Geniposide augments apoptosis in fibroblast-like synoviocytes by restoring hypoxia-enhanced JNK-BNIP3-mediated autophagy.
As the main effector cells of chronic inflammation and hyperplasia of synovium, fibroblast-like synoviocytes (FLSs) show abnormal proliferation and insufficient apoptosis in the hypoxic microenvironment, which is due to the increase of BNIP3-mediated autophagy. This study aimed to explore the mechanism of geniposide (GE) on hypoxia-induced hyper-proliferative FLSs with a focus on autophagy and the JNK-BNIP3 pathway. The dynamic changes of autophagy, apoptosis, and hypoxia-related proteins in adjuvant arthritis (AA) rats were detected by immunohistochemistry and Western blot. The proliferation, autophagy, apoptosis, and mitochondrial state of FLSs were detected by CCK-8, flow cytometry, immunofluorescence, and transmission electron microscopy, respectively. Western blot, qRT-PCR, and co-immunoprecipitation were used to detect the expression of the JNK-BNIP3 pathway. The excessive accumulation of BNIP3 in the synovium of AA rats was accompanied by inhibition of apoptosis and an increase in autophagy. GE inhibited the expression of BNIP3, enhanced apoptosis, decreased autophagy, and improved chronic inflammation and hyperplasia of synovium. The amount of autophagy under different oxygen concentrations was the key to mediating the different survival rates of FLSs, and the inhibition of autophagy triggered apoptosis. GE suppressed the proliferation of FLSs and down-regulated autophagy, leading to the accumulation of ROS and the decrease of mitochondrial membrane potential, induced the increase of apoptosis, and suppressed the accumulation of BNIP3 and the hyperphosphorylation of JNK. GE inhibited autophagy by restoring the hypoxia-induced activated JNK-BNIP3 pathway, inducing mitochondrial oxidative damage, augmented apoptosis, and decreased survival rate of FLSs.


Microsomal electron transfer in higher plants: cloning and heterologous expression of NADH-cytochrome b5 reductase from Arabidopsis.
AtCBR, a cDNA encoding NADH-cytochrome (Cyt) b5 reductase, and AtB5-A and AtB5-B, two cDNAs encoding Cyt b5, were isolated from Arabidopsis. The primary structure deduced from the AtCBR cDNA was 40% identical to those of the NADH-Cyt b5 reductases of yeast and mammals. A recombinant AtCBR protein prepared using a baculovirus system exhibited typical spectral properties of NADH-Cyt b5 reductase and was used to study its electron-transfer activity. The recombinant NADH-Cyt b5 reductase was functionally active and displayed strict specificity to NADH for the reduction of a recombinant Cyt b5 (AtB5-A), whereas no Cyt b5 reduction was observed when NADPH was used as the electron donor. Conversely, a recombinant NADPH-Cyt P450 reductase of Arabidopsis was able to reduce Cyt b5 with NADPH but not with NADH. To our knowledge, this is the first evidence in higher plants that both NADH-Cyt b5 reductase and NADPH-Cyt P450 reductase can reduce Cyt b5 and have clear specificities in terms of the electron donor, NADH or NADPH, respectively. This substrate specificity of the two reductases is discussed in relation to the NADH- and NADPH-dependent activities of microsomal fatty acid desaturases.


Monitored environment system to control cell growth, morphology, and metabolic rate in fungi by oxidation-reduction potentials.
A device for the adjustment, maintenance, and monitoring of a desired oxidation-reduction potential in a liquid environment is described. The filamentous species, Penicillium lilacinum and Trichophyton schoenleinii, and the dimorphic species, Histoplasma capsulatum, developed budding yeastlike cells when grown in a liquid medium with a low oxidation-reduction potential. When the organisms were inoculated into fresh medium, they returned to the filamentous condition as the oxidation-reduction potential was restored to a more positive (oxidizing) environment.


[Update on the diagnosis and treatment of vulvodynia].
Vulvodynia is a complex and multifactorial clinical condition. It is defined as chronic vulvar discomfort characterized by burning, stinging or irritation. Its diagnostic difficulty and treatment is known. To review the medical literature of the last 10 years from a critical point of view. A search was made in Medline/Pubmed and the Cochrane Library using the terms vulvodynia and vestibulodynia to which etiology, epidemiology, diagnosis, neurophysiological test and treatment or management, were added. In spite of the advances achieved in all of the aspects of vulvodynia, the methodology used at present in many cases does not have the desirable statistical soundness: there are few control or placebo-controlled groups and double-blind studies. Uniformity is lacking in the scales, indexes and questionnaires for the correct evaluation of pain before and after the treatment and debatable diagnostic criteria are use. The limited use of neurophysiological diagnostic resources that validate the clinical findings has been observed in the studies analyzed. In most of the works, the medical treatments have been shown to be ineffective. Physiotherapy and cognitive-behavioral therapy seem to be promising therapeutic tools. Surgery (vestibulectomy) stands out by its demonstrated efficacy in the publications studied. A multidisciplinary approach is always necessary. Topical medical, psychological and physical therapy treatments may have sum effects and become an alternative to surgery. New pathways of research and more regulated studies are required.


Endosperm gene imprinting and seed development.
Imprinting occurs in the endosperm of flowering plants. Endosperm, produced by fertilization of the central cell in the female gametophyte, is essential for embryo and seed development. Several imprinted genes play an important role in endosperm development. The mechanism of gene imprinting involves DNA methylation and histone modification. DNA methylation is actively removed at the imprinted alleles to be activated. Histone methylation mediated by the Polycomb group complex provides another layer of epigenetic regulation at the silenced alleles. Endosperm gene imprinting can be uncoupled from seed development when fertilization of the central cell is prevented. Imprinting may be a mechanism to ensure fertilization of the central cell thereby preventing parthenogenic development of the endosperm.


Hematoma complicating permanent pacemaker implantation: the role of periprocedural antiplatelet or anticoagulant therapy.
Periprocedural management of antiplatelet or anticoagulant therapy at the time of device implantation remains controversial. We reviewed all cases for whom a pacemaker was implanted in our institution between January 2008 and June 2009. In addition, beginning in June 2009, we prospectively collected data from all patients admitted to our institution, for whom a pacemaker was placed. Clinical characteristics and anticoagulant/antiplatelet drug use were evaluated. A total of 574 patients underwent a permanent pacemaker implantation. Of these, 20 patients (3.6%, 9 women) experienced a hematoma on pacemaker pocket site. Patients were aged between 35 and 79 years (mean 60.6 ± 12 years). The frequency of hematoma formation was significantly higher (p<0.001) in those who used warfarin than in those who did not. Aspirin (ASA), clopidogrel, dual antiplatelet therapy (DAT), and bridging to low-molecular-weight heparin (LMWH) did not increase the risk of hematoma formation (p>0.05). Eleven pocket revisions for hematoma evacuation were needed in 9 patients (1.6%), six of whom were on warfarin therapy (p>0.05). Co-morbidities were similar in patients with and without hematoma (p>0.05). The frequency of hematoma is within acceptable ranges after pacemaker placement. The use of warfarin seriously increases the risk of hematoma. Bridging to LMWH safely prevents thromboembolism.


Donor ambivalence: a key issue in families of children with end-stage renal disease.
This paper is based on the writers' clinical experience with children and adolescents who receive kidney transplants and members of their families who are involved in the process of identifying the best donor match. Specific concerns of the patients and their significant others are described, and two cases are used as illustrations. The role of ambivalence in donor selection is investigated and selected intervention sites are suggested.


Effects of the naturally-occurring chemosensitizer malagashanine and its combination with chloroquine on KB and P388 cell lines and isolated auricle.
Besides the determination of its LD50 value, the cytotoxicity against KB and P388 cell lines and the toxicity on isolated guinea pig auricle of malagashanine and its combination with chloroquine were assessed. Malagashanine alone was devoid of cytotoxicity and cardiac effect on isolated auricle, and importantly, when combined to chloroquine, did not affect the inherent toxicity and cardiac toxicity of this antimalarial agent.


[Death due to fatal hypothermia in victims dissected in Department of Forensic Medicine in Hradec Králové between 1992-2003].
Death due to hypothermia is diagnosed on the base of the unspecific morphological lesions. These lesions such as Wischewski spots, haemorrhage into the pancreas and haemorrhage into the skeletal paravertebral muscles etc. are not found periodically and regularly. We must know the anamnestic settings and the results of laboratory tests for final complete evaluation. Fatal hypothermia is under climate condition of our country quite often with the exception of summer months.


Catabolite modulator factor: physiological properties and in vivo effects.
Catabolite modulator factor (CMF) specifically inhibits the expression of operons sensitive to catabolite repression. Systems known to be catabolite independent are not affected by CMF. The rate of metabolism of CMF depends on the extent of catabolite repression: it is slow under conditions of strong repression and high in catabolically derepressed cells. Cyclic AMP does not interfere with the rate of CMF metabolism. It has been found that a certain class of crp mutants are partially resistant to the repressive effect of CMF. Our results provide considerable support for the existence of an additional negative control in the regulation of catabolite repression.


Batch fabrication process of biomimetic wing with high flexibility of stiffness design for flapping-wing micro aerial vehicles.
A lamination-based batch-fabrication process of biomimetic wing for flapping-wing micro aerial vehicles is presented. The key benefits of this process are:•One of the advantages of the process is high productivity; eight wings were successfully fabricated simultaneously in our experiment.•The wing fabricated with the reported process is made of soft polyimide and partially reinforced by a titanium layer. This configuration enables the flexible design of the bending stiffness distribution on the wing, which is the key specification for generating lift force.•The reinforcing material can be replaced with other metals or heat-resistant polymers, and the number of layers and layer thicknesses are also variable. This indicates that the reported process can be customized considerably to suit individual needs.


Changing patient characteristics with increased methadone maintenance availability.
Over the past several years there have been repeated calls for expansion of availability of methadone maintenance in several jurisdictions. Important stakeholders in the expansion of methadone maintenance treatment (MMT) are existing treatment providers. This study describes the impact of the rapid expansion in treatment availability in Ontario on the long-standing MMT program of the Centre for Addiction and Mental Health (CAMH). This expansion occurred through enlarging existing treatment programs, the provision of MMT in private physicians' offices and the establishment of new clinics. With expansion in the community, demand for the clinic-based treatment of the CAMH MMT program did not drop, in fact the patient population was able to continue to grow. There was a broadening of the patient profile in the program including patients who were better educated, more likely to be employed and less likely to be currently injecting (although with a significant history of past injection drug use). Moreover, in the face of these changes, excellent treatment retention was maintained. This suggests that the expansion in treatment availability did not impact negatively on the existing program but rather enabled access for a group of higher functioning opioid dependent patients who were previously being deterred from treatment entry by the large waiting lists and the need for priority access for pregnant and HIV positive heroin users. These findings should provide encouragement for MMT providers in jurisdictions anticipating or undergoing expansion of treatment availability.


Structured prostate MRI reporting: how and why.
Over the past decade, the Prostate Imaging-Reporting and Data System (PI-RADS) has revolutionized the manner in which prostate cancer is screened for, detected, biopsied, and managed. The single greatest contribution of PI-RADS has been the standardization of interpretation and reporting of findings on MRI of the prostate. This standardization has led to the wide acceptance of the PI-RADS lexicon at a time when structured reporting templates are becoming more widespread in radiology and other medical fields. The author reviews the benefits of structured reporting templates with a focus on prostate MRI, prior studies on this topic, and details of a suggested template.


Survivorship patterns in an annual plant community.
Age-specific survivorship was studied in a number of plant species which occur in a distinct, predominantly annual plant community of Texas, in association with the activities of pocket gophers. Of eleven species analyzed in detail, all functioned as annuals. Contrary to theoretical expectations, the species had low rates of juvenile mortality, and did not exhibit the demographic specializations of weedy or colonizing species. It is suggested that the annual habit in this case may be adaptive in sites with continual disturbance, such as that due to pocket gopher activity.


Engaging and empowering patients to manage their type 2 diabetes, Part II: Initiatives for success.
Type 2 diabetes (T2D) has reached pandemic proportions. The impact of it and its long-term sequelae represent a significant burden for many healthcare systems around the world, and a significant number of patients struggle to achieve the internationally recommended targets for the modifiable risk factors that optimize healthy outcomes. In the first part of this two-part review, the scene was set showing that there seems to be a knowledge, attitude, and practice (KAP) gap hindering successful management of T2D. Although theoretical knowledge about how T2D should be managed exists, the attitude of patients and healthcare professionals seems to influence the practicalities of implementing life-enhancing changes for patients living with diabetes. Following the chronic care model, macro-level initiatives such as Finland's national diabetes program, "The Development Programme for the Prevention and Care of Diabetes" (DEHKO), encourage a coordinated, supportive policy and financial environment for healthcare system change, and are advocated by the International Diabetes Federation. Over a 10-year period, the DEHKO program aims to demonstrate that a top-down population approach to prevention, focusing on reducing obesity, increasing physical activity, and encouraging healthier eating habits, may improve the overall health of the nation. However, the patient is the focus of day-to-day management of T2D, and innovative strategies that use a community (meso-level) approach to encourage self-management, or that embrace new technologies to access diabetes self-management education or support networks, are likely to be the way forward. Such measures may close the apparent KAP gap and bring about real and measurable benefits in quality of life and life expectancy. The second part of this review describes some of the many and varied initiatives designed to engage and empower patients to self-manage their T2D, with the aim of increasing the proportion of patients reaching health-related targets. This will ultimately impact on national health systems and the quality of life of the nation.


Gene diversity at allozyme loci in the cottonwood leaf beetle, Chrysomela scripta.
Gene diversity was studied in beetles collected from a poplar plantation at Ames, Iowa. The beetles are widely distributed throughout North America wherever poplars (Populus spp) occur. Of 38 loci interpretable by simple Mendelian criteria, 22 were polymorphic (58%). Nei's mean heterozygosity per locus was 20.1 +/- 4.0%. A mean 2.29 +/- 1.35 alleles per locus was detected. The foregoing levels of diversity are typical of Coleoptera. There were significant deviations from Hardy-Weinberg expectations at six loci, and of these loci, four deviations were judged to have been caused by technical problems in resolving heterozygotes. Twelve polymorphic loci are considered suitable to carry out studies on the breeding structure of this important pest.


Effects of exercise on microRNA expression in young males peripheral blood mononuclear cells.
MicroRNAs are increasingly seen as targets of drug discovery because they influence gene function acting both to silence and subtly modulate protein translation. Little is known about effects of dynamic physiological states on microRNA regulation in humans. We hypothesized that microRNA expression in peripheral blood mononuclear cells (PBMCs) would be affected by brief exercise. Twelve young men performed brief bouts of heavy exercise. PBMC microRNA was analyzed before and immediately after exercise using the Agilent Human microRNA V2 Microarray. Exercise altered expression level of 34 microRNAs (FDR < 0.05). Many of them play roles in inflammatory processes (e.g., miR-125b[↓], down-regulated by proinflammatory factor LPS; and miR-132[↑], 125b[↓] and let-7e[↓] involved inTLR4 signaling). Using previous exercise data in PBMCs, we linked the microRNA changes to specific gene pathways. This analysis identified 12 pathways including the TGF-β and MAPK signaling. We also compared exercise-associated microRNA changes in PBMCs with the exercise-associated microRNAs previously identified in neutrophils. Nine microRNAs were affected in both PBMCs and neutrophils, but only six changed in the same direction. A commonly occurring physiologic perturbation, brief heavy exercise, changes microRNA profiles in PBMCs, many of which are related to inflammatory processes. The pattern of change suggests that exercise differentially influences microRNAs in leukocyte subtypes.


Evaluation and management of osteoporosis in liver disease.
This article discusses the clinical importance of hepatic osteopenia, the identification of risk factors for the individual patient, and the selection of patients, timing, and methods for diagnostic screening. General supportive measures to maximize bone health should be used in all patients at risk. In addition, for the patient with established osteoporosis, specific therapeutic measures may be justified, despite the lack of adequate randomized trials of these agents in patients with hepatic osteopenia.


HIPEC with CRS versus cytoreductive surgery (CRS) for the gastric cancer metastasis to peritoneum.
Peritoneal metastases (PM) have a poor prognosis in gastric cancer (GC). Cytoreductive surgery (CRS) gives favorable outcomes, but the influence of hyperthermic intraperitoneal chemotherapy (HIPEC) remains contentious. We designed to distinguish results between CRS versus HIPEC-CRS in patients with peritoneal metastases from gastric cancer. PubMed, Scopus, Embase and Cochrane library accessed to collect data and language is restricted to English. RevMan 5.4 was used to perform statistical analysis. The outcomes for categorical variables are mentioned in the risk ratio. Ten trials involving 1367 patients in which 707 were CRS-HIPEC, while 660 CRS. We got significant results in 3rd year survival (P < 0.05), while 1st and 5th years are not statistically significant P > 0.05. To compare with CRS, CRS-HIPEC has improved survival rate in deprived of further morbidity or mortality.


Practice patterns and work environments that influence gender inequality among academic surgeons.
Practice pattern and work environment differences may impact career advancement opportunities and contribute to the gender gap within highly competitive surgical specialties. Using a 2000-2015 New York statewide dataset, we compared board-certified pediatric surgeons by specialist case volume and Herfindahl-Hirschman Index (HHI), which quantifies surgeon focus within specialist case mix. 51 pediatric surgeons were analyzed for 461 surgeon-years. Female surgeons had lower case volume (159 cases/year versus 214, p < 0.01), lower shares of specialist cases (14.1% versus 16.7%, p = 0.04), and less focused practices (HHI 0.16 versus 0.20, p = 0.03). Female surgeons' networks had fewer colleagues (7.2 versus 12.1, p < 0.01), and lower annual total (388 versus 726, p < 0.01) and specialist case volume (83 versus 159, p < 0.01), even after accounting for career length. However, female surgeons performed more cases within their networks (49% versus 36%, p = 0.04) and worked at major teaching hospitals as often as men (76% versus 76%, p = 0.97). The challenges that female surgeons face may be reflective of organizational inequities that necessitate intentional scrutiny and change.


Abnormal left ventricular contraction pattern in the systolic click-late systolic murmur syndrome.
A contraction abnormality of the left ventricle has previously been described in patients with systolic click-late systolic murmur syndrome. To determine if the contraction abnormality is present in the preprolapse period, LV dimensions and the instantaneous velocity of circumferential fiber shortening (VCF) were studied in 18 patients with the mitral valve prolapse and 16 normal subjects using computer analysis of echocardiograms. VCF attained its maximum (max VCF) during the preprolapse period an average of 94 msec before the mid-systolic click. Max VCF was significantly reduced in patients with mitral valve prolapse (2.06 vs 2.55 circ/sec in normal subjects, P less than 0.001). Despite the reduction in max VCF, no difference in the extent and percentage of diameter shortening was found between patients and normal subjects. This discrepancy is explained by a sustained rate of mid-to-late systolic diameter shortening in the presence of mitral valve prolapse as manifested by a typical VCF profile (P less than 0.001) and a longer duration of diameter shortening (353 vs 306 msec in normal subjects, P less than 0.01). The decrease of max VCF in patients with mitral valve prolapse suggests a reduction in LV contractility. Since the abnormality is present in the preprolapse period, it is unrelated to a direct mechanical effect of the prolapse itself. Additional fiber shortening in mid-to-late systole indicates that the sudden displacement of the mitral leaflets may have an unloading effect on the left ventricle.


Chronic paroxysmal hemicrania: from the index patient to the disease.
The first patient with chronic paroxysmal hemicrania (CPH), a 41-year-old woman, first seen in 1961, was followed until an adequate treatment was found, 12 years later. Clinically, attack frequency and duration differed widely from the general pattern of cluster headache. Ocular variables, such as intraocular pressure and corneal indentation pulse amplitudes, also differed in our case (clear symptomatic side increment during attacks) and cluster headache. Pupil reactions to directly and indirectly acting sympathicomimetic drugs were also vastly different in our case and cluster headache: no signs of Horner s syndrome in our patient, while cluster headache exhibits a "Horner-like pattern." In cluster headache, there is a relative hypohidrosis in the forehead on the symptomatic side if body temperature is increased, and a clear hyperhidrosis on direct parasympathomimetic stimulation. This was not so in our case. Indomethacin was highly effective in our case, while "cluster headache drugs," such as ergotamine/sumatriptan, were ineffective. Indomethacin was inactive in cluster headache. Accordingly, our case seemed to differ decisively from cluster headache: CPH had been discovered.


Coating of proteins to polystyrene ELISA plates in the presence of detergents.
The influence of several detergents on protein coating of polystyrene plates has been investigated. At concentrations equal to or higher than their respective critical micelle concentration (CMC) all detergents prevent attachment of proteins to polystyrene. However, coating of proteins on polystyrene plates can be achieved in the presence of detergents at concentrations 10-100 times lower than their CMC values. There is a strong correlation between the CMC and the detergent concentration inhibiting protein binding to polystyrene by 50%. The rank correlation coefficient for the binding of thyroid plasma membrane antigens was 0.97 (P less than 0.01). The influence of a detergent on the efficiency of protein coating of plastic surfaces also depends to some extent on protein-detergent interactions. Attachment of small hydrophilic proteins such as human IgG is more strongly inhibited by detergents than is the coating of hydrophobic thyroid plasma membrane antigens or thyroglobulin. Some detergents do not interfere with protein attachment to plastics and permit subsequent ELISA assays for hydrophobic, detergent solubilized plasma membrane proteins.


New Model to Predict Recurrence After Endoscopic Mucosal Resection of Non-pedunculated Colonic Polyps ≥ 20 mm.
Polyp recurrence is common after endoscopic mucosal resection (EMR) of non-pedunculated colonic polyps ≥ 20 mm. Two models haven been published for polyp recurrence prediction: Sydney EMR recurrence tool (SERT) and the size, morphology, colonic site, and access to target (SMSA) score. None of these models have been evaluated in a real-world United States (U.S.) cohort. We aimed to evaluate the external validity of these two models and develop a new model. Retrospective cohort study of patients with non-pedunculated polyps ≥ 20 mm that underwent EMR between 1/1/2012 and 6/30/2020. Univariate and multivariate analysis were performed to identify predictors of polyp recurrence to build a new model. Receiver Operating Characteristic (ROC) curves for the new model, SERT and a modified version of SMSA were derived and compared. A total of 461 polyps from 461 unique patients were included for analysis. The average polyp size was 29.1 ± 12.4 mm. Recurrence rate at first or second surveillance colonoscopy was 29.0% at a 15.6 months median follow up (IQR 12.3-17.4). A model was created with 4 variables from index colonoscopy: size > 40 mm, tubulovillous adenoma histology, right colon location and piecemeal resection. ROC curves showed that the Area Under the ROC (AUC) for the new model was 0.618, for SERT 0.538 and for mSMSA 0.550. SERT score and mSMSA have poor external validity to predict polyp recurrence after EMR of non-pedunculated polyps > 20 mm. Our new model is simpler and performs better in this multiethnic, non-referral cohort from the U.S.


[Repeat operations after surgical interventions in perforated gastroduodenal ulcers].
Indications to reoperations and conditions of performing them are analyzed on the basis of an experience with 188 reoperations. Principles of choice of the method of reoperations are given which depend on the defects of the primary operations.


Morphology and Interconnected Microstructure-Driven High-Rate Capability of Li-Rich Layered Oxide Cathodes.
A Li-rich layered oxide (LLO) cathode with morphology-dependent electrochemical performance with the composition Li1.23Mn0.538Ni0.117Co0.114O2 in three different microstructural forms, namely, randomly shaped particles, platelets, and nanofibers, is synthesized through the solid-state reaction (SSR-LLO), hydrothermal method (HT-LLO), and electrospinning process (ES-LLO), respectively. Even though the cathodes possess different morphologies, structurally they are identical. The elemental dispersion studies using energy-dispersive X-ray spectroscopy mapping in scanning transmission electron microscopy show uniform distribution of elements. However, SSR-LLO and ES-LLO nanofibers show slight Co-rich regions. The electrochemical studies of LLO cathodes are evaluated in terms of charging/discharging, C-rate capability, and cyclic stability performances. A high reversible capacity of 275 mA h g-1 is achieved in the fibrous LLO cathode which also demonstrates good high-rate capability (80 mA h g-1 at 10 C-rate). These capacities and rate capabilities are superior to those of SSR-LLO [210.5 mA h g-1 (0.1 C-rate) and 4 mA h g-1 (3 C-rate)] and HT-LLO [242 mA h g-1 (0.1 C-rate) and 22 mA h g-1 (10 C-rate)] cathodes. The ES-LLO cathode exhibits 88% capacity retention after 100 cycles at 1 C-rate. A decrease in voltage on cycling is found to be common in all three cathodes; however, minimal voltage decay and capacity loss are observed in ES-LLO upon cycling. Well-connected small LLO particles constituting fibrous microstructural forms in ES-LLO provide an enhanced electrolyte/cathode interfacial area and reduced diffusion path length for Li+. This, in turn, facilitates superior electrochemical performance of the electrospun Co-low LLO cathode suitable for quick charge battery applications.


Hydrogen Sulfide Is a Novel Regulator of Bone Formation Implicated in the Bone Loss Induced by Estrogen Deficiency.
Hydrogen sulfide (H2 S) is a gasotransmitter known to regulate bone formation and bone mass in unperturbed mice. However, it is presently unknown whether H2 S plays a role in pathologic bone loss. Here we show that ovariectomy (ovx), a model of postmenopausal bone loss, decreases serum H2 S levels and the bone marrow (BM) levels of two key H2 S-generating enzymes, cystathione β-synthase (CBS) and cystathione γ-lyase (CSE). Treatment with the H2 S-donor GYY4137 (GYY) normalizes serum H2 S in ovx mice, increases bone formation, and completely prevents the loss of trabecular bone induced by ovx. Mechanistic studies revealed that GYY increases murine osteoblastogenesis by activating Wnt signaling through increased production of the Wnt ligands Wnt16, Wnt2b, Wnt6, and Wnt10b in the BM. Moreover, in vitro treatment with 17β-estradiol upregulates the expression of CBS and CSE in human BM stromal cells (hSCs), whereas an H2 S-releasing drug induces osteogenic differentiation of hSCs. In summary, regulation of H2 S levels is a novel mechanism by which estrogen stimulates osteoblastogenesis and bone formation in mice and human cells. Blunted production of H2 S contributes to ovx-induced bone loss in mice by limiting the compensatory increase in bone formation elicited by ovx. Restoration of H2 S levels is a potential novel therapeutic approach for postmenopausal osteoporosis. © 2015 American Society for Bone and Mineral Research.


Options for sphincter preservation in surgery for low rectal cancer.
Abdominoperineal excision of the rectum with a permanent end-sigmoid colostomy was the classical operation for cancer of the distal third of the rectum. A number of factors have recently led to a more conservative approach, allowing sphincter preservation when excising tumours that are not invading the anal sphincter. The review is based on the published literature of the treatment of low rectal cancers accessed by searching Medline and other online databases. It includes a description of all the surgical options currently available for low rectal tumours, and a discussion of the advantages and disadvantages of the types of anastomosis and reconstruction. It is now technically possible to remove rectal cancer that is extending into the anal canal with preservation of the anal sphincter mechanism and with a satisfactory oncological outcome. Ultra-low colorectal and coloanal anastomosis, together with a colonic pouch or coloplasty, produces acceptable function in many patients. However, there is still controversy about the risk of tumour implantation, the place of downsizing neoadjuvant therapy, and true long-term functional outcome. Despite these concerns, surgeons should strive to perform rectal resection with sphincter preservation for low-lying rectal cancer whenever possible.


The binding of Vibrio parahaemolyticus 125I-labeled thermostable directhemolysin to erythrocytes.
Thermostable direct hemolysin (TDH) produced by Vibrio parahaemolyticus was iodinated using chloramine T. The 125I-labeled TDH retained up to 80% of the activity of intact toxin. The binding of 125I-TDH to rabbit erythrocytes was inhibited by addition of nonlabeled TDH. The binding of 125I-TDH to rabbit erythrocytes was completed in the 1st or 2nd min of incubation at 37 degrees C in contrast to that at 4 degrees C. 125I-TDH, which cannot lyse horse erythrocytes as does intact TDH, bound to horse erythrocytes as to those of rabbit. The dissociation constants (KD) derived Scatchard plots were 2.85, 4.39, 4.33 and 5.35 x 10-8M for rabbit, horse, human and sheep erythrocytes, respectively. The lytic sensitivity of various erythrocytes to TDH showed no relationship to the binding capacity.


Importance of congenital cytomegalovirus in the neonatal hearing screening program.
In newborns, hearing loss secondary to congenital Cytomegalovirus (CMVc) infection, despite its low prevalence, can cause a serious problem in the personal development and social integration of patients. Therefore, it is important to include the determination of CMV DNA as a neonatal screening tool. We have carried out a 5-year retrospective study, by describing the CMVc in the Autonomous Community of the Basque Country in newborns who did not pass the hearing screening in the early hearing loss detection program. The times of detection, confirmation (incidence) and intervention (treatment) are described. Of 18,782 subjects studied, 58 (three per thousand live births) presented hearing loss. Of these, CMVc is guaranteed in four patients (one woman and three men). The mean time to hearing screening was 6.5 days (SD: ±3.69) and to detect CMV by polymerase chain reaction (PCR) in urine and saliva was 4.2 days (SD: ± 3.94). Time to confirm hearing loss by BAEP and audiological intervention 2.2 (SD: ±0.957) and 5 months (SD: ±3.741), respectively. Four hearing aid adaptations and one cochlear implant were performed. Neonatal hearing screening has established itself as a good public health program. The determination of viral DNA allows an early, specific and interdisciplinary diagnosis and treatment, in which otorhinolaryngology plays a fundamental role. Our study highlights the importance of including CMV PCR as a universal screening tool.


PM2.5 associated with gray matter atrophy reflecting increased Alzheimers risk in older women.
To examine whether late-life exposure to PM2.5 (particulate matter with aerodynamic diameters <2.5-µm) contributes to progressive brain atrophy predictive of Alzheimer's disease (AD) using a community-dwelling cohort of women (aged 70-89) with up to two brain MRI scans (MRI-1: 2005-6; MRI-2: 2010-11). AD pattern similarity (AD-PS) scores, developed by supervised machine learning and validated with MRI data from the AD Neuroimaging Initiative, was used to capture high-dimensional gray matter atrophy in brain areas vulnerable to AD (e.g., amygdala, hippocampus, parahippocampal gyrus, thalamus, inferior temporal lobe areas and midbrain). Based on participants' addresses and air monitoring data, we implemented a spatiotemporal model to estimate 3-year average exposure to PM2.5 preceding MRI-1. General linear models were used to examine the association between PM2.5 and AD-PS scores (baseline and 5-year standardized change), accounting for potential confounders and white matter lesion volumes. For 1365 women aged 77.9±3.7 years in 2005-6, there was no association between PM2.5 and baseline AD-PS score in cross-sectional analyses (β=-0.004; 95% CI: -0.019, 0.011). Longitudinally, each interquartile range increase of PM2.5 (2.82-µg/m3) was associated with increased AD-PS scores during the follow-up, equivalent to a 24% (hazard ratio=1.24; 95% CI: 1.14, 1.34) increase in AD risk over 5-years (n=712; aged 77.4±3.5 years). This association remained after adjustment for socio-demographics, intracranial volume, lifestyle, clinical characteristics, and white matter lesions, and was present with levels below US regulatory standards (<12-µg/m3). Late-life exposure to PM2.5 is associated with increased neuroanatomical risk of AD, which may not be explained by available indicators of cerebrovascular damage.


Glutamate levels in the associative striatum before and after 4 weeks of antipsychotic treatment in first-episode psychosis: a longitudinal proton magnetic resonance spectroscopy study.
Increased glutamate levels in the right associative striatum have been described in patients during a first episode of psychosis. Whether this increase would persist after effective antipsychotic treatment is unknown. To compare the glutamate levels in antipsychotic-naive patients with first-episode psychosis in the right associative striatum and right cerebellar cortex using proton magnetic resonance spectroscopy before and 4 weeks after antipsychotic treatment and to compare these results with normative data from sex-matched healthy control subjects. Before-after trial in an inpatient psychiatric research unit among 24 antipsychotic-naive patients with first-episode psychosis and 18 healthy controls matched for age, sex, handedness, and cigarette smoking. Participants underwent 2 proton magnetic resonance spectroscopy studies: patients were imaged at baseline and after 4 weeks of antipsychotic treatment, while controls were imaged at baseline and at 4 weeks after the baseline measurement. Patients were treated with oral risperidone (open label) for 4 weeks with dosages that were titrated on the basis of clinical judgment. Glutamate levels were estimated using LCModel (version 6.2-1T) and were corrected for the cerebrospinal fluid proportion within the voxel. Patients with first-episode psychosis had higher levels of glutamate in the associative striatum and the cerebellum during the antipsychotic-naive condition compared with controls. After clinically effective antipsychotic treatment, glutamate levels significantly decreased in the associative striatum, with no significant change in the cerebellum. No differences in glutamate levels were observed between groups at 4 weeks. Increased glutamate levels observed at baseline in patients with first-episode psychosis normalized after 4 weeks of clinically effective antipsychotic treatment. These results provide support for the hypothesis that improvement in clinical symptoms might be related to a decrease in glutamate levels.


Influence of maternal murine immunization with Dermatophagoides pteronyssinus extract on the type I hypersensitivity response in offspring.
Maternal exposure to environmental ubiquitous allergens could exert an influence on the newborn's immune repertoire and the later development of allergy. The aim of this study was to investigate the effects of maternal immunization with Dermatophagoides pteronyssinus (Dp) on the hypersensitivity response and IgG subclass production in offspring using a murine model. A/Sn mice were immunized with Dp before mating with normal A/Sn males. Diaplacental serum samples were collected from newborn mice delivered by cesarean section, and maternal milk samples were extracted from the stomachs of newborn mice. Groups of offspring 25 or 45 days old were Dp immunized and boosted on the 10th day after sensitization. The animals were bled 7 days after the booster. High levels of anti-Dp IgG subclasses - mainly IgG1, but also IgG2a and IgG2b - were transmitted by immunized mice via the placenta to the offspring. In the milk from immunized mothers, significant levels of anti-Dp IgG subclasses and anti-Dp IgM and IgA antibodies were detected. Moreover, the increase in total IgA antibodies in the milk of the immunized females correlated with a significantly increased level of TGF-beta1. TGF-beta2 levels were markedly higher than the beta1 isoform in the milk, although no difference was observed between the groups. When offspring from immunized mothers were sensitized at 25 days, a significant decrease in total and anti-Dp IgE antibodies as well as total and anti-Dp IgG1, IgG2a and IgG2b subclasses was observed compared to normal female offspring, whereas when offspring were sensitized at 45 days, both offspring groups showed similar levels of IgE and IgG subclasses. Our study showed that maternal immunization with Dp promotes the transference of specific antibodies and/or TGF-beta, which can negatively modulate the allergic response in offspring, and suggests that maternal preexposure to allergen before mating can protect mice during the early phase.


Psychological interventions for depression in Chinese university students: A systematic review and meta-analysis.
University students in China are vulnerable to depression with a high estimated prevalence. It is currently unknown which types of psychological interventions are being delivered to treat depression in this population and whether they are effective. Therefore, a systematic review was conducted to address this issue. We searched records in English and Chinese databases up to January 2019. From 2,739 records, we identified 39 randomized controlled trails (RCTs) and 54 non-RCTs. A range of psychological interventions were identified including cognitive behaviour therapy, interpersonal therapy, and local interventions. Hedge's g pooled effect size of 23 comparisons from 21 RCTs (N =858) compared to a control group (N = 802) was 1.08 (95% CI: 0.72 to 1.45). Heterogeneity was moderate with I2 = 47 (95%CI: 14 to 68). Type of control group was significantly associated with the effect size (p =0.039). Comparisons between the intervention condition and the 'no intervention' condition yielded a higher effect size (Hedges' g =1.38, 95% CI: 0.89 to 1.87) than comparisons between the intervention condition and the 'usual care/control' condition (Hedges' g = 0.56, 95% CI 0.08 to 1.05). No other significant differences based on the study characteristics were observed. Publication bias and quality of inclusions. Collectively, there is evidence that psychological interventions for depression in Chinese university students are effective as compared to control groups, although the effects merit further examination by research of higher quality. Innovations in treatment delivery could facilitate wider dissemination of evidence-based interventions.


Iris nevus syndrome.
We present a case of iris-nevus or Cogan-Reese syndrome with its characteristic pathological findings. Although a rare entity, it should be considered in the differential diagnosis of heterochromia associated with elevated intra-ocular pressure. To avoid unnecessary enucleation, it should not be confused with diffuse iris melanoma.


Latent tuberculosis infection screening prior to biological treatment in Tunisian patients.
The screening of latent tuberculosis infection (LTBI) is necessary to prevent infection in patients with chronic inflammatory disease (CID) undergoing biological treatment. We aimed to assess the efficacy of LTBI screening prior to biological treatment in Tunisia, considered as a high-incidence area of active TB disease. We conducted a retrospective study over a period of 8 years [2007-2014] including patients with chronic inflammatory rheumatism receiving biologic agents since at least 6 months. The screening of LTBI was performed according to national Tunisian guidelines. There were 35 men and 78 women. The mean age was 47.67±13.50 years. Rheumatoid arthritis (70.8%) was the most common cause of CID. The diagnosis of LTBI was established in 23 cases. Among these 23 patients, 12 patients had negative tuberculin skin test (TST) associated with positive QuantiFERON-TB Gold (QFT-G), 10 had TST more than 10mm, one patient had a TST between 5 and 10mm associated with positive QFT-G and one patient had a history of tuberculosis inadequately treated. Preventive anti-tuberculous therapy was prescribed before biological therapy initiation in cases of LTBI. During the follow-up period (3.91 years), no case of tuberculosis reactivation has been reported among patients diagnosed with LTBI. However, 2 cases of active pulmonary tuberculosis were reported in patients with initially negative TST and QFT-G. Our study showed that the Tunisian recommendations allowed detecting a LTBI in 20% of biologic therapy candidates. Preventive measures including screening of LTBI and eventually a prophylactic treatment improve the safety of biological treatments.


Extended resuscitative endovascular balloon occlusion of the aorta (REBOA)-induced type 2 myocardial ischemia: a time-dependent penalty.
Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) increases cardiac-afterload and is used for patients in hemorrhagic shock. The cardiac tolerance of prolonged afterload augmentation in this context is unknown. The aim of this study is to quantify cardiac injury, if any, following 2, 3 and 4 hours of REBOA. Anesthetized swine (70-90 kg) underwent a 40% controlled hemorrhage, followed by supraceliac resuscitative endovascular balloon occlusion of the aorta (REBOA) for 2 (n=5), 3 (n=5), and 4 hours (n=5). High-fidelity arterial wave form data were collected, and signal processing techniques were used to extract key inflection points. The adjusted augmentation index (AIx@75; augmentation pressure/pulse pressure, normalized for heart rate) was derived for use as a measure of aortic compliance (higher ratio = less compliance). Endpoints consisted of electrocardiographic, biochemical, and histologic markers of myocardial injury/ischemia. Regression modeling was used to assess the trend against time. All animals tolerated instrumentation, hemorrhage, and REBOA. The mean (±SD) systolic blood pressure (mm Hg) increased from 65±11 to 212±39 (p<0.001) during REBOA. The AIx@75 was significantly higher during REBOA than baseline, hemorrhage, and resuscitation phases (p<0.05). A time-dependent rise in troponin (R2=0.95; p<0.001) and T-wave deflection (R2=0.64; p<0.001) was observed. The maximum mean troponin (ng/mL) occurred at 4 hours (14.6±15.4) and maximum T-wave deflection (mm) at 65 minutes (3.0±1.8). All animals demonstrated histologic evidence of acute injury with increasing degrees of cellular myocardial injury. Prolonged REBOA may result in type 2 myocardial ischemia, which is time-dependent. This has important implications for patients where prolonged REBOA may be considered beneficial, and strategies to mitigate this effect require further investigation. II.


Coexisting conical bipolar and equatorial outflows from a high-mass protostar.
The BN/KL region in the Orion molecular cloud is an archetype for the study of the formation of stars much more massive than the Sun. This region contains luminous young stars and protostars but, like most star-forming regions, is difficult to study in detail because of the obscuring effects of dust and gas. Our basic expectations are shaped to some extent by the present theoretical picture of star formation, the cornerstone of which is that protostars accrete gas from rotating equatorial disks and shed angular momentum by ejecting gas in bipolar outflows. The main source of the outflow in the BN/KL region may be an object known as radio source I, which is commonly believed to be surrounded by a rotating disk of molecular material. Here we report high-resolution observations of silicon monoxide (SiO) and water maser emission from the gas surrounding source I. We show that within 60 AU of the source (about the size of the Solar System), the region is dominated by a conical bipolar outflow, rather than the expected disk. A slower outflow, close to the equatorial plane of the protostellar system, extends to radii of 1,000 AU.


Calcium-induced ventricular contraction during cardioplegic arrest.
Cardiac arrest induced by hyperkalemic perfusion is generally considered to represent a state of complete electromechanical arrest. However, high-energy phosphate concentrations and ventricular function decrease with increasing cardioplegic calcium concentrations, possibly because of elevated resting muscle tone produced by calcium influx. We examined isolated rat hearts containing an isovolumic intraventricular balloon for the presence of contractile activity during the administration at 10 degrees C of a cardioplegic solution containing potassium, 20 mEq/L. Significant left ventricular pressure was developed (35.6% +/- 4.3% of prearrest systolic pressure) during administration of a solution containing a calcium concentration of 1.0 mmol/L and far less (9.7% +/- 1.6% of prearrest systolic pressure) with a calcium-free cardioplegic solution. The muscle contraction diminished with repeated doses, was increased by increasing cardioplegic calcium content, and was inhibited by magnesium. Adenosine triphosphate and creatine phosphate concentrations were 9.0 +/- 1.4 and 7.0 +/- 0.9 nmol/mg dry weight immediately after infusion of 15 ml of a hypoxic cardioplegic solution containing calcium, versus 13.3 +/- 1.3 (p less than 0.02) and 31.9 +/- 3.5 nmol/mg dry weight (p less than 0.0001) after a hypoxic acalcemic solution was given. When repeated doses of a hypoxic cardioplegic solution containing calcium in a concentration of 1.0 mmol/L were given at 15 minute intervals at 10 degrees C, ischemic contracture (a sustained development of ventricular pressure, mean 51% +/- 4% of prearrest systolic pressure) resulted within 1 hour. Coronary vascular resistance was increased during the muscle contractions induced by calcium-containing solutions, markedly so during contracture. Calcium-related mechanical activity was also observed during hypothermic cardioplegic arrest in five of six isolated isovolumic canine hearts. We conclude that hearts remain potentially active mechanically during cold hyperkalemic arrest and undergo energetically wasteful contraction when stimulated with calcium-containing hyperkalemic cardioplegic solutions.


Allergen-specific IgE and IgGd antibodies in atopic and normal dogs.
Intradermal skin tests (IDSTs) were performed on 65 atopic and 24 normal dogs. The levels of allergen-specific IgE and IgGd antibodies were determined in serum samples by enzyme-linked immunosorbent assay (ELISA) using the same 12 allergens that were used in the IDST on normal dogs. The correlation between the levels of IgE and IgGd to Dermatophagoides farinae (DF) and Dermatophagoides pteronyssinus (DP) was examined. The sensitivity, specificity and positive and negative predictive values of allergen-specific IgE and IgGd levels in the total dog population were also compared. Results were consistent and reproducible for 9/12 allergens, but in the case of house dust, flea and Alternaria tenuis, a less discriminating standard curve and the fact that the negative control gave positive results, suggests non-specific binding and that these allergens are complex and should not be employed without further purification. A high percentage of atopic dogs had positive IDSTs and detectable IgE and IgGd antibodies to DF, DP and house dust. Similar results were obtained in the normal dog population. There were significant correlations between allergen-specific IgE and IgGd levels to DF and DP. However, in contrast to IgE, allergen-specific IgGd in normal dogs was higher than in atopic dogs. Furthermore, a high percentage of the atopic population had detectable IgGd to unrelated allergens, despite negative IDSTs. Overall, the negative predictive values were similar for both IgE and IgGd. Sensitivities were higher in the allergen-specific IgGd assays, but the specificities and positive predictive values were higher in the allergen-specific IgE assays. In conclusion, the concordance of IDSTs with ELISA results to DF and DP in normal dogs without clinical signs implied the possible heterogeneity of IgE in dogs. The presence of IgGd directed against apparently irrelevant allergens in atopic patients and the high levels of IgGd in normal dogs to the most common allergens, DF and DP, implied an uncertain role of IgGd in canine atopic disease. Therefore, the detection of allergen-specific IgE is a more useful adjunct to the diagnosis of atopic disease in the dog than IgGd.


Amyloidogenic and non-amyloidogenic molten globule conformation of β-lactoglobulin in self-crowded regime.
Molecular insights on the β-lactoglobulin thermal unfolding and aggregation are derived from FTIR and UV Resonance Raman (UVRR) investigations. We propose an in situ and in real-time approach that thanks to the identification of specific spectroscopic markers can distinguish the two different unfolding pathways pursued by β-lactoglobulin during the conformational transition from the folded to the molten globule state, as triggered by the pH conditions. For both the investigated pH values (1.4 and 7.5) the greatest conformational variation of β-lactoglobulin occurs at 80 °C and a high degree of structural reversibility after cooling is observed. In acidic condition β-lactoglobulin exposes to the solvent its hydrophobic moieties in a much higher extent than in neutral solution, resulting on a highly open conformation. Moving from the diluted to the self-crowded regime, the solution pH and consequently the different molten globule conformation select the amyloid or non-amyloid aggregation pathway. At acidic condition the amyloid aggregates form during the heating cycle leading to the formation of transparent hydrogel. On the contrary, in neutral condition the amyloid aggregates never form. Information on the secondary structure conformational change of β-lactoglobulin and the formation of amyloid aggregates are obtained by FTIR spectroscopy and are related to the information of the structural changes localized around the aromatic amino acid sites by UVRR technique. Our results highlight a strong involvement of the chain portions where tryptophan is located on the formation of amyloid aggregates.


Batch to batch imprecision in the affinity chromatography assay of glycated hemoglobin.
An affinity chromatographic method (AC) was compared with ion exchange chromatography (IEC) for determination of glycated hemoglobin (gHb). In vitro, increasing glucose concentration produced no change on AC-determined gHb. gHb measurement by AC was highly correlated with mean blood glucose (r = 0.96). Mean values of gHb were apparently higher, and variation greater, by AC than by IEC. Intra-assay variation was 2.0% and 3.0%, respectively. Inter-assay variation was 4.8% by IEC and 6.4% by AC. When different batches of AC-columns were compared, mean values as well as precision differed considerably. The affinity chromatographic method tested here shows several expected advantages, but precision and inter-batch variation of the columns remain to be improved.


In vitro conjugal transfer of tetracycline resistance from Lactobacillus isolates to other Gram-positive bacteria.
The ability of 14 Lactobacillus strains, isolated from fermented dry sausages, to transfer tetracycline resistance encoded by tet(M) through conjugation was examined using filter mating experiments. Seven out of 14 tetracycline-resistant Lactobacillus isolates were able to transfer in vitro this resistance to Enterococcus faecalis at frequencies ranging from 10(-4) to 10(-6) transconjugants per recipient. Two of these strains could also transfer their resistance to Lactococcus lactis subsp. lactis, whereas no conjugal transfer to a Staphylococcus aureus recipient was found. These data suggest that meat lactobacilli might be reservoir organisms for acquired resistance genes that can be spread to other lactic acid bacteria. In order to assess the risk of this potential hazard, the magnitude of transfer along the food chain merits further research.


Selection on spur shape in Impatiens capensis.
Rapid speciation within some plant families has been attributed to the evolution of floral spurs and to the effect of spur length on plant reproductive success. The flowers of Impatiens capensis (jewelweed) possess a long, curved spur in which nectar is produced and stored. Spur length and curvature varies among plants within one population. Here I document that spur shape is variable in natural populations, variation within plants is less than variation among plants, and spur shape is correlated with components of female and male reproductive success. The apparent natural selection is weakly directional in 1 of 2 years, with greatest seed production and pollen removal occurring in flowers with the greatest spur curvature. Bee pollinator visit length is longest at flowers with highly curved spurs, and they leave less nectar in these spurs than in flowers with straighter spurs. Spur angle evolution may be limited, at least in part, by opposing selection by nectar-robbers who prefer to visit flowers with greater spur curvature. Other factors that might contribute to the maintenance of spur angle variation are temporal variation in the strength of selection and potential genetic correlations of spur shape with other traits under selection.


The impact of structural genomics: the first quindecennial.
The period 2000-2015 brought the advent of high-throughput approaches to protein structure determination. With the overall funding on the order of $2 billion (in 2010 dollars), the structural genomics (SG) consortia established worldwide have developed pipelines for target selection, protein production, sample preparation, crystallization, and structure determination by X-ray crystallography and NMR. These efforts resulted in the determination of over 13,500 protein structures, mostly from unique protein families, and increased the structural coverage of the expanding protein universe. SG programs contributed over 4400 publications to the scientific literature. The NIH-funded Protein Structure Initiatives alone have produced over 2000 scientific publications, which to date have attracted more than 93,000 citations. Software and database developments that were necessary to handle high-throughput structure determination workflows have led to structures of better quality and improved integrity of the associated data. Organized and accessible data have a positive impact on the reproducibility of scientific experiments. Most of the experimental data generated by the SG centers are freely available to the community and has been utilized by scientists in various fields of research. SG projects have created, improved, streamlined, and validated many protocols for protein production and crystallization, data collection, and functional analysis, significantly benefiting biological and biomedical research.


Changes in Perioperative Outcomes after Robotic-Assisted Pulmonary Lobectomy during the COVID-19 Era.
The COVID-19 pandemic presented patients with barriers to receiving healthcare. We sought to determine whether changes in healthcare access and practice during the pandemic affected perioperative outcomes after robotic-assisted pulmonary lobectomy (RAPL). We retrospectively analyzed 721 consecutive patients who underwent RAPL. With March 1st, 2020, defining the start of the COVID-19 pandemic, we grouped 638 patients as "PreCOVID-19" and 83 patients as "COVID-19-Era" based on surgical date. Demographics, comorbidities, tumor characteristics, intraoperative complications, morbidity, and mortality were analyzed. Variables were compared utilizing Student's t-test, Wilcoxon rank-sum test, and Chi-square (or Fisher's exact) test, with significance at p ≤ 0.05 . Multivariable generalized linear regression was used to investigate predictors of postoperative complication. COVID-19-Era patients had significantly higher preoperative FEV1%, lower cumulative smoking history and higher incidences of preoperative atrial fibrillation, peripheral vascular disease (PVD), and bleeding disorders compared to PreCOVID-19 patients. COVID-19-Era patients had lower intraoperative estimated blood loss (EBL), reduced incidence of new-onset postoperative atrial fibrillation (POAF), but higher incidence of effusion or empyema postoperatively. Overall postoperative complication rates between the groups were similar. Older age, increased EBL, lower preoperative FEV1%, and preoperative COPD are all predictive of an increased risk for postoperative complication. COVID-19-Era patients having lower EBL and less new-onset POAF, despite greater incidences of multiple preoperative comorbidities, demonstrates that RAPL is safe during the COVID-19 era. Risk factors for development of postoperative effusion should be determined to minimize risk of empyema in COVID-19-Era patients. Age, preoperative FEV1%, COPD, and EBL should all be considered when planning for complication risk.


Investigation of the phytochemical composition and remedial effects of southern grape hyacinth (Muscari neglectum Guss. ex Ten.) plant extract against carbon tetrachloride-induced oxidative stress in rats.
We aimed to determine the phytochemical contents of the aerial part M. neglectum aerial part (MAP) and M. neglectum bulb (MB) ethanolic extract of Muscari neglectum and to investigate their protective effects on gastric damage induced by carbon tetrachloride (CCl4) in rats. After the toxicity testing, 42 female Wistar albino rats were divided into 7 groups, Control, MAP, MB, CCl4, CCl4 + MAP, CCl4 + MB, and CCl4 + Silymarin groups. At the end of the experiment, the serum biochemical parameters, antioxidant defense enzymes, and malondialdehyde (MDA) contents in the stomach tissue were evaluated to determine the antioxidant role of the M. neglectum extracts. According to the gas chromatography-mass spectroscopy, fatty acid analysis, octadecadienoic, and 9,12,15 octadecatrienoic fatty acids were found as major fatty acids in the MAP, whereas 9,12 octadecadienoic and octadecanoic acids were the major fatty acids in the MB. According to the liquid chromatography-tandem mass spectrometry, quinic acid, fumaric acid, gentisic acid, caffeic acid, kaempferol, and apigenin were found in the MAP, while quinic acid, fumaric acid, caffeic acid, and kaempferol were found in the MB. The total phenolic and flavonoid contents in the extract were determined in the MAP and MB. The MAP and MB extracts generally caused a statistically significant decrease in the MDA content and increase in the antioxidant parameters in the stomach tissue. It was concluded that MAP and MB extracts may have antioxidant and gastric protective effects due to the phytochemical content of M. neglectum.HighlightsAccording to LC-MS/MS results, quinic acid, fumaric acid, chemferol, apigenin, and caffeic acid were determined as major compounds in M. neglectum extracts.According to GC-MS results, octadecadienoic, octadecatrienoic, and octadecanoic methyl esters were the major fatty acids of the M. neglectum extracts.The M. neglectum extracts regulated the levels of stomach damage and biochemical parameters.The M. neglectum extracts extract might have pharmaceutical-nutritional potential.


Purification and characterization of tryptophan dioxygenase from Streptomyces parvulus.
Tryptophan dioxygenase, derived from Streptomyces parvulus, was purified to near homogeneity and shown to have a native Mr of 88,000. Kinetic parameters of the enzyme were determined and evidence suggesting that it is a hemoprotein was obtained. Tryptophan dioxygenase has a high specificity toward L-tryptophan with an apparent Km of 0.3 mM. L-3-Hydroxykynurenine was a competitive inhibitor with respect to L-tryptophan with a Ki of 0.16 mM. In vitro, the enzyme displayed little activity in the absence of a reducing agent; ascorbate, at 50 mM, was the preferred reductant providing almost a 50-fold increase in enzyme activity. The regulation of tryptophan dioxygenase synthesis and activity is described. The expression of the enzyme is correlated with the biosynthesis of actinomycin D in S. parvulus. These results support the hypothesis that tryptophan dioxygenase functions as the first enzyme in the sequence converting L-tryptophan to the chromophore of this antibiotic.


Linkage relationship between the genes for adenosine deaminase and S-adenosyl-homocysteine hydrolase on human chromosome 20.
The genes for adenosine deaminase (ADA) and S-adenosyl homocysteine hydrolase (AHCY or SAHH) are known to be syntenic and within measurable distance from each other, on chromosome 20 in man. In the present study an informative family is described in which the recombination fraction (theta) between the respective genes is estimated to be about 0.18. Together with the published finding of theta = 0.15 (Eiberg and Mohr 1985) in informative Danish families, the recombination fraction for the pooled data is calculated to be theta = 0.14 (in men), theta = 0.08 (in women) and theta = 0.13 (both sexes taken together).


Cost-effectiveness of revised US pneumococcal vaccination recommendations in underserved minority adults < 65-years-old.
The 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recently recommended for US adults, giving either PCV20 alone or PCV15 followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) to all 65 + -year-olds and to high-risk younger adults. However, general population recommendations to vaccinate all 50-year-olds could reduce racial pneumococcal disease disparities given greater risk in underserved minority populations. A Markov model examining hypothetical 50-year-old Black cohorts (serving as a proxy for underserved minorities) and non-Black cohorts estimated the incremental cost effectiveness of US adult pneumococcal vaccination recommendations compared to PCV20 or PCV15/PPSV23 for all 50-year-olds with no vaccination thereafter, or PCV20 or PCV15/PPSV23 for all at ages 50 and 65 years (50/65). Model parameters came from US databases, clinical trials, and Delphi panels. Cohorts were followed over their lifetimes from a healthcare perspective discounted at 3 %/year. PCV15/PPSV23 given at ages 50/65 had greatest public health impact. In Black cohorts, PCV15/PPSV23 at age 50 cost $104,723/quality adjusted life year (QALY) gained compared to PCV20 at age 50, while PCV15/PPSV23 at 50/65 cost $240,952/QALY gained compared to PCV15/PPSV23 at age 50. Both current recommendation options were more expensive and less effective than other strategies in both cohorts. In sensitivity analyses, age-based PCV20 or PCV15/PPSV23 use at ages 50 or 50/65 could be favorable depending on vaccine effectiveness or differential vaccine uptake, while current recommendations remained unfavorable. Recent risk-based US adult pneumococcal vaccination recommendations for adults < 65-years-old, were economically and clinically unfavorable compared to general population vaccination of all 50-year-olds in Black and non-Black cohorts. An age-based pneumococcal vaccination recommendation at age 50 years may reduce inequities in pneumococcal disease burden.


Can compost improve Quercus pubescens Willd establishment in a Mediterranean post-fire shrubland?
The aim of the study was to evaluate the effects of sewage sludge compost (control, 20 kg m(-2), 40 kg m(-2)) supplied to Quercus pubescens Willd seedlings planted in a post-fire calcareous site in Provence (France). Changes in soil properties, seedling survival, growth and nutrition were monitored 7 months, 1.5 years and 2.5 years after amendment, and possible trace metal contamination of soil and seedlings by compost was also evaluated. Compost improved overall soil fertility by increasing organic matter, cation exchange capacity, total N and exchangeable P, K, Mg and B concentrations, but 40 kg m(-2) induced a more significant and more durable effect than 20 kg m(-2). However, the compost had no effect on seedling survival and growth, but increased foliar P and B concentrations at 40 kg m(-2). No foliar contamination of seedlings by trace metals occurred, although amendment increased exchangeable Cu and Zn concentrations in soil. Compost P and exchangeable Cu and Zn concentrations could induce eutrophication and water pollution, and limit rates that can be applied without environmental hazard.


New chemotypes acting as isozyme-selective carbonic anhydrase inhibitors with low affinity for the offtarget cytosolic isoform II.
Considering phenols and coumarins as lead molecules for obtaining non-sulfonamide inhibitors of carbonic anhydrases (CAs, EC 188.8.131.52), we screened a large number of compounds possessing diverse chemotypes, but structural features which resemble the two chemical classes. Here we report an investigation of such derivatives which do not significantly inhibit CA II, but show interesting inhibition profiles against other isozymes. Pyridine-N-oxide-2-thiophenol, thiobenzoic acid, thimerosal, two oximes derived from a six-membered-ring lactone and from coumarin; 2-hydroxyquinoline and coumaphos, were investigated as inhibitors of CA I-XIV. All these compounds did not inhibit CA II, whereas the two oximes and 2-hydroxyquinoline were low nanomolar inhibitors of CA I, IX, XII, XIII and XIV, showing a very different inhibition profile compared to sulfonamides and sulfamates. Some other compounds showed low micromolar inhibition of other isoforms of interest, such as CA VA/VB, CA VI and VII. This study demonstrates that a rather wide range of structures show low nanomolar-micromolar inhibitory activity against many CA isozymes, without inhibiting significantly the offtarget isoform CA II.


Perioperative Changes in Cerebral Perfusion Territories Assessed by Arterial Spin Labeling Magnetic Resonance Imaging Are Associated with Postoperative Increases in Cerebral Blood Flow in Patients with Carotid Stenosis.
The magnetic resonance imaging technique known as territorial arterial spin labeling (TASL) allows for noninvasive visualization of perfusion territories. The objective of this study was to use TASL to assess the relationship between perioperative changes in the perfusion territories of the internal carotid artery (ICA) and cerebral blood flow (CBF) after carotid revascularization. In 32 patients, ICA perfusion volume (PV) and CBF were measured before and after carotid endarterectomy/carotid artery stenting using TASL and single-photon emission computed tomography, respectively. ICA flow was measured during carotid endarterectomy before and after reconstruction, using an electromagnetic flowmeter. Eleven healthy volunteers, as the normal control group, underwent TASL evaluation. We classified patients into 2 groups: the normal PV group (ICA PV ≥ mean-2 standard deviation of healthy volunteers; n = 13) and the reduced PV group (ICA PV < mean-2 standard deviation; n = 19). The postoperative increase in the ICA PV and CBF were significantly greater in the reduced PV group than in the normal group (90.4% ± 131.8% vs. 10.5 ± 9.8%, P = 0.017, 32.0 ± 25.7% vs. 10.5% ± 10.7%, P = 0.0032, respectively). ICA flow increased significantly after reconstruction in both the normal PV group (115.1 ± 48.1 mL/minute to 159.1 ± 53 mL/minute; P = 0.016) and reduced PV group (57.8 ± 38.3 mL/minute to 182.3 ± 52.6 mL/minute; P < 0.0001). However, in some patients in the reduced PV group, the PV increased only slightly, whereas the ICA flow markedly increased, which resulted in a large CBF increase, such as hyperperfusion. The TASL study suggested that an imbalance between increases in the PV and ICA flow could play an important role in the pathophysiology underlying postoperative abnormal increases in CBF.


A new class of small inhibitory interneurones in the lamprey spinal cord.
Paired intracellular recordings of interneurones and motoneurones have been performed in the lamprey spinal cord in vitro. One new type of small interneurone (10-15 microns in diameter) which produces monosynaptic inhibitory postsynaptic potentials (IPSPs) in motoneurones is described. The IPSP is strychnine-sensitive and thus presumably glycinergic. This type of interneurone undergoes rhythmical membrane potential oscillations during fictive locomotion and intracellular stimulation can have a profound effect on the burst generation occurring during fictive locomotion.


High-throughput mass finger printing and Lewis blood group assignment of human milk oligosaccharides.
The structural diversity of human milk oligosaccharides (HMOs) strongly depends on the Lewis (Le) blood group status of the donor which allows a classification of these glycans into three different groups. Starting from 50 μL of human milk, a new high-throughput, standardized, and widely automated mass spectrometric approach has been established which can be used for correlation of HMO structures with the respective Lewis blood groups on the basis of mass profiles of the entire mixture of glycans together with selected fragment ion spectra. For this purpose, the relative abundance of diagnostically relevant compositional species, such as Hex(2)Fuc(2) and Hex(3)HexNAc(1)Fuc(2), as well as the relative intensities of characteristic fragment ions obtained thereof are of key importance. For each Lewis blood group, i.e., Le(a-b+), Le(a+b-), and Le(a-b-), specific mass profile and fragment ion patterns could be thus verified. The described statistically proven classification of the derived glycan patterns may be a valuable tool for analysis and comparison of large sets of milk samples in metabolic studies. Furthermore, the outlined protocol may be used for rapid screening in clinical studies and quality control of milk samples donated to milk banks.


Prospective study of port wine stain treatment with dye laser: comparison of two wavelengths (585 nm vs. 595 nm) and two pulse durations (0.5 milliseconds vs. 20 milliseconds).
The conventional pulsed-dye laser (wavelength 585 nm, pulse duration 0.5 milliseconds) is seen as the standard treatment for port wine stains (PWS). Using the pulsed-dye laser at wavelengths of 590, 595, and 600 nm and at varying pulse durations of 1.5-40 milliseconds is one of the newest developments in the field, the therapeutic value of which has been examined in only a few studies. Treatment of PWS with short- and long-pulse dye lasers. Comparison of two wavelengths (585 nm vs. 595 nm) and two pulse durations (0.5 milliseconds vs. 20 milliseconds). Fifteen patients with untreated PWS were included in a randomized prospective study with three different laser settings. Patients underwent one treatment session. The following treatment parameters were chosen at a uniform spot size of 7 mm: (1) 585 nm/0.5 milliseconds/5.5 J/cm(2), (2) 595 nm/0.5 milliseconds/5.5 J/cm(2), and (3) 595 nm/20 milliseconds/13 J/cm(2). The clearance as well as side effects was evaluated. All treatments were performed with cold air-cooling. Follow-up took place immediately, 2 days and 4 weeks after the treatment. The PWS was assigned a clearance score (CS) from 1 to 4 (1 = poor to 4 = excellent). Descriptively, 585 nm/0.5 milliseconds generated the best average CS of 2.7, followed by 595 nm/20 milliseconds (2.5) and 595 nm/0.5 milliseconds (1.6)); statistically, there is no difference between the CS of 585 nm/0.5 milliseconds and 595 nm/20 milliseconds. The best lightening rates overall were achieved in purple PWS (CS = 3.5) versus red (CS = 2.5) and pink (CS = 2.0). Purple PWS responded best to 585 nm/0.5 milliseconds; red and pink PWS yielded similar results with 585 nm/0.5 milliseconds and 595 nm/20 milliseconds. The setting, 595 nm/0.5 milliseconds was clearly not as effective as the other laser settings. Purpura, pain, and crusting were most commonly reported after treatments with 585 nm/0.5 milliseconds (93%/93%/33%), closely followed by treatments at 595 nm/20 milliseconds (86%/93%/20%). The settings 595 nm/0.5 milliseconds yielded the lowest rate of adverse effects (67%/60%/0%). Hypopigmentation only occurred in one case (585 nm/0.5 milliseconds), and there were no reports of hyperpigmentation or scarring. With respect to treating PWS, the conventional pulsed-dye laser set to 585 nm/0.5 milliseconds yields a significantly greater clearance rate than it does at a setting of 595 nm (with the same pulse duration, fluence, and spot size), although the former also entails the highest spectrum of adverse effects. In this study, purple PWS treated at these parameters showed the best results. In dealing with pink PWS, the results were similar to those of the conventional pulsed-dye laser when the pulse duration was increased to 20 milliseconds and fluence was increased. As a rule, the clearance rate corresponded to the extent of the postoperative purpura.


Low impact of exposure to environmentally relevant doses of 226Ra in Atlantic cod (Gadus morhua) embryonic cells.
The aim of this study was to investigate whether (226)Ra, a radionuclide present in produced water from oil platforms in the North Sea and other offshore drilling areas, could affect vulnerable early life stages of Atlantic cod (Gadus morhua). Blastula-stage embryonic cells (EC) from fertilized eggs of Atlantic cod were isolated and exposed to environmental relevant concentrations of (226)Ra and transcription of selected genes quantified. The results showed a weak, but significant up-regulation of GPx3 and HSP70 transcripts after 48 h of exposure to 2.11 Bq/L. In EC exposed to three (226)Ra concentrations (2.11, 23 and 117 Bq/L) for 12 h, metallothionein, HSP90AA, thioredoxin and caspase 8 were significantly up-regulated in cells exposed to 117 Bq/L, whereas thioredoxin was also significantly up-regulated in EC exposed to 23 Bq/L. When EC were exposed to the same (226)Ra concentrations for 48 h, only heme oxygenase was significantly up-regulated in the 23 Bq/L exposure group. The results suggest that environmentally relevant activities of (226)Ra may induce oxidative stress and apoptosis in fish ECs. Exposure of Atlantic cod EC to Cd, selected as a model toxicant, supported the ability of EC around blastula stage to respond to toxicants by altered transcription. Due to dilution, environmentally relevant concentrations of radionuclides present in produced water would be expected to pose a minor threat to early life stages of fish.


Shame facets as predictors of problematic eating behaviors: An ecological momentary assessment study.
It is well-established that negative affect acts as predictor and maintenance factor of problematic eating behaviors. However, the relevance of different facets of negative affect is unclear. While guilt was consistently shown as having a relevant contribution in relation with problematic eating patterns, shame might play a similar role. The current study used an ecological momentary assessment design to assess associations between facets of shame and subsequent disturbed eating behaviors. The study included 57 females with high levels of eating disorders (ED) symptomatology who completed five surveys per day for 14 consecutive days. Participants completed measures of facets of shame (i.e., general shame, body shame, shame around eating), negative affect and problematic eating behaviors (i.e., binge eating, restriction, weighting, body checking, purging, taking laxative/diuretics and excessive exercise). Data were analyzed using multilevel models. In general, between-subjects facets of shame were associated with more disturbed eating behaviors, with shame explaining a significantly and clinically relevant percent of the variance of these problematic eating behaviors. At the within-subject level, facets of shame predicted subsequent binge eating, body checking and excessive exercise. These findings support the role of shame in ED symptomatology and the relevance of directly tackling shame in psychological treatments.


6-[6-(Pyridin-2-yl)-1,2,4,5-tetra-zin-3-yl]pyridin-3-amine monohydrate.
The packing of the title compound, C12H9N7·H2O, is dominated by hydrogen bonding and π-stacking. Layers parallel to [010] are established by hydrogen bonds involving all amine donor functions and one of the water donor functions, while the remaining water donor function enables the stacking of the layers along [10-1], which is accompanied by π-stacking. In the molecule, the plane of the central tetra-zine ring forms angles of 5.33 (7) and 19.84 (8)° with the adjacent 3-amine-pyridine and pyridine rings, respectively.


Detection of macular changes by optical coherence tomography after inferior oblique muscle surgery.
To detect macular changes after inferior oblique muscle myectomy and anterior transposition by the use of 3-dimensional optical coherence tomography (OCT). Patients who received surgery for correction of horizontal strabismus and weakening of inferior oblique muscle overaction were included. OCT was performed shortly before surgery and again 1 day, 1 week, and 1 month postoperatively. A total of 23 eyes of 16 patients were included. OCT showed no significant macular changes after inferior oblique myectomy or anterior transposition. We documented no harmful effects on the macula after manipulation of the inferior oblique muscle during standard weakening procedures.


A corneal elastic dynamic model derived from Scheimpflug imaging technology.
To simultaneously extract the corneal Young's modulus and the damping ratio from Scheimpflug imaging data. A spherical diaphragm model can better represent the geometry and physics of an eyeball than the popular mass-spring-damper model. This research derived the dynamic model of a water-filled spherical diaphragm based on the hydrodynamics and wave propagation theories. By applying modal analysis on the model, one can decouple the cornea vibration into individual modes and reconstruct the air puff vibration from the decoupled responses. By matching this response with the Scheimpflug imaging data from the Corvis(®) ST, it was then possible to extract multiple physiological properties as desired. The dynamic modal analysis was employed to extract the corneal physiological properties of 25 Taiwanese normal subjects. Specifically, the corneal Young's moduli and damping ratios were estimated. In fact the model is dependent on the physiological parameters such as cornea thickness, densities, and intraocular pressure. It is thus also possible to extract these parameters through multi-goal minimisation processes. The spherical diaphragm model was able to better describe the dynamic response of the eyeball. The model analysis also provides additional corneal physiological properties that were not available through other means.


Treatment options in early stages of Hodgkin's Lymphoma, high cure rate with lower short and long-term toxicity.
The definition of early stages in HL varied among cooperative groups and clinical trials. Most of them considered early stages; stage I, II, and IIIA without bulky disease. Bulky disease has been defined at the Costwolds Meeting as those tumors with more than 10 cm or a mediastinal involvement of more than one-third of the chest wall diameter. Other factors that have been considered unfavorable within the early stages are old age, high ESR, mixed cellularity or lymphocyte depleted histology, B symptoms or multiple sites of disease.


An Outstanding Role of Adipose Tissue in Canine Stem Cell Therapy.
Adipose tissue, previously known as connective tissue with a role in energy storage, is currently changing the course of treatments in veterinary medicine. Recent studies have revealed one particularly impressive function among all the newly discovered functions of adipose tissue. The interactive cells hosted by adipose tissue, the stromal vascular fraction (SVF), and their role in treating numerous diseases have provided a prospective course of research with positive outcomes in regenerative veterinary medicine (RVM). This review describes the main features of adipose tissue, emphasizing an eclectic combination of cells within the SVF and its thus far researched therapeutic possibilities in canine RVM. An afterwards focus is on a highly researched component of the SVF, adipose-derived mesenchymal stem cells (ASCs), which were shown to have an extraordinary impact relying on several proposed mechanisms of action on mitigating pathologies in canines. Furthermore, ASC therapy showed the most significant results in the orthopaedics field and in neurology, dermatology, ophthalmology, gastroenterology, and hepatology, which elevates the possibilities of ASC therapy to a whole new level. Therefore, this review article aims to raise awareness of the importance of research on cellular components, within abundant and easily accessible adipose tissue, in the direction of regenerative therapy in canines, considering the positive outcomes so far. Although the focus is on the positive aspects of cellular therapy in canines, the researchers should not forget the importance of identifying the potential negative aspects within published and upcoming research. Safe and standardized treatment represents a fundamental prerequisite for positively impacting the lives of canine patients.


Resensitizing multidrug-resistant Gram-negative bacteria to carbapenems and colistin using disulfiram.
The increasing incidence of bacterial infections caused by multidrug-resistant (MDR) Gram-negative bacteria has deepened the need for new effective treatments. Antibiotic adjuvant strategy is a more effective and economical approach to expand the lifespan of currently used antibiotics. Herein, we uncover that alcohol-abuse drug disulfiram (DSF) and derivatives thereof are potent antibiotic adjuvants, which dramatically potentiate the antibacterial activity of carbapenems and colistin against New Delhi metallo-β-lactamase (NDM)- and mobilized colistin resistance (MCR)-expressing Gram-negative pathogens, respectively. Mechanistic studies indicate that DSF improves meropenem efficacy by specifically inhibiting NDM activity. Moreover, the robust potentiation of DSF to colistin is due to its ability to exacerbate the membrane-damaging effects of colistin and disrupt bacterial metabolism. Notably, the passage and conjugation assays reveal that DSF minimizes the evolution and spread of meropenem and colistin resistance in clinical pathogens. Finally, their synergistic efficacy in animal models was evaluated and DSF-colistin/meropenem combination could effectively treat MDR bacterial infections in vivo. Taken together, our works demonstrate that DSF and its derivatives are versatile and potent colistin and carbapenems adjuvants, opening a new horizon for the treatment of difficult-to-treat infections.


Design of an institutional decision-making process: the case of urban water management.
Urban water infrastructure expenditures cause a major financial burden to municipalities. In the opinion of many policy-makers, public funds may alleviate this burden and facilitate environmental policies. However, practice has shown that despite ambitious policies, funding often follows traditional cost-dominated thinking. In Austria, national policy-makers were interested in new guidelines for funding that increase the transparency of the planning, ensure the adequate treatment of ecological problems, and foster stakeholder involvement, but keep the process as simple as possible, and require minimal changes of the current guidelines. An interdisciplinary project team conducted such a study. Its outcome was tested in two pilot projects. Based on these experiences, policy-makers finally implemented the recommended guidelines for the funding of communal urban water infrastructure projects. A general observation about the policy-making process was a conservative attitude of policy-makers. They prefer simple constraints (precautionary principle) and flexible negotiations (delegation) to complex assessment and decision-aid methodologies.


Bladder cancer risk in painters: a review of the epidemiological evidence, 1989-2004.
Epidemiological studies on the potential association between painting and the risk of bladder cancer published after the Monograph of the International Agency for Research on Cancer N. 47 of 1989 have been systematically reviewed. These included four cohort studies on the incidence of bladder cancer among painters, with a pooled relative risk (RR) of 1.10 (95% confidence interval, CI, 1.03-1.18), based on 893 cases observed. The corresponding summary RR from four cohort studies on mortality was 1.23 (95% CI 1.11-1.37), based on 370 deaths. The pooled RR from 14 case-control studies and a pooled-analysis of other 11 case-control studies was 1.35 (95% CI 1.19-1.53), based on 465 cases exposed. Overall, the RR from all epidemiological studies was 1.17 (95% 1.11-1.27). Thus, recent epidemiological evidence indicates a moderate excess risk for bladder cancer in painters. Some studies, however, suggested that any such risk would have been greater for exposures in the distant past. Open issues for interpretation include residual confounding by social class and tobacco smoking, and understanding the time-risk relation. In particular, the potential residual risk related to exposure over the last two to three decades remains to be defined.


Enhancement of the inositol 1,4,5-trisphosphate-releasable Ca2+ pool by GTP in permeabilized hepatocytes.
Permeabilized rat hepatocytes were used to study the effects of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and GTP on Ca2+ uptake and release by ATP-dependent intracellular Ca2+ storage pools. Under conditions where these Ca2+ pools were completely filled, maximal doses of Ins(1,4,5)P3 released only 25-30% of the sequestered Ca2+. The residual Ca2+ was freely releasable with the Ca2+ ionophore ionomycin. Addition of GTP in the absence of Ins(1,4,5)P3 did not cause Ca2+ release and had no effect on the steady-state level of Ca2+ accumulation by intracellular storage pools. However, after a 3-4-min treatment with GTP the size of the Ins(1,4,5)P3-releasable Ca2+ pool was increased by about 2-fold, with a proportional decrease in the residual Ca2+ available for release by ionomycin. In contrast to the situation with freshly permeabilized cells, permeabilized hepatocytes from which cytosolic components had been washed out exhibited direct Ca2+ release in response to GTP addition. The potentiation of Ins(1,4,5)P3-induced Ca2+ release by GTP in permeabilized hepatocytes was concentration-dependent with half-maximal effects at about 5 microM GTP. The dose response to Ins(1,4,5)P3 was not shifted by GTP; instead GTP increased the amount of Ca2+ released at all Ins(1,4,5)P3 concentrations. The effects of GTP were not mimicked by other nucleotides or nonhydrolyzable GTP analogues. In fact, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) inhibited the actions of GTP. However, this inhibition only occurred when GTP gamma S was added prior to GTP, suggesting that the GTP effect is not readily reversible once the cells have been permeabilized. Experiments using vanadate to inhibit the ATP-dependent Ca2+ uptake pump showed that Ins(1,4,5)P3 releases all of the Ca2+ within the Ins(1,4,5)P3-sensitive Ca2+ pool even in the absence of GTP. The increase of Ins(1,4,5)P3-induced Ca2+ release brought about by GTP was also unaffected by vanadate. It is concluded that GTP increases the proportion of the sequestered Ca2+ which is available for release by Ins(1,4,5)P3, either by unmasking latent Ins(1,4,5)P3-sensitive Ca2+ release sites or by allowing direct Ca2+ movement between Ins(1,4,5)P3-sensitive and Ins(1,4,5)P3-insensitive Ca2+ storage pools.


Intra-pancreatic Distal Bile Duct Carcinoma is Morphologically, Genetically, and Clinically Distinct from Pancreatic Ductal Adenocarcinoma.
Differentiating intra-pancreatic distal bile duct carcinoma invading the pancreas from pancreatic ductal adenocarcinomas (PDAC) surrounding the distal common bile duct (CBD) can be challenging. Our aim is to identify clinical, morphological, and genetic features characteristic of intra-pancreatic distal bile duct carcinoma. Clinicopathologic data of 550 patients undergoing a pancreaticoduodenectomy between September 1990 and May 2008 were reviewed. KRAS status was assessed with mass-spectrometric genotyping. Ninety-seven patients with intra-pancreatic adenocarcinomas surrounding the CBD were identified; slides were available for 80. Two relationships with the CBD were recognized as follows: type I (n = 42): cancer grew concentrically around the CBD and type II (n = 38): cancer grew asymmetrically around the CBD. Type I adenocarcinomas were associated with high-grade biliary dysplasia (45 vs. 13 %; p = 0.003); type II were associated with high-grade pancreatic intra-epithelial neoplasia (PanIN-2 or -3) (39 vs. 9 %; p = 0.003). Type I tumors had a better median survival (46 months) compared to type II (23 months) or other PDAC (20 months) (p < 0.001). Mutated KRAS was identified in 3/26 (11 %) type I and 20/21 (95 %) type II cancers (p < 0.001). There may be poorer survival in the presence of a KRAS mutation than wild-type KRAS (22.9 vs. 41.6 months; p = 0.3). Distal periductal adenocarcinomas fall into two distinct groups with biologic, morphologic and genetic differences. Those growing symmetrically around the CBD are more likely to be intra-pancreatic distal bile duct carcinomas and are associated with improved survival whereas cancers with asymmetric growth are more likely to have KRAS mutations and to be PDACs. These findings facilitate a more accurate histopathological diagnosis, which could improve patient selection for therapeutic trials.


Age differences in suprathreshold sensory function.
While there is general agreement that vision and audition decline with aging, observations for the somatosensory senses and taste are less clear. The purpose of this study was to assess age differences in multimodal sensory perception in healthy, community-dwelling participants. Participants (100 females and 78 males aged 20-89 years) judged the magnitudes of sensations associated with graded levels of thermal, tactile, and taste stimuli in separate testing sessions using a cross-modality matching (CMM) procedure. During each testing session, participants also rated words that describe magnitudes of percepts associated with differing-level sensory stimuli. The words provided contextual anchors for the sensory ratings, and the word-rating task served as a control for the CMM. The mean sensory ratings were used as dependent variables in a MANOVA for each sensory domain, with age and sex as between-subject variables. These analyses were repeated with the grand means for the word ratings as a covariate to control for the rating task. The results of this study suggest that there are modest age differences for somatosensory and taste domains. While the magnitudes of these differences are mediated somewhat by age differences in the rating task, differences in warm temperature, tactile, and salty taste persist.


COVID-19 vaccine coverage targets to inform reopening plans in a low incidence setting.
Since the emergence of SARS-CoV-2 in 2019 through to mid-2021, much of the Australian population lived in a COVID-19-free environment. This followed the broadly successful implementation of a strong suppression strategy, including international border closures. With the availability of COVID-19 vaccines in early 2021, the national government sought to transition from a state of minimal incidence and strong suppression activities to one of high vaccine coverage and reduced restrictions but with still-manageable transmission. This transition is articulated in the national 're-opening' plan released in July 2021. Here, we report on the dynamic modelling study that directly informed policies within the national re-opening plan including the identification of priority age groups for vaccination, target vaccine coverage thresholds and the anticipated requirements for continued public health measures-assuming circulation of the Delta SARS-CoV-2 variant. Our findings demonstrated that adult vaccine coverage needed to be at least 60% to minimize public health and clinical impacts following the establishment of community transmission. They also supported the need for continued application of test-trace-isolate-quarantine and social measures during the vaccine roll-out phase and beyond.


All Together Now: Health Care Mergers Reshape the Way Texas Physicians Practice.
Consolidation has touched just about every part of today's health care industry. Hospitals, medical practices, pharmacies, insurance companies are all merging in various ways - a trend epitomized by the 2018 announcement that hospital systems Baylor Scott & White Health in Dallas and Memorial Hermann in Houston planned to become one big nonprofit. The systems announced on Feb. 5 that they cancelled that merger.


Gender differences in managers' attitudes towards employees with depression: a cross-sectional study in Sweden.
Depression is prevalent among employees and a major reason for sickness absence. First-line managers' attitudes towards employees with depression might influence return to work and the scant literature indicates gender differences in attitudes. The objective of this study was to investigate gender differences in managers' attitudes to employees with depression. A cross-sectional study was conducted among 4737 Swedish managers in 2017 (response rate 71%, n = 3358). Attitudes towards depression were measured with the instrument "Managerial stigma towards employees with depression" (12 items). The response patterns of women and men, the level of stigma and the direction of the gender differences were investigated with independent t tests and binary logistic regression analyses with covariates. The likelihood of reporting high negative attitudes (score ≥ 36) was lower among women than men (odds ratio, 1.64; 95% confidence interval, 1.28-2.10) after adjusting for age, level of education, work sector, distribution of women and men among the staff, current workplace experience in management, lifetime experience in management, managerial position and presence of staff members at the current workplace who had depression and/or anxiety disorders. Based on these findings, a gender-sensitive approach is suggested for future interventions to improve managers' attitudes towards employees with depression and other mental disorders.