Iron biodistribution profile changes in the rat spleen after administration of high-fat diet or iron supplementation and the role of curcumin.
Curcumin as active metal chelating and antioxidant agent has a potential role in metal reduction and free radicals' neutralization in tissues. Of note, long-term administration of high fat diet (HFD) is considered as a main factor of blood serum iron deficiency. This study aimed to investigate the biodistribution profiles of iron in the spleen after long-term administration of HFD along with iron supplementation. Furthermore, the ameliorative role of curcumin to reduce iron accumulation level and improve the histological abnormalities produced by iron in spleen will be evaluated in the rats. Treated albino rats of this experiment were divided into six groups. Group I was a control group where group II was treated with HFD. Group III and group IV were treated with combination of HFD and curcumin or HFD and iron supplement respectively. Additionally, group V and group VI were treated with combination of HFD, iron supplement and curcumin or curcumin only respectively. Mainly histological analysis was used to investigate iron biodistribution and induced abnormalities in spleen under light microscope. The histochemical specific staining of iron in the spleen showed different biodistribution profiles of iron in the spleen. Administration of the HFD or HFD and iron supplementation increased the iron accumulation in the spleen. Where, curcumin administration with HFD (Group III) or with HFD and iron supplementation (Group V) significantly reduced the iron levels in the spleen. The splenic tissue inflammation, cellular apoptosis and fibrosis produced by higher iron accumulation was ameliorated after administration of curcumin supplementation as shown in the animals treated with HFD/curcumin (Group III) or HFD/iron supplement/curcumin (Group V). This study recommended that, it is preferable to use iron supplementation along with curcumin supplement for less than 4 months to avoid additional iron accumulation in the healthy organs.


[On the mechanism of evagination ofDrosophila imaginai discs culturedin vitro: Effects of substances affecting the cell membrane].
The mechanism of evagination of isolated imaginai discs has been studiedin vitro. Pro-, meso-, or metathoracic leg discs were obtained from late 3rd instarDrosophila larvae and cultured in the presence or absence of α-ecdysone and of various substances (cytochalasin B, concanavalin A, neuraminidase, trypsin) known to affect the cell membrane and morphogenetic movements in vertebrates.In the presence of cytochalasin B, evagination was reversibly inhibited. Cytochalasin B apparently does not act on intracellular microfilaments, which could not be detected in the disc cells. It does not prevent ecdysone from being fixed in the cells. It probably modifies the physico-chemical properties of the plasma membrane, precluding the change in cell shape which is required for evagination.In the presence of concanavalin A, which binds specifically to hydroxyl groups of D-mannopyranose or D-glucopyranose, evagination was irreversibly inhibited. The inhibitory effect could however be neutralized by the addition of α-methyl-D-glucopyranose in the medium or prevented by pre-treating the discs in a 0.1% trypsin solution for 2 min.In the presence of neuraminidase, discs evaginated normally under the influence of α-ecdysone; in a few cases, neuraminidase caused partial evagination in the absence of moulting hormone.After treatment by a 0.1% trypsin solution for 2 min, discs evaginated normally under the influence of the moulting hormone; whereas in the absence of ecdysone, evagination was never observed. In the latter case, evagination could however be obtained by a mechanical pull.When normal evagination was inhibited by one of the tested substances, cells did not secrete either a pupal or an imaginai cuticle and did not form any integumentary differentiations.It is concluded that change in cell shape during evagination is related to changes of the cell membrane. The alterations of the physico-chemical properties of the cell membrane, which are required for evagination, are probably caused, during normal development, by the moulting hormone.


The Safety of Tranexamic Acid in Total Joint Arthroplasty: A Direct Meta-Analysis.
Tranexamic acid (TXA) is effective in reducing blood loss in total joint arthroplasty (TJA), but concerns still remain regarding the drug's safety. The purpose of this direct meta-analysis was to evaluate and establish a basis for the safety recommendations of the combined clinical practice guidelines on the use of TXA in primary TJA. A search was completed for studies published before July 2017 on TXA in primary TJA. We performed qualitative and quantitative homogeneity testing and a direct comparison meta-analysis. We used the American Society of Anesthesiologists (ASA) score of 3 or greater as a proxy for patients at higher risk for complications in general and performed a meta-regression analysis to investigate the influence of comorbidity burden on the risk of arterial thromboembolic event and venous thromboembolic event (VTE). Topical, intravenous, and oral TXA were not associated with an increased risk of VTE after TJA. In addition, meta-regression demonstrated that TXA use in patients with an ASA status of 3 or greater was not associated with an increased risk of VTE after total knee arthroplasty. Although most studies included in our analysis excluded patients with a history of prior thromboembolic events, our findings support the lack of evidence of harm from TXA administration in patients undergoing TJA. Moderate evidence supports the safety of TXA in patients undergoing total knee arthroplasty with an ASA score of 3 or greater. The benefits of using TXA appear to outweigh the potential risks of thromboembolic events even in patients with a higher comorbidity.


Association between indocyanine green clearance test and ischemic type biliary lesions within one year after orthotopic liver transplantation.
Ischemic type biliary lesions (ITBLs), a particular subset of non-anastomotic biliary strictures (NAS), are characterized by intra and extrahepatic strictures that occur in the absence of either hepatic artery thrombosis or stenosis. When they occur within the first year after liver transplantation their development is mostly related to ischemia-reperfusion injury (IRI). The indocyanine green plasma disappearance rate (ICG-PDR) might be able to predict the probability of IRI-induced graft damage after liver transplantation. Our aim was to evaluate the association between ICG-PDR and the occurrence of ITBLs. Secondly, we searched for evidence of IRI in patients presenting ITBLs. This retrospective single-center observational study assessed a cohort of 60 liver transplant patients. Each patient underwent ICG-PDR on the 1st postoperative day. ITBLs were identified by means of either cholangiography or magnetic resonance imaging evidence of a deformity and narrowing of the biliary tree in the absence of hepatic artery thrombosis/stenosis. ITBLs were discovered in 10 patients out of 60 liver recipients (16.67%) within one year after transplantation. A low ICG-PDR value was found to be a significant predictive factor for ITBL development, with an OR of 0.87 and a 95% CI of 0.77-0.97. Liver biopsies were performed in 56 patients presenting unexplained abnormal liver function test results. A statistically significant association was found between the development of ITBLs and anatomopathological evidence of IRI. Retrospective, single-center study. The findings from this study show a relationship between low ICG-PDR values on first post-operative-day and the occurrence of ITBLs within 1 year after transplantation.


Protective effect of lycopene on oxidative stress and cognitive decline in rotenone induced model of Parkinson's disease.
Evidence from clinical and experimental studies indicate that oxidative stress is involved in pathogenesis of Parkinson's disease. The present study was designed to investigate the neuroprotective potential of lycopene on oxidative stress and neurobehavioral abnormalities in rotenone induced PD. Rats were treated with rotenone (3 mg/kg body weight, intraperitoneally) for 30 days. NADH dehydrogenase a marker of rotenone action was observed to be significantly inhibited (35%) in striatum of treated animals. However, lycopene administration (10 mg/kg, orally) to the rotenone treated animals for 30 days increased the activity by 39% when compared to rotenone treated animals. Rotenone administration increased the MDA levels (75.15%) in striatum, whereas, lycopene administration to rotenone treated animals decreased the levels by 24.33%. Along with this, significant decrease in GSH levels (42.69%) was observed in rotenone treated animals. Lycopene supplementation on the other hand, increased the levels of GSH by 75.35% when compared with rotenone treated group. The activity of SOD was inhibited by 69% in rotenone treated animals and on lycopene supplementation; the activity increased by 12% when compared to controls. This was accompanied by cognitive and motor deficits in rotenone administered animals, which were reversed on lycopene treatment. Lycopene treatment also prevented release of cytochrome c from mitochondria. Collectively, these observations suggest that lycopene supplementation along with rotenone for 30 days prevented rotenone-induced alterations in antioxidants along with the prevention of rotenone induced oxidative stress and neurobehavioral deficits. The results provide an evidence for beneficial effect of lycopene supplementation in rotenone-induced PD and suggest therapeutic potential in neurodegenerative diseases involving accentuated oxidative stress.


Assessing the impact of Social Networking Site use on older people's loneliness and social isolation. A randomized controlled trial: The Aging in a Networked Society-Social Experiment Study (ANS-SE).
An ageing society poses unprecedented challenges to societies. Information and Communication Technologies (ICTs), including Social Networking Sites (SNSs), may contribute to contrast loneliness and social isolation in old age. Despite of the potentialities of SNSs, there is only a handful of studies assessing the causal relationship of SNS use and older people's well-being. This paper aims to provide further evidence on the design of randomised controlled trials exploring the causal impact of SNS use on loneliness and social isolation in old age. The Aging in a Networked Society-Social Experiment Study (ANS-SE) is a randomised controlled trial conducted on people aged 75 and over residing in a town located in the Milan area (Italy) aiming to assess the impact of SNS use on loneliness and social isolation (i.e. the primary outcomes of this study). The study is constituted of two stages, i.e. the baseline and the follow up. The experiment is structured into one treatment group and two control groups; the interventions are the attendance to a course on SNS use (T1) and lifestyle education and brain functioning (C1). The inactive control group (C) is constituted of a waiting list. We will perform bivariate and regression analysis. The study has been approved by the Ethic Committee of the University of Milano Bicocca (prot. 431/2019) and was registered at Clinical Trials.gov (NCT04242628). Written consent was obtained from all respondents. Results from the study will be discussed with the local community and stakeholders, presented in national and international conferences and published in leading peer-review journals. The consent forms, the anonymised dataset, and the relevant statistical codes will be deposited with the Italian Unidata archive, also in charge of releasing the data to the public, upon a short embargo period.


A microcomputed tomographic study of canal isthmuses in the mesial root of mandibular first molars in a Chinese population.
Untreated isthmuses can be a cause of endodontic treatment failure. We investigated the anatomic features of the isthmus in the mesial root of mandibular first molars using microcomputed tomography scans. Thirty-six extracted mandibular first molars were collected from the Chinese population and divided into three age groups as follows: 20 to 39 years (group A), 40 to 59 years (group B), and > or = 60 years (group C). Each tooth was scanned and reconstructed, and then the prevalence and type of isthmus were recorded. The percentage of sections showing isthmuses for groups A, B, and C were 50%, 41%, and 24%, respectively. The chi-square test indicated a significant correlation of the distribution of isthmuses with age (p < 0.001). The ratio of partial isthmus to complete isthmus for group C (17.1:1) was significantly higher than group A (5.9:1) and group B (7.0:1) (p < 0.001). By understanding the configuration and location of isthmus, a more efficient endodontic microsurgery can be guaranteed.


In vitro susceptibility of characterized β-lactamase-producing Gram-negative bacteria isolated in Japan to ceftazidime-, ceftaroline-, and aztreonam-avibactam combinations.
Avibactam displays potent inhibition of extended-spectrum, AmpC, KPC and some OXA β-lactamases. We examined the combinations of avibactam with ceftazidime, ceftaroline and aztreonam by the broth microdilution method against Gram-negative bacteria harboring molecularly-characterized β-lactamase genes collected in Toho University, Japan. Bacterial isolates included: Ambler class A β-lactamase-producing Enterobacteriaceae (n = 26); class C β-lactamase-producing Enterobacteriaceae (n = 9) and class D β-lactamase-producing Acinetobacter baumannii (n = 9) and Enterobacteriaceae (n = 3). Ceftazidime-avibactam, ceftaroline-avibactam ands aztreonam-avibactam were active against the strains with an extended-spectrum β-lactamase (ESBL) or AmpC enzymes, but combination with avibactam did not reduce β-lactam MICs against A. baumannii with OXA β-lactamases including carbapenemases, such as OXA-40 and -69.


Implementation of optical associative memory by a computer-generated hologram with a novel thresholding scheme.
An associative memory based on a model by Rizvi and Zubairy [Appl. Opt. 33, 3642 (1994)] is experimentally demonstrated. The parallel optical interconnection is realized compactly by computer-generated holograms. A novel scheme of real-time thresholding is proposed and is proved to be effective and simple to implement. Stored images are successfully retrieved with both complete and partial inputs.


Evaluation of Duck Egg Hatching Characteristics with a Lightweight Multi-Target Detection Method.
Since it is difficult to accurately identify the fertilization and infertility status of multiple duck eggs on an incubation tray, and due to the lack of easy-to-deploy detection models, a novel lightweight detection architecture (LDA) based on the YOLOX-Tiny framework is proposed in this paper to identify sterile duck eggs with the aim of reducing model deployment requirements and improving detection accuracy. Specifically, the method acquires duck egg images through an acquisition device and augments the dataset using rotation, symmetry, and contrast enhancement methods. Then, the traditional convolution is replaced by a depth-wise separable convolution with a smaller number of parameters, while a new CSP structure and backbone network structure are used to reduce the number of parameters of the model. Finally, to improve the accuracy of the network, the method includes an attention mechanism after the backbone network and uses the cosine annealing algorithm in training. An experiment was conducted on 2111 duck eggs, and 6488 duck egg images were obtained after data augmentation. In the test set of 326 duck egg images, the mean average precision (mAP) of the method in this paper was 99.74%, which was better than the 94.92% of the YOLOX-Tiny network before improvement, and better than the reported prediction accuracy of 92.06%. The number of model parameters was only 1.93 M, which was better than the 5.03 M of the YOLOX-Tiny network. Further, by analyzing the concurrent detection of single 3 × 5, 5 × 7 and 7 × 9 grids, the algorithm achieved a single detection number of 7 × 9 = 63 eggs. The method proposed in this paper significantly improves the efficiency and detection accuracy of single-step detection of breeder duck eggs, reduces the network size, and provides a suitable method for identifying sterile duck eggs on hatching egg trays. Therefore, the method has good application prospects.


Antithrombotic Therapy After Transcatheter Aortic Valve Replacement.
Transcatheter aortic valve replacement (TAVR) is a treatment option for symptomatic patients with severe aortic stenosis who are candidates for a bioprosthesis across the entire spectrum of risk. However, TAVR carries a risk for thrombotic and bleeding events, underscoring the importance of defining the optimal adjuvant antithrombotic regimen. Antithrombotic considerations are convoluted by the fact that many patients undergoing TAVR are generally elderly and present with multiple comorbidities, including conditions that may require long-term oral anticoagulation (OAC) (eg, atrial fibrillation) and antiplatelet therapy (eg, coronary artery disease). After TAVR among patients without baseline indications for OAC, recent data suggest dual-antiplatelet therapy to be associated with an increased risk for bleeding events, particularly early postprocedure, compared with single-antiplatelet therapy with aspirin. Concerns surrounding the potential for thrombotic complications have raised the hypothesis of adjunctive use of OAC for patients with no baseline indications for anticoagulation. Although effective in modulating thrombus formation at the valve level, the bleeding hazard has shown to be unacceptably high, and the net benefit of combining antiplatelet and OAC therapy is unproven. For patients with indications for the use of long-term OAC, such as those with atrial fibrillation, the adjunctive use of antiplatelet therapy increases bleeding. Whether direct oral anticoagulant agents achieve better outcomes than vitamin K antagonists remains under investigation. Overall, single-antiplatelet therapy and OAC appear to be reasonable strategies in patients without and with indications for concurrent anticoagulation. The aim of the present review is to appraise the current published research and recommendations surrounding the management of antithrombotic therapy after TAVR, with perspectives on evolving paradigms and ongoing trials.


[Admission diagnosis contusion: etiology, epidemiology and cost-causing factors].
The admission of patients with minor injuries, such as contusions is a regular practice in acute care hospitals. The pathophysiological changes resulting from the accident are seldom the primary reason for hospitalization. The aim of this retrospective monocentric study was therefore to examine the etiology as well as the cost-causing factors and refinancing on admission. Patients were identified due to a retrospective query in the hospital information system (HIS) according to the ICD-10 German modification codes at discharge. A total of 117 patients were enrolled over a period of 2 years. The classification was carried out according to the accident mechanism and the division into age groups. In addition, the cost calculation was based on department and clinic-specific daily rates. In terms of etiology low impact falls in the domestic environment were the most common cause (48.7%), followed by high-energy trauma (22.8%). Within the group with domestic falls, the mean age was 77.8 years. This group also showed the longest length of stay (LOS) with 5.2 days. As part of the calculated costs, the group of domestic falls showed the highest costs of 2596.24 € with an average DRG cost revenue of 1464.51 €. The evaluation of the clinic internal data confirmed the subjective perception that the majority of patients admitted with the diagnosis of contusions came from the age group >65 years. Admission is primarily based on the increasing comorbidities and to avert secondary diseases and the consequences of immobilization. It could also be shown that the resulting costs are relevant to health economics and that the treatment does not appear to cover the costs.


Bovine major histocompatibility complex (BoLA) heterozygote advantage against the outcome of bovine leukemia virus infection.
Bovine leukemia virus (BLV) causes enzootic bovine leucosis. Host genetic heterozygosity at the major histocompatibility complex can enhance the ability to combat infectious diseases. However, heterozygote advantage is loci specific and depends on disease type. Bovine leukocyte antigen (BoLA)-DRB3 polymorphisms are related with BLV-infection outcome; however, whether BoLA-DRB3 heterozygotes have an advantage against BLV-induced lymphoma and proviral load (PVL) remains unclear. By analyzing 1567 BLV-infected individuals, we found that BoLA-DRB3 heterozygous status was significantly associated with lymphoma resistance irrespective of cattle breeds (p < 0.0001). Similarly, decreased PVL was observed in BoLA-DRB3 heterozygotes (p = 0.0407 for Holstein cows; p = 0.0889 for Japanese Black cattle). Our report provides first evidence of BoLA-DRB3 heterozygote advantage against BLV infection outcome.


Depletion of casein kinase II by antisense oligonucleotide prevents neuritogenesis in neuroblastoma cells.
Casein kinase II is a multifunctional protein kinase which has been implicated in the regulation of cell growth and differentiation. This enzyme is much more abundant in neurons than in any other cell type. The treatment of neuroblastoma cells with an antisense oligodeoxyribonucleotide which specifically results in the depletion of casein kinase II catalytic subunits blocks neuritogenesis. Accordingly, this enzyme may perform an essential role during neurite growth in developing neurons. Casein kinase II depletion induced by antisense oligodeoxyribonucleotide is accompanied by a site-specific dephosphorylation of microtubule-associated protein MAP1B (also referred to as MAP5, MAP1.X or MAP1.2), which is paralleled by a release of MAP1B from microtubules. We therefore propose that phosphorylation by casein kinase II may be required for the proper MAP1B functioning in the promotion of the assembly of microtubules which constitute the cytoskeletal scaffolding of growing axon-like neurites.


Should photographic triage become common practice?
Design Cross-sectional, exploratory study collecting photographic referral data over three months.Sample selection Paediatric referrals to the orthodontic and maxillofacial department at Alder Hey Hospital during the COVID-19 pandemic.Data analysis Photographic referrals were analysed using Microsoft Excel to determine treatment outcomes, including 'not to see', 'plan to see' and 'need to see'. Demographic information collected and analysed were patient age, gender, referral source and presenting complaint.Results In total, 220 photographic referrals were received, with swelling (30%) and dental trauma (27%) being the most common presenting complaints. Fifty-seven percent of the referrals were not seen, 23% were seen semi-urgently and 20% booked for outpatient review. Of those seen, seven children were examined elsewhere, with 44 receiving face-to-face consultations at Alder Hey Children's Hospital, with eight being admitted.Conclusions Photographic triage has potential to be a useful adjunctive assessment tool for new patient referrals, with secondary benefits for training junior staff and for populations who already find access to dental services challenging. Feasibility studies on the application should be seriously considered. However, the unique circumstances which resulted in the development of a photographic triage method need to be considered when generalising its use to normal working conditions.


Computation of AlO B2Σ+ → X2Σ+ emission spectra.
Application of molecular spectroscopy to analytical chemistry usually requires accurate description of the particular transition of interest. In this communication we describe the creation of a list of spectral lines. Following the introduction and definition of the line strength, we present a recipe for computation of diatomic-line-strengths, including the Hönl-London factor and electric dipole line strength for each spectral line. The diatomic eigenfunction is discussed including Hund's case basis functions. In our data tables we prefer use of Hund's case (a) basis, and we apply the usual Born-Oppenheimer approximation for the electronic-vibrational strengths. This allows us to generate the table of line strengths that we frequently apply for spectroscopic temperature determination. Using these line-strength tables, we present theoretical AlO emission spectra for the B-X system of AlO. These emission spectra are computed for temperatures of 3000 and 6000 K and for typical spectroscopic resolution used in laser-induced optical breakdown studies.


Burnout, depression, perceived stress, and self-efficacy in vascular surgery trainees.
Burnout is a work-related syndrome involving emotional exhaustion, depersonalization, and a sense of reduced personal accomplishment that has become prevalent in all levels of medical training. We sought to understand factors associated with burnout identified in vascular surgery trainees. An anonymous electronic survey consisting of demographic and programmatic information as well as validated scales for burnout, depression, perceived stress, self-efficacy, and social support was given to all vascular surgery trainees in the United States. Univariate and multivariate analyses were used to compare responses. Residents were grouped into quartiles based on burnout level, and predictors of burnout were determined. Of the 514 invitations sent, 177 (34%) respondents completed the survey. Trainees in the highest quartile of burnout were more likely to have moderate to severe depression (40% vs 4%; P < .01), higher perceived stress score (odds ratio [OR], 1.3; P < .01), lower social support (OR, 0.89; P < .01), and lower self-efficacy (OR, 0.76; P < .01), and they were less likely to reconsider vascular surgery as a career if given the chance to do it over (χ2 = 20; P < .01). Trainees without a self-identified mentor were significantly more likely to report burnout (χ2 = 15; P < .01). In addition, trainees who reported more frequent 80-hour work infractions each month (3.6 vs 2.3; P < .01) and those without access to programmatic social events (χ2 = 11; P < .01) had higher levels of burnout. In contrast, trainees with the lowest quartile of burnout scores reported lower depression (OR, 0.43; P < .01), lower stress (OR, 0.63; P < .01), more social support (OR, 0.1.2; P < .01), higher self-efficacy (OR, 1.2; P < .01), and fewer work week violations each month (2.3 vs 2.9; P = .04). Lower burnout scores were associated with program mentorship (χ2 = 7.3; P < .01), program-sponsored social events (χ2 = 8.7; P < .01), and being more likely to choose vascular surgery again if given the chance (χ2 = 6.3; P < .01). Highest burnout scores did not correlate with sex (χ2 < .01; P = 1), age (32 years vs 32 years; P = .65), marital status (χ2 < .01; P = 1), proximity to family (OR, 1.2; P = .26), alcohol consumption (χ2 = 0.23; P = .63), postgraduate year (OR, 1.1; P = .47), number of prior program graduates (OR, 0.95; P = .73), use of physician extenders in the program (OR, 0.93; P = .74), or total debt (OR, 1.0; P = .63). Similarly, there were no significant associations with these variables among trainees with the lowest quartile of burnout scores. On multivariate analysis, higher depression (OR, 1.6; P < .01) and higher perceived stress (OR, 1.2; P < .01) were associated with higher burnout scores, and lower burnout scores were associated with lower perceived stress (OR, 0.67; P < .01). Burnout in vascular surgery trainees is associated with higher levels of depression and perceived stress and lower levels of social support and self-efficacy. The addition of programmatic social events, limiting 80-hour work week violations, and addition of formal mentoring programs may decrease levels of burnout.


Neurobehavioral effects from acute exposures to methyl isobutyl ketone and methyl ethyl ketone.
Subjects were tested for neurobehavioral performance in an environmental chamber to detect the presence of subclinical central nervous system effects from 4-hr exposures to methyl isobutyl ketone (MIBK) at 100 ppm, methyl ethyl ketone (MEK) at 200 ppm, MIBK at 50 ppm with MEK at 100 ppm, or a placebo (i.e., a 5-min presentation of 25 ppm MEK-MIBK at each exposure period outset). Subjects were 68 males and 75 females recruited from local universities; ages ranged from 18 to 32 years. Ethanol by ingestion (95%-0.84 ml/kg) was used as a positive control. Five psychomotor tests (choice reaction time [CRT], simple reaction time [SRT], visual vigilance, dual task [auditory tone discrimination and tracking], memory scanning), one sensorimotor test (postural sway), and a test of mood (profile of mood states) were used to measure neurobehavioral effects. Additionally, chemical measurements (blood and breath) and reports of sensory and irritant effects were measured. The chemical exposures produced statistically significant performance effects on only 4 of 32 measures (% correct responses-visual vigilance, movement time-CRT, SRT, % incorrect responses-dual task). These effects, however, were not substantial and could not be attributed directly to the chemical exposures. Alcohol ingestion, however, produced significant decrements on every performance test except memory scanning and mood. An interaction occurred between gender and alcohol ingestion, such that more statistically significant performance decrements were found for females than for males. Significant odor sensations and irritant effects were reported by the subjects during the chemical exposures. The MEK results agree with earlier MEK experiments at comparable exposure conditions, and the MIBK results are consistent with a recent Swedish study that used MIBK exposures and showed no significant behavioral performance decrements from single MIBK exposures at 50 ppm with 50 W exercise. Additionally, the MIBK-MEK combination exposure showed no evidence of any interaction effects on either the behavioral or chemical measurements. The principal effects resulting from exposures to MEK and MIBK at the durations and concentrations used in the study are limited to sensory and irritant effects.


Partial Fundoplication is Effective Treatment for Female Patients with Gastroesophageal Reflux and Scleroderma: A Multicenter Comparative Cohort Study.
Patients with scleroderma often suffer from dysphagia and gastroesophageal reflux disease (GERD). Partial fundoplication is a validated anti-reflux procedure for GERD but may worsen dysphagia in scleroderma patients. Its utility in these patients is unknown. Here, we evaluate the efficacy and acceptability of partial fundoplication for the treatment of medically refractory GERD in patients with scleroderma. Analysis of a prospectively maintained database of patients who underwent fundoplication across 14 hospitals between 1991 and 2019. Perioperative outcomes, reintervention rates, heartburn, dysphagia, and patient satisfaction were assessed at 3 months, 1- and 3-years post-surgery. A total of 17 patients with scleroderma were propensity score matched to 526 non-scleroderma controls. All underwent a partial fundoplication. Perioperative outcomes including complication rate, length of stay, and need for reoperation were similar between the two groups. Compared to baseline, both groups reported significantly improved heartburn at 3 months, 1- and 3-years following partial fundoplication. Surgery was equally effective at controlling heartburn across all follow-up timepoints in patients with or without scleroderma. Dysphagia to solids was more common in patients with scleroderma than controls at 3-months post-surgery, but was not significantly different to controls at 1- and 3-year follow-up. Satisfaction scores were high and comparable between both groups across all postoperative timepoints, with 100% of patients with scleroderma reporting that their initial choice to undergo surgery was correct. Partial fundoplication controls reflux and is associated with a transient period of dysphagia to solids in patients with scleroderma. This approach is safe, effective and acceptable for patients with scleroderma and medically refractory GERD.


Successful resumption of trimethoprim-sulfamethoxazole after oral desensitisation in patients with chronic granulomatous disease.
Two patients with chronic granulomatous disease who had previously been intolerant to trimethoprim-sulfamethoxazole because of various adverse reactions completed a desensitisation protocol with a favourable clinical outcome.


Morphological and genetic identification of fungal genus/species in formalin-fixed, paraffin-embedded specimens obtained from patients with histologically proven fungal infection.
Although fungi are found relatively easily by microscopic examination of pathological samples, identification of fungal genus and species in pathological samples is not easy because the morphological features of fungi are similar among genera and species. A multiple real-time PCR was developed for identification of fungal genus/species, and morphological characterizations of fungi were analysed in pathological samples. Seventy-five formalin-fixed paraffin-embedded (FFPE) samples morphologically proven to contain any fungus were examined. A multiple real-time PCR system was developed to identify 25 fungal genus/species in pathological samples. Morphology of fungus in the specimens was re-reviewed retrospectively based on the results of real-time PCR. Real-time PCR identified fungal genus/species in 56 of 75 (74.6%) specimens with histologically proven fungal infection. In 53 specimens of filamentous fungi, Aspergillus spp. (22 specimens), Cladosporium (8), Scedosporium apiospermum (4), Malassezia sympodialis (1) and Candida albicans (1) were identified. Pseudohyphae of Candida were confused with filamentous fungus in a case. Morphological observation suggested differences in the presence of septated or non-septated hyphae, the filament size, and the branch angle among genus/species of filamentous fungi; however, genus/species was not able to be determined by their morphological features. In 22 specimens of yeasts, real-time PCR allowed for the identification of Candida albicans (12 specimens), Candida glabrata (2), Cladosporium (2), Scedosporium apiospermum (2), Pichia kudriavzevii (1) and Aspergillus sydowii (1). These data suggest that it is difficult to identify fungal genus/species by morphological features alone. Real-time PCR is useful to identify fungal genus/species in pathological samples.


Lattice model of resonant inelastic x-ray scattering in metals: relation of a strong core hole to the x-ray edge singularity.
We show how the classic approach of Nozières and di Domenicis for treating the edge singularity in x-ray absorption and emission can be generalized to treat the more complex case of the resonant inelastic x-ray scattering (RIXS) process, including effects of the intermediate states involved therein in the presence of the core hole. We solve our lattice model essentially exactly (numerically) to obtain a novel form of edge singularity at the RIXS threshold energy. Our RIXS spectrum naturally includes both the well and poorly screened spectral components and their dispersions and allows its separation into pair and multiple-pair excitations.


Food insecurity associated with elevated eating disorder symptoms, impairment, and eating disorder diagnoses in an American University student sample before and during the beginning of the COVID-19 pandemic.
This study tested the association between food insecurity and eating disorder (ED) pathology, including probable ED diagnosis, among two cohorts of university students before and during the beginning of the COVID-19 pandemic. Students (n = 579) from a large Midwestern American university completed self-report questionnaires assessing frequency of ED behaviors, ED-related impairment, and individual food insecurity as measured by the Eating Disorder Diagnostic Scale 5, Clinical Impairment Assessment, and Radimer/Cornell, respectively. Chi-square tests and MANOVA with post-hoc corrections were conducted to compare demographic characteristics, ED pathology, and probable ED diagnosis prevalence between students with and without individual food insecurity. Partially supporting hypotheses, MANOVA indicated significantly greater frequency of objective binge eating, compensatory fasting, and ED-related impairment for students with food insecurity compared with individuals without food insecurity. Chi-squared tests showed higher prevalence of ED diagnoses among individuals with food insecurity compared with those without food security (47.6 vs. 31.1%, respectively, p < .01, NNT = 6.06), specifically bulimia nervosa and other specified feeding and eating disorder. There were no differences in food insecurity before or during the beginning of the COVID-19 pandemic. Consistent with prior literature, food insecurity was associated with elevated ED psychopathology in this sample. Findings emphasize the importance of proper ED screening for college students vulnerable to food insecurity and EDs.


Brucella Peritonitis in a Patient on Peritoneal Dialysis: Case Report and Literature Review.
Peritonitis is the most common complication in patients undergoing peritoneal dialysis (PD). Peritoneal dialysis-related peritonitis caused by Brucella species has been reported in only 7 patients before. Here, we report a further case of Brucella peritonitis. This patient was successfully treated with both intraperitoneal and prolonged oral antibiotics, without removal of the PD catheter. We review relevant literature and make recommendations for the diagnosis and treatment of Brucella PD-related peritonitis from the cumulative published clinical experience.


Substrate recognition by the 2 micron circle site-specific recombinase: effect of mutations within the symmetry elements of the minimal substrate.
The minimal substrate for the 2 microns circle site-specific recombinase FLP consists of a nearly perfect 13-base-pair dyad symmetry with an 8-base-pair core. By using a series of chemically synthesized FLP substrates in in vitro FLP recombination and FLP-binding assays, we have identified four positions within each of the symmetry elements that are important contact points for the FLP protein. Furthermore, the binding and recombination data provide evidence for cooperativity between the two symmetry elements of a substrate and between the symmetry elements of two partner substrates during FLP recombination.


Review of the Poecilimon (Poecilimon) zonatus species group and description of new species from Turkey with data on bioacoustics and morphology (Orthoptera: Phaneropterinae).
The aim of this study is to conduct a detailed taxonomic revision of the Poecilimon (Poecilimon) zonatus species-group (Orthoptera: Phaneropterinae) using both morphology and bioacoustics. Two new species (Poecilimon (Poecilimon) salmani, P. (P) azizsancar) and one new subspecies (P. (P) zonatus datca) are described. Based on the data, we conclude that the species complex can be separated into two subgroups (P. tauricola and P. zonatus). Within the P. zonatus subgroup, song structures indicate P. variicercis as basal branch since producing two syllable types is possibly a derived character. From both, from bioacoustics and morphology, it is concluded that the relationships between species of the group are as follows: P. tauricola subgroup (P. tauricola + P. azizsancar) + P. zonatus subgroup (P. variicercis + (P. varicornis + (P. zonatus zonatus+P. zonatus datca)) + (P. salmani+P. vodnensis)))). Except for two species (P. vodnensis and P. varicornis), the other species of the group are all distributed in Anatolia. P. vodnensis is known only from Macedonia, whereas, P. varicornis has been recorded only from Syria and Lebanon. We assume that the group originated from an Anatolian ancestral stock and expanded its distribution to the Balkans through Taurus Way and Dardanelles. Other ancestral populations may have also spread in the north-south directions through the appropriate steppe corridors in the Anatolian Diagonal Mountains and in its vicinity.


Food and alcohol disturbance among young adults during the COVID-19 lockdown in Italy: risk and protective factors.
The COVID-19 lockdown measures have had a significant impact on risk behaviors as alcohol use and disordered eating. However, little is known about a serious health-risk-behavior named "food and alcohol disturbance" (FAD), characterized by engaging in dysfunctional eating on days of planned alcohol consumption. The aim of the present study was to investigate potential factors that may have put young adults at risk or protected against FAD during the COVID-19 lockdown. A sample of 447 young adults (280 females, 167 males; range 18-26) completed an online survey during the country's nationwide lockdown composed of self-reported measures assessing FAD behaviors, alcohol consumption, compensatory behaviors, eating and weight concerns, social support, emotion regulation strategies, and living arrangement. Our findings showed that FAD was significantly and positively correlated to alcohol consumption, use of laxatives, self-induced vomiting, eating and weight concerns, and expressive suppression, and negatively correlated to social support and living with family. Hierarchical regression analysis revealed that alcohol consumption, eating concern, and expression suppression positively predicted FAD, while social support and living with family were negative predictors. Our results suggest that during the COVID-19 lockdown, preoccupation with eating and the use of expressive suppression may have increased vulnerability to FAD; conversely, perceived social support and living with family may have been a source of protection against this dysfunctional behavior. Level V, descriptive study.


A multiprofessional education programme for patients with inflammatory bowel disease: a randomized controlled trial.
Health-related quality of life is impaired in patients with inflammatory bowel disease and improved disease-related information can improve this situation. The aims of this study were to create an education programme that could be readily applicable at the clinic and would be suitable for newly diagnosed patients with inflammatory bowel disease, and to investigate whether the programme could improve their health-related quality of life. Ninety-three patients with inflammatory bowel disease in remission were included and randomized to an intervention group or a control group. The intervention group attended a multiprofessional education programme while the control group received regular information. Four questionnaires were used for measuring health-related quality of life. Both groups completed the questionnaires at baseline and after 6 months. The intervention group also completed the questionnaires after 1 month. No significant differences were found when comparing the two groups at 6 months. However, the multi-professional education programme was highly appreciated by the patients. In the present study no improvement could be seen in health-related quality of life in patients with inflammatory bowel disease after participating in an education programme in comparison with the control group. This might be due to the fact that the questionnaires were not sensitive enough or that some patients were not in clinical remission. The patients' enthusiasm for the multiprofessional education programme has led to its being part of the regular care at the clinic.


Additional slides from residual ThinPrep Pap tests: Of potential diagnostic benefit in equivocal cases?
The aim of this study was to further evaluate the diagnostic significance of additional slides prepared from residual ThinPrep (TP) Pap Tests. Up to 10 repeat slides were prepared from 105 residual TP cervical samples. All additional slides were evaluated for the presence of diagnostic elements which were not found on the primary TP slide. After the evaluation of the repeat slides, an upgraded diagnosis was noted in 15 cases (14.3%). The reclassified cases included: three negative cases reclassified as two ASC-US and as one LSIL, seven cases of ASC-US reclassified as six LSIL and as one HSIL, and five cases of LSIL reclassified as HSIL. The highest rate (7/15 cases, 46.7%) of cases with an upgraded diagnosis was noted in the ASC-US diagnostic category. Our results suggest that repeat processing of residual TP cervical samples may represent an adjunctive diagnostic tool for a more accurate classification of ASC-US cases. Nevertheless, the practical value of this approach seems to be limited by its significant cost and its uncertain effectiveness.


Chronic opioid use following anterior cervical discectomy and fusion surgery for degenerative cervical pathology.
Although prescribing opioid medication on a limited basis for postoperative pain control is common practice, few studies have focused on chronic opioid use following anterior cervical discectomy and fusion (ACDF). To determine the prevalence of and risk factors for chronic opioid use following one and two-level ACDF for degenerative cervical pathology. Retrospective cohort. Using an insurance claims database, we identified patients aged 18-64 who underwent one or two-level primary ACDF from 2010 to 2015 for degenerative cervical pathology. Opioid prescription strength at various timepoints pre- and postoperatively and development of chronic postoperative opioid use. Prescription opioid use was examined during the following periods: 90 days before 7 days preceding surgery (preoperative), 6 days preceding surgery to 90 days following surgery (perioperative) and from 91 to 365 days following surgery (postoperative). The primary outcome was chronic postoperative opioid use, defined as ≥120 days' supply of opioid prescriptions filled or ≥10 opioid prescriptions between 3 and 12 months postoperatively. Secondary outcomes were high-dose (>90 morphine milligram equivalents [MME]/day) and very high-dose (>200 MME/day) opioid prescriptions. A multivariate logistic model (area under the ROC curve 0.75, p<.001) was built to predict long-term opioid use. Among 28,813 patients who underwent ACDF, most were female (55%) and underwent single-level ACDF (68%), with mean age of 50±8.0 years. Fifty-two percent of patients filled an opioid prescription in the preoperative period, 95% of patients filled a prescription in the perioperative period, and 39% of patients filled a prescription in the postoperative period. High-dose and very high-dose opioid prescriptions in the perioperative period were identified in 45% and 24% of patients, respectively, whereas 17% met criteria for chronic postoperative opioid use. The odds of chronic opioid use were highest in the Western US (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.3, 1.6). Duration of opioids prescribed was also highest in the Western US (median 111 days, interquartile range 11-336), p<.001. Factors associated with the highest risk for chronic opioid use were preoperative opioid use (OR 5.7, 95% CI 5.3, 56.2), drug abuse (OR 3.5, 95% CI 2.6, 4.5), depression (OR 1.7, 95% CI 1.6, 1.9), anxiety (OR 1.5, 95% CI 1.4, 1.6), and surgery in the western region of the United States (OR 1.5, 95% CI 1.3, 1.6). Patients undergoing ACDF commonly receive high-dose opioid prescriptions after surgery, and certain patient factors increase risk for chronic opioid use following ACDF. Intervention focusing on patients with these factors is essential to reduce long-term use of prescription opioids and postoperative care.


On the dynamics of the human endocrine pancreas and potential consequences for the development of type 1 diabetes.
Little is known about the human islet life span, and beta-cell neogenesis is generally considered rare in adults. However, based on available data on beta-cell proliferation, calculations can be made suggesting that the dynamics of the endocrine pancreas is considerable even during adulthood, with islet neogenesis and a sustained increase in size of already formed islets. Islet-associated hemorrhages, frequently observed in most mammals including humans, could account for a considerable loss of islet parenchyma balancing the constant beta-cell proliferation. Notably, in subjects with type 1 diabetes, periductal accumulation of leukocytes and fibrosis is frequently observed, findings that are likely to negatively affect islet neogenesis from endocrine progenitor cells present in the periductal area. Impaired neogenesis would disrupt the balance, result in loss of islet mass, and eventually lead to beta-cell deficiency and compromised glucose metabolism, with increased islet workload and blood perfusion of remaining islets. These changes would impose initiation of a vicious circle further increasing the frequency of vascular events and hemorrhages within remaining islets until the patient eventually loses all beta-cells and becomes c-peptide negative.


Occurrence of microplastics and phthalate esters in urban runoff: A focus on the Persian Gulf coastline.
Urban runoff seems an obvious pathway for the transfer of microplastics (MPs) and phthalate acid esters (PAEs) from land-based sources to the marine environment; an issue that still lacks attention. This study presents the first results on MP and PAE levels in the urban runoff into the northern part of the Persian Gulf during the dry season. Average concentrations of MPs and PAEs in the urban runoff of eight selected sampling sites (N = 72) along the Bushehr coast were 1.86 items/L and 53.57 μg/L, respectively. MPs with a size range of 500-1000 μm had the highest abundance, and the mean levels of PAEs in MPs were 99.77 μg/g. The results of this study show that urban runoff is a main source of MP and PAE contaminants that are discharged into the Persian Gulf. Therefore, to decrease these pollutants from entering the aquatic environment, decision-makers in the area should consider this problem and stop the direct discharging of urban runoff into water bodies.


Plasminogen and plasmin activity in patients with coronary artery disease.
While coronary artery disease (CAD) is associated with disturbances of the plasma fibrinolytic system, the nature of these disturbances is not fully defined. Fibrinolysis is regulated by plasmin, whose production is mediated by plasminogen activator conversion of plasminogen (Plg) to plasmin. The cascade is modulated by feedback loops that include Plg activator inhibitor 1 (PAI-1). Molecular interactions with Plg kringle domains play an important role in regulating plasmin production and its modulation of fibrinolysis. We hypothesized that interactions of tissue plasminogen activator (tPA) with Plg kringle domains regulates plasmin levels in patients with stable CAD. Plasma was collected from patients (n = 33) with an angiographically significant CAD and controls (n = 18) with angiographically established normal or minimally diseased arteries. Plasmin activity, tPA activity, and plasma levels of Plg, PAI-1, uPA, and tPA were determined. CAD patients had 1.7-fold greater plasmin activity (P = 0.02) that correlated with 1.5-fold higher tPA activity when compared to controls. Epitope mapping of Plg domains showed Plg differences in epitope exposure between the two groups. Plasma from CAD patients had 50% less (P < 0.001) detectable kringle 4 and 48% less (P = 0.007) detectable kringles 1-3. Based on detectable differences in Plg, we conclude that in patients with stable CAD, Plg complexed with tPA exists in a conformation that enables increased tPA activity and Plg conversion to plasmin.


Regulation of bovine IL-12R beta 2 subunit mRNA expression in bovine lymph node cells.
The beta 2 subunit of the interleukin (IL)-12 receptor (IL-12R beta 2) has been shown to play an essential role in differentiation of T helper 1 (Th1) cells in the murine and human system, and antibodies raised against IL-12R beta 2 recognized this molecule on human Th1 but not Th2 cells. However, while the cytokines secreted by clones of murine cells allowed the definition of distinct T helper cell subsets, bovine clones with polarized Th1 and Th2 cytokine profiles were rarely found. This raised important questions about the regulation of immune responses in cattle. We therefore cloned bovine IL-12R beta2 (boIL-12R beta 2) DNA complementary to RNA (cDNA) from the start codon to the 3' end of the mRNA. Comparison of boIL-12R beta 2 cDNA with human and murine IL-12R beta 2 cDNA sequences revealed homologies of 85 and 78%, respectively. The deduced protein sequence showed the hallmark motifs of the cytokine receptor superfamily including the four conserved cysteine residues, the WSXWS motif and fibronectin domains in the extracellular part as well as a STAT4 binding site in the intracellular part of the molecule. Using real-time reverse transcription-polymerase chain reaction, upregulation of mRNA expression of this molecule could be demonstrated in cultured bovine lymph node cells stimulated with phytohemagglutinin. Furthermore, cells with upregulated boIL-12R beta 2 mRNA responded with enhanced expression of interferon gamma to treatment with interleukin 12.


An association between human papillomavirus 16/18 deoxyribonucleic acid in peripheral blood with p16 protein expression in neoplastic cervical lesions.
Human papillomavirus (HPV) infection plays a crucial role in cervical carcinogenesis. Apart from the detection of p16 protein in cervical tissues, the feasibility of the presence of HPV DNA in peripheral blood being an auxiliary marker of cervical lesions was examined. Peripheral blood samples and cervical tissues, from 36 cervical tissues from high-grade squamous intraepithelial lesions (HSIL) and 31 early invasive cervical cancers (EICC), were analyzed for HPV 16/18 DNA and HPV 16/18 E7 mRNA expression, as well as the in situ expressions of p16 and pRb to investigate the in-between associations. The prevalence of HPV 16/18 DNA in patients with EICC was relatively higher than those of HSIL, in both of cervical tissues and peripheral blood. The presence of HPV 16/18 DNA in peripheral blood was positively correlated with that in cervical tissue, as well as with p16 overexpression in cervical tissues together with a significant correlation between E7 mRNA and pRb and p16 protein expressions. A positive correlation between the presence of HPV 16 or 18 DNA in peripheral blood and p16 overexpression in tissues of patients with cervical lesions was confirmed. Together with p16 immunostaining in cervical tissues, the detection of high-risk HPV 16 or 18 DNA in peripheral blood may act as an auxiliary biomarker for HPV-associated neoplastic cervical lesions.


Sphaerotilus natans isolated from activated sludge and its production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate).
Sphaerotilus natans is a sheathed bacterium existing in the activated sludge of wastewater treatment plants. It is one of the filamentous bacteria causing the bulking and foaming difficulties of activated sludge. Isolating the strain and culturing it in an axenic environment could not only provide the metabolic knowledge of the strains that would be useful in the development of wastewater treatment methods, but also could enable us to gain an understanding of the mechanism by which poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (poly[3-HB-co-3-HV]) is produced by this strain. This article reports the screening and isolation of the strain from the activated sludge using the Nile blue staining method together with Fourier transform infrared analysis. We investigated the ability of the selected strain to produce poly(3-HB-co-3-HV) copolymer using glucose and peptone, or by adding valeric acid or sodium propionate as precursor. Proper precursor feeding could dramatically enhance its 3HV content in the copolymer P(3HB-co-3HV). By controlling the different feeding times in fed-batch fermentation, different desired copolymers were obtained with 15, 40, and 70% 3HV mole fraction of the copolymer. Polymer properties were analyzed by gas chromatography, differential scanning calorimetry, thermo-gravimetry, and nuclear magnetic resonance analysis.


[Sleep and pain: a bi-directional relation?].
This review gives an overview about the consequences of sleep deprivation (SD) on pain perception and discusses the bi-directional relation between sleep and pain. A MEDLINE research (16.7.2010) for the terms "sleep" AND "pain" AND ("sleep deprivation" OR "sleep loss" OR "sleep restriction" OR "sleep interruption") showed 177 hits. Only studies with control group or cross-over design that investigated sleep deprivation (total or partial form) as independent and pain as dependent variable were included. 7 studies fulfilled the inclusion criteria. SD leads in 5 of 6 studies to an increase of bodily complaints measured by self rating tests and a decrease of pain inhibition. 3 of 5 studies show a decrease of mechanical or thermal pain threshold after SD. Not only can pain lead to sleep disruption, but SD can also reduce pain threshold. Sleep and pain might be mutually related, by shared neurotransmitter pathways. A further explanation is an influence of SD on opioid protein synthesis and / or opioid receptors. So when chronic pain and sleep disorder coexist, both conditions should be treated.


Electrical Impedance Dermography Differentiates Squamous Cell Carcinoma In Situ from Inflamed Seborrheic Keratoses.
There are no currently available low-cost, noninvasive methods for discerning the depth of squamous cell carcinoma (SCC) invasion or distinguishing SCC from its benign mimics, such as inflamed seborrheic keratosis (SK). We studied 35 subjects with subsequently confirmed SCC or SK. Subjects underwent electrical impedance dermography measurements at six frequencies to assess the electrical properties of the lesion. Averaged greatest intrasession reproducibility values were 0.630 for invasive SCC at 128 kHz, 0.444 for SCC in situ at 16 kHz, and 0.460 for SK at 128 kHz. Electrical impedance dermography modeling revealed significant differences between SCC and inflamed SK in normal skin (P < 0.001) and also between invasive SCC and SCC in situ (P < 0.001), invasive SCC and inflamed SK (P < 0.001), and SCC in situ and inflamed SK (P < 0.001). A diagnostic algorithm classified SCC in situ from inflamed SK with an accuracy of 0.958, a sensitivity of 94.6%, and a specificity of 96.9%; it also classified SCC in situ from normal skin with an accuracy of 0.796, a sensitivity of 90.2%, and a specificity of 51.2%. This study provides preliminary data and a methodology that can be used in future studies to further advance the value of electrical impedance dermography and inform biopsy decision making in patients with lesions suspicious of SCC.


Sizing Milking Groups in Small Cow Dairies of Mediterranean Countries.
A dairy farmer chooses the number of milking groups in function of the herd size, stall type and milking system also in small cow dairies (number of animals lower than 100-120). In these dairies, there are different milking systems (bucket, trolley, pipeline, little autotandem, herringbone or parallel parlors) and each of them has a different work routine. The knowledge of the routine is the starting point for assessing the milking installation, because it determines the number of milked cows per hour. Different milking systems have common tasks (as pre-dipping, inspecting foremilk, udder preparation, attaching teat cups, post-dipping), but in the meantime there are different operations that characterize each specific routine (e.g., animal entry and exit if there is a parlor, bucket, trolley or milking group positioning if tie-stall). For this reason, we surveyed twenty small dairy farms located in the Piedmont Region (Italy) with different milking systems to correctly acquire the specific milking routines. Different models were therefore studied using the observed routines in in the examined farms. These models were then used to calculate the number of milked cows per hour and the number of milking groups. The main findings were simple equations, specific for each milking system, easily accessible by the farmer to correctly size his milking system.


Management of Salivary Gland Injury.
Although a rare sequala of soft tissue injury, salivary gland trauma may result in significant morbidity. Salivary gland injury can involve the major as well as the minor glands. Because of the proximity of adjacent vital structures, a thorough history and physical examination are mandatory during patient evaluation. Trauma to the major salivary glands may involve the parenchyma, duct, or neural injury. Treatment requires adherence to primary principles of soft tissue management. Ductal and neural injury should be repaired primarily. Sialocele and fistula are potential complications of repaired and unrepaired salivary gland injury.


Mischievous malakoplakia: A potential pitfall of mpMRI of the prostate?
Interpretation of multiparametric magnetic resonance imaging (mpMRI) for prostate cancer diagnosis and staging can be challenging and, in some cases, benign prostate disease can mimic locally advanced malignancy. We present the case of a 57 year-old male with biopsy-proven Gleason 3 + 4 prostate cancer and a preoperative mpMRI showing extraprostatic extension who was later found to have infiltrating malakoplakia on final surgical pathology. This case highlights the importance of recognizing that malakoplakia of the prostate can present as a PI-RADS 5 lesion with extracapsular extension on mpMRI. Such cases can result in wide-excision, non-nerve sparing radical prostatectomies that may be unwarranted.


The organization of room geometry and object layout geometry in human memory.
Research with humans and with nonhuman species has suggested a special role of room geometry in spatial memory functioning. In two experiments, participants learned the configuration of a room with four corners, along with the configuration of four objects within the room, while standing in a fixed position at the room's periphery. The configurations were either rectangular (Experiment 1) or irregular (Experiment 2). Room geometry was not recalled better than object layout geometry, and memories for both configurations were orientation dependent. These results suggest that room geometry and object layout geometry are represented similarly in human memory, at least in situations that promote long-term learning of object locations. There were also some differences between corners and objects in orientation dependence, suggesting that the two sources of information are represented in similar but separate spatial reference systems. [corrected]


Characterization of an Escherichia coli lysA insertion targeted mutant using phenotype arrays.
The objective of this study was to investigate the effect of a lysine biosynthesis insertion mutation on the growth response and phenotype of Escherichia coli. The lysA gene encodes the last enzyme in the lysine biosynthetic pathway in most bacteria. This E. coli insertion mutant exhibited altered growth physiology and phenotype of the recipient E. coli. The constructed mutant could grow in the absence of lysine supplementation although the extent of growth after 7 h incubation in the presence of most lysine concentration was significantly (p<0.05) decreased compared to that observed with the parent E. coli strain. The mutant was also less able to utilize carbon and nitrogen substrates than the parent E. coli strain as determined by using phenotype arrays. These results suggest that the carbon and nitrogen phenotype profiles of E. coli when measured on phenotype arrays are altered after targeted insertion mutagenesis in the lysA gene. Creation of altered phenotypes may have potential for pharmaceutical and biotechnological applications of lysine E. coli metabolism.


BDD Knowledge, Attitude and Practice Among Aesthetic Plastic Surgeons Worldwide.
Body dysmorphic disorder (BDD) is a controversial topic in the field of plastic surgery. Our aim was to determine whether BDD knowledge, attitude and practice (KAP) are affected by the experience of the surgeon in the field, sex of the surgeon, country of practice, and the number of patients the surgeon sees annually. We were particularly interested in uncovering any significant relations in KAP of BDD between plastic surgeons practicing in developed versus developing countries. We created a two-page survey of 24 questions about the KAP of BDD. The survey was sent to aesthetic plastic surgeons worldwide via ISAPS global email list. The data were collected over a period of 20 days at the end of 2020. A total of 464 plastic surgeons completed the survey. The only factor that determines the awareness of BDD is the experience of the surgeon. The more experienced the surgeon is, the more likely he/she is to be familiar with the clinical picture of BDD. Although aware, the more experienced surgeons tend to dismiss the importance of referring BDD patients to psychiatrists/psychologists. Male surgeons tend to diagnose more patients with BDD than female surgeons. Surgeons who estimated the correct prevalence of BDD among patients seeking surgery acquired knowledge of BDD from scientific journals. The KAP is relatively similar between surgeons practicing in developed and developing countries, and the main statistically significant difference was in the questions used during the course of the interviews to diagnose BDD. We can deduce from the results that most aesthetic surgeons worldwide have got knowledge of the presentation of BDD and are keen to diagnose the disorder in their practice. It is worth noting that surgeons usually have their unique approach in the management of BDD. Our study highlights the importance of not only raising awareness of the best management of BDD, but also of establishing a consensus that BDD is a contraindication to aesthetic treatment. The best methods to raise awareness are through journals and plastic surgery residency. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .


Assay for Transposase-Accessible Chromatin Using Sequencing of Freshly Isolated Muscle Stem Cells.
Actively transcribed genes harbor cis-regulatory modules with comparatively low nucleosome occupancy and few high-order structures (="open chromatin"), whereas non-transcribed genes are characterized by high nucleosome density and extensive interactions between nucleosomes (="closed chromatin"), preventing transcription factor binding. Knowledge about chromatin accessibility is crucial to understand gene regulatory networks determining cellular decisions. Several techniques are available to map chromatin accessibility, among which the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) is one of the most popular. ATAC-seq is based on a straightforward and robust protocol but requires adjustments for different cell types. Here, we describe an optimized protocol for ATAC-seq of freshly isolated murine muscle stem cells. We provide details for the isolation of MuSC, tagmentation, library amplification, double-sided SPRI bead cleanup, and library quality assessment and give recommendations for sequencing parameters and downstream analysis. The protocol should facilitate generation of high-quality data sets of chromatin accessibility in MuSCs, even for newcomers to the field.


Gastric Proteins MUC5AC and TFF1 as Potential Diagnostic Markers of Colonic Sessile Serrated Adenomas/Polyps.
A subset of colon cancers originates from sessile serrated adenomas/polyps (SSA/Ps). Our goal was to identify markers for SSA/Ps that could aid in distinguishing them from hyperplastic polyps (HPs). We performed immunostaining for gastric proteins MUC5AC and TFF1 in formalin-fixed, paraffin-embedded (FFPE) samples of HPs (n = 47), SSA/Ps (n = 37), and normal colon (n = 30). Control mucosa expressed only trace amounts of MUC5AC and TFF1. HPs exhibited an 11.3- and 11.4-fold increase in MUC5AC and TFF1 expression confined to the upper segments of the crypts near the luminal surface of the polyps. SSA/Ps displayed on average 1.6-fold (MUC5AC, P < .008) and 1.4-fold (TFF1, P < .03) higher signal intensity for these markers than HPs, with a dramatic coexpression of MUC5AC and TFF1 typically occupying the entire length of the crypt. Immunoperoxidase results were similar to immunofluorescence staining for both MUC5AC and TFF1. Our results suggest that the analysis of expression of MUC5AC and TFF1 may be useful for differentiating SSA/Ps from HPs. We also suggest the possibility that crypt morphology may be at least partly due to overproduction of highly viscous gastric mucins and that these proteins may play a role in the serrated pathway to colon carcinogenesis.


Extremely and Very Preterm Deliveries in a Maternity Unit of Inappropriate Level: Analysis of Socio-Residential Factors.
To analyze the socio-residential factors associated with extremely and very preterm deliveries occurring in non-level 3 maternity units in France. This is a population-based observational retrospective study using national hospital data from 2012 to 2014. A generalized estimating equations regression model was used to study the characteristics of women who delivered very preterm and the socio-residential risk factors for not delivering in a level 3 maternity unit at 24-31+6d weeks of gestation. Among deliveries resulting in live births and without contraindication to in-utero transfer, we identified 9198 extremely or very preterm deliveries; 2122 (23.1%) of these were managed in a non-level 3 unit. Our study showed that young maternal age (women under 20 years at delivery) was associated with the risk of giving birth prematurely in a non-level 3 maternity, and particularly in a level 1 maternity unit (adjusted relative risk, 1.53; 95% CI 1.09-2.16). Living more than 30 minutes away from the closest level 3 unit increased the risk of delivering very preterm in a level 1 or 2 unit. Living in an urban area or urban periphery increased the risk of giving birth in a level 2 maternity unit (adjusted relative risk, 1.53; 95% CI 1.28-1.83 and 1.42; 95% CI 1.17-1.71, respectively). This study shows that young pregnant women living more than 30 minutes from a level 3 hospital have an increased risk of delivering in a maternity unit that is not equipped to deal with premature births. The risk also increases with an urban place of residence when the delivery occurs in a level 2 unit. A clearer understanding of the population at risk of delivering prematurely in a non-level 3 maternity could lead to improvements in structuring healthcare to encourage earlier management and better support.


Prevalence of metabolic syndrome among 40- and 50-year-old inhabitants of Wroclaw, Poland.
The metabolic syndrome (MetS) has been discussed for many years, but there is no doubt that those who have confirmed the presence of risk factors comprising the MetS had a higher risk of cardiovascular disease. The aim of this study was to evaluate the prevalence of MetS among 40- and 50-year-old (y.o.) inhabitants of Wroclaw, Poland. The study group included Wroclaw inhabitants who were recruited between 2001-2004 into the Cardiovascular Disease Prevention Programme. The study group consisted of 18,583 participants (females: 40 y.o.--5,248 and 50 y.o.--5,329; males: 40 y.o.--4,229 and 50 y.o.--3,777). The MetS was defined by IDF/NHLBI/AHA (2009) criteria. MetS was found in 12.7% of 40 y.o. and in 33.1% of 50 y.o. females, while in males, respectively, in 30.4% and 42.1%. Overall, MetS occurred in 28.5% of the study group. MetS occurred significantly more frequent among the older than the younger groups, both in females and males. MetS was found significantly more frequent among males than females from Wroclaw, in both 40- and in 50 y.o. participants. Among those females with MetS, the most frequently (more than 90% in both age groups) occurred excessive waist circumference (WC), followed by elevated blood pressure-BP (72.1% of 40 y.o., 86.8% of 50 y.o.). Excessive WC, elevated BP and triglycerides-TG was found in more than 80% of males aged 40 and with diagnosed MetS. Among the older group of males with MetS, the most frequently occurred elevated BP (90.4%), followed by excessive WC (87%) and elevated TG (78.5%). MetS was diagnosed more frequent in males than females of Wroclaw. Prevalence of MetS increased with age. The most significant impact on reducing the prevalence of MetS in the study group would be the lowering of BP and WC to recommended values.


A prospective evaluation of atherosclerotic risk factors and hypercoagulability in young adults with premature lower extremity atherosclerosis.
Fifty-one consecutive patients with premature lower extremity atherosclerosis were prospectively evaluated for atherogenic risk factors and primary or acquired hypercoagulability, which might contribute to early ischemia and revascularization failure. Laboratory tests included plasma assays of (1) natural anticoagulants (NAC), lipoprotein (a) (Lp[a]), and anticardiolipin antibodies, and (2) fibrinolytic activators and inhibitors at baseline and stimulated after 20 minutes of upper extremity venous occlusion. Forty-six (90%) of these 51 patients had laboratory abnormalities. One or more NAC deficiencies were found in 15 (30%) patients and included antithrombin III (n = 5), protein C (n = 8), protein S (n = 4), and heparin cofactor II (n = 2). Hypofibrinolysis was identified as a deficiency of stimulated tissue plasminogen activator in 22 (45%) patients and elevated plasminogen activator inhibitor-1 (PAI-1) in 29 (59%). Elevated Lp(a) was found in 43 (86%) patients. Five (10%) patients had anticardiolipin antibodies. Ten patients had combined NAC deficiency and hypofibrinolysis. Five (10%) patients had no abnormality. NAC deficiencies, especially protein C deficiency, were associated with acute ischemia (p < 0.01), prior vascular intervention (p < 0.01), an increasing number of total vascular procedures (p < 0.01), and major amputation (p < 0.01). PAI-1 was associated with a history of heart disease (p < 0.05) and prior vascular procedures (p < 0.05). Elevated Lp(a) was associated with elevated PAI-1 (p < 0.05). Retesting in 20 patients suggested that 80% of NAC deficiencies were acquired, but abnormalities persisted in 66% of patients with elevated PAI-1 and in 93% of those with elevated Lp(a). These data strongly support the hypothesis that the convergence of atherogenic risk factors and hypercoagulability play an important role in early ischemia and poor results reported for lower extremity vascular procedures in young adults.


West Nile virus activity--United States, November 9-16, 2004.
During November 9-16, a total of 31 cases of human West Nile virus (WNV) illness were reported from eight states (Arizona, Georgia, Maryland, Michigan, Missouri, New York, Pennsylvania, and Texas).


Investigation of relationships between collagens, elastin and proteoglycans in bovine thoracic aorta by immunofluorescence techniques.
Types I, III and V collagens and proteoglycan were localized in the aorta by indirect immunofluorescence techniques. Type I collagen was more prominent in media and adventitia than in intima while type III collagen predominated in intima and media but appeared less significant in adventitia. Type V collagen was observed in intima and media only and was seen surrounding smooth muscle cells. Type I collagen was located between elastic fibres but type III collagen appeared to envelop the fibres, suggesting an interaction between elastic fibres and type III collagen. Pretreatment of sections with testicular hyaluronidase caused no changes in staining for type I collagen, but adventitial areas showed increased staining for type III collagen. After digestion with chondroitinase ABC, intimal and medial areas showed increased staining for type III collagen. Therefore, type III collagen forms stronger interactions with proteoglycans and hyaluronic acid than does type I collagen and type III collagen in adventitia is largely masked by hyaluronic acid, while type III collagen in intima and media is associated with proteoglycan. Thus, type III collagen is a more significant component of adventitia than previously recognized. Proteoglycan was also partly localized along elastic fibres. It is, therefore, suggested that elastic fibres are coated with type III collagen, which itself is coated with proteoglycan.


Decoding cyclase-dependent assembly of hapalindole and fischerindole alkaloids.
The formation of C-C bonds in an enantioselective fashion to create complex polycyclic scaffolds in the hapalindole- and fischerindole- type alkaloids from Stigonematales cyanobacteria represents a compelling and urgent challenge in adapting microbial biosynthesis as a catalytic platform in drug development. Here we determine the biochemical basis for tri- and tetracyclic core formation in these secondary metabolites, involving a new class of cyclases that catalyze a complex cyclization cascade.


Large-scale identification of coevolution signals across homo-oligomeric protein interfaces by direct coupling analysis.
Proteins have evolved to perform diverse cellular functions, from serving as reaction catalysts to coordinating cellular propagation and development. Frequently, proteins do not exert their full potential as monomers but rather undergo concerted interactions as either homo-oligomers or with other proteins as hetero-oligomers. The experimental study of such protein complexes and interactions has been arduous. Theoretical structure prediction methods are an attractive alternative. Here, we investigate homo-oligomeric interfaces by tracing residue coevolution via the global statistical direct coupling analysis (DCA). DCA can accurately infer spatial adjacencies between residues. These adjacencies can be included as constraints in structure prediction techniques to predict high-resolution models. By taking advantage of the ongoing exponential growth of sequence databases, we go significantly beyond anecdotal cases of a few protein families and apply DCA to a systematic large-scale study of nearly 2,000 Pfam protein families with sufficient sequence information and structurally resolved homo-oligomeric interfaces. We find that large interfaces are commonly identified by DCA. We further demonstrate that DCA can differentiate between subfamilies with different binding modes within one large Pfam family. Sequence-derived contact information for the subfamilies proves sufficient to assemble accurate structural models of the diverse protein-oligomers. Thus, we provide an approach to investigate oligomerization for arbitrary protein families leading to structural models complementary to often-difficult experimental methods. Combined with ever more abundant sequential data, we anticipate that this study will be instrumental to allow the structural description of many heteroprotein complexes in the future.


Gastric cancer. Radiologic diagnosis.
The development and refinement of double-contrast barium techniques over the past two decades have dramatically improved the radiologist's ability to detect gastric cancer and characterize gastric ulcers. This article presents the radiologic findings of both early and advanced gastric cancer and offers guidelines for differentiating benign versus malignant gastric ulcers.


Clinical progress of sealed and unsealed caries. Part I: Depth changes and bacterial counts.
1. A method for measuring depth changes in carious lesions has been developed. 2. A method for estimating bacterial viability in the study lesions has been developed. 3. Sealed cavities showed little or no change in depth over a 1-year period. 4. Open lesions showed a significant increase in depth as compared to sealed lesions. 5. Elimination or marked decrease in viable organisms under the sealant occurred.


Acute administration of lithium carbonate interferes with suckling in neonatal rats.
These studies provide an animal model for the lithium-induced decrease in suckling reported in the clinical literature that allows for more precise determination of causal mechanisms. Nine-day-old rat pups were administered lithium carbonate via either intraperitoneal (IP) injections or intragastric (IG) gavage in doses approximating that which human infants might receive via breast milk. The pups were tested for their ability to locate and attach to the nipples of an anesthetized dam. Lithium significantly increased the pups' latency to attach to a nipple. Further tests of milk extraction using oxytocin-induced milk-letdowns indicate that lithium also interferes with milk withdrawal. Tests of motor and sensory deficits using an open-field and an olfactory choice test indicated that lithium did not similarly impair these behavioral facets of suckling. Alternative mechanisms for lithium-produced suppression of suckling are discussed.


Anterior uveitis in Kawasaki's disease.
Kawasaki's disease (mucocutaneous lymph node syndrome) is an acute febrile illness primarily affecting children. Slit-lamp examinations of six children with kawasaki's disease, ranging in age from 22 months to 16 years, showed that five had anterior uveitis during the acute phase of the illness. Two of the children were treated with corticosteroids and cycloplegic drugs and three received no treatment. In all five, the anterior uveitis resolved completely within a few weeks.


Retinal arterial occlusion in a child with factor V Leiden and thermolabile methylene tetrahydrofolate reductase mutations.
To analyze the potential cause of retinal arterial occlusion in a 9-year-old child. Case report. Antithrombin III, protein C, free protein S, activated protein C resistance, and antiphospholipid antibodies in plasma were determined. Determination of factor V R506Q (Leiden mutation), thermolabile methylene tetrahydrofolate reductase by polymerase chain reaction, and restriction enzyme analysis were performed. The patient was found to be heterozygous for factor V R506Q (Leiden mutation) and homozygous for thermolabile methylene tetrahydrofolate reductase. Coexistence of two mild hereditary thrombophilic states may result in severe thrombotic manifestations in young people.


Effect of HIV antibody testing and AIDS education on communication about HIV risk and sexual behavior. A randomized, controlled trial in college students.
To evaluate the effects of human immunodeficiency virus (HIV) antibody testing and education about HIV infection on communication about sexual risk behaviors for HIV transmission. Randomized, controlled trial with three arms. University student health center. Of 2196 heterosexual university students attending the student health clinic for medical care, 435 were interested in education about HIV and HIV testing and were randomly assigned to three groups. Follow-up at 6 months was done in 370 subjects (85%): 90 control subjects, 144 subjects who received education alone, and 136 subjects who received education plus HIV testing. Subjects who received HIV testing plus education questioned sexual partners about their HIV status more than subjects receiving education alone or those in the control group (56%, 42%, and 41% of subjects, respectively; P = 0.01). No consistent differences among groups in the number of sexual partners or in the use of condoms were found at follow-up. Heterosexual university students who received education about HIV infection plus HIV testing had increased communication with sexual partners about the risk for HIV infection after 6 months. Further reduction in risk behaviors for HIV transmission may require additional interventions in this population.


CT appearance of incidental pancreatic lipomas: a case series.
Pancreatic lipomas are rare benign lesions, with only 15 examples documented in the current literature. We describe five cases of intrapancreatic lipomas from a single institution, all incidentally found using computed tomography within a 14-month period. Computed tomography depicted lipomas as homogeneous, nonenhancing, well-marginated lesions with a density coefficient consistent with adipose tissue.


A simple sonochemical approach for synthesis of selenium nanostructures and investigation of its light harvesting application.
Selenium (Se) nanostructures were synthesized by a sonochemical method using SeCl₄ as a new precursor for Se nanostructures. Moreover, hydrazine, potassium borohydride, and thioglycolic acid were used as reducing reagents in aqueous solution. Ultrasonic power, irradiation time, reducing agent, solvent, HCl, NaOH, and the surfactant were changed in order to investigate the effect of preparation parameters on the morphology and particle size of selenium. The obtained Se with different morphologies and sizes was characterized by XRD, SEM, TEM, EDS, and DRS. The selenium nanostructures exhibited enhanced photocatalytic activity in the degradation of methylene blue (MB) under visible light irradiation. Furthermore, to examine the solar cell application of as-synthesized selenium nanostructure, FTO/TiO₂/Se/Pt-FTO and FTO/Se/CdS/Pt-FTO structures were created by deposited selenium film on top of the TiO₂ layer and FTO glass prepared by Doctor's blade method, respectively.


Zika Virus Update: More on an Emerging Arboviral Disease in the Western Hemisphere.
Zika virus has captivated the world with its quick spread throughout the Western Hemisphere. Increased emphasis has been placed on the infection of pregnant women and subsequent adverse and severe effects in the developing fetus and newborn. This article supplements a previous article and provides updated information on new and evolving evidence that strengthens the association between Zika virus and unique congenital and neurologic diseases, updates what is known about the epidemiology of the disease, and provides new and updated material for primary care providers as they counsel patients who may be exposed or infected. With the extent of disease spread, it is expected that Zika virus will become endemic to the Western Hemisphere and will change the public health parameters and approach in this area of the world. (Disaster Med Public Health Preparedness. 2017;11:163-167).


Safety assessment of intraparenchymal central nervous system biopsies: Single institution healthcare value review.
The study objective was to evaluate a single institution experience with adult stereotactic intracranial biopsies and review any projected cost savings as a result of bypassing intensive care unit (ICU) admission and limited routine head computed tomography (CT). The authors retrospectively reviewed all stereotactic intracranial biopsies performed at a single institution between February 2012 and March 2019. Primary data collection included ICU length of stay (LOS), hospital LOS, ICU interventions, need for reoperation, and CT use. Secondarily, location of lesion, postoperative hematoma, neurological deficit, pathology, and preoperative coagulopathy data were collected. There were 97 biopsy cases (63% male). Average age, ICU LOS, and total hospital stay were 58.9 years (range; 21-92 years), 2.3 days (range; 0-40 days), and 8.8 days (range 1-115 days), respectively. Seventy-five (75 of 97) patients received a postoperative head CT. No patients required medical or surgical intervention for complications related to biopsy. Eight patients required transfer from the ward to the ICU (none directly related to biopsy). Nine patients transferred directly to the ward postoperatively (none required transfer to ICU). Of the patients who did not receive CT or went directly to the ward, none had extended LOS or required transfer to ICU for neurosurgical concerns. Eliminating routine head CT and ICU admission translates to approximately $584,971 in direct cost savings in 89 cases without a postoperative ICU requirement. These practice changes would save patients' significant hospitalization costs, decrease healthcare expenditures, and allow for more appropriate hospital resource use.


Investigation of rat liver microsomal 6 beta-hydroxylation of 4-androstene-3,17-dione and 4-pregnene-3,20-dione using methodology which excludes steroid-3-imine induced introduction of the 6 beta-hydroxyl group.
To avoid artefactual 6 beta-hydroxylation of 3-oxo-4-ene steroids due to steroid-3-imine formation and rearrangement a combined extraction and liquid chromatography purification procedure for incubated rat liver microsomes has been worked out. With this procedure no nonenzymatic 6 beta-hydroxylation could be observed. Conventional termination of incubations with male rat liver microsomes (105,000 g sediments) and 4-14 C-labelled 4-androstene-3,17-dione (or progesterone) by solvent extraction and evaporation might lead to a 30% overestimation of the formation of 6 beta-hydroxy-derivatives at substrate saturation. Furthermore this work-up procedure produces 6-oxo-derivatives which were not observed when the new procedure was used. By elimination of the artefactual 6-oxygenation some properties of the male rat liver microsomal 4-androstene-3,17-dione 6 beta-hydroxylase have been studied, and the activity has been compared to the artefact produced by solvent extraction and evaporation. Using the combined extraction-liquid chromatography purification it was demonstrated that the microsomal 6 beta-hydroxylase active on 4-androstene-3,17-dione and progesterone was inhibited to 95% by carbon monoxide. This makes previous suggestions regarding participation of a non cytochrome P450-dependent 4-androstene-3,17-dione 6 beta-hydroxylase less likely.


Parthenium weed (Parthenium hysterophorus L.) and climate change: the effect of CO2 concentration, temperature, and water deficit on growth and reproduction of two biotypes.
Climate change will have a considerable impact upon the processes that moderate weed invasion, in particular to that of parthenium weed (Parthenium hysterophorus L.). This study evaluated the performance of two Australian biotypes of parthenium weed under a range of environmental conditions including soil moisture (100 and 50% of field capacity), atmospheric carbon dioxide (CO2) concentration (390 and 550 ppm), and temperature (35/20 and 30/15 °C/day/night). Measurements were taken upon growth, reproductive output, seed biology (fill, viability and dormancy) and soil seed longevity. Parthenium weed growth and seed output were significantly increased under the elevated CO2 concentration (550 ppm) and in the cooler (30/15 °C) and wetter (field capacity) conditions. However, elevated CO2 concentration could not promote growth or seed output when the plants were grown under the warmer (35/20 °C) and wetter conditions. Warm temperatures accelerated the growth of parthenium weed, producing plants with greater height biomass but with a shorter life span. Warm temperatures also affected the reproductive output by promoting both seed production and fill, and promoting seed longevity. Dryer soil conditions (50% of field capacity) also promoted the reproductive output, but did not retain high seed fill or promote seed longevity. Therefore, the rising temperatures, the increased atmospheric CO2 concentration and the longer periods of drought predicted under climate change scenarios are likely to substantially enhance the growth and reproductive output of these two Australian parthenium weed biotypes. This may facilitate the further invasion of this noxious weed in tropical and sub-tropical natural and agro-ecosystems.


[Logarithmo-normal distributions of relative and absolute values of human lymphocytes forming spontaneous rosettes in presence of sheep and mouse erythrocytes in normal adult].
The percentages and absolute numbers of peripheral blood lymphocytes forming rosettes with sheep and mouse red blood cells were established in 135 normal human beings. We found SRFC values almost similar to the proportion of so called "active" rosettes, whereas the values of MRFC were low. SRFC and MRFC values had a logarithmico-normal distribution. The absolute number of the two types of rosettes was decreased in the subjects more than 70 years old.


PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity.
Cerebral small vessel diseases (SVDs) are a central link between stroke and dementia-two comorbidities without specific treatments. Despite the emerging consensus that SVDs are initiated in the endothelium, the early mechanisms remain largely unknown. Deficits in on-demand delivery of blood to active brain regions (functional hyperemia) are early manifestations of the underlying pathogenesis. The capillary endothelial cell strong inward-rectifier K+ channel Kir2.1, which senses neuronal activity and initiates a propagating electrical signal that dilates upstream arterioles, is a cornerstone of functional hyperemia. Here, using a genetic SVD mouse model, we show that impaired functional hyperemia is caused by diminished Kir2.1 channel activity. We link Kir2.1 deactivation to depletion of phosphatidylinositol 4,5-bisphosphate (PIP2), a membrane phospholipid essential for Kir2.1 activity. Systemic injection of soluble PIP2 rapidly restored functional hyperemia in SVD mice, suggesting a possible strategy for rescuing functional hyperemia in brain disorders in which blood flow is disturbed.


Sonochemical synthesis and characterization of microrod to nanoparticle of new mixed-ligand zinc(II) fumarate metal-organic polymer.
Micro and nano-structures of a new mixed-ligand Zn(II) fumarate metal-organic polymer, {[Zn(tptz)(fum)].DMF}n (1), (tptz=2,4,6-tris(2-pyridyl)-s-triazine, fum=fumarate, DMF=N,N-dimethylforamide), were synthesized by sonochemical method. These new micro and nano-structures were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), IR spectroscopy and elemental analyses. Compound 1 was structurally characterized by single-crystal X-ray diffraction and consists of the primary unit of [Zn(tptz)(fum)]. Self assembly between the units of [Zn(tptz)(fum)] from Zn-O bonds results in the formation of a one-dimensional zinc(II) coordination polymer. The ZnII-ion in compound 1 has ZnO2N3 coordination sphere with a trigonal bipyramidal molecular geometry. Compound 1 was synthesized by ultrasound irradiation under different concentrations and times. The microrods structure of compound 1 with increasing of concentration and ultrasound radiation time were synthesized as nanoparticles structure successfully. So ultrasound radiation change morphology from microrods to nanoparticles.


DRAM-4 and DRAM-5 are compensatory regulators of autophagy and cell survival in nutrient-deprived conditions.
Macroautophagy is a membrane-trafficking process that delivers cytoplasmic material to lysosomes for degradation. The process preserves cellular integrity by removing damaged cellular constituents and can promote cell survival by providing substrates for energy production during hiatuses of nutrient availability. The process is also highly responsive to other forms of cellular stress. For example, DNA damage can induce autophagy and this involves up-regulation of the Damage-Regulated Autophagy Modulator-1 (DRAM-1) by the tumor suppressor p53. DRAM-1 belongs to an evolutionarily conserved protein family, which has five members in humans and we describe here the initial characterization of two members of this family, which we term DRAM-4 and DRAM-5 for DRAM-Related/Associated Member 4/5. We show that the genes encoding these proteins are not regulated by p53, but instead are induced by nutrient deprivation. Similar to other DRAM family proteins, however, DRAM-4 principally localizes to endosomes and DRAM-5 to the plasma membrane and both modulate autophagy flux when over-expressed. Deletion of DRAM-4 using CRISPR/Cas-9 also increased autophagy flux, but we found that DRAM-4 and DRAM-5 undergo compensatory regulation, such that deletion of DRAM-4 does not affect autophagy flux in the absence of DRAM-5. Similarly, deletion of DRAM-4 also promotes cell survival following growth of cells in the absence of amino acids, serum, or glucose, but this effect is also impacted by the absence of DRAM-5. In summary, DRAM-4 and DRAM-5 are nutrient-responsive members of the DRAM family that exhibit interconnected roles in the regulation of autophagy and cell survival under nutrient-deprived conditions.


Increased Use of Intra-Articular Steroid Injection to Treat Osteoarthritis is Associated With Chronic Opioid Dependence After Later Total Knee Arthroplasty But Not Total Hip Arthroplasty.
Intra-articular (IA) injections of corticosteroid (CO) and hyaluronic acid (HA) are commonly used for osteoarthritis. The efficacy of these interventions is controversial. Furthermore, research regarding the potential association of IA injection with later postoperative pain trajectories is lacking. We performed analysis on Truven Health MarketScan database (2012-2016) in total hip arthroplasty (THA) and total knee arthroplasty (TKA). Trends over time were assessed. Multivariable logistic regression analyses were executed to evaluate the impact of IA injections on postoperative chronic opioid use. Preoperative CO and HA injections decreased throughout the study period in both THA and TKA. Preoperative CO and HA injections, regardless of frequency, had no significant impact on the odds of THA patients becoming chronic opioid users postoperatively. TKA patients who had 1 CO injection in the year before surgery experienced lower odds of postoperative chronic opioid use (odds ratio [OR], 0.89; 95% confidence interval [95% CI], 0.82-0.97), whereas patients who had 2 or more CO injections experienced significantly greater odds (OR, 1.14; 95% CI, 1.04-1.24). TKA patients who received 2 or more HA injections before surgery had significantly lower odds of chronic opioid use (OR, 0.90; 95% CI, 0.81-0.99). The utilization of IA injections in patients with hip and knee osteoarthritis appears to be decreasing over time. TKA patients who received 2 or more preoperative CO injections experienced greater odds of chronic opioid utilization, whereas TKA patients with 2 or more HA injections in the year before surgery had decreased odds of chronic opioid use.