Temperature-dependent conformational transitions and hydrogen-bond dynamics of the elastin-like octapeptide GVG(VPGVG): a molecular-dynamics study.
A joint experimental/theoretical investigation of the elastin-like octapeptide GVG(VPGVG) was carried out. In this article a comprehensive molecular-dynamics study of the temperature-dependent folding and unfolding of the octapeptide is presented. The current study, as well as its experimental counterpart (see companion article in this issue) find that this peptide undergoes an inverse temperature transition (ITT), leading to a folding at approximately 40-60 degrees C. In addition, an unfolding transition is identified at unusually high temperatures approaching the normal boiling point of water. Due to the small size of the system, two broad temperature regimes are found: the ITT regime at approximately 10-60 degrees C and the unfolding regime at approximately T > 60 degrees C, where the peptide has a maximum probability of being folded at T approximately 60 degrees C. A detailed molecular picture involving a thermodynamic order parameter, or reaction coordinate, for this process is presented along with a time-correlation function analysis of the hydrogen-bond dynamics within the peptide as well as between the peptide and solvating water molecules. Correlation with experimental evidence and ramifications on the properties of elastin are discussed.


[Optimization of a floating osmotic pump system of ambroxol hydrochloride using central composite design-response surface methodology and its pharmacokinetics in Beagle dogs].
This paper reported that a new type of floating osmotic pump of ambroxol hydrochloride was designed. Third method apparatus (Chinese Pharmacopeia 2010, appendix XD) was employed to simultaneously evaluate the release and floating behavior in vitro. The system was optimized using central composite design-response surface methodology. Similar factor (f2) between the release profile of self-made formulation and the target release profile was chosen as dependent factor. The amount of glucose (A, mg), pore former (B, %) and weight of coating (C, %) were employed as independent factors. Optimized formulation was: A (100.99 mg), B (1.70%), C (4.21%). The value of f2 (89.14) was higher than that of market capsules (69.02) and self-made tablets (72.15). It was showed that self-made capsules possessed character of zero-order release (r = 0.994 4) and drug release completely (>90%). It was showed in result of in vivo study that tmax and Cmax of self-made capsules were significantly lower than that of market capsules and self-made tablets. The correlation coefficient between the fraction of absorption in vivo and the release rate in vitro was 0.985 1, and relative bioequivalence of self-made capsules was 110.77%. Accordingly, self-made capsules displayed obviously characteristics of controlled release both in vivo and in vitro.


Socioeconomic Considerations and Shared-Care Models of Cancer Care for Older Adults.
Older adults with cancer require a geriatrics approach to treatment. Such an approach targets appropriate treatments based on physiologic, not chronologic, age. Patients older than 65 years of age constitute the largest group of patients with cancer, making them the most expensive group of patients with cancer, especially with the advent of expensive new treatments with minimal impact on overall survival. Geriatric assessment, combined with targeted inventions, can optimize the value propositions in caring for older patients with cancer. Over the past 20 years, geriatric oncology care models have emerged applying these care principles in clinical practice.


Cerebral ischemia due to compression of the brain by ossified and hypertrophied muscle used for encephalomyosynangiosis in childhood moyamoya disease.
Encephalomyosynangiosis is one of the indirect method in which ischemic brain surface is covered by temporal muscle for the treatment of moyamoya disease. A 14-year-old girl who had been treated with bilateral STA-MCA anastomosis and EMS in 1999 was admitted on January 5, 2005. She showed transient incomplete palsy on the left side of the face and the ipsilateral upper extremity. On the day of admission, MRIs/MRA and 3-dimensional regional CBF measurement using stable xenon and CT scanning were conducted after performance of plain CT scanning. The MRI and CT studies showed that ossified and hypertrophied temporal muscle used for EMS to the right MCA territory compressed the brain just under the muscle. MRA demonstrated well-developed collaterals to the territories of the bilateral MCAs via the previously performed anastomosis. The CBF studies disclosed a low CBF value just under ossified and hypertrophied muscle used for EMS on the right side. She showed same transient ischemic attacks repetitively after January 5, 2005. The repetitive attacks with the transient motor palsy on her left side was thought to be caused by direct compression of the brain by the ossified and hypertrophied muscle used for EMS and decrease in CBF just under it, and its removal was thought to be the treatment of choices. However, the patient and her parents refused the surgical procedure, and she is treated conservatively at present.


Internationalization: the Hong Kong-China experience as a model for collaborative education in Asia.
The Hong Kong model for collaboration in education in Asia is based on internationalization. Hong Kong benefits from being an international city combining an Eastern heritage and a Western society. The University of Hong Kong ranks among the world's top 25 universities (2012/2013 QS world university rankings), and its Division of Paediatric Surgery has an international reputation in research and training. In the past two decades, Hong Kong has leading roles in major international pediatric surgical organizations including Pacific Association of Pediatric Surgeons, International Pediatric Endosurgery Group, Asian Association of Pediatric Surgeons and World Federation of Associations of Pediatric Surgeons. While Hong Kong has close collaboration with Japan and other advanced economies, the talk will focus on our transfer of international experience to Mainland China. (1) A Train-the-Trainer scheme consisting of a 1-year structured education program for next-generation leaders from selected centers enabled replication and proliferation of similar training nationwide. (2) A series of laparoscopic workshops resulted in training of over 1,300 surgeons in basic and advanced skills in minimally invasive surgery within 5 years and the establishment of a national specialist organization overseeing development and quality assurance. (3) A series of Cross-Strait Symposia on Pediatric Oncology established the foundation of multidisciplinary, multicenter collaboration in education and research in Mainland China, Taiwan and Hong Kong. (4) Initiation of a scientific writing course will enhance surgical research and training in China. The Hong Kong experience may serve as a model of collaboration with other developing economies in Asia.


Hospitalized hunger-striking prisoners: the role of ethics consultations.
We refer to hospitalized convicted hunger strikers in Padua Hospital who decided to fast for specific reasons, often demanding, to be heard by the judge, to complain about the existing custodial situation or to claim unjust treatment. The medical ethics of hunger strikers are debated because the use of force feeding by physicians is widely condemned as unethical, but courts, in Italy, sometimes order to transfer the convicted person to hospital and oblige healthcare practitioners to perform forcible feeding. This can engender a profound insecurity for the physicians taking action on the one hand, while preventing patients from fully availing themselves of this principle of self-determination on the other. Physicians are mainly concerned about how to manage this situation and they may request ethical consultation. When it comes to managing hospitalized hunger strikers, the ethics consultant may be able to facilitate the relationship between physicians and hunger strikers, enhance the latter's trust in the former, ensuring that strikers are aware of the risks associated with their fasting, and helping them to arrive of their own free will at the right decision concerning their behavior and their demands.


Production of tumor growth-inhibiting protein by the neonatal mouse brain: dependence on intracellular glutamine metabolism.
We previously reported that the mouse brain at the neonatal stage but not at the adult stage secreted a carcinostatic factor of 62,000 Da, termed NBCF, which inhibited clonal growth and DNA synthesis of malignant cells preferentially over those of normal cells. In the present study, NBCF production by the neonatal mouse brain in culture was investigated. Addition of L-glutamine to the culture medium markedly promoted NBCF production in a concentration-dependent manner. The production seemed to be specific to glutamine, since no promotive effect was exerted by L-glutamic acid, its analogue DL-alpha-aminoadipic acid, L-aspargine, or L-aspartic acid or by other amino acids or vitamins. NBCF production was markedly reduced in culture medium either devoid of L-glutamine or containing 6-diazo-5-oxo-L-norleucine, a glutamine antagonist, or L-methionine sulfoximine, an inhibitor of glutamine synthetase. Thus NBCF production was promoted by extracellular supply, intracellular synthesis, and utilization of L-glutamine but was not affected by its deamidated form or homologue amino acids. On the other hand, NBCF production was completely repressed by addition of cycloheximide to the culture medium. The repressive effect was also exerted by actinomycin D although not completely, whereas cytosine beta-D-arabinofuranoside did not repress NBCF production. These results indicated that NBCF production by cultivation was independent of DNA replication but dependent mostly on a transcription stage and its following stages and partly on a translation stage from the preexisting mRNA to the protein.


Visual Sensor Placement Optimization with 3D Animation for Cattle Health Monitoring in a Confined Operation.
Computer vision has been extensively used for livestock welfare monitoring in recent years, and data collection with a sensor or camera is the first part of the complete workflow. While current practice in computer vision-based animal welfare monitoring often analyzes data collected from a sensor or camera mounted on the roof or ceiling of a laboratory, such camera placement is not always viable in a commercial confined cattle feeding environment. This study therefore sought to determine the optimal camera placement locations in a confined steer feeding operation. Measurements of cattle pens were used to create a 3D farm model using Blender 3D computer graphic software. In the first part of this study, a method was developed to calculate the camera coverage in a 3D farm environment, and in the next stage, a genetic algorithm-based model was designed for finding optimal placements of a multi-camera and multi-pen setup. The algorithm's objective was to maximize the multi-camera coverage while minimizing budget. Two different optimization methods involving multiple cameras and pen combinations were used. The results demonstrated the applicability of the genetic algorithm in achieving the maximum coverage and thereby enhancing the quality of the livestock visual-sensing data. The algorithm also provided the top 25 solutions for each camera and pen combination with a maximum coverage difference of less than 3.5% between them, offering numerous options for the farm manager.


Role of the multidrug resistance protein 1 gene in the carcinogenicity of aflatoxin B1: investigations using mrp1-null mice.
The multidrug resistance protein 1 (MRP1) protects cells from xenobiotics by extruding from the intracellular compartment glutathione (GSH)-S-conjugates, glucuronyl conjugates and sulfate conjugates and by the co-export of xenobiotic(s) and GSH. An ATP-dependent transport of aflatoxin B1 (AFB1) and its GSH conjugates by MRP1 has been previously demonstrated in vitro. In the present study, we have sought to investigate the in vivo role of MRP1 in AFB1 carcinogenicity, by comparing the incidence of tumors occurring in mrp1 (+/+) and mrp1 (-/-) mice 12 months after an 8 weeks exposure to AFB1. The carcinogen induced a similar number of lung and liver tumors in both strains. Most lung tumors were of the solid type and showed a moderate degree of differentiation in both mrp1 (+/+) and mrp1 (-/-) mice. These data provide direct evidence that in vivo MRP1 does not protect from AFB1 carcinogenicity. Due to the redundancy of transmembrane export pumps, other pump(s) may effectively vicariate for MRP1-mediated transport of AFB1 and its glutathione conjugates.


Comparison of dermoscopic features between congenital and acquired acral melanocytic nevi in Korean patients.
The dermoscopic patterns of acral melanocytic nevi (AMNs) are crucial in differentiating them from acral melanoma. Several studies have reported the dermoscopic patterns of acquired acral melanocytic nevi (AAMNs). However, few have investigated the dermoscopic patterns of congenital acral melanocytic nevi (CAMNs). To compare the clinical and dermoscopic features of CAMNs and AAMNs. The present study included 43 patients with CAMNs and 40 with AAMNs. We reviewed their medical records as well as their clinical and dermoscopic findings. Congenital acral melanocytic nevis were more asymmetrical than AAMNs (P = 0.002) and presented more frequently as comma-shaped (P = 0.005). Regarding dermoscopic findings, globular pattern (55.8%) was the most common feature of CAMNs, while parallel furrow pattern (37.5%) was the most common feature of AAMNs. The presence of fibrillar, globular, and parallel ridge patterns, and diffuse multi-component pigmentation differed significantly between the groups (P < 0.05). Furthermore, CAMNs showed melanoma-specific dermoscopic patterns, such as parallel ridge (18.6%) and diffuse multi-component pigmentation (25.6%). The dermoscopic patterns of CAMNs and AAMNs differed markedly. In terms of dermoscopic patterns, CAMNs resembled acral melanoma more often than AAMNs did.


Global Detection of Proteins by Label-Based Antibody Array.
Because of narrow availability of antibody pairs and potential cross-reactivity between antibodies, the development of sandwich-based antibody arrays which need a pair of antibodies for each target has been restricted to higher density resulting in limited proteomic breadth of detection. Label-based array is one way to overcome this obstacle by directly labeling all targets in samples with fluorescent dyes such as Cy3 and Cy5. The labeled samples are then applied on the antibody array chip composed of capture antibodies. In this chapter, we will introduce this technology including array production and sample detection assay.


Telomere length, oxidative and epigenetic changes in blood DNA of patients with exacerbated psoriasis vulgaris.
The pathogenesis of psoriasis vulgaris involves changes in DNA molecules, genomic instability, telomere attrition, and epigenetic alterations among them. These changes are also considered important mechanisms of aging in cells and tissues. This study dealt with oxidation damage, telomere length and methylation status in DNA originating from peripheral blood of 41 psoriatic patients and 30 healthy controls. Oxidative damage of serum DNA/RNA was determined immunochemically. Real-time PCR was used for the analysis of the telomere length. ELISA technique determined levels of 5-methylcytosine in blood cells' DNA. Oxidative damage of serum DNA/RNA was higher in patients than in controls (median, 3758 vs. 2286pg/mL, p<0.001). A higher length of telomeres per chromosome was found in patients whole-cell DNA than in controls (3.57 vs. 3.04 kilobases, p=0.011). A negative correlation of the length of telomeres with an age of the control subjects was revealed (Spearman's rho=-0.420, p=0.028). Insignificantly different levels of 5-methylcytosine in patients and controls were observed (33.20 vs. 23.35%, p=0.234). No influences of sex, smoking, BMI, PASI score, and metabolic syndrome on the methylation status were found. i) A relatively small number of the participants, particularly for reliable subgroup analyses, ii) the Caucasian origin of the participants possibly influencing the results of the parameters determined, and iii) Telomerase activity was not directly measured in serum or blood cells. The study demonstrated increased levels of oxidized DNA/RNA molecules in the serum of patients with exacerbated psoriasis vulgaris. The results were minimally influenced by sex, the presence of metabolic syndrome, or cigarette smoking. In the psoriatic blood cells' DNA, the authors observed longer telomeres compared to healthy controls, particularly in females. Insignificantly higher global DNA methylation in psoriasis cases compared to the controls indicated marginal clinical importance of this epigenetic test performed in the blood cells' DNA.


Application of noninvasive techniques for measuring cardiac output in hypertensive patients.
The hemodynamic hallmark of hypertension is increased systemic vascular resistance, although this variable is usually not determined in hypertensive patients because it has generally required invasive procedures to measure cardiac output. Reliable, totally noninvasive methods are now available that measure cardiac output accurately enough under a variety of conditions, including rest, exercise, and pharmacologic interventions. These methods include echocardiography, Doppler echocardiography, CO2 rebreathing, and impedance cardiography. Their serial application to large numbers of patients offers the opportunity to significantly broaden our understanding of the spectrum and course of hemodynamic alterations associated with hypertension. A more complete knowledge of underlying hemodynamics could improve our diagnostic and prognostic accuracy in hypertensive patients and enhance our understanding of the pathophysiology of hypertension and the mechanism of action of antihypertensive interventions.


A trial of tiaramide in asthma.
Tiaramide hydrochloride is a new non-steroidal anti-inflammatory agent previously shown to inhibit allergic responses both in vitro and in vivo. Clinical studies in asthmatic adults and children have also shown benefit. We report a double blind cross-over study in 35 adult asthmatic patients comparing oral tiaramide 200 mg four times daily with oral salbutamol 4 mg four times daily and placebo. Symptoms and bronchodilator inhaler usage were recorded in diary cards and morning and evening peak expiratory flow rates were also monitored. Both tiaramide and salbutamol had a significant therapeutic effect compared with placebo. More patients preferred tiaramide than salbutamol and there were fewer side effects during treatment with tiaramide. Tiaramide may be a useful oral therapy in asthma particularly for those patients intolerant of oral beta-adrenergic agonists.


(2E)-2-[(3E)-4-Phenyl-but-3-en-2-yl-idene]hydrazinecarboxamide.
In the title compound, C(11)H(13)N(3)O, the phenyl ring is disordered over two sites, with occupancy factors in a 0.520 (17):0.480 (17) ratio. The dihedral angle between the ring planes of the major and minor components of the disordered ring is 12.9 (2)°. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds, forming R(2) (2)(8) ring motifs. C-H⋯O, C-H⋯N and C-H⋯π inter-actions also occur.


Anomalous left coronary artery from the pulmonary artery presenting with aborted sudden death in an octogenarian: a case report.
We report a rare coronary anomaly presenting with aborted sudden death in an octogenarian. An anomalous left coronary artery from the pulmonary artery is a rare coronary anomaly which usually presents in the first year of life. Survival into adulthood and the elderly years is extremely rare. An 85-year-old Caucasian woman was brought to our hospital following cardiopulmonary arrest. After prolonged resuscitation and stabilization of our patient, further evaluation revealed an anomalous left coronary artery from pulmonary artery syndrome. She was discharged on medication. An anomalous left coronary artery from the pulmonary artery can present in elderly and even octogenarian patients. Careful history, physical examination and an appropriate invasive study are needed to confirm the diagnosis.


Diagnosis of Renal Cell Carcinoma: A Clinician's Perspective.
Renal cell carcinoma (RCC) is a heterogeneous disease. A rigorous diagnostic assessment by a pathologist with close communication with the clinician provides more accurate prognostication and informed treatment decisions. In the localized setting, an accurate prognostic assessment directs patients to potential adjuvant clinical trials. For patients with advanced disease, the pathologic assessment may have a direct impact on the systemic therapy algorithm. Additionally, it provides the basis for continuous efforts in biomarker development. In rare histologic subtypes, the interaction between clinicians and pathologists provides an opportunity to offer patients specific clinical trials. Molecular characterization platforms may identify targets for therapeutic intervention.


New prediction models for dental age estimation in Thai children and adolescents.
The aims of this study were to develop new prediction models for dental age estimation and to test the accuracy of the resulting models in comparison with the Demirjian et al. and the Willems et al. methods in Thai children and adolescents. Digital panoramic radiographs of 1,134 Thai individuals (487 males and 647 females) aged from 6 to 15 years were selected and evaluated for dental age estimation. Quadratic regression was used to generate new models. The results showed that the new prediction models indicated a strong correlation coefficient between the dental maturity score and the chronological age in both sexes (r=0.951 for males, r=0.945 for females). The new age prediction models were: y=0.006297x(2) - 0.804930x+32.591843 for males and y=0.010677x(2) - 1.538823x+61.955056 for females, where y is the dental age, x is the dental maturity score according to Demirjian et al. Moreover, these new models were tested showing the greatest accuracy for estimating the age in Thai samples using the mean difference values between the dental and the chronological ages (-0.04 years for males, 0.02 years for females) when compared with the Demirjian et al. and the Willems et al. In addition, the new models revealed a high percentage of accuracy in the absolute difference values between the dental and the chronological ages within 1 year (76.26% and 74.49% for males and females, respectively). Furthermore, our results in mean difference values indicated that the Demirjian et al. method (0.11 and 0.10 years for males and females, respectively) was more accurate than the Willems et al. method (-0.37 and -0.39 years for males and females, respectively) in Thai samples. In conclusion, the new age prediction models in this study provide accurate age estimation in both sexes, suggesting that these models be applied for forensic age estimation, especially in Thai children and adolescents.


A technique for the management of a large median lobe in robot-assisted laparoscopic radical prostatectomy.
An enlarged median lobe is encountered 8% to 18% of the time during robot-assisted laparoscopic prostatectomy. A large intravesical lobe can obscure the anatomy of the bladder neck and generate a large bladder neck, necessitating reconstruction. In addition, it may increase the likelihood of ureteral injury, positive surgical margin, and residual prostate tissue. When encountering this anatomic variant, a clear surgical plan is required. We describe our approach to the large median lobe and highlight a specific technique that may be beneficial in managing this anatomic variant.


Metabolic effects of an insulin-like factor causing hypoglycaemia in a patient with a haemangiopericytoma.
We have studied a patient with fasting hypoglycaemia and skin lesions (sign of Leser-Trélat) related to a retroperitoneal haemangiopericytoma in whom removal of the tumour resulted in immediate cure of hypoglycaemia. Before removal of the tumour, severe fasting hypoglycaemia was associated with undetectable insulin and C-peptide levels. She required 16.9 mumol/kg/min (10.4 g/h) of glucose intravenously to prevent hypoglycaemia and endogenous glucose production (measured using tritiated glucose) was suppressed to 1.3 mumol/kg/min while the whole-body glucose utilization rate was elevated at 18.2 mumol/kg/min. After removal of the tumour both endogenous glucose production rate and utilization rate returned to normal (11.5 mumol/kg/min). Resting energy expenditure, measured by indirect calorimetry, was markedly elevated at 2109 kcal/day (161% of predicted) and fell to 1205 (97% of predicted) after the tumour was removed. Glucose oxidation was also enhanced at 8.5 mumol/kg/min and fell to 3.3 mumol/kg/min after removal of the tumour. Other metabolites and hormones measured, and their response to oral glucose, were all consistent with the presence of a circulating substance with similar properties to insulin. We conclude that her hypoglycaemia resulted primarily from suppression of endogenous glucose production but also from enhanced glucose utilization. These effects were the result of a circulating growth factor sharing many metabolic effects with insulin, but with a much greater effect on resting energy expenditure and glucose oxidation.


Gene transfer strategies for metabolic diseases.
Recent advances in molecular genetics and biotechnology will revolutionize the practice of medicine and surgery during the next decade. Surgeons must understand and begin to use the new technologies in the study of surgical biology and patient care. A brief overview of the principles of gene transfer and how this technology is used for treating metabolic disease is presented. Two examples of how recombinant viruses (vectors) can be used to study fundamental biology in the liver and pancreas are given. Familial hypercholesterolemia is used as a paradigm for a clinical gene transfer study and underscores the importance of surgeons in the development of novel therapeutic strategies.


Characteristics of neuronal systems in the visual cortex.
The coupling complexity of cortical areas makes it very difficult to analyse them experimentally. Studies of model systems provide the possibility of adapting the analysis to the available data base and elaborating the fundamental properties that depend on the structure of the system. We propose a model system of variable complexity that is spatially two-dimensional and time-dependent, uses feedback for iteration and smoothing, includes the mapping of the cortical networks and can be nonlinear as the case requires. Combining such elementary systems on the basis of neuroanatomical findings enables us to simulate cortical mappings and to interpret neurophysiological data. The decisive factor is that the dynamics of the system and the neuroanatomically based spatial coupling are closely connected with each other.


Purification and characterization of the myofibrillar form of myosin light-chain phosphatase from turkey gizzard smooth muscle.
The myofibrillar form of smooth-muscle myosin light-chain phosphatase (MLCP) was isolated from turkey gizzards. The enzyme was extracted from washed myofibrils and purified by affinity chromatography on a column of thiophosphorylated myosin 20 kDa light-chain (LC20). The purified enzyme was a monomeric protein of 35 kDa and bound to unphosphorylated myosin with a binding constant of 5.45 x 10(4) M-1. It dephosphorylated both isolated phosphorylated light-chain (PLC20) and intact myosin as well as myosin light-chain kinase. The enzyme activity was stimulated by Mn2+, Mg2+, Ca2+, and inhibited by Co2+ ions. Okadaic acid inhibited the phosphatase activity with an IC50 (concentration required for 50% inhibition) value of 250 nM, that is around 25-times higher than required for type 1 protein phosphatase; however, the heat stable inhibitor-2 had no effect. The unique properties of the myofibrillar phosphatase as compared to smooth-muscle phosphatases so far described, suggest that the myofibrillar MLCP is a novel protein of this class. It has been also suggested that in vivo the myofibrillar MLCP exists in a complex with myosin light-chain kinase (MLCK) and a 63 kDa protein.


Ganglioglioma of the optic nerve.
We examined a 15-year-old boy who had a ganglioglioma involving the left optic nerve, which caused proptosis, decreased vision, and optic atrophy. Computed tomography demonstrated an intraconal mass along the course of the orbital portion of the optic nerve. The only evidence of systemic neurofibromatosis was axillary freckling. The patient underwent a combined medial and lateral orbitotomy and excision of the tumor. Histologic examination demonstrated a mass composed of neurons and glial cells characteristic of ganglioglioma. After a one-year follow-up period, we have found no evidence of recurrence.


Sex-related differences in the prevalence of cognitive impairment among overweight and obese adults with type 2 diabetes.
Type 2 diabetes mellitus and obesity may increase risks for cognitive decline as individuals age. It is unknown whether this results in different prevalences of cognitive impairment for women and men. The Action for Health in Diabetes, a randomized controlled clinical trial of a 10-year intensive lifestyle intervention, adjudicated cases of cross-sectional cognitive impairment (mild cognitive impairment or dementia) 10-13 years after enrollment in 3802 individuals (61% women). The cross-sectional prevalences of cognitive impairment were 8.3% (women) and 14.8% (men): adjusted odds ratio 0.55, 95% confidence interval [0.43, 0.71], P < .001. Demographic, clinical, and lifestyle risk factors varied between women and men but did not account for this difference, which was limited to individuals without apolipoprotein E (APOE)-ε4 alleles (interaction P = .034). Among overweight and obese adults with type 2 diabetes mellitus, traditional risk factors did not account for the lower prevalence of cognitive impairment observed in women compared with men.


Solar ultraviolet irradiance and cancer incidence and mortality.
Evidence supporting the UVB/vitamin D/cancer theory continues to mount with little detraction, although there are some inconsistent results, such as some from Nordic countries, with respect to serum calcidiol levels. Also, studies designed and conducted before it was realized that dietary sources are largely inadequate to have a pronounced effect on cancer risk were largely unable to confirm a beneficial role for vitamin D in reducing the risk of cancer. The analysis of the economic burden of solar UVB irradiance and vitamin D deficiencies compared to excess solar UV irradiance for the United States yielded interesting findings. One was that the US economic burden due to vitamin D insufficiency from inadequate exposure to solar UVB irradiance, diet and supplements was estimated at $40 billion to $56 billion in 2004, whereas the economic burden for excess UV irradiance was estimated at $6 billion to $7 billion. These findings are probably still approximately correct, if not on the low side, with respect to vitamin D because of the additional benefits found recently, such as protection against infectious diseases.


Randomized clinical trial of a brief, scalable intervention for mental health sequelae in college students during the COVID-19 pandemic.
This randomized clinical trial aimed to determine feasibility, acceptability, and initial efficacy of brief Dialectical Behavior Therapy (DBT) skills videos in reducing psychological distress among college students during the COVID-19 pandemic. Over six weeks, 153 undergraduates at a large, public American university completed pre-assessment, intervention, and post-assessment periods. During the intervention, participants were randomized to receive animated DBT skills videos for 14 successive days (n = 99) or continue assessment (n = 54). All participants received 4x daily ecological momentary assessments on affect, self-efficacy of managing emotions, and unbearableness of emotions. The study was feasible and the intervention was acceptable, as demonstrated by moderate to high compliance rates and video ratings. There were significant pre-post video reductions in negative affect and increases in positive affect. There was a significant time × condition interaction on unbearableness of emotions; control participants rated their emotions as more unbearable in the last four vs. first two weeks, whereas the intervention participants did not rate their emotions as any more unbearable. Main effects of condition on negative affect and self-efficacy were not significant. DBT skills videos may help college students avoid worsening mental health. This brief, highly scalable intervention could extend the reach of mental health treatment.


Health risk assessment of volatile organic compounds (VOCs) emitted from landfill working surface via dispersion simulation enhanced by probability analysis.
The assessment of the health risks of volatile organic compounds (VOCs) emitted from landfills via dispersion model is crucial but also challenging because of remarkable variations in their emissions and meteorological conditions. This study used a probabilistic approach for the assessment of the health risks of typical VOCs by combining artificial neural network models for emission rates and a numerical dispersion model enhanced by probability analysis. A total of 8753 rounds of simulation were performed with distributions of waste compositions and the valid hourly meteorological conditions for 1 year. The concentration distributions and ranges of the typical health-risky VOCs after dispersion were analyzed with 95% probability. The individual and cumulative non-carcinogenic risks of the typical VOCs were acceptable with all values less than 1 in the whole study domain. For individual carcinogenic risks, only ethylbenzene, benzene, chloroform, and 1, 2-dichloroethane at extreme concentrations showed minor or moderate risks with a probability of 0.1%-1% and an impact distance of 650-3000 m at specific directions. The cumulative carcinogenic risks were also acceptable at 95% probability in the whole study domain, but exceeded 1 × 10-6 or even 1 × 10-4 at some extreme conditions, especially within the landfill area. The vertical patterns of the health risks with height initially increased, and then decreased rapidly, and the peak values were observed around the height of the emission source. The dispersion simulation and health risk assessment of the typical health-risky VOCs enhanced by Monte Carlo can accurately reflect their probabilistic dispersion patterns and health risks to surrounding residents from both spatial and temporal dimensions. With this approach, this study can provide important scientific basis and technical support for the health risk assessment and management of landfills.


Multiplexed base editing through Cas12a variant-mediated cytosine and adenine base editors.
Cas12a can process multiple sgRNAs from a single transcript of CRISPR array, conferring advantages in multiplexed base editing when incorporated into base editor systems, which is extremely helpful given that phenotypes commonly involve multiple genes or single-nucleotide variants. However, multiplexed base editing through Cas12a-derived base editors has been barely reported, mainly due to the compromised efficiencies and restricted protospacer-adjacent motif (PAM) of TTTV for wild-type Cas12a. Here, we develop Cas12a-mediated cytosine base editor (CBE) and adenine base editor (ABE) systems with elevated efficiencies and expanded targeting scope, by combining highly active deaminases with Lachnospiraceae bacterium Cas12a (LbCas12a) variants. We confirm that these CBEs and ABEs can perform efficient C-to-T and A-to-G conversions, respectively, on targets with PAMs of NTTN, TYCN, and TRTN. Notably, multiplexed base editing can be conducted using the developed CBEs and ABEs in somatic cells and embryos. These Cas12a variant-mediated base editors will serve as versatile tools for multiplexed point mutation, which is notably important in genetic improvement, disease modeling, and gene therapy.


Reactions of 2,6-dinitro-4-trifluoromethylbenzenesulfonate with human serum albumin.
The reaction of the title compound with human serum albumin has been examined at various concentrations of the sulfonate. Kinetic data suggest that there are two highly reactive lysine amino groups on the protein, five lysine residues which are less reactive and an undetermined number of additional nucleophilic groups that react very slowly with the reagent at pH 7.5. One of the rapidly reacting lysines is tentatively identified as lysine-199 in the protein sequence. Fluorine NMR experiments indicate the presence of tight binding sites on the protein for the sulfonate which are not near reactive functional groups.


Influence of age, postmortem delay and freezing storage period on cannabinoid receptor density and functionality in human brain.
It has been suggested that cannabimimetic drugs could be of interest in the treatment of several nervous disorders. Thus, it is important to analyse the distribution and properties of cannabinoid (CB) receptors directly in human brain. As postmortem human tissue is subjected to the effects of several biological variables, we have analyzed by autoradiography the influence of age, postmortem delay and freezing storage period (at -25 degrees C) on two parameters corresponding to cannabinoid CB1 receptors in human frontal cortex: receptor density and degree of activation of G-proteins ([35S]GTPgammaS assays). A significant decrease in the amount of both receptor density and agonist-stimulated G-protein activity was observed with age, revealing a mean reduction of about 10% per decade. In contrast, no significant correlations were found with postmortem delay either for CB1 receptors density or functionality. Finally, both parameters (receptor density and [35S]GTPgammaS response) were significantly reduced with freezing storage period at -25 degrees C in frontal cortical layers. Non-linear analysis of these data yielded values between 12 and 24 months of storage for a 50% reduction. In conclusion, when studying CB1 receptor properties in human brain samples, a careful analysis (and matching) for variables such as age and freezing storage period has to be carried out.


Impact of additional pleurodesis in video-assisted thoracoscopic bullectomy for primary spontaneous pneumothorax.
Bullectomy for primary spontaneous pneumothorax has been associated with high postoperative recurrence rates when video-assisted thoracoscopic surgery (VATS) has been used rather than thoracotomy. The aim of this study was to evaluate the efficacy and identify the disadvantages, if any, of adding pleurodesis to VATS bullectomy to prevent recurrent pneumothorax. Fifty-three patients who underwent VATS bullectomy with additional pleurodesis for pneumothorax after November 1996 and 50 who underwent VATS bullectomy alone before October 1996 were compared retrospectively in terms of intraoperative factors and postoperative chest pain, pulmonary function, and pneumothorax recurrent rates. Pleurodesis was achieved by electrocauterizing the upper surface of the parietal pleura in a patchy fashion. There were no significant differences between the additional pleurodesis group and the bullectomy alone group in terms of age, sex, operating time, intraoperative bleeding, number of resected bullae, duration of chest drainage, or volume of fluid drained. Postoperative chest pain and pulmonary function were also similar in both groups. A recurrent pneumothorax occurred in one patient (1.9%) in the additional pleurodesis group; this recurrence rate was significantly lower than that for the bullectomy alone group (eight patients, 16%; p = 0.029). Although the mean postoperative follow-up period was considerably shorter in the additional pleurodesis group (38 months [range, 26-49]) than in the bullectomy alone group (63 months [range, 50-72] ), eight (89%) of all nine recurrences occurred within 26 months of surgery-i.e., within the minimum follow-up period for the additional pleurodesis group. Pleurodesis is a minimally invasive technique that is effective in preventing postoperative recurrences of pneumothorax when added to VATS bullectomy. Additional pleurodesis has no disadvantages vs bullectomy alone in terms of worsening postoperative chest pain or pulmonary function.


Understanding digital bubbles amidst the COVID-19 pandemic: Evidence from DeFi and NFTs.
This paper investigates digital financial bubbles amidst the COVID-19 pandemic. Using a sample of 9 DeFi tokens, 3 NFTs, Bitcoin, and Ethereum, we detect several bubbles overlapping the examined cryptoassets. We also uncover DeFi and NFT-specific bubbles in Summer 2020 suggesting distinct driving factors for this class of assets. We document that DeFi and NFTs bubbles are less recurrent but have higher magnitudes than cryptocurrencies' bubbles. We also find that COVID-19 and trading volume exacerbate bubble occurrences, while Total Value Locked (TVL) is negatively associated with cryptoassets' bubbles. Our results suggest that TVL can be used as a tool for market monitoring.


N-terminal domain of pepsin as a model for retroviral dimeric aspartyl protease.
Autolysis of porcine pepsin at pH 4 affords a derivative possessing intrinsic proteolytic activity. This derivative was isolated by alumina pseudo-affinity chromatography and gel-filtration and was found to result from the tight association of two identical molecules, 135 amino acids long, emerging from the N-terminal domain of pepsin. This finding emphasizes a similarity with the only aspartyl-proteases known to act as dimers, the retroviral proteases.


Encapsulation of cisplatin as an anti-cancer drug into boron-nitride and carbon nanotubes: Molecular simulation and free energy calculation.
Encapsulation of cisplatin anticancer drug into the single walled (10, 0) carbon nanotube and (10, 0) boron-nitride nanotube was investigated by quantum mechanical calculations and Monte Carlo Simulation in aqueous solution. Solvation free energies and complexation free energies of the cisplatin@ carbon nanotube and cisplatin@ boron-nitride nanotube complexes was determined as well as radial distribution functions of entitled compounds. Solvation free energies of cisplatin@ carbon nanotube and cisplatin@ boron-nitride nanotube were -4.128kcalmol(-1) and -2457.124kcalmol(-1) respectively. The results showed that cisplatin@ boron-nitride nanotube was more soluble species in water. In addition electrostatic contribution of the interaction of boron- nitride nanotube complex and solvent was -281.937kcalmol(-1) which really more than Van der Waals and so the electrostatic interactions play a distinctive role in the solvation free energies of boron- nitride nanotube compounds. On the other hand electrostatic part of the interaction of carbon nanotube complex and solvent were almost the same as Van der Waals contribution. Complexation free energies were also computed to study the stability of related structures and the free energies were negative (-374.082 and -245.766kcalmol(-1)) which confirmed encapsulation of drug into abovementioned nanotubes. However, boron-nitride nanotubes were more appropriate for encapsulation due to their larger solubility in aqueous solution.


Obesity and peripheral arterial disease: A Mendelian Randomization analysis.
Observational studies showed that obesity is a major risk factor for peripheral arterial disease (PAD). However, conventional epidemiology studies are vulnerable to residual bias from confounding factors. We aimed to explore the causality of obesity in development of PAD using Mendelian Randomization (MR) approach. A MR analysis was performed in 11,477 community-dwelling adults aged 40 years and above recruited from two nearby communities during 2011-2013 in Shanghai, China. We genotyped 14 body mass index (BMI) associated common variants identified and validated in East Asians. PAD was defined as ankle-to-brachial index (ABI) <0.90 or >1.40. Weighted BMI genetic risk score (GRS) was used as the Instrumental Variable (IV). After adjusted for confounding factors, we found that each standard deviation (SD, 2.76 points) increase in BMI-GRS was associated with 0.43 (95% confidence interval [CI]: 0.36-0.49) kg/m(2) increase in BMI (P < 0.0001) and an odds ratio (OR) for PAD of 1.17 (95% CI: 1.07-1.27; P = 0.0004). Compared with the lowest quartile of BMI-GRS, the second, third and highest quartile associated with 9%, 19% and 45% increment of PAD risk, respectively (P for trend = 0.002). In the MR analysis, we demonstrated a causal relationship between obesity and PAD (OR = 1.44 per BMI-unit, 95% CI: 1.18-1.75; P = 0.0003). This study suggested that obesity may be causally associated with PAD after controlling for the potential intermediate factors like hypertension, dyslipidemia and hyperglycemia.


MNK kinases facilitate c-myc IRES activity in rapamycin-treated multiple myeloma cells.
When mTOR inhibitor rapalogs prevent cap-dependent translation of cell-cycle proteins like c-myc, continuing tumor cell growth depends on cap-independent translation, which is mediated by internal ribosome entry sites (IRESes) located in the 5'-UTR (untranslated region) of transcripts. To investigate if rapalog-induced activation of MNK kinases had a role in such IRES activity, we studied multiple myeloma (MM) cells. Rapamycin (RAP)-activated MNK1 kinase activity in MM cell lines and primary specimens by a mitogen-activated protein kinase-dependent mechanism. Pharmacological inhibition of MNK activity or genetic silencing of MNK1 prevented a rapalog-induced upregulation of c-myc IRES activity. Although RAP, used alone, had little effect on myc protein expression, when combined with a MNK inhibitor, myc protein expression was abrogated. In contrast, there was no inhibition of myc RNA, consistent with an effect on myc translation. In a RAP-resistant MM cell lines as well as a resistant primary MM specimen, co-exposure to a MNK inhibitor or MNK1 knockdown significantly sensitized cells for RAP-induced cytoreduction. Studies in MNK-null murine embryonic fibroblasts additionally supported a role for MNK kinases in RAP-induced myc IRES stimulation. These results indicate that MNK kinase activity has a critical role in the fail-safe mechanism of IRES-dependent translation when mTOR is inhibited. As kinase activity also regulated sensitivity to RAP, the data also provide a rationale for therapeutically targeting MNK kinases for combined treatment with mTOR inhibitors.


Prevalence of beta2-toxigenic Clostridium perfringens in horses with intestinal disorders.
The incidence of a new, yet unassigned toxin type of Clostridium perfringens containing the genes for the alpha-toxin and the recently described beta2-toxin in horses with intestinal disorders is reported. The study included 18 horses suffering from typical typhlocolitis, 7 horses with atypical typhlocolitis, 16 horses with other intestinal disorders, and 58 horses without intestinal disease. In total, 20 samples of ingesta of the small and large intestines, five biopsy specimens of the intestinal wall, and 74 fecal samples were analyzed bacteriologically. C. perfringens isolates were typed for the presence of the alpha-, beta-, beta2-, and epsilon-toxin and enterotoxin genes by PCR, including a newly developed PCR for the detection of the beta2-toxin gene cpb2. beta2-Toxigenic C. perfringens was detected in samples from 13 of 25 (52%) horses with typical or atypical typhlocolitis, with a particularly high incidence in specimens of ingesta and biopsy specimens (75%), whereas only 6 of 16 specimens from horses with other intestinal diseases yielded beta2-toxigenic C. perfringens. No beta2-toxigenic C. perfringens was found in the samples from the 58 control horses, of which only one fecal sample contained C. perfringens type A. Among the samples from the 15 horses with fatal cases of typical and atypical typhlocolitis 9 (60%) were positive for beta2-toxigenic C. perfringens, whereas samples from only 4 of the 10 (40%) animals with nonfatal cases of infection were positive. We found an interesting correlation between the antibiotic-treated horses which were positive for beta2-toxigenic C. perfringens and lethal progression of the disease. No C. perfringens strains isolated in this study contained genes for the beta- and epsilon-toxins and enterotoxin. The high incidence of beta2-toxigenic C. perfringens in samples of ingesta, biopsy specimens of the intestinal wall, and feces from horses suffering or dying from typhlocolitis together with the absence of this organism in healthy horses provides strong evidence that beta2-toxigenic C. perfringens play an important role in the pathogenesis of typhlocolitis.


Stomach Deformities Recognition Using Rank-Based Deep Features Selection.
Doctor utilizes various kinds of clinical technologies like MRI, endoscopy, CT scan, etc., to identify patient's deformity during the review time. Among set of clinical technologies, wireless capsule endoscopy (WCE) is an advanced procedures used for digestive track malformation. During this complete process, more than 57,000 frames are captured and doctors need to examine a complete video frame by frame which is a tedious task even for an experienced gastrologist. In this article, a novel computerized automated method is proposed for the classification of abdominal infections of gastrointestinal track from WCE images. Three core steps of the suggested system belong to the category of segmentation, deep features extraction and fusion followed by robust features selection. The ulcer abnormalities from WCE videos are initially extracted through a proposed color features based low level and high-level saliency (CFbLHS) estimation method. Later, DenseNet CNN model is utilized and through transfer learning (TL) features are computed prior to feature optimization using Kapur's entropy. A parallel fusion methodology is opted for the selection of maximum feature value (PMFV). For feature selection, Tsallis entropy is calculated later sorted into descending order. Finally, top 50% high ranked features are selected for classification using multilayered feedforward neural network classifier for recognition. Simulation is performed on collected WCE dataset and achieved maximum accuracy of 99.5% in 21.15 s.


Strongyloides stercoralis larvae found for the first time in tap water using a novel culture method.
Strongyloides stercoralis (S. stercoralis) is a soil-borne helminth but its prevalence in water samples is underestimated. The aim of the present study is to propose non-nutrient agar (NNA) as a novel culture method in the diagnosis of Strongyloides and to detect the prevalence rate of S. stercoralis larvae in tap water samples in Beni-Suef Governorate, Egypt. Eighty tap water samples were collected from Beni-Suef Governorate and each sample was filtered in three steps using three filters: one filter for microscopic examination of wet mount, while the remaining two filters were cultured on both NNA and nutrient agar plate (APC). S. stercoralis larvae, adults, and eggs were detected in two (2.5%) and four (5%) out of 80 samples after examination of wet mount preparation and cultures on both NNA and APC, respectively. NNA succeeded to maintain Strongyloides alive for up to 1 month. Our study is the first to detect Strongyloides larvae in tap water in Egypt and the first to use NNA as a novel culture media for Strongyloides.


Label-free DNA methylation analysis using opto-fluidic ring resonators.
The opto-fluidic ring resonator (OFRR) is a sensitive label-free optical biosensor that is uniquely well suited for photonic and fluidic integration. For the first time we have explored the utility of this novel instrument for the analysis of methylation in oligonucleotides using the MBD-2 (methyl binding) protein as the capture molecule. This application has strong relevance to cancer research and future clinical tools through the study of methylation patterns in important gene promoters. In this work we quantitatively characterized the OFRR's response to artificially methylated ssDNA and dsDNA as a function of the number of methylated cytosines and DNA concentration. The effect of hemi- versus fully methylated oligonucleotides was also investigated. Additionally, anti 5-methylcytidine antibody was also used as the capture molecule and compared with MBD-2. It is found that the antibody has stronger affinity for ssDNA, whereas MBD-2 is much better at binding dsDNA.


Eudesmane sesquiterpenoid glycosides from the leaves of Pittosporum lenticellatum with anti-neuroinflammatory activity.
Chemical investigation of the EtOAc extract of the leaves of Pittosporum lenticellatum led to the isolation of twenty-five previously undescribed eudesmane sesquiterpenoid glycosides, pitlencosides A-Y (1-25); their structures were elucidated by extensive spectroscopic analysis, including 1D and 2D NMR, HR-ESI-MS, ECD spectra, and X-ray crystallographic analysis. Among them, compounds 4, 5, 7, 8, 15 and 16 exhibited significant inhibitory effects on the production of nitric oxide in lipopolysaccharide-induced BV-2 microglial cells by suppressing the expression of inducible nitric oxide synthase and cyclooxygenase-2, with IC50 values ranging from 7.95 to 25.88 μM, which showed stereo-chemical and substituent dependents. Western blot analysis and molecular docking simulation confirmed the anti-inflammatory activity of compounds 4, 5, 7, 8, 15 and 16.


The holistic way of tackling the COVID-19 pandemic: the one health approach.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is causing a global pandemic had a zoonotic origin in China. Considering the inter-connectedness between human, environment, and animal health, the One Health approach is the appropriate strategy to control and mitigate the effects of the ongoing coronavirus disease 2019 (COVID-19). This letter explains the benefits of the One Health approach and recommends specific measures that could be taken to accelerate the fight against COVID-19 and prevent the spread of newly emerging infectious diseases.


The association between prior infection with five serotypes of Coxsackievirus B and incident type 2 diabetes mellitus in the EPIC-Norfolk study.
Infections with Coxsackieviruses have been linked to beta cell dysfunction. Given the importance of beta cell dysfunction in the aetiology of type 2 diabetes, we hypothesised that prior infection with Coxsackieviruses B would increase the risk of type 2 diabetes. The aims of the study were to estimate cross-sectional associations between potential predictors of previous infection and seropositivity for Coxsackievirus B serotypes 1-5 (CBV1-5), and then to assess the association between seropositivity and incident type 2 diabetes. Using a case-cohort design nested within the European Prospective Investigation of Cancer (EPIC)-Norfolk study, we ascertained n = 603 cases of incident type 2 diabetes. From within the entire cohort we identified a random subcohort of n = 835, without diabetes at baseline. The presence of Coxsackievirus B neutralising antibodies against serotypes 1-5 was assessed using a plaque neutralisation assay. Weighted Cox regression was used to examine the association between presence of antibodies to CBV1-5 and the development of type 2 diabetes. Seropositivity in the subcohort for CBV1-5 was 50%, 67%, 66%, 75% and 45%, respectively. After adjustment for age, sex, BMI, physical activity and family history of diabetes, the presence of antibodies against CBV1-5 was not associated with incident type 2 diabetes, over a mean follow-up of 5.7 years (HR [95% CIs] 0.94 [0.72,1.25], 0.92 [0.68, 1.23], 1.33 [0.98,1.81], 1.16 [0.83,1.61] and 1.03 [0.77,1.39] for CBV1-5, respectively). The presence of antibodies against any of five serotypes of Coxsackievirus B was not associated with incident type 2 diabetes.


Changes in hepatic drug metabolizing enzymes and lipid peroxidation by methanol extract and major compound of Orostachys japonicus.
The effects of methanol extract and gallic acid (3,4,5-trihydroxybenzoic acid) of Orostachys japonicus A. Berger on hepatic drug metabolizing enzymes and lipid peroxidation were investigated in rats treated with bromobenzene. The methanol extract of Orostachys japonicus reduced the activities of phase I enzymes, aminopyrine N-demethylase and aniline hydroxylase, that had been increased by i.p. injection of bromobenzene. Gallic acid isolated from Orostachys japonicus also reduced the aniline hydroxylase activity, while it did not affect the aminopyrine N-demethylase activity. The methanol extract and gallic acid restored the activity of epoxide hydrolase which had been decreased by bromobenzene. Hepatic glutathione content was lowered, along with increase in hepatic lipid peroxide, by bromobenzene administration. The hepatic lipid peroxidation induced by bromobenzene was prevented with the methanol extract and gallic acid of Orostachys japonicus. However, the decrease in glutathione was not altered by gallic acid. The present results suggest that the methanol extract and gallic acid of Orostachys japonicus may protect liver from bromobenzene toxicity through, at least in part, inhibiting the cytochrome P450-dependent monooxygenase activities and enhancing the activity of epoxide hydrolase. Antioxidant effect also may contribute to the protection of Orostachys japonicus against the bromobenzene-induced hepatotoxicity.


[Inflammatory reactions in patients suffering from coronary artery disease with concomitant obesity and type 2 diabetes mellitus].
Of late, inflammatory reactions have been considered to play an important part in the development of atherosclerosis. Acute-phase inflammatory reaction, being initially a protective response directed within the homeostasis system towards lesion repair, may by itself due to various factors favor the development of pathological processes. Considering the role played by inflammation in the development of atherosclerosis, and inflammatory activity in obesity and diabetes mellitus (DM), a range of common and interrelated elements of these processes may be marked out. These are acute phase proteins and cytokines. Insulinoresistance, being the common precursor of obesity and DM, plays the key role in vascular lesion. The use of cytokine activity index seems to be a promising method of revealing patients with high risk of atherosclerosis.


Outcome of hepatocellular carcinoma in human immunodeficiency virus-infected patients.
Although the number of human immunodeficiency virus-infected patients with chronic liver disease is increasing, the impact of human immunodeficiency virus on hepatocellular carcinoma outcome remains unclear. This single centre study investigated whether human immunodeficiency virus infection per se affects the hepatocellular carcinoma prognosis. Forty-eight human immunodeficiency virus-infected and 234 uninfected patients consecutively diagnosed with hepatitis virus-related hepatocellular carcinoma from January 2000 to December 2009 were retrospectively enrolled. Hepatocellular carcinoma was staged according to Cancer of the Liver Italian Program criteria. Survival and independent prognostic predictors were evaluated. Survivals were also compared after adjustment and matching by propensity score. Compared to human immunodeficiency virus-uninfected subjects, infected patients were more likely to be males, were younger, had fewer comorbidities and the tumour was more often detected during surveillance. Liver function, tumour characteristics and treatments did not significantly differ between the two groups. Nevertheless, median survival of human immunodeficiency virus-infected patients was approximately half that of their counterpart (16 months [95% confidence interval: 7-25] vs. 30 months [95% confidence interval: 25-35]; p=0.0354). Human immunodeficiency virus infection, Cancer of the Liver Italian Program score and hepatocellular carcinoma treatment were independently associated with mortality. Notably, human immunodeficiency virus infection doubled the risk of dying. These results were confirmed by propensity analysis. Human immunodeficiency virus infection per se worsens the prognosis of patients with virus-related hepatocellular carcinoma.


Can Central Sensitization After Injury Persist as an Autonomous Pain Generator? A Comprehensive Search for Evidence.
To conduct a comprehensive search for evidence with regard to whether central sensitization after an injury can act as a persistent autonomous pain generator after the inducing injury has healed. We searched Medline on PubMed and the Cochrane Library, screening 3,572 abstracts, from which 937 full-text articles were obtained, with 186 of these discarded as irrelevant to the question being posed. The remaining 751 articles were studied for evidence. Fourteen publications were judged to provide weak evidence for the hypothesis of central sensitization as a persisting autonomous pain generator, but none addressed the question directly. No strong evidence for the affirmative answer was found. Sixty-one publications were judged to provide weak evidence for a negative answer, and ten were judged to provide strong evidence. Unexpectedly, serious weaknesses were discovered in the literature underpinning the validity of the clinical diagnosis of central sensitization in humans: 1) inappropriate extrapolation, in many publications, of laboratory animal data to humans; 2) failure to demonstrate the absence of peripheral pain generators that might be perpetuating central sensitization; and 3) many factors now shown to confound what is being measured by quantitative sensory testing, conditioned pain modulation, and the Central Sensitization Inventory. We found no evidence proving that central sensitization can persist as an autonomous pain generator after the initiating injury has healed. Our review has also shown that the evidential basis for the diagnosis of central sensitization in individual patients is seriously in question.


Outcomes After Intensive Rehabilitation for Mechanically Ventilated Patients: A Nationwide Retrospective Cohort Study.
To examine the effects of intensive rehabilitation on mortality and liberation from mechanical ventilation among patients with mechanical ventilation in intensive care units. Retrospective cohort study using the Diagnosis Procedure Combination inpatient database. Patients discharged from acute care hospitals from April 2010 to March 2016. Patients (N=46,438) aged 20 years and older who were admitted to intensive care units and who started rehabilitation within 3 days of starting mechanical ventilation. Intensive rehabilitation in intensive care unit in the first 5 days after admission. Amount of rehabilitation was defined as the average number of units per day in the first 5 days after admission and was dichotomized as intensive (≥1.0 unit/d) or nonintensive (<1.0 unit/d) rehabilitation. The primary outcome was in-hospital mortality. The secondary outcome was liberation from mechanical ventilation. We identified 29,982 eligible patients, including intensive (n=7745) and nonintensive (n=22,237) rehabilitation groups. In the propensity score-matched analysis, the intensive rehabilitation group had significantly lower in-hospital mortality (risk difference: -3.4%; 95% CI, -4.9% to -1.9%) and a higher proportion of liberation from mechanical ventilation (subdistribution hazard ratio, 1.08; 95% CI, 1.03-1.13) compared with the nonintensive rehabilitation group. Patients receiving a higher amount of rehabilitation in intensive care units were less likely to die and more likely to be liberated from mechanical ventilation.


Residue behavior and efficacy of benzothiazole in grains under different fumigation conditions.
Benzothiazole is a potential grain fumigant for Tribolium castaneum. However, its safety profile and suitable fumigation conditions remain unknown. We therefore investigated the insecticidal efficacy, accumulation and dissipation of benzothiazole in grains (wheat, corn and rice) under different temperatures. We established a universal detection method (modified QuEChERS coupled with GC-MS/MS) of benzothiazole residues in three grains, which provided high linearity (R2 > 0.999), sensitivity (limits of detection = 0.001 mg/kg, limits of quantification = 0.002-0.005 mg/kg), accuracy (recoveries = 88.18-118.75%) and precision (relative standard deviations < 4.78%). The insecticidal efficacy order of benzothiazole was 30 ≥ 10 > 20 °C and corn > wheat > rice. Temperature positively affected the accumulation/dissipation rate of benzothiazole. Rice was the most easily accumulated and dissipated grain for benzothiazole residues, while corn accumulated benzothiazole more than wheat but less than rice, with dissipation slower than wheat and rice. Our results provide important references for the application of benzothiazole and other fumigants. © 2023 Society of Chemical Industry.


Induction of methamphetamine-specific antibody using biodegradable carboxymethyl-chitin.
Induction of a specific antibody for methamphetamine, an antihypnotic drug, has been studied using carboxymethyl-chitin (CM-chitin) as a hapten carrier. The hapten-specific antiserum was induced by only a couple of hypodermal injections every 2 weeks. Inhibition of antigen-antibody complex formation was linearly related to methamphetamine concentration in the range 0.5 to 50 ng/50 microliter when an enzyme-linked immunosorbent assay was performed using an avidin-biotin-peroxidase complex. Little antibody directed against CM-chitin and CM-chitin oligomer was detected. Thus it seems to be advantageous in the hapten-bovine serum albumin system. The specificity of the antibody was high as shown by the use of various methamphetamine analogs.


Ectopic pregnancies: Catch them early, treat them wisely!
Ectopic pregnancy (EP) is a common condition encountered in Obstetrics and Gynecology. Different management protocols are currently available for haemodymanically stable patients but definitive recommendations is yet to be established, especially in developing countries with limited resources. To determine the outcome of EP in patients who are haemodynamically stable and to evaluate the factors that would predict success of specific management protocols in them. Haemodynamically stable patients with HCG levels <1500 mIU/ml were recruited for expectant management, 1500-5000 mIU/ml were given MTX and those with >5000 mIU/ml were managed surgically. The overall success rate for expectant management was 92.7% and that with MTX was 80%. Baseline HCG values was found to be the only significant factor for predictor of success of treatment in the expectant group (P 0.05). The size of mass seen on USG did not have a significant correlation with beta HCG values (P 0.257). Of all the predictors for success of treatment that have been studied, the initial HCG value alone remains of paramount importance. Women with initial values of HCG <1500 mIU/ml can be offered expectant management, with a much better assurance of success for those with values <1000 mIU/ml. Those with values <5000 mIU/ml can be given MTX, with single dose being sufficient most often for <3000 mIU/ml. The presence of fluid restricted to the pelvis on USG can be managed non-surgically. One should not opt for surgical management only on the basis of size of the adnexal mass on USG.


Effect of inhibiting N-glycosylation on the stability and binding activity of the low density lipoprotein receptor.
Tunicamycin, a specific inhibitor of N-glycosylation, was used to study the function of asparagine-linked oligosaccharides of the low density lipoprotein (LDL) receptor in cultured human skin fibroblasts. When cells were preincubated in the presence of 0.5 micrograms/ml of the drug the incorporation of [3H]mannose into the receptor was completely prevented and that of [3H]glucosamine was reduced to approximately 41% of the control value. The [35S]methionine radioactivity detected in receptor core protein of tunicamycin-treated cells was about 52% of that measured in the receptor of control cells. The decrease in the radioactivity was similar in both the mature receptor as well as in its precursor form, and it was significantly greater than that found in total protein. The rates of receptor degradation in control- and tunicamycin-treated cells were comparable. Neither cell surface appearance of the newly synthesized LDL receptor nor its recycling were affected by tunicamycin. However, the LDL receptor produced in tunicamycin-treated cells was smaller in molecular size, and it exhibited an about 50% lower binding capacity when compared with its counterpart synthesized in control cells. This indicates that there is a relationship between N-glycosylation and the ligand binding activity of the LDL receptor. The possible role of asparagine-linked oligosaccharides in optimizing the biological activity of the LDL receptor is discussed.


Intermolecular copper-catalyzed carbon [bond] hydrogen bond activation via carbene insertion.
A series of catalysts of general formula TpXCu (TpX = homoscorpionate ligand) promote the insertion of :CHCO2Et (ethyl diazoacetate as the carbene source) into the C-H bonds of cycloalkanes and cyclic ethers in moderate to high yield. A correlation between the steric hindrance of these catalysts and the yield of the transformation has been observed.


Differential detection of porcine reproductive and respiratory syndrome virus genotypes by a fluorescence melting curve analysis using peptide nucleic acid probe-mediated one-step real-time RT-PCR.
Peptide nucleic acids (PNAs), artificially synthesized DNA analogues, hybridize strongly with DNA and are useful for fluorescence melting curve analyses (FMCA) based on the thermal denaturation of the probe-target duplex. In this study, we developed a PNA-based one-step real-time RT-PCR assay for the differential and qualitative detection of the porcine reproductive and respiratory syndrome virus genotypes PRRSV1 and PRRSV2. The specificity of the assay was analyzed in silico using previously reported primers and probes and was subsequently verified using Korean PRRSV panels and clinical samples. Seven clinical samples showing low curves with high Ct values were confirmed as negative by FMCA. The sensitivities of one-step real-time PCR for PRRSV1 and PRRSV2 were 15 and 11 copies, respectively, and the results were in 100% agreement with those of conventional RT-PCR combined with nested PCR using clinical samples. Therefore, the assay is highly specific for the detection of current PRRSV1 and PRRSV2 without non-specific amplification by FMCA.


SYBR Green-based real-time PCR targeting kinetoplast DNA can be used to discriminate between the main etiologic agents of Brazilian cutaneous and visceral leishmaniases.
Leishmaniases control has been hampered by the unavailability of rapid detection methods and the lack of suitable therapeutic and prophylactic measures. Accurate diagnosis, which can distinguish between Leishmania isolates, is essential for conducting appropriate prognosis, therapy and epidemiology. Molecular methods are currently being employed to detect Leishmania infection and categorize the parasites up to genus, complex or species level. Real-time PCR offers several advantages over traditional PCR, including faster processing time, higher sensitivity and decreased contamination risk. A SYBR Green real-time PCR targeting the conserved region of kinetoplast DNA minicircles was able to differentiate between Leishmania subgenera. A panel of reference strains representing subgenera Leishmania and Viannia was evaluated by the derivative dissociation curve analyses of the amplified fragment. Distinct values for the average melting temperature were observed, being 78.95 °C ± 0.01 and 77.36 °C ± 0.02 for Leishmania and Viannia, respectively (p < 0.05). Using the Neighbor-Joining method and Kimura 2-parameters, the alignment of 12 sequences from the amplified conserved minicircles segment grouped together L. (V.) braziliensis and L. (V.) shawii with a bootstrap value of 100%; while for L. (L.) infantum and L. (L.) amazonensis, two groups were formed with bootstrap values of 100% and 62%, respectively. The lower dissociation temperature observed for the subgenus Viannia amplicons could be due to a lower proportion of guanine/cytosine sites (43.6%) when compared to species from subgenus Leishmania (average of 48.4%). The method was validated with 30 clinical specimens from visceral or cutaneous leishmaniases patients living in Brazil and also with DNA samples from naturally infected Lutzomyia spp. captured in two Brazilian localities. For all tested samples, a characteristic amplicon melting profile was evidenced for each Leishmania subgenus, corroborating the data from reference strains. Therefore, the analysis of thermal dissociation curves targeting the conserved kinetoplast DNA minicircles region is able to provide a rapid and reliable method to identify the main etiologic agents of cutaneous and visceral leishmaniases in endemic regions of Brazil.


Neurodevelopmental Follow-up of Preterm Infants: What Is New?
There is increasing evidence of ongoing changes occurring in short-term and long-term motor and language outcomes in former premature infants. As rates of moderate to severe cerebral palsy (CP) have decreased, there has been increased awareness of the impact of mild CP and of developmental coordination disorder on the preterm population. Language delays and disorders continue to be among the most common outcomes. In conjunction with medical morbidities, there is increased awareness of the negative impact of family psycho-socioeconomic adversities on preterm outcomes and of the importance of intervention for these adversities beginning in the neonatal ICU.


Hand function in cerebral palsy. Report of 367 children in a population-based longitudinal health care program.
To describe aspects of hand function in a total population of children with cerebral palsy (CP). Upper extremity data were collected for 367 children who were born between 1992 and 2001 and were registered in a population-based health care program for children with CP. Hand function was classified according to the Manual Ability Classification System (MACS), the House functional classification, and the Zancolli classification. The type of spastic thumb-in-palm deformity was evaluated according to House. In the total population of children with CP aged 4 to 14 years, 60% had more than minor problems with hand function (>MACS I). Independence in age-relevant, daily manual activities (MACS I-II) was noted in 87% of children with spastic unilateral CP and in 63% of children with spastic bilateral CP, but in only 20% of children with dyskinetic CP. According to the House functional classification, both hands were spontaneously and independently used in 55% of children (House 7-8), whereas 5% did not use either of their hands (House 0). Minor increase of flexor muscle tone (Zancolli level 1) was found in 69% of all children. Only 2% were in level 3 in both hands. Spastic thumb-in-palm deformity in 1 hand was found in 25% and in both hands in another 15%. Limitations in hand function are common in all types of CP, but characteristics of the disability vary considerably between different CP subtypes. The MACS classification is useful to evaluate how well children can handle objects in daily activities. The House functional classification describes grip function in each hand separately; the Zancolli classification of finger and wrist extension and the classification of thumb-in-palm deformity according to House give an estimate of dynamic spasticity. All these classifications were shown to be useful in a population-based health care program, but further studies of the psychometric properties are required.


Hydrodynamics in Acute Ischemic Stroke Catheters Under Static and Cyclic Aspiration Conditions.
Previous studies have suggested improved recanalization efficiency by using cyclic aspiration as opposed to static aspiration for mechanical thrombectomy in the treatment of acute ischemic stroke (AIS). However, there has not been an investigation into which parameters optimize this theoretical approach. Therefore, this study was designed to investigate the application of static and cyclic pressure in AIS aspiration catheters. An experimental flow system was designed to apply and measure both static and cyclic aspiration pressures in four commercial aspiration catheters. A medical aspirator and solenoid-valve were used to generate a range of applied pump pressures and cyclic valve frequencies. The measured mean and oscillatory pressure amplitudes were analyzed and compared across catheters and operating conditions. The greatest mean pressures and forces were achieved under contact-aspiration conditions using the largest diameter catheter, while the largest oscillating pressure (ΔP) and force (ΔF) values were generated in the least compliant catheter, determined to be proportional to both its inner radius and wall thickness. Furthermore, lower frequency cyclic aspiration was able to generate the largest values of ΔP and ΔF. For future investigations of cyclic aspiration AIS therapy, the best options are to use large inner diameter and low compliance catheters operating at lower cyclic frequencies to generate the greatest mean and oscillating forces on lodged thromboemboli.


The mechanism of liposomal damage by taurocholate.
The stability of small unilamellar vesicles formed by egg-yolk phosphatidylcholine (PC) has been examined in the presence of sodium taurocholate. The permeability of the vesicular membrane changes as the total taurocholate concentration increases, until a transformation from mixed bile salt/PC vesicles to mixed micelles occurs. Based on experiments in which the bile salt-induced release of either hydrophilic (carboxyfluorescein) or hydrophobic (Bromothymol blue) probes was studied, and on fluorescence polarization of the probe 1,6-diphenyl-1,3,5-hexatriene and turbidity measurements, a two-step process for the initial stage of liposomal damage by taurocholate is postulated.


Chemokines in the pathogenesis of endometriosis and infertility.
Endometriosis is a chronic benign disease that affects women of reproductive age causing abdominal pain and infertility. Its pathogenesis remains obscure despite all the research conducted over the past 100 years. However, there is a consensus among the specialists that the basis of its pathophysiology would be multifactorial. Many publications have demonstrated that chemokines are somehow associated with the development of endometriosis and infertility. In this study, we reviewed all PubMed literature using MeSH terms "chemokines" and "endometriosis" as well as "chemokines" and "female infertility" to establish what we know and what we do not yet know about this relationship.


Enhanced adenovirus transduction of hMSCs using 3D hydrogel cell carriers.
Hydrogels are increasingly being investigated as a means to implant cells for tissue engineering. One way to further enhance the repair response would be to combine the hydrogel cell carrier with gene transfer. Gene therapy, using adenoviral vectors, is an effective way to provide transient delivery of bioactive factors. However, current protocols require further optimization, especially if they are to be transferred into the clinic. This study opted to compare the efficiency of protocols for standard two-dimensional (2D) versus three-dimensional (3D), adenoviral-mediated, transduction of human mesenchymal stem cells. Two different multiplicities of infection were tested. After encapsulation in fibrin, alginate or agarose, cells were cultured for 28 days. Transduction in 3D showed a much higher efficiency, compared to standard 2D transduction protocols. In 3D, the amount of transgene produced was significantly higher, for every condition investigated. Furthermore, transduction in 3D does not require a cell culture step and can be conducted within the operating theatre. In conclusion, it was demonstrated that 3D transduction, using adenoviral vectors, is superior to standard transduction protocols in 2D. It therefore, might help increasing its administration in tissue engineering and clinical applications.


[Chemical reactions in double-stranded nucleic acids. The nature of the bond formed during chemical ligation using a cis-diol group].
Chemical and enzymatic ligation between the 5'-terminal phosphate of one oligonucleotide and the 3'-terminal 2',3'-cis-diol group of the other oligonucleotide on a complementary template was studied. Carbodiimide, imidazolide and N-hydroxybenzotriazole ester methods were used for chemical activation of the phosphate group, and T4 DNA ligase for enzymatic ligation. All the chemical activation methods produced 3',5'- and 2',5'-phosphodiester bonds (40-45 and 55-60%, resp.), whereas enzymatic ligation gave the product only with 3',5'-phosphodiester bond.


Vertical and seasonal patterns in competition for microalgae between intertidal gastropods.
Grazing by the snail Nerita atramentosa and the limpet Cellana tramoserica caused similarly great reductions in abundance of microalgae - measured by direct counts and by estimation of chlorophyll analyses. A smaller snail, Bembicium nanum, caused smaller reductions of microalgal resources, compared with ungrazed areas. These results were consistent with the competitive abilities of these three species. Chlorophyll concentrations in samples of grazed rocks were reliable estimates of the nature and abundance of food available to the grazers.Inter- and intra-specific competition amongst Nerita and Cellana were investigated at various densities in experimental cages. To examine the effects of different availability of food resources, the experiments were repeated at three heights on the shore (abundance of food decreases with height) and during autumn/winter and spring/summer periods of the year (less food is available during summer).Density-dependent mortality of Cellana was caused by the presence of other limpets, or of Nerita. Mortality was greatest at higher levels and during the spring/summer and was significantly, negatively correlated with mean chlorophyll concentration in the experimental cages. The only exception was that all limpets suddenly died in cages at the highest level during the summer period, which cannot be explained solely by competitive interactions. Nerita showed no density-dependent mortality during the short periods of these experiments. Tissue-weights of Nerita declined with increased density, but the effect of Cellana was not as great as the intraspecific effect of Nerita. Snails retained weight better at lower than at higher levels, and during the autumn/winter which is consistent with the availability of food. Tissue weights of both Nerita and Cellana were positively correlated with chlorophyll concentrations inside the cages in both seasons investigated.These experimental results demonstrate that intensity of competition will vary from place to place and time to time according to the densities and mixtures of the grazers, and according to the availability of microalgal food.


Customized noise-stimulation intensity for bipedal stability and unipedal balance deficits associated with functional ankle instability.
Stochastic resonance stimulation (SRS) administered at an optimal intensity could maximize the effects of treatment on balance. To determine if a customized optimal SRS intensity is better than a traditional SRS protocol (applying the same percentage sensory threshold intensity for all participants) for improving double- and single-legged balance in participants with or without functional ankle instability (FAI). Case-control study with an embedded crossover design. Laboratory. Twelve healthy participants (6 men, 6 women; age = 22 ± 2 years, height = 170 ± 7 cm, mass = 64 ± 10 kg) and 12 participants (6 men, 6 women; age = 23 ± 3 years, height = 174 ± 8 cm, mass = 69 ± 10 kg) with FAI. The SRS optimal intensity level was determined by finding the intensity from 4 experimental intensities at the percentage sensory threshold (25% [SRS₂₅], 50% [SRS₅₀], 75% [SRS₇₅], 90% [SRS₉₀]) that produced the greatest improvement in resultant center-of-pressure velocity (R-COPV) over a control condition (SRS₀) during double-legged balance. We examined double- and single-legged balance tests, comparing optimal SRS (SRS(opt1)) and SRS₀ using a battery of center-of-pressure measures in the frontal and sagittal planes. Anterior-posterior (A-P) and medial-lateral (M-L) center-of-pressure velocity (COPV) and center-of-pressure excursion (COPE), R-COPV, and 95th percentile center-of-pressure area ellipse (COPA-95). Data were organized into bins that represented optimal (SRS(opt1)), second (SRS(opt2)), third (SRS(opt3)), and fourth (SRS(opt4)) improvement over SRS₀. The SRS(opt1) enhanced R-COPV (P ≤ .05) over SRS₀ and other SRS conditions (SRS₀ = 0.94 ± 0.32 cm/s, SRS(opt1) = 0.80 ± 0.19 cm/s, SRS(opt2) = 0.88 ± 0.24 cm/s, SRS(opt3) = 0.94 ± 0.25 cm/s, SRS(opt4) = 1.00 ± 0.28 cm/s). However, SRS did not improve R-COPV over SRS₀ when data were categorized by sensory threshold. Furthermore, SRS(opt1) improved double-legged balance over SRS₀ from 11% to 25% in all participants for the center-of-pressure frontal- and sagittal-plane assessments (P ≤ .05). The SRS(opt1) also improved single-legged balance over SRS₀ from 10% to 17% in participants with FAI for the center-of-pressure frontal- and sagittal-plane assessments (P ≤ .05). The SRS(opt1) did not improve single-legged balance in participants with stable ankles. The SRS(opt1) improved double-legged balance and transfers to enhancing single-legged balance deficits associated with FAI.


[Fibrous dysplasia of the rib. Ten case reports].
Fibrous dyplasia is a rare sporadic disease accounting for 0.8% of primary bone tumors. This benign pseudotumor results from proliferation of fibrous tissue in bone and the production of immature bone tissue without an osteoblastic crown. The disease can involve one or more bones, ribs are rarely involved. We report a series of 10 cases of costal fibrous dysplasia. This series of 10 cases was collected over a period of 10 years (1996-2005). There were five men and five women, mean age 38.4 years, range 27-52 years. One rib was involved in eight patients, two ribs in two. Pain was the most frequent symptom. Plain X-rays showed signs suggestive of fibrous dysplasia. To confirm the diagnosis, rib resection was performed in all ten patients. Pathology examination provided the diagnosis. The postoperative period was uneventful in all patients and all are recurrence free at mean 50 months follow-up. Management of fibrous dysplasia can be simple surveillance in the majority of patients. Nevertheless, in the event of a single focus, particularly in a rib, fibrous dysplasia can raise a difficult problem of differential diagnosis with malignant tumors. Surgical resection is therefore required in selected cases.


Assessing groundwater quality in Greece based on spatial and temporal analysis.
The recent industrial growth together with the urban expansion and intensive agriculture in Greece has increased groundwater contamination in many regions of the country. In order to design successful remediation strategies and protect public health, it is very important to identify those areas that are most vulnerable to groundwater contamination. In this work, an extensive contamination database from monitoring wells that cover the entire Greek territory during the last decade (2000-2008) was used in order to study the temporal and spatial distribution of groundwater contamination for the most common and serious anionic and cationic trace element pollutants (heavy metals). Spatial and temporal patterns and trends in the occurrence of groundwater contamination were also identified highlighting the regions where the higher groundwater contamination rates have been detected across the country. As a next step, representative contaminated aquifers in Greece, which were identified by the above analysis, were selected in order to analyze the specific contamination problem in more detail. To this end, geostatistical techniques (various types of kriging, co-kriging, and indicator kriging) were employed in order to map the contaminant values and the probability of exceeding critical thresholds (set as the parametric values of the contaminant of interest in each case). The resulting groundwater contamination maps could be used as a useful tool for water policy makers and water managers in order to assist the decision-making process.


Emerging role of ubiquitin-specific protease 14 in oncogenesis and development of tumor: Therapeutic implication.
Ubiquitin (Ub) is a small protein that can be attached to substrate proteins to direct their degradation via the proteasome. Deubiquitinating enzymes (DUBs) reverse this process by removing ubiquitin from its substrate protein. Over the past few decades, ubiquitin-specific protease 14 (USP14), a member of the DUBs, has emerged as an important player in various types of cancers. In this article, we review and summarize biological function of USP14 in tumorigenesis and multiple signaling pathways. To determine its role in cancer, we analyzed USP14 gene expression across a panel of tumors, and discussed that it could serve as a novel bio-marker in several types of cancer. And recent contributions indicated that USP14 has been shown to act as a tumor-promoting gene via the AKT, NF-κB, MAPK pathways etc. Besides, drugs targeting USP14 have shown potential anti-tumor effect and clinical significance. We focus on recent studies that explore the link between USP14 and cancer, and further discuss USP14 as a novel target for cancer therapy.


Concurrent hypercortisolism and hypermineralocorticoidism.
Hypertension and hypokalemia occur in patients with Cushing's syndrome whereas aldosterone production is normal and plasma renin activity is usually normal or increased. A normal aldosterone level in the face of suppressed plasma renin activity is unusual and suggests excess mineralocorticoid hormone activity. Our patient, who had Cushing's syndrome due to adrenocortical adenoma, can be classified as having low renin hypertension (suppressed renin and normal aldosterone levels). The mineralocorticoid hormone in excess was deoxycorticosterone which suppressed renin. The aldosterone production was normal and was produced solely by the adenoma. Contralateral adrenal gland suppression of both the zona glomerulosa by deoxycorticosterone via renin, and of the fasciculata by cortisol via ACTH was demonstrated after removal of the adenoma. Normal adrenal function was gradually restored.


Diversity and association of HLA/KIR receptors with type 2 diabetes in South India.
The present study was undertaken to delineate the association(s) of KIR-HLA combination in South Indian Type 2 diabetes mellitus (T2DM) patients. The T2DM patients (n = 343) and healthy controls (n = 309) were genotyped for KIR/HLA ligands by PCR-SSP method. The increased frequency of activatory KIR (aKIR) 2DS2 (OR = 1.91; p < 2.91 × 10-4 ) was observed in patients suggesting a susceptible association. The frequencies of iKIR 2DL2 (OR = 0.38; p < 1.55 × 10-5 ) and aKIRs 2DS1 (OR = 0.60; p < 0.001) and 3DS1 (OR = 0.52; p < 5.83 × 10-5 ) were decreased in patients suggesting protective associations. The C1/C2 combinatorial analysis has revealed an increased frequency of C1+ /C2- in T2DM patients (OR = 1.62; p < 0.014). The KIR "AB" genotype (OR = 2.41; p < 3.87 × 10-5 ) was observed to be higher in patients. However, the "BB" genotype (OR = 0.32; p < 4.71 × 10-7 ) was increased in controls. The KIR motifs, "Tel-B/B" (OR = 1.84; p < 0.007), were observed higher among patients. However, the frequency of "Tel-A/B" motif genotype was decreased in patients (OR = 0.56; p < 3.13 × 10-4 ). The iKIR/HLA combinations such as 2DL2/3 +C1 and 3DL2+A3/A11 were increased in patients (OR = 3.90; p < 7.5 × 10-5 ) suggesting susceptible associations. On the contrary, the aKIR+HLA combinations such as 2DS2+C1, 2DS1+C2 and 3DS1+Bw4 were less frequent in patients (OR = 0.32; p < 4.2 × 10-4 ) suggesting protective associations. Thus, the present study clearly establishes the positive and negative associations of different KIR-HLA receptor combinations with T2DM in South India.


Organization and development of the brain stem auditory nuclei of the chicken: primary afferent projections.
The pattern of primary auditory projections to the brain stem of young chickens was investigated using terminal degeneration methods and orthograde transport of horseradish peroxidase (HRP) or tritiated amino acid. Of particular interest was the question of whether nucleus laminaris (NL) receives primary afferents. A study of silver-stained degeneration pattersn in nucleus magnocellularis (NM) and NL at three intervals following unilateral interruption of the cochlear nerve revealed that by 48 hours after the lesion, degenerating terminals were found only in the ipsilateral nucleus angularis (NA), NM and lagenar projection areas but not in NL. Five- and eight-day survival times, however, also revealed degeneration bilaterally in NL. The appearance of terminal degeneration in NL at the longer survival times is attributed to the previously-reported severe and rapid transneuronal degeneration of neurons in NM following deafferentation and not to the presence of cochlear nerve terminals in NL. Injection of HRP or tritiated proline into the basilar papilla produced patterns of labeling similar to that seen in the 2-day degeneration material; HRP reaction product or autoradiographic label were seen only in the ipsilateral NA and NM and in the ipsilateral projection areas of the macula lagena but not in either NL. The patterns of primary auditory projections revealed by the three methods were quite similar to each other and to that previously reported for the pigeon and confirm the conslucion that the laminar nucleus of chickens does not receive primary afferents.


Mechanisms of competition among insectivorous mammals.
This study investigates the mechanisms of competition between congeneric pairs of insectivorous mammals in two communities in Australia and England. Direct field observations showed that physical interactions between species do not occur, whereas conspecific encounters are frequent. In field enclosures the smaller, subordinate species in each community (Antechinus stuartii: Marsupialia: Sorex minutus: Eutheria) remained alert in the presence of the dominant species (A. swainsonii, S. araneus), and moved quickly away when the latter approached. The rate of prey capture by subordinate individuals also increased immediately after removal of the dominants. Hourly removals of some individuals of the dominant species in each community over 24 h produced hourly increases in the numbers of subordinate individuals that were captured. The rapidity of these responses suggests strongly that the dominant insectivores in each community interfered with the resource use of the subordinate species. Biomass of invertebrates increased inconsistently or slowly within 3 months of removal of the dominant insectivores; hence the rapid responses by subordinate individuals in experiments were not due to simple exploitation or tracking of resource levels. The subordinate insectivores probably detected and avoided contact with dominants instantaneously using auditory or olfactory cues; reciprocal avoidance of congeneric odours was demonstrated using odour-scented traps. Insectivorous mammals may usually compete by interference (or encounter competition, sensu Schoener 1983). For dominant species within communities the cost of interference is minimal and the benefit of gaining exclusive access to resource-rich microhabitats is high. Conversely for subordinate species the benefit of temporarily exploiting the same rich microhabitats may exceed the small costs of vigilance and movement to nearby refugia.


Testing of a potential mechanism for E. coli temporal cycle imprecision with a structural model.
A structured model for E. coli B/r-A was used to test a potential mechanism for cell cycle temporal imprecision. The mechanism assumes that variations in the activity of septation enzymes can occur. Such variations result in D period imprecision while the chromosome replication schedule is not directly affected. The main results of inserting the mechanism were the predicted ratio of cell doubling time to fission size coefficient of variations agreed with reported data as did the predicted negative correlation between parent-offspring cycle times. Consequently, the proposed mechanism, which suggests that D period fluctuations are the primary source of cell cycle variations, appears consistent with observed cell behavior.