A risk-group classification model in patients with bladder cancer under neoadjuvant cisplatin-based combination chemotherapy.
The objective of the current research was to explore the potential prognostic value of readily available clinical and pathologic variables in bladder cancer. The novel association found between cholesterol levels and prognosis may provide the rationale for exploring novel treatments. Patients included had histologically confirmed urothelial bladder cancer and were treated with at least 3 cycles of cisplatin-based neoadjuvant chemotherapy before radical cystectomy with lymphadenectomy. A total of 245 patients at low, intermediate and high risk, presenting with 0-1, 2 or 3-4 risk factors, including positive lymph nodes, Hb <12.8, NLR ≥2.7 and cholesterol levels ≥199, were included. Five-year cancer-specific survival rate was 0.67, 0.78 and 0.94 at high, intermediate and low risk, respectively. Total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and may be incorporated in a clinically meaningful risk-group classification model.


Nanomechanical motion of Escherichia coli adhered to a surface.
Nanomechanical motion of bacteria adhered to a chemically functionalized silicon surface is studied by means of a microcantilever. A non-specific binding agent is used to attach Escherichia coli (E. coli) to the surface of a silicon microcantilever. The microcantilever is kept in a liquid medium, and its nanomechanical fluctuations are monitored using an optical displacement transducer. The motion of the bacteria couples efficiently to the microcantilever well below its resonance frequency, causing a measurable increase in the microcantilever fluctuations. In the time domain, the fluctuations exhibit large-amplitude low-frequency oscillations. In corresponding frequency-domain measurements, it is observed that the mechanical energy is focused at low frequencies with a 1/fα -type power law. A basic physical model is used for explaining the observed spectral distribution of the mechanical energy. These results lay the groundwork for understanding the motion of microorganisms adhered to surfaces and for developing micromechanical sensors for bacteria.


Change of quality of life in patients with chronic pain with prescription opioid usage after opioid detoxification.
Managing patients with chronic pain with long-term opioid therapy can be challenging for the prescribers, as the development of treatment complications such as addiction and opioid-induced hyperalgesia has to be considered. There is a paucity of information on the use of opioid detoxification protocols in patients with chronic pain on a long-term opioid therapy who have developed opioid-induced complications. To determine the effectiveness of detoxification treatment while presenting a different opioid detoxification protocol intended to cease patient's prescription opioid use while assessing patient's quality of life (QoL) changes, implicated by our treatment. We retrospectively studied 41 patients with chronic pain with long-term prescription opioid usage who underwent elective opioid detoxification in years 2010-2019 at the Toxicology Centre of Republican Vilnius University Hospital. We ceased prescription opioids during detoxification treatment and monitored withdrawal symptoms, pain intensity, and QoL by using SF-36 scores before and right after and a minimum of 3 months after detoxification. This study was fully completed by 14 patients. At the third SF-36 evaluation, 12 out of 14 patients (85.71 percent) reported the detoxification treatment as beneficial to their overall health status compared to that before the treatment, and SF-36 scores after detoxification were significantly higher than before the treatment (p = 0.001). A decreased pain level right after detoxification was indicated by 11 patients (78.6 percent). Significant pain decrease was observed both right after and at least 3 months after the opioid detoxification treatment (p < 0.05). As significant pain reduction, QoL life improvement, and opioid usage cessation were observed after opioid detoxification in the majority of patients with chronic pain, this leads us to believe that such a treatment can be safely administered and appropriated.


Disposable electrochemical immunosensor for environmental applications.
An Immunosensor for the detection of polychlorinated biphenyls (PCB) has been developed, using carbon-based screen-printed electrodes as solid-phase and signal transducers. The immunosensor realised is based on a direct competitive immunoassay scheme, in which the antibody against PCB was directly immobilised onto the carbon surface of the screen-printed electrode. Competition between the PCBs present in the sample and a fixed concentration of an enzyme-labelled congener was realised and evaluated by electrochemical detection. The immunosensor developed was tested on Arochlor mixtures (1242 and 1248), and was applied in environmental and food analysis by testing some real samples (from animal tissues and marine sediments). Results obtained demonstrate the ability of this device to detect PCBs in complex matrices.


Caloric restriction affects liver microsomal monooxygenases differentially in aging male rats.
Caloric restriction (CR) extends life span and retards the onset of physiological changes and pathologies associated with aging, but the underlying mechanisms remain unresolved. This study demonstrates that CR postpones the documented age-related declines in and/or enhances the activity and microsomal concentration of several liver monooxygenases in male rats, i.e., NADPH cytochrome P-450 reductase, total cytochromes P-450. However, the relative concentration of cytochrome P-450b+C did not exhibit statistically significant changes, whereas another isozyme, the male specific P-450h, declined significantly in both ad libitum-fed and CR rats as a function of increasing age. While CR appears to retard age-associated changes in certain liver enzymes, this effect is by no means universal. The hepatic monooxygenases constitute a well-characterized enzyme system in which to examine the perturbation of the aging process by CR.


Reasoning for registrars--an overview for supervisors and medical educators.
As supervisors and medical educators, one of the most difficult tasks we face is helping a general practice registrar who is struggling to adapt to the primary care environment. Of course, there are many features of the registrar that can make this process difficult: a need for certainty, a lack of flexibility, or personal or professional qualities. And sometimes we find it difficult to create an environment conducive to effective learning: interpersonal conflicts, lack of educational experience or resources, and the perennial lack of time may affect our capacity to support our registrars.


Efficacy of STI571 for a patient with metastatic gastrointestinal stromal tumor.
A 65-year-old man was referred to our hospital for evaluation of his huge abdominal tumor. He was diagnosed as having a gastrointestinal stromal tumor arising from the stomach. Seven months after surgery, multiple liver metastases and mesenteric dissemination occurred. He was medicated with STI571, which works by blocking proliferation of malignant cells with expression of c-kit. The tumors shrank and serum lactate dehydrogenase and alkaline phosphatase concentrations fell to below the normal limit three months later. STI571 was effective medicine for the metastatic gastrointestinal stromal tumor for six months in this case.


[Induced pluripotent stem (iPS) cell-based cell therapy for muscular dystrophy: current progress and future prospects].
Duchenne muscular dystrophy (DMD) is a devastating muscle disorder caused by mutations in the dystrophin gene. There is currently no effective treatment for DMD. Muscle satellite cells are tissue-specific stem cells found in the skeletal muscle; these cells play a central role in postnatal muscle growth and regeneration, and are, therefore, a potential source for stem cell therapy for DMD. However, transplantation of satellite cell-derived myoblasts has not yet been successful in humans. Patient-specific induced pluripotent stem (iPS) cells are expected to be a source for autologous cell transplantation therapy for DMD, because iPS cells can proliferate vigorously in vitro and can differentiate into multiple cell lineages both in vitro and in vivo. Here, we discuss the strategies to generate muscle stem cells from iPS cells. So far, the most promising method for generating muscle stem cells from iPS cells is the conditional overexpression of Pax3 or Pax7 in the differentiating mouse embryoid bodies. However, induction methods for human iPS cells have not yet been developed. Thus, iPS cells are expected to serve as an in vitro disease model system, which will enable us to determine the pathology of muscle diseases and develop pharmaceutical treatments.


The role of visual-spatial attention in reading development: a meta-analysis.
The association between visual attention and reading development has been investigated as a possible core causal deficit in dyslexia, in addition to phonological awareness. This study aims to provide a meta-analytic review of the research on attentional processes and their relation to reading development, to examine the possible influence on it of orthographic depth, age, and attentional tasks (interpreted as serial or parallel processing indices). We included studies with participants up to 18 years of age that have considered the visual spatial attention orienting that sustains the serial visual analysis involved in the phonological pathway of decoding, and the visual attention span that supports the multielement parallel processing that is thought to influence lexical decoding. The results confirm a strong association between visual attention and reading development; we evaluate the evidence and discuss the possibility that visual attention processes play a causal role in determining individual differences in reading acquisition.


ERP Detection Based on Smoothness Priors.
Detection of event-related potentials (ERPs) in electroencephalography (EEG) is of great interest in the study of brain responses to various stimuli. This is challenging due to the low signal-to-noise ratio of these deflections. To address this problem, a new scheme to detect the ERPs based on smoothness priors is proposed. The problem is considered as a binary hypothesis test and solved using a smooth version of the generalized likelihood ratio test (SGLRT). First, we estimate the parameters of probability density functions from the training data under the Gaussian assumption. Then, these parameters are treated as known values and the unknown ERPs are estimated under the smoothness constraint. The performance of the proposed SGLRT is assessed for ERP detection in post-stimuli EEG recordings of two oddball settings. We compared our method with several powerful methods regarding ERP detection. The presented method performs better than the competing algorithms and improves the classification accuracy. SGLRT can be employed as a powerful means for different ERP detection schemes. The proposed scheme is opening a new direction in ERP identification which provides better classification results compared to several popular ERP detection methods.


Attitudes, beliefs, and practices regarding smoking and smoking cessation among African-American physicians and dentists.
African-American physicians and dentists in metropolitan Atlanta were surveyed to assess smoking cessation practices and perceptions. Questionnaires were mailed to 373 physicians and 90 dentists. A total of 154 questionnaires were returned, for an overall response rate of 33.3%. More physicians than dentists considered smoking a "very serious" threat to patients' health, and physicians were more likely to document smoking status in charts and to counsel smokers to quit. Physicians also were approached more frequently by patients seeking cessation advice. Both types of practitioners considered the nicotine patch, formal cessation programs, and behavior modification/psychotherapy to be among the most effective cessation methods, and nicotine gum and acupuncture to be among the least effective. These results indicate African-American physicians are much more involved than dentists in promoting smoking cessation among patients. Advice of health professionals generally is viewed as a powerful influence for African-American patients. Further work is needed to utilize fully the power of health care providers, especially dentists, in the fight against tobacco-related morbidity and mortality.


Partial nucleotide sequence of the Xanthomonas maltophilia chorionic gonadotropin-like receptor.
Xanthomonas maltophilia possesses a unique high-affinity binding site which binds human chorionic gonadotropin (hCG), but not human luteinizing hormone (hLH) or other glycoprotein hormones. We designed primers from the known nucleotide sequence of the human LH/CG receptor, spanning an area extending from transmembrane region 2 to transmembrane region 6. Genomic DNA extracted from Xanthomonas maltophilia was used to obtain a PCR amplified product using the above primers. The primary amplification product was cloned in a pCR11 TA cloning vector, and the partial nucleotide sequence of the gene determined. This determined sequence showed 73% identity with the human, as well as the rat LH/CG receptor. Comparison of the translated protein sequence with the human, rat and porcine receptor protein sequences showed a 52% similarity.


Chemometric analysis of chromatographic fingerprints shows potential of Cyclopia maculata (Andrews) Kies for production of standardized extracts with high xanthone content.
Cyclopia species are used for the production of honeybush tea and food ingredient extracts associated with many health benefits. A species-specific high-performance liquid chromatography (HPLC) method for Cyclopia maculata, developed and validated, allowed quantification of the major compounds in extracts from "unfermented" and fermented C. maculata. Two xanthones were tentatively identified for the first time in a Cyclopia species, whereas an additional four compounds were tentatively identified for the first time in C. maculata. "Fermentation" (oxidation) decreased the content of all compounds, with the exception of vicenin-2. Similarity analysis of the chromatographic fingerprints of unfermented C. maculata aqueous extracts showed extremely low variation (r ≥ 0.97) between samples. Some differences between wild-harvested and cultivated seedling plants were, however, demonstrated using principal component analysis. Quantitative data of selected compounds confirmed the low level of variation, making this Cyclopia species ideal for the production of standardized food ingredient extracts.


Calculation of the point-by-point error in protein crystallographic electron-density functions.
In protein crystallographic studies, the mean-square error at each point in the electron-density function is given, in space group P1, by [formula: see text] Here, Fo is the observed structure-factor amplitude; m(h) exp [i alpha B(h)] = P[alpha(h)] exp (i alpha) d alpha is the weighted phase factor in the 'best' Fourier coefficient of Blow & Crick; m2(h) exp (i alpha 2) = P[alpha(h)] exp (2i alpha) d alpha is similar to a traditional second moment. P[alpha(h)] d alpha is the probability that the phase angle for a given reflection has value between alpha and alpha + d alpha.


Physical training increases eNOS vascular expression and activity and reduces restenosis after balloon angioplasty or arterial stenting in rats.
The effects of dynamic exercise on restenosis after vascular injury are still unknown. The consequences of balloon dilation-induced injury on neointimal hyperplasia, vascular negative remodeling, and reendothelialization were assessed in sedentary and trained rats. Ex vivo eNOS vascular expression and activity were investigated in carotid arteries isolated from sedentary and exercised rats. The in vivo effects of eNOS inhibition by L-NMMA on vessel wall after balloon dilation were evaluated in sedentary and exercised rats. We also investigated the effects of exercise on neointimal formation in a rat stent model of vascular injury. Compared with sedentary group, the arteries isolated from trained rats showed higher levels of eNOS protein expression and activity 7 days after balloon dilation. A significant reduction of both neointimal hyperplasia and negative remodeling was observed 14 days after balloon injury in trained compared with sedentary rats. Moreover, we demonstrated that exercise training produced accelerated reendothelialization of the balloon injured arterial segments compared with sedentary. L-NMMA administration eliminated the benefits of physical training on vessel wall after balloon dilation. Finally, a decrease of neointimal hyperplasia as well as of platelet aggregation was observed after stent deployment in trained rats compared with sedentary. In conclusion, physical exercise could favorably affect restenosis after balloon angioplasty and stenting. Increase in eNOS expression and activity might contribute to the potential beneficial effects of exercise on the vessel wall after vascular injury.


Annexin A4 self-association modulates general membrane protein mobility in living cells.
Annexins are Ca2+-regulated phospholipid-binding proteins whose function is only partially understood. Annexin A4 is a member of this family that is believed to be involved in exocytosis and regulation of epithelial Cl- secretion. In this work, fluorescent protein fusions of annexin A4 were used to investigate Ca2+-induced annexin A4 translocation and self-association on membrane surfaces in living cells. We designed a novel, genetically encoded, FRET sensor (CYNEX4) that allowed for easy quantification of translocation and self-association. Mobility of annexin A4 on membrane surfaces was investigated by FRAP. The experiments revealed the immobile nature of annexin A4 aggregates on membrane surfaces, which in turn strongly reduced the mobility of transmembrane and plasma membrane associated proteins. Our work provides mechanistic insight into how annexin A4 may regulate plasma membrane protein function.


Barriers and facilitators to person-centred infection prevention and control: results of a survey about the Dementia Isolation Toolkit.
People working in long-term care homes (LTCH) face difficult decisions balancing the risk of infection spread with the hardship imposed on residents by infection control and prevention (ICP) measures. The Dementia Isolation Toolkit (DIT) was developed to address the gap in ethical guidance on how to safely and effectively isolate people living with dementia while supporting their personhood. In this observational study, we report the results of a survey of LTCH staff on barriers and facilitators regarding isolating residents, and the impact of the DIT on staff moral distress. We completed an online cross-sectional survey. Participants (n = 207) were staff working on-site in LTCH in Ontario, Canada since March 1, 2020, with direct or indirect experience with the isolation of residents. LTCH staff were recruited through provincial LTCH organizations, social media, and the DIT website. Survey results were summarized, and three groups compared, those: (1) unfamiliar with, (2) familiar with, and (3) users of the DIT. 61% of respondents identified distress of LTCH staff about the harmful effects of isolation on residents as a major barrier to effective isolation. Facilitators for isolation included delivery of 1:1 activity in the resident's room (81%) and designating essential caregivers to provide support (67%). Almost all respondents (84%) reported an increase in moral distress. DIT users were less likely to report an impact of moral distress on job satisfaction (odds ratio (OR) 0.41, 95% CI 0.19-0.87) with 48% of users reporting the DIT was helpful in reducing their level of moral distress. Isolation as an ICP measure in LTCH environments creates moral distress among staff which is a barrier to its effectiveness. ICP guidance to LTCH would be strengthened by the inclusion of a dementia-specific ethical framework that addresses how to minimize the harms of isolation on both residents and staff.


Melatonin reduces the expression of chemokines in rat with trinitrobenzene sulfonic acid-induced colitis.
To investigate the effect of melatonin on the colon inflammatory injury of rats with colitis and determine whether this effect is associated with inhibition of chemoattractant molecules interleukin (IL-8) and monocyte chemoattractant protein (MCP-1). The study was designed and implemented in JingMen No.1 People's Hospital, HuBei Province, from May 2006 to April 2007. It involved 72 animals divided into 6 groups of 12 each: normal group, model group, 5-aminosalisalicylic acid group,and melatonin group (dose of 2.5, 5.0, and 10.0mg/kg). Rat colitis model was established by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) enema. Interlukin-8 and MCP-1 proteins in colon tissue were examined by immunohistochemistry and western blot. The messenger-RNA expressions of chemokines were determined by reverse transcription polymerase chain reaction analysis. Trinitrobenzene sulfonic acid enema resulted in pronounced pathological changes of colonic mucosa in model rats, which were in accordance with the significantly elevated myeloperoxidase activity. Expressions of chemokines were up-regulated in colitis. Melatonin treatment reduced colonic lesions and improved colitis symptom, and decreased the protein and mRNA expressions of IL-8 and MCP-1 significantly in colon tissues of rats with colitis. Chemokines IL-8 and MCP-1 are elevated in mucosal tissues in colitis and play an important role in the perpetuation of tissue destructive inflammatory processes; melatonin reduces colonic inflammatory injury of rats colitis through down-regulating the expressions of chemokines. Melatonin can be considered as a novel therapeutic alternative for the treatment of inflammatory bowel disease.


Novel compound, (2Z,6E)-1-hydroxy-3,7-dimethyl-2,6-octadien-8-oic acid produced from biotransformation of nerol by Spodoptera litura larvae.
Biotransformation of nerol by larvae of the common cutworm (Spodoptera litura) was investigated. The resulting major metabolites were (2Z,6E)-1-hydroxy-3,7-dimethyl-2,6-octadien-8-oic acid and 8-hydroxynerol, and the minor metabolites were 9-hydroxynerol and (2Z,6E)-1-hydroxy-3,7-dimethyl-2,6-octadien-8-al. (2Z,6E)-1-Hydroxy-3,7-dimethyl-2,6-octadien-8-oic acid is a novel compound. The results indicate that biotransformation of nerol by S. litura larvae involved 2 pathways; the main pathway involved oxidation at the methyl group of the geminal dimethyl at C-8 position followed by carboxylation, and the minor pathway involved oxidation at the methyl group of the geminal dimethyl at C-9 position.


Detection of CMV DNA in peripheral blood leukocytes as a long-range harbinger of CMV disease in HIV-infected patients. Swiss HIV Cohort Study.
The incidence of cytomegalovirus (CMV) end-organ disease can be reduced in AIDS patients by oral ganciclovir. However, the cost effectiveness of this prophylaxis is low. Targeting prophylaxis to patients with the highest risk of developing CMV disease might be useful. Several studies have shown the potential of various polymerase chain reaction (PCR) assays and of the antigenemia assay to identify the subset of patients with a definitely higher risk of developing CMV disease. We studied the CMV viral load using quantitative PCR in the leukocytes and plasma (or serum) of 28 patients in the four years before they experienced a CMV event. We observed rising CMV DNA copy numbers in the patients' leukocytes a year before the event. In contrast, plasma or serum copy numbers rose later and in fewer patients. In a control population of 21 profoundly immunodeficient patients (median CD4+ T cell count: 31/mm(3)) without history of CMV disease, only five had detectable CMV DNA in the leukocytes, three of whom had barely above-threshold levels. We suggest that, at the present time, leukocyte CMV DNA PCR might represent a sensitive test providing an early warning signal of increased risk of CMV disease. Performing it twice a year might identify patients at risk so that closer monitoring and targeted prophylaxis can be conducted.


William Osler and the "fixed period" of creativity.
In 1905, William Osler was the pre-eminent physician in American medical circles but was unknown to the general public. The latter suddenly learned of him through damning newspaper accounts of his address announcing his retirement from the Johns Hopkins Medical School. In it Osler mentioned two "fixed ideas" he held-(1) that most major advances in civilization have been made by men under age 40 (the "fixed period") and (2) that those over 60 should retire because they create little of significance and sometimes stifled the initiatives of younger colleagues. He highlighted the second idea with a Victorian novel describing a mythical society which chloroformed men at age 60. He never imagined that this literary allusion would be taken as a serious solution for his second idea. However, countless newspaper articles ridiculed the first and condemned him for the second. Scurrilous press attacks on him continued for several months and resurfaced occasionally thereafter. The extent of the public approbation can also be found in poems and stories linking him with euthanasia. Also discussed here are the sources of Osler's equanimity in the face of such public derision and the inner drives which accounted for over 1300 publications by him-nearly half of which were composed after age 40.


Amantadine acetylation may be effected by acetyltransferases other than NAT1 or NAT2.
Amantadine is a drug with a primary amino group, and consequently a likely candidate for metabolism by acetylation. This study assessed the possibility that a person's polymorphic (NAT2) acetylator phenotype could be used to predict the extent of amantadine acetylation. Thirty-eight normal, healthy volunteers were NAT2 acetylator phenotyped with sulfapyridine. Of the six fastest (75-86%) and six slowest (34-40%) sulfapyridine acetylators, two and three, respectively, had acetylamantadine present (18-338 microg) in the 8-h urine collection. There was no correlation between NAT2 acetylator phenotype and amantadine acetylation (p<0.5), and no difference in the total urine amantadine excreted over 8 h between acetylators and nonacetylators (28.3+/-9.7 vs. 30.4+/-9.6 mg, respectively, mean +/- SD). Acetylamantadine represented 0.1-1.5% (median 0.5%) of urinary drug content over 8 h. Our data confirm that amantadine is acetylated in humans and demonstrate for the first time that the extent is not correlated with NAT2 acetylator phenotype. Parallel in vitro enzyme studies indicate the possibility that neither NATI nor NAT2 is responsible for acetylation of amantadine.


Transient improvement in chronic psoriasis after treatment of TNF-α blocker induced disseminated M. tuberculosis infection.
Improvement in psoriasis after treatment of reactivated latent tuberculosis following initiation of TNF-α inhibitor therapy has yet to be described in the literature. The authors present a case of transient, yet significant, improvement in chronic plaque psoriasis after antibiotic therapy for reactivated TB.


Multi-Institutional, Prospective Clinical Utility Study Evaluating the Impact of the 92-Gene Assay (CancerTYPE ID) on Final Diagnosis and Treatment Planning in Patients With Metastatic Cancer With an Unknown or Unclear Diagnosis.
Metastatic cancers of unknown primary or with unclear diagnoses pose diagnostic and management challenges, often leading to poor outcomes. Studies of the 92-gene assay have demonstrated improved diagnostic accuracy compared with standard pathology techniques and improved survival in patients treated on the basis of assay results. The current study assessed the clinical impact of the 92-gene assay on diagnostic and treatment decisions for patients with unknown or uncertain diagnoses. Patients in this prospective, multi-institutional, decision-impact study included those for whom the 92-gene assay was ordered as part of routine care. Participating physicians completed electronic case report forms that contained standardized, specialty-specific questionnaires. Data collection included patient and tumor characteristics and clinical history. The key study objective of clinical impact was calculated on the basis of changes in final diagnosis and treatment after testing. Data collection included 444 patients, 107 physicians (73 oncologists and 34 pathologists), and 28 sites. Molecular diagnoses from 22 different tumor types and subtypes across all cases were provided in 95.5% of patients with a reportable result (n = 397). Physicians reported that the 92-gene assay was used broadly for diagnostic dilemmas that ranged from single suspected tumor type (29%) to a differential diagnosis of two or more suspected tumor types (30%) or cancers of unknown primary (41%). Integration of 92-gene assay results led to a change in the recommended treatment in 47% of patients. Findings from this clinical utility study demonstrate that the 92-gene assay led to a change in treatment decisions in every other patient case. These data additionally define the role of this assay in clinical practice and strongly support the consideration of molecular tumor typing in the diagnosis and treatment planning of patients with metastatic cancer with unknown or uncertain diagnosis.


Dock3-NMDA receptor interaction as a target for glaucoma therapy.
Glaucoma is a neurodegenerative disease of the eye and it is one of the major causes of blindness. Glaucoma is usually associated with elevated intraocular pressure (IOP) and the current therapy focuses on reduction of IOP. However, neuroprotective strategies could also be beneficial for treatment of glaucoma because the pathology of the disease involves retinal ganglion cell (RGC) death and damage to the optic nerve. Dedicator of cytokinesis 3 (Dock3) is an atypical guanine exchange factor (GEF) that belongs to a family of Dock proteins, Dock1-11. Dock3 exerts neuroprotective effects on the retina and optic nerve, and studies revealed that some of the Dock3-mediated effects are GEF-independent. One of these mechanisms is that Dock3 directly binds to the GluN2B subunit of the N-methyl-D-aspartate (NMDA) receptor. Upon stimulation by NMDA or optic nerve crush, overexpression of Dock3 promotes internalization and degradation of the NMDA receptor in the retina in vivo. It is suggested that this process is mediated by inhibition of Fyn, a Src family tyrosine kinase. Reduction in NMDA receptor expression results in decreased excitotoxic damage and oxidative stress, thereby promoting RGC survival. In this review, we discuss the therapeutic potential of neuroprotection for glaucoma and the effects of Dock3 on NMDA receptors. We also discuss apoptosis signal-regulating kinase 1 (ASK1), a member of mitogen-activated protein kinase kinase kinase that is a key regulator of cellular responses to oxidative stress, as an innovative therapeutic target for glaucoma.


Dissipative soliton resonance mode-locked double clad Er:Yb laser at different values of anomalous dispersion.
Emission of an all-fiber, Dissipative Soliton Resonance (DSR) mode-locked, Double-Clad (DC), Erbium-Ytterbium (Er:Yb) laser configuration is investigated under several different values of large anomalous dispersion. The laser was mode-locked by means of Nonlinear Amplifying Loop Mirror (NALM) in a Figure-8 (F8) resonator configuration. The boundaries of anomalous dispersion in which the laser operated in purely DSR regime was experimentally verified by changing the length of passive SMF28 fiber spliced into the NALM. The influence of 6 different values of dispersion (-1.061 ps2 to -10.7 ps2) on the pulse properties is presented and discussed.


Angiostrongylus costaricensis in a black-eared marmoset.
A case of Angiostrongylus costaricensis in a captive C. penicillata in a German zoological garden is described. Clinical symptoms were lacking, the morphological lesions consisted of intestinal granulomas harbouring rhabdidiform larvae. The adult worms were present in the ileo-caecal branches of the mesenteric artery.


Effect of a Lactobacillus fermentation product on postweaning heifer performance.
The objective of the experiment was to compare the effect of dietary inclusion of a prebiotic fermentation product of Lactobacillus acidophilus (LaP, RumaCell; 5 mL animal-1 d-1) or monensin on performance of replacement beef heifers. Heifers received a total mixed ration containing either LaP (n = 77) or monensin (MON; Rumensin; 200 mg animal-1 d-1; n = 79). Heifers were fed for 71 d in a GrowSafe unit, so individual feed intake could be measured. Heifers were weighed every 2 wk and feed efficiency calculated by residual feed intake (RFI). At the end of the RFI trial, heifers remained on their diets for an additional 27 d and were estrus synchronized using the 14-d CIDR + PG protocol and bred by artificial insemination (AI) followed by natural service. Prior to estrous synchronization, reproductive tract scores (RTS; 1 = infantile to 5 = cycling/presence of corpus luteum) were measured. Continuous variables were analyzed using generalized mixed models, whereas categorical data were analyzed by logistic regression. Body weights, average daily gain, feed intake, and RFI value were similar (P > 0.30) among MON- and LaP-supplemented heifers. Across treatments, heifers gained 0.9 ± 0.1 kg/d while consuming 9.3 ± 0.5 kg of diets daily. Reproductive development as indicated by RTS was similar (P > 0.28) between treatments. However, estrus response increased (P < 0.01) and AI pregnancy rates tended to be greater (P < 0.07) for MON compared to LaP heifers. In contrast, the percentage of heifers pregnant by 60 and 100 d (80.4% and 90.5%, respectively) was not different (P > 0.33) for MON and LaP heifers. In conclusion, addition of LaP to replacement heifer diets may result in growth and reproductive performance similar to an ionophore, if dietary energy is adequate for normal heifer growth.


Gene therapy and informed consent decision making: nursing research directions.
Recent gene therapy clinical trials have demonstrated significant promise for treating a number of genetic neuromuscular disorders. Although nurses are experienced in educating patients and families about the benefits and risks of conventional therapeutics, there are significant challenges for guiding patients through the decision-making phase of gene therapy clinical trial participation. The first part of this review provides an overview and update on neuromuscular gene therapy, including viral delivery principles and historical progress. The second part discusses risk/benefit perception of gene therapy and factors affecting the decision making for patients interested in participating in a trial. Future challenges for gene therapy are targeted high-efficiency delivery, and additional research on developing patient-centered decision support interventions.


The influence of the tumor necrosis factor-alpa-308G>A polymorphism on the efficacy of immunosuppressive therapy in patients after kidney transplantation.
Cytokines play an important role in the immune response. The calcineurin inhibitors (cyclosporine CsA, tacrolimus TAC) widely used after renal transplantation to prevent allograft rejection are immunosuppressive drugs suppressing the production of cytokines. These drugs are characterized by interindividual variability and require monitoring their blood concentrations to predict their optimal dosage. Therefore, the aim of the study was to determine the correlation between therapeutic effects of immunosuppressants and the tumor necrosis factor-α (TNF-α)-308G>A polymorphism in renal transplant patients. A total of 412 patients receiving TAC and CsA were included in the study. Genotype frequencies were determined using the real-time PCR method. Patients with the GG genotype received higher doses of TAC as compared to carriers of the GA genotype (5.24 mg versus 3.35 mg) and had lower mean drug concentration in blood (5.86 ng/ml versus 6.92 ng/ml). Similar results were also obtained for CsA (GG: 185.33 mg versus GA: 153.30 mg, P < 0.05). The comparison of the TNF-α-308G>A polymorphism with the biochemical parameters did not reveal a potential risk for transplant rejection. These results indicate that the TNF-α-308G>A polymorphism may influence the dosage of immunosuppressive drugs in patients after transplantation as far as individualization of drug therapy is concerned.


[Self-closing flaps in the treatment of scalp burns due to high-voltage electricity].
Electrical burns caused by high voltage are responsible for extensive tissue damage. This damage continues in the days following the accident because of the heat deriving from the Joule effect and vascular microthrombosis. In such cases of destruction of the periostum and the calvarium we use coverage flaps. From June 1997 to June 2008, 15 patients were treated for loss of scalp substance due to high-voltage electric burns. The loss, in the tonsural region and varying in size from 9 to 11 cm, was reliably covered per primam in the first week following the accident using axial and multiple coverage flaps. We report the experience of the Division of Plastic Surgery, Ibn-Sina, Rabat, Morocco.


Impact of early diagnosis of impaired glucose regulation in tuberculosis: Comparison of clinical outcomes in people with tuberculosis in Tanzania.
Diabetes mellitus (DM) has been known to compromise tuberculosis (TB) treatment outcomes. Association data are limited for early hyperglycaemia detection and TB treatment outcomes. Thus, we assessed treatment outcomes including time to sputum conversion and death in TB participants with or without hyperglycaemia. A prospective cohort study recruited TB participants receiving anti-TB treatment at health facilities in Tanzania between October 2019 and September 2020. Hyperglycaemia was defined as having pre-existing DM or pre-treatment random blood glucose of ≥7.8 mmol/L, in combination categorised as impaired glucose regulation (IGR). Those with IGR were further screened for hyperglycaemia severity using glycated haemoglobin. In case of unknown status, participants were tested for HIV. Time to death was determined at 6 months of TB treatment. Of 1344 participants, 187 (13.9%) had IGR, of whom 44 (23.5%) were HIV co-infected. Overall treatment success was 1206 (89.7%), and was similar among participants with or without IGR (p > 0.05). Time to death for participants with and without IGR was 18 versus 28 days (p = 0.870), respectively. Age ≥ 40 years (p = 0.038), bacteriological positive (p = 0.039), HIV (p = 0.009), or recurrent TB (p = 0.017) predicted death or treatment success during TB treatment in adjusted multivariable models. IGR did not influence clinical outcomes in TB patients with or without IGR in a programme of early IGR diagnosis and integration TB, HIV and DM care. Early detection and co-management of multi-morbidities among people diagnosed with TB may reduce likelihood of poor treatment outcomes in a programmatic setting.


Photochemistry of DNA fragments via semiclassical nonadiabatic dynamics.
Forming upon absorption of a UV photon, excited states of DNA are subject to nonadiabatic evolution, via either internal conversion (IC) back to the ground state or mutagenesis. Nonadiabatic processes following the formation of the first singlet excited states, S1, in 10 different small DNA fragments--4 single 4'H-nucleosides, 2 Watson-Crick base pairs, and 4 nucleotide quartets--have been investigated. Simulations were done via the nonadiabatic direct trajectory surface hopping semiclassical dynamics. The electronic wave function was obtained with configuration interaction, based on the semiempirical AM1 and PM3 Hamiltonians with fractional orbital occupation numbers. The evolution of the electronic wave function was governed by the time-dependent Schrödinger equation with a locally diabatic representation, intrinsically stable near surface crossings. The nuclei evolved on adiabatic potential energy surfaces, as prescribed by classical Newtonian dynamics, with sudden hops between potential energy surfaces to account for nonadiabatic transitions. The "fewest switches" surface hopping algorithm coupled the quantum and classical parts of the system. The dynamics simulations revealed several routes of nonadiabatic relaxation in these systems, which were not reported previously, and also recovered known routes of IC.


Lifestyle modification in school-going children before and after COVID-19 lockdown.
To evaluate the impact of COVID-19 lockdown restrictions on lifestyle of school-going children. This was a questionnaire-based prospective study of 1237 school children aged 9-14 years enrolled from various private and government schools across Delhi in October-December 2020. These children were being followed-up over the previous 2 years (before pandemic) with details of their lifestyle like near/outdoor/reading activities using a questionnaire as a part of another study. The data during the COVID-19 lockdown was collected by telephonic interview. This was compared to similar information collected from this cohort in the pre-Covid period in 2019 when the students had a regular physical school curriculum. A significant decline was noted in time spent on outdoor activity (from 8.5 hours/week in pre-COVID-19 time to 1.6 hours/week during COVID-19 lockdown; P < 0.001) and doing homework offline (from 15.3 hour/week to 14 hours/week; P < 0.001). A significant increase was noted in screen time spent on digital devices (from 6.2 hours/week to 19.8 hours/week; P<0.001), and watching television (from 12.2 hours/week to 13.4 hours/week; P < 0.001). The rise in the digital on-screen time was significantly more in boys (P < 0.001) and in students from private schools (P < 0.001). The rise in the duration of watching television was significantly more in girls than boys (P < 0.05). COVID-19 lockdown has markedly impacted the lifestyle of school children by significantly decreasing the outdoor activity and increasing the screen time, thereby pre-disposing them to ocular ill-health and myopia. This necessitates the adoption of guidelines for promoting healthy digital habits in children.


Theoretical study of HOCl-catalyzed keto-enol tautomerization of β-cyclopentanedione in an explicit water environment.
The mechanism of acid-catalyzed keto-enol tautomerization of β-cyclopentanedione (CPD) in solution is studied computationally. Reaction profiles are first calculated for a limited solvation environment using ab initio and density functional methods. Barrier heights for systems including up to one hydration shell of explicit water molecules depend strongly on the number of waters involved in proton transfer and to a lesser but significant extent on the number of waters forming hydrogen bonds with waters in the proton-transfer chain (each such water reduces the barrier by 4.4 kcal/mol on average). Barriers of 8-13 kcal/mol were obtained when a full or nearly full hydration shell was present, consistent with calculations for nonacid-catalyzed keto-enol tautomerization of related molecules. The presence of HOCl reduced the barrier by 4.5 kcal/mol in relation to the gas phase, consistent with the well-known principle that keto-enol tautomerization can be acid- or base-catalyzed. The reaction was also modeled beginning with snapshots of reactant conformations taken from a 300 K molecular dynamics simulation of CPD, HOCl, and 324 explicit waters. Reaction profiles were calculated at a QM/MM level with waters in the first hydration shell either fixed or energy-minimized at each step along the reaction coordinate. A substantial variation in barrier height was observed in both cases, depending primarily on electrostatic interactions (hydrogen bonding) with first-hydration-shell waters and, to a lesser extent, on electrostatic interactions with more distant waters and geometric distortion effects. For the lowest barriers, the extent of barrier reduction by waters involved in proton transfer is consistent with the limited solvation results, but further barrier reduction due to hydrogen bonding to waters involved in proton transfer is not observed. It is postulated that this is because highly flexible structures such as extensive hydrogen bonding networks optimal for reaction are entropically disfavored and so may not contribute significantly to the observed reaction rate.


Divergent effects of distinct perivascular cell subsets for intra-articular cell therapy in posttraumatic osteoarthritis.
Intra-articular injection of mesenchymal stem cells has shown benefit for the treatment of osteoarthritis (OA). However, mesenchymal stem/stromal cells at the origin of these clinical results are heterogenous cell populations with limited cellular characterization. Here, two transgenic reporter mice were used to examine the differential effects of two precisely defined perivascular cell populations (Pdgfrα+ and Pdgfrβ+ cells) from white adipose tissue for alleviation of OA. Perivascular mesenchymal cells were isolated from transgenic Pdgfrα-and Pdgfrβ-CreERT2 reporter animals and delivered as a one-time intra-articular dose to C57BL/6J mice after destabilization of the medial meniscus (DMM). Both Pdgfrα+ and Pdgfrβ+ cell preparations improved metrics of cartilage degradation and reduced markers of chondrocyte hypertrophy. While some similarities in cell distribution were identified within the synovial and perivascular spaces, injected Pdgfrα+ cells remained in the superficial layers of articular cartilage, while Pdgfrβ+ cells were more widely dispersed. Pdgfrβ+ cell therapy prevented subchondral sclerosis induced by DMM, while Pdgfrα+ cell therapy had no effect. In summary, while both cell therapies showed beneficial effects in the DMM model, important differences in cell incorporation, persistence, and subchondral sclerosis were identified.


Why are individuals over age 60 still committed as sexually violent persons?
Civilly committed sexually violent persons (SVPs) are a select group of individuals designated as high risk for future sexual violence. Despite risk reduction in older age, SVP programs are seeing aging client populations, with many individuals remaining committed after age 60 (60+). Recent research found a sexual recidivism rate of 7.5% for 60+ individuals released from an SVP civil commitment program. The current paper follows up by examining reasons why individuals remain committed after age 60. It compares SVPs discharged after age 60 to those who are 60+ but remain civilly committed. Results of bivariate analyses reveal older SVPs who remain committed have significantly higher actuarial risk scores and are more likely to be of minority race. Multivariate logistic regression analyses found actuarial risk scores (Static-99R) predicted continued commitment, after controlling for other relevant variables. Barriers to community reintegration and suggestions for multi-disciplinary case management for older SVPs are discussed.


Clinical Characteristics of Cryoglobulinemia With Cardiac Involvement in a Single Center.
Background: Cryoglobulinemia is a syndrome characterized by the presence of cryoglobulins (CGs) in serum, and cardiac involvement is a rare occurrence that can affect treatment and prognosis. This study aimed to explore the clinical characteristics of cryoglobulinemia with cardiac involvement. Methods: 108 patients diagnosed with cryoglobulinemia who were admitted and treated in Peking Union Medical College Hospital (PUMCH) between June 1985 and June 2019 were enrolled in the present study. Clinical characteristics, therapy, and prognosis of patients with cardiac involvement were retrospectively analyzed. Results: The cryoglobulinemia with cardiac involvement was found in 7 patients, thus reaching the incidence of 6.5%. Heart failure was the main cardiac manifestation found in these patients, all with the involvement of external cardiac organs. Laboratory examinations showed significant elevation of N-terminal brain natriuretic peptide precursor (NT-proBNP) and brain natriuretic peptide (BNP) with negative troponin (cTnI). Electrocardiogram (ECG) was generally normal or only showed low-flat and biphasic multi-lead T waves. Echocardiography was performed in 6 patients, all of whom showed enlargement of heart cavity. Five patients had reduced left ventricular myocardial contractible motion with decreased ejection fraction, 3 patients had pericardial effusion, and 1 patient had left ventricular hypertrophy or severe aortic insufficiency. Cardiac magnetic resonance imaging showed delayed myocardial enhancement in 2 patients. One patient underwent a myocardial biopsy, which showed perivasculitis. Condition in 6 patients who received active treatment targeting improved in the early stage. Three patients (3/7, 42.9%) died due to disease progression during follow-up period. Conclusions: Cryoglobulinemia with cardiac involvement is a rare but serious condition that has relatively high risk of death. When patients with cryoglobulinemia without underlying heart disease experience heart failure, chest pain, or elevation of asymptomatic NT-proBNP and BNP, there is a high possibility of cardiac involvement, even if the electrocardiogram and troponin are negative. Further examinations such as echocardiography, cardiac magnetic resonance imaging, and myocardial biopsy examination could contribute to the diagnosis. Cardiac manifestations could be timely reversed after active targeted treatment. NT-proBNP and echocardiography could be used for the monitoring of disease efficacy.


Neurocranium versus Face: A Morphometric Approach with Classical Anthropometric Variables for Characterizing Patterns of Cranial Integration in Extant Hominoids and Extinct Hominins.
The relative importance of the two main cranial complexes, the neurocranium and the splanchnocranium, has been examined in the five species of extant hominoids and in a huge sample of extinct hominins using six standard craniometric variables that measure the length, width and height of each cranial module. Factor analysis and two-block partial least squares were used for establishing the major patterns of developmental and evolutionary integration between both cranial modules. The results obtained show that all extant hominoids (including the anatomically modern humans) share a conserved pattern of developmental integration, a result that agrees with previous studies. The pattern of evolutionary integration between both cranial modules in australopiths runs in parallel to developmental integration. In contrast, the pattern of evolutionary and developmental integration of the species of the genus Homo is the opposite, which is probably the consequence of distinctive selective regimes for both hominin groups.


Effect of fatigue on reaction time, response time, performance time, and kick impact in taekwondo roundhouse kick.
Reaction time and response time are considered important abilities and can potentially affect combat performance. This study investigated the effect of a specific fatigue protocol on reaction time, response time, performance time, and kick impact. Seven male athletes reported to the laboratory on two different days. During day one, athletes performed a specific progressive taekwondo test, and on day two, a protocol for determining reaction time, response time, performance time, and kick impact before and after a time to exhaustion test at an intensity level corresponding to the maximal kick frequency obtained during the specific progressive taekwondo test. Muscle activation from rectus femoris and kick impact of the preferred limb were assessed. No differences were observed for response time and performance time. However, kick impact decreased (43 ± 27 to 13 ± 10 g, p < 0.01) while reaction time increased (145 ± 51 to 223 ± 133 ms, p < 0.05). Moderate correlation was observed between kick impact and response time (r = 0.565; p < 0.01), and kick impact and performance time (r = 0.494; p < 0.05). Results indicate that coaches and athletes may use taekwondo training programmes on coordination-based exercises leading to improve response time and to reduce fatigue effects in order to improve technique effectiveness and enhance the possibilities of scoring in a competitive situation.


Diabetes mellitus after renal transplantation: characteristics, outcome, and risk factors.
The incidence and risk factors of posttransplant diabetes mellitus were evaluated in 1325 consecutive renal transplant recipients. Thirty-three (2.5%) patients developed diabetes mellitus requiring insulin therapy. Onset occurred a mean of 5.7 +/- 1.5 months following transplantation. The patients were compared with 33 paired-control kidney recipients. The patients were significantly older than the controls (46.8 +/- 1.9 vs. 40.6 +/- 2.1 years) (P<0.05), and chronic renal failure was more often related to interstitial nephritis (P<0.05). A family history of diabetes mellitus, the body mass index, ethnic origin, HLA phenotype, and the total doses of steroids and cyclosporine were similar in the two groups. The number of patients with at least one rejection episode was significantly higher among the diabetic patients (21 versus 9) but the number of episodes was similar. Diabetes occurred a mean of 1.1 +/- 0.3 months following rejection treatment. Intravenous pulsed prednisolone was always used for anti-rejection therapy. Insulin was withdrawn in 16 cases after a mean of 4 +/- 1 months, independently of steroid dosage reductions. Actuarial patient and graft survival rates were not significantly different, although 6-year outcome tended to be better in the controls (86% versus 93% for patient survival and 67% versus 93% for graft survival). This study suggests that pulsed steroid therapy might be the critical factor in the onset of posttransplant diabetes and that the risk is increased in older patients with chronic interstitial nephrititis.


Combined in Vivo Amperometric Oximetry and Electrophysiology in a Single Sensor: A Tool for Epilepsy Research.
Seizures are paroxysmal events in which increased neuronal activity is accompanied by an increase in localized energetic demand. The ability to simultaneously record electrical and chemical events using a single sensor poses a promising approach to identify seizure onset zones in the brain. In the present work, we used ceramic-based platinum microelectrode arrays (MEAs) to perform high-frequency amperometric recording of local pO2 and local field potential (LFP)-related currents during seizures in the hippocampus of chronically implanted freely moving rats. Resting levels of O2 in the rodent brain varied between 6.6 ± 0.7 μM in the dentate gyrus (DG) region of the hippocampus and 22.1 ± 4.9 μM in the cerebral cortex. We also observed an expected increase in hippocampal pO2 (15 ± 4% from baseline) in response to tail pinch stress paradigm. Finally, induction of status epilepticus by intrahippocampal injection of pilocarpine induced biphasic changes in pO2 in the hippocampus. The initial dip at seizure onset (ΔO2 = -4.5 ± 0.7 μM) was followed by a prolonged hyperoxygenation phase (ΔO2 = +10.4 ± 2.9 μM). By acquiring the amperometry signal with a high sampling rate of 100 Hz we decomposed the raw signal in an oximetry recording (<1 Hz) and LFP recording (>1 Hz), demonstrating that each individual Pt site can simultaneously report changes in local pO2 and LFP-related currents during pilocarpine-induced seizure activity. This has high potential for translation into the clinical setting supported on intracranial grid or strip electrodes.


Murine T cells with invariant gamma delta antigen receptors: origin, repertoire, and specificity.
T cells bearing invariant gamma delta T cell antigen receptors localize to distinct epithelial sites in the adult mouse. These gamma delta T cells differ from the lymphoid alpha beta and gamma delta T cells in several ways. The epithelial gamma delta T cells appear to be the product of the earliest waves of TCR expressing cells in the fetal thymus. Additionally, the rearranged TCR junctions exhibit a distinct lack of diversity, possibly a result of the fetal origin and a specialized selection process. The use of a single invariant TCR and strict tissue localization suggest that these gamma delta T cells may provide a specialized function in the epithelial tissues distinct from that of the circulating alpha beta and gamma delta T cells.


Highly efficient blue-green quantum dot light-emitting diodes using stable low-cadmium quaternary-alloy ZnCdSSe/ZnS core/shell nanocrystals.
High-quality blue-green emitting ZnxCd(1-x)S(1-y)Se(y)/ZnS core/shell quantum dots (QDs) have been synthesized by a phosphine-free method. The quantum yields of as-synthesized ZnxCd(1-x)S(1-y)Se(y)/ZnS core/shell QDs can reach 50-75% with emissions between 450 and 550 nm. The emissions of such core/shell QDs are not susceptible to ligand loss through the photostability test. Blue-green light-emitting diodes (LEDs) based on the low-cadmium ZnxCd(1-x)S(1-y)Se(y)/ZnS core/shell QDs have been successfully demonstrated. Composite films of poly[9,9-dioctylfluorene-co-N-[4-(3-methylpropyl)]-diphenylamine] (TFB) and ZnO nanoparticle layers were chosen as the hole-transporting and the electron-transporting layers, respectively. Highly bright blue-green QD-based light-emitting devices (QD-LEDs) showing maximum luminance up to 10000 cd/m(2), in particular, the blue QD-LEDs show an unprecedentedly high brightness over 4700 cd/m(2) and peak external quantum efficiency (EQE) of 0.8%, which is the highest value ever reported. These results signify a remarkable progress in QD-LEDs and offer a practicable platform for the realization of QD-based blue-green display and lighting.


Daphnetin protects oxidative stress-induced neuronal apoptosis via regulation of MAPK signaling and HSP70 expression.
Neurodegenerative disorders are characterized by progressive degeneration and loss of neurons in the brain. Oxidative stress is implicated in the pathogenesis of neurological disorders, although the pathological mechanism remains unelucidated. Daphnetin, an active ingredient extracted from Changbai daphne (Daphne Korean Nakai), exhibits various pharmacological effects, including anti-inflammatory, anti-oxidative and anti-tumor effects. However, the neuroprotective effects, as well as the specific mechanisms of daphnetin, remain unclear. Neuronal-like rat pheochromocytoma PC12 cells were pretreated with daphnetin for 2 h, then treated with or without H2O2 for various times. Cell morphology was detected using an inverted microscope, the apoptotic ratio was determined by Annexin V fluorescein isothiocyanate/propidium iodide assay, nuclear morphology was observed and photographed using a fluorescence microscope following 4',6-diamidino-2-phenylindole staining. The levels of pro-caspase 3, cleavage of poly ADP-ribose polymerase and caspase 3 were detected by western blotting. In addition, the activation of mitogen-activated protein kinase (MAPK) signal pathway and the expression of HSP70 were detected by western blotting. The present study demonstrated that daphnetin attenuated hydrogen peroxide (H2O2)-induced apoptosis in a concentration-dependent manner, reduced the cleavage of poly ADP ribose polymerase and caspase 3, and inhibited the phosphorylation of p38 MAPK and c-Jun N-terminal kinases (JNK) in H2O2-induced PC12 cells. In addition, daphnetin induced the expression of HSP70 in a dose- and time-dependent manner, and daphnetin-induced HSP70 expression was reduced by extracellular signal-regulated kinase (ERK) 1/2 inhibitor U0126 in PC12 cells. Therefore, the present results indicate that daphnetin protects PC12 cells against oxidative stress injury by regulating p38 MAPK and JNK signaling and increasing the expression of HSP70 via ERK signaling. This suggests that daphnetin may have the potential to treat certain neurodegenerative diseases. The present results not only provide insight into the potential use of daphnetin in H2O2-induced PC12 cell apoptosis, but also highlight the potential role of HSP70 in neuroprotection.


Risk factors for adult overweight and obesity: the importance of looking beyond the 'big two'.
To compare two traditional (high dietary lipid intake and non-participation in high-intensity physical exercise, namely the 'Big Two' factors) versus three nontraditional (short sleep duration, high disinhibition eating behavior, and low dietary calcium intake) risk factors as predictors of excess body weight and overweight/obesity development. Adult participants aged 18-64 years of the Quebec Family Study were selected for cross-sectional (n = 537) and longitudinal (n = 283; 6-year follow-up period) analyses. The main outcome measure was overweight/obesity, defined as a BMI ≥ 25 kg/m(2). We observed that both the prevalence and incidence of overweight/obesity was best predicted by a combination of risk factors. However, short sleep duration, high disinhibition eating behavior and low dietary calcium intake seemed to contribute more to the risk of overweight and obesity than high dietary lipid intake and non-participation in high-intensity physical exercise. Globally, the risk of being overweight or obese was two-fold higher for individuals having the three nontraditional risk factors combined (OR 6.05; 95% CI 4.26-7.88) compared to those reporting a high percentage of lipids in their diet together with no vigorous physical activity in their daily schedule (OR 2.95; 95% CI 2.18-3.73). Furthermore, the risk of overweight/obesity was also higher for the combination of any two of the nontraditional risk factors than for the combination of the 'Big Two' factors. These results are concordant with previous reports showing that obesity is a multifactorial condition, and emphasize the importance of looking beyond reported measures of the 'Big Two' factors.


Molecular characterization and expression of AMP-activated protein kinase in response to low-salinity stress in the Pacific white shrimp Litopenaeus vannamei.
AMP-activated protein kinase (AMPK) serves as a major regulator of cellular energy metabolism by activating ATP production pathways and blocking ATP consumption. However, information on AMPK genes in aquatic animals is limited. In this study, three subunits of AMPK were cloned from the Pacific white shrimp Litopenaeus vannamei. The full-length cDNAs of the α, β and γ subunits were 1617, 1243 and 3467bp long, respectively, with open reading frames of 1566, 873 and 2988bp encoding for 521, 290 and 996 amino acids, respectively. Amino acid sequence alignments of the three subunits showed that the functional domains in the L. vannamei proteins retained the highest similarity with those of other animals, at 89%, 58%, and 75%, respectively. The expression levels of the three subunits were higher in the muscle and gills than in the eyestalk and hepatopancreas. The mRNA levels of AMPK-α and AMPK-β were up-regulated in the hepatopancreas and muscle after acute low-salinity stress at 3psu for 6h compared with control salinity at 20psu. After 8-week salinity stress at 3psu, AMPK-α and AMPK-β mRNA levels in the hepatopancreas were significantly higher than those of the control at 30psu. However, in the muscle only AMPK-γ mRNA was significantly up-regulated at low salinity relative to controls. Muscle and hepatopancreas showed increases in AMPK protein after 6h exposure to low salinity, but there were no differences seen after long term acclimation. The change patterns of protein were slightly differing from the mRNA patterns due to the distinguishing function of individual subunits of AMPK. These findings confirm that three AMPK subunits are present in L. vannamei and that all encode proteins with conserved functional domains. The three AMPK subunits are all regulated at the transcriptional and protein levels to manage excess energy expenditure during salinity stress.


HTLV-1 associated myelopathy diagnosed during lepromatous leprosy reaction treatment: a case report.
Leprosy and human T cell lymphotropic virus type 1 infection are prevalent in Brazil. Coinfection by Mycobacterium leprae and HTLV-1 is reviewed and a case is reported. A 59 year-old woman was followed and HTLV-1 associated myelopathy was diagnosed during leprosy treatment. The clinical and neurological aspects of this unusual association were initially reviewed. Immunological markers and the possible prognoses due to the association of the diseases were discussed. The unexpected association of leprosy and HTLV-1 associated myelopathy may occur in endemic areas and causes difficulties in determining the correct diagnosis and adequate management of the neurological manifestations.


Generation of chicken Z-chromosome painting probes by microdissection for screening large-insert genomic libraries.
A strategy for rapid generation of chicken sex chromosome-Z painting probes has been developed using microdissection. Whole chromosome painting probes (WCPs) were prepared from 10-15 copies of mitotic metaphase chicken Z chromosomes. The microisolated chromosomes were subjected to PEG/proteinase K treatment in a collection drop to release DNA, which was then amplified using a degenerate oligonucleotide-primed shuttle PCR (DOP-Shuttle-PCR) strategy. Size distributions of the PCR products were analyzed by agarose gel electrophoresis and smears of DNA were revealed that ranged in size from 200-800 bp, without any evidence of preferential amplification. Both specificity and complexity of the probes have been analyzed by Southern blot and fluorescence in situ hybridization (FISH). Non-specific hybridization was efficiently blocked by using chicken competitor DNA. Analysis of the WCPs produced shows that collectively they provide uniform hybridization signals along the entire length of the chicken Z chromosome. To demonstrate one possible application of these complex probes, we screened a large-insert bacterial artificial chromosome (BAC) chicken genomic library to select Z chromosome-specific clones. To address specificity of the selected clones and to physically map them to the Z chromosome, FISH analysis was used. Of the 3 clones initially tested, one clone (C3) carrying a 250-kb insert mapped to the distal portion of the short arm of the chicken Z chromosome. Therefore, this technique has provided appropriate probes for screening large-insert genomic libraries. Further application of these probes includes the analysis of chromosome rearrangements, studies of cases of heteroploidy involving the Z chromosome, positional cloning of Z-linked genes and studies on mechanisms of sex-chromosome evolution in birds.


Effects of the 755-nm Alexandrite laser on fine dark facial hair: review of 90 cases.
Laser hair removal is a relatively effective method for thick hair. Despite the risk for induction of fine hair growth, application of laser for fine dark hair is sometimes inevitable. We investigate the effects of 755-nm Alexandrite laser on fine dark facial hair and evaluate the induction rates of fine hair growth and case satisfaction. In the present study, the thickening rate of hairs (33.33%) was found to be higher than the previously published rates. However, reduction of hair density can be obtained when the laser sessions are continued.


[Intravenous anesthesia in the horse: comparison of xylazine-ketamine and xylazine-tiletamine-zolazepam combinations].
Intravenous anesthesia in the horse: Comparison of xylazine-ketamine and xylaxine-tiletamine-zolazepam combinations. Six healthy adult horses were anesthetized twice at random with following intravenous combinations: 1.1 mg/kg of body weight (BW) of xylazine followed by 2.2 mg/kg BW of ketamine (X-K) and 1.1 mg/kg BW of xylazine followed by 1.65 mg/kg BW of tiletamine-zolazepam (X-TZ). The modifications of some cardiorespiratory parameters and the duration of anesthesia were evaluated and compared for the 2 protocols used. Few significant differences were observed between the 2 protocols in regard to the cardiorespiratory parameters measured. The respiratory rate was lower (7 breaths per minute) and the heart rate was higher (34 beats per minute) with the X-TZ combination. The duration of anesthesia with this technique was 33 +/- 3 minutes (X +/- Sx) and longer than with X-K (18 +/- minutes (X +/- Sx)). Superficial analgesia lasted 14,5 +/- 3 minutes with the X-K combination and 31,7 +/- 3,2 minutes for the X-TZ combination. The 2 protocols are associated with a reduction of PaO2.


Effects of T2 * on accuracy and precision of dynamic T1 measurements using the single reference variable flip angle method: a simulation study.
To study in simulation and in theory the accuracy and precision of dynamic T1 measurements obtained using the previously published single-reference variable flip angle (SR-VFA) technique, with a focus on the effects of dynamic changes in T2 * on the calculation. Monte Carlo simulations were performed over 1000 noisy iterations for the VFA method, the SR-VFA method, and a proposed method, SR-VFA with a T2 * correction (SR-VFA-T2 *). Dynamic T1 estimates were calculated analytically for each method, with signals modeled by the steady-state spoiled gradient echo equation. The mean and standard deviation of these estimates were calculated and compared to truth, while varying repetition time (TR), baseline and dynamic T1 , echo time (TE), baseline and dynamic T2 *, flip angles, and the number of averages on baseline scans. Additionally, the variance of T1 in the SR-VFA and SR-VFA-T2 * methods was derived analytically based on the theory of propagation of errors. This equation was used to produce an inverse-variance weighted linear combination to improve T1 mapping precision in the SR-VFA-T2 * method. Flip angle sensitivity of dynamic T1 precision in the SR-VFA and SR-VFA-T2 * methods was also performed. Substantial bias can be produced by the SR-VFA method when the ratio of the T2 * decay of the dynamic signal versus that of the baseline signals deviates from 1, with a 0.01 deviation leading to approximately a 1% bias in cases of high SNR and TR ≫ T1 . This bias can be corrected by estimating the baseline and dynamic T2 * values in this ratio via multiecho measurements. The bias and precision of the SR-VFA-T2 * method, when normalized to scan time, is found to rival and sometimes improve upon the two flip angle VFA method when an inverse variance weighted linear combination is applied across its multiecho T1 maps. The analytic variance equation presented is found to be accurate within 1% relative to the Monte Carlo simulations over a broad parameter space. Flip angle ranges that maximize SR-VFA and SR-VFA-T2 *T1 precision over a broad parameter space are given, and each is defined relative to TR and T1 . Multiecho SR-VFA-T2 * T1 mapping is found in simulation and theory to be a promising alternative to the VFA method that maintains speed of the SR-VFA method with accuracy and precision similar to the VFA method.


Screening of peptides recognizing simple polycyclic aromatic hydrocarbons.
Peptides that specifically bind to the simplest polycyclic aromatic hydrocarbon, naphthalene, were obtained by affinity-based screening using a phage-displayed peptide library. The identified peptide with a β-turn structure showed specific binding to naphthalene present not only on substrates but also in aqueous solutions.


Morphology as a risk factor for the malignant potential of T2 colorectal cancer.
Currently, depressed type T1 colorectal cancer is often detected and its malignant potential is being revealed. However, few reports have focused on the morphology of T2 colorectal cancer types. The aim of the present retrospective study was to clarify the characteristics of colorectal T2 cancer types derived from depressed type T1 cancer. The present study included 195 patients with colorectal T2 cancer surgically resected at a referral hospital between April 2001 and April 2009. A total of 48 lesions (25%) with lymph node metastasis and 4 (2%) with distant metastasis were found. The lesions were classified by their form during endoscopy into four categories: Group A, depressed type (the periphery consists of normal mucosa); group B, laterally spreading type; group C, protruded type; group D, ulcerative type (the periphery consists of neoplastic mucosa). Tumor size, lymphatic and venous involvement, lymph node metastasis, and distant metastasis were compared between the four categories. The distribution of patients were as follows: Group A, 73 (37%), group B, 26 (13%), group C, 24 (12%) and group D, 72 (37%). The average tumor size for each category was 23, 51, 30 and 36 mm for groups A, B, C and D, respectively. The number of positive findings for lymphatic involvement, venous involvement, lymph node metastasis and distant metastasis for each category were: Group A, 50 (69%), 54 (74%), 19 (26%) and 1 (1%); group B, 14 (54%), 12 (46%), 8 (31%) and 0 (0%); group C, 14 (58%), 8 (33%), 6 (25%) and 0 (0%); group D 35 (49%), 41 (57%), 16 (22%) and 3 (4%). Group A demonstrated a significantly smaller tumor size (P<0.01), and higher rates of lymphatic and venous involvement (P=0.0333 and P=0.0019, respectively). No significant differences were observed between categories with regards to nodal and distant metastases. Of the T2 cancer types, ~40% were the depressed type. Compared with the other forms, depressed type lesions exhibited a smaller tumor size, and higher rates of lymphatic and venous involvement, which suggested these lesions were of a more malignant nature.


Correlation of chondroitin sulfate proteoglycan expression on proliferating brain capillary endothelial cells with the malignant phenotype of astroglial cells.
Human glioblastomas (five of five), the most malignant astroglial-derived tumors, specifically express a chondroitin sulfate proteoglycan that is recognized by monoclonal antibody 9.2.27 and localized to the glioma cell surface, proliferating endothelial cells, and the perivascular extracellular matrix within the tumor bed. In contrast, the expression of this proteoglycan in normal adult neocortex and white matter is limited to the smooth muscle of small arteries, while normal glia, endothelial cells, and endothelial cell basement membranes are nonreactive. Moreover, two anaplastic astrocytomas, representing medium-grade astroglial-derived tumors, fail to react with monoclonal antibody 9.2.27. In culture, glioblastoma and capillary brain endothelial cells specifically synthesize a 250-kDa core protein and a high-molecular-mass chondroitin sulfate proteoglycan, recognized by monoclonal antibody 9.2.27. These data suggest a correlation between the expression of this chondroitin sulfate proteoglycan on proliferating brain capillary endothelial cells and the malignant phenotype of astroglial cells. The prominent perivascular localization of chondroitin sulfate proteoglycan makes it a marker for both proliferating brain capillary endothelial cells and the most malignant transformed astroglial cells, thus providing an ideal target for the immunotherapy of glioblastoma.


Development of a Transition Process Scale for High-risk Infant's Caregiver.
Transition into parenthood is a major developmental life event and is very significant because development in infanthood is affected by the transition process of mothers parenting an infant. This study aimed to develop the assessment tool for transition process of high risk infant's caregiver in Korea. The participants were 246 mothers of premature infant born with gestational age (< 37 weeks) or low birth weight (< 2500 gm), of less than 24 months of age. Preliminary items were derived from transition process scale for parent of children with autism. Factor analysis was performed to test construct validity of the scale, the correlation between transition processes and parenting efficacy was used for testing predictive validity. The final scale was composed of 23 items divided into 5 factors: wandering (7 items), devotion (5 items), acceptance (4 items), denial (4 items), frustration (3 items). The total variance for validity described by the 5 factors was 60.8% and the reliability of the scale was total Cronbach's α 0.90 and wandering 0.85, devotion 0.78, acceptance 0.72, denial 0.72, and frustration 0.71. Correlation between transition process and parenting efficacy was statistically significant; wandering(r=-0.61, P <.001), devotion (r=-0.60, P<.001), acceptance (r=0.30, P <.001), denial (r=-0.31, P <.001) and frustration (r= -0.27, P <.001). This final assessment scale will be used to investigate high-risk infant caregiver's transition process and provide basic data for program development to provide differentiated support and care at each process.


Axial temperature gradient and stress measurements in the deformation-DIA cell using alumina pistons.
The deformation-DIA apparatus (D-DIA) coupled with synchrotron X-rays allows investigating materials elastic and plastic properties at high pressure. Most D-DIA deformation cells use alumina pistons that can also be used for measurement of the differential stress in the compression column by in situ X-ray diffraction. Here, we quantify the axial temperature (T) gradient in the D-DIA deformation cell and better constrain stress measurements in its compression column by studying an alumina specimen compressed and deformed at pressure P in the range 3.9-5.5 GPa and nominal temperature To = 1673 K. The axial T gradient, obtained from alumina equation of state, is ∼155 K∕mm at the centre of the cell and does not vary significantly during deformation to 20% specimen strain. This T gradient, if not taken into account when measuring the experimental pressure in the alumina pistons, leads to significantly overestimating pressure. Unlike pressure, stress measurements in alumina are weakly sensitive to temperature. During deformation, the "true" differential stress in the compression column is evaluated at 596 ± 20 MPa using an elastoplastic self-consistent model, while raw uncertainties on experimental differential stresses reach 84 MPa. A comparison between the simulated and experimental data allows to conclude that, although dislocation glide in the basal plane is the primary slip system at run condition, with an estimated critical resolved shear stress (CRSS) of 120 MPa, prism plane slips and pyramidal plane slips also contribute significantly to the aggregate homogenous deformation and texture development, with CRSS on the order of 280 MPa.


Effect of Pore Confinement of NaNH2 and KNH2 on Hydrogen Generation from Ammonia.
The development of efficient catalysts for hydrogen generation via ammonia decomposition is crucial for the use of ammonia as an energy carrier. Here, we report the effect of pore confinement of NaNH2 and KNH2 on ammonia decomposition catalysis. For the first time, Ni- or Ru-doped NaNH2 and KNH2 were confined in carbon nanopores using a combination method of solution impregnation and melt infiltration. Structure characterization indicates the nanoscale intimacy between transition metals and alkali metal amides inside the pores of the carbon support. As a result, 8 wt % Ni-doped NaNH2 and KNH2 nanocomposites give NH3 conversions of 79 and 60%, respectively at 425 °C, close to the performance of a 5 wt % Ru/C reference catalyst. 0.8 wt % Ru-doped nanocomposites exhibit even better catalytic performance, with about 95% NH3 conversion at a moderate temperature of 375 °C. The hydrogen production rates of these Ni- and Ru-doped nanocomposites in a pure NH3 flow are about 3-4 times higher than for the recently reported novel catalysts such as Ni-Li2NH and Ru-Li2NH/MgO. Interestingly, the apparent activation energies of the Ru- or Ni-based catalysts decrease 20-30 kJ mol-1 by co-confinement with alkali metal amides. The strategy of nanoconfinement of alkali metal amides in porous hosts may open a new avenue for effectively generating H2 from NH3 at low temperatures.


A prospective clinical study of stereotactic subcaudate tractotomy.
This study describes a cohort of 23 patients undergoing stereotactic subcaudate tractotomy. Research Diagnostic Criteria indicated that 70% suffered major depressive disorder; the remainder mostly had a bipolar affective disorder. There were serial assessments pre-operatively and at 2 weeks and 6 months post-operatively using the Hamilton Rating Scale for depression, the Present State Examination (PSE), Newcastle Scale, the Beck Depression Inventory, and the Taylor Manifest Anxiety Scale. Neuropsychological assessment included tests thought to be sensitive to frontal lobe dysfunction, as well as tests of general intelligence, attention, memory, language and visuo-spatial function. Post-operatively, depression rating scale scores decreased significantly but most patients continued to exhibit a number of PSE syndromes. Depression rating scale scores were correlated with 1 year global outcome: there was no significant correlation except for the 6 month assessment when lower Hamilton scores were found to be associated with better global outcome. Correlations between the neuropsychological tests and the Hamilton and Beck depression scales at 2 weeks post-operatively suggested that an improvement in psychiatric condition was associated with greater efficiency on some tests of attention and verbal recall, as well as faster performance on a sorting task. By contrast, the changes at 6 months suggested an association between improvement in psychiatric condition and less efficient performance on certain neuropsychological tests including verbal recognition memory, attention and two tests of frontal lobe dysfunction.


HeLa-cell adherence patterns and actin aggregation of enteropathogenic Escherichia coli (EPEC) and Shiga-toxin-producing E. coli (STEC) strains carrying different eae and tir alleles.
A collection of 69 eae-positive strains expressing 29 different intimin types and eight tir alleles was characterized with respect to their adherence patterns to HeLa cells, ability to promote actin accumulation in vitro, the presence of bfpA alleles in positive strains, and bundle-forming pilus (BFP) expression. All of the nine typical enteropathogenic Escherichia coli (tEPEC) studied harbored the enteropathogenic E. coli adherence factor (EAF) plasmid, as shown by PCR and/or EAF probe results. In addition, they were positive for bfpA, as shown by PCR, and BFP expression, as confirmed by immunofluorescence (IFL) and/or immunoblotting (IBL) assays. Localized adherence (LA) was exclusively displayed by those nine tEPEC, while localized-adherence-like (LAL) was the most frequent pattern among atypical EPEC (aEPEC) and Shiga-toxinproducing E. coli (STEC). All LA and LAL strains were able to cause attaching and effacing (AE) lesions, as established by means of the FAS test. There was a significant association between the presence of tir allele alpha1 and bfpA-positive strains, and consequently, with the LA pattern. However, intimin type or bfpA was not associated with the adherence pattern displayed in HeLa cells. Among the eight bfpA alleles detected, a new type (beta10; accession number FN391178) was identified in a strain of serotype O157:H45, and a truncated variant (beta3.2-t; accession number FN 391181) in four strains belonging to different pathotypes.


Optogenetics to Interrogate Neuron-Glia Interactions in Pups and Adults.
In just over 10 years, the use of optogenetic technologies in neuroscience has become widespread, having today a tremendous impact on our understanding of brain function. An extensive number of studies have implemented a variety of tools allowing for the manipulation of neurons with light, including light-activated ion channels or G protein-coupled receptors, among other innovations. In this context, the proper calibration of photostimulation in vivo remains crucial to dissect brain circuitry or investigate the effect of neuronal activity on specific subpopulations of neurons and glia. Depending on the scientific question, the design of specific stimulation protocols must consider from the choice of the animal model to the light stimulation pattern to be delivered. In this chapter, we describe a detailed framework to investigate neuron-glia interactions in both mouse pups and adults using an optogenetic approach.


Monosaccharide induced temporal delay in cholesterol self-aggregation.
Self-assembly of cholesterol (CHL) is infamous for its diverse deleterious effects on human health. Clinical research over several decades indicates that a diet rich in CHL typically leads to arterial plaques, cataracts and gall stones among others. Carbohydrates like the β-glucans efficiently lower serum CHL, possibly by inhibiting CHL absorption in the digestive tract. Using molecular dynamics simulations, we explore how β-D-glucose (BGLC), the building block of β-glucans, interferes with CHL aggregation. BGLC slows down CHL diffusion and disrupts the formation of the robust hydrophobic CHL assembly. Estimation of the translational entropy of the CHL molecules shows the extent of retardation induced by BGLC. Coordination numbers obtained from the adjacency matrix and collective variable analysis of the packing of the CHL molecules in presence of BGLC show the time evolution of CHL aggregation. In presence of BGLC, small isolated CHL islands form, consolidate and disintegrate over time as compared to the blank CHL system. The predominance of smaller CHL clusters is an effect of the significant retardation of the translational motion of CHL molecules induced by BGLC.Communicated by Ramaswamy H. Sarma.


Biosynthetic hydrogels--studies on chemical and physical characteristics on long-term cellular response for tissue engineering.
Biosynthetic hydrogels can meet the drawbacks caused by natural and synthetic ones for biomedical applications. In the current article we present a novel biosynthetic alginate-poly(propylene fumarate) copolymer based chemically crosslinked hydrogel scaffolds for cardiac tissue engineering applications. Partially crosslinked PA hydrogel and fully cross linked PA-A hydrogel scaffolds were prepared. The influence of chemical and physical (morphology and architecture of hydrogel) characteristics on the long term cellular response was studied. Both these hydrogels were cytocompatible and showed no genotoxicity upon contact with fibroblast cells. Both PA and PA-A were able to resist deleterious effects of reactive oxygen species and sustain the viability of L929 cells. The hydrogel incubated oxidative stress induced cells were capable of maintaining the intra cellular reduced glutathione (GSH) expression to the normal level confirmed their protective effect. Relatively the PA hydrogel was found to be unstable in the cell culture medium. The PA-A hydrogel was able to withstand appreciable cyclic stretching. The cyclic stretching introduced complex macro and microarchitectural features with interconnected pores and more structured bound water which would provide long-term viability of around 250% after the 24th day of culture. All these qualities make PA-A hydrogel form a potent candidate for cardiac tissue engineering.


A rare cause of hydrops fetalis in two Gaucher disease type 2 patients with a novel mutation.
Gaucher disease type 2 is the most progressive and the rarest form of Gaucher disease, defined as the acute neuronopathic type. We presented two GD2 patients who died before three months of age due to severe septicemia, respiratory and liver failure. One was homozygous for a novel GBA variant c.590 T > A (p.197 K), and the second homozygous for the known GBA mutation c.1505G > A (p.R502H). Ichthyosis, hydrops fetalis, apnea, myoclonic seizures, and hepatosplenomegaly occurred in both patients, but hypertrophic cardiomyopathy was observed only in the second and unilateral cataract in the first patient. Due to the disease's early and rapid neurological progression, we did not administer ERT to our patients. It is strongly believed that early diagnosis is essential, and prenatal diagnosis makes genetic counselling possible for future pregnancies.


SARS-CoV-2 vaccines: A double-edged sword throughout rapid evolution of COVID-19.
After more than 2 years of the coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2, several questions have remained unanswered that affected our daily lives. Although substantial vaccine development could resist this challenge, emerging new variants in different countries could be considered as potent concerns regarding the adverse effects of reinfection or postvaccination. Precisely, these concerns address some significant and probable outcomes in vaccinated or reinfected models, followed by some virus challenges, such as antibody-dependent enhancement and cytokine storm. Therefore, the importance of evaluating the effectiveness of neutralizing antibodies (nAbs) elicited by vaccination and the rise of new variants must be addressed.


3D macroporous solids from chemically cross-linked carbon nanotubes.
Suzuki reaction for covalently interconnected 3D carbon nanotube (CNT) architectures is reported. The synthesis of 3D macroscopic solids made of CNTs covalently connected via Suzuki cross-coupling, a well-known carbon-carbon covalent bond forming reaction in organic chemistry, is scalable. The resulting solid has a highly porous, interconnected structure of chemically cross-linked CNTs. Its use for the removal of oil from contaminated water is demonstrated.


Cyclic polyamides for recognition in the minor groove of DNA.
Small molecules that specifically bind with high affinity to any designated DNA sequence in the human genome would be useful tools in molecular biology and potentially in human medicine. Simple rules have been developed to rationally alter the sequence specificity of minor groove-binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids. Crescent-shaped polyamides bind as antiparallel dimers with each polyamide making specific contacts with each strand on the floor of the minor groove. Cyclic polyamides have now been synthesized that bind designated DNA sequences at subnanomolar concentrations.


Resonant photocurrent generation in dye-sensitized periodically nanostructured photoconductors by optical field confinement effects.
Herein we show experimental evidence of resonant photocurrent generation in dye-sensitized periodically nanostructured photoconductors, which is achieved by spectral matching of the sensitizer absorption band to different types of localized photon modes present in either periodic or broken symmetry structures. Results are explained in terms of the calculated spatial distribution of the electric field intensity within the configurations under analysis.


Primary percutaneous coronary intervention for ST elevation myocardial infarction complicated by cardiogenic shock.
To determine the outcomes of primary percutaneous coronary intervention for ST elevation myocardial infarction complicated by cardiogenic shock. The retrospective study was conducted at the Tabba Heart Institute, a private-sector facility in Karachi. It reviewed the medical records of 56 consecutive patients between January 2009 and June 2011 with acute ST elevation myocardial infarction complicated by cardiogenic shock and subjected to primary percutaneous coronary intervention. The primary end point was in-hospital mortality and its predictors. SPSS 14 was used for statistical analysis. The mean age of the study patients was 63 +/- 11.7 years; 38 (68%) were male; 32 (57%) were hypertensive; and 39 (69%) were diabetic. Most infarcts were anterior in location (n = 36; 64%). Besides, 33 (59%) required ventilatory support. Intra-aortic balloon pump was placed in 30 (54%), and 33 (59%) patients had multivessel coronary artery disease. In-hospital mortality occurred in 26 (46%). Multivariate logistic regression analysis showed that age > 60 years (p < 0.05), diabetes (p < 0.01) and left ventricular ejection fraction < 40% (p < 0.01) were independent predictors of in-hospital mortality. Results emphasise the need of aggressive management of patients with cardiogenic shock utilising primary percutaneous coronary intervention as a reperfusion strategy to improve clinical outcomes.


Functional Application of Sulfur-Containing Spice Compounds.
Sulfur-containing spice compounds possess diverse biological functions and play an important role in food, chemicals, pharmaceuticals, and agriculture. The development of functional spices has become increasingly popular, especially for medicinal functions for dietary health. Thus, this review focuses on the properties and functions of sulfur-containing spice compounds, including antioxidant, anti-inflammatory, antiobesity, anticancer, antibacterial, and insecticidal functions, among others. Developments over the last five years concerning the properties of sulfur-containing spice compounds are summarized and discussed.


Partial liquid ventilation protects lung during resuscitation from shock.
Preliminary animal experience with partial liquid ventilation (PLV) suggests that this therapy may diminish neutrophil invasion and capillary leak during acute lung injury. We sought to confirm these findings in a model of shock-induced lung injury. Sixty anesthetized rats were studied. After hemorrhage to an arterial pressure of 25 mmHg for 45 min, animals were resuscitated with blood and saline and treated with gas ventilation alone or with 5 ml/kg of intratracheally administered perflubron. Myeloperoxidase activity was used to measure lung neutrophil content. A permeability index (the bronchoalveolar-to-blood ratio of 125I-labeled albumin activity) quantified alveolar leak. Injury caused an increase in myeloperoxidase that was reversed by PLV (injury = 0.837 +/- 0.452, PLV = 0.257 +/- 0.165; P < 0.01). Capillary permeability also increased with hemorrhage, with a strong trend toward improvement in the PLV group (permeability indexes: injury = 0.094 +/- 0.102, PLV = 0.045 +/- 0.045; 95% confidence interval for injury--PLV: -0.024, 0.1219). We conclude that PLV is associated with a decrease in pulmonary neutrophil accumulation and a trend toward decreased capillary leak after hemorrhagic shock.


Atmospheres of science: Experiencing scientific mobility.
This article uses notions of the atmospheric to engage with empirical material concerned with international mobility in science. It draws on recent conceptual work on atmospheres that frames them as allowing access to the affective qualities of everyday life and as 'productively nebulous': atmospheres exist between the local and the globally diffuse, the emergent and the staged, the intangible and the brutally present. Using atmospheric thinking, I devise 'apparatuses of attunement' to capture elusive aspects of life in science, as discussed in interviews with natural scientists about their experiences of international mobility. In particular I use ideas of the situation, atmospheric threads, and the staging of atmospheres to argue that scientists represent themselves as existing in between the particular and the general: they are never wholly at the mercy of the structures and expectations of globalized science, but are also never not in the grip of them. In closing I reflect on what this analysis reveals about the affective qualities of contemporary science, the forms of life being nurtured by the norms and expectations of research (policy), and the kinds of agency available to (these) scientists. The aim of the article is thus twofold: to demonstrate how concepts of atmospheres can be put to work in STS, and to contribute to research on international mobility in science and contemporary scientific careers.


Storage of gastrointestinal endoscopes: when is the safe time for re-use?
to identify the safe storage time for the use of flexible gastrointestinal endoscopes after high-level disinfection, as well as the defining criteria for this time. an integrative literature review was carried out in the Virtual Health Library, PubMed, Scopus, and Web of Science, considering original articles published since 2000. eleven articles were selected, whose storage times ranged from 1 to 56 days, with a predominance of one to seven days (73%). Several criteria were used to define this time, predominantly the premise of efficient processing (100%), use of alcohol flush (64%), use of drying cabinets (18%), among others. the criteria for determining the storage time did not show a consensus for clinical practice. Expanding the discussion of this theme with the definition of the minimum necessary conditions is of fundamental importance for the reduction of risks and safety of the procedure and the patient.


Moderate hemolytic disease of the newborn due to anti-Hr0 in a mother with the D--/D-- phenotype.
Hemolytic disease of the newborn (HDN) due to anti-Hr0 antibody is typically severe and often fatal. We report a case of moderate HDN due to anti-Hr0 in a woman with the D--/D-- phenotype. A 33-year-old woman delivered her second child who was mildly jaundiced. The highest level of bilirubin was 26.1 mg/dL on the third day postpartum and the hemoglobin concentration was 14.0 g/dL. The newborn recovered after phototherapy and no mental retardation was noticed after 1 year of follow up. An exchange transfusion was excluded due to the lack of a compatible donor and the physical condition of the mother precluded blood donation. The maternal RBCs were D+C-c-E-e-; only G and Rh29 of the Rh system were expressed. Thus, her probable phenotype was D--/D--. Her alloantibody was identified as anti-Hr0 (anti-Rh17) as it reacted with all red blood cells (RBCs) but not her own, other D--- RBCs, and Rhnull RBCs. The results of the antibody titer (64) and activity in a chemiluminescense test (CLT; 34%) were consistent with a moderate HDN. Family studies were negative for the D--/D-- phenotype and consanguinity was not proved. This is the first described case of moderate HDN due to anti-Hr0. The result of antibody activity in the CLT might be helpful in predicting the severity of HDN in other rare HDN cases.


The impact of a child's chronic illness on fathers.
The purpose of this study was to examine the lived experience of fathers with a child having a chronic illness. This study used phenomenology as the design and the theoretical framework. Research on fathers with a child having a chronic illness is very limited. Five fathers were interviewed for this study to obtain their perspective. Living with financial strain, limited social life, lack of intimacy, being the primary caregiving parent to another child, and concerns about the future were the overriding themes of this study. Nurse practitioners must offer fathers professional support and encouragement to discuss fears and feelings openly in an effort to assist fathers in adaptation to their child's diagnosis of a chronic illness.