A one-health approach to design an mRNA-based vaccine candidate against the lumpy skin disease virus as an alternative to live-attenuated vaccines.
Recently, lumpy skin disease (LSD) has been spread over the Asian, European, and Middle Eastern regions making it a significant hazard to the chain of cattle production, milk production, and human milk consumption, requiring prompt attention. Lumpy skin disease virus has high morbidity and low fatality rates, but its infections have led to terrible economic and agricultural consequences. Although live-attenuated vaccines have been commercialized, farmers in different regions have not taken them well because of the allergic responses against the vaccines. The study aims to develop an mRNA-based vaccine candidate for LSDV, using immunoinformatic approaches to minimize allergenicity and homology while maximizing immunogenic potential. The study used extensive immunoinformatic approaches to shortlist five proteins from the LSDV genome that belong to the transmembrane region and are crucial in early viral interaction with host cells. The B-cell and T-cell-specific epitopes were chosen based on non-allergenicity, antigenicity, non-homology, surface accessibility, and lower IC50 inhibition values. The construct's stability, hydrophilicity, and antigenic potential were analyzed using the instability index, Grand Average of Hydropathicity (GRAVY) index, and antigenicity, respectively. We selected a total of 34 epitopes, consisting of 12 B-cell-specific epitopes and 22 T-cell-specific epitopes. These epitopes were chosen based on their characteristics such as non-allergenicity, antigenicity, non-homology, surface accessibility, and lower IC50 inhibition values. Specifically, 11 epitopes were selected for Major Histocompatibility Complex-I, and another 11 epitopes were chosen for Major Histocompatibility Complex-II. The inclusion of the RS09 adjuvant enhanced the immunogenic potential of the vaccine. The instability index was found to be 38.60. Additionally, the GRAVY index, indicating hydrophilicity, was calculated as -0.151. Furthermore, the antigenicity value of 0.6073 confirmed its potential to elicit an immune response. Further supporting its immunogenic potential, strong immune stimulation was observed, with IgM+IgG titers reaching 6,000 (arbitrary units) and IFNg titers measuring 400,000 ng/mL. These results provide additional evidence of the vaccine's ability to stimulate a robust immune response. The study results indicate that the developed mRNA-based vaccine candidate for LSDV has high immunogenic potential and could serve as an effective alternative to live-attenuated vaccines. Further experimental validations are required to test its efficacy. The study also highlights the potential of the One-Health approach to tackle non-zoonotic diseases that have significant consequences for the environment and humanity.


Guilty until proven innocent?--the Assumption of Care of a baby at birth.
This paper provides an overview of the history of child protection, the associated law and the 2008 amendments to the Child and Young Persons (Care and Protection) Act 1998 in relation to the Assumption of Care at birth practice. To explore the current practice of an Assumption of Care (AOC) where a newborn baby is removed from his/her mother at the time of birth, particularly focussing on the impact of the AOC on midwives. Assumption of Care practices in NSW raise significant issues for midwives in relation to the midwifery codes of ethics and conduct and importantly, to their ability to work in ways that honour a "woman-centred care" philosophy. When midwives are exposed to conflict between workplace and personal or professional values such as the practice of AOC cognitive dissonance can occur. Further research is required to understand the impact of current Assumption of Care. Broader research to not only look at effect on the midwife but also on other health professionals involved and the women who personally experience the removal of their baby at the time of birth. Consideration must also be given to ways of working with vulnerable families to enhance the acceptability and efficacy of maternity services and with associated agencies will decrease the need for Assumption of Care at birth.


Potential impact of antiviral drug use during influenza pandemic.
The recent spread of highly pathogenic strains of avian influenza has highlighted the threat posed by pandemic influenza. In the early phases of a pandemic, the only treatment available would be neuraminidase inhibitors, which many countries are considering stockpiling for pandemic use. We estimate the effect on hospitalization rates of using different antiviral stockpile sizes to treat infection. We estimate that stockpiles that cover 20%-25% of the population would be sufficient to treat most of the clinical cases and could lead to 50% to 77% reductions in hospitalizations. Substantial reductions in hospitalization could be achieved with smaller antiviral stockpiles if drugs are reserved for persons at high risk.


Temporal analysis of murine lymphocyte subpopulations by monoclonal antibodies and dual-color flow cytometry after burn and nonburn injury.
The immune suppression that frequently accompanies severe injury undoubtedly contributes to subsequent infectious complications. Various lymphocyte subpopulations may be identified by surface antigen expression, and alterations in antigen expression by lymphocytes may reflect host immune competence. Using monoclonal antibodies (Moabs) and dual-color flow cytometry, we studied lymphocyte phenotypic expression in mice after either controlled burn injury or hind-limb amputation, with use of peripheral blood, lymph node, and spleen for cell preparation. Moabs were utilized specific for T cells (Lyt-1), helper/inducer cells (L3T4), suppressor/cytotoxic cells (Lyt-2), B cells (IgG), and activated T cells (Ia or IL-2 receptor). The assay techniques called for small amounts of tissue and avoided gradient procedures that might result in selective loss of some lymphocyte populations. The most consistent changes observed were depressions in percentages of L3T4+ and Lyt-2+ cells in spleens of burned mice, accompanied by depression in Ia+ (possibly activated or proliferating) subsets of L3T4+ and Lyt-2+ cells, and the appearance of increased percentages of non-B, non-T lymphocytes. Changes in lymph node cells were minimal. The major alteration seen in peripheral blood was substantial depression of Ia+ subsets, although burned mice had increased circulating Lyt-2+ cells on several late postburn days. Burned mice, unlike limb-trauma mice, had marked splenic hypertrophy with more than a 300% increase in spleen weight after the 30-day postburn period. Eschar excision/implantation experiments indicated that splenic hypertrophy and splenocyte phenotypic changes are related to the presence of burned tissue, which suggests that burned tissue may partially mediate immune changes that accompany severe burn injury.


Crewmember microbiome may influence microbial composition of ISS habitable surfaces.
The International Space Station (ISS) is a complex built environment physically isolated from Earth. Assessing the interplay between the microbial community of the ISS and its crew is important for preventing biomedical and structural complications for long term human spaceflight missions. In this study, we describe one crewmember's microbial profile from body swabs of mouth, nose, ear, skin and saliva that were collected at eight different time points pre-, during and post-flight. Additionally, environmental surface samples from eight different habitable locations in the ISS were collected from two flights. Environmental samples from one flight were collected by the crewmember and samples from the next flight were collected after the crewmember departed. The microbial composition in both environment and crewmember samples was measured using shotgun metagenomic sequencing and processed using the Livermore Metagenomics Analysis Toolkit. Ordination of sample to sample distances showed that of the eight crew body sites analyzed, skin, nostril, and ear samples are more similar in microbial composition to the ISS surfaces than mouth and saliva samples; and that the microbial composition of the crewmember's skin samples are more closely related to the ISS surface samples collected by the crewmember on the same flight than ISS surface samples collected by other crewmembers on different flights. In these collections, species alpha diversity in saliva samples appears to decrease during flight and rebound after returning to Earth. This is the first study to compare the ISS microbiome to a crewmember's microbiome via shotgun metagenomic sequencing. We observed that the microbiome of the surfaces inside the ISS resemble those of the crew's skin. These data support future crew and ISS microbial surveillance efforts and the design of preventive measures to maintain crew habitat onboard spacecraft destined for long term space travel.


ACTH-mediated aldosterone hypersecretion during endotoxin-induced fever with apparent influence upon renal sodium excretion.
Febrile, endocrine, and renal responses to i.v. injection of endotoxin (E. coli lipopolysaccharide, 0.25 microgram kg-1) were studied in hyperhydrated goats without, and after dexamethasone pre-treatment, performed with the aim of inhibiting the adenohypophyseal secretion of ACTH. As expected from previous investigations, the administration solely of endotoxin induced biphasic fever, pronounced and long-lasting (less than 4 h) elevation of plasma cortisol (PC), and a prompt inhibition of the water diuresis. Apparently the observation that endotoxin also induced a pronounced biphasic elevation of plasma aldosterone (PA) where the two rising phases coincided with the early, and respectively the second elevation in rectal temperature is original. The endotoxin had no obvious influence upon the renal Na excretion for 3 h post-injection, and did not affect plasma renin activity (PRA). After dexamethasone pre-treatment (0.02 mg kg-1, i.v. 75 min prior to endotoxin) the endotoxin-induced rise in rectal temperature initially was less steep and no biphasic pattern of the fever was observed. The PC and antidiuretic responses became delayed for about 2 h and were then much attenuated. Endotoxin-induced rise in PA was no longer observed, and a conspicuous natriuresis developed within 90 min post-endotoxin. It is concluded that endotoxin at the dose used causes liberation of ACTH to such an extent that adrenocortical hypersecretion not only of glucocorticoids, but also of aldosterone occurs. The observed differences in Na excretion suggest that this aldosterone hypersecretion may be of pathophysiological importance as a protection against inappropriate renal waste of Na during the early phase of endotoxin-induced fever.(ABSTRACT TRUNCATED AT 250 WORDS)


Safe abortions in an illegal context: perceptions from service providers in Belgium.
Until April 1990 abortion was illegal in Belgium all circumstances. However, a small group of health professionals had long provided high-quality abortion services in outpatient facilities and in hospitals. This study is a qualitative analysis of perceptions among providers of safe abortion in Belgium before and after it was made legal there. The providers' personal, psychological, and ethical reactions to abortion are investigated, as well as their opinions on how their activities should be organized in order to minimize problems. Standardized questionnaires with closed and open questions were used; 143 questionnaires were completed. Emotional reactions were reported as being the most difficult aspects of practicing abortion. The experience of Belgian practitioners is of value for health professionals working in a legally restricted setting who are willing to assume some judicial risks to facilitate legal change while demonstrating the public health utility of low-cost, safe abortion.


The frequency and cancer risk associated with the atypical cytologic diagnostic category in endoscopic ultrasound-guided fine-needle aspiration specimens of solid pancreatic lesions: a meta-analysis and argument for a Bethesda System for Reporting Cytopathology of the Pancreas.
The atypical cytologic diagnostic category is ambiguous and presents a management problem for pathologists and clinicians. This meta-analysis reviewed the frequency and cancer risk associated with atypical diagnoses in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens of solid pancreatic lesions. PubMed and Scopus were searched using the keywords "EUS-FNA" and "pancreas." Articles were screened focusing on studies of solid lesions. Studies with information regarding the frequency and outcomes of atypical diagnoses were included; the "suspicious" category was excluded from the analysis. The frequency of atypical diagnoses and the associated risk were calculated using the Comprehensive Meta-Analysis software. The authors assessed whether the following factors explained the heterogeneity of the studies: rapid on-site interpretation; type of reference standard; the study type, size, and site; and the frequency of inadequate, atypical, and positive categories. A total of 23 studies with complete data regarding atypical diagnoses were identified, 12 of which had complete data available regarding outcomes. The frequency of the atypical category ranged from 1% to 14% (mean, 5.3%; 95% confidence interval, 4.1%-6.9%). The risk of malignancy associated with an atypical diagnosis ranged from 25% to 100% (mean, 58%; 95% confidence interval, 47%-69%). There was significant heterogeneity noted among the studies (I-squared, 62%; P = .0004). The frequency of the atypical category and its associated risk were found to be correlated only with the frequency of the specimens being positive for malignancy. The rate of atypical diagnoses of the pancreas is similar to that of the thyroid but the risk of malignancy is higher. Significant heterogeneity exists among the studies reporting atypical diagnoses. There is a need for standardization of the reporting and management of atypical diagnoses in EUS-FNA specimens from the pancreas.


Yeast Biofilm as a Bridge Between Medical and Environmental Microbiology Across Different Detection Techniques.
Medical and environmental microbiology have two distinct, although very short, histories stemming, the first from the pioneering works of Sommelweiss, Pasteur, Lister and Koch, the second mainly from the studies of Bejerink and Winogradsky. These two branches of microbiology evolved and specialized separately producing distinct communities and evolving rather different approaches and techniques. The evidence accumulated in recent decades indicate that indeed most of the medically relevant microorganisms have a short circulation within the nosocomial environment and a larger one involving the external, i.e. non-nosocomial, and the hospital environments. This evidence suggests that the differences between approaches should yield to a convergent approach aimed at solving the increasing problem represented by infectious diseases for the increasingly less resistant human communities. Microbial biofilm is one of the major systems used by these microbes to resist the harsh conditions of the natural and anthropic environment, and the even worse ones related to medical settings. This paper presents a brief outline of the converging interest of both environmental and medical microbiology toward a better understanding of microbial biofilm and of the various innovative techniques that can be employed to characterize, in a timely and quantitative manner, these complex structures. Among these, micro-Raman along with micro-Brillouin offer high hopes of describing biofilms both at the subcellular and supercellular level, with the possibility of characterizing the various landscapes of the different biofilms. The possibility of adding a taxonomic identification of the cells comprising the biofilm is a complex aspect presenting several technical issues that will require further studies in the years to come.


The Influence of Vitamin D Treatment on the Inducible Nitric Oxide Synthase (INOS) Expression in Primary Hippocampal Neurons.
Neurodegeneration is a process that is characterized by the loss of neuronal structure and function and eventually ends with neuronal death. An elevated level of inducible nitric oxide synthase (iNOS) is suggested to accompany this process by inducing oxidative and nitrosative damage. Vitamin D is reported to protect glial cells against neurotoxicity via suppressing iNOS synthesis. Though there was no data about whether iNOS is regulated by vitamin D in hippocampal neurons. In this study our aim was to determine any alteration in iNOS expression of hippocampal neurons in response to vitamin D treatment. Twenty four and 48 hours of vitamin D treatments were performed on primary hippocampal neuron cultures that were prepared from Sprague dawley rat embryos (E18). The alterations in the iNOS mRNA expression were determined with quantative real time polymerase chain reaction (qRT-PCR). The cytotoxicity levels of each group were investigated by the measurement of lactate dehydrogenase (LDH) that is released to culture medium. No difference was observed between groups in 24 hours of treatment regarding the iNOS expression. Though the iNOS mRNA level of vitamin D treated group was significantly lower than that of control group on the 48th hours of treatment (p<.001). Vitamin D treatment also attenuated the LDH release which is an indicator of cytotoxicity (p<.001). Our results indicated that vitamin D has the potential to prevent oxidative damage by suppressing iNOS expression.


Predicting, preventing and managing persistent pain after breast cancer surgery: the importance of psychosocial factors.
Persistent pain after breast cancer surgery (PPBCS) is increasingly recognized as a potential problem facing a sizeable subset of the millions of women who undergo surgery as part of their treatment of breast cancer. Importantly, an increasing number of studies suggest that individual variation in psychosocial factors such as catastrophizing, anxiety, depression, somatization and sleep quality play an important role in shaping an individual's risk of developing PPBCS. This review presents evidence for the importance of these factors and puts them within the context of other surgical, medical, psychophysical and demographic factors, which may also influence PPBCS risk, as well as discusses potential perioperative therapies to prevent PPBCS.


The semi-open approach to the gracilis muscle flap: aesthetic refinements in gracilis muscle harvest.
The gracilis muscle flap is certainly among the most versatile sources of vascularized tissue available for microsurgical reconstruction. However, the aesthetic appearance of the resultant scar has frequently been a source of dissatisfaction. Various minimal invasive techniques have been proposed, all of which aim to reduce scar formation. Drawbacks of endoscopic techniques, however, include a steep learning curve as well the need for special technical equipment. A semi-open approach without endoscopic assistance is presented, characterized by a short transverse incision in the groin area without a counterincision distally. This technique was performed in six patients (mean age, 48.8 years). Mean incision length was 8.8 cm, and average muscle harvesting time was 49 minutes. We suggest the semi-open approach to the gracilis muscle flap because it does not require special instruments and training and is characterized by easy performance and a short incision in the inconspicuous groin area with resultant better cosmesis.


Persistent synovial lymphocyte responses to cytomegalovirus antigen in some patients with rheumatoid arthritis.
Synovial lymphocytes from 6 of 40 patients with rheumatoid arthritis responded to cytomegalovirus antigen stimulation. 3H-thymidine uptakes were more than 3 times greater than were those of the responses to 13 other microbial antigens. Similar results were obtained in 1 patient on 7 occasions over 17 months, and in the 5 other patients on each of 2 occasions. In 3 of the 6 patients, synovial lymphocyte responses to cytomegalovirus antigen were markedly different from simultaneous peripheral blood lymphocyte responses.


Besides an ITIM/SHP-1-dependent pathway, CD22 collaborates with Grb2 and plasma membrane calcium-ATPase in an ITIM/SHP-1-independent pathway of attenuation of Ca2+i signal in B cells.
CD22 is a surface immunoglobulin implicated in negative regulation of B cell receptor (BCR) signaling; particularly inhibiting intracellular Ca2+ (Ca2+i)signals. Its cytoplasmic tail contains six tyrosine residues (Y773/Y783/Y817/Y828/Y843/Y863, designated Y1~Y6 respectively), including three (Y2/5/6) lying within immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that serve to recruit the protein tyrosine phosphatase SHP-1 after BCR activation-induced phosphorylation. The mechanism of inhibiting Ca2+i by CD22 has been poorly understood. Previous study demonstrated that CD22 associated with plasma membrane calcium-ATPase (PMCA) and enhanced its activity (Chen, J. et al. Nat Immunol 2004;5:651-7). The association is dependent on BCR activation-induced cytoplasmic tyrosine phosphorylation, because CD22 with either all six tyrosines mutated to phenylalanines or cytoplasmic tail truncated loses its ability to associate with PMCA. However, which individual or a group of tyrosine residues determine the association and how CD22 and PMCA interacts, are still unclear. In this study, by using a series of CD22 tyrosine mutants, we found that ITIM Y2/5/6 accounts for 34.3~37.1% Ca2+i inhibition but is irrelevant for CD22/PMCA association. Non-ITIM Y4 and its YEND motif contribute to the remaining 69.4~71.7% Ca2+i inhibition and is the binding site for PMCA-associated Grb2. Grb2, independently of BCR cross-linking, is constitutively associated with and directly binds to PMCA in both chicken and human B cells. Knockout of Grb2 by CRISPR/Cas9 completely disrupted the CD22/PMCA association. Thus, our results demonstrate for the first time that in addition to previously-identified ITIM/SHP-1-dependent pathway, CD22 holds a major pathway of negative regulation of Ca2+i signal, which is ITIM/SHP-1-independent, but Y4/Grb2/PMCA-dependent.


Serum isoamylase activities in diabetes mellitus.
Serum pancreatic isoamylase activities were used to assess exocrine pancreatic function in 39 patients with diabetes mellitus (21 on insulin, 12 on sulphonylureas, and six on biguanides or diet), and the results were compared with serum immunoreactive trypsin concentrations. Thirteen patients had decreased pancreatic isoamylase activity, the insulin-dependent diabetics showing the highest incidence of abnormality. This incidence of abnormality is similar to that previously described for serum immunoreactive trypsin, and the two procedures gave excellent overall correlation (r = 0.9). Our observations offer further evidence that pancreatic exocrine function is impaired in diabetes mellitus. Serum isoamylase determination provides a convenient, inexpensive, and rapid procedure for its detection.


A fatal case of primary cardiac chondrosarcoma presenting with amaurosis fugax.
A 64-year-old previously healthy woman consulted her general practitioner because of recurrent episodes of right-sided monocular transient visual loss (ie, amaurosis fugax). At first, these symptoms were followed over time, but as the attacks worsened, and were accompanied by dizziness and general discomfort, the patient was admitted to the department of neurology for further investigations. CT of the brain was normal; however, during admission, the patient developed rapid atrial fibrillation and was transferred to the department of cardiology. Transthoracic echocardiography revealed a massive tumour on the atrial side of the anterior mitral valve leaflet, partly obstructing the mitral valve inflow. The tumour was excised and a biological prosthetic mitral valve inserted. The tumour was histologically determined to be a highly malignant dedifferentiated chondrosarcoma. After 6 months, the tumour relapsed and expanded aggressively to completely obstruct the mitral valve inflow, ultimately leading to cardiac arrest and death.


Competing Developmental Demands Among Suicide-Bereaved Emerging Adults.
This qualitative group case study was ascertained to conceptualize theory on the topic of grief and emerging adulthood. A literature review proved no research to this specific experience. The aim of this study was to understand the suicide grief experience in this developmental stage. Based on the exploration of 150 suicide-bereaved emerging adults, participants in the Catholic Charities Young Adult Support Group expressed common themes related to the their unique grief experiences. Criterion sampling was used, as all these individuals voluntarily attended this group after losing a loved one to suicide. The methodology was observation and recording of oral data, and participants were asked to provide quarterly program evaluations. The analysis of data was recorded based on observed themes of statements made by participants. The conceptualized grief experiences that underpin this stage of development appear to work in opposition with grief tasks. This population would benefit from further research.


[Risk factors for nausea and vomiting after adolescent idiopathic scoliosis surgery].
To explore risk factors for postoperative nausea and vomiting (PONV) that requires intervention with medications during adolescent idiopathic scoliosis (AIS) surgery. We analyzed the data of 986 patients with AIS (including 156 male and 830 female patients) undergoing scoliosis surgery through a posterior approach between December, 2012 and January, 2016 in Nanjing Drum Tower Hospital. The data were collected from the patients including ASA grade, body mass index (BMI), Cobb angle, preoperative respiratory and cardiovascular diseases, operation time, type of anesthesia, quantity of intraoperative liquid infusion, blood loss, urine volume, the lowest MAP and CVP, intraoperative fentanyl consumption, and intraoperative administration of dexmedetomidine, dexamethasone, ondansetran and droperidol. The incidence of PONV in 48 h following the surgery, hemoglobin variation after operation (ΔHb), postoperative analgesia, times of use and types of antiemetic drugs, and postoperative hospital stay were recorded for all the patients. The potential risk factors of PONV within 48 h were analyzed using univariate analysis and multivariate logistic regression. Of the 986 patients analyzed, 151 (15.3%) experienced PONV within 48 h following surgeries for AIS. Multivariate logistic regression analysis suggested that an high intraoperative fentanyl dose (> 0.65 mg; OR=9.303, 95% CI: 2.373-8.622, P < 0.001), an obvious ΔHb (> 28.5 g/L; OR=1.107, 95% CI: 1.060-1.157, P < 0.001), and postoperative analgesia with fentanyl (OR=11.671, 95% CI: 2.381-11.284, P < 0.001) were risk factors for PONV. Intraoperative administration of dexmedetomidine (OR=0.027, 95% CI: 0.006-0.123, P=0.002) and dexamethasone combined with ondansetron (OR=0.241, 95%CI: 0.066-0.886, P=0.032) were protective factors against PONV. A high-dose intraoperative fentanyl consumption, a marked ΔHb, and postoperative analgesia with fentanyl are risk factors for PONV while intraoperative administration of dexmedetomidine and dexamethasone combined with ondansetron are protective factors against PONV following surgeries for AIS.


Reviewing two types of addiction - pathological gambling and substance use.
Gambling, including pathological gambling and problem gambling, has received increased attention from clinicians and researchers over the past three decades since gambling opportunities have expanded around the world. Gambling disorders affect 0.2-5.3% of adults worldwide, although measurement and prevalence varies according to the screening instruments and methods used, and availability and accessibility of gambling opportunities. Several distinct treatment approaches have been favorably evaluated, such as cognitive behavioral and brief treatment models and pharmacological interventions. Although promising, family therapy and support from Gamblers Anonymous are less well empirically supported. Gambling disorders are highly comorbid with other mental health and substance use disorders, and a further understanding is needed of both the causes and treatment implications of this disorder. This article reviews definition, causes and associated features with substance abuse, screening and diagnosis, and treatment approaches.


Effect of different sharpening stones on periodontal curettes evaluated by scanning electron microscopy.
The purpose of this study was to evaluate sharpening effect of different sharpening stones on periodontal curettes. In conjunction with 21 brand-new Gracey No. 1/2 curette blades, the Arkansas, India synthetic and ceramic stones were used in this study. The simulated root planing procedure was performed with 45 strokes on freshly extracted, single-rooted teeth. Positive and negative controls were provided. All sharpening procedures were carried out by a clinician and 10 sharpening strokes were applied to each blade with an angle of approximately 70 degrees. The blades were then examined by scanning electron microscopy (SEM). The working edges were investigated within the first 1 to 2 mm from the top of the blade under 500 times of magnification and 3 SEM micrographs were taken from each blade. Micrographs were examined for sharp wire edges, narrow bevel and wide bevel. The Fisher's exact test, Mantel-Haenszel test for trend and 1% probability were used for data analysis. Results indicate that (1) following the simulated root planing procedure, blades became dull, (2) among all the sharpening stones, the ceramic stone was least effective (p less than 0.01) in limited sharpening strokes, (3) with the India synthetic stones, no significant difference was found and they had better sharpening effects than others. This study demonstrates that the sharpening effect of India synthetic stones is the best under SEM examination with a standardized sharpening procedure.


Tazarotene-loaded in situ gels for potential management of psoriasis: biocompatibility, anti-inflammatory and analgesic effect.
Psoriasis is a chronic autoinflammatory disorder characterized by patches of abnormal skin. For psoriasis management, the application of topical retinoids as Tazarotene is recommended. However, Tazarotene could induce skin irritation limiting its use. Herein, it is evaluated the possible usage of in situ gels for tazarotene skin delivery. The topical in situ gels were developed using thermosensitive poloxamers via cold method. They were examined for their appearance, sol-gel temperature, clarity, pH, viscosity, in vitro release, and stability. Their biocompatibility was evaluated by investigating their cytotoxicity and irritation inducing capacity. The possible anti-inflammatory and analgesic activities were determined by measuring the nitric oxide and prostaglandin E2 levels production in LPS-stimulated RAW264.7 murine macrophage cells. It was revealed that the in situ gels had no cytotoxic effect (∼95-100% cell viability) and nor irritation potential (∼97% cell viability), according to the in vitro EpiDerm™ reconstituted skin irritation test. Additionally, the 10% tazarotene-in situ gels showed possible analgesic activity since the production of prostaglandin E2 (PGE2) was decreased. In further, both concentrations of 5% and 10% tazarotene-in situ gels inhibited significantly the nitrite oxide production at 16% and 19%, respectively. Finally, the prepared in situ gels can act as a potential non-irritant alternative option for tazarotene topical skin delivery.


Characterization of a restriction modification system from the commensal Escherichia coli strain A0 34/86 (O83:K24:H31).
Type I restriction-modification (R-M) systems are the most complex restriction enzymes discovered to date. Recent years have witnessed a renaissance of interest in R-M enzymes Type I. The massive ongoing sequencing programmes leading to discovery of, so far, more than 1 000 putative enzymes in a broad range of microorganisms including pathogenic bacteria, revealed that these enzymes are widely represented in nature. The aim of this study was characterisation of a putative R-M system EcoA0ORF42P identified in the commensal Escherichia coli A0 34/86 (O83: K24: H31) strain, which is efficiently used at Czech paediatric clinics for prophylaxis and treatment of nosocomial infections and diarrhoea of preterm and newborn infants. We have characterised a restriction-modification system EcoA0ORF42P of the commensal Escherichia coli strain A0 34/86 (O83: K24: H31). This system, designated as EcoAO83I, is a new functional member of the Type IB family, whose specificity differs from those of known Type IB enzymes, as was demonstrated by an immunological cross-reactivity and a complementation assay. Using the plasmid transformation method and the RM search computer program, we identified the DNA recognition sequence of the EcoAO83I as GGA(8N)ATGC. In consistence with the amino acids alignment data, the 3' TRD component of the recognition sequence is identical to the sequence recognized by the EcoEI enzyme. The A-T (modified adenine) distance is identical to that in the EcoAI and EcoEI recognition sites, which also indicates that this system is a Type IB member. Interestingly, the recognition sequence we determined here is identical to the previously reported prototype sequence for Eco377I and its isoschizomers. Putative restriction-modification system EcoA0ORF42P in the commensal Escherichia coli strain A0 34/86 (O83: K24: H31) was found to be a member of the Type IB family and was designated as EcoAO83I. Combination of the classical biochemical and bacterial genetics approaches with comparative genomics might contribute effectively to further classification of many other putative Type-I enzymes, especially in clinical samples.


Super Strong Be-Be Bonds: Theoretical Insight into the Electronic Structure of Be-Be Complexes with Radical Ligands.
The electronic structure of complexes formed by the interaction of Be2 with radical ligands (L:Be-Be:L) has been studied by means of the high-level theoretical protocol CCSD(T)/cc-pVTZ. At this level of theory, no matter the nature of the ligand, the Be-Be bond becomes up to 300 times stronger compared to isolated Be2, indicating that these kinds of complexes are thermodynamically stable and, thus, that they could be experimentally detected. Moreover, among all of the ligands considered, the strength of the Be-Be bond for L = [CN]• was calculated to be 330 kJ·mol-1, slightly greater than the strongest up to date L = F• complex, thus setting a new mark for the strongest Be-Be bond reported so far in the literature. Wave function analysis methods explain this strong interaction as a result of the oxidation of the Be2 moiety to Be22+ due to charge transfer toward the L ligands. In this study, we have also considered F:Mg-Mg:F complexes, which show very similar properties as the ones described for the analogous F:Be-Be:F.


[Epidemiology of headache].
We discuss here the epidemiology of chronic headache. Headache is a widespread and costly public health problem. Few people do not experience headache: in men, the lifetime prevalence for headache of any kind is 93 %, and for women it is up to 99%. Approximately 8.4 million people in Japan suffer from migraine, and 22 million have tension-type headache. Despite the painful, costly, and disabling impact of headache, many patients with headache do not seek medical advice. It is important to recognize the incidence of various kinds of chronic headache, and to diagnose and treat them correctly. In this article, we review the incidence, precipitating factors, regional prevalence, and age dependence of the incidence of each type of chronic headache.


Preparation and oral bioavailability study of curcuminoid-loaded microemulsion.
Curcuminoid, a dietary polyphenolic compound, has poor water solubility and low bioavailability following oral administration. The aim of this study was to develop a formulation of curcuminoid-loaded microemulsion (Cur-ME) to improve its oral bioavailability. The optimized Cur-ME formulation was prepared by using labrafac lipophile WL 1349, cremophor RH 40, and glycerine as the oil phase, the surfactant, and the cosurfactant, respectively. Pharmacokinetics and bioavailability of curcuminoid suspension and Cur-ME were evaluated and compared in rats. Plasma bisdemethoxycurcumin (BDMC), treated as the representing component of curcuminoid, was determined by high-performance liquid chromatography with fluorescence detector. After gavage administration of curcuminoid suspension, the plasma BDMC level was very low, below 5 ng/mL, whereas for Cur-ME, double peak of maximum concentrations were observed. The relative bioavailability of Cur-ME was enhanced in an average of 9.6-fold that of curcuminoid suspension. It was concluded that the bioavailbility of curcuminoid was enhanced greatly by the microemulsion.


Pseudotumoral neuroparacoccidioidomycosis of the posterior fossa: A case report and review of the literature.
Paracoccidioidomycosis is a systemic mycosis of significant importance in some Latin American countries. The widespread use of neuroimaging methods has shown that involvement of the central nervous system was more frequent than previously reported. The most common form of occurrence of neuroparacoccidioidomycosis is the pseudotumoral one. The authors report a case of pseudotumoral neuroparacoccidioidomycosis localized in the posterior fossa. A 49-year-old single man, rural worker, born and raised in Laranjal Paulista-SP, was admitted to the hospital with 3 months history of bilateral occipital headache every day. Along with a history of active smoking and previous use of alcohol, the patient reported personal history of mild occipitotemporal injury 3 months ago. The patient was submitted to computed tomography in a 16-row multidetector scanner, which revealed a nodular hypodense lesion with a ring-enhancement and associated perilesional edema in the left cerebellar hemisphere. Radiological workup was initiated to investigate the eventual primary neoplastic site. The analysis of the lipid peak by spectroscopy of proton magnetic resonance may indicate the neurological involvement by paracoccidioidomycosis, notably in patients with concomitant risk and pulmonary involvement signals.


[Conductivity of the radial nerve following its injury].
Evoked muscle potentials are usually lacking in cases of complete anatomical interruption of the radial nerve. With all other data considered, such patients are subject to surgery. In cases when evoked muscle potentials are recorded in the presence of neurological signs of a complete interruption of the nerve, its anatomical continuity is usually retained. In such patients the velocity of conduction falls to 6.37 +/- 1.9 (sigma4) m/sec. In such patients non-sucrgial treatment results in the appearance of active fingers extension and sensations improvement.


Chronic fatigue syndrome: clinical condition associated with immune activation.
There is much conflicting immunological and viral data about the causes of chronic fatigue syndrome (CFS); some findings support the notion that CFS may be due to one or more immune disorders that have resulted from exposure to an infectious agent. In the present study, flow cytometry and several different monoclonal antibodies recognising T, B, and natural killer (NK) cell populations as well as activation and cell adhesion antigens were used to study 147 individuals with CFS. Compared with healthy controls, a reduced CD8 suppressor cell population and increased activation markers (CD38, HLA-DR) on CD8 cells were found. The differences were significant (p = 0.01) in patient with major symptoms of the disease. These immunological indices were not observed in 80 healthy individuals, in 22 contacts of CFS patients, or in 43 patients with other diseases. No correlation of these findings in CFS patients with any known human viruses could be detected by serology. The findings suggest that immune activation is associated with many cases of CFS.


Full-ring Intrastromal Corneal Implantation for Correcting High Myopia in Patients with Severe Keratoconus.
The aim of this study was to evaluate the effect of the mechanical implantation of a MyoRing in patients with severe keratoconus and high myopia. The study involved 32 eyes of 32 patients (14 men and 18 women; mean age: 29.6 ± 6.7; age range: 20 - 44). The patients underwent MyoRing implantation with mechanical dissection using a Pocket Maker microkeratome, and outcomes were assessedat3 months after surgery. The main outcome measures were uncorrected and corrected distance visual acuity (UDVA and CDVA, both in Logarithm of the Minimum Angle of Resolution [logMAR] units), manifest refraction, and keratometry readings. There was a significant improvement in the UDVA, from 1.14 ± 0.32 to 0.35 ± 0.24 (P ˂ 0.001), and in the CDVA, from 0.47 ± 0.20 to 0.22 ± 0.15 (P ˂ 0.001). There was also a significant improvement in the spherical equivalent refractive error (-10.51 ± 2.81 D to -1.32 ± 2.29 D) (P ˂ 0.001). There was a significant decrease of manifest refraction in the mean sphere and cylinder of 7.70 and 2.6 D, respectively (P < 0.001). Furthermore, with regard to corneal topography, there was a significant reduction of 3.55 D (P ˂ 0.001) in the mean keratometry reading. The results show that the mechanical implantation of a MyoRing is effective for the correction of myopia in patients with keratoconus and high myopia.


The dynamics of providing street medicine to a geographically diverse homeless population in Hawaii.
Since Hawaii has the highest rate of per capita of persons experiencing homelessness (PEH) in the United States, the purpose of this qualitative evaluation study was to evaluate the experiences of both the providers and clients of a Street Medicine (SM) program serving one side of the island of O'ahu. This evaluation used Story Inquiry to qualitatively assess one SM program serving one side of the island of O'ahu in Hawa'i. Since the culture in Hawaii is largely based upon stories, a qualitative approach was taken to better understand the lived experiences of PEH who utilized the SM services, as well as provider perspectives. The findings of this evaluation include strengths of increased primary care engagement and improved quality of life for PEH; barriers to success included transportation scarcity and limitations of services available. The findings lend implications for new SM programs, including gathering community support, having culturally aware outreach and that mobility and flexibility can overcome health-care barriers for PEH.


[Clinical features of pulmonary disease caused by Mycobacterium fortuitum].
We analyzed clinical and microbiological features of six cases involving Mycobacterium fortuitum isolated from sputum or surgical lung specimen. Patients were five men and one woman with an average age of 59. Four cases had a history of pulmonary tuberculosis and three had nontuberculous mycobacterial lung disease. Three out of six cases had underlying chronic obstructive pulmonary disease. Diabetes mellitus was complicated in five cases. All diseases were in the upper lobes of either lung. Clinical symptoms were mainly cough and sputum, while two cases developed pneumothorax. Although all strains showed low sensitivity to standard anti-tuberculous agents, chemotherapy including those drugs or fluoroquinolones and macrolides were successful in all treated cases.


Neurogenesis in the adult ischemic brain: generation, migration, survival, and restorative therapy.
This article reviews current data on the induction of neurogenesis after stroke in the adult brain. The discussion of neurogenesis is divided into production, migration, and survival of these newly formed cells. For production, the subpopulations and the types of cell division are presented. Discussion of cell migration entails presenting data on both the pathways as well as the molecular targeting of newly formed neural progenitor cells to sites of injury. The role of the vascular and the astrocytic microenvironment in promoting the survival and integration of progenitor cells is also presented. Cell-based and pharmacological therapies designed to restore neurological function that promote neurogenesis are described. These therapies also induce angiogenesis and astrocytic changes that brain tissue, which prime the ischemic brain to foster the survival of the newly formed progenitor cells. Signaling pathways that regulate neurogenesis and angiogenesis are also addressed. This review summarizes recent data on neurogenesis and provides insight into the potential for restorative treatments of stroke.


Two regions of simian virus 40 large T-antigen independently extend the life span of primary C57BL/6 mouse embryo fibroblasts and cooperate in immortalization.
Expression of the SV40 large T-antigen allows primary cells to escape senescence and thereby become immortalized. Immortalization occurs in two steps, extension of life span and acquisition of unlimited cell division potential. By following the increase in expression of a senescence-associated marker with increased cell passage, we show that C57Bl/6 mouse embryo fibroblast (B6MEF) cultures senesce by passage 4. Thus, the development of colonies from cultures transfected with T-antigen expressing constructs indicates extension of life span. Two T-antigen regions independently extended the life span of B6MEF. Expression of either a T-antigen consisting of amino acids 1-147 (T1-147) or a T-antigen consisting of amino acids 251-708 (T251-708) resulted in colony development. However, the colonies expressing these truncated T-antigens could not be expanded into cell lines efficiently. In contrast, coexpression of T1-147 and T251-708 produced colonies that could be expanded into cell lines as efficiently as could colonies expressing full-length T-antigen. Thus, the two regions of T-antigen contain analogous activities that are sufficient to extend cell life span; they cooperate to immortalize primary B6MEF; and they act in trans, indicating that the functions involved are independent.


Printable Energy Storage: Stay or Go?
In the era of rapidly evolving smart electronic devices, the development of power supplies with miniaturization and versatility is imperative. Prevailing manufacturing approaches for basic energy modules impose limitations on their size and shape design. Printing is an emerging technique to fabricate energy storage systems with tailorable mass loading and compelling energy output, benefiting from elaborate structural configurations and unobstructed charge transports. The derived "printable energy storage" realm is now focusing on materials exploration, ink formulation, and device construction. This contribution aims to illustrate the current state-of-the-art in printable energy storage and identify the existing challenges in the 3D printing design of electrodes. Insights into the future outlooks and directions for the development of this field are provided, with the goal of enabling printable energy storage toward practical applications.


Relationship of the effective refractory period and monophasic action potential duration after a step increase in pacing frequency.
Adaptation of effective refractory period (ERP) and monophasic action potential (MAP) shortening after a step increase in drive frequency was determined at adjacent endocardial sites in the right ventricle of six patients without myocardial disease. ERP and MAP shortening occurred simultaneously. ERP shortening and MAP shortening were similar in time course in individuals, although the degree of shortening varied between individuals as the size of the step increase in pacing frequency varied. Shortening of both ERP and MAP was complete after a mean of 67 +/- 7.5 seconds. To allow group analysis, the percent change from baseline of action potential duration and ERP was calculated for each patient at intervals during adaptation and mean percent change for the group plotted against time from the beginning of the step rate increase. A mean step increase in pacing frequency of 49.3% of baseline for the group caused the ERP to shorten by a mean of 18.12%, and MAP90 by 17.43% of baseline. There was no significant difference (P = 0.05) between the action potential and ERP adaptation curves of the group. We conclude that in normal myocardium, there is a close relationship between shortening of ventricular ERP and action potential duration after a change in rate.


The baboon as a good model for studies of human kidney development.
Because of the improved survival of premature neonates in recent years, it is important to investigate the effects of premature delivery on the kidney, in which nephrogenesis is still ongoing during the third trimester. Hence, an appropriate animal model that is similar to humans is essential. The aim of the current study is to determine the time course of nephrogenesis in the baboon, to establish whether it is a suitable model of human nephrogenesis. At the Southwest Foundation for Biomedical Research (San Antonio, TX), fetal baboons were delivered prematurely by cesarean delivery and at term by natural delivery. Fixed kidneys from 125-, 140-, 175-, and 185-d gestation baboons were assessed morphologically for evidence of a nephrogenic zone. Nephron number, kidney volume, and glomerular and corpuscle volume were also estimated using unbiased stereology. Morphologic assessment confirmed the presence of metanephric mesenchyme and immature glomeruli in the nephrogenic zone of the kidneys from the prematurely delivered fetuses at 125 and 140 d gestation. At 175 d gestation and at term, the nephrons seemed to be mature. Both kidney weight (R2= 0.918, p = 0.0002) and kidney volume (R2= 0.837, p = 0.001) were very strongly correlated with nephron number. There was also a direct relationship between gestational age (R2= 0.589, p = 0.03) and birth weight (R2= 0.562, p = 0.03) with nephron number. In conclusion, in this study, nephrogenesis in the baboon is complete before term by 175 d gestation, which is similar to humans. Hence, the baboon is a suitable model for future studies to investigate human kidney development.


A novel rasopathy caused by recurrent de novo missense mutations in PPP1CB closely resembles Noonan syndrome with loose anagen hair.
Noonan syndrome is a rasopathy caused by mutations in multiple genes encoding components of the RAS/MAPK pathway. Despite its variable phenotype, limited genotype-phenotype correlations exist. Noonan syndrome with loose anagen hair (NS-LAH) is characterized by its distinctive hair anomalies, developmental differences, and structural brain abnormalities and is caused by a single recurrent missense SHOC2 mutation. SHOC2 forms a complex with protein phosphatase 1 (PP1C). Protein phosphatases counterbalance kinases and control activation of signaling proteins, such as the mitogen-activated protein kinases of the RAS/MAPK pathway. Here we report four patients with de novo missense mutations in protein phosphatase one catalytic subunit beta (PPP1CB), sharing a recognizable phenotype. Three individuals had the recurrent PPP1CB c.146G>C, p.Pro49Arg mutation, the fourth had a c.166G>C, p.Ala56Pro change. All had relative or absolute macrocephaly, low-set and posteriorly angulated ears, and developmental delay. Slow growing and/or sparse hair and/or an unruly hair texture was present in all. Three individuals had feeding difficulties requiring feeding tubes. One of two males had cryptorchidism, another had pectus excavatum. Short stature was present in three. A female with the recurrent mutation had a Dandy-Walker malformation and optic nerve hypoplasia. Mild ventriculomegaly occurred in all, cerebellar tonsillar ectopia was seen in two and progressed to Chiari 1 malformation in one individual. Based on the combination of phenotypic findings and PPP1CB's effect on RAF dephosphorylation within the RAS/MAPK pathway, this novel condition can be considered a rasopathy, most similar to NS-LAH. Collectively, these mutations meet the standardized criteria for pathogenicity. © 2016 Wiley Periodicals, Inc.


[Percutaneous dilatation tracheostomy. A preliminary study].
Fifteen patients electively selected for percutaneous dilatational tracheostomy as performed with the Ciaglia Percutaneous Tracheostomy Introducer Set are reported in this preliminary study. The median time for insertion of the tracheostomy tube was 13.1 min. Complications were cuff puncture of the translaryngeal tube at an early stage of the procedure in one case, and minor bleeding controllable by the compressible effect of the dilatational procedure in three cases. During the posttracheostomy period complications included one case of minor bleeding controllable by digital compression and one case of minor infection, i.e. cellulitis in a few millimetres around the stoma without purulent secretion. Our preliminary results indicate that the technique as performed with the Ciaglia Introducer Set is effective and safe with only minor complications. Furthermore, we now use it as a bed-side procedure in the ICU, thus avoiding the transportation of critically ill patients to the operating theatre. A conclusion on the superiority of percutaneous tracheostomy to dissectional tracheostomy has to await clinical randomized studies including more patients.


Integrated healthcare for chronically ill. Reflections on the gap between science and practice and how to bridge the gap.
Integrated care offers an opportunity to address healthcare efficiency and effectiveness concerns and is especially relevant for elderly patients with different chronic illnesses. In current care standards for chronic care focus is often on one disease. The chronic care model (CCM) is used as the basis of integrated care programs. It identifies essential components that encourage high-quality chronic disease care, involving the community and health system and including self-management support, delivery system design, decision support, and clinical information systems. Improvements in those interrelated components can produce system reform in which informed, activated patients interact with prepared, proactive practice teams. There is however a lack of research evidence for the impact of the chronic care model as a full model. Integrated care programs have widely varying definitions and components and failure to recognize these variations leads to inappropriate conclusions about the effectiveness of these programs and to inappropriate application of research results. It seems important to carefully consider the type and amount of data that are collected within the disease management programs for several purposes, as well as the methods of data collection. Understanding and changing the behavior of complex dynamic chronic care system requires an appreciation of its key patterns, leverage points and constraints. A different theoretical framework, that embraces complexity, is required. Research should be design-based, context bound and address relationships among agents in order to provide solutions that address locally defined demands and circumstances.


Development of an Immune-Pathology Informed Radiomics Model for Non-Small Cell Lung Cancer.
With increasing use of immunotherapy agents, pretreatment strategies for identifying responders and non-responders is useful for appropriate treatment assignment. We hypothesize that the local immune micro-environment of NSCLC is associated with patient outcomes and that these local immune features exhibit distinct radiologic characteristics discernible by quantitative imaging metrics. We assembled two cohorts of NSCLC patients treated with definitive surgical resection and extracted quantitative parameters from pretreatment CT imaging. The excised primary tumors were then quantified for percent tumor PDL1 expression and density of tumor-infiltrating lymphocyte (via CD3 count) utilizing immunohistochemistry and automated cell counting. Associating these pretreatment radiomics parameters with tumor immune parameters, we developed an immune pathology-informed model (IPIM) that separated patients into 4 clusters (designated A-D) utilizing 4 radiomics features. The IPIM designation was significantly associated with overall survival in both training (5 year OS: 61%, 41%, 50%, and 91%, for clusters A-D, respectively, P = 0.04) and validation (5 year OS: 55%, 72%, 75%, and 86%, for clusters A-D, respectively, P = 0.002) cohorts and immune pathology (all P < 0.05). Specifically, we identified a favorable outcome group characterized by low CT intensity and high heterogeneity that exhibited low PDL1 and high CD3 infiltration, suggestive of a favorable immune activated state. We have developed a NSCLC radiomics signature based on the immune micro-environment and patient outcomes. This manuscript demonstrates model creation and validation in independent cohorts.


Effects of anthropogenic nitrogen discharge on dissolved inorganic nitrogen transport in global rivers.
Excess nutrients from fertilizer application, pollution discharge, and water regulations outflow through rivers from lands to oceans, seriously impacting coastal ecosystems. A reasonable representation of these processes in land surface models and River Transport Models (RTMs) is very important for understanding human-environment interactions. In this study, the schemes of riverine dissolved inorganic nitrogen (DIN) transport and human activities including nitrogen discharge and water regulation, were synchronously incorporated into a land surface model coupled with a RTM. The effects of anthropogenic nitrogen discharge on the DIN transport in rivers were studied based on simulations of the period 1991-2010 throughout the entire world, conducted using the developed model, which had a spatial resolution of about 1° for land processes and 0.5° for river transport, and data on fertilizer application, point source pollution, and water use. Our results showed that rivers in western Europe and eastern China were seriously polluted, on average, at a rate of 5,000-15,000 tons per year. In the Yangtze River Basin, the amount of point source pollution in 2010 was about four times more than that in 1991, while the amount of fertilizer used in 2010 doubled, which resulted in the increased riverine DIN levels. Further comparisons suggested that the riverine DIN in the USA was affected primarily by nitrogen fertilizer use, the changes in DIN flow rate in European rivers was dominated by point source pollution, and rivers in China were seriously polluted by both the two pollution sources. The total anthropogenic impact on the DIN exported to the Pacific Ocean has increased from 10% to 30%, more significantly than other oceans. In general, our results indicated that incorporating the schemes of nitrogen transport and human activities into land surface models could be an effective way to monitor global river water quality and diagnose the performance of the land surface modeling.


Multi-Spectral Imaging of Circumscribed Choroidal Hemangioma Introduction.
To illustrate the features of a circumscribed choroidal hemangioma (CCH) using Annidis RHA multi-spectral imaging (MSI) technology (Annidis Corporation, Ottawa, Canada). This novel imaging technique uses non-overlapping, narrow-band LED light sources ranging from 520 nm to 940 nm to create a monochromatic series of en face fundus images and oxy/deoxyhemoglobin contrasted maps of the retina and choroid. Annidis RHA MSI images were taken of a 67-year-old Chinese male with CCH. These en face fundus images are presented alongside the traditional fundus photograph, optical coherence tomography, and fluorescein and indocyanine green angiograms. Multi-spectral en face images of the outer retina and choroid demonstrated a clearly delineated lesion with a disorganized choroidal vascular network and increased reflectance/ oxyhemoglobin levels within. MSI technology is a noninvasive imaging technique that can depict the vascular features and choroidal oxygenation of CCH lesions and has a potential role in monitoring its growth complications. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:572-575.].


Psychopathic Personality Traits in the Military: An Examination of the Levenson Self-Report Psychopathy Scales in a Novel Sample.
The Levenson Self-Report Psychopathy Scale is a short, self-report measure initially developed to assess psychopathic traits in noninstitutionalized samples. The present study aimed to explore factor structure and convergent and discriminant validity of the Levenson Self-Report Psychopathy Scale in a large U.S. military sample (90.7% Army National Guard). Factor analytic data, regression, and correlational analyses point to the superiority of Brinkley, Diamond, Magaletta, and Heigel's three-factor model in this sample. Implications for theory and the study of psychopathic personality traits in a military sample are discussed.


Changes of aerobic capacity, fat ratio and flexibility in older TCC practitioners: a five-year follow-up.
The objective of this study was to evaluate the 5-year changes of aerobic capacity, fat ratio and flexibility in older Tai Chi Chuan (TCC) practitioners and sedentary controls. Sixty-nine community-dwelling elderly individuals (mean age: 68.6 +/- 6.3 years) completed this study. The TCC group (18 M; 17 F) had been practicing TCC regularly for 6.3 +/- 3.7 years at baseline and continued training in the study interval. The control group (16 M; 18 F) did not participate in any regular exercise program. A graded bicycle exercise testing was conducted at the baseline and at 5-year to evaluate the age-related decline in aerobic capacity. Triceps and subscapular skinfolds, and thoracolumbar flexibility were also measured. At baseline, the TCC group displayed higher peak oxygen uptake $({\dot{\rm V}}{\rm O}_{2{\rm peak}})$ and thoraolumbar flexibility, and lower fat ratio than the control group. At the 5-year follow-up, the TCC group displayed a smaller decrease in $\dot{\rm V}{\rm O}_{2{\rm peak}}$ than the sedentary group. The annual decrease of $\dot{\rm V}{\rm O}_{2{\rm peak}}$ in TCC men and women was 0.32 and 0.22 ml . kg(-1) . min(-1), respectively. In the control group, the annual decrease of $\dot{\rm V}{\rm O}_{2{\rm peak}}$ was 0.50 and 0.36 ml . kg(-1) . min(-1) in men and women, respectively. The TCC group also showed a smaller increase of body fat ratio, and a less decrease of flexibility than the control group. In conclusion, long-term practice of TCC attenuates the age-related decline of aerobic capacity, and it also reduces the increase of body fat ratio in older individuals. TCC may be prescribed as a conditioning exercise for the elderly to maintain their health fitness.


Effects on function and quality of life of postoperative home-based physical therapy for patients with hip fracture.
To evaluate the effects of a 3-month home-based physical therapy (PT) program for patients with hip fracture after surgery. Randomized controlled trial. Home. Twenty-five patients recently discharged from an acute orthopedic department. Patients were randomized to the home-based PT group (n=13), where they received home-based PT 8 times from discharge to month 3 postdischarge, or to the control group (n=12). The home-based PT program included exercises for muscle strengthening, range of motion (ROM), balance, and functional training. Patients in the control group were instructed to practice the exercise program given at bedside before discharge. Patients were evaluated for hip ROM, strength, walking velocity, Harris hip score, and health-related quality of life (HRQOL) at the week of discharge and at 1, 3, and 6 months after discharge. The baseline characteristics showed no difference between the 2 groups. Harris score of the home-based PT group progressed from 58.6+/-8.5 to 90.1+/-5.4 at month 3, whereas Harris score of the control group progressed from 54.6+/-14.5 to 77.4+/-10.0 (P<.01). Scores of the psychologic domain of HRQOL for the home-based PT group were significantly better at month 1 (P<.05) and month 3 (P<.01) after discharge. Moreover, the physical domain score of the home-based PT group was also significantly better (P<.05) at 3 months after discharge. Home-based PT programs could help patients regain function and HRQOL earlier.


Combined effects of maternal smoking status and dietary intake related to weight gain and birth size parameters.
To investigate the interaction of smoking status and dietary intake during pregnancy and its relationship to maternal weight gain and birth size parameters. An observational prospective study. Free-living conditions. Four hundred and eight healthy pregnant Icelandic women. Maternal smoking status, lifestyle factors and dietary habits were evaluated with questionnaires. Intake of foods and supplements was also estimated with a semiquantitative food frequency questionnaire for the previous 3 months. All questionnaires were filled out between 11 and 15 weeks and between 34 and 37 weeks of gestation. Smoking status in relation to optimal and/or excessive weight gain during pregnancy was represented with logistic regression controlling for potential confounding factors. Maternal weight gain, smoking status, dietary intake and birthweight. Women who smoked throughout pregnancy were unlikely to gain optimal weight or more (OR 0.51, 95% CI 0.27-0.97), whereas smoking cessation in connection with pregnancy ('former smokers') doubled the risk of excessive weight gain (OR 2.03, 95% CI 1.24-3.35). The latter association was no longer significant after adjustment for dietary factors and other confounding factors. Former smokers ate the least amount of fruit and vegetables (fruit: 129 versus 180 and 144 g/day (median), P= 0.038; vegetables: 53 versus 76 and 72 g/day, P= 0.026 for former smokers, nonsmokers and smokers, respectively). Birthweight was lowest among infants born to smokers, but birthweight was similar for former smokers and nonsmokers (3583 +/- 491 g versus 3791 +/- 461 g and 3826 +/- 466 g, respectively; P= 0.003). Smoking cessation in early pregnancy or pre-pregnancy is not associated with low birthweight. It is, however, associated with excessive maternal weight gain and a low fruit and vegetable intake.


Block Forests: random forests for blocks of clinical and omics covariate data.
In the last years more and more multi-omics data are becoming available, that is, data featuring measurements of several types of omics data for each patient. Using multi-omics data as covariate data in outcome prediction is both promising and challenging due to the complex structure of such data. Random forest is a prediction method known for its ability to render complex dependency patterns between the outcome and the covariates. Against this background we developed five candidate random forest variants tailored to multi-omics covariate data. These variants modify the split point selection of random forest to incorporate the block structure of multi-omics data and can be applied to any outcome type for which a random forest variant exists, such as categorical, continuous and survival outcomes. Using 20 publicly available multi-omics data sets with survival outcome we compared the prediction performances of the block forest variants with alternatives. We also considered the common special case of having clinical covariates and measurements of a single omics data type available. We identify one variant termed "block forest" that outperformed all other approaches in the comparison study. In particular, it performed significantly better than standard random survival forest (adjusted p-value: 0.027). The two best performing variants have in common that the block choice is randomized in the split point selection procedure. In the case of having clinical covariates and a single omics data type available, the improvements of the variants over random survival forest were larger than in the case of the multi-omics data. The degrees of improvements over random survival forest varied strongly across data sets. Moreover, considering all clinical covariates mandatorily improved the performance. This result should however be interpreted with caution, because the level of predictive information contained in clinical covariates depends on the specific application. The new prediction method block forest for multi-omics data can significantly improve the prediction performance of random forest and outperformed alternatives in the comparison. Block forest is particularly effective for the special case of using clinical covariates in combination with measurements of a single omics data type.


Duck Complement Factor H Binds to Outer Membrane Protein Omp24 of Riemerella anatipestifer.
The resistance to serum complement-mediated killing is a vital virulence property of microbial pathogens. Complement factor H (FH) is a key negative regulator of the complement alternative pathway (AP) that prevents formation and accelerates the decay of AP C3 convertase and acts as a cofactor in the inactivation of C3b. Pathogens can recruit host FH through their surface proteins to escape the clearance of the complement system. Riemerella anatipestifer could also evade the complement system attack to achieve host infection, but the mechanism is still unclear. In this study, the R. anatipestifer proteins that could interact with FH in host serum were screened and analyzed, and the functions were determined. Affinity chromatography with a Ni-nitrilotriacetic acid Sefinose column and mass spectrometry identified three outer membrane proteins (Omp) of R. anatipestifer, Omp54, Omp53, and Omp24, as potential FH-binding proteins. We then successfully conducted the prokaryotic expression and polyclonal antibody preparation of three candidate proteins. Indirect immunofluorescence assay showed that three candidate proteins were all present in R. anatipestifer. The affinity blotting assay, anti-serum-inhibiting assay, and serum bactericidal assay presented evidence that Omp24 could bind FH. Moreover, FH bound to Omp24 was associated with resistance to the alternative pathway and functional for R. anatipestifer survival in the normal duck serum. These results suggested that R. anatipestifer Omp24 was a FH-binding protein and the interaction with FH blocked the alternative pathway. Recruitment of complement regulatory proteins may facilitate better R. anatipestifer resistance to this vital line of host defense.


Micromethod for analysis for chloride in physiological fluids.
A micromethod for the analysis for chloride, based on the chemical precipitation of silver chloride by radial diffusion through agar gel containing silver nitrate, is described. The method is simple to run, requires little or no instrumentation, and requires only 10 mul of sample. Results by coulometric titration (Buchler Cotlove Chloridometer) correlated well for serum (r = 0.961), urine (r = 0.997), cerebrospinal fluid (r = 0.991), and sweat (r = 0.998). Other halide ions or protein do not interfere. Precision studies gave a within-day reproducibility (CV) of 1.3% and a day-to-day variability of 2.1% for a serum sample averaging 115 mmol/liter.


The effect of variation in mesh-base design on the shear bond strength of orthodontic brackets.
This study compared the shear bond strengths of two metallic orthodontic brackets, one with a single-mesh bracket base and the other with a double-mesh bracket base. The Transbond XT adhesive system was used to bond all brackets to the teeth. Two types of brackets were compared, ie, 20 Ovation metal bracket series, with a double-mesh base (Super-mesh) and an 81.50 gauge (0.126 inch), and 20 Victory series metal brackets that have a miniature single-mesh base. The teeth were bonded and debonded within half an hour from the initial bonding. The enamel surface was examined under 10x magnification to determine how much residual adhesive remained on the tooth. Student's t-test was used to compare the shear bond strength of the two groups. Chi-square test was used to compare the adhesive remnant index (ARI) scores for the two bracket types. The mean shear bond strength for the double-mesh brackets was 5.2 +/- 3.9 MPa and for the single-mesh brackets was 5.8 +/- 2.8 MPa. The t-test comparisons indicated that they were not significantly different from each other (P = .157). The ARI comparisons indicated that both bracket types had similar bracket failure modes and were not significantly different from each other (chi2 = 2.0, P = .5). These results indicated that single- and double-mesh bracket bases have comparable shear bond strength and bracket failure modes.


Congenital hypothyroidism due to defects of thyroid development and mild increase of TSH at screening: data from the Italian National Registry of infants with congenital hypothyroidism.
Over the years lower TSH cutoffs have been adopted in some screening programs for congenital hypothyroidism (CH) worldwide. This has resulted in a progressive increase in detecting additional mild forms of the disease, essentially with normally located and shaped thyroid. However, the question of whether such additional mild CH cases can benefit from detection by newborn screening and early thyroid hormone treatment is still open. The aim of this study was to estimate the frequency of cases with mild increase of TSH at screening in the Italian population of babies with permanent CH and to characterize these babies in terms of diagnosis classification and neonatal features. Data recorded in the Italian National Registry of infants with CH were analyzed. Between 2000 and 2006, 17 of the 25 Italian screening centers adopted a TSH cutoff at screening of <15.0 μU/mL. It was found that 21.6% of babies with permanent CH had TSH at screening of 15.0 μU/mL or less, whereas this percentage was 54% in infants with transient hypothyroidism. Among the babies with permanent CH and mild increase of TSH at screening (≤15 μU/mL), 19.6% had thyroid dysgenesis with serum TSH levels at confirmation of the diagnosis ranging from 9.9 to 708 μU/mL. These babies would have been missed at screening if the cutoff had been higher. Lowering TSH cutoff in our country has enabled us to detect additional cases of permanent CH, a number of which had defects of thyroid development and severe hypothyroidism at confirmation of the diagnosis.


Electrochemical degradation of psychoactive drug caffeine in aqueous solution using graphite electrode.
In this study, the electrochemical degradation of caffeine (1,3,7-trimethylxanthine) in aqueous solution by a graphite electrode was investigated. Electrochemical degradation was tested by the cyclic voltametry technique performed in the potential range of -1.0 to +1.0 V versus Ag/AgCl, which confirmed the electro-activity of the selected caffeine. The effects of the treatment process variables, such as initial pH, current density, electrolyte concentration and electrolysis time on the degradation of caffeine, were explored. During the various stages of electrolysis, parameters such as chemical oxygen demand (COD), total organic carbon (TOC) were analysed. The maximum COD and TOC removal efficiencies of 85% and 77% were achieved at neutral pH 7, operated at a current density of 5.1 mA/cm2, electrolyte (Na2SO4) concentration of 0.1 M and at 240 min electrolysis time. From this study, it can be concluded that the electrochemical treatment process could effectively reduce the COD and TOC from the caffeine in aqueous medium. The degradation of the caffeine was confirmed by UV spectra, IR spectra and HPLC analysis.


Effect of Histone Deacetylase HDAC3 on Cytokines IL-18, IL-12 and TNF-α in Patients with Intrahepatic Cholestasis of Pregnancy.
The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is poorly understood. This study aimed to explore the possible effect of HDAC3 (histone deacetylase) on cytokines IL-18, IL-12 and TNF-α in ICP. Serum levels of cytokines IL-18, IL-12 and TNF-α, bile acids and hepatic function parameters were measured. The expression of HDAC3 in the placenta was determined by immunohistochemistry (IHC), western blotting and RT-PCR. IL-18, IL-12 and TNF-α serum levels were significantly higher in the severe ICP group than in the mild ICP group and the control group, and the difference between the mild ICP group and control group was not significant. HDAC3 protein expression was identified in the nucleus of the placental trophoblast by IHC. HDAC3 mRNA and protein expression were significantly lower in the ICP groups (mild ICP and severe ICP groups) than in the control groups, and no significant difference was found between the mild ICP and severe ICP groups. The low expression of HDAC3 and overexpession of inflammatory cytokines (IL-18, IL-12 and TNF-α) in ICP may be involved in liver cell apoptosis. We suspect that HDAC3 may play an important role in the pathophysiology of ICP.


Topographic electroencephalogram in children during mask induction of anaesthesia with sevoflurane.
Epileptiform patterns, spikes, polyspikes and periodic epileptiform discharges (PED) have been reported in electroencephalograms (EEGs) during anaesthesia induction with sevoflurane in healthy adults and children. Published recordings have been performed with a limited number of channels, and therefore the topographic distributions of these patterns are not known. Twenty ASA I children aged 4-10 years undergoing routine operations were anaesthetized with 8% sevoflurane in 50%/50% oxygen and nitrous oxide using mask induction with controlled normoventilation. An EEG was recorded with a full 10-20 electrode system including orbitofrontal and ear electrodes, and a recording band of 0.016-70 Hz. Beat-to-beat heart rate (HR) was calculated off-line. Nineteen out of 20 children developed multifocal spikes and polyspikes with a maximum over the frontal lobes. Four patients developed suppression, which was almost continuous and lasted several minutes, and thereafter a continuous EEG resumed, a few spikes were seen and then a nonepileptiform pattern. In three children a couple of PED waves were seen at the onset of a continuous EEG. HR increased maximally before the onset of spikes. No motor phenomena were seen. These recordings confirm the epileptogenic property of sevoflurane in mask induction. The spikes and polyspikes had frontal multifocal maxima and may be missed in recordings from frontopolar electrodes used by depth-of-anaesthesia monitors. PED and burst suppression were synchronous over the whole cortex. Epileptiform activity was indiscernible from epileptiform waveforms without anaesthesia, such as the patterns seen in status epilepticus.


Herpes simplex pneumonia in a young immunocompetent man.
We report the case of a 33 year old man with herpetic bronchitis and bilateral pneumonitis. He presented without mucocutaneous lesions, and his cellular and humoral immunity were not compromised. Diagnosis was established on histological and cytological findings and confirmed by serology. Acyclovir treatment led to a favourable outcome.


Decreased oocyte quality in patients with endometriosis is closely related to abnormal granulosa cells.
Infertility and menstrual abnormalities in endometriosis patients are frequently caused by aberrant follicular growth or a reduced ovarian reserve. Endometriosis typically does not directly harm the oocyte, but rather inhibits the function of granulosa cells, resulting in a decrease in oocyte quality. Granulosa cells, as oocyte nanny cells, can regulate meiosis, provide the most basic resources required for oocyte development, and influence ovulation. Endometriosis affects oocyte development and quality by causing granulosa cells apoptosis, inflammation, oxidative stress, steroid synthesis obstacle, and aberrant mitochondrial energy metabolism. These aberrant states frequently interact with one another, however there is currently relatively little research in this field to understand the mechanism of linkage between abnormal states.


Changes in brain white matter integrity after systemic treatment for breast cancer: a prospective longitudinal study.
An increasing number of studies suggest chemotherapy for breast cancer may be neurotoxic. Cross-sectional MRI diffusion tensor imaging (DTI) studies suggest a vulnerability of brain white matter to various chemotherapeutic regimens. Up till now, this was confirmed in one prospective DTI study: Deprez et al. (2012) showed a widespread decline in fractional anisotropy (FA) of breast cancer patients after chemotherapy consisting of 5-fluorouracil (5-FU), epirubicin and cyclophosphamide (FEC) +/- taxanes +/- endocrine treatment. Our aim was to evaluate whether similar detrimental effects on white matter integrity would be observed with the currently widely prescribed anthracycline-based chemotherapy for breast cancer (predominantly doxorubicin and cyclophosphamide +/- taxanes +/- endocrine treatment (=BC + SYST; n = 26) compared to no systemic treatment (BC; n = 23) and no-cancer controls (NC; n = 30). Assessment took place before and six months after chemotherapy, and matched intervals for the unexposed groups. DTI data were analyzed using voxel-based tract-based spatial statistics and region of interest (ROI) analysis. Voxel-based analysis did not show an effect of chemotherapy +/- endocrine treatment on white matter integrity. ROI analysis however indicated subtle detrimental effects of chemotherapy +/- endocrine treatment by showing a larger decline in WM integrity in the superior longitudinal fasciculus and corticospinal tract in BC + SYST than BC. Indications for relatively mild neurotoxicity in our study might be explained by patient characteristics and specific aspects of data analysis. The omission of 5-FU in current treatment regimens or the administration of doxorubicin instead of epirubicin is also discussed as an explanation for the observed effects.


Association of the CTLA4 gene with Graves' disease in the Chinese Han population.
To determine whether genetic heterogeneity exists in patients with Graves' disease (GD), the cytotoxic T-lymphocyte associated 4 (CTLA-4) gene, which is implicated a susceptibility gene for GD by considerable genetic and immunological evidence, was used for association analysis in a Chinese Han cohort recruited from various geographic regions. Our association study for the SNPs in the CTLA4 gene in 2640 GD patients and 2204 control subjects confirmed that CTLA4 is the susceptibility gene for GD in the Chinese Han population. Moreover, the logistic regression analysis in the combined Chinese Han cohort revealed that SNP rs231779 (allele frequencies p = 2.81x10(-9), OR = 1.35, and genotype distributions p = 2.75x10(-9), OR = 1.42) is likely the susceptibility variant for GD. Interestingly, the logistic regression analysis revealed that SNP rs35219727 may be the susceptibility variant to GD in the Shandong population; however, SNP, rs231779 in the CTLA4 gene probably independently confers GD susceptibility in the Xuzhou and southern China populations. These data suggest that the susceptibility variants of the CTLA4 gene varied between the different geographic populations with GD.


A stable lipase from Candida lipolytica: cultivation conditions and crude enzyme characteristics.
Although lipases have been intensively studied, some aspects of enzyme production like substrate uptake, catabolite repression, and enzyme stability under long storage periods are seldom discussed in the literature. This work deals with the production of lipase by a new selected strain of Candida lipolytica. Concerning nutrition, it was observed that inorganic nitrogen sources were not as effective as peptone, and that oleic acid or triacylglycerides (TAG) were essential carbon sources. Repression by glucose and stimulation by oleic acid and long chain TAG (triolein and olive oil) were observed. Extracellular lipase activity was only observed at high levels at late stationary phase, whereas intracellular lipase levels were constant and almost undetectable during the cultivation period, suggesting that the produced enzyme was attached to the cell wall, mainly at the beginning of cultivation. The crude lipase produced by this yeast strain shows the following optima conditions: pH 8.0-10.0, temperature of 55 degrees C. Moreover, this preparation maintains its full activity for at least 370 d at 5 degrees C.


KLF4 loss in hepatocellular carcinoma: Improving prognostic prediction and correlating immune infiltrates.
Introduction: Although the molecular mechanisms of Krüpple-like factor 4 (KLF4) as a tumor suppressor in HCC tumorigenesis have been thoroughly examined, its clinical application in terms of precise prognostication and its influence on tumor immune microenvironment in patients with HCC require further investigation. Methods: Bioinformatics and immunohistochemistry (IHC) were used to validate KLF4 expressions in a tissue microarray (TMA) containing HCC samples. Using Cox regression models, independent prognostic factors were identified and employed in the development of nomograms. Decision curve analysis (DCA) demonstrated the superiority of the nomograms. GO and KEGG pathway analyses were applied to the functional study of KLF4. The GSVA program explored the link between KLF4 expression and tumor-infiltrating immune cells, and CAMOIP was used to construct KLF4 expression immune scores. Changes in immune-related gene markers were also investigated in relation to KLF4 expression. The association between immune cell infiltration and KLF4 expression was validated by IHC in TMA. Results: HCC was reported to have a notable depletion of KLF4. The absence of KLF4 was associated with advanced clinicopathological characteristics of HCC and predicted a bad prognosis for patients. Nomograms constructed using KLF4 expression, tumor differentiation, and TNM stage provided a more accurate prognostic assessment of HCC patients than TNM stage alone. KLF4 expression was associated with immunological-related functions, infiltration of macrophages, CD8+ T cells, and other immune cells, and elevation of immune checkpoints. Higher levels of CD8+ T cells and macrophage infiltration are associated with increased KLF4 expression in HCC TMA. Conclusion: KLF4 loss in HCC is a prognostic biomarker that influences the tumor immune microenvironment (TIME).


A controlled trial of stimulant medication in children with the fragile X syndrome.
Attentional deficits and hyperactivity frequently are major problems for fra(X) boys. This study evaluated the effectiveness of 2 stimulant medications, methylphenidate and dextroamphetamine compared to placebo in 15 children (13 males, 2 females) with the fra(X) syndrome. A double-blind crossover design was used with outcome measures which included parent and teacher behavior checklists, a controlled observation period, continuous performance tasks and an actometer measure of movement. When the children were treated with methylphenidate only, improvement was seen in socialization skills and attention span according to teacher checklists. Ten children were clinically considered responders and treatment was continued after the study was completed.


The Underlying Function and Structural Organization of the Intracellular Protein Corona on Graphdiyne Oxide Nanosheet for Local Immunomodulation.
Nanomaterial-biology interaction is the critical step in the fate of biomedical nanomedicines, influencing the consequent biological outcomes. Herein, we present two-dimensional carbon-based nanomaterials-graphdiyne oxide (GDYO) nanosheets that interact with an intracellular protein corona consisting of signal transducer and activator of transcription 3 (STAT3), inducing the reeducation of immunosuppressive macrophages. The interaction at the GDYO-STAT3 interface, driven by structure matching, hydrogen bonding, and salt bridges, simultaneously triggers the immune response in the tumor microenvironment, facilitating cancer immunotherapy. For the first time, our data reveal an interaction mechanism between the nanoparticle-protein interfaces inevitably formed inside the cells that determines the macrophage phenotype. Our results suggest that GDYO nanosheets could be applied for local immunomodulation due to their function and structural organization of the intracellular protein corona occurred inside macrophages.


Linking remote sensing data to the estimation of pollination services in agroecosystems.
Wild bees are key providers of pollination services in agroecosystems. The abundance of these pollinators and the ecosystem services they provide rely on supporting resources in the landscape. Spatially explicit models that quantify wild bee abundance and pollination services in food crops are built on the foundations of foraging and nesting resources. This dependence limits model implementation as land-cover maps and pollination experts capable of evaluating habitat resource quality are scarce. This study presents a novel approach to assessing crop pollination services using remote sensing data (RSD) as an alternative to the more conventional use of land-cover data and local expertise on spatially explicit models. We used landscape characteristics derived from remote sensors to qualify nesting resources in the landscape and to evaluate the delivery of pollination services by mining bees (Andrena spp.) in 30 fruit orchards located in the Flemish region of Belgium. For this study, we selected mining bees for their importance as local pollinators and underground nesting behavior. We compared the estimated pollination services derived from RSD with those derived from the conventional qualification of nesting resources. We did not observe significant differences (p = 0.68) in the variation in mining bee activity predicted by the two spatial models. Estimated pollination services derived from RSD and conventional characterizations explained 69% and 72% of the total variation, respectively. These results confirmed that RSD can deliver nesting suitability characterizations sufficient for estimating pollination services. This research also illustrates the importance of nesting resources and landscape characteristics when estimating pollination services delivered by insects like mining bees. Our results support the development of holistic agroenvironmental policies that rely on modern tools like remote sensors and promote pollinators by considering nesting resources.


Cocaine dependence: a case series from India.
Cocaine use and dependence is a wellknown phenomenon in the West but has not been reported in the medical literature from India, despite recent media reports of its use by drug abusers and seizure by authorities. We report 5 patients with cocaine dependence who came for treatment to the Department of Psychiatry, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh. All the patients were young adult men (age range 20-27 years). They were either unemployed or in medium level occupation. All used cocaine by 'snorting' (inhaling cocaine hydrochloride salt in a powder form through the nose so that cocaine gets rapidly absorbed into the bloodstream through the nasal mucosal epithelial capillary vasculature). None reported smoking or inhaling the vapour of heated freebase cocaine ('crack'). All reported intense and specific craving for cocaine (and met criteria for dependence syndrome as per ICD-10), though 3 patients were also dependent on opioid preparations (heroin, dextropropoxyphene or codeine containing cough syrups). We started them on clonidine for opioid detoxification followed by naltrexone. Since there is no approved medication for cocaine withdrawal or relapse prevention, our focus was on relapse prevention counselling using cognitive behavioural principles. The outcome was variable. Cocaine dependence is present among the population in India. Patients are not necessarily from the affluent class. This case series of cocaine dependence, the first from India, intends to be both a curtain raiser and an eye opener.


Toward Sustainable Metal-Iodine Batteries: Materials, Electrochemistry and Design Strategies.
Due to the natural abundance of iodine, cost-effective, and sustainability, metal-iodine batteries are competitive for the next-generation energy storage systems with high energy density, and large power density. However, the inherent properties of iodine such as electronic insulation and shuttle behavior of soluble iodine species affect negatively rate performance, cyclability, and self-discharge behavior of metal-iodine batteries, while the dendrite growth and metal corrosion on the anode side brings potential safety hazards and inferior durability. These problems of metal-iodine system still exist and need to be solved urgently. Herein, we summarize the research progress of metal-iodine batteries in the past decades. Firstly, the classification, design strategy and reaction mechanism of iodine electrode are briefly outlined. Secondly, the current development and protection strategy of conventional metal anodes in metal-iodine batteries are highlighted, and some potential anode materials and their design strategies are proposed. Thirdly, the key electrochemical parameters of state-of-art metal-iodine batteries are compared and analyzed to solve critical issues for realizing next-generation iodine-based energy storage systems. Therefore, the aim of this review is to promote the development of metal-iodine batteries and provide guidelines for their design.


Influence of nitrogen and sulfur fertilization on quality of canola (Brassica napus L.) under rainfed conditions.
Field experiments were conducted at Cereal Crops Research Institute, Pirsabak, Nowshera, Pakistan, during winter 2003-2004 and 2004-2005 to evaluate the effect of nitrogen and sulfur levels and methods of nitrogen application on canola (Brassica napus L. cv. Bulbul-98) under rainfed conditions. Four levels of S (0, 10, 20, and 30 kg/ha) and three levels of N (40, 60, and 80 kg/ha) and a control treatment with both nutrients at zero level were included in the experiments. Sulfur levels were applied at sowing while N levels were applied by three methods (100% soil application, 90% soil+10% foliar application, and 80% soil +20% foliar application). The experiments were laid out in randomized complete block (RCB) design having four replications. Oil content increased significantly up to 20 kg S/ha but further increase in S level did not enhance oil content. Glucosinolate content increased from 13.6 to 24.6 micromol/g as S rate was increased from 0 to 30 kg/ha. Protein content increased from 22.4% to 23.2% as S rate was increased from 0 to 20 kg/ha. Oil content responded negatively to the increasing N levels. The highest N level resulted in the highest values for protein (23.5%) and glucosinolate (19.9 micromol/g) contents. Methods of N application had no significant impact on any parameters under study.


Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain.
N,N-dimethyltryptamine (DMT), a psychedelic compound identified endogenously in mammals, is biosynthesized by aromatic-L-amino acid decarboxylase (AADC) and indolethylamine-N-methyltransferase (INMT). Whether DMT is biosynthesized in the mammalian brain is unknown. We investigated brain expression of INMT transcript in rats and humans, co-expression of INMT and AADC mRNA in rat brain and periphery, and brain concentrations of DMT in rats. INMT transcripts were identified in the cerebral cortex, pineal gland, and choroid plexus of both rats and humans via in situ hybridization. Notably, INMT mRNA was colocalized with AADC transcript in rat brain tissues, in contrast to rat peripheral tissues where there existed little overlapping expression of INMT with AADC transcripts. Additionally, extracellular concentrations of DMT in the cerebral cortex of normal behaving rats, with or without the pineal gland, were similar to those of canonical monoamine neurotransmitters including serotonin. A significant increase of DMT levels in the rat visual cortex was observed following induction of experimental cardiac arrest, a finding independent of an intact pineal gland. These results show for the first time that the rat brain is capable of synthesizing and releasing DMT at concentrations comparable to known monoamine neurotransmitters and raise the possibility that this phenomenon may occur similarly in human brains.


Detection of isoflavones in mouse tibia after feeding daidzein.
Many studies suggest that diets rich in isoflavones protect against bone loss or slow the loss of bone mass that occurs because of estrogen withdrawal. Although in vitro studies have reported effects of isoflavones on bone cells, the presence of daidzein and/or equol in bone tissue in vivo has not been reported. The objective of this study was to determine if daidzein and equol were present in bone tissue (tibias) after feeding mice a diet containing purified daidzein. Sham mice (n = 9) received control diet, and ovariectomized mice were randomized to control diet (Ovx) (n = 9) or control diet containing 200 mg of daidzein/kg of diet (n = 8) for 12 weeks. At necropsy, tibias and serum were collected. Mice in the Daidzein group had significantly higher (P < .05) levels of both daidzein and equol in tibias than Sham and Ovx mice. Tibia levels of daidzein and equol were approximately five and four times higher, respectively, than the Sham and Ovx groups. Similarly, mice fed daidzein also had significantly higher (P < .05) serum daidzein and equol than the Sham and Ovx mice. In conclusion, feeding a level of daidzein that is attainable by dietary intervention alone results in a high level of both daidzein and equol in tibias. These findings suggest that daidzein and its metabolite, equol, have the potential to act directly on bone cells in vivo.