein/albumin ratio.
Plenty of studies have demonstrated the prognostic value of various inflammation-based indexes in cancer. This study was designed to investigate the prognostic value of the C-reactive protein/albumin (CRP/Alb) ratio in esophageal squamous cell carcinoma. A retrospective study of 423 cases with newly diagnosed esophageal squamous cell carcinoma was conducted. We analyzed the association of the CRP/Alb ratio with clinicopathologic characteristics. The prognostic value was explored by univariate and multivariate survival analysis. In addition, we compared the discriminatory ability of the CRP/Alb ratio with other inflammation-based prognostic scores by evaluating the area under the receiver operating characteristics curves (AUC), including the modified Glasgow Prognostic Score (mGPS), neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR). The optimal cut-off value was identified to be 0.095 for the CRP/Alb ratio. A higher level of the CRP/Alb ratio was associated with larger tumor size (P < 0.001), poorer differentiation (P = 0.019), deeper tumor invasion (P = 0.003), more lymph node metastasis (P = 0.015), more distant metastasis (P < .001) and later TNM stage (P < 0.001). The CRP/Alb ratio was identified to be the only inflammation-based prognostic score with independent association with overall survival by multivariate analysis (P = 0.031). The AUC value of the CRP/Alb ratio was higher compared with the NLR and PLR, but not mGPS at 6, 12 and 24 months of follow-up. In addition, the CRP/Alb ratio could identify a group of patients with mGPS score of 0 who had comparable overall survival with those with mGPS score of 1. The CRP/Alb ratio is a novel but promising inflammation-based prognostic score in esophageal squamous cell carcinoma. It is a valuable coadjutant for the mGPS to further identify patients' survival differences.


Regulation of the NLRP3 inflammasome with natural products against chemical-induced liver injury.
The past decades have witnessed significant progress in understanding the process of sterile inflammation, which is dependent on a cytosolic complex termed the nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome. Activation of NLRP3 inflammasome requires two steps, including the activation of Toll-like receptor (TLR) by its ligands, resulting in transcriptional procytokine and inflammasome component activation, and the assembly and activation of NLRP3 inflammasome triggered by various danger signals, leading to caspase-1 activation, which could subsequently cleave procytokines into their active forms. Metabolic disorders, ischemia and reperfusion, viral infection and chemical insults are common pathogenic factors of liver-related diseases that usually cause tissue damage and cell death, providing numerous danger signals for the activation of NLRP3 inflammasome. Currently, natural products have attracted much attention as potential agents for the prevention and treatment of liver diseases due to their multitargets and nontoxic natures. A great number of natural products have been shown to exhibit beneficial effects on liver injury induced by various chemicals through regulating NLRP3 inflammasome pathways. In this review, the roles of the NLRP3 inflammasome in chemical-induced liver injury (CILI) and natural products that exhibit beneficial effects in CILI through the regulation of inflammasomes were systematically summarized.


Oral microflora and their relation to risk factors in HIV+ patients with oropharyngeal candidiasis.
The purpose of this study was to determine the prevalence of oral microflora and association of oral candidiasis and multiple risk factors in HIV(+) patients. The present study included 100 HIV-infected patients participated in Imam Khomeini Hospital, Tehran, Iran for Oropharyngeal candidiasis (OPC) and HIV. We assessed the presence or absence of OPC, and samples were obtained from the oral cavity and direct microscopic examination, gram staining and culture on standard microbiological media were performed in all patients. CD4(+) cell count/CD4(+) percentage were also calculated. The demographic characteristics showed that the patients had a mean age of 32.3 years old, 78% male and 22% female. Patients belonging to 'O(+)' blood group (27%) were more prone to develop OPC. A total of 460 bacterial colonies were obtained and Streptococcus mutans (15.4%) was the most frequently isolated species in the HIV(+) patients, followed by Staphylococcus epidermidis (12.8%) and Corynebacterium (8.7%). In addition, 254 yeasts (from four different genera) were isolated from the patient under study. Candida species (94.4%) were the most frequently obtained genera, followed by Saccharomyces (2.4%), Kluyveromyces and Cryptococcus (1.6% for both) species. Candida albicans (37.2%) was the most common species isolated from HIV(+) patients with OPC and its frequency was significantly higher than that of other Candida species (P<0.05). Candida glabrata, C. dubliniensis, C. tropicalis, C. parapsilosis, C. krusei, C. lusitaniae, C. guilliermondii and C. norvegensis were also identified. Forty percent of the patients had angular cheilitis as the most frequent clinical variant. The mean CD4(+) cell counts were 154.5 cells/μL, with a range of 8 to 611 cells/μL. Thirty percent patients had a CD4(+) cell count between 101 and 200 cells/μL (28.7% of total yeasts isolated). Yeast and bacteria counts did not differ statistically among HIV(+) patients' subgroups with different levels of CD4(+) cells counts. Our results showed that yeasts of the genus Candida were isolated at a comparable rate from the oral cavity of HIV(+) patients and there was no significant difference of the variables CD4(+) cell count and yeast counts. The findings of this study would be helpful in any further study, which, if done prospectively on a large cohort, can be confirmatory.


The hemodynamic effects of potassium deficiency in the dog.
Potassium deficiency for 3 weeks in dogs caused 374 +/- 38 mEq of sodium retention with increase in body weight, plasma volume, and inulin space. Cardiac output increased from 3.7 +/- 0.6 to 5 +/- 0.6 liters/min (P less than 0.02) and systemic vascular resistance decreased from 3,050 +/- 590 to 2,000 +/- 286 dynes/cm per sec2 (P less than 0.05). Plasma renin activity (PRA) increased from 0.4 +/- 0.1 to 17.2 +/- 0.9 ng/ml per hour (P less than 0.01) without change in plasma aldosterone. Angiotensin sensitivity decreased from a rise of 37 +/- 4 mm Hg in mean arterial pressure (MAP) to 10 ng/kg per min before potassium depletion to a rise of 10 +/- 2 mm Hg after hypokalemia. Urinary prostaglandin E (PGE) excretion increased from control values of 1,224 to 1,556 ng/day to 9,352 +/- 3,670 after 21 days of hypokalemia (P less than 0.01). Indomethacin, 150 mg a day for 3 days, decreased urinary PGE to control values as PRA decreased from 17.2 +/- 5.9 to 1.1 +/- .3 ng/ml per hour and angiotensin sensitivity was partially restored. These findings indicate that hypokalemia increased urinary PGE with extracellular fluid volume expansion, decreased sensitivity to angiotensin and increase in PRA.


Plasma levels of oestrone, oestradiol and gonadotrophins in postmenopausal women after oral and vaginal administration of conjugated equine oestrogens (Premarin).
Peripheral plasma from five postmenopausal women was analyzed for oestrone and oestradiol during 48 hours after administration of 1.25 mg Premarin (conjugated equine oestrogen) orally and vaginally. Oestrone and oestradiol were separated on columns of Sephadex LH 20 before radioimmunoassay. Administration of 1.25 mg of Premarin produced a marked increase in plasma oestrone levels and 24 hours after treatment the oestrone levels were still above follicular phase levels. The plasma pattern of oestradiol was similar but the elevation was less pronounced. The biological activity of Premarin as indicated by depressed gonadotrophin levels was similar with the intravaginal and oral routes of administration.


Preoperative classification of submucosal fibrosis in colorectal laterally spreading tumors by endoscopic ultrasonography.
Although endoscopic submucosal dissection (ESD) is an established therapy for colon neoplasms including laterally spreading tumors (LSTs), its application to advanced fibrotic lesions is very difficult owing to the thin walls of the large intestine. We examined the ability of preoperative endoscopic ultrasonography (EUS) to predict lesion fibrosis in patients undergoing colorectal ESD. From 2009 to 2013, 58 LSTs were evaluated retrospectively with EUS and treated using colorectal ESD. The degree of submucosal fibrosis was determined during ESD and classified as F0 (no fibrosis), F1 (mild fibrosis), or F2 (severe fibrosis). The sensitivity and specificity of fibrosis prediction by preoperative EUS of all cases were 77.8 % and 57.1 %, respectively. However, there was a high accuracy (97.2 %, 35/36) for only the 36 LSTs with clear and visible images. In one case, EUS diagnosed no fibrosis but significant fibrosis was found during ESD, the result of colon cancer invasion into the submucosa. Preoperative EUS before colorectal ESD successfully predicted the degree of fibrosis in a number of cases.


The Changing Face of the Cornea in a Case of Juvenile Glaucoma and Subclinical Keratoconus.
We report on a 23-year-old man who presented with bilateral subclinical keratoconus and juvenile glaucoma (JG). With intraocular pressures (IOPs) of 30 and 28 mmHg, both eyes were consecutively operated by adjusted trabeculotomy, leading to a remarkable decrease in IOP to well below the mean for this surgery in JG. Meanwhile, most keratoconus indices clearly progressed in the first 5 months postoperatively, with increases in corneal hysteresis, associated with a remarkable drop in the corneal resistance factor. During the following years, IOP remained low, and all changes (except the increase in corneal hysteresis) reverted to near preoperative levels through the follow-up course of 5 years. This report complements a few existing reports that show the coincidence of keratoconus and JG, and, more importantly, documents a novel pattern of remarkable and prolonged corneal changes following surgical lowering of IOP in eyes with these changes. Postoperative biomechanical disturbances in the cornea and possibly limbus are proposed in cases of JG and subclinical keratoconus.


Coordination of Rho and Rac GTPase function via p190B RhoGAP.
The Rac GTPase regulates Rho signaling in a broad range of physiological settings and in oncogenic transformation [1-3]. Here, we report a novel mechanism by which crosstalk between Rac and Rho GTPases is achieved. Activated Rac1 binds directly to p190B Rho GTPase-activating protein (RhoGAP), a major modulator of Rho signaling. p190B colocalizes with constitutively active Rac1 in membrane ruffles. Moreover, activated Rac1 is sufficient to recruit p190B into a detergent-insoluble membrane fraction, a process that is accompanied by a decrease in GTP-bound RhoA from membranes. p190B is recruited to the plasma membrane in response to integrin engagement [4]. We demonstrate that collagen type I, a potent inducer of Rac1-dependent cell motility in HeLa cells, counteracts cytoskeletal collapse resulting from overexpression of wild-type p190B, but not that resulting from overexpression of a p190B mutant specifically lacking the Rac1-binding sequence. Furthermore, this p190B mutant exhibits dramatically enhanced RhoGAP activity, consistent with a model whereby binding of Rac1 relieves autoinhibition of p190B RhoGAP function. Collectively, these observations establish that activated Rac1, through direct interaction with p190B, modulates subcellular RhoGAP localization and activity, thereby providing a novel mechanism for Rac control of Rho signaling in a broad range of physiological processes.


[Morphology of a malignant parotideal lymphoma with paraproteinaceous cytoplasmic inclusions (author's transl)].
A female patient presented with a lump in the right parotedeal region. A needle aspiration biopsy was performed which revealed numerous monomorphous atypical lymphoid cells with PAS-negative cytoplasmic inclusions. This raised the suspicion of malignancy. Therefore, the tumour was excised. Histologically, a nodular lymphoma of low grade of malignancy was diagnosed. The tumour contained many epithelioid histiocytes, sometimes with PAS-positive material. The case was difficult to classify after the Kiel-nomenclature, whilst classification on the basis of Rappaport's system was much easier.


Do Hospital or Surgeon Volume Affect Outcomes After Surgical Management of Tibial Shaft Fractures?
To determine whether hospital and surgeon volume are associated with outcomes after operative fixation of tibial shaft fractures. Adults (≥18 year old) who underwent operative fixation of diaphyseal tibial fractures were identified in the New York Statewide Planning and Research Cooperative System data set from 2001 to 2015. Reoperation, nonunion, and other adverse event rates were compared across surgeon and hospital volume using multivariable Cox proportional hazards regression, adjusting for clinical and demographic factors. Low-volume providers (lowest 20%) were compared with high-volume providers (highest 20%). Low volume constituted <5 cases/year for hospitals and 1 case/year for surgeons. High volume constituted ≥40 cases/year for hospitals and ≥8 cases/year for surgeons. Nine thousand one hundred forty-seven patients were included. Relative to high-volume surgeons, low-volume surgeons experienced slightly higher rates of pneumonia [2% vs. 1%, hazard ratio (HR) 2.50, 95% confidence interval (CI) 1.38-4.53, P = 0.003], and respiratory failure (5% vs. 3%, HR 1.88, 95% CI 1.30-2.71, P = 0.001). Compared with high-volume hospitals, low-volume hospitals experienced slightly lower rates of compartment syndrome (1% vs. 3%, HR 0.45, 95% CI 0.24-0.85, P = 0.01) and fasciotomies (3% vs. 7%, HR 0.57, 95% CI 0.38-0.85, P = 0.005). The rates of all other reoperations and adverse events compared among hospitals and surgeons were not significantly different. We did not detect a clinically meaningful volume-outcome relationship for either surgeons or hospitals despite the use of a robust database with rigorous statistical methodology. Of note, these findings should not be applied to rare complex injuries such as those with extensive bone loss or articular extension, which are not well represented by this study population. Therefore, we conclude that typical tibial shaft fracture, including open or closed injuries, can be safely managed in the vast majority of orthopaedic settings and that this care does not necessarily require transfer to a specialty centers. Future research into orthopaedic volume-outcome relationships could be strengthened by the use of functional outcomes (which would likely require well-organized multicenter prospective registries). Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Novel plasmid marker rescue transformation system for molecular cloning in Bacillus subtilis enabling direct selection of recombinants.
A versatile plasmid marker rescue transformation system was developed for homology-facilitated cloning in Bacillus subtilis. It is based on the highly efficient host-vector system 6GM15-pHPS9, which allows the direct selection of recombinants by means of beta-galactosidase alpha-complementation. The system offers several advantages over previously described cloning systems: (1) the convenient direct selection of recombinants; (2) the ability to effectively transform B. subtilis competent cells with plasmid monomers, which allows the forced cloning of DNA fragments with high efficiency; (3) the availability of 6 unique target sites, which can be used for direct clone selection, SphI, NdeI, NheI, BamHI, SmaI and EcoRI; and (4) the rapid segregational loss of the helper plasmid from the transformed cells.


The impact of anthropogenic nitrogen deposition on global forests: Negative impacts far exceed the carbon benefits.
Humans have drastically altered the nitrogen (N) cycle during the past century, enriching ecosystems from the tropics to the tundra with unpresented inputs of novel nitrogen. The study by Schulte-Uebbing et al. (2021) quantified the impact of atmospheric N deposition on C uptake by forests globally, and weighed this climate benefit against the global warming impact of N2 O emissions. A major conclusion was that the C benefits of atmospheric deposition in global forests are smaller than previously estimated (only 41 Tg C year-1 ), accounting for only 2% of the net annual forest C uptake.


Effect of pre-operative hypoxemia on the occurrence and outcomes of post-operative ARDS in Stanford type a aortic dissection patients.
Pre-operative and post-operative hypoxemia are frequent complications of Stanford type A aortic dissection (AAD). This study explored the effect of pre-operative hypoxemia on the occurrence and outcome of post-operative acute respiratory distress syndrome (ARDS) in AAD. A total of 238 patients who underwent surgical treatment for AAD between 2016 and 2021 were enrolled. Logistic regression analysis was conducted to investigate the effect of pre-operative hypoxemia on post-operative simple hypoxemia and ARDS. Post-operative ARDS patients were divided into pre-operative normal oxygenation group and pre-operative hypoxemia group that were compared for clinical outcomes. Post-operative ARDS patients with pre-operative normal oxygenation were classified as the real ARDS group. Post-operative ARDS patients with pre-operative hypoxemia, post-operative simple hypoxemia, and post-operative normal oxygenation were classified as the non-ARDS group. Outcomes of real ARDS and non-ARDS groups were compared. Logistic regression analysis showed that pre-operative hypoxemia was positively associated with the risk of post-operative simple hypoxemia (odds ratios (OR) = 4.81, 95% confidence interval (CI): 1.67-13.81) and post-operative ARDS (OR = 8.514, 95% CI: 2.64-27.47) after adjusting for the confounders. The post-operative ARDS with pre-operative normal oxygenation group had significantly higher lactate, APACHEII score and longer mechanical ventilation time than the post-operative ARDS with pre-operative hypoxemia group (P < 0.05). Pre-operative the risk of death within 30 days after discharge was slightly higher in ARDS patients with pre-operative normal oxygenation than in ARDS patients with pre-operative hypoxemia, but there was no statistical difference(log-rank test, P = 0.051). The incidence of AKI and cerebral infarction, lactate, APACHEII score, mechanical ventilation time, intensive care unit and post-operative hospital stay, and mortality with 30 days after discharge were significantly higher in the real ARDS group than in the non-ARDS group (P < 0.05). After adjusting for confounding factors in the Cox survival analysis, the risk of death within 30 days after discharge was significantly higher in the real ARDS group than in the non-ARDS group (hazard ratio(HR): 4.633, 95% CI: 1.012-21.202, P < 0.05). Preoperative hypoxemia is an independent risk factor for post-operative simple hypoxemia and ARDS. Post-operative ARDS with pre-operative normal oxygenation was the real ARDS, which was more severe and associated with a higher risk of death after surgery.


The Effect of CAPE-V Sentences on Cepstral/Spectral Acoustic Measures in Dysphonic Speakers.
To investigate the effect of connected speech stimuli from the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) on cepstral/spectral acoustic measurements. Recordings from 20 participants seeking treatment for dysphonia were analyzed in this study. The participants read the 6 sentence stimuli from the CAPE-V at a comfortable pitch and loudness. Acoustic measures of cepstral peak prominence (CPP) and its standard deviation, the low-to-high spectral ratio and its standard deviation (LH and LHsd) and the multiparametric measure Cepstral Spectral Index of Dysphonia were acquired from each sentence recording and applied to analyses. A significant main effect for sentence type was present on the measurements of CPP, LH and LHsd. Post hoc pairwise comparisons revealed the most robust effect on CPP from the all-voiced sentence 'We were away a year ago'. For the measures of LH and LHsd, sentence effects were significant for the majority of comparisons. The connected speech stimuli from the CAPE-V affected cepstral/spectral acoustic measurements differentially. These findings support the rationale for using the various CAPE-V stimuli during clinical assessment, and indicate the need for further investigations to inform clinical practice.


Dorsolateral prefrontal cortex volume as a mediator between socioeconomic status and executive function.
Lower socioeconomic status (SES) is related to poorer cognitive performance, but the neural underpinnings of this relation are not fully understood. This study examined whether SES-linked decrements in executive function were mediated by smaller dorsolateral prefrontal cortex (DLPFC) volumes. Given the literature demonstrating that SES-brain relations differ by race, we examined whether race moderated these mediations. Participants were 190 socioeconomically diverse, self-identified African American (AA) and White adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) SCAN study. Regional brain volumes were derived using T1-weighted MP-RAGE images. Adjusting for age and sex, moderated mediation analyses examined if the DLPFC mediated SES-executive function relations differently across racial groups. Executive function was measured using Trail Making Test part B (Trails B), Digit Span Backwards (DSB), and verbal fluency. Moderated mediation demonstrated that DLPFC volume significantly mediated the association between SES and Trails B in Whites (lower confidence interval [CI] = 0.01; upper CI = 0.07), but not in AAs (lower CI = -0.05; upper CI = 0.01). No mediations were found for DSB or verbal fluency, although SES was related to all tests. The DLPFC may be important in the association of SES and mental flexibility for White, but not AA adults. It is possible that the well-replicated advantages of high SES among Whites do not readily translate, on average, to AAs. These findings highlight the importance of brain volume for cognitive functioning, while adding to the literature on sociodemographic health disparities. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


[Atrioventricular septal defect in an adult patient: There are 'clefts' and clefts].
In this report, we present the case of an adult male with severe mitral regurgitation due to an atrioventricular septal defect. Anatomical assessment by two- and three-dimensional transesophageal echocardiography was essential for detailed morphological characterization and surgical planning. The different features of a 'cleft' in an atrioventricular septal defect compared to an anterior leaflet cleft in an otherwise normal mitral valve are here discussed.


Cytosine methylation as an effector of right-handed to left-handed DNA structural transitions.
Cytosine methylation has energetic and structural influences on left-handed Z-DNA formation in supercoiled plasmids. The restriction and modification enzymes from Haemophilus haemolyticus (HhaI and M.HhaI) provide a system to locate and analyze small segments of Z-DNA in large supercoiled plasmids. An approach is outlined that uses M.HhaI as an in vivo conformational probe for the detection of unusual DNA structures in a living cell. Also, characteristic features of the M.HhaI gene and protein are discussed.


Impact of COVID-19 on gynaecological patient care: results of patient's survey with 327 patients.
The pandemic SARS-CoV-2 poses new and unprecedented challenges for health care systems on a national and global level. Although the current situation has been going on for more than 1 year, there is limited data on the impact of the pandemic on general hospital and medical practice care. This survey captures the perspective of patients with gynaecological diseases of this impact. Using a paper-based questionnaire, 327 patients were asked about medical care and their experiences during the pandemic at the University Hospital Bonn and the University Hospital Charité Berlin. The study was performed from the 1st June to 30th September 2020. A total of 327 patients participated in the study: 156 stated to have been tested for coronavirus, and 1 patient reported a positive test. 41.3% of the patients felt insecure about the current situation, 30.4% were concerned about the risk of infection during the hospital stay. The pandemic-specific measures in hospitals and medical practices unsettled 6.8% of patients. 18.1% of patients feared that their gynaecological disease would not be treated adequately due to the pandemic. 55.7% of patients reported that their confidence in their physicians has increased during the pandemic. The results show that patients' confidence in the healthcare system and the physicians acting significantly increased during the COVID-19 crisis. Transparent and comprehensive information policy regarding actions and restrictions within the COVID-19 crisis eases patients concerns and improves patients' confidence in their physicians, which is crucial for a successful treatment's outcome.


The histone variant H2A.Z is dynamically expressed in the developing mouse placenta and in differentiating trophoblast stem cells.
The histone variant H2A.Z is important in establishing new chromatin environments necessary for permitting changes in gene expression and thus differentiation in mouse embryonic stem (mES) cells. In this study we show that H2A.Z is highly expressed in the early mouse placenta, and is specifically limited to progenitor-like trophoblast cells. Using in vitro models, we revealed distinct differences in H2A.Z abundance between undifferentiated, differentiating and differentiated mouse trophoblast stem (mTS) cells. Our work supports the hypothesis that in addition to roles in differentiating mES cells, H2A.Z is also involved in the differentiation of extra-embryonic tissues.


Comparable Accuracy of Quantitative and Visual Analyses of [18F]FDG PET/CT for the Detection of Lymph Node Metastases from Head and Neck Squamous Cell Carcinoma.
In head and neck squamous cell carcinoma (HNSCC), [18F]FDG PET/CT is recommended for detecting recurrent disease and in the initial staging for evaluating distant metastases, but its use in detecting cervical lymph metastases remains unclear. The aim of this study is to evaluate and compare the diagnostic accuracy of [8F]FDG-PET/CT using visual and semi-quantitative analyses for detecting the nodal involvement in HNSCC. We analyzed consecutive patients who underwent a preoperative [18F]FDG-PET/CT and neck dissection for HNSCC at our tertiary hospital. A blinded evaluation of the [18F]FDG uptake in each neck level was performed using a semi-quantitative approach (SUVmax and SUVR) and a visual grading system (uptake superior to the internal jugular vein for grade 1 and superior to the liver for grade 2). Analyses were compared to the histological results. In our 211 patients, analyses demonstrated similar diagnostic accuracy using a semi-quantitative approach or a visual grading system. Regarding the visual grading system, [18F]FDG-PET/CT detected nodal metastases with a specificity of 83% for lymph nodes classified as grade 1 and 98% for those classified as grade 2. The sensitivity was moderate, ranging from 60 to 63%. [18F]FDG PET/CT has a high specificity for detecting lymph node metastases in HNSCC and therefore must be considered in the nodal clinical staging.


Serological Biomarkers of Chronic Migraine.
Chronic migraine (CM) is a chronic form of migraine that differs from episodic migraine (EM) in terms of prevalence, comorbidities, response to treatment, and biomarkers. The aim of this review was to summarize the recent findings on serological biomarkers of CM. Neuronal, inflammatory, and vascular markers have been investigated to assess their diagnostic and prognostic ability and treatment effectiveness. Several markers showed significant alterations according to disease status and treatment response in CM. Calcitonin gene-related peptide (CGRP), glutamate, and adiponectin appear to be the most promising blood biomarkers for CM. Most studies have shown altered ictal and interictal levels of these markers in CM compared with those in EM and controls. Additionally, they showed a significant association with treatment outcomes. Total adiponectin and high-molecular-weight adiponectin levels were less studied as biomarkers of CM than CGRP and glutamate levels but showed promising results. The development of suitable biomarkers could revolutionize the diagnosis and treatment of CM and ultimately decrease the disability and societal costs of the disease.


Tumor induction in the glandular stomach of rats after oral administration of a single or a few doses of N-methyl-N'-nitro-N-nitrosoguanidine during the newborn period.
When N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was orally intubated to conventional newborn rats by the catheter technique, the rats were found with tumors almost exclusively developed in the glandular stomach, mostly until 280 days after the first intubation. Tumor incidence was about 50% in both sexs of rats that survived the intubation of a single dose of MNNG in rats of less than 24 hr after birth and almost 100% in both sexes of rats that survived the intubation of three consecutive daily doses of MNNG on 5th day after birth. Out of 52 rats treated with MNNG, 40.4% developed carcinomas (20 adenocarcinomas and 1 squamous cell carcinoma), three of them having metastatic lesions. The predilective localization of tumors in the glandular, especially fundic, portion of the stomach, might be attributed to the use of newborns and to the catheter technique devised here.


Prevalence and risk factors for dystocia in dairy cattle: a review.
This review focuses on the case definition of dystocia, its current prevalence and recent temporal trends, the different types of dystocia and their associated risk factors in dairy cattle. The reported dystocia rates in dairy cattle internationally are generally <5%, apart from those in the United States, where they are higher. Given the skewed distribution of herd dystocia rates, average figures mask high prevalence herds. Phenotypic dystocia trends are generally increasing internationally and this trend has been partially attributed to the introduction of Holstein genes. The principal types of dystocia differ between primiparae and pluriparae, with feto-pelvic disproportion (FPD) predominating in the former and fetal malposition in the latter. In order of importance, the two major determinants of FPD are calf birthweight and maternal pelvic size. Abnormal fetal position is most influenced by the number of fetuses, parity and calf sire breed. Adequate weighting of dystocia in selection indices, achievement of heifer rearing targets prior to both service and calving, and appropriate periparturient management decisions are prerequisites for controlling dystocia in dairy cattle.


Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4.
The chromatin protein positive coactivator 4 (PC4) has multiple functions, including chromatin compaction. However, its role in immune cells is largely unknown. We show that PC4 orchestrates chromatin structure and gene expression in mature B cells. B-cell-specific PC4-deficient mice show impaired production of antibody upon antigen stimulation. The PC4 complex purified from B cells contains the transcription factors (TFs) IKAROS and IRF4. IKAROS protein is reduced in PC4-deficient mature B cells, resulting in de-repression of their target genes in part by diminished interactions with gene-silencing components. Upon activation, the amount of IRF4 protein is not increased in PC4-deficient B cells, resulting in reduction of plasma cells. Importantly, IRF4 reciprocally induces PC4 expression via a super-enhancer. PC4 knockdown in human B cell lymphoma and myeloma cells reduces IKAROS protein as an anticancer drug, lenalidomide. Our findings establish PC4 as a chromatin regulator of B cells and a possible therapeutic target adjoining IKAROS in B cell malignancies.


Audit of patient experience of day-case inguinal hernia repair.
This study was prompted by a complaint from a patient citing he had suffered postoperative pain and scrotal bruising. We audit postoperative pain following inguinal herniorrhaphy and patient understanding of postoperative complications. A telephone survey was carried out to assess patient experience of day-case inguinal herniorrhaphy (DIH). Having identified that there was some dissatisfaction with the outcome of DIH, a prospective audit was carried out to assess causative factors. Changes in practice were made; chiefly, the provision of patient-information leaflets and the standardisation of intraoperative and postoperative analgesia. Repeat audit then assessed the effects of these changes. Ten percent of patients had a poor understanding of postoperative complications following inguinal herniorrhaphy. Thirty-eight percent had early postoperative pain; wound infiltration of local anaesthetic at the end of inguinal herniorrhaphy reduced the incidence of early postoperative pain to 23%. Audit is an important tool in surgical quality assurance for DIH. Small changes in practice with adherence to good protocols can have a marked effect on patients' experience.


Time-Dependent Effects of Cryoablation for Renal Tumor on Overall and Split Renal Function.
To evaluate the influence of percutaneous cryoablation for renal cell carcinoma on function of the affected kidney. Between June 2016 and September 2017 at our institution, 12 inoperable patients underwent 15 cryoablation sessions for 17 small renal tumors. Of these, 9 patients who underwent 11 sessions of cryoablation were the focus of this study. For those patients, time-dependent changes in postoperative renal function were investigated by a retrospective review of clinical records. Evaluated were the estimated glomerular filtration rate (eGFR) and scintigraphy using 99m technetium-mercaptoacetyltriglycine (99mTc-MAG3) before and 1 week, 1-2 months, and more than 6 months after cryoablation. Mean baseline eGFR was 76.88 ± 29.82 mL/min/1.73 m2 (mean ± standard deviation; range, 23.4-112.5). Mean eGFR 1 week, 1-2 months, and more than 6 months after cryoablation were 74.56 ± 26.68 mL/min/1.73 m2 (21.0-101.1), 69.5 ± 25.28 mL/min/1.73 m2 (24.1-105.6), and 75.08 ± 26.25 mL/min/1.73 m2 (29.0-107.3), respectively. Changes were statistically insignificant (P = .6044, P = .6699, and P = .9038, respectively). Regarding split renal function, the mean baseline contribution of the affected kidney determined by 99mTc-MAG3 was 47.27% ± 6.14 (38.8%-57.0%). Mean contributions of the affected kidney 1 week after, 1-2 months after, and more than 6 months after cryoablation were 44.40% ± 5.37 (38.3%-53.6%), 44.57% ± 6.52 (34.35%-55.0%), and 45.41% ± 7.77 (34.4%-56.5%), respectively. Differences from baseline were significant for the earliest 2 periods (P = .0473 and P = .0334, respectively) but not the later period (P = .2532). Results suggested that total renal function does not worsen after cryoablation; however, function of the affected kidney worsened after cryoablation but later partially recovered.


Molecular mechanisms of membrane impermeability in clinical isolates of Enterobacteriaceae exposed to imipenem selective pressure.
Intrinsic mechanisms leading to carbapenem-induced membrane impermeability and multidrug resistance are poorly understood in clinical isolates of Enterobacteriaceae. In this study, molecular behaviours during the establishment of membrane impermeability in members of the Enterobacteriaceae family under imipenem selective pressure were investigated. Clinical isolates (n = 22) exhibiting susceptibility to multiple antibiotics or characterised as extended-spectrum β-lactamase (ESBL)- or AmpC-producers were submitted to progressive passages on Mueller-Hinton agar plates containing subclinical concentrations of imipenem [0.5 × the minimum inhibitory concentration (MIC)]. Changes in outer membrane permeability were evaluated by determination of antimicrobial MICs, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), and gene expression analysis related to membrane permeability (i.e. omp35-like, omp36-like and acrA) and regulatory mechanisms (i.e. marA and ompR) by quantitative reverse transcription PCR. Following imipenem induction, 73% of isolates showed increased carbapenem MICs by ≥2 doubling dilutions. At an early stage of treatment, imipenem modulated the expression of porins and efflux pump genes, represented by a reduction of 78% in omp36-like and a two-fold increase in acrA expression. Transcriptional factors marA and ompR were also affected by imipenem induction, increasing mRNA expression by 14- and 4-fold, respectively. High marA expression levels were associated with higher values of acrA expression. These results suggest that imipenem is an important factor in the development of an adaptive response to carbapenems by regulating key genes involved in the control of efflux pumps and porins, which could lead to a multidrug-resistant profile in clinical isolates, contributing to possible treatment failure.


Blood pressure and plasma catecholamine responses to various challenges during exercise-recovery in man.
The purpose of this study was to assess the effects of a 2 h cycle exercise (50% VO2max) on heart rate (HR) and blood pressure (BP), and on plasma epinephrine (E) and norepinephrine (NE) concentrations, during the recovery period in seven normotensive subjects. Measurements were made at rest in supine (20 min) and standing (10 min) positions, during isometric exercise (hand-grip, 3 min, 25% maximal voluntary, contraction), in response to a mild psychosocial challenge (Stroop conflicting color word task) and during a 5-min period of light exercise (42 +/- 3% VO2max). Data were compared to measurements taken on another occasion under similar experimental conditions, without a previous exercise bout (control). The results showed HR to be slightly elevated in all conditions following the exercise bout. However, diastolic and systolic BP during the recovery period following exercise were not significantly different from the values observed in the control situation. Plasma NE concentrations in supine position and in response to the various physiological and/or psychosocial challenges were similar in the control situation and during the recovery period following exercise. On the other hand plasma E (nmol.1-1) was about 50% lower at rest (0.11 +/- 0.03 vs 0.23 +/- 0.04) as well as in response to hand-grip (0.21 +/- 0.04 vs 0.41 +/- 0.20) and the Stroop-test (0.21 +/- 0.05 vs 0.41 +/- 0.15) following the exercise bout.(ABSTRACT TRUNCATED AT 250 WORDS)


Advancement of Mechanical Properties of Nickel-Titanium Rotary Endodontic Instruments by Spring Machining on the File Shaft.
Nickel-titanium (NiTi) endodontic rotary instruments are used extensively in root canal procedures by both general dentists and specialists. However, their vulnerability to fracture is the major reason for clinicians' concern regarding their use. The objective of this study was to investigate the potential effects of spring machining of the file shaft on the fatigue and torsional resistances of NiTi rotary instruments. Three types of NiTi rotary systems with (S) and without (NS) spring machining were used in this study (n = 15 each): a spring file (SPR; #25/.06, SPR-S, SPR-NS), a ProTaper Next X2 (PTN; #25/variable taper, PTN-S, PTN-NS), and a ProTaper Gold F2 (PTG; #25/variable taper, PTG-S, PTG-NS). Spring machining was adjusted on the 6 mm of each file system's shaft via a laser cutting process. The number of rotation cycles until fracture (i.e., cyclic fatigue resistance), ultimate torsional strength, the distortion angle, and the toughness of each subgroup were estimated with specially designed devices. The results were analyzed using a paired t-test at a significance level of 95%. NiTi rotary instruments with spring machining exhibited a higher cyclic fatigue resistance than instruments without spring machining. The groups with spring machining exhibited a higher toughness and larger distortion angle than the groups without it (p < 0.05). In conclusion, spring machining on the shank of NiTi instruments may provide a stress-bearing area and attenuate the torsional and cyclic fatigue of NiTi rotary instruments.


Infantile spasms in a patient with septo-optic dysplasia, partial agenesis of the corpus callosum and an interhemispheric cyst.
An uncommon association of infantile spasms, septo-optic dysplasia, partial agenesis of the corpus callosum and an interhemispheric cyst is described in a child. The combination of these findings has not, to our knowledge, been previously reported.


Energy drink use and adverse effects among emergency department patients.
Energy drink usage is common and contains caffeine or other stimulants. We evaluated demographics, prevalence, reasons and adverse effects with consuming energy beverages. Cross-sectional study of a convenience sample of patients recruited from two San Diego Emergency Departments from January to December 2009. One-thousand-two-hundred-ninety-eight subjects participated of which 52.6% were male. Ethnicity: Caucasian 48.3%, African American 17%, Hispanic 18%, Other 16.7%. Age ranges: 18-29 years (38.4%), 30-54 years (49.6%) and greater than 55 years (12%). Reasons for use: 57% to "increase energy", 9.5% for studying/work projects, 2.4% while prolonged driving, improve sports performance 2%, with ethanol 6.3%, "other" reasons 22.1%. Adverse reactions reported by 33.5% (429) patients. Two-hundred-eighty report feeling "shaky/jittery", insomnia 136, palpitations 150, gastrointestinal upset 82, headache 68, chest pain 39, and seizures in 6. Eighty-five patients reported co-ingestion with illicit "stimulants" including cocaine and methamphetamine. We identified one-third of patients reported at least one adverse effect. Whilst most were not severe, a small number were serious e.g., seizures. In addition, some report purposely ingesting with illicit drugs.


Cyclic nucleotide-gated channel α-3 (CNGA3) interacts with stereocilia tip-link cadherin 23 + exon 68 or alternatively with myosin VIIa, two proteins required for hair cell mechanotransduction.
Previously, we obtained evidence for a photoreceptor/olfactory type of CNGA3 transcript in a purified teleost vestibular hair cell preparation with immunolocalization of CNGA3 protein to stereocilia of teleost vestibular and mammalian cochlear hair cells. The carboxyl terminus of highly Ca(2+)-permeable CNGA3 expressed in the mammalian organ of Corti and saccular hair cells was found to interact with an intracellular domain of microfibril interface-located protein 1 (EMILIN 1), a member of the elastin superfamily, also immunolocalizd to hair cell stereocilia (Selvakumar, D., Drescher, M. J., Dowdall, J. R., Khan, K. M., Hatfield, J. S., Ramakrishnan, N. A., and Drescher, D. G. (2012) Biochem. J. 443, 463-476). Here, we provide evidence for organ of Corti proteins, of Ca(2+)-dependent binding of the amino terminus of CNGA3 specifically to the carboxyl terminus of stereocilia tip-link protein CDH23 +68 (cadherin 23 with expressed exon 68) by yeast two-hybrid mating and co-transformation protocols, pulldown assays, and surface plasmon resonance analysis. Myosin VIIa, required for adaptation of hair cell mechanotransduction (MET) channel(s), competed with CDH23 +68, with direct Ca(2+)-dependent binding to the amino terminus of CNGA3. Based upon the premise that hair cell stereocilia tip-link proteins are closely coupled with MET, these results are consistent with the possibility that CNGA3 participates in hair-cell MET. Together with the demonstration of protein-protein interaction between HCN1 and tip-link protein protocadherin 15 CD3 (Ramakrishnan, N. A., Drescher, M. J., Barretto, R. L., Beisel, K. W., Hatfield, J. S., and Drescher, D. G. (2009) J. Biol. Chem. 284, 3227-3238; Ramakrishnan, N. A., Drescher, M. J., Khan, K. M., Hatfield, J. S., and Drescher, D. G. (2012) J. Biol. Chem. 287, 37628-37646), a protein-protein interaction for CNGA3 and a second tip-link protein, CDH23 +68, further suggests possible association of two different channels with a single stereocilia tip link.


The relationship between maltreatment victimisation and sexual and violent offending: differences between adolescent offenders with and without intellectual disability.
Juveniles with intellectual disabilities (ID) are more often victims of maltreatment and more often perpetrators of abuse than juveniles without ID. Because previous research on the relationship between maltreatment victimisation and subsequent offending behaviour was primarily performed in non-disabled samples, the present study aimed to examine differences between juvenile offenders with and without ID in the relationship between maltreatment victimisation and sexual and violent offending. The sample consisted of juvenile offenders with ID (n = 102) and without ID (n = 526) who appeared before the courts for a criminal act and for whom the Washington State Juvenile Court Assessment (WSJCA) was completed. Pearson correlation coefficients were calculated to determine the strength of the relationship between maltreatment and offending, Fisher's z tests were calculated to assess the significance of the differences between the two groups in the strength of the correlations, and multiple logistic regression analyses were performed to examine the unique contribution of maltreatment victimisation to the prediction of violent and sexual offending. Seventy per cent of the juvenile offenders with ID and 42% of the juvenile offenders without ID had experienced abuse and/or neglect. Both sexual and violent offending were more common in juvenile offenders with ID than in juvenile offenders without ID. Moreover, the relationship between different forms of maltreatment and sexual offending was stronger in juvenile offenders with ID than in juvenile offenders without ID. Given the high rates of abuse and neglect victimisation and the strength of the association between victimisation and sexual offending, especially in juvenile offenders with ID, treatment should focus on potential trauma and other problems associated with the abuse.


Extracellular volume and left ventricular hypertrophy by cardiac magnetic resonance are independent predictors of cardiovascular outcome in obesity.
This retrospective cohort study investigated for association between increased extracellular volume (ECV) and left ventricular hypertrophy (LVH) by cardiac magnetic resonance (CMR) and cardiovascular composite outcomes in obesity. Native T1 was measured at the ventricular septum. ECV was calculated from native and post-contrast T1 and hematocrit. Cardiovascular (CV) composite outcomes included acute myocardial infarction, unstable angina requiring hospitalization, myocardial revascularization (excluding early revascularization), heart failure, and CV death. A total of 456 patients with a mean follow-up of 2.1 ± 0.4 years were enrolled. LGE and LVH was detected in 30.5% and 9.2%. 107 patients (23.5%) had the composite outcomes. Multivariable analysis revealed that LGE, LVH, and high ECV as independent predictors for cardiovascular composite outcomes The event rate in the LVH and high ECV, the LVH alone, the high ECV alone, and the no-LVH with lower ECV group was 57.1%, 38.1%, 32.6%, and 17.7%, respectively. Assessment of incremental prognostic value by comparing global chi-square showed that high ECV had additional prognostic value on top of LGE, and LVH. LVH and high ECV are independent predictors of CV composite outcomes in obesity. This is the first study that demonstrate the prognostic value of ECV in obese population.


The cardioprotective and anxiolytic effects of Chaihujialonggumuli granule on rats with anxiety after acute myocardial infarction is partly mediated by suppression of CXCR4/NF-κB/GSDMD pathway.
Over-expression of CXCR4 activates nuclear translocation of NF-κB, induces high expression of NLRP3, GSDMD, IL-1β and IL-18, which promotes severe inflammatory response following myocardial infarction. Previous studies revealed inflammation induces anxiety after myocardial infarction. The Chaihujialonggumuli granule has anti-inflammatory properties and could tranquillize mind. But the mechanism of its efficacy remains unknown. This study was to investigate the possible mechanism of BFG on cardioprotective and anxiolytic. The expression of CXCR4, NF-κB, NLRP3and GSDMD was measured with western-blot, QRT-PCR. The expression location of CXCR4, NLRP3, GSDMD were determined by immunohistochemistry. IL-1β、IL-18 in the peripheral blood were measured by ELISA. HE staining, Masson staining and transmission electron microscopy were used to observe morphological changes of cardiomyocytes. Echocardiography was used to assess cardiac function after cardiac surgery. Elevated cross maze test and open field test were used to evaluate behaviours. Western blot was used to detect the protein expressions of 5-HT, DA, IL-1β, IL-18 and neuron damage was investigated by Nissl staining in the hippocampus. The up-regulation of CXCR4, NF-κB, NLRP3 and GSDMD were found in the infarcted area after left coronary artery ligation. Pathological staining and analysis showed that more severe inflammatory cytokines infiltration, myocardial fibrosis, were found in myocardial tissue of the complex group rats. And when compared to the sham group, the levels of IL-1β, IL-18 was increased of the complex group in both peripheral blood and brain. Behavioural test and echocardiography indicated that the rats in complex group exploration behaviours was significantly reduced, and with poor cardiac functional recovery. The AMD3100 had an inhibitory impact of CXCR4 on the activition of its downstream effectors, alleviating inflammatory reaction. Furthermore, the BFG decreased the expression level of CXCR4, NF-κB, GSDMD, NLRP3 in the infarcted area after myocardial infarction, when compared to the complex group. The assays in the brain indicated the BFG suppressed expression and activity of IL-1β, IL-18, and improved 5-HT and DA synthesis. In sum, our study indicated that BFG may reduce inflammation, treat co-existing anxiety after myocardial infarction through inhibition of CXCR4/NF-κB/GSDMD signalling.


Carotid endarterectomy for symptomatic low-grade carotid stenosis.
Although the management of carotid disease is well established for symptomatic lesions ≥ 70%, the surgical treatment for a symptomatic ≤ 50% stenosis is not supported by data from randomized trials. Factors other than lumen narrowing, such as plaque instability, seem to be involved in cerebral and retinal ischemic events. This study analyzes the early-term and long-term outcomes of carotid endarterectomy (CEA) performed in patients with low-grade (≤ 50% on North American Symptomatic Carotid Endarterectomy Trial criteria) symptomatic carotid stenosis. The study involves 57 consecutive patients undergoing CEA for symptomatic low-grade carotid disease at our institution over 5 years, and 21 (36.8%) had experienced more than one ischemic event. Overall, 48 (84.2%) had a minor stroke, and nine (15.8%) had an episode of retinal ischemia. Diagnosis was made by a vascular neurologist based on an ultrasound examination combined with noninvasive imaging studies, after ruling out other possible causes of embolization. Before CEA, all patients were receiving antiplatelet treatment, and 87% were taking statins. All patients underwent eversion CEA under general deep anesthesia, with selective shunting. All carotid plaques were examined histologically. Long-term follow-up (median, 28 months; mean, 32 ± 5 months; range, 3-56 months) was obtained for 55 patients. No 30-day strokes or deaths occurred, and no patients had recurrent neurologic events related to the revascularized hemisphere during the follow-up. No late carotid occlusions were detected, but one asymptomatic moderate restenosis was documented. There were seven late deaths (12.7%), none of which were stroke-related. Survival rates were 98% at 1 year and 90% at 3 years. All removed carotid plaques showed different features of ulceration or rupture, with underlying hemorrhage associated with a thrombus. This study shows that CEA is a safe, effective, and durable treatment for patients with symptomatic low-grade carotid stenosis associated with unstable plaque. Patients had excellent protection against further ischemic events and survived long enough to justify the initial surgical risk. Plaque instability seems to play a major part in the onset of ischemic events, regardless the entity of lumen narrowing.


Identification of a 5-[3-phenyl-(2-cyclic-ether)-methylether]-4-aminopyrrolo[2,3-d]pyrimidine series of IGF-1R inhibitors.
We report structure-guided modifications of the benzyloxy substituent of the Insulin-like Growth Factor-1 Receptor (IGF-1R) inhibitor NVP-AEW541. This chemical group has been shown to confer selectivity against other protein kinases but at the expense of a metabolism liability. X-ray crystallography has revealed that the benzyloxy moiety interacts with a lysine cation of the IGF-1R kinase domain via its ether function and its aromatic π-system and is nicely embedded in an induced hydrophobic pocket. We show that 1,4-diethers displaying an adequate hydrophobic and constrained shape are advantageous benzyloxy replacements. A single digit nanomolar inhibitor (compound 20, IC50=8.9 nM) was identified following this approach.


Acute obstructive respiratory diseases (ARD) and bacterial complications of ARD (pneumonia, sinusitis) in infants and children associated with human herpesvirus-6 infection.
The existence of catharreal respiratory symptoms (such as pharyngitis, tracheitis, bronchitis etc.) is established as the usual manifestation of "exanthema subitum" due to acute human herpesvirus-6 (HHV-6) infection. But so far pneumonia, purulent sinusitis, purulent otitis media and/or acute obstructive bronchitis (bronchiolitis) in infants and children have not been described. Here we report the results of observations of 2 children with bronchopneumonia/sinusitis maxillaris and severe bronchiolitis associated with an acute HHV-6 infection. Other respiratory viruses were excluded as agents causing the ARD.


Is birthweight associated with total and aggressive/lethal prostate cancer risks? A systematic review and meta-analysis.
It has been hypothesised that intrauterine exposures are important for subsequent prostate cancer risk. Prior epidemiological studies have used birthweight as a proxy of cumulative intrauterine exposures to test this hypothesis, but results have been inconsistent partly because of limited statistical power. We investigated birthweight in relation to prostate cancer in the Medical Research Council (MRC) National Survey of Health and Development (NSHD) using Cox proportional hazards models. We then conducted a meta-analysis of birthweight in relation to total and aggressive/lethal prostate cancer risks, combining results from the NSHD analysis with 13 additional studies on this relationship identified from a systematic search in four major scientific literature databases through January 2015. Random-effects models found that per kg increase in birthweight was positively associated with total (OR=1.02, 95% confidence interval (95% CI)=1.00, 1.05; I(2)=13%) and aggressive/lethal prostate cancer (OR=1.08, 95% CI=0.99, 1.19; I(2)=40%). Sensitivity analyses restricted to studies with birthweight extracted from medical records demonstrated stronger positive associations with total (OR=1.11, 95% CI=1.03, 1.19; I(2)=0%) and aggressive/lethal (OR=1.37, 95% CI=1.09, 1.74; I(2)=0%) prostate cancer. These studies heavily overlapped with those based in Nordic countries. This study provides evidence that heavier birthweight may be associated with modest increased risks of total and aggressive/lethal prostate cancer, which supports the hypothesis that intrauterine exposures may be related to subsequent prostate cancer risks.


Mean platelet volume and neutrophil to lymphocyte ratio in patients with tinnitus: a case-control study.
Different theories have been proposed on the etiology of tinnitus, including metabolic and audiologic causes. We suggest that mean platelet volume and neutrophil to lymphocyte ratio levels change in tinnitus, indicating microcirculatory disturbance and inflammatory process in the etiopathogenesis of tinnitus. We aimed to evaluate the mean platelet volume and neutrophil to lymphocyte ratio in patients with tinnitus in comparison to healthy controls. Retrospective case-control study. Two-hundred and eighty-seven patients aged 18-59 years and diagnosed with tinnitus in the Ear, Nose, and Throat Clinic between December 2014 and May 2017 (patient group) and 275 healthy individuals who applied for a hearing screening within the same time period (control group). Demographics, concomitant diseases, laboratory results, and audiometric data were recorded. Mean platelet volume and neutrophil to lymphocyte ratio were the outcome measures. Patients with hearing loss due to presbycusis or another reasons, and patients with anatomical disorders in the external and middle ear were excluded from the study by using physical examinations, pure audio audiometry results and radiological imaging. The upper age limit was set at 59 to exclude presbycusis patients. The ratio of female patients was higher in patient group than control group (58.5%, n=168 vs. 49.4%, n=127; respectively; p=0.033). The mean age of patient group was significantly higher than those of control group (44.89±10.96 years and 38.37±10.65 years, respectively; p=0.001). The percentage of subjects with high mean platelet volume level was significantly higher in patient group than control group (9.4%, n=27, and 3.1%, n=8 respectively; p=0.008). The mean neutrophil to lymphocyte ratio was higher in patients with tinnitus than control group (1.95±1.02 and 1.67±0.57, p=0.012). A neutrophil to lymphocyte ratio level of 2.17 and above is associated with 1.991 times higher risk of tinnitus (odds ratio=1.99, 95% confidence interval 1.31-3.02). High mean platelet volume and neutrophil to lymphocyte ratio values are associated with idiopathic tinnitus, suggesting the role of vascular pathologies in etiology of tinnitus. Tinnitus may be a sign of underlying systemic or local disorders. Therefore, patients with tinnitus should undergo detailed evaluation including hematological indices.


Intrapartum fetal heart rate patterns of trisomy 21 fetuses: A case-control study.
To determine whether there are specific characteristic intrapartum heart rate patterns for fetuses with trisomy 21(T21). Intrapartum fetal heart rate (FHR) tracings of T21 fetuses were compared to those of euploid fetuses in a retrospective, observational, matched, case-control study. The study group consisted of 42 fetuses with T21 and 42 matched euploid controls. Matching was designed to accommodate possible confounders. The sign test and McNemar's test were used for categorical variables. The paired t test was used for comparison between quantitative variables. Intrapartum baseline FHR of fetuses with T21 was found to be slightly decreased compared to controls (122.5 vs 129.05 beats per minute, p=0.028). No differences were detected in the presence of periodic changes, or FHR variability between the groups. When evaluating intrapartum FHR of fetuses with T21, decreased baseline FHR can be expected.


Optimized Production of Medically Significant Enzyme L-Asparaginase Under Submerged and Solid-State Fermentation From Agricultural Wastes.
L-asparaginase has prime medical significance due to its chemotherapeutic applications and action against a wide range of diseases. L-asparaginase obtained from commercial producer bacterial strains causes anaphylaxis, some sensitive reactions, and other side effects. To overcome these issues, eukaryotes like fungi can be used to produce L-asparaginase. Penicillium lilacinum was explored for its enhanced production through a statistically optimized fermentation approach. Firstly, the significant fermentation parameters (influencing the production) were screened through the Plackett-Burman approach. Thereafter, Response Surface Methodology (RSM) was employed for achieving higher production of L-asparaginase under specified fermentation conditions. The study explored both submerged (SmF) and solid-state (SSF) fermentation conditions to put forward a comparative analysis of the best suitable fermentation condition for the enhanced production of L-asparaginase. The Plackett-Burman optimization result suggested that pH, L-asparagine, ammonium nitrate, and temperature were significantly affecting enzyme production in SmF conditions, whereas wheat bran, arhar bran, kulthi bran, and temperature were identified as significant process parameters for SSF. The final enzyme activity obtained in SmF was 82.29 IU/mL and 190.439 U/gds in SSF after the implication of RSM. The statistical optimization tool fosters 2.47-fold and 6.36-fold enzyme activity in SmF and SSF, respectively. The study suggested that L-asparaginase can be efficiently produced using P. lilacinum at an optimized SSF condition.


Identifying protein interactions with metal-modified DNA using microarray technology.
Protein microarrays have been used extensively to identify protein-protein interactions; however, this technology has not been widely applied to protein-DNA interactions. In particular, this work demonstrates the utility of this technique for rapidly identifying interactions of proteins with metal-modified DNA. Protein macroarray experiments were carried out with high mobility group protein 1 (HMG-1) and cisplatin- and chromium-modified 50-mer oligonucleotides to demonstrate "proof of principle." Commercially available protein microarrays containing many different classes of human proteins were then employed to search for additional interactions with cisplatin-modified DNA. The results of the microarray experiments confirmed some known interactions and, more importantly, identified many novel protein interactions, demonstrating the utility of this method as a rapid, high-throughput technique to discover proteins that interact with metal-modified DNA.