Immunocytochemical localization of the major glycoprotein of epididymal fluid from the cauda in the epithelium of the mouse epididymis.
The most abundant protein in fluid from the mouse cauda epididymidis, designated CP 27, is a glycoprotein that migrates at approximately 27000 daltons on SDS-polyacrylamide gels. Samples of CP 27 were isolated by preparative gel electrophoresis and were used to raise a guinea-pig polyclonal antiserum, which reacted with a single band on western blots of caudal epididymal fluid. This antiserum was used for immunocytochemical localization of CP 27 in histological sections of mouse epididymis using the peroxidase-antiperoxidase and protein A-gold methods. The most proximal staining with anti-CP 27 was in segment 6 of the distal caput epididymidis, where the lumen and a portion of the supranuclear cytoplasm of principal cells were stained. In contrast, in the distal corpus and cauda epididymidis (segments 8-11), there was pronounced staining of the luminal contents, sterocilia, and scattered cells identified as the "light" cells of the epididymal epithelium. Although CP 27 was found in the epididymal lumen of all segments distal to segment 6, the intensity of staining appeared to decline distally in the cauda epididymidis. Control sections exposed to pre-immune serum instead of anti-CP 27 showed no reaction. The results suggest that CP 27, the major glycoprotein of cauda epididymal fluid, is synthesized by principal cells of segment 6 of the distal caput epididymidis. CP 27 may be among the substances absorbed from the lumen by the light cells of the distal epididymis.


Comparison of fracture healing and long-term patient-reported functional outcome between dorsal and volar plating for AO C3-type distal radius fractures.
This study aimed to evaluate the differences in long-term functional outcome and radiographic fracture healing between volar and dorsally approached comminuted intra-articular distal radius fractures (DRF) (AO C3-type). A retrospective, age-matched, case-control study with a 1:2 allocation ratio was conducted in 84 patients C3-type DRFs patients who underwent either dorsal locking plating (DLP) group (n = 28) or volar locking plating (VLP) group (n = 56). Standardized wrist radiographs (posterior-anterior and 15° lateral) were assessed immediately postoperative and at final follow. To evaluate for loss of reduction standard radiographic measurements were performed. Fracture healing was assessed radiologically. Patient-reported outcomes were assessed with the patient-related wrist evaluation and the EQ-5D-3L for health-related quality of life. Patient satisfaction was assessed with the use of a numeric analog scale ranging from 0 (not satisfied) to 100 (very satisfied). All fractures united within 3 months postoperatively. Average age was 59 ± 12 years. Fifty-five patients (66%) participated in the follow-up survey at an average of 76.6 ± 23.8 months. DLP group showed a significant change in sagittal tilt compared with VLP group (3.4 ± 3.0° vs - 0.4 ± 4.1°, p < 0.001). No significant difference in other radiographic and long-term functional outcome was found between both groups (p > 0.05). Dorsal locking plating fixation in C3-type DRFs resulted in a minimal, but statistically significant, volar collapse of sagittal tilt compared with volar locking plating fixation. However, this difference in volar collapse did not significantly influence the long-term clinical outcome.


Diagnostic and prognostic value of carcinoembryonic antigen in pancreatic cancer: a systematic review and meta-analysis.
Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers and is increased in 30%-60% of patients with pancreatic cancer. Although carbohydrate antigen 19-9 (CA19-9) is the most important serum biomarker in pancreatic cancer, the diagnostic and prognostic value of CEA is gradually being recognized. The MEDLINE, EMBASE, and Web of Science databases were searched for related literature published until January 2017. Diagnostic accuracy variables were pooled using the Meta-Disc software. The pooled hazard ratios (HRs) for prognostic data were calculated and analyzed using Stata software. A total of 3,650 participants enrolled in 19 studies met our inclusion criteria. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of a CEA-based panel were 0.45 (95% confidence interval [CI], 0.41-0.50), 0.89 (95% CI, 0.86-0.91), 5.39 (95% CI, 3.16-9.18), and 0.55 (95% CI, 0.41-0.72), respectively. The area under the curve (AUC, 0.90) and Q-value (0.84) of the CEA-based panel indicated a significantly higher diagnostic accuracy compared with CEA or CA19-9 alone. Moreover, there was also a significant association between high levels of CEA and worse overall survival (HR, 1.43; 95% CI, 1.31-1.56). Our meta-analysis indicated that elevated serum CEA level, as a vital supplementary to CA19-9, can play an important role in the clinical diagnosis of pancreatic cancer patients and predict poor prognosis.


Physical and antimicrobial properties of anise oil loaded nanoemulsions on the survival of foodborne pathogens.
The purpose of this research was to investigate antimicrobial effects of nano emulsions of anise oil (AO) on the survival of common food borne pathogens, Listeria monocytogenes and Escherichia coli O157:H7. Series of emulsions containing different level of anise oil as potential antimicrobial delivery systems were prepared. Antimicrobial activities of bulk anise oil and its emulsions (coarse and nano) was tested by the minimum inhibitory concentration and time kill assay. Our results showed that bulk anise oil reduced the population of E. coli O157:H7 and L. monocytogenes by 1.48 and 0.47 log cfu/ml respectively after 6 h of contact time. However, under the same condition anise oil nanoemulsion (AO75) reduced E. coli O157:H7 and L. monocytogenes count by 2.51 and 1.64 log cfu/ml, respectively. Physicochemical and microbial analyses indicated that both nano and coarse emulsions of anise oil showed better and long-term physicochemical stability and antimicrobial activity compared to bulk anise oil.


Efficiency of Ontario primary care physicians across payment models: a stochastic frontier analysis.
The study examines the relationship between the primary care model that a physician belongs to and the efficiency of the primary care physician in Ontario, Canada. Survey data were collected from 183 self-selected physicians and linked to administrative databases to capture the provision of services to the patients served for the 12 month period ending June 30, 2013, and the characteristics of the patients at the beginning of the study period. Two stochastic frontier regression models were used to estimate efficiency scores and parameters for two separate outputs: the number of distinct patients seen and the number of visits. Because of missing data, only 165 physicians were included in the analyses. The average efficiency was 0.72 for both outputs with scores varying from 4 % to 93 % for the visits and 5 % to 94 % for the number of patients seen. We observed that there were both very low and very high efficiency scores within each model. These variations were larger than variations in average scores across models.


Clinical signs associated with Triple Antigen (DTP) vaccination in infants.
The perceived reactogenicity of pertussis-containing vaccines is of considerable public health importance. The purpose of this study was to establish prospectively the incidence of systemic and local clinical signs associated with the first three doses of the diphtheria-tetanus-pertussis vaccine (DTP) currently used in Australia. In addition, in order to determine whether variability in reporting of such phenomena might be associated with variation in DTP batches, infant behaviour was studied with three batches for the first of the three DTP vaccinations. Double blind, randomized controlled trial. There were 591 eligible infants who were recruited sequentially from centres for vaccination in three large Melbourne municipalities, of whom 531 (mean age 10 weeks, 45% female) were randomized and immunized. Of 181 subjects who received DTP from batch 1, 151 were studied at the time of their second DTP dose, and 98 at the third. Infants were assigned randomly to receive one of three batches of DTP vaccine. Parents were provided with a thermometer and a clinical sign diary. Research nurses visited the home 24 h after vaccination, and telephoned 7 days after vaccination to record local and systemic signs. There was no significant variation between DTP batches in rates of local or systemic signs. At the time of the first vaccination, the rates of local signs were: redness 16%, induration 29%, swelling 46%, and tenderness 54%. Systemic signs included: irritability 93%, intermittent inconsolable crying 43%, and persistent crying 12%. An axillary temperature of greater than 38 degrees C was recorded in 13% (CI 9-19%) of babies following the first immunization, 20% (CI 14-27%) following the second, and 14% (CI 8-23%) following the third immunization. There were significant reductions in the rates of observed signs over the immunization course for diarrhoea, irritability, intermittent inconsolable crying and persistent crying. There is little difference in the rates of clinical signs or presumed minor adverse effects associated with the DTP vaccine used in Australia today compared to that used 10 years ago, despite increases in the diphtheria and tetanus toxoid concentration, and the addition of aluminium phosphate adjuvant. Rates are comparable to those for other DTP vaccines manufactured in North America and Europe.


Novel compound from Trachyspermum ammi (Ajowan caraway) seeds with antibiofilm and antiadherence activities against Streptococcus mutans: a potential chemotherapeutic agent against dental caries.
The objective of this study was to isolate and characterize the active compound from Trachyspermum ammi seeds, exhibiting antibiofilm activity against Streptococcus mutans, a major causal organism of dental caries. Purification of the active compound from the seeds was performed by silica gel chromatography, and spectroscopic methods (FTIR, NMR and MS) were employed for its identification and structure determination. Antibiofilm and antiadherence activities of the active compound against S. mutans were analysed. Confocal microscopy was performed to visualize the effect of the compound on biofilm structure of S. mutans. Around 50% reduction was observed in adherence at 39·06 μg ml(-1) and in biofilm at 78·13 μg ml(-1) . It was found effective against adherent cells of S. mutans, reduced water-insoluble glucan synthesis and inhibited the reduction in pH. Confocal microscopy revealed scattered cells at sub-MIC concentration of the compound, resulting in distorted biofilm architecture in contrast to clustered cells seen in control. This study revealed a novel compound, a naphthalene derivative, isolated first time from T. ammi seeds with antibiofilm activity against S. mutans. Trachyspermum ammi represents an interesting source of a novel compound, (4aS, 5R, 8aS) 5, 8a-di-1-propyl-octahydronaphthalen-1-(2H)-one, with a great potential to be used as a therapeutic agent against dental caries.


Plant sex affects plant-microbiome assemblies of dioecious Populus cathayana trees under different soil nitrogen conditions.
Dioecious plants have coevolved with diverse plant microbiomes, which are crucial for the fitness and productivity of their host. Sexual dimorphism in morphology, physiology, or gene expression may relate to different microbial compositions that affect male and female fitness in different environments. However, sex-specific impacts on ecological processes that control the microbiome assembly are not well known. In this study, Populus cathayana males and females were planted in different nitrogen conditions. It was hypothesized that males and females differently affect bacterial and fungal communities in the rhizosphere soil, roots, old leaves, and young leaves. Physiological traits and transcriptome profiles of male and female plants were investigated to reveal potential mechanisms that control the microbiome assembly. Our results showed strong niche differentiation that shapes microbial communities leading to a rapid loss of diversity along a decreasing pH gradient from the rhizosphere soil to leaves. Sex had different impacts on the microbial assembly in each niche. Especially fungal endophytes showed great differences in the community structure, keystone species, and community complexity between P. cathayana males and females. For example, the fungal co-occurrence network was more complex and the alpha diversity was significantly higher in young female leaves compared to young male leaves. Transcriptome profiles revealed substantial differences in plant-pathogen interactions and physiological traits that clearly demonstrated divergent internal environments for endophytes inhabiting males and females. Starch and pH of young leaves significantly affected the abundance of Proteobacteria, while tannin and pH of roots showed significant effects on the abundance of Chloroflexi, Actinobacteria, and Proteobacteria, and on the bacterial Shannon diversity. Our results provided important knowledge for understanding sexual dimorphism that affects microbial assemblies, thus advancing our understanding of plant-microbiome interactions. Video Abstract.


Pyruvate carboxylase deficiency in yeast: a mutant affecting the interaction between the glyoxylate and Krebs cycles.
A single-gene nuclear mutant has been isolated in Saccharomyces cerevisiae which cannot grow on minimal medium supplemented with ethanol, acetate, pyruvate, aspartate, or oxaloacetate as sole carbon sources. It will grow on complete medium with these carbon sources, and on minimal medium with dextrose as carbon source. The only supplement which will permit growth on minimal medium with ethanol or pyruvate is aspartate, so the mutant is an aspartate auxotroph when grown on these nonfermentable substrates. It exhibits enhanced levels of phosphoenolpyruvate carboxykinase (EC 22.214.171.124) when grown on dextrose. The mutant can survive as an alcohol dehydrogenase-negative, indicating that the defect is not in the Krebs Cycle or in electron transport. When grown on pyruvate, it produces two to three times as much free alanine and half as much aspartate plus asparagine as the wild type. Two different assays show that the mutant phenotype is due to a deficiency of pyruvate carboxylase (EC 220.127.116.11), an important anaplerotic enzyme. Inferences that can be drawn from the characteristics of this mutant include (a) the glyoxylate cycle is probably located entirely outside the mitochondria, (b) the inner mitochondrial membrane appears to be impermeable to oxaloacetate, and (c) a succinate-malate exchange across the inner mitochondrial membrane connects the glyoxylate and Krebs cycles when yeast is grown on minimal medium with ethanol as a sole carbon source.


Piperacillin-induced magnesium and potassium loss in intensive care unit patients.
Broad spectrum penicillins such as piperacillin are used extensively in the intensive care unit (ICU) because of their wide bacterial spectrum and low level of toxicity. Although some cases of interstitial nephritis induced by piperacillin have been reported, this problem is thought to be rare. However, in view of the large number of other risk factors for renal disorders that are frequently present in ICU patients, we speculated that ICU patients might be more at risk for renal side effects. We therefore decided to measure serum electrolyte levels in patients before and after piperacillin administration. Prospective observational study. University teaching hospital. Forty-three consecutive patients with normal renal function treated with piperacillin; 40 patients treated with other antibiotics. Serum levels of magnesium (Mg), potassium (K) and, to a lesser degree, calcium (Ca) decreased significantly in patients treated with piperacillin, but not in patients treated with other antibiotics ( p<0.01). This decrease was especially pronounced in a subgroup of patients concurrently treated with furosemide. We conclude that treatment with piperacillin may cause or aggravate electrolyte disorders and tubular dysfunction in ICU patients even when serum creatinine levels remain normal.


Racial variance in rationale for HIV testing in community-based setting in the United States: evidence from the National Health Interview Survey.
HIV testing varies across racial/ethnic groups in the United States, but it is unclear whether the rationale for testing differs as well racially. The authors aimed to assess the rationale for HIV testing and the racial/ethnic variation therein. Using the National Health Interview Survey 2003 (n = 29 753), the authors examined the association between rationale for HIV testing and race. Chi-square statistic and multinomial logistic regression analyses were used to test for racial differences and the effect of race/ethnicity on the rationale for HIV testing. There was a statistically significant racial difference with respect to HIV testing rationale, chi(2) = (24, N = 10,481) = 808.9, P < .001. After adjustment for relevant covariates, compared with Caucasians, African Americans were 37% less likely to be tested due to exposure to sex/drugs, whereas Hispanics were not (prevalence risk ratio [PRR], 0.63, 95% confidence interval [CI] = 0.47-0.84, respectively). Likewise African Americans and Hispanics were less likely to be tested if they were sick or had a medical problem (PRR = 0.66, 95% CI = 0.44-0.99 and PRR = 0.65, 95% CI = 0.43-0.98). Substantial racial variation occurred in the reasons for being tested for HIV in the United States, indicative of the need to understand such rationale for effective HIV screening and testing.


The role of exercise training in the management of chronic kidney disease.
In this review, we summarize recent studies of exercise interventions in chronic kidney disease (CKD), potential benefits, discuss barriers to implementation and make practical recommendations for incorporating exercise training into the care of patients with CKD. Interventions targeting increased fitness and physical activity are effective and may have multiple potential benefits. Recommendations regarding physical activity advice have been incorporated into the recent update of the KDIGO CKD guidelines, which suggest that patients perform 30 min of moderate intensity exercise on most days of the week. Exercise as simple, popular and inexpensive as walking appears to be associated with significant health benefits. More vigorous exercise requires increased supervision but can be safely prescribed to patients with a broad range of comorbidities and may be associated with greater gains in health. Physical activity, cardiorespiratory fitness and muscle function are low in patients with CKD. A sedentary lifestyle has been associated with increased mortality, morbidity and the risk factors that drive progression of both kidney and cardiac disease. There is much to learn about the benefits of different modalities of exercise but the time has come to routinely prescribe exercise interventions as part of standard nephrological care.


Improving and maintaining oral health for people with special needs.
The number of people in the United States population with disabilities and other special needs is growing dramatically. These individuals present unique challenges for oral health professionals in planning and carrying out dental treatment and for the oral health delivery system. Because it has been recognized that the current delivery system is not working well for these populations, new workforce, financing, and delivery models are beginning to emerge that may hold promise for creating and maintaining oral health for currently underserved populations, including people with disabilities and other special needs. This article discusses the implications of this for the oral health profession, describes the challenges of providing oral health services for this population, and discusses the implications of these challenges for the organization of the oral health delivery system.


Endometrial Adenocarcinoma: Analysis of Circulating Tumour Cells by RT-qPCR.
Endometrial adenocarcinoma is a frequently occurring cancer in women, accounting for 42,000 deaths every year. Despite treatment with standard therapy, occurrence of remote metastases and local recurrences is high. Through help of RT-qPCR minimal residual disease could be detected and characterized, facilitating therapeutic decision making. A number of marker genes were first tested in model systems and genes that performed best, were consequently used for the examination of 13 blood samples from endometrial carcinoma patients. Cytokeratin 19 and MIG7 were chosen for the analysis in patient samples. Both genes were found up-regulated in small tumours and in one large tumour, but no statistical correlations could be revealed between expression levels of these two genes and tumour characteristics. There seems to be a coherence between gene expression and the stage of tumorigenesis, but the number of samples is still too small, to be able to obtain statistical significant differences.


Recombinant vaccinia viruses. Design, generation, and isolation.
The technologies of recombinant gene expression have greatly enhanced the structural and functional analyses of genetic elements and proteins. Vaccinia virus, a large double-stranded DNA virus and the prototypic and best characterized member of the poxvirus family, has been an instrumental tool among these technologies and the recombinant vaccinia virus system has been widely employed to express genes from eukaryotic, prokaryotic, and viral origins. Vaccinia virus is also the prototype live viral vaccine and serves as the basis for well established viral vectors which have been successfully evaluated as human and animal vaccines for infectious diseases and as anticancer vaccines in a variety of animal model systems. Vaccinia virus technology has also been instrumental in a number of unique applications, from the discovery of new viral receptors to the synthesis and assembly of other viruses in culture. Here we provide a simple and detailed outline of the processes involved in the generation of a typical recombinant vaccinia virus, along with an up to date review of relevant literature.


Association of Defects and Zinc in Hematite.
Zn is an essential micronutrient that is often limited in tropical, lateritic soils in part because it is sequestered in nominally refractory iron oxide phases. Stable phases such as goethite and hematite, however, can undergo reductive recrystallization without a phase change under circumneutral pH conditions and release metal impurities such as Zn into aqueous solutions. Further, the process appears to be driven by Fe vacancies. In this contribution, we used ab initio molecular dynamics informed extended X-ray absorption fine structure spectra to show that Zn incorporated in the structure of hematite is associated with coupled O-Fe and protonated Fe vacancies, providing a potential link between crystal chemistry and the bioavailability of Zn.


Chagas' disease: polyspecificity of antibodies against Trypanosoma cruzi acidic antigens.
The aim of this work was to study the reactivity of chagasic patient sera against a panel of natural antigens and its relationship with the immune response against T. cruzi acidic antigens. The presence of IgG and IgM antibodies reactive with myosin, myoglobin, actin and thyroglobulin was investigated in sera with positive serology for Chagas' disease classified into groups (G) I, n = 7, with normal electrocardiogram (ECG) and no signs or symptoms of the disease; GII, n = 7, with ECG abnormalities but without cardiomegaly and GIII, n = 7, with cardiomegaly and congestive heart failure. Healthy individual sera were analyzed in parallel as controls. In the three groups of chagasic patients, a high proportion of sera exhibited an enhancement of IgG response anti actin ranging from 71 to 100%. IgM against this antigen was found positive in GI, 21%; GII and GIII, 57%. The antibodies binding to myosin and myoglobin were mainly of IgM type. When myosin was assayed, the frequency of reactive sera was gradually diminished as heart involvement increased: GI 57%, GII 28% and GIII 14%. Only IgG antibodies against thyroglobulin were detected in the three groups of chagasic patients ranging from 43 to 86%. IgG natural antibodies showed to be polyreactive, since a diminished reactivity against each one of the natural antigens assayed and against T. cruzi acidic antigens (FIV) was observed in the sera absorbed with any of the selected antigens irrespective of the absorbing ones. Moreover, the antibodies against FIV parasite's antigens purified by immunoabsorption showed a similar reactivity with FIV, myosin and actin, and a slight lower reactivity with thyroglobulin. These results indicate that in chagasic patients, the specific humoral response against FIV is associated with an increase of the natural autoantibodies along with their polyspecificity.


Developmental regulation of a Plasmodium gene involves the generation of stage-specific 5' untranslated sequences.
The B7 gene of Plasmodium berghei, highly conserved within the genus Plasmodium, encodes a nuclear protein most likely involved in chromatin assembly. In this study we describe the transcription pattern of B7 during asexual multiplication and sexual differentiation of the parasites in the blood of the vertebrate host. Two alternative transcripts have been identified: one, 1.4 kb in length is specific for asexual blood stages; the other, 1.8 kb in length is specific for sexually differentiated cells (gametocytes). The processed mRNAs are identical in their coding region and differ only in their 5' untranslated regions (5' UTRs). We show here that the differences in 5' UTRs are the result of two mechanisms: (1) the use of alternative transcription initiation sites mapped at least 1.4 kb apart, which imply the existence of separate, stage-specific promoters; (2) the splicing of a 765 bp gametocyte-specific intron at the 5' UTR of the 1.8 kb transcript.


Origin for electrochemically driven phase transformation in the oxygen electrode for a solid oxide cell.
The next generation of fuel cells, electrolyzers, and batteries requires higher power, faster kinetics, and larger energy density, which necessitate the use of compositionally complex oxides to achieve multifunctionalities and activity. These compositionally complex oxides may change their phases and structures during an electrochemical process-a so-called "electrochemically driven phase transformation." The origin for such a phase change has remained obscure. The aim of this paper is to present an experimental study and a theoretical analysis of phase evolution in praseodymium nickelates. Nickelate-based electrodes show up to 60 times greater phase transformation during operation when compared with thermally annealed ones. Theoretical analysis suggests that the presence of a reduced oxygen partial pressure at the interface between the oxygen electrode and the electrolyte is the origin for the phase change in an oxygen electrode. Guided by the theory, the addition of the electronic conduction in the interface layer leads to the significant suppression of phase change while improving cell performance and performance stability.


Well-distributed 1T/2H MoS2 nanocrystals in the N-doped nanoporous carbon framework by direct pyrolysis.
Molybdenum disulfide (MoS2) has been a promising anode material in lithium-ion batteries (LIBs) because of its high theoretical capacity and large interlayer spacing. However, its intrinsic poor electrical conductivity and large volume changes during the lithiation/delithiation reactions limit its practical application. An efficient synthesis strategy was developed to prepare the MoS2 nanocrystals well-anchored into the N-doped nanoporous carbon framework to deal with these challenges by a confined reaction space in an acrylonitrile-based porous polymer during the carbonization process. The prepared hybrid material comprises small 1T/2H-MoS2 nanoparticles surrounded by a nanoporous carbon matrix. In addition to the highly crystalline nature of the synthesized MoS2, the low ID/IG of the Raman spectrum demonstrated the development of graphitic domains in the carbon support during low-temperature pyrolysis (700 °C). This novel three-dimensional (3D) hierarchical composite shows superior advantages, such as decreased diffusion lengths of lithium ions, preventing the agglomeration of MoS2 nanocrystals, and maintaining the whole structural stability. The prepared C/MoS2 hybrid demonstrated fast rate performance and satisfactory cycling stability as an anode material for LIBs.


Egg predation by copepods in Daphnia brood cavities.
Both field observations and enclosure experiments show that juvenile copepods enter Daphnia brood cavities to feed on Daphnia eggs and embryos. The ability to perform such in vivo exploitation is reported for both cyclopoid and calanoid copepods. Copepodites of Acanthocyclops robustus (G.O. Sars) were found to eat eggs in brood cavities of D. magna, D. pulex and D. pulicaria in experimental enclosures rich in algae. Copepodites of Eudiaptomus gracilus (G.O. Sars) were found in brood cavities of D. hyalina in a mesotrophic lake. The copepods' intrusions into brood cavities caused dramatic declines in the clutch size of infested Daphnia, and this predation effect could easily be confused with the effect of severe food limitation.


The association between comorbid anxiety disorders and the risk of stroke among patients with diabetes: An 11-year population-based retrospective cohort study.
Diabetes and anxiety disorders are independent risk factors for stroke. However, it remains unclear whether the risk of stroke is higher among diabetic patients with comorbid anxiety than without comorbid anxiety. Therefore, the purpose of this study was to investigate the association between comorbid anxiety and the risk of stroke among patients with diabetes. This is a retrospective cohort study. We used the National Health Insurance Research Database in Taiwan to identify a diabetes cohort with a new diagnosis of an anxiety disorder but without a history of stroke. The enrollment period was 2001-2006 with up to 11 years of follow-up data. Comorbid anxiety was defined by both a clinical diagnosis of the DSM-IV (ICD-9-CM) and prescriptions for anxiolytic medications. Propensity score matching was performed to balance the selected confounders between the anxiety-exposed group and anxiety non-exposed group. Cox-propositional hazard regression models were used to evaluate the association between comorbid anxiety and the risk of stroke. Among patients with diabetes (N=40,846), an estimated 5.8% (N=2374) of patients had comorbid anxiety disorders. Diabetic patients with comorbid anxiety were significantly associated with a higher risk of stroke compared to patients without comorbid anxiety (hazard ratio: 1.33, 95% confidence interval: 1.02-1.72). The severity of anxiety or diabetes could not be measured from the claims data. Residual confounding may still exist. A significantly elevated risk of stroke was observed in association with comorbid anxiety among patients with diabetes. Psychiatrists should consider routine screening for anxiety disorders to prevent a stroke event among patients with diabetes.


Plasma cells in the bronchoalveolar lavage fluid of a patient with eosinophilic pneumonia. Morphologic proof of local production of antibodies.
We describe a case of eosinophilic pneumonia in which plasma cells appeared in bronchoalveolar lavage fluid (BALF). A 49-year-old man presented with wheezing, lung infiltrates, peripheral eosinophilia, and extremely high IgE levels in serum and BALF. A differential count of BALF revealed 56.6 percent lymphocytes and 1.3 percent plasma cells. The appearance of plasma cells suggests local maturation of B cells and represents a morphologic proof of local production of immunoglobulins. The increased number of lymphocytes suggests their role in B cell differentiation via the lymphokine network.


Topological phase transitions and chiral inelastic transport induced by the squeezing of light.
There is enormous interest in engineering topological photonic systems. Despite intense activity, most works on topological photonic states (and more generally bosonic states) amount in the end to replicating a well-known fermionic single-particle Hamiltonian. Here we show how the squeezing of light can lead to the formation of qualitatively new kinds of topological states. Such states are characterized by non-trivial Chern numbers, and exhibit protected edge modes, which give rise to chiral elastic and inelastic photon transport. These topological bosonic states are not equivalent to their fermionic (topological superconductor) counterparts and, in addition, cannot be mapped by a local transformation onto topological states found in particle-conserving models. They thus represent a new type of topological system. We study this physics in detail in the case of a kagome lattice model, and discuss possible realizations using nonlinear photonic crystals or superconducting circuits.


Young females in the athletic arena.
There are factors that uniquely affect young females in sports. The sociologic aspects of female youth sports can be understood from a historical perspective. Athletics have an influence on the development of young girls, from gender identity and sexual orientation to the foundations of self-esteem and moral development. There is a relationship between certain psychopathologic conditions common in girls and athletics, including eating disorders, depression, and anxiety disorders. Although involvement in sports may engender some of these problems, others may be successfully treated through physical exercise.


Recent advances: osteoporosis in the "oldest old".
Osteoporosis and related fractures disproportionately impact patients with advanced age, those with the frailty phenotype, and those with multiple comorbidities. Recent studies report a changing incidence in fracture type among the oldest old throughout the world, a finding not satisfactorily explained by advances in treatment of lifestyle factors. A growing recognition of the importance of muscle and bone interaction is leading to improved understanding of the underlying biochemical pathways linking them and new therapeutic targets. New models of care for frail older populations, particularly after hip fracture, are being developed but have been challenged to identify appropriate outcomes to target. An appreciation for the relationship between age-related comorbidities, fracture risk, and competing mortality risk is essential for practitioners caring for the oldest-old population.


The association between family history of diabetes mellitus and offspring long-term neurological hospitalisation.
The aim of the present study was to determine whether being born to non-diabetic mother with a family history of diabetes mellitus (DM) is associated with higher rates of long-term neurological hospitalisations of the offspring. A retrospective analysis of all live births and paediatric hospitalisations at Soroka University Medical Center between 1991 and 2014 was performed. Family history of DM was collected from prepartum women using anamnesis. During the study period, 208 728 deliveries met the inclusion criteria, and of them 8.2% (n = 17 040) were of non-diabetic mothers with family history of DM. Rates of neurological hospitalisation with or without family history were analysed. Offspring born to non-diabetic mothers with family history of DM had higher rates of neurological hospitalisations. The cumulative incidence of long-term neurological hospitalisations was higher as compared with those without family history of DM (log-rank test P = .007). Neurological hospitalisations was higher by 13% in the study group, after controlling for confounders such as maternal age, maternal obesity, hypertensive disorders, birth weight and caesarean delivery. (adjusted odds ratio 1.13, 95% confidence interval 1.04-1.23). Being born to a non-diabetic mother with a family history of DM is independently associated with higher long-term neurological hospitalisations of the offspring.


Sugarcane scum as a novel substrate for rapid biogas production from the non-centrifugal cane sugar agribusiness sector in developing countries.
Sugarcane scum (SCS) is a waste from the non-centrifugal cane sugar making process. Due to its physicochemical characteristics, it has a high-energy potential to produce biomethane via anaerobic digestion (AD). However, (i) the total solids concentration in the SCS exceeds the limit for wet digestion and (ii) the SCS has a low pH. The aim of this research was to evaluate the utilization capacity of the SCS for methane production through a biochemical methane potential test and extent of disintegration, using dilution pretreatment. The highest methane yield, 0.227 N m3 CH4 kg-1 VS, was achieved at a 12.5% SCS dilution, with an organic matter removal greater than 70% and an extent of disintegration of 34.5%. This is evidence that the AD process is a feasible alternative for SCS treatment.


[Presurgical evaluation and surgical treatment of medically refractory epilepsy: a report of 162 cases].
To study presurgical evaluation and surgical treatment of medically refractory epilepsy. One hundred and sixty-two cases of refractory epilepsy were analysed by their clinical manifestation, neuroradiology and neuroelectrophysiology. Different operative techniques were performed to all the 162 cases according to those analyses. Total effective rate of the surgical treatment was 87.7% and most patients have better life than preoperation. Surgical treatment with accurate preoperative location of the epileptogenic zone and suitable operative techniques is an effective method in the treatment of refractory epilepsy.


Menace of antimicrobial resistance in LMICs: Current surveillance practices and control measures to tackle hostility.
Antimicrobial Resistance (AMR) is significant challenge humanity faces today, with many patients losing their lives every year due to AMR. It is more widespread and has shown a higher prevalence in low- and middle-income countries (LMICs) due to lack of awareness and other associated reasons. WHO has suggested some crucial guidelines and specific strategies such as antimicrobial stewardship programs taken at the institutional level to combat AMR. Creating awareness at the grassroots level can help to reduce the AMR and promote safe and effective use of antimicrobials. Control strategies in curbing AMR also comprise hygiene and sanitation as microbes travel from contaminated surroundings to the human body surface. As resistance to multiple drugs increases, vaccines can play a significant role in curbing the menace of AMR. This article summarizes the current surveillance practices and applied control measures to tackle the hostility in these countries with particular reference to the role of antimicrobial stewardship programs and the responsibilities of regulatory authorities in managing the situation.


Extended string-like binding of the phosphorylated HP1α N-terminal tail to the lysine 9-methylated histone H3 tail.
The chromodomain of HP1α binds directly to lysine 9-methylated histone H3 (H3K9me). This interaction is enhanced by phosphorylation of serine residues in the N-terminal tail of HP1α by unknown mechanism. Here we show that phosphorylation modulates flexibility of HP1α's N-terminal tail, which strengthens the interaction with H3. NMR analysis of HP1α's chromodomain with N-terminal tail reveals that phosphorylation does not change the overall tertiary structure, but apparently reduces the tail dynamics. Small angle X-ray scattering confirms that phosphorylation contributes to extending HP1α's N-terminal tail. Systematic analysis using deletion mutants and replica exchange molecular dynamics simulations indicate that the phosphorylated serines and following acidic segment behave like an extended string and dynamically bind to H3 basic residues; without phosphorylation, the most N-terminal basic segment of HP1α inhibits interaction of the acidic segment with H3. Thus, the dynamic string-like behavior of HP1α's N-terminal tail underlies the enhancement in H3 binding due to phosphorylation.


Gaze-evoked amaurosis.
Gaze-evoked amaurosis is a transient monocular loss of vision occurring in a particular direction of eccentric gaze. Six cases are reported with a mean follow-up of 5 years; three with optic nerve sheath meningiomas and three with orbital cavernous hemangiomas. Five of the six patients have had no visual deterioration during follow-up. Bilateral optic nerve sheath meningiomas led to visual deterioration in both eyes of one patient, but gaze-evoked amaurosis was present in only one eye. The symptom of gaze-evoked amaurosis, while alarming, is not predictive of permanent visual loss. Possible mechanisms for gaze-evoked amaurosis include inhibition of axonal impulses or transient optic nerve ischemia.


MicroRNA mediators of early life stress vulnerability to depression and suicidal behavior.
Childhood environment can have a profound impact on brain structure and function. Epigenetic mechanisms have been shown to play a critical role in adaptive and maladaptive processes by regulating gene expression without changing the genome. Over the past few years, early life stress (ELS) has been established as a major risk factor for major depression and suicidal behavior along with other psychiatric illnesses in adulthood. In recent years, the emergence of small noncoding RNAs as a mega controller of gene expression has gained attention for their role in various disease processes. Among various noncoding RNAs, microRNAs (miRNAs) are the most studied and well characterized and have emerged as a major regulator of neural plasticity and higher brain functioning. More recently, although limited in number, studies are focusing on how miRNAs can play a role in the maladaptive processes associated with ELS both at adolescent and adult age and whether these processes are critical in developing depression and suicidal behavior. In this review, we critically evaluate how postnatal ELS relates to abnormalities in miRNA expression and functions from both animal and human literature and draw connections from these findings to depression and suicidal behavior later in life.


Cardiovascular Magnetic Resonance of Myocardial Fibrosis, Edema, and Infiltrates in Heart Failure.
Cardiac magnetic resonance (CMR) imaging is a unique imaging modality, which provides accurate noninvasive tissue characterization. Various CMR sequences can be utilized to identify and quantify patterns of myocardial edema, fibrosis, and infiltrates, which are important determinants for diagnosis and prognostication of heart failure. This article describes available methods of tissue characterization imaging applied in CMR. The presence and patterns of abnormal tissue characterization are related to common etiologies of heart failure and the techniques employed to demonstrate this. CMR provides the opportunity to identify the etiology of heart failure based on the recognition of different patterns of myocardial abnormalities.


hsa_circ_0085539 Promotes Osteosarcoma Progression by Regulating miR-526b-5p and SERP1.
This study aimed to expand the competing endogenous RNA network in osteosarcoma (OS) involving hsa_circ_0085539 and its downstream target miR-526b-5p. The expression levels of circ_0085539, miR-526b-5p, and stress-associated endoplasmic reticulum protein 1 (SERP1) mRNA in OS tissues and cells were detected and analyzed by qRT-PCR. After that, the interrelationships between these three genetic materials were validated with a luciferase reporter assay system. The effect of the circ_0085539/miR-526b-5p/SERP1 axis on OS cell malignancy phenotypes was further assessed using in vitro assays, including cell counting kit-8 (CCK-8) assays, colony foci formation assays, wound-healing migration assays, and transwell invasion assays. To determine the function of circ_0085539 on OS tumor growth in vivo, a xenograft formation assay was performed. In OS tissues and cells, the expression of circ_0085539 and SERP1 was upregulated, while that of miR-526b-5p was downregulated. After experimental analyses, it was found that silencing circ_0085539 inhibited the aggression of OS in vivo and in vitro. Mechanistic investigations also revealed that circ_0085539 could sponge miR-526b-5p and that miR526b-5p could directly target SERP1. The cytological experiments in vitro demonstrated that miR-526b-5p could restore the effect of circ_0085539 in terms of promoting OS malignancy phenotypes by suppressing SERP1. Overall, the present study validated that hsa_circ_0085539 could promote the progression of OS by regulating miR-526b-5p/SERP1.


Is cortisol a modulator of interferon tau action in the endometrium during early pregnancy in cattle?
Glucocorticoids (GCs) were recently found to be potent modulators of the secretion of uterine prostaglandins (PGs) in ruminants. The aim of the present study was to examine whether GCs may serve as a mediator/modulator of interferon-τ (IFNT) action during early pregnancy in cows. We examined whether IFNT affects cortisol output and expression of GC receptors (NR3C1) and 11β-hydroxysteroid dehydrogenases (enzymes responsible for GC conversion: HSD11B1 and HSD11B2) in bovine endometrium. Endometrial tissues were collected from cyclic and pregnant cows on Days 16-17. Endometrial stromal and epithelial cells were isolated from uteri from cyclic cows in the early luteal phase (Days 2-5). The mRNA and protein expressions of NR3C1, HSD11Bs in endometrial strips and cultured cells were analyzed. Endometrial slices and isolated cells were incubated with cortisone in the presence or absence of IFNT and HSD11B1 activity was evaluated. IFNT increased HSD11B1 activity in endometrial strips and both types of endometrial cells. IFNT influenced NR3C1 and HSD11Bs mRNA and protein expression in epithelial and stromal cells. Expressions of HSD11Bs and NR3C1 mRNA and protein in bovine endometrium were different on Days 16-17 of the estrous cycle compared with early pregnancy. Cortisol changed basal and IFNT-stimulated PGE2 secretion in the bovine endometrium. The overall results suggest that cortisol acts as modulator and/or mediator of IFNT actions in bovine uterus and that IFNT regulates PG secretion by up-regulating local cortisol, resulting in the maintenance of the corpus luteum during early pregnancy in cattle.


Impact of COVID-19 on Croatian mariculture: Findings from the first national surveys.
An overview of the negative effects of the COVID-19 pandemic on the mariculture industry of the republic of Croatia is provided. An initial online survey was circulated early after the onset of the pandemic and a follow-up field survey was performed a year into the pandemic. The surveyed companies varied in size (micro to medium enterprises), location (north, central and southern coast) and cultured organism (European flat oyster, Mediterranean mussel, European sea bass, Gilthead sea bream and/or Bluefin tuna) and were asked questions on the subject of economic and job losses, aquaculture supply chain processes and implemented or proposed measures for mitigation of negative effects. Results from the online survey showed higher economic loss than job loss, but companies reported increased job loss in the period leading to the field survey. Most companies reported reductions in sales and avenues of procurement, which, in addition to direct stressors, indirectly affected business processes. Micro enterprises fared well due to their part-time nature, low capital investments and running costs, while small to medium enterprises were under the most pressure. Large enterprises were barely affected as they had secure local and/or international distribution chains and dominated the market. Producers most affected were those that relied on the HoReCa market for product placement and/or had difficulty coping with existing stressors. Bivalve producers generally experienced a higher drop in sales than finfish farms and companies with specialized production were not able to adapt to market changes to the degree that more versatile businesses seemed capable of.


A pharmacist-led community-based survey study: Determining the impact of the Covid-19 pandemic on actionable factors associated with worse cancer outcomes and cancer health disparities.
The goals of this cross-sectional community-based survey study were to assess the impact of the Covid-19 pandemic on actionable factors which are known to contribute to worse cancer outcomes, and to determine whether race and ethnicity-based differences exist. A survey study which captured demographic information and changes in cancer outcomes-related factors since the start of the Covid-19 pandemic, was conducted at a public Covid-19 vaccination clinic over a period of 10 days during March 2021. Surveys were administered in multiple languages. Chi-square tests and ANOVA followed by post-hoc Dunnett testing assessed for race and ethnicity-based differences. A total of 949 people participated (61.6% participation rate). Ninety-three surveys were removed based on inclusion criteria giving a final participant number of 856. Many participants reported postponing cancer screenings (17.8%) and cancellation of medical appointments (22.8% and 25.8% reported cancelled appointments by providers or themselves, respectively) due to the pandemic. Participants also reported decreased physical activity (44.7%) and increased tobacco and/or marijuana usage (7.0%). Conversely, participants reported consuming more fruits and vegetables (21.4%) and decreasing alcohol consumption (21.4%). Several race-related differences but no ethnicity-related differences were observed. Our data can be used to help guide pharmacist-led targeted outreach in our community which will help mitigate Covid-19 pandemic-driven changes in behaviors associated with worse cancer outcomes and exacerbation of cancer health disparities. To our knowledge, this is the first cancer outcomes-related study to be conducted at a public Covid-19 vaccination site and is the first pharmacist-led study in this area.


Bezold-Jarisch reflex mediated syncope in pulmonary arterial hypertension: An illustrative case series.
We present a novel description of Bezold-Jarisch Reflex (BJR) during cardiopulmonary exercise testing (CPET) in three young female patients with Group 1 pulmonary arterial hypertension (PAH). These three cases presented within 26 months, representing only 0.8% of 11,387 tests on patients with PAH undergoing CPET during this time frame.


Tolerance of Chemoradiation in Advanced Head and Neck Cancers: Comparison Between Inpatients and Outpatients.
Concurrent chemoradiation (CCRT) is the mainstay of treatment for majority of locally advanced head and neck carcinomas (LAHNC). Addition of chemotherapy to radiotherapy increases the probability of local control and improved disease-free survival but at the cost of acute and delayed toxicities. A retrospective observational study. To compare the tolerance of CCRT and its toxicity profile amongst two groups, first arm (Arm A) being outdoor patients and the second group (Arm B) was hospitalized patients of LAHNC in an oncology centre of a tertiary care hospital. A total of 100 patients were enrolled, 50 in each arm. Overall, the most common site was oropharynx, followed by larynx and hypopharynx. 38 patients in Arm A received full 6 cycles of weekly chemotherapy with Inj Cisplatin infusion. 39 of the hospitalized patients completed 6 cycles of weekly Cisplatin, 04 patients also received 3 weekly Cisplatin. Average duration of treatment was 49.18 days in arm A and 50.92 days in arm B. Incidence of Grade II onwards dysphagia was 48 and 45 (96 and 90%) in Arm A and Arm B respectively; Chi Square value-0.6 (Yate's corrected); P value-0.43. Grade III oral mucositis was seen in 14% patients in Arm A and 34% patients in Arm B. 3 patients (6%) in Arm A and 14 patients (28%) in Arm B has Grade II and III hematological toxicities and nephrological toxicities. Aspiration pneumonia was seen in 2 patients (4%) in Arm A and in 4 patients (8%) in Arm B, Chi Square value-0.2 (Yate's corrected) P value-0.67. The incidence of febrile neutropenia was 3 and 10 in Arms A and B (6 and 20%) respectively. The tolerance of CCRT in hospitalized patients is marginally better, with relatively few associated complications as compared to outdoor setting. Every institute should promulgate its own guidelines regarding hospitalization of such patients.


Neuroradiological examination of thoracic radiculomyelopathy due to ossification of the ligamentum flavum.
Sixteen cases of thoracic radiculomyelopathy due to ossification of the ligamentum flavum (OLF) were analyzed. The patients ranged in age from 39 to 78 years (average 57 years). There were 13 men and 3 women. A significant predilection of OLF for the lower thoracic spine (T9/10, T10/11, T11/12) was noticed. Plain X-ray of the thoracic spine and multidirectional tomography could give important information about the site of ossification. Computed tomography with the intrathecal injection of the water-soluble contrast material clearly demonstrated the ossification and the degree of compression of the spinal cord. The disadvantages of using computed tomography for diagnosing OLF included the necessity for the scan level to be previously decided by other methods because computed tomography of the entire spine was impractical. Magnetic resonance imaging was performed in 14 patients and gave important information about OLF and the compression of the spinal cord. The combination of MRI and computed tomography seems the most useful for the precise diagnosis of OLF.


A study of values of baccalaureate nursing students and graduate nurses from a secular and a nonsecular program.
This study examined the relationship between professional values of senior baccalaureate nursing students and graduate nurses compared to the values reflected in the Code for Nurses. A questionnaire was completed by 199 students and graduates of a secular and a nonsecular university. Data were analyzed using content analysis, frequency distributions, and multivariate procedures. Findings indicated that values identified most frequently by all respondents related to patient care issues rather than social issues of the profession. Analyses showed no significant difference in value identification between respondents from the secular and the nonsecular institutions. Implications for nursing education, nursing service, and future research are also discussed.


Idiotype expression and fine specificity of Glu60Ala30Tyr10-specific T proliferating cells.
The fine specificity of anti-Glu60Ala30Tyr10 (GAT) and anti-Glu60Ala40 (GA) proliferating cells was studied. T cells primed with GAT proliferate both to GAT and GA and GA-primed T cells proliferate also to GA and GAT. This cross-reactivity was unexpected given the results previously reported on the fine specificity of anti-GAT antibodies. The effect on the proliferation of BALB/c lymph node cells (LNC) of a syngeneic anti-idiotypic serum, prepared in BALB/c against anti-GAT antibodies, was studied. Two major points are made in this paper: (i) the in vitro addition of the anti-idiotypic serum in cultures containing GAT-primed LNC and GAT enhances the proliferation of GAT-specific T cells; (ii) the anti-idiotypic serum is effective in priming in vivo LNC which then acquire the capacity to proliferate specifically with GAT in vitro. These results further confirm the existence of idiotype-like determinants on T cells.


Hinokitiol functions as a ferroptosis inhibitor to confer neuroprotection.
The intrinsic link of ferroptosis to neurodegeneration, such as Parkinson's disease and Alzheimer's disease, has set promises to apply ferroptosis inhibitors for treatment of neurodegenerative disorders. Herein, we report that the natural small molecule hinokitiol (Hino) functions as a potent ferroptosis inhibitor to rescue neuronal damages in vitro and in vivo. The action mechanisms of Hino involve chelating irons and activating cytoprotective transcription factor Nrf2 to upregulate the antioxidant genes including solute carrier family 7 member 11, glutathione peroxidase 4 and Heme oxygenase-1. In vivo studies demonstrate that Hino rescues the deficits of locomotor activity and neurodevelopment in zebrafishes. In addition, Hino shows the efficient blood-brain barrier permeability in mice, supporting the application of Hino for brain disorders. Paclitaxel is one of the most widely used broad-spectrum antineoplastic agents. However, its neurotoxic side effect is a severe concern. We demonstrate that the neurotoxicity of paclitaxel is ferroptosis-related and Hino also alleviates the paclitaxel-induced neurotoxicity without compromising its cytotoxicity to cancer cells. Hino also salvages the neurobehavioral impairment by paclitaxel in zebrafishes. Collectively, the discovery of Hino as a novel ferroptosis inhibitor and disclosure of its action mechanisms establish a foundation for the further development of Hino as a neuroprotective agent.


[Effect of extracorporeal autohemomagnetic therapy on oxygen balance in patients with acute lung injury syndrome in sepsis].
The paper shows the results of a study evaluating the impact of impulse magnetic fields on the blood of patients with acute lung injury concurrent with sepsis. Extracorporeal autohemomagnetic therapy has been ascertained to reduce blood and tissue hypoxia. Thus it normalizes basic oxygen homeostasis more effectively than do traditional methods.


Synthesis and X-ray characterization of 15- and 16-vertex closo-carboranes.
Carboranes are a class of carbon-boron molecular clusters with three-dimensional aromaticity, and inherent robustness. These endowments enable carboranes as valuable building blocks for applications ranging from functional materials to pharmaceuticals. Thus, the chemistry of carboranes has received tremendous research interest, and significant progress has been made in the past decades. However, many attempts to the synthesis of carboranes with more than 14 vertices had been unsuccessful since the report of a 14-vertex carborane in 2005. The question arises as to whether these long sought-after molecules exist. We describe in this article the synthesis and structural characterization of 15- and 16-vertex closo-carboranes as well as 16-vertex ruthenacarborane. Such a success relies on the introduction of silyl groups to both cage carbons, stabilizing the corresponding nido-carborane dianions and promoting the capitation reaction with HBBr2·SMe2. This work would shed some light on the preparation of carboranes with 17 vertices or more, and open the door for studying supercarborane chemistry.


Metal toxicity to embryos and larvae of eight species of freshwater fish-II: copper.
Fish larvae and early juveniles of all species tested (brook trout, rainbow trout, brown trout, lake trout, northern pike, white sucker, herring, and smallmouth bass) were more sensitive to copper than the embryos. Embryo survival was affected only at the higher concentrations tested, for all species except the rainbow trout. The concentrations of copper that caused significant effects on the larval standing crop were similar for all species (31.7-43.5 microgram Cu/1) except the northern pike, which seemed to be considerably more resistant (104.1 microgram Cu/1). Copper concentrations shown to have no significant effects on the early developmental stages of these species are considered close estimates of the copper concentrations that would have no measurable adverse effects during a complete life cycle toxicity test under similar test conditions.


Molecular Dynamics Simulation for Investigating Antigen-Antibody Interaction.
Molecular dynamics (MD) simulation is a computational method which elucidates the protein dynamics. Following analyses characterize the dynamics and structural change as well as interaction energy. To characterize the protein structure effectively, the internal angular coordinates are often useful. Directional analysis provides the averages and variances of those coordinates in a mathematically rigorous way. Here, we describe not only a standard MD simulation procedure for the antigen-antibody system but also an umbrella sampling method following a multistep targeted MD simulation (US/mTMD), which is useful for evaluating the free energy profile along the antigen-antibody dissociation coordinate.


The position 68(E11) side chain in myoglobin regulates ligand capture, bond formation with heme iron, and internal movement into the xenon cavities.
After photodissociation, ligand rebinding to myoglobin exhibits complex kinetic patterns associated with multiple first-order geminate recombination processes occurring within the protein and a simpler bimolecular phase representing second-order ligand rebinding from the solvent. A smooth transition from cryogenic-like to solution phase properties can be obtained by using a combination of sol-gel encapsulation, addition of glycerol as a bathing medium, and temperature tuning (-15 --> 65 degrees C). This approach was applied to a series of double mutants, myoglobin CO (H64L/V68X, where X = Ala, Val, Leu, Asn, and Phe), which were designed to examine the contributions of the position 68(E11) side chain to the appearance and disappearance of internal rebinding phases in the absence of steric and polar interactions with the distal histidine. Based on the effects of viscosity, temperature, and the stereochemistry of the E11 side chain, the three major phases, B --> A, C --> A, and D --> A, can be assigned, respectively, to ligand rebinding from the following: (i) the distal heme pocket, (ii) the xenon cavities prior to large amplitude side chain conformational relaxation, and (iii) the xenon cavities after significant conformational relaxation of the position 68(E11) side chain. The relative amplitudes of the B --> A and C --> A phases depend markedly on the size and shape of the E11 side chain, which regulates sterically both ligand return to the heme iron atom and ligand migration to the xenon cavities. The internal xenon cavities provide a transient docking site that allows side chain relaxations and the entry of water into the vacated distal pocket, which in turn slows ligand recombination markedly.


Digital subtraction angiography: the intravenous approach.
With further improvement of digital subtraction angiography (DSA) equipment, and the development of sophisticated soft-ware programs, the intravenous approach again has become an promising diagnostic alternative in certain clinical settings, if the patient's cardiac output is not severely diminished. In many cases an additional arterial study is not necessary. The diagnostic results, advantages and limitations of the intravenous approach in imaging the brachiocephalic, renal and peripheral vessels are discussed.


Potassium depletion selectively inhibits sustained diacylglycerol formation from phosphatidylinositol in angiotensin II-stimulated, cultured vascular smooth muscle cells.
Potassium depletion decreases blood pressure in vivo and blunts the pressor response to angiotensin II (ang II) without down-regulating the receptor. In cultured rat aortic smooth muscle cells, the ang II-induced signaling sequence is biphasic with rapid hydrolysis of the polyphosphoinositides producing an early (15 s) diacylglycerol (DG) peak and a transient rise in inositol trisphosphate (IP3) and more delayed phosphatidylinositol (PI) hydrolysis resulting in sustained DG formation (peak at 5 min). Exposure of intact vascular smooth muscle cells to low potassium growth medium for 24 h or acutely potassium-depleting cells with nigericin causes selective, marked inhibition of late DG formation (5-min peak inhibited by 60 +/- 8% and 84 +/- 7%, respectively). The early cell response, namely polyphosphoinositide hydrolysis, inositol bis- and trisphosphate production and the 15-s DG peak, is not affected. Analysis of 125I-ang II-binding data reveals no significant differences in either receptor number or binding affinity (Kd) in potassium-depleted cells. Together with its marked inhibitory effect on sustained ang II-induced DG formation, acute potassium depletion effectively blocks internalization of 125I-ang II: there is no significant internalization of the ligand after 5 min at 37 degrees C versus 64 +/- 7% internalization in control cells. Thus, potassium depletion does not alter ang II binding or initial membrane signaling in rat aortic smooth muscle but blocks ligand internalization and selectively and markedly inhibits the development of direct PI hydrolysis and sustained diacylglycerol formation. These findings suggest a role for ligand-receptor processing in generating the sustained cell response and potentially explain the lower blood pressure and decreased pressor response to ang II seen in hypokalemic states in vivo. Furthermore, the ability of K+ depletion to alter secondary signal generation may provide insight into the mechanisms underlying the K+ dependence of a variety of cell functions.


Pharmacologic investigations on the role of Sirt-1 in neuroprotective mechanism of postconditioning in mice.
Cerebral ischemia-reperfusion (I-R) injury is one of the primary causes of ischemic stroke. Ischemic postconditioning (iPoCo) is evolving as an important adaptive technique to contain I-R injury. Some recent studies have shown neuroprotective effects of iPoCo. However, the neuroprotective mechanism of iPoCo is not clear. So, the present study has been undertaken to investigate the possible role of Sirtinol, a selective class III histone deacetylase (HDAC) inhibitor in the neuroprotective mechanism of iPoCo in mice. Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was used to produce I-R-induced cerebral injury in Swiss albino mice. iPoCo involving three episodes of 10-s carotid artery occlusion and reperfusion instituted immediately after BCAO just before prolonged reperfusion of 24 h. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using a Morris water maze test. Rotarod test, inclined beam-walking test, and neurologic severity score (NSS) were used to assess motor incoordination. Acetylcholine esterase levels, brain thiobarbituric acid reactive species (TBARS), and glutathione level were also estimated. BCAO for 12 min followed by reperfusion for 24 h produced a significant rise in cerebral infarct size and NSS along with impairment of memory and motor coordination and biochemical alteration (↑acetylcholine esterase, ↓glutathione, and ↑TBARS). iPoCo, involving three episodes of 10-s carotid artery occlusion with intermittent reperfusion of 10 s applied just after ischemic insult of 12 min produced a significant decrease in cerebral infarct size and NSS along with the reversal of I-R-induced impairment of memory and motor coordination. iPoCo-induced neuroprotective effects were significantly abolished by pretreatment with selective SIRT 1 (class III HDAC) blocker Sirtinol (10 mg/kg intraperitoneal). It may be concluded that the neuroprotective effect of iPoCo probably involves activation of SIRT 1 (class III HDAC) enzyme.


Methane oxidation and formation of EPS in compost: effect of oxygen concentration.
Oxygen concentration plays an important role in the regulation of methane oxidation and the microbial ecology of methanotrophs. However, this effect is still poorly quantified in soil and compost ecosystems. The effect of oxygen on the formation of exopolymeric substances (EPS) is as yet unknown. We studied the effect of oxygen on the evolution of methanotrophic activity. At both high and low oxygen concentrations, peak activity was observed twice within a period of 6 months. Phospholipid fatty acid analysis showed that there was a shift from type I to type II methanotrophs during this period. At high oxygen concentration, EPS production was about 250% of the amount at low oxygen concentration. It is hypothesized that EPS serves as a carbon cycling mechanism for type I methanotrophs when inorganic nitrogen is limiting. Simultaneously, EPS stimulates nitrogenase activity in type II methanotrophs by creating oxygen-depleted zones. The kinetic results were incorporated in a simulation model for gas transport and methane oxidation in a passively aerated biofilter. Comparison between the model and experimental data showed that, besides acting as a micro-scale diffusion barrier, EPS can act as a barrier to macro-scale diffusion, reducing the performance of such biofilters.


Spiroaminal Model Systems of the Marineosins with Final Step Pyrrole Incorporation.
In this Letter, we describe a short, 6-step enantioselective route to spiroaminal lactam model systems reminiscent of marineosins A and B has been developed starting from either (R)- or (S)-hydroxysuccinic acid, respectively, in ~9% overall yield. This route enables late stage incorporation of the pyrrole ring at C5 via nucleophilic displacement of an iminium triflate salt.


Effect of activity-based training versus strengthening exercises on upper extremity functions in Parkinson's patients; A randomized controlled, single blind, superiority trial.
Idiopathic Parkinson's disease is a neurodegenerative disease which is appeared by symptoms such as resting tremor, bradykinesia, rigidity, and postural instability. Such symptoms as tremor, bradykinesia, and rigidity significantly affect patients' upper extremity function. Rehabilitation programs should be implemented to improve the upper extremity functions of patients. Activity-based training would improve dexterity and functional activities to a larger extent than strengthening exercises. This study aimed at evaluating the effect of activity-based training and strengthening exercises on upper extremity functions in Parkinson's disease and to compare the two methods. 40 Parkinson's patients with mean of 64.45 ± 9.13 age were randomized and divided into two groups as activity-based training and strengthening exercise group. Patients were evaluated at the beginning and after 6 weeks of treatment with Unified Parkinson's Disease Rating Scale, Parkinson's Disease Questionnaire-39, Duruöz Hand Index, Jebsen Taylor Hand Function Test, Nine-Hole Peg Test, Jamar dynamometer, Jamar pinch meter, Semmes Weinstein Monofilament Test and two-point discrimination. In both groups, upper extremity functions, handgrip strengths and quality of life of patients improved significantly. Tactile sense improved only in the activity-based training group. Activity-based training is not superior to strengthening exercise programs at improving upper extremity functions and dexterity of Parkinson's patients.


Investigating how interprofessional simulation influences tolerance of ambiguity.
Decision making in clinical practice is only possible if we are able to understand the limits of our own knowledge and manage the associated uncertainty. Tolerance of ambiguity is therefore an important attribute for trainee pharmacists and medical students to develop. This study aimed to explore the impact of an interprofessional simulation on the tolerance of ambiguity of trainee pharmacists and medical students. Trainee pharmacists and final year medical students participated in interprofessional simulation in two regions of Scotland. Participants completed pre- and post-session tolerance of ambiguity questionnaires. Analysis included differences between the pre-session scores of the two groups; the trainee pharmacists' pre- and post-session scores; and the medical students' pre- and post-session scores. A total of 15 trainee pharmacists and 15 medical students participated. Baseline tolerance of ambiguity was slightly higher in medical students than trainee pharmacists (56.9 vs. 52.6), but the study was insufficiently powered to detect whether this was a true difference (P = .21). Trainee pharmacists showed a statistically significant increase in self-reported tolerance of ambiguity (52.6 to 60.8, P = .004), but medical students did not (56.9 to 63.8, P = .04). Trainee pharmacists' tolerance of ambiguity was improved following participation in an interprofessional simulation. Further research could establish whether the improvements differ between professional groups, and explore the reasons why tolerance of ambiguity may be affected by interprofessional simulation.


Rectifying the output of vibrational piezoelectric energy harvester using quantum dots.
Piezoelectric energy harvester scavenges mechanical vibrations and generates electricity. Researchers have strived to optimize the electromechanical structures and to design necessary external power management circuits, aiming to deliver high power and rectified outputs ready for serving as batteries. Complex deformation of the mechanical structure results in charges with opposite polarities appearing on same surface, leading to current loss in the attached metal electrode. External power management circuits such as rectifiers comprise diodes that consume power and have undesirable forward bias. To address the above issues, we devise a novel integrated piezoelectric energy harvesting device that is structured by stacking a layer of quantum dots (QDs) and a layer of piezoelectric material. We find that the QD can rectify electrical charges generated from the piezoelectric material because of its adaptable conductance to the electrochemical potentials of both sides of the QDs layer, so that electrical current causing energy loss on the same surface of the piezoelectric material can be minimized. The QDs layer has the potential to replace external rectification circuits providing a much more compact and less power-consumption solution.


Influence of occlusion and mandibular position on foot support and head posture in adult patients.
To study postural changes, taking into account different mandibular positions and the cephalic and plantar body segments. A cross-sectional, descriptive, clinical, and observational study was carried out on 76 patients, (mean age 28.79 years), in whom body posture and plantar support were evaluated in the maximum mandibular intercuspal position and the mandibular rest position without dental contact. When the mandibular position was altered, 71.01% of the patients showed changes in the bipupillary line (p = 0.008), while those who did not show such changes did, however, show changes in plantar support. More than 85% of the sample experienced alterations in the plantar plane when the mandibular position was changed, with statistically significant results (p < 0.001). There is a positive relationship between the different segments in body posture. In the sample, changes in plantar support with respect to the different mandibular positions were noticeable.


Comprehensive Analysis of circRNA-miRNA-mRNA Network in Cervical Squamous Cell Carcinoma by Integrated Analysis.
Cervical squamous cell carcinoma (CSCC) seriously affects women's health worldwide, and it is of great significance to illuminate the specific role of circRNAs in CSCC. Three mRNA datasets, two miRNA datasets and one circRNA dataset of CSCC, downloaded from GEO, were utilized in this study. Differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and circRNAs (DEcircRNAs) were identified, and a ceRNA (DEcircRNA-DEmiRNA-DEmRNA) regulatory network was constructed. GO and pathway analyses of DEcircRNAs and DEmRNAs in the ceRNA regulatory network were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) validation of the expression of the selected DEmRNAs, DEmiRNAs and DEcircRNAs was performed. A total of 1356 DEmRNAs, 13 DEmiRNAs and 77 DEcircRNAs were obtained. The ceRNA network contained 3 circRNA-miRNA pairs and 158 miRNA-mRNA pairs, including 3 circRNAs, 3 miRNAs, and 138 mRNAs. Functional annotation of DEmRNAs in the ceRNA regulatory network revealed that these DEmRNAs were significantly enriched in cell cycle, p53 signalling pathway and DNA replication. The qRT-PCR results were generally consistent with those of our integrated analysis. In conclusion, we speculate that the regulation of the hsa_circ_0000069/hsa-miR-125b-5p/CDKN2A and hsa_circ_0020594/hsa-let-7c-5p/CCNB2 axes may be involved in CSCC.


Selectivity of serum immunoreactive prolyl 4-hydroxylase as a marker for hepatic necrosis.
To investigate the selectivity of serum immunoreactive prolyl 4-hydroxylase (S-IRPH) as a marker for hepatic necrosis, sera were taken from patients with hepatic inflammation and hepatic necrosis. The concentration of immunoreactive prolyl 4-hydroxylase in the sera was determined by radio-immunoassay, and S-IRPH and alanine aminotransferase (ALT) data were plotted. Patients with hepatic necrosis showed mainly prolyl 4-hydroxylase elevation while patients with inflammation had both prolyl 4-hydroxylase and alanine aminotransferase elevations. The addition of serum immunoreactive prolyl 4-hydroxylase to current serum markers would be useful in investigating the pathophysiology of hepatocellular damage, particularly in differentiating between hepatic necrosis and inflammation.


Synthetic peptides mimic gp75 from Paracoccidioides brasiliensis in the diagnosis of paracoccidioidomycosis.
Paracoccidioidomycosis (PCM) is a systemic granulomatous disease, endemic in Latin America, caused by the thermal dimorphic fungus Paracoccidioides brasiliensis. Although some fungal antigens have already been characterized and used for serological diagnosis, cross-reactions have been frequently observed. Thus, the examination of fungal forms in clinical specimens or isolation of P. brasiliensis by culture is still the most frequent method for the diagnosis of this mycosis. In this study, a random peptide phage display library was used to select mimotopes of P. brasiliensis, which were employed as antigens in an indirect enzyme-linked immunosorbent assay. The protective monoclonal antibody against experimental PCM (anti-gp75) was used as molecular target to screen a phage display library. That approach led to a synthetic peptide named P2, which was synthesized and tested against PCM patients' sera to check whether it was recognized. There was significant recognition of P2 by sera of untreated PCM patients when compared with normal human sera. Sera from treated PCM group, patients with other mycosis or co-infected with HIV had much lower recognition of P2 than untreated patient group. The test showed a sensitivity of 100 and 94.59% of specificity in relation to human sera control. These data indicate a potential use of P2 as diagnostic tool in PCM. Its application for serological diagnosis of PCM may contribute to the development and standardization of simpler, faster and highly reproducible immunodiagnostic tests at low cost.


Antimicrobial activity of selected plants employed in the Spanish Mediterranean area.
Eighty-one plants from the Spanish Mediterranean area employed as antimicrobial agents in folk medicine have been identified. The in vitro antimicrobial activity of chloroform and methanol extracts of the plants were studied using the agar dilution method against six selected microorganisms. Thirty extracts had activity against some of the microorganisms tested. Bioautography showed that the antimicrobial activity is probably due to flavonoids, terpenoids and phenolic acids.


Laboratory experiments on HMC coupling mechanisms in innovative clean foundation treatments for Zn-contaminated dredger fills.
Large-scale contaminated dredger fills have comprehensively resulted from human activities and geological deposition processes, and their disposal is a worldwide challenge. Innovative soil remediation coupling foundation treatment methods, namely, clean foundation treatment methods (CFTMs), were proposed and verified using a hydraulic-mechanical-chemical coupling triaxial testing system. The CFTM exploration triaxial tests on undisturbed clayey, silty, and sandy dredger fills showed that the critical injection significantly dilated soil volume even after the soil was vacuum pumped. Critical injection-vacuum soil flushing (CIVF), critical injection soil flushing (CIF), and vacuum soil flushing (VF) were proposed to perform clean foundation treatment for clayey silt, sandy silt, and silty sand of 1900-2300 ppm Zn. EDDS, HCl + CaCl2, and HCl were selected as the three chelating agents. Orthogonal tests on three factors (CFTM, soil type, and eluent) showed that CIF with 5:1 EDDS aq. of pH 3.8 was the best CFTM scheme for the three soil types at a depth of 2.5-10 m. CIF with HCl aq. of pH 3.8 also reached a high comprehensive clean foundation treatment efficiency for silty sand at a depth of 2.5 m. The deep depth and heterogeneous texture resulted in low Zn contamination extraction efficiency.


Revealing the mechanisms of polypyrrole (Ppy) enhancing methane production from anaerobic digestion of waste activated sludge (WAS).
Anaerobic digestion (AD) is a promising method for treating waste activated sludge (WAS), but the low methane yield limits its large-scale application. The addition of conductive nanomaterials has been demonstrated to enhance the activity of AD via promoting the direct interspecies electron transfer (DIET). In this study, novel conductive polypyrrole (Ppy) was prepared to effectively improve the AD performance of WAS. The results showed that the accumulative methane production was enhanced by 27.83% by Ppy, with both acidogenesis and methanogenesis being efficiently accelerated. The microbial community analysis indicated that the abundance of bacteria associated with acidogenesis process was significantly elevated by Ppy. Further investigation by metatranscriptomics revealed that fadE and fadN genes (to express the key enzymes in fatty acid metabolism) were highly expressed in the Ppy-driven AD, suggesting that Ppy promoted electron generation during acid production. For methanogenesis metabolism, genes related to acetate utilization and CO2 utilization methanogenesis were also up-regulated by Ppy, illustrating that Ppy facilitates the utilization of acetate and electrons by methanogenic archaea, thus potentially promoting the methanogenesis through DIET.


Fraxinellone ameliorates intracerebral hemorrhage-induced secondary brain injury by regulating Krüppel-like transcription factor 2 expression in rats.
Damage to the blood-brain barrier (BBB) is an important factor leading to intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). Krüppel-like transcription factor 2 (KLF2) plays an important role in the maintenance of the BBB. This study aims to detect the changes of KLF2 after ICH and evaluate the potential effects of fraxinellone on ICH-induced SBI and its correlation with KLF2. An ICH model was established by injecting autologous blood into the right basal ganglia of Sprague-Dawley (SD) rats. First, after ICH induction, the protein levels of KLF2 were reduced. Then, we found that the decrease of KLF2 protein levels induced by ICH could be effectively reversed with the treatment of fraxinellone in vascular endothelial cells. Furthermore, fraxinellone treatment effectively alleviated brain edema, decreased the levels of TNF-α and IL-1β, and improved neuronal cell degeneration induced by ICH. Meanwhile, fraxinellone ameliorated neurobehavioral disorders, motor and sensory impairments, and neurobehavioral disorders and memory loss caused by ICH. Collectively, these findings reveal that KLF2 may be a potential target for fraxinellone to exert neuroprotective effects after ICH, and fraxinellone could be a potential therapeutic agent for SBI after ICH.


The effect of age and gender on epidermal nerve fiber density.
Sensory neuropathies often involve small-diameter myelinated and unmyelinated nerve fibers, and neurologic and electrophysiologic findings may be normal unless larger nerve fibers are involved. The small (intra)epidermal nerve fibers (ENFs) now can be visualized with immunohistochemical techniques using the panaxonal marker anti-protein gene product 9.5 (PGP 9.5). Using this technique, the authors have established a reference range for ENF in a healthy white population and evaluated the reliability of the method. Two punch biopsies, 3 mm in diameter, were taken from the distal part of the leg in 106 healthy volunteers (mean age, 49.0 +/- 19.6 years). Fifty-micrometer frozen thick sections were incubated with rabbit polyclonal antibodies to human PGP 9.5. The number of ENF/mm then was reported as the mean of counts in six sections (three sections from each of the two biopsies). The mean number of ENFs was 12.4 +/- 4.6 mm. In a multiple regression model, the density of ENF depended on age and gender (Y = 13.92 + 2.25 (gender) - 0.06 x age). The mean difference in ENF by intraobserver analysis was 0.2 +/- 1.2 ENF/mm, and by interobserver analysis, it was 0.4 +/- 1.5 fibers/mm. Normal means and ranges for the density of epidermal nerve fibers in a reference population have been established. The density of epidermal nerve fibers decreases with age and is lower in men compared with women. Intraobserver and interobserver analysis proves the reliability of the method.


Change in hypothermia and catalepsy induced by cannabinoids or morphine in mice tolerant to these substances.
delta 8-Tetrahydrocannabinol (THC)- and 8 beta, 9 beta-epoxyhexahydrocannabinol (EHHC)-tolerant mice were tolerant to the hypothermia produced by morphine while 8 alpha, 9 alpha-EHHC-tolerant mice were not. Morphine-tolerant mice acquired partial tolerance to the hypothermic effect of 8 alpha,9 alpha-EHHC, but not to the effect of delta 8-THC and 8 beta,9 beta-EHHC. Cataleptogenic effects of all cannabinoids were enhanced in morphine-tolerant mice as compared to non-tolerant animals. It seems that morphine-tolerant mice exhibited hypersensitivity to the cataleptogenic effect of the cannabinoids without potentiation of the hypothermia. These results suggest that the morphine-tolerant mouse may acquire 'latent' cross-tolerance to the hypothermic effect of the cannabinoids.


Temporal trends in the utilization of advanced therapies among patients with acute pulmonary embolism: insights from a national database.
There is a paucity of data regarding the contemporary temporal trends in the adoption of advanced pulmonary embolism (PE) therapies in the United States as well as the parallel trends in outcomes of patients with acute PE. Therefore, we queried the Nationwide Readmissions Database (years 2016-2020) to report the temporal trends in utilization of advanced PE therapies. Our final analysis included 920 770 hospitalizations with acute PE. We demonstrated an increase in the proportion of patients diagnosed with high-risk PE during the study years. Overall, there was an increase in the use of advanced PE therapies, which was mainly due to the increase in the utilization of systemic thrombolytics, and catheter-directed therapies. Also, extracorporeal membrane oxygenation cannulation showed an incremental increase over the study years. The use of inferior vena cava filter has declined, while the use of surgical embolectomy did not change during the study years. The use of advanced therapies has increased among urban teaching, but not among urban non-teaching hospitals. During the study years, there was no change in unadjusted or adjusted in-hospital mortality rates among patients with acute PE, while the 90-day unplanned readmission rate has declined.


Dynamics and Composition of Small Heat Shock Protein Condensates and Aggregates.
Small heat shock proteins (sHSPs) are essential ATP-independent chaperones that protect the cellular proteome. These proteins assemble into polydisperse oligomeric structures, the composition of which dramatically affects their chaperone activity. The biomolecular consequences of variations in sHSP ratios, especially inside living cells, remain elusive. Here, we study the consequences of altering the relative expression levels of HspB2 and HspB3 in HEK293T cells. These chaperones are partners in a hetero-oligomeric complex, and genetic mutations that abolish their mutual interaction are associated with myopathic disorders. HspB2 displays three distinct phenotypes when co-expressed with HspB3 at varying ratios. Expression of HspB2 alone leads to formation of liquid nuclear condensates, while shifting the stoichiometry towards HspB3 resulted in the formation of large solid-like aggregates. Only cells co-expressing HspB2 with a limited amount of HspB3 formed fully soluble complexes that were distributed homogeneously throughout the nucleus. Strikingly, both condensates and aggregates were reversible, as shifting the HspB2:HspB3 balance in situ resulted in dissolution of these structures. To uncover the molecular composition of HspB2 condensates and aggregates, we used APEX-mediated proximity labelling. Most proteins interact transiently with the condensates and were neither enriched nor depleted in these cells. In contrast, we found that HspB2:HspB3 aggregates sequestered several disordered proteins and autophagy factors, suggesting that the cell is actively attempting to clear these aggregates. This study presents a striking example of how changes in the relative expression levels of interacting proteins affects their phase behavior. Our approach could be applied to study the role of protein stoichiometry and the influence of client binding on phase behavior in other biomolecular condensates and aggregates.


Life fulfillment in an epilepsy sample from the United States.
This study examined the life fulfillment of a sample of 420 people with epilepsy drawn from affiliates of the Epilepsy Foundation of America in various urban and rural regions of the United States and also a private clinic. At the time of the study, all respondents were attending hospital outpatient neurological or epilepsy clinics for treatment, monitoring or advice. Life fulfillment was operationalized in terms of the discrepancy between people's desired and actual circumstances, and the scale developed for the research covered the following life domains: family and social relationships; leisure; worries; material security; employment. The findings revealed that the respondents were most fulfilled in the areas of family/social relationships, getting help with problems, leisure and housing. Health concerns seemed to be the prime source of non-fulfillment, with employment, marriage and money also appearing problematic. When factors associated with variations in overall life fulfillment were examined, unemployment, seizure predictability, polytherapy and living with a spouse/partner seemed to be of particular significance. The study findings are discussed and the need to pursue medical and vocational goals alongside each other in intervention strategies is emphasized.


Conserved features of yeast and mammalian mitochondrial DNA replication.
Mammalian mitochondrial DNA replication is initiated by the processing of RNA transcripts derived from an upstream promoter to create RNA primers for DNA replication. In the yeast Saccharomyces cerevisiae, mitochondrial ori/rep sequences contain a transcription promoter upstream of the site of transition from RNA to DNA synthesis, suggesting a common mode of replication initiation. Recent research has identified features in the mode and machinery of DNA replication conserved from yeast to mammals.


Reduced alcohol drinking following patterned feeding: Role of palatability and acute contingent availability.
Recent studies from our lab have demonstrated that intermittent high-fat diet access reduces alcohol drinking in rats. However, it was unclear if caloric overload, palatability, or diet itself triggered reduced alcohol drinking. It is also unknown if a similar paradigm could reduce relapse-like alcohol drinking. The presented study tested the hypothesis that acute intermittent palatable diet (PD) access would rescue relapse-like drinking and palatability, but not diet itself contributes to reduced drinking. Male Long Evans rats received six-weeks intermittent or chronic chow (controls) or PDs (high-fat diet, high-sugar diet) exposure, and alcohol testing occurred following PDs suspension. Alcohol intake was not significantly different among groups in either condition, suggesting that diet itself did not impact alcohol drinking. A subset of these rats received two-weeks intermittent PDs (Int-PDs) exposure and alcohol testing reinitiated while Int-PDs access continued. Alcohol intake significantly escalated (~137% compared to baseline; alcohol deprivation effect) in the chow controls, whereas it remained unchanged in PD groups. These data demonstrate the critical importance of acute intermittent PDs availability and its protective effect in relapse-like drinking. To assess the contribution of palatability in reduced alcohol drinking, a separate group of rats received two-weeks intermittent high-sugar diet (Int-HSD) or saccharin (Int-SAC) access and tested for alcohol drinking while Int-HSD/SAC continued. Alcohol drinking significantly decreased (~30%) in both HSD and SAC groups compared to the controls. These data identify the critical parameters by which acute intermittent PD access reduces alcohol drinking and could have important therapeutic implications in the management of alcoholism.


Developmental origins of obesity: early feeding environments, infant growth, and the intestinal microbiome.
Pediatric overweight and obesity are growing problems worldwide, with increasing prevalence among even infants and young children. The refractory nature of early overweight necessitates identifying the factors contributing to early excess weight gain for successful intervention. Early feeding practices may be particularly important in shaping long-term vulnerability to obesity. How and what infants are fed can influence weight gain, adiposity, and energy metabolism during infancy and across the life course through a number of interacting physiological and behavioral pathways. This article argues that these biological mechanisms interact with the social and behavioral context of infant feeding to create differential vulnerability to later obesity. This article reviews recent research on the potential mechanisms linking infant feeding and risk of later obesity, focusing on the emerging role of microflora colonization. The nutritive and non-nutritive components of breastmilk, formula and solid foods and the practices surrounding feeding shape the infant metabolome, programming growth rates and body composition, altering metabolism and physiology, promoting differential microfloral colonization, and shaping behavioral responses to foods and eating. The occurrence of chronic disease precursors at increasingly younger ages and the tendency of overweight young children to become overweight adolescents and adults underscore the importance of understanding this complex early exposure and intervening early to prevent the development of obesity in increasingly weight-promoting environments.


Hemolytic-uremic syndrome: a diagnostic and therapeutic dilemma for the surgeon.
The hemolytic-uremic syndrome consists of microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia following a prodromal illness of gastroenteritis or upper respiratory infection. The syndrome can present in dramatic fashion with severe abdominal pain and signs of peritonitis suggesting an acute surgical crisis. In a series of 25 patients, 40% had abdominal pain, 25% had abdominal tenderness, and 20% had peritoneal signs. Clues to diagnosis in the early stages of the acute illness were mild to moderate hypertension, abnormal peripheral blood smear, anemia despite dehydration, and proteinuria. Significant abdominal pain and x-ray evidence of colitis may occur before development of typical laboratory findings, and these were evident in at least one case. Three patients underwent laparotomy for suspected bowel perforation. Colitis without perforation was found in all cases. In the absence of documented perforation, toxic megacolon, or intussusception, the decision to perform laparotomy in patients with hemolytic-uremic syndrome who have signs of peritonitis must be individualized. Failure to recognize the underlying renal problem can lead to serious errors in fluid and electrolyte management and delay of appropriate therapy.


Seasonal changes in photosynthetic activity of snow tussocks (Chionochloa spp.) along an altitudinal gradient in Otago, New Zealand.
Photosynthetic characteristics were studied in Chionochloa rigida, an altitudinally widespread snow tussock and a closely related high-altitude species C. macra. Along a gradient from near sea level to 1600 m there were no consistent differences in maximum photosynthetic capacity which averaged 4.5 μmol CO2 m-2s-1. The photosynthetic temperature optimum ranged between 15 and 18°C and there was only a limited capacity for seasonal adjustment. Net photosynthesis was light-saturated at about 500 μmol photons m-2s-1. In winter, the photosynthetic capacity decreased significantly with increasing altitude of origin of the snow tussocks. A transplant experiment indicated this was partly genetically controlled.