Raman spectroscopic study on solvation of diphenylcyclopropenone and phenol blue in room temperature ionic liquids.
We investigated the solvation of several room temperature ionic liquids by Raman spectroscopy using diphenylcyclopropenone (DPCP) and phenol blue (PB) as probe molecules. We estimated acceptor numbers (AN) of room temperature ionic liquids by an empirical equation associated with the Raman band of DPCP assigned as a C=C stretching mode involving a significant C=O stretching character. According to the dependence of AN on cation and anion species, the Lewis acidity of ionic liquids is considered to come mainly from the cation charge. The frequencies and bandwidths of the C=O and C=N stretching modes of phenol blue are found to be close to those in conventional polar solvents such as methanol and dimethyl sulfoxide. The frequencies of these vibrational modes show similar dependence upon the electronic absorption band center as is observed in conventional liquid solvents. However, peculiar behavior was found in the Raman bandwidths and the excitation wavelength dependence of the C=N stretching mode in room temperature ionic liquids. Both the bandwidth of the C=N stretching mode and the extent of the excitation wavelength dependence of the Raman shift of the C=N stretching mode tend to decrease as the absorption band center decreases, in contrast to the case of conventional solvents. This anomaly is discussed in terms of the properties of room temperature ionic liquids.


Silent Illumination: A Case Study Exploring the Spiritual Needs of a Transgender-Identified Elder Receiving Hospice Care.
With a growing population of transgender-identified elders in the United States, their unique spiritual end-of-life needs are coming to light. This article presents a case study of a hospice volunteer who used skillful means as an artist to help a transgender-identified woman express her spirituality in the last 6 months of her life. After data analysis, 4 themes emerged related to the expression of spirituality by lesbian, gay, bisexual, transgender, and queer (LGBTQ) elders at end of life. The themes that emerged included (1) the human element in advocacy for spiritual care, (2) the importance of safe spaces for reflection and meditation, (3) the importance of skillful means to work with LGBTQ people, and (4) acknowledgement of gender identity as a spiritual need. This case study serves as a springboard to advance research into the end-of-life needs of LGBTQ elders and the ways in which members of the hospice team can support spiritual care and alleviate suffering for this population.


Assessment of prognostic significance of cytoplasmic survivin expression in advanced oesophageal cancer.
Survivin is a member of the family of proteins, which inhibit apoptosis (inhibitor of apoptosis proteins - IAP). Expression of survivin was found in colorectal cancer, neuroblastoma, bladder cancer, non-small cell lung cancer, and breast cancer. There is some recent data indicating the correlation of poor prognosis and worse response to chemotherapy in patients with oesophageal squamous cell carcinoma (OSCC) expressing survivin. The aim of the present study was to assess survivin expression in cancerous tissue of patients with advanced OSCC and to test the potential correlation between survivin expression and clinicopathological data. Forty two patients (mean age 58.36+/-8.97 yrs), who were oesophagectomised due to squamous cell carcinoma of the thoracic oesophagus between 1998 and 2000, were retrospectively analysed. Cytoplasmic survivin expression, examined immunohistochemically, was found in 35 (83.33%) cases. No statistically significant correlation between survivin expression in the tumour and patients' gender, TNM stage, or vascular involvement was noted. The mean survival of patients with cytoplasmic survivin expression (17.81+/-5.51 months) was not statistically different to those with negative survivin staining (16+/-6.28 months) as assessed by Mantel-Cox test (p=0.49). Univariate regression analysis revealed UICC staging as the only predictor of survival in the analysed group (p<0.05). These results indicate that the cytoplasmic survivin expression does not seem to be the prognostic factor in advanced cases of OSCC.


Comparison of medical and surgical treatment of nasal polyposis.
Nasal polyposis is the end result of a variety of pathologic processes. The aims of treatment are to relieve nasal blockage, restore olfaction, and improve sinus drainage. Treating any accompanying rhinitis is also an aim, which requires that medical treatment be given to all patients with an inflammatory problem. Most forms of nasal polyp recur after treatment, whether medical or surgical. There are few direct comparisons of medical and surgical treatment in the literature. Those that exist suggest that most patients should be treated medically, with surgery reserved for patients who respond poorly. Large prospective randomized trials of surgical versus medical therapy are needed in groups of well-characterized patients to determine the optimum approach for each and to decrease relapse rates. Topical corticosteroids are the mainstay of treatment. All patients with inflammatory polyps should receive topical corticosteroid treatment in the long-term, unless there is a compelling contraindication. Adverse effects of surgery are rare but can be devastating. The major side effects of medical therapy are those of oral corticosteroids, which need to be used carefully. The choice of topical corticosteroid is important because long-term use is necessary; the least absorbed should be used. No cost-benefit analysis has been undertaken in this area, although medical therapy is probably cheaper and involves less work/school absence than sinonasal surgery, even when the latter is performed with an endoscope.


Quantification of heterocyclic amine carcinogens in cooked meats using isotope dilution liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry.
Heterocyclic aromatic amines (HAAs) are formed in cooked meats through pyrolysis reactions of different amino acids in the presence or absence of creatine/creatinine and sugars. HAAs are mutagens, colon/mammary gland carcinogens in rodents, and are suspected in the etiology of human cancers. In this study, cooked meats containing incurred HAAs as well as control (microwave) meat, were spiked with four labeled HAA internal standards (MeIQx, IQ, AAC and PhIP) and extracted using a liquid/liquid cleanup procedure. Isotope dilution measurements were made using on-line liquid chromatography atmosphere pressure chemical ionization tandem mass spectrometry with multiple reaction monitoring to provide the sensitivity and specificity needed for trace analysis in these complex matrices. The procedure was validated using control meat spiked with the four native HAAs at 0-50 ppb. The levels of HAAs found in cooked meats ranged from non-detectable (limit of detection 0.1-1.0 ppb) in microwave-cooked hamburger to 226 ppb PhIP and 104 ppb AAC in well-done grilled chicken. This methodology has the potential to provide accurate data on the consumption of HAAs in the diet for use in human cancer risk assessment.


Eosinophils, but not neutrophils, exhibit an efficient DNA repair machinery and high nucleolar activity.
Traditionally eosinophils have been considered terminally differentiated cells that play a role in host protection against parasites. However, there is some evidence showing that eosinophils are, in fact, multifunctional leukocytes involved in inflammatory responses, as well as in tissue homeostasis. We characterized the transcriptome profile of human eosinophils, and, for the purpose of comparison, the transcriptome profile of neutrophils, monocytes and hematopoietic progenitor cells. Moreover, we studied the activation of selected cellular processes for which a significant differential expression was demonstrated. We profiled gene expression using Affymetrix GeneChips. DNA repair capacity was tested using the comet assay. Nucleoli and their activity were characterized by transmission electron microscopy analysis, silver staining of nucleolus regions (AgNOR) and RNA staining. Gene expression profiling showed that eosinophils appear hierarchically closer to monocytes than to neutrophils. Gene ontology mapping of differentially expressed genes revealed that eosinophils express categories very similar to those expressed by monocytes, related to DNA repair and nucleolar functions. Moreover, our data show that eosinophils and monocytes maintain the ability to repair both double and single strand DNA breaks, whereas neutrophils lack this capacity. Furthermore, eosinophils exhibit nucleolar activity, which is lacking in neutrophils, but resembles that in monocytes. The presence of large, active nucleoli in eosinophils, coupled to marked activity of DNA repair systems, suggests that eosinophils are not terminally differentiated cells. Indeed, their transcriptome profile and functional properties are more similar to those of non-terminally differentiated cells such as monocytes, rather than to neutrophils.


Modulation of IGFBP2 mRNA expression in white adipose tissue upon aging and obesity.
The insulin/IGF-1 signaling pathway is a determinant of aging and age-related diseases. IGF-binding protein 2 (IGFBP2) is secreted by white adipocytes and contributes to the prevention of diet-induced obesity and age-related insulin resistance in mice. However, the expression levels of IGFBP2 in insulin resistance disorders have not been evaluated. The present study was aimed at determining IGFBP2 mRNA levels in adipose tissue in conditions of insulin resistance such as aging and obesity. In visceral white adipose tissue (WAT), but not in subcutaneous WAT, IGFBP2 mRNA levels were significantly lower in obese OB/OB, DB/DB and high fat-fed mice compared with those of their respective lean and chow-fed littermates. IGFBP2 mRNA levels were also decreased in visceral WAT of 12 and 24 months old mice compared with those of their 4 months old counterparts. Visceral WAT IGFBP2 expression was significantly associated with IGFBP2 circulating levels in mice, suggesting an important contribution from this tissue. The negative effect of aging on IGFBP2 mRNA levels in visceral WAT was confirmed in obese men. These findings demonstrate that the transcription of the IGFBP2 gene is modulated in a depot-specific fashion in obesity and aging in mice and men. Because IGFBP2 is an adipokine, an altered production from visceral WAT depots could impact on IGF-1 signaling and its downstream targets. This supports the need for further molecular and clinical studies to determine the factors regulating IGFBP2 expression and its relevance to metabolic diseases.


[Maxillofacial growth and dental implants in the maxillary anterior region].
Single tooth replacement with a dental implant is an increasingly popular solution in patients with loss of an upper anterior tooth. There is a risk, however, of placing the implant prematurely in youths. In a case series the effects of residual maxillary growth on the results of implant treatment in the anterior maxillary region were measured. The results confirm findings from other studies on this subject and indicate that cessation and degree of vertical growth are unpredictable. This may result in infraposition of the implant and lead to periodontal bone loss around the implant region and its neighbouring teeth. Clinicians should be aware of this and inform their patients that these changes may eventually compromise the aesthetic result of the treatment.


(D-Ser2) oxyntomodulin recovers hippocampal synaptic structure and theta rhythm in Alzheimer's disease transgenic mice.
In our previous studies, we have shown that (D-Ser2) oxyntomodulin (Oxm), a glucagon-like peptide 1 (GLP-1) receptor (GLP1R)/glucagon receptor (GCGR) dual agonist peptide, protects hippocampal neurons against Aβ1-42-induced cytotoxicity, and stabilizes the calcium homeostasis and mitochondrial membrane potential of hippocampal neurons. Additionally, we have demonstrated that (D-Ser2) Oxm improves cognitive decline and reduces the deposition of amyloid-beta in Alzheimer's disease model mice. However, the protective mechanism remains unclear. In this study, we showed that 2 weeks of intraperitoneal administration of (D-Ser2) Oxm ameliorated the working memory and fear memory impairments of 9-month-old 3×Tg Alzheimer's disease model mice. In addition, electrophysiological data recorded by a wireless multichannel neural recording system implanted in the hippocampal CA1 region showed that (D-Ser2) Oxm increased the power of the theta rhythm. In addition, (D-Ser2) Oxm treatment greatly increased the expression level of synaptic-associated proteins SYP and PSD-95 and increased the number of dendritic spines in 3×Tg Alzheimer's disease model mice. These findings suggest that (D-Ser2) Oxm improves the cognitive function of Alzheimer's disease transgenic mice by recovering hippocampal synaptic function and theta rhythm.


MiniMed 670G hybrid closed loop artificial pancreas system for the treatment of type 1 diabetes mellitus: overview of its safety and efficacy.
Introduction: Automated insulin delivery for people with type 1 diabetes has been a major goal in the diabetes technology field for many years. While a fully automated system has not yet been accomplished, the MiniMed™ 670G artificial pancreas (AP) system is the first commercially available insulin pump that automates basal insulin delivery, while still requiring user input for insulin boluses. Determining the safety and efficacy of this system is essential to the development of future devices striving for more automation. Areas Covered: This review will provide an overview of how the MiniMed 670G system works including its safety and efficacy, how it compares to similar devices, and anticipated future advances in diabetes technology currently under development. Expert Opinion: The ultimate goal of advanced diabetes technologies is to reduce the burden and amount of management required of patients with diabetes. In addition to reducing patient workload, achieving better glucose control and improving hemoglobin A1c (HbA1c) values are essential for reducing the threat of diabetes-related complications further down the road. Current devices come close to reaching these goals, but understanding the unmet needs of patients with diabetes will allow future technologies to achieve these goals more quickly.


Predisposing Factors to Lymphatic Filariasis among Residents in Igbo-Eze North: An Endemic Area in Nigeria.
The study on lymphatic filariasis (LF) in Igbo-Eze North was conducted to determine the prevalence and predisposing factors to LF among its residents between May and October 2018. A total of 201 residents who have lived in the area for at least one year were recruited. They were stratified according to age, gender and occupation, and were clinically examined firstly by rapid assessment method for any lymphoedema and hydrocele. At recruitment, blood samples were collected from all volunteered participants for LF test. In addition, demographic information and risk factors of the respondents were captured using a structured questionnaire by oral interview. The overall prevalence for LF was 84 (41.8%). Furthermore, LF prevalence was significant (P < 0.05) in all the studied communities: 61.5% in Umuogbuagu, 48.1% in Aguibege, 32.7% in Umuagama and 21.7% in Umuopu. The sex-related prevalence of LF was higher among females than males, with slight significant difference (P = 0.046). In relation to age and occupation, higher prevalences (P < 0.0001) were recorded among older (≥ 50 years) subjects (49, 61.2%) and traders (55, 57.9%) respectively. The risk associated with LF implicated lack of knowledge, non-use of mosquito nets, as well as visit and proximity to water bodies as major predispositions (P < 0.05). The prevalence of LF in this study was high. Higher prevalence was among females, older people and traders. Notable risks to the disease outcome are environmental, attitudinal and occupational with chances of scaled up prevalence and burden overtime.


Effect of oxygen tension and serum during IVM on developmental competence of bovine oocytes.
With an aim to improve the in vitro production of bovine embryos, the present study investigated the effect of serum and oxygen tension during IVM on oocyte developmental competence. Four experimental groups were evaluated: G1, 10% oestrus cow serum (OCS) with 20% O(2); G2, 0.1% polyvinyl alcohol (PVA) with 20% O(2); G3, 10% OCS with 5% O(2); and G4, 0.1% PVA with 5% O(2). The proportion of MII oocytes, blastocyst rates and total cell number were not affected (P > 0.05) when the OCS was replaced with PVA under 5% O(2), whereas a higher (P < 0.05) blastocyst rate and total cell number were found with OCS compared with PVA under 20% O(2). The apoptosis index was lower in blastocysts from oocytes matured with PVA under 5% O(2) (G4) compared with other groups (G1, G2 and G3), but no differences (P > 0.05) were found in maturation and blastocyst rates. Significant differences were found in the amount of specific transcripts in oocytes matured under different conditions. In conclusion maturation with PVA and 5% O(2) provides an efficient in vitro culture condition for the maturation of bovine oocytes.


Bronchogenic cyst presenting as dysphagia.
We report an adult patient who masqueraded as a case of gastroesophageal reflux disease for over 6 years. On close questioning he was found to have severe constricting pain in the retrosternal region and non progressive dysphagia for 6 years. Cineradiography of the oesophagus and CT scan chest revealed a large bronchogenic cyst compressing the oesophagus and the trachea. Excision of the cyst relieved the symptoms.


Microwave measurements and ab initio calculations of structural and electronic properties of N-Et-1,2-azaborine.
Rotational transitions for N-Et-1,2-azaborine were measured in the 5-13 GHz range using a Flygare-Balle type Fourier transform spectrometer system. Twelve distinct rotational transitions with over 130 resolved hyperfine components, which included a-dipole and b-dipole transitions, were measured and analyzed to obtain rotational constants and (11)B and (14)N nuclear quadrupole coupling constants in the principal rotational axis system. Rotational constants obtained are A=4477.987(4), B=1490.5083(7), and C=1230.6728(6) MHz. The quadrupole coupling constants for (11)B are eQq(aa)=-1.82(1), (eQq(bb)-eQq(cc))=-3.398(4) MHz, and for (14)N, eQq(aa)=1.25(1), (eQq(bb)-eQq(cc))=0.662(4) MHz. Quantum electronic structure calculations predict a ground-state structure with the ethyl group perpendicular to the azaborine plane and rotational constants in very good agreement with the measured structure and rotational constants. The theoretical conformational analysis of the ethyl group rotation around the N[Single Bond]C bond in relation to the heterocyclic ring yielded an asymmetric torsional potential energy surface with barrier heights of about 900 and 1350 cm(-1) for the N-Et-1,2-azaborine. Results of the measurements and calculations indicate that the basic molecular structure of N-Et-1,2-azaborine is similar to ethylbenzene. Electrostatic potential calculations qualitatively show that pi-electron density is somewhat delocalized around the 1,2-azaborine ring.


The synthesis of nano silver-graphene oxide system and its efficacy against endodontic biofilms using a novel tooth model.
The deleterious caustic effects of sodium hypochlorite (NaOCl) as a root canal irrigant makes it imperative that alternative methods are developed for root canal disinfection. The purpose of this study was to examine the antimicrobial efficacy of silver nanoparticles (AgNPs) synthesized on an aqueous graphene oxide (GO) matrix (Ag-GO), with different irrigant delivery methods to enhance the disinfection regimen, using a novel ex vivo infected tooth model. AgNPs were prepared by reducing AgNO3 with 0.01M NaBH4 in presence of GO. Elemental analysis was performed with scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS) and scanning transmission electron microscopy (STEM) was used for size and morphology analysis of GO and Ag-GO. Nutrient stressed, multi-species biofilms were grown in prepared root canals of single-rooted teeth. The irrigants used were sterile saline, 1% and 2.5% NaOCl, 2% chlorhexidine gluconate (CHX), 17% EDTA and an aqueous suspension of 0.25% Ag-GO. The antimicrobial efficacy of the irrigants were performed with paper point sampling and measurement of microbial counts. The biofilm disruption in dentine tubule surfaces was analysed with confocal laser scanning microscopy (CLSM). The acquisition of total biovolume (μm3/μm2) and biofilm viability was performed using software BioImage_L. Two-way analysis of variance (ANOVA) with post hoc Tukey tests was used for data analysis with level of statistical significance set at P<0.05. SEM/EDS analysis confirmed impregnation of Ag within the GO matrix. TEM images showed polygonal GO sheets and spherical AgNPs of diameter 20-50nm, forming a network on the surface of GO sheets. The use of ultrasonic activation enhanced the efficacy of Ag-GO compared to 1% NaOCl, 2% CHX, 17% EDTA and sterile saline (P<0.05). The microbial killing efficacy of 2.5% NaOCl was superior compared to the experimental groups. The maximum biofilm disruption, in dentine tubule surfaces, was achieved by 2.5% NaOCl, however Ag-GO caused a significant reduction of total biovolumes compared to the rest of the experimental groups (P<0.05%). The successful documentation of the microbial killing and biofilm disruption capacity of Ag-GO is a promising step forward to explore its unique properties in clinical applications and biomaterials in dentistry.


Applying public health screening criteria: how does universal newborn screening compare to universal tumor screening for Lynch syndrome in adults with colorectal cancer?
Institutions have increasingly begun to adopt universal tumor screening (UTS) programs whereby tumors from all newly diagnosed patients with colorectal cancer (CRC) are screened to identify who should be offered germline testing for Lynch syndrome (the most common cause of hereditary CRC). Given limited information about the impact of universal screening programs to detect hereditary disease in adults, we apply criteria used to evaluate public health screening programs and compare and contrast UTS with universal newborn screening (NBS) for the purpose of examining ethical implications and anticipating potential outcomes of UTS. Both UTS and a core set of NBS conditions clearly meet most of the Wilson and Jungner screening criteria. However, many state NBS panels include additional conditions that do not meet several of these criteria, and there is currently insufficient data to confirm that UTS meets some of these criteria. Comparing UTS and NBS with regard to newer screening criteria raises additional issues that require attention for both UTS and NBS. Comparisons also highlight the importance of evaluating the implementation of genomic tests to ensure or improve their effectiveness at reducing morbidity and mortality while minimizing potential harms.


Levels of resilience and delivery of HIV care in response to urban violence and crime.
To understand the impact of urban violence and crime on HIV care delivery. Urban violence and crime can put pressure on the healthcare system and on nursing staff. Whilst there is research about the impact this has at the individual level, there is less research that places this in the context of the overall social eco-system. A qualitative design using inductive thematic analysis. Between July 2016 - February 2017, we conducted in-depth interviews with 10 nurses working in two neighbourhoods with high levels of violence in Cape Town, South Africa. The effects of crime and violence were evident at multiple levels resulting in participants feeling "safe and unsafe" in a context where people view crime as endemic. Resilience emerged as a key concept in the findings. Resilience was apparent at individual, community, and organizational levels and enabled continued delivery of HIV care. The findings demonstrate the potential role of resilience in the social eco-health system required to sustain delivery of HIV care in the midst of urban violence and gangsterism. This study examined the impact of and response to urban violence on HIV care delivery. The findings indicate that resilience manifests at all levels of the social eco-system. Understanding the mechanisms employed to cope with endemic violence helps to address these challenges in the study setting, but also has a much wider application to other areas with endemic urban violence and crime.


Muscle strength capacities in elite football players after anterior cruciate ligament reconstruction.
The aim of this study was to explore the strength capacities of the injured and non-injured leg following a unilateral anterior cruciate ligament reconstruction. Eight elite soccer players (age = 25.5 ± 3.9 years; height = 1.83 ± 0.04 m; body mass = 78.9 ± 4.5 kg) volunteered to participate in this study. Nine months after the anterior cruciate ligament reconstruction and just before initiating the full training process, the maximal peak torque of the quadriceps and hamstring muscles were measured at 60 and 180 degrees/ second using isokinetic dynamometry. Obtained peak torques were used for calculating hamstring-to-quadriceps ratio, limb symmetry index, and to estimate maximal torque capacity using a two-velocity method (i.e., linear torque-velocity relationship modeled considering peak torque obtained at 60 and 180 degrees/second). No differences were found between hamstring-to- -quadriceps ratios of the injured and non-injured leg ( p = 0.165), nor between limb symmetry index of the quadriceps and hamstring muscles ( p = 0.985), regardless of the angular velocity applied during tests. The two-point method revealed significant differences between quadriceps and hamstring muscle groups both in the injured and non-injured leg ( p < 0.001; maximal estimated torque was higher for quadriceps compared to hamstring muscles), while the differences between same muscle groups of the different legs were not significant. Collectively, these findings indicate that 9 months were enough for reaching a certain strength level of the injured leg that permits a safe return to play.


Sinus node artery-preserving superior transseptal approach: a simple technique.
With the use of the superior transseptal approach during mitral valve surgery, good exposure of the mitral valve can be achieved with simple traction sutures, which minimize the risk of deformation of the mitral valve. For this reason, we routinely perform mitral valvoplasty using the superior transseptal approach; however, we, occasionally encounter cases that develop postoperative atrial dysrhythmia. We have therefore, devised a very simple technique for preservation of the sinus node artery in the superior transseptal approach, which is effective for reducing the incidence of postoperative sinus node dysfunction. In this technique, during incision of the dome of the left atrium, the sinus node artery is carefully dissected and preserved.


[When should the anti-glaucoma treatment start?].
The decision to start a glaucoma treatment in a newly diagnosed patient is easy when the disease is clearly identified with typical optic nerve cupping, visual field defect, and elevated intraocular pressure. However it often appears more complicated, especially in young patients for whom a careful analysis of the fundus and an examination of nerve fiber layers should be assessed to detect an early sign of glaucoma before any visual field change. If glaucoma is present, patients with intraocular pressure above 14 mmHg should be treated, as in such cases there is always a "pressure risk factor". In case of isolated elevated ocular pressure, in France it is usually considered that a pressure above 25 mmHg should be reduced, with a target pressure at least of--20% from baseline. Other factors should also be considered such as quality of life and cost of the treatment. The psychological profile of the patient should also be taken in to account and clear information concerning the risks and potential severity of the disease should be given before the onset of treatment.


Influence of early postnatal dexamethasone therapy on ventilator dependency in surfactant-substituted preterm infants.
We examined 26 preterm infants with respiratory distress syndrome in a randomized controlled prospective study to determine whether early postnatal dexamethasone therapy (< 2 h; 0.5 mg/kg per day) over 5 days in addition to substitution of surfactant (100 mg/kg) facilitates extubation and the course of RDS. Control (n = 12) and treated (n = 14) groups were comparable in birthweight (mean +/- SD: 1219 +/- 292 versus 1446 +/- 442 g), gestational age (29.3 +/- 2.2 versus 30.6 +/- 2.7 weeks), prenatal characteristics and initial respiratory and blood gas parameters. In both groups one infant died. Infants in the dexamethasone group responded better to surfactant (12/14 versus 3/12; p < 0.01), were extubated earlier (6.6 versus 14.2 days; p < 0.02) and required less time on supplemental oxygen (4.2 versus 12.5 days; p < 0.02). Pulmonary complications tended to be lower in the dexamethasone group (1/14 versus 4/12), as was the frequency of retinopathy (2/14 versus 6/12; p < 0.05). We conclude that early postnatal dexamethasone therapy improves response to surfactant therapy resulting in better weaning and earlier extubation in premature infants.


Pathophysiologic glucocorticoid levels and survival of translocating bacteria.
Burn wound sepsis in rats results in sustained corticosterone elevations and the prolonged presence of translocated bacteria in the mesenteric lymph nodes (MLNs). To determine if survival of bacteria in the MLNs may be influenced by pathophysiologic corticosterone levels, MLNs were quantitatively analyzed from rats randomized to the following groups: burn wound sepsis (BI); BI with adrenocortical response attenuated by cyclosporine (cyclosporine/BI); or cyclosporine/BI with corticosterone replacement (cyclosporine/BI + P). Although rates of bacterial translocation were similar, corticosterone levels were significantly different among the three groups and correlated with the number of lymphocytes and the number of enteric bacteria present per gram of MLN. Thus, pathophysiologic elevations of corticosterone levels during sepsis may exert an effect that allows survival of translocated bacteria in the MLNs of rats, perhaps due to glucocorticoid-associated alterations in regional immunity.


Domain III of the envelope protein as a dengue vaccine target.
A dengue vaccine should induce long-lasting, simultaneous protection to the four dengue viruses while avoiding the immune enhancement of viral infection. Domain III of the dengue envelope protein has been implicated in receptor binding, and is also the target of specific neutralizing antibodies. Domain III has emerged as a promising region for a subunit vaccine candidate. Here, we review the current state of knowledge on vaccine candidates based on domain III. Due to the results obtained concerning the immune response and protection in mice and monkeys, particular attention is paid to the chimeric protein domain III fused to p64k of Neisseria meningitidis.


AT(2) receptor-dependent vasodilation is mediated by activation of vascular kinin generation under flow conditions.
Physiological roles of angiotensin II type 2 receptor (AT(2)) are not well defined. This study was designed to investigate the mechanisms of AT(2)-dependent vascular relaxation by studying vasodilation in pressurized and perfused rat mesenteric arterial segments. Perfusion of angiotensin II in the presence of AT(1) antagonist elicited vascular relaxation, which was completely dependent on AT(2) receptors on endothelium. FR173657 (>1 microM), a bradykinin (BK) B(2)-specific antagonist, significantly suppressed AT(2)-dependent vasodilation (maximum inhibition: 68.5% at 10 microM). Kininogen-deficient Brown Norway Katholiek rats showed a significant reduction in AT(2)-mediated vasodilatory response compared with normal wild-type Brown Norway rats. Indomethacin (>1 microM), aprotinin (10 microM) and soybean trypsin inhibitor (10 microM) also reduced AT(2)-dependent vasodilation. Our results demonstrated that stimulation of AT(2) receptors caused a significant vasodilation through local production of BK in resistant arteries of rat mesentery in a flow-dependent manner. Such vasodilation counterbalances AT(1)-dependent vasoconstriction to regulate the vascular tone.


2,4-Dichloro-benzyl 2-meth-oxy-benzoate.
In the title compound, C15H12Cl2O3, the aromatic rings make a dihedral angle of 10.78 (4)°. In the molecule, there is a short C-H⋯O contact. In the crystal, C-H⋯O contacts connect the mol-ecules into C(7)C(8) chains along the b axis. The shortest inter-centroid distance between two benzoic acid aromatic systems is 3.7416 (8) Å.


Efficacy and side effects of salbutamol in acute asthma in children: comparison of oral route and two different nebulizer systems.
Thirty-five separate episodes of acute bronchial asthma were studied in 21 asthmatic children. The bronchodilator, cardiovascular, and tremorogenic responses following three modes of administration of salbutamol were compared: open continuous nebulization (ON), closed-port intermittent nebulization (CN), and oral route (OR), for a period of 8 hours. Eleven acute attacks were treated by ON, 11 by CN, and 13 by OR. Pulmonary function was evaluated by clinical assessment and by the spirometric indices FEV1 and FEF25-75. Tremor was objectively measured, as well as heart rate (HR), respiratory rate (RR), and blood pressure (BP). Fastest onset of bronchodilator action, maximal response, and longest duration were seen when the drug was administered by the CN. Onset of tremorogenic effect was registered at 5 minutes when salbutamol was used by CN and ON and at 30 minutes when used by OR. During the first 30 minutes, tremor was significantly greater when salbutamol was used by CN than by OR. There were minor cardiovascular effects, except regarding HR after CN, which was significantly greater than after OR, at 5 and 30 minutes. Our findings indicate the inhaled route as the most effective route for administration of salbutamol to treat acute bronchospasm in children. The use of CN is a good alternative to jet nebulizers, but the greater dose of drug effectively administered by this system can briefly cause more tremor and heart acceleration.


Quality of life and long-term clinical outcome following robot-assisted radical trachelectomy.
Quality of Life and long-term clinical outcome following robot-assisted radical trachelectomy. To evaluate quality of life (QoL) and long-term clinical outcome following robot-assisted radical trachelectomy (RRT). Prospectively retrieved clinical data were rereviewed on all women planned for a fertility sparing RRT for early stage cervical cancer at Skåne University Hospital, Sweden between 2007 and 2020. QoL was assessed using the validated questionnaires EORTC QLQ-C30, QLQ-CX24 and the Swedish LYMQOL. Data was analyzed from 49 women, 42 with a finalised RRT and seven with an aborted RRT due to nodal metastases (n = 3) or insufficient margins (n = 4). At a median follow-up time of 54 months one recurrence (2%) occurred (aborted RRT). According to QLQ-C30 the median global health status score was 75. The disease specific QLQ-C24 showed an impact on symptoms related to sexual function where sexual/vaginal functioning had a median score of 25 and 48% of patients reported worry that sex would cause physical pain. Despite this the functional items sexual activity and sexual enjoyment both had a median score of 66.7. Lymphoedema was reported in 45%, where 9% reported severe symptom with an impact on their QoL. No intraoperative complications and no postoperative complications ≥ Clavien Dindo grade III were observed. Twenty-two of 28 (79%) women who attempted to conceive were successful. A metronidazole/no intercourse regimen was applied between GW 15 + 0-21 + 6 in 26 of 28 pregnancies beyond first trimester resulting in a 92% term (≥GW 36 + 0) delivery rate. Although robot-assisted radical trachelectomy in this cohort was associated with a low recurrence rate, a high fertility rate and an exceptionally high term delivery rate, women's quality of life was affected postoperatively, particularly with regards to their sexual well-being and lymphatic side-effects.


Understanding catalysis.
The large majority of chemical compounds underwent at least one catalytic step during synthesis. While it is common knowledge that catalysts enhance reaction rates by lowering the activation energy it is often obscure how catalysts achieve this. This tutorial review explains some fundamental principles of catalysis and how the mechanisms are studied. The dissociation of formic acid into H2 and CO2 serves to demonstrate how a water molecule can open a new reaction path at lower energy, how immersion in liquid water can influence the charge distribution and energetics, and how catalysis at metal surfaces differs from that in the gas phase. The reversibility of catalytic reactions, the influence of an adsorption pre-equilibrium and the compensating effects of adsorption entropy and enthalpy on the Arrhenius parameters are discussed. It is shown that flexibility around the catalytic centre and residual substrate dynamics on the surface affect these parameters. Sabatier's principle of optimum substrate adsorption, shape selectivity in the pores of molecular sieves and the polarisation effect at the metal-support interface are explained. Finally, it is shown that the application of a bias voltage in electrochemistry offers an additional parameter to promote or inhibit a reaction.


Accumulation and release of triglycerides by rat liver following partial hepatectomy.
Regenerating liver accumulates lipid for about 20 hr following partial hepatectomy. During this time incorporation of intravenously administered palmitate-9, 10-(3)H into beta-lipoprotein increased. 13 hr after partial hepatectomy, there was no change in the level of serum beta-lipoproteins, but the specific activities of the triglycerides in the liver and beta-lipoproteins were significantly diminished. Extension of these studies to the isolated perfused liver system demonstrated that 13 hr after partial hepatectomy the regenerating liver is capable of secreting greater quantities of the lipid, but not the protein, moiety of the beta-lipoproteins in comparison with liver taken immediately from a partially hepatectomized animal, although there was no difference between the weights of the livers. However following addition of palmitate-(3)H and (14)C-labeled amino acids to the perfusate, the specific activity of the hepatic and beta-lipoprotein triglycerides of the liver excised 13 hr after partial hepatectomy was diminished, but that of the protein was not affected. Prelabeling of the accumulated triglyceride with palmitate-1-(14)C in vivo revealed that the proportions of the accumulated triglyceride secreted as beta-lipoproteins by perfused livers excised immediately and 13 hr after partial hepatectomy were identical. It is concluded that regenerating liver rapidly acquires the ability to mobilize triglycerides at a rate equal to that of the much larger normal liver, so that it can handle all free fatty acids presented to it.


First Report of Seedling Rot of Castor (Ricinus communis) caused by Choanephora cucurbitarum in China.
Castor (Ricinus communis L.) oil is used in the manufacture of cosmetics, lubricants, plastics, pharmaceuticals, and soaps and is grown in more than 40 countries with India and China leading in oil production(Tunaru et al. 2012). In June 2021, a seedling rot disease was observed on castor cv. Zibi-5 in a plant nursery in Zhanjiang (21°17' N, 110°18' E), China. Initial symptoms on leaves and stems were water-soaked and dark green lesions that resulted in rapid rotting. Disease incidence was 25% and resulted in seedling death. White fungal mycelia developed on the rotting plant tissues. Leaves and stems were collected from 10 diseased plants, surface disinfected in 0.5% sodium hypochlorite and 75% ethyl alcohol, and tissue pieces placed in plates of potato dextrose agar (PDA) which were maintained at 28℃. Hyphal tips from fungal mycelia that developed in the PDA plates were selected to establish pure cultures and three representative fungal isolates, designated RCC-1, RCC-2, and RCC-3, were selected for further study. The fungal isolates produced sporangiophores that were smooth, hyaline, aseptate, and apically swollen. Sporangiophores bore monosporous sporangiola that were broadly ellipsoidal, longitudinally coarsely striate, brown to dark brown, and measured 6.2 to 14.8 x 10.5 to 26.5 um (n=30). Sporangia contained few to many spores that were spherical, brown, and measured 59 to 150 um in diameter (n=20). Sporangiospores were ellipsoid, striate, and brown with multiple hyaline polar appendages and measured 6.6 to 12.3 x 10.6 to 25.5 um (n=30) in size. Based on these morphological characteristics, the fungus was identified as Choanephora cucurbitarum (Berk. & Ravenel) Thaxt. (Kirk, 1984). Molecular identification was done using the colony PCR method with MightyAmp DNA Polymerase (Takara-Bio, Dalian, China) (Lu et al. 2012) used to amplify the internal transcribed spacer (ITS) region and large subunit (LSU) with ITS1/ITS4 and NL1/LR3 (Walther et al. 2013). The amplicons were sequenced and the sequences were deposited in GenBank with accession numbers ITS, OL376748-OL376750, and LSU, OL763430-OL763432. BLAST analysis of these sequences revealed a 100% to 99% identity with the sequences (ITS, MG650194; 573/573, 573/573, and 573/573; LSU, AF157181; 673/676, 673/676, and 673/676) of C. cucurbitarum in GenBank. Pathogenicity tests, to fulfill Koch's postulates, were performed in a greenhouse with a temperature range of 24℃ to 30℃ and 80% relative humidity. Thirty-day-old cv. Zibi-5 castor plants were grown in pots and used for inoculation tests. Ten plants were inoculated by placing agar plugs with mycelia of fungal isolate RCC-1 on leaves or stems. Ten control plants were inoculated with agar plugs only and the test was repeated three times in total. Five days after inoculation, all plants, with either leaf or stem inoculations, became infected and began rotting. Symptom progression was consistent with that observed in the nursery and all control plants remained healthy. C. cucurbitarum was successfully reisolated from all inoculated plants and identified by morphological characteristics and by sequence analysis. This fungus is known to cause serious damage on a wide range of hosts (Liu et al. 2019) and previously was reported on castor in India (Shaw 1984) and Papua New Guinea (Peregrin and Ahmad 1982). We observed that the pathogen grows very rapidly and causes serious damage to castor seedlings, warranting further investigation on the epidemiology and control of this disease.


Cytotoxic and Anti-Inflammatory Sesquiterpenes from the Whole Plants of Centipeda minima.
Sixteen new sesquiterpene lactones (1-16) along with 13 known analogues (17-29) were isolated from the whole plants of Centipeda minima. The structures of 1-16 were delineated by the combination of NMR spectroscopic experiments, HRESIMS, single-crystal X-ray diffraction analyses, and ECD spectra. Compounds 23-26 showed potent cytotoxicity against Hela, HCT-116, and HepG2 cells with IC50 values of 0.8-2.6, 0.4-3.3, and 1.1-2.6 μM, respectively. Compounds 8, 15, and 24 exhibited significant inhibitory activity on the production of nitric oxide in the lipopolysaccharide-activated RAW 264.7 mouse macrophage cell line, with IC50 values ranging from 0.1 to 0.2 μM.


Ultrasensitive Detection of COVID-19 Causative Virus (SARS-CoV-2) Spike Protein Using Laser Induced Graphene Field-Effect Transistor.
COVID-19 is a highly contagious human infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the war with the virus is still underway. Since no specific drugs have been made available yet and there is an imbalance between supply and demand for vaccines, early diagnosis and isolation are essential to control the outbreak. Current nucleic acid testing methods require high sample quality and laboratory conditions, which cannot meet flexible applications. Here, we report a laser-induced graphene field-effect transistor (LIG-FET) for detecting SARS-CoV-2. The FET was manufactured by different reduction degree LIG, with an oyster reef-like porous graphene channel to enrich the binding point between the virus protein and sensing area. After immobilizing specific antibodies in the channel, the FET can detect the SARS-CoV-2 spike protein in 15 min at a concentration of 1 pg/mL in phosphate-buffered saline (PBS) and 1 ng/mL in human serum. In addition, the sensor shows great specificity to the spike protein of SARS-CoV-2. Our sensors can realize fast production for COVID-19 rapid testing, as each LIG-FET can be fabricated by a laser platform in seconds. It is the first time that LIG has realized a virus sensing FET without any sample pretreatment or labeling, which paves the way for low-cost and rapid detection of COVID-19.


The Timing Hypothesis: Hormone Therapy for Treating Symptomatic Women During Menopause and Its Relationship to Cardiovascular Disease.
The risks and benefits of menopausal hormonal therapy (HT) have been evaluated extensively over the past three decades. While the efficacy of HT for management of menopausal symptoms, including vasomotor symptoms and vaginal dryness is well established, its relationship to cardiovascular outcomes is complex. The timing hypothesis, which posits that the cardiovascular effects of HT depend on the timing of initiation of HT in relation to menopause, has helped shape our understanding of the cardiovascular outcomes related to HT. Based on results from female monkey studies, the timing hypothesis provides a framework to explain discrepancies in results between multiple observation studies and the Women's Health Initiative (WHI) hormone therapy trials. The WHI trials closed early in 2002 in part because of increased cardiovascular events seen in women on treatment. Subanalysis of the WHI results by age group, and more recent randomized control studies, including the Kronos Early Estrogen and Prevention Study (KEEPS) and Early Versus Late Intervention Trial (ELITE), demonstrate that the risk of adverse cardiovascular events for HT are low for women <60 years of age or within 10 year from menopause. Although current data does not support using HT for primary prevention of cardiovascular disease, it does suggest that HT can be safely used to treat symptoms in appropriately selected women close to menopause.


Effects of nimodipine on posttraumatic spinal cord ischemia in baboons.
Posttraumatic ischemia appears to be largely responsible for the extension of lesions in acute injury of the spinal cord. In the present study, we have evaluated the putative improvement of axonal function by the calcium channel blocker nimodipine after acute trauma of the spinal cord. Three techniques were used: (1) spinal cord blood flow (SCBF) using a scanographic technique with stable xenon, (2) somatosensory evoked potentials (SEPs), and (3) magnetic resonance imaging (MRI). Thirteen baboons were used in this study. Acute trauma was achieved by compression of the spinal cord at level L1 by applying pressure for 5 sec with an inflated balloon catheter injected with Ringer's solution. Following the injury, one group (n = 5) received a saline infusion (placebo) for seven days, and a second group (n = 8) received a nimodipine infusion (0.04 mg/kg/h) during the same period of time. SCBF and SEP were first recorded prior to trauma. SCBF, SEPs, and MRI were then recorded on the day of the injury and eight days prior to histologic examination of the spinal cord. In these studies nimodipine significantly improved SCBF. The decrease in SCBF observed at day one and day eight following trauma was significantly reduced in the treated group. Two baboons in the treated group also showed improvement of axonal function as assessed by SEP. No significant difference was observed with MRI, however, histologic study revealed that the lesions were significantly smaller in the treated group. Based on these observations we conclude that a week of nimodipine treatment following spinal cord injury enhances SCBF, limits the size of the spinal cord lesion, and perhaps improves functional recovery.


Gene therapy of the hemophilias.
Development of hemophilia gene therapy depends on testing gene transfer vectors in hemophilic and nonhemophilic animals. Available animal models include factor VIII or factor IX knockout mice as well as dogs with spontaneous hemophilia A or B. Large animals (particularly dogs) more closely replicate the requirements for correction of human hemophilia than do mice. Small animals are more convenient to maintain and require significantly less vector for testing than do large animals. Nonhemophilic animals (mice or nonhuman primates), whose endogenous factor VIII and factor IX complicate analysis of the human proteins, have utility for safety testing of vectors; some assays can discriminate between human coagulation factors and the endogenous coagulation factors. Most animal models suffer the limitations imposed by the immune response to human factor VIII or IX protein. Clinical trials have failed to achieve significant factor VIII expression in hemophilia A patients, while one clinical trial in hemophilia B patients showed only transient therapeutic increments of factor IX expression. Gene therapy remains an investigational method with many obstacles to overcome before it can be widely used as treatment for hemophilia.


Abnormal route to aging transition in a network of coupled oscillators.
In this article, we investigate the dynamical robustness in a network of Van der Pol oscillators. In particular, we consider a network of diffusively coupled Van der Pol oscillators to explore the aging transition phenomena. Our investigation reveals that the route to aging transition in a network of Van der Pol oscillator is different from that of typical sinusoidal oscillators such as Stuart-Landau oscillators. Unlike sinusoidal oscillators, the order parameter does not follow smooth second-order phase transition. Rather, we observe an abnormal phase transition of the order parameter due to the sudden appearance of unbounded trajectories at a critical point. We provide detailed bifurcation analysis of such an abnormal phase transition. We show that the boundary crisis of a limit-cycle oscillator is at the helm of such an unusual discontinuous path of aging transition.


Collective Intelligence: Aggregation of Information from Neighbors in a Guessing Game.
Complex systems show the capacity to aggregate information and to display coordinated activity. In the case of social systems the interaction of different individuals leads to the emergence of norms, trends in political positions, opinions, cultural traits, and even scientific progress. Examples of collective behavior can be observed in activities like the Wikipedia and Linux, where individuals aggregate their knowledge for the benefit of the community, and citizen science, where the potential of collectives to solve complex problems is exploited. Here, we conducted an online experiment to investigate the performance of a collective when solving a guessing problem in which each actor is endowed with partial information and placed as the nodes of an interaction network. We measure the performance of the collective in terms of the temporal evolution of the accuracy, finding no statistical difference in the performance for two classes of networks, regular lattices and random networks. We also determine that a Bayesian description captures the behavior pattern the individuals follow in aggregating information from neighbors to make decisions. In comparison with other simple decision models, the strategy followed by the players reveals a suboptimal performance of the collective. Our contribution provides the basis for the micro-macro connection between individual based descriptions and collective phenomena.


Validation study of the Victorian Birth Defects Register.
To determine whether there has been an improvement in ascertainment of birth defects cases ('case validity') by the Victorian Birth Defects Register (BDR) since an earlier study (conducted in 1993), to ascertain the accuracy of registered data ('item validity') and to investigate another possible source of notification. The medical records were reviewed of 500 children born after 1 January 1993 who were consecutively admitted after 1 January 1999 to two paediatric teaching hospitals in Victoria. In addition, records of 200 children referred to a clinical genetics service were reviewed for children born after 1 January 1993 and who were seen in two periods: 2 months after 1 January 2001 and 2 months after 1 January 2002. The records from the hospitals and clinical genetics service were reviewed separately to determine whether children recorded as having a birth defect had previously been notified to the BDR. Twenty percent of the hospital records related to a child with a birth defect, as did 70% of the clinical genetics service records. Overall case validity for birth defect cases from the hospitals was 88%. There was 100% ascertainment for three of five categories. Sixty per cent of birth defects cases from the clinical genetics service had been notified to the BDR. When all diagnoses in matched cases were considered, item validity was 54%, however, if only primary diagnoses were included then 92% of cases had the same diagnosis. Overall case validity from the two paediatric teaching hospitals has significantly improved since our previous study. The addition of an extra data source from a clinical genetics service would identify new cases, particularly genetic disorders and developmental delay, as well as adding new diagnoses to existing ones. This study has highlighted the need to improve item validity, perhaps through routine education for all coders and notifiers on the inclusion and exclusion of specific associated conditions when notifying major birth defects.


The effect of "group detailing" on drug prescribing in primary care.
The quality of physician prescribing is suboptimal. Patients are at risk of potentially adverse reaction because of inappropriate or writing error in the drug prescriptions. We assess the effect of "group academic detailing" to reduce writing drug name using brand name and short form in the drug prescriptions in a controlled study at two primary health care clinics in Negeri Sembilan. Five medical officers in Ampangan Health Clinic received an educational intervention consisting of group academic detailing from the resident Family Medicine Specialist, as well as a drug summary list using generic names. The academic detailing focused on appropriate prescribing habit and emphasized on using the full generic drug name when writing the drug prescription. Analyses were based on 3371 prescriptions that were taken from two clinics. The other health clinic was for comparison. The prescribing rates were assessed by reviewing the prescriptions (two months each for pre- and post-intervention phase). Statistically significant reduction in writing prescription using brand name and using short form were observed after the educational intervention. Writing prescription using brand name for pre- and postintervention phase were 33.9% and 19.0% (postintervention vs pre-intervention RR 0.56, 95% CI 0.48 to 0.66) in the intervention clinic. Prescription writing using any short form for pre- and post-intervention phase were 49.2% and 29.2% (post-intervention vs pre-intervention RR 0.59, 95% CI 0.53 to 0.67). This low cost educational intervention focusing on prescribing habit produced an important reduction in writing prescription using brand name and short form. Group detailing appears to be feasible in the public health care system in Malaysia and possibly can be used for other prescribing issues in primary care.


Brain tissue oxygenation during hemorrhagic shock, resuscitation, and alterations in ventilation.
Recently developed polarographic microelectrodes permit continuous, reliable monitoring of oxygen tension in brain tissue (PbrO2). The aim of this study was to investigate the feasibility and utility of directly monitoring PbrO2 in cerebral tissue during changes in oxygenation or ventilation and during hemorrhagic shock and resuscitation. We also sought to develop a model in which treatment protocols could be evaluated using PbrO2 as an end point. Licox Clark-type polarographic probes were inserted in the brain tissue of 16 swine to monitor PbrO2. In eight swine, changes in PbrO2 were observed over a range of fractional concentrations of inspired O2 (FiO2) as well as during periods of hyperventilation and hypoventilation. In eight other swine, PbrO2 was monitored during a graded hemorrhage of up to 70% estimated blood volume and during the resuscitation period. When FiO2 was elevated to 100%, PbrO2 increased from a baseline of 15+/-2 mm Hg to 36+/-11 mm Hg. Hyperventilation while breathing 100% oxygen resulted in a 40% decrease in PbrO2 (p < 0.05), whereas hypoventilation increased PbrO2 to 88 mm Hg (p < 0.01). A graded hemorrhage to 50% estimated blood volume significantly reduced PbrO2, mean arterial pressure, and intracranial pressure (p < 0.01). Continued hemorrhage to 70% estimated blood volume resulted in a PbrO2 of 2.9+/-1.5 mm Hg. After resuscitation, PbrO2 was significantly elevated, reaching 65+/-13 mm Hg (p < 0.01), whereas mean arterial pressure and cerebral perfusion pressure simply returned to baseline. Directly measured PbrO2 was highly responsive to changes in FiO2, ventilatory rate, and blood volume in this experimental model. In particular, hypoventilation significantly increased PbrO2, whereas hyperventilation had the opposite effect. The postresuscitation increase in PbrO2 may reflect changes in both O2 delivery and O2 metabolism. These experiments set the stage for future investigations of a variety of resuscitation protocols in both normal and injured brain.


UDP-glucuronic acid:anthocyanin glucuronosyltransferase from red daisy (Bellis perennis) flowers. Enzymology and phylogenetics of a novel glucuronosyltransferase involved in flower pigment biosynthesis.
In contrast to the wealth of biochemical and genetic information on vertebrate glucuronosyltransferases (UGATs), only limited information is available on the role and phylogenetics of plant UGATs. Here we report on the purification, characterization, and cDNA cloning of a novel UGAT involved in the biosynthesis of flower pigments in the red daisy (Bellis perennis). The purified enzyme, BpUGAT, was a soluble monomeric enzyme with a molecular mass of 54 kDa and catalyzed the regiospecific transfer of a glucuronosyl unit from UDP-glucuronate to the 2''-hydroxyl group of the 3-glucosyl moiety of cyanidin 3-O-6''-O-malonylglucoside with a kcat value of 34 s(-1) at pH 7.0 and 30 degrees C. BpUGAT was highlyspecific for cyanidin 3-O-glucosides (e.g. Km for cyanidin 3-O-6''-O-malonylglucoside, 19 microM) and UDP-glucuronate (Km, 476 microM). The BpUGAT cDNA was isolated on the basis of the amino acid sequence of the purified enzyme. Quantitative PCR analysis showed that transcripts of BpUGAT could be specifically detected in red petals, consistent with the temporal and spatial distributions of enzyme activity in the plant and also consistent with the role of the enzyme in pigment biosynthesis. A sequence analysis revealed that BpUGAT is related to the glycosyltransferase 1 (GT1) family of the glycosyltransferase superfamily (according to the Carbohydrate-Active Enzymes (CAZy) data base). Among GT1 family members that encompass vertebrate UGATs and plant secondary product glycosyltransferases, the highest sequence similarity was found with flavonoid rhamnosyltransferases of plants (28-40% identity). Although the biological role (pigment biosynthesis) and enzymatic properties of BpUGAT are significantly different from those of vertebrate UGATs, both of these UGATs share a similarity in that the products produced by these enzymes are more water-soluble, thus facilitating their accumulation in vacuoles (in BpUGAT) or their excretion from cells (in vertebrate UGATs), corroborating the proposed general significance of GT1 family members in the metabolism of small lipophilic molecules.


Interventional MR-guided neuroendoscopy: A new therapeutic option for children.
Neuroendoscopic treatment of hydrocephalic children is an established surgical modality. Open magnetic resonance imaging (MRI) technology introduces new imaging features that, in combination with endoscopy, seem particularly valuable for performing these operations. "Near" real-time production of MR images in 3 dimensions during the procedure allows real-time neuronavigation, thus, facilitating guidance of an endoscope. Additionally, intraoperative changes such as brain shift, effects of perforation, and drainage of cysts are shown during an ongoing procedure. The patency of cysts or fluid compartments inside the ventricular system can be controlled by intraoperative injection of diluted gadolinium into the cystic compartments. These new therapeutic options were applied in 2 hydrocephalic children with complex ventricular cysts: a 3-month-old girl with a large, septated arachnoidal cyst and internal hydrocephalus and a boy of 7 years, 2 months with congenital hydrocephalus and premature closure of the coronary sutures.


Association between prevalence of laboratory-identified Clostridioides difficile infection (CDI) and antibiotic treatment for CDI in US acute-care hospitals, 2019.
To evaluate hospital-level variation in using first-line antibiotics for Clostridioides difficile infection (CDI) based on the burden of laboratory-identified (LabID) CDI. Using data on hospital-level LabID CDI events and antimicrobial use (AU) for CDI (oral/rectal vancomycin or fidaxomicin) submitted to the National Healthcare Safety Network in 2019, we assessed the association between hospital-level CDI prevalence (per 100 patient admissions) and rate of CDI AU (days of therapy per 1,000 days present) to generate a predicted value of AU based on CDI prevalence and CDI test type using negative binomial regression. The ratio of the observed to predicted AU was then used to identify hospitals with extreme discordance between CDI prevalence and CDI AU, defined as hospitals with a ratio outside of the intervigintile range. Among 963 acute-care hospitals, rate of CDI prevalence demonstrated a positive dose-response relationship with rate of CDI AU. Compared with hospitals without extreme discordance (n = 902), hospitals with lower-than-expected CDI AU (n = 31) had, on average, fewer beds (median, 106 vs 208), shorter length of stay (median, 3.8 vs 4.2 days), and higher proportion of undergraduate or nonteaching medical school affiliation (48% vs 39%). Hospitals with higher-than-expected CDI AU (n = 30) were similar overall to hospitals without extreme discordance. The prevalence rate of LabID CDI had a significant dose-response association with first-line antibiotics for treating CDI. We identified hospitals with extreme discordance between CDI prevalence and CDI AU, highlighting potential opportunities for data validation and improvements in diagnostic and treatment practices for CDI.


Preclinical studies and potential clinical applications of c-mpl ligand.
The cloning of the gene for the endogenous c-mpl ligand, also known as thrombopoietin, was first reported less than 2 years ago. Recombinant mpl ligands based on this gene have been extensively evaluated in preclinical studies and are now in the early stages of clinical development. In vivo studies have confirmed that c-mpl ligand is a lineage-dominant cytokine and is the primary physiologic regulator of megakaryocytopoiesis. Recombinant mpl ligands can substantially reduce the severity and duration of thrombocytopenia due to myelosuppressive irradiation, chemotherapy, or both. Moreover, when recombinant mpl ligand is used in combination with r-metHuG-CSF, both thrombocytopenia and neutropenia can be prevented to the same degree as with either cytokine alone. In normal animals, the platelets produced in response to recombinant mpl ligand function appropriately and should not pose an undue risk for thrombosis when administered to thrombocytopenic patients. Initial clinical data confirm the safety and biologic activity of these new agents in humans. Clinical development will likely target the most myelosuppressive regimens, including those used in hematopoietic cell transplantation and acute myelocytic leukemia. Ultimately, the clinical benefit of these drugs will likely be judged on their ability to reduce the duration of severe thrombocytopenia and the need for platelet transfusions.


Egyptian propolis: 3. Antioxidant, antimicrobial activities and chemical composition of propolis from reclaimed lands.
The free radical scavenging effect of two propolis samples collected from reclaimed land, Egypt as well as of vitamin C and caffeic acid in 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical system was determined. The antimicrobial (Staphylococcus aureus; Escherichia coli and Candida albicans) activity was also investigated. The results of the free radical scavenging effect of El-Saff and Ismailia propolis showed a concentration-dependent activity. The antioxidant activity was varied according to the examined material. It was obvious that caffeic acid and vitamin C showed the highest activity if compared with the propolis samples. El- Saff propolis had a higher antioxidant activity than Ismailia propolis, it showed a higher antibacterial activity against Staphylococcus aureus and a higher anti-fungal activity against Candida albicans. While the Ismailia propolis had a higher antibacterial activity against Escherichia coli, than El-Saff propolis. The chemical composition of propolis samples was investigated by GC/MS, where 75 compounds were identified, 22 being new for propolis. The Ismailia propolis was characterized by the presence of a highly significant amount of aromatic acid esters (47.3%) and triterpenoids (17.3%), while El-Saff propolis contained 3% and 1.9% respectively. The new esters belonged to 4-methoxyhydrocinnamic acid, hydroferulic acid and ferulic acid. El-Saff propolis had a very high significant amount (27%) of 2,6-bis-(pentanyloxy)-4-pentanylphenethanol, which is also a new compound for propolis.


Characterization of Vibrio cholerae O1 El Tor biotype variant clinical isolates from Bangladesh and Haiti, including a molecular genetic analysis of virulence genes.
Vibrio cholerae serogroup O1, the causative agent of the diarrheal disease cholera, is divided into two biotypes: classical and El Tor. Both biotypes produce the major virulence factors toxin-coregulated pilus (TCP) and cholera toxin (CT). Although possessing genotypic and phenotypic differences, El Tor biotype strains displaying classical biotype traits have been reported and subsequently were dubbed El Tor variants. Of particular interest are reports of El Tor variants that produce various levels of CT, including levels typical of classical biotype strains. Here, we report the characterization of 10 clinical isolates from the International Centre for Diarrhoeal Disease Research, Bangladesh, and a representative strain from the 2010 Haiti cholera outbreak. We observed that all 11 strains produced increased CT (2- to 10-fold) compared to that of wild-type El Tor strains under in vitro inducing conditions, but they possessed various TcpA and ToxT expression profiles. Particularly, El Tor variant MQ1795, which produced the highest level of CT and very high levels of TcpA and ToxT, demonstrated hypervirulence compared to the virulence of El Tor wild-type strains in the infant mouse cholera model. Additional genotypic and phenotypic tests were conducted to characterize the variants, including an assessment of biotype-distinguishing characteristics. Notably, the sequencing of ctxB in some El Tor variants revealed two copies of classical ctxB, one per chromosome, contrary to previous reports that located ctxAB only on the large chromosome of El Tor biotype strains.


[DNase I sensitivity of nucleus and chromatin in six different tissues of old rates].
In order to investigate the mechanism of aging, we studied the DNase I sensitivity of nucleus and chromatin in six different tissue (heart, liver, spleen, lung, kidney and brain of old and weanling wistar rats. The results showed that the DNase I digestive sensitivity levels of nucleus and chromatin in the tissue of the old rats were lower than those of the weanling rats respectively that in the old rats, the DNase I digestive sensitively in the tissue varied, the lowest sensitivity was in brain (P < 0.01); and that in the weanling rats, lowest DNase I digestive sensitivity of nucleus and chromatin was also in the brain, but the difference was not significant.


Phytogenic Fabrication of Ag-Fe Bimetallic Nanoparticles for Cell Cycle Arrest and Apoptosis Signaling Pathways in Candida auris by Generating Oxidative Stress.
Novel green synthetic nanomedicines have been recognized as alternative therapies with the potential to be antifungal agents. Apoptosis induction, cell cycle arrest and activation of the antioxidant defense system in fungal cells have also gained attention as emerging drug targets. In this study, a facile and biodegradable synthetic route was developed to prepare Ag-Fe bimetallic nanoparticles using aqueous extract of Beta vulgaris L. Surface plasmon resonance of Beta vulgaris-assisted AgNPs nanoparticles was not observed in the UV-visible region of Ag-Fe bimetallic NPs, which confirms the formation of Ag-Fe nanoparticles. Beta vulgaris-assisted Ag-Fe NPs were characterized by FTIR spectroscopy, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction and TGA-DTG analysis for their structural and morphological properties. The as-prepared Ag-Fe NPs were well dispersed and spherical with the average particle size of 15 nm. The antifungal activity of these Ag-Fe NPs against clinical isolates of Candida auris was determined by broth microdilution and cell viability assays. For insights into mechanisms, induction of apoptosis and triggering cell cycle arrest were studied following standard protocols. Furthermore, analysis of antioxidant defense enzymes was determined spectrophotometrically. Antifungal susceptibility results revealed high antifungal activity with MIC values ranging from 0.19 to 0.39 µg/mL. Further studies showed that Ag-Fe NPs were able to induce apoptosis, cell cycle arrest in G2/M phase and disturbances in primary and secondary antioxidant enzymes. This study presents the potential of Ag-Fe NPs to inhibit and potentially eradicate C. auris by inducing apoptosis, cell cycle arrest and increased levels of oxidative stress.


[Regulatory effect of small nuclear ribonucleoprotein-associated protein B on proliferation and metastasis of liver cancer cells].
Objective: To study the expression and effect of small nuclear ribonucleoprotein-associated protein B (SNRPB) on proliferation and metastasis of liver cancer tissues and cells. Methods: The bioinformatics database starBase v3.0 and GEPIA were used to analyze the expression of SNRPB in liver cancer tissue and normal liver tissue, as well as the survival and prognosis of liver cancer patients. The expression of SNRPB mRNA and protein in liver cancer cell lines were analyzed by qRT-PCR and Western blot. RNA interference technique (siRNA) was used to determine SNRPB protein expression down-regulation. The proliferation effect on hepatocellular carcinoma cells was observed by MTT assay. Transwell invasion and migration assay was used to detect the changes in the metastatic ability of liver cancer cells after SNRPB down-regulation. Western blot was used to detect the changes of epithelial mesenchymal transition (EMT) markers in liver cancer cells after down-regulation of SNRPB expression. Data were compared between two groups and multiple groups using t-test and analysis of variance. Results: The expression of SNRPB was significantly higher in liver cancer tissue than normal liver tissue, and its expression level was correlated with the prognosis of liver cancer patients. Compared with the immortalized hepatocyte LO(2), the expression of SNRPB was significantly increased in the liver cancer cells (P < 0.01). siRNA-SNRPB had significantly inhibited the expression of SNRPB mRNA and protein in liver cancer cells. MTT results showed that the absorbance value was lower in SNRPB knockdown group than negative control group, and the difference at 96 h after transfection was most significant (P < 0.01). Transwell assay results showed that compared with the negative control group, the SNRPB knockdown group (MHCC-97H: 121.27 ± 8.12 vs. 46.38 ± 7.54; Huh7: 126.50 ± 6.98 vs. 41.10 ± 8.01) invasion and migration (MHCC-97H: 125.20 ± 4.77 vs. 43.18 ± 7.32; Huh7: 132.22 ± 8.21 vs. 38.00 ± 6.78) ability was significantly reduced (P < 0.01) in liver cancer cells. Western blot showed that the expression level of epithelial phenotype marker E-cadherin was decreased after down-regulation of SNRPB, while the expression levels of mesenchymal phenotype markers N-cadherin and vimentin was increased, suggesting that down-regulation of SNRPB inhibited EMT in liver cancer cells. Conclusion: SNRPB expression is significantly increased in liver cancer tissues and cells, and it is involved in regulating the proliferation, metastasis and EMT of liver cancer cells.


"Their Sleep Means More Harmony": Maternal Perspectives and Experiences of Preschoolers' Sleep in Ethnically and Socioeconomically Diverse Families in Aotearoa/New Zealand.
Viewing sleep through a socioecological lens, maternal perceptions, and experiences of preschoolers' sleep were explored using semistructured interviews with 15 Māori (indigenous) and 16 non-Māori mothers, with low- and high socioeconomic position. Thematic analysis identified four themes: child happiness and health, maternal well-being, comfort and connection, and family functioning and harmony. Mothers perceived healthy preschooler sleep as supporting children's mental and physical health, parents' sleep/wake functioning, family social cohesion and emotional connectedness, and poor preschooler sleep as negatively influencing child, maternal and family well-being. Although many experiences were shared, some perceptions of sleep and sleep practices differed between mothers. Influences included health paradigms, socioeconomic circumstances, maternal autonomy, employment, parenting approaches, and societal expectations. Healthy preschooler sleep is valued by mothers and may play a protective role in family health and resilience. Preschooler sleep initiatives need to be responsive to maternal perspectives and address societal drivers of sleep experiences.


[Laparoscopic surgery for renal cancers].
327 patients with renal adenocarcinoma underwent laparoscopic radical nephrectomy (n=123), radical open nephrectomy (n=113), laparoscopic partialnephrectomy (n=47) or partial open nephrectomy (n=20) for stage T1 disease. Eighteen patients underwent open radical nephrectomy and six laparoscopic radical nephrectomy for stage T2 and T3 disease. Median tumor size was 9.6 cm after open surgery and 4.1 cm after laparoscopic surgery (p<0.01). Intraoperative blood loss was 254 ml during laparoscopy and 460 ml during open surgery (p<0.01). The hospital stay lasted 4.5 days after laparoscopic surgery and 10 days after open surgery (p<0.01). Complications were the same in the two groups, affecting 21.5 and 27.5% of patients, respectively (NS). Oncological results: stage for stage, the results were identical in the open and laparoscopic groups. The specific actuarial recurrence-free survival rate at 5 years among patients with stage PT1 disease was 97% after open radical nephrectomy and 96.8% after laparoscopic surgery; the corresponding rates were 100% after partial open surgery and 100% after laparoscopic partial surgery. Thus, laparoscopic surgery for renal adenocarcinoma offers identical oncological results to open surgery for patients with non metastatic tumors measuring less than 7 cm. Partial laparoscopic surgery offers the same results as partial open nephrectomy.


Amino Acid levels in carrot cell suspension culture: no correlation with aspartate kinase isoenzyme levels.
Free and protein amino acids were analyzed during the growth cycle of a suspension culture of carrot (Daucus carota L.) in which there is a 10-fold increase in a lysine-sensitive isoenzyme of aspartate kinase during the early part of the growth cycle. There is little change in either total amino acids or in the amino acids derived from aspartate between 3 and 24 days of culture. It is estimated that the demand for net synthesis of aspartate-derived amino acids is decreased as the growth rate declines and that there is no correlation between the amount of extractable lysine-sensitive aspartate kinase and the amounts of amino acids being synthesized.


Additive Effects of Lithium Salts with Various Anionic Species in Poly (Methyl Methacrylate).
We report that lithium salts in lithium-ion batteries effectively modify the physical properties of poly (methyl methacrylate) (PMMA). The glass transition temperature (Tg) is an indicator of the heat resistance of amorphous polymers. The anionic species of the salts strongly affected the glass transition behavior of PMMA. We focused on the additive effects of various lithium salts, such as LiCF3SO3, LiCOOCF3, LiClO4, and LiBr, on the Tg of PMMA. The large anions of the former three salts caused them to form macroscopic aggregates that acted as fillers in the PMMA matrix and to combine the PMMA domains, increasing Tg. On the other hand, LiBr salts dispersed microscopically in the PMMA matrix at the molecular scale, leading to the linking of the PMMA chains. Thus, the addition of LiBr to PMMA increased Tg as well as the relaxation time in the range of glass to rubber transition.


MR imaging in multiple sclerosis: review and recommendations for current practice.
MR imaging is widely used for the diagnosis and monitoring of patients with MS. Applications and protocols for MR imaging continue to evolve, prompting a need for continual reassessments of the optimal use of this technique in clinical practice. This article provides updated recommendations on the use of MR imaging in MS, based on a review of the trial evidence and personal experiences shared at a recent expert meeting of radiologists and neurologists.


[Promoter region methylation of DNA damage repair genes in human gastric cancer].
To detect the status of promoter region methylation of damage repair genes in gastric cancer and analyze its association with clinicopathologic characteristics. A total of 70 human gastric cancer tissue samples representing all stages of disease were obtained from surgical resection specimens. DNA was extracted with the phenol-chloroform method. The technique of methylation specific polymerase chain reaction (MSP) was used to examine the methylation status of MLH1, CHFR, MGMT, FANCF, Rassf1A, BRCA1 and GSTpi in gastric cancer specimens. And MSP products were analyzed with 2% agarose gel electrophoresis. The methylation rates of DNA damage related genes in human gastric cancer were as follows: MLH1 22.9% (16/70) , CHFR 47.1% (33/70), MGMT 34.3% (24/70), FANCF 11.4% (8/70), RASSF1A 7.1% (5/70), BRCA1 1.4% (1/70) and GSTpi 0% (0/70). And CHFR methylation was correlated with patient age (<60 year) (P = 0.035), tumor size (diameter ≥ 5 cm) (P = 0.031) and low differentiation (P = 0.019). In addition, CHFR methylation was associated with MLH1 methylation and MGMT methylation respectively. In human gastric cancer, the DNA damage repair genes of MLH1, CHFR and MGMT are frequently methylated while FANCF, RASSF1A, BRCA1 and GSTpi infrequently. Thus MLH1, CHFR and MGMT may play important roles during carcinogenesis of gastric cancer. And these methylated genes may serve as potential detection markers for gastric cancer.


Common Laboratory Mice Are Susceptible to Infection with the SARS-CoV-2 Beta Variant.
Small animal models are of crucial importance for assessing COVID-19 countermeasures. Common laboratory mice would be well-suited for this purpose but are not susceptible to infection with wild-type SARS-CoV-2. However, the development of mouse-adapted virus strains has revealed key mutations in the SARS-CoV-2 spike protein that increase infectivity, and interestingly, many of these mutations are also present in naturally occurring SARS-CoV-2 variants of concern. This suggests that these variants might have the ability to infect common laboratory mice. Herein we show that the SARS-CoV-2 beta variant attains infectibility to BALB/c mice and causes pulmonary changes within 2-3 days post infection, consistent with results seen in other murine models of COVID-19, at a reasonable virus dose (2 × 105 PFU). The findings suggest that common laboratory mice can serve as the animal model of choice for testing the effectiveness of antiviral drugs and vaccines against SARS-CoV-2.


Ulcerating nodules on a background of lower leg lymphoedema.
A patient presented with a 3-month history of a rapidly enlarging ulcerated tumour on his lower leg, occurring on a background of chronic idiopathic lymphoedema of approximately 10 years' duration. Histology revealed extensive infiltration of the dermis by a vascular tumour with pleomorphic and hyperchromatic endothelial cells, which stained positive for vascular markers CD31, CD34 and ERG. A diagnosis of lymphoedema-associated angiosarcoma was reached and our patient was treated with isolated limb perfusion with high-dose melphalan and tumour necrosis factor-alfa.


Active principle of swine prostate extract: II. Effect of a peptide isolated from swine prostate extract on rat prostate.
Previously, we purified a substance from swine prostate extract (PE) that had been reported to have therapeutic effect on benign prostatic hypertrophy. The purified substance (PPE) suppressed 3H-testosterone uptake into the prostate in castrated rats. The present study was carried out to examine the effect of PPE on the weight of accessory sexual organs including the prostate and biochemical parameters in the prostate of normal and/or castrated and testosterone-treated rats. 1) In normal rats, the p.o. administration of PPE daily for a total of 30 days did not affect the prostate weight, but reduced the citric acid content in the prostate. The treatment had little or no influence tissue O2 uptake, aconitase activity or isocitrate dehydrogenase activity in the prostate. 2) In castrated and testosterone-treated rats, the p.o. treatment with PPE for 15 or 30 days reduced the weight of the prostate as well as the total citric acid, DNA and RNA contents in prostatic tissue. However, these biochemical parameters per tissue weight were not obviously affected except for the citric acid content. These findings suggest that PPE is one of the active principals of PE for the therapeutic efficiency on benign prostatic hypertrophy, probably due to its suppressive effect on excessive uptake of androgen by the prostate.


Regulation of the growth of Epstein-Barr virus-infected B cells. I. Growth regression by E rosetting cells from VCA-positive donors is a combined effect of autologous mixed leukocyte reaction and activation of T8+ memory cells.
Regression of B cell proliferation in co-cultures of EBV-infected B cells (BEBV) and autologous T cells at 1:4 ratio was studied. 3H-TdR incorporation was used to measure proliferation by the participating lymphocyte populations and a 51Cr release assay was used to document the generation of cells capable of killing autologous EBV-transformed B lymphoblastoid cell lines (LCLEBV). EBV-infected B cells cultured alone transformed to blasts by culture day 10, and continued to proliferate throughout the 22 day observation period. When EBV-infected B cells were co-cultured with E rosetted cells from VCA-positive donors, there was a characteristic proliferative response on day 10 (an augmented autologous mixed lymphocyte reaction; AMLR), followed by the development of T8+ cells capable of killing autologous LCLEBV, as well as over 90% suppression of EBV growth by day 22 as assessed by 3H-TdR incorporation, and confirmed in a visual outgrowth assay. Negative and positive selection techniques were used to define the regulatory components in the T cell population. Depletion of T8+ cells from the blood lymphocytes of VCA-positive donors did not significantly reduce the 10 day proliferative response, but the subsequent development of cytotoxic cells and the regression of BEBV outgrowth was not observed. Thus, the circulating T8+ cells are required for the subsequent appearance of autologous LCLEBV cytotoxicity and BEBV growth regulation. However, when the responder population consisted only of T8+ cells, the augmented AMLR response was absent, cytotoxic cell development was weak or absent, and there was no regression of EBV outgrowth. Therefore, the cells participating in the AMLR, as well as T8+ memory cells from VCA-positive donors, are necessary for the control of the in vitro EBV infection. Growth regression is dependent on the proliferation of the regulatory T cells. Mitomycin C treatment of fresh E rosetting cells or those exposed to BEBV for up to 10 days in culture abrogates growth regression and the subsequent appearance of LCLEBV killer cells. However, E rosetting cells exposed to BEBV for 14 days or more already have developed the ability to kill LCLEBV and no longer need to proliferate to induce growth regression when cultured with newly infected BEBV. These results lend additional support to the view that the control of EBV-induced B cell expansion requires a AMLR-dependent clonal amplification of EBV-specific, T8+ cytotoxic cells.


[Recent clinical applications of MR medicine as functional medical imaging in the brain and heart].
This paper reviewed recent clinical applications of MR medicine as functional imaging in the brain and heart. Functional and metabolic imaging of brain and heart can be evaluated by the development of fast MR technique (fast SE, echo planar imaging, etc) and chemical shift imaging. The clinical applications of MR medicine to the brain are follows. 1. higher nerve activity assessment using functional MRI, 2. brain perfusion imaging by dynamic contrast MRI, 3. brain diffusion imaging and 4. brain metabolic function by 1H and 31P-MRS. Those of MR medicine to the heart are as follows. 1. left ventricular function assessment by snapshot and/or echo planar imaging. 2. regional wall motion assessment by magnetic tagging, 3. myocardial perfusion imaging by dynamic contrast MRI, 4. coronary flow reserve assessment and 5. cardiac metabolic function by 31P and 1H MRS. Most of these data are thought to be compatible with nuclear medicine technique such as PET and SPECT. In the future, MR medicine may be used as the tool of functional and metabolic diagnosis in addition to anatomical diagnosis in the field of cerebral and cardiac disorders.


Three-dimensional blind deconvolution of SPECT images.
Thanks to its ability to yield functionally rather than anatomically-based information, the three-dimensional (3-D) SPECT imagery technique has become a great help in the diagnostic of cerebrovascular diseases. Nevertheless, due to the imaging process, the 3-D single photon emission computed tomography (SPECT) images are very blurred and, consequently, their interpretation by the clinician is often difficult and subjective. In order to improve the resolution of these 3-D images and then to facilitate their interpretation, we propose herein to extend a recent image blind deconvolution technique (called the nonnegativity support constraint-recursive inverse filtering deconvolution method) in order to improve both the spatial and the interslice resolution of SPECT volumes. This technique requires a preliminary step in order to find the support of the object to be restored. In this paper, we propose to solve this problem with an unsupervised 3-D Markovian segmentation technique. This method has been successfully tested on numerous real and simulated brain SPECT volumes, yielding very promising restoration results.


Serous microcystic adenoma of the pancreas: case report and review of the literature.
Cystic tumors of the pancreas are rare neoplasms. They are more frequently identified given the improvements in imaging techniques. Serous cystadenomas are the most common among cystic neoplasms of the pancreas. In this case report we present a patient who was incidentally found to have a cystic mass in the pancreas during an abdominal imaging done for unrelated reasons and was diagnosed as serous cystadenoma of the pancreas. She was asymptomatic on admission and was operated six years later because of the progressive growth of the tumor during that period. Distal pancreatectomy was performed. Histopathologic examination of the surgery specimen confirmed the diagnosis of serous microcystic adenoma. Despite their rarity, serous cystadenomas should be kept in mind in the differential diagnosis of the cystic lesions of the pancreas. Furthermore, the differentiation of serous cystadenoma from other cystic tumors as well as from non-neoplastic cysts is very important because of the great difference in their management.


Use of the argon-pumped tunable dye laser for port-wine stains in children.
The authors reported previously a new technique using a low power argon-pumped tunable dye laser at a wave-length of 577nm (yellow light) to treat port-wine stains in adults. The authors report their results using this same technique as a form of treatment for 92 children with facial port-wine stains.


Functional material-mediated wireless physical stimulation for neuro-modulation and regeneration.
Nerve injuries and neurological diseases remain intractable clinical challenges. Despite the advantages of stem cell therapy in treating neurological disorders, uncontrollable cell fates and loss of cell function in vivo are still challenging. Recently, increasing attention has been given to the roles of external physical signals, such as electricity and ultrasound, in regulating stem cell fate as well as activating or inhibiting neuronal activity, which provides new insights for the treatment of neurological disorders. However, direct physical stimulations in vivo are short in accuracy and safety. Functional materials that can absorb energy from a specific physical field exerted in a wireless way and then release another localized physical signal hold great advantages in mediating noninvasive or minimally invasive accurate indirect physical stimulations to promote the therapeutic effect on neurological disorders. In this review, the mechanism by which various physical signals regulate stem cell fate and neuronal activity is summarized. Based on these concepts, the approaches of using functional materials to mediate indirect wireless physical stimulation for neuro-modulation and regeneration are systematically reviewed. We expect that this review will contribute to developing wireless platforms for neural stimulation as an assistance for the treatment of neurological diseases and injuries.


Stereoselective construction of seven-membered rings with an all-carbon quaternary center by direct Tiffeneau-Demjanov-type ring expansion.
Insertion of one methylene unit into the C-C bond of cyclohexanones is a potentially useful, straightforward method for the construction of seven-membered carbocycles. An especially appealing but largely unexplored method in this arena is the nucleophilic addition of diazoalkanes to the Lewis acid-activated cyclohexanones and subsequent ring expansion accompanied by the extrusion of nitrogen (direct Tiffeneau-Demjanov-type ring expansion). Our primary finding is the unprecedented insertion of alpha-alkyldiazoacetates to cyclohexanone and its heteroanalogues, generating seven-membered rings with one all-carbon quaternary center. On the basis of this finding, highly diastereoselective ring expansion of substituted cyclohexanones was developed, furnishing seven-membered rings with 1,4-quaternary-tertiary, 1,4-quaternary-quaternary, or 1,3,5-quaternary-tertiary-tertiary stereogenic centers in a single operation starting from readily available materials. The stereochemical outcome of the product can be easily predicted from the conformation of starting cyclohexanones. Enantioenriched products could be also accessed by the use of (-)-phenylmenthyl alpha-alkyldiazoacetates.


Charge and size heterogeneity of C3d following in vivo and in vitro activation of the complement system.
Split products of the third complement factor (C3) expressing D but not C epitopes (C3d) were analyzed by crossed immunoelectrophoresis and size chromatography. Four molecular forms (termed 1, 2, 3, and 4 from the anodic side) were identified. The precipitation pattern of C3d in serum following acute in vivo activation was similar to the patterns observed using in vitro activation by MgCl2, zymosan, Escherichia coli, and delta IgG. These patterns were different from those observed in normal human serum and serum from a patient suffering from systemic lupus erythematosus. The molecular weights of forms 1 and 4 were approximately 170,000 daltons and those of forms 2 and 3 approximately 40,000 daltons.


Outer membrane protein P1 is the CEACAM-binding adhesin of Haemophilus influenzae.
Haemophilus influenzae is a Gram-negative pathogen colonizing the upper respiratory tract mucosa. H. influenzae is one of several human-restricted bacteria, which bind to carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) on the epithelium leading to bacterial uptake by the eukaryotic cells. Adhesion to CEACAMs is thought to be mediated by the H. influenzae outer membrane protein (OMP) P5. However, CEACAMs still bound to H. influenzae lacking OMP P5 expression, and soluble CEACAM receptor ectodomains failed to bind to OMP P5, when heterologously expressed in Escherichia coli. Screening of a panel of H. influenzae OMP mutants revealed that lack of OMP P1 completely abrogated CEACAM binding and supressed CEACAM-mediated engulfment of H. influenzae by epithelial cells. Moreover, ectopic expression of OMP P1 in E. coli was sufficient to induce CEACAM binding and to promote attachment to and internalization into CEACAM-expressing cells. Interestingly, OMP P1 selectively recognizes human CEACAMs, but not homologs from other mammals and this binding preference is preserved upon expression in E. coli. Together, our data identify OMP P1 as the bona fide CEACAM-binding invasin of H. influenzae. This is the first report providing evidence for an involvement of the major OMP P1 of H. influenzae in pathogenesis.


Dose, timing, and duration of flaxseed exposure affect reproductive indices and sex hormone levels in rats.
Flaxseed ingestion produces large amounts of mammalian lignans. Since lignans have weak estrogenic/antiestrogenic properties, the objective of this study was to determine in rats whether exposure to 5% or 10% flaxseed affects sex hormone levels and reproductive indices when given at different developmental stages. Rats were exposed to either a basal diet (control), 5%, or 10% flaxseed diet starting at weaning on postnatal day (PND) 21 or continuously from gestation to PND 132 for lifetime exposure. Compared to the control, exposure to 5% or 10% flaxseed after weaning produced no marked reproductive effects, whereas lifetime flaxseed exposure caused significant changes that differed depending on the dose. In female rats, lifetime exposure to 5% flaxseed affected the reproductive tract as indicated by delayed puberty onset. In contrast, lifetime exposure to 10% flaxseed caused earlier puberty onset, higher relative ovarian weight, higher serum estradiol levels, and lengthened estrous cycles. In male rats, lifetime 10% flaxseed exposure raised serum testosterone and estradiol levels and produced higher relative sex organ weights and prostate cell proliferation. In contrast, lifetime exposure to 5% flaxseed reduced adult relative prostate weight and cell proliferation, suggesting potential protection against prostatic disease, although sex hormone levels were unaffected. In conclusion, flaxseed can potentially alter reproduction, depending on the dose and timing of exposure.


A rare case of intraductal tubulopapillary neoplasm of the pancreas - case report (with video).
Intraductal tubulopapillary neoplasm (ITPN) is a premalignant epithelial tumor of the pancreas. We report a case of ITPN detected incidentally during histopathology examination (HPE) from a specimen taken at the time of endosonography in a patient with pancreatitis. A 53-year-old man presented with severe recurrent epigastric pain, associated with episodic nonbilious vomiting, with a weight loss of about 7 Kg since 15 days. He underwent Magnetic resonance cholangiopancreatography which showed an ovoid soft tissue lesion in the Pancreatic duct (PD) reported as possible intraductal neoplasm. Patient underwent Endoscopic Ultrasound, whereby the PD was dilated and a large hypoechoic lesion was noted in the PD (head region) causing upstream dilatation. Lesion did not show any vascularity on Doppler. Fine needle biopsy was sent from the intraductal lesion for histopathology examination (HPE). Patient then underwent an ERCP. After performing a pancreatic sphincterotomy, pancreaticoscopy was done using SPYGLASS DS system which showed a nodular intraluminal lesion in the head region with irregular and abnormal vascularity and papillary fronds. Biopsies were taken from this lesion using SpyBite biopsy forceps. To our surprise this HPE report came out to be ITPN. Patient was then referred for surgery. There is often a difference of opinion in distinguishing and classifying such tumors when compared to the subtypes of mucinous neoplasm. Identification of this neoplasm is often challenging for pathologists as well as radiologists. We present this case since it is infrequent and atypical in routine medical practice.